literature review on prevalence of hypertension pdf

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The global epidemiology of hypertension

Hypertension is the leading cause of cardiovascular disease and premature death worldwide. Owing to widespread use of antihypertensive medications, global mean blood pressure (BP) has remained constant or decreased slightly over the past four decades. By contrast, the prevalence of hypertension has increased, especially in low and middle-income countries (LMICs). Estimates suggest that in 2010, 31.1% of adults (1.39 billion) worldwide had hypertension. The prevalence of hypertension among adults was higher in LMICs (31.5%, 1.04 billion people) than in high-income countries (HICs; 28.5%, 349 million people). Variations in the levels of risk factors for hypertension, such as high sodium intake, low potassium intake, obesity, alcohol consumption, physical inactivity and unhealthy diet, may explain some of the regional heterogeneity in hypertension prevalence. Despite the increasing prevalence, the proportions of hypertension awareness, treatment and BP control are low, particularly in LMICs, and few comprehensive assessments of the economic impact of hypertension exist. Future studies are warranted to test implementation strategies for hypertension prevention and control, especially in low-income populations, and to accurately assess the prevalence and financial burden of hypertension worldwide.

INTRODUCTION

Hypertension is the leading preventable risk factor for cardiovascular disease (CVD) and all-cause mortality worldwide. 1 , 2 In 2010, 31.1% of the global adult population (1.39 billion people) had hypertension, defined as systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg. 3 The prevalence of hypertension is rising globally owing to ageing of the population and increases in exposure to lifestyle risk factors including unhealthy diets (i.e. high sodium and low potassium intake and lack of physical activity. 3 However, changes in hypertension prevalence are not uniform worldwide. In the past two decades, high-income countries (HICs) experienced a modest decrease in hypertension prevalence, while low and middle-income countries (LMICs) experienced significant increases. 3 These disparities in hypertension prevalence trends suggest that health care systems in LMICs could be facing a rapidly increasing burden of hypertension and BP-related cardiovascular diseases, in some cases in addition to a substantial burden of infectious diseases.

In this Review, we discuss estimates and trends in mean BP levels and hypertension prevalence, awareness, treatment, and control worldwide. We also examine risk factors for hypertension, strategies for hypertension control, and evidence of the financial burden of hypertension. We conclude by discussing the consequences of current trends in hypertension and areas where more research is needed.

GLOBAL MEAN BLOOD PRESSURE

A study that analyzed data from 844 studies performed in 154 countries with 8.69 million participants estimated that in 2015, the global mean age-standardized systolic BP was 127.0 mmHg in men and 122.3 mmHg in women, whereas the mean age-standardized diastolic BP was 78.7 mmHg in men and 76.7 mmHg in women. 4 Higher mean systolic and diastolic BPs in both men and women were found in South Asia, Sub-Saharan Africa, and Central and Eastern Europe, while lower mean BPs were found in high-income Western and high-income Asia-Pacific regions. 4 Social and environmental factors, including healthcare access, availability of antihypertensive medications, and regional variations in hypertension risk factors, such as obesity, alcohol consumption, unhealthy diet and lack of physical activity, likely contribute to these regional differences 3 , 4

This study also reported that over the past 40 years, estimated mean BP has remained constant or decreased slightly worldwide. 4 Estimated global mean age-standardized systolic BP remained fairly constant in men between 1975 (126.6 mmHg) and 2015 (127.0 mmHg) but decreased slightly in women during this period (from 123.9 mmHg to 122.3 mmHg). Trends for men and women were similar for estimated global mean age-standardized diastolic BP, with very little change in men and a slight decrease in women. However, regional changes in estimated mean BP between 1975 and 2015 were more heterogeneous ( Figure 1 ). In general, HICs experienced a significant BP decrease, while BP in LMIC regions increased. 4 Substantial decreases in estimated age-standardized mean systolic and diastolic BP occurred in both men and women in high-income Western and Asia-Pacific regions between 1975 and 2015. 4 Estimates suggest that the largest decrease in systolic BP was in the high-income Asia-Pacific region in which systolic BP decreased by 2.4 mmHg per decade in men and 3.2 mmHg per decade in women, whereas the largest decrease in diastolic BP was in the high-income Western region in which diastolic BP decreased by 1.5 mmHg per decade in men and 1.8 mmHg per decade in women. Decreases in mean systolic and diastolic BP were also observed in women in Central and Eastern Europe, Latin America and the Caribbean, the Middle East and North Africa, and Central Asia, while no change in BP was seen in men in these regions. 4 In both men and women, systolic and diastolic BP increased in East and Southeast Asia, South Asia, Oceania, and sub-Saharan Africa.

A. Change in systolic blood pressure (BP) in men. B. Change in systolic BP in women. C. Change in diastolic BP in men. D. Change in diastolic BP in Women. Data obtained from reference 4 .

These regional changes in mean systolic and diastolic BP have led to disparities in the burden of hypertension. 3 Improvements in prevention, detection, and treatment of BP in HICs have likely contributed to lower BP levels in these regions. 3 – 7 By contrast, limited healthcare resources together with population ageing and urbanization, which is associated with reductions in physical activity and increases in unhealthy diets, are potential drivers of BP increases in LMICs. 8 – 10 In both HICs and LMICs, women have higher proportions of hypertension awareness, treatment, and control than men. 3 These differences could contribute to the greater BP reductions observed in women than men in some regions

GLOBAL BURDEN OF HYPERTENSION

Based on an analysis of data from 135 population-based studies that included 968,419 adults from 90 countries, we estimated that in 2010 the global age-standardized prevalence of hypertension (defined as systolic BP ≥140 mm Hg, diastolic BP ≥90 mm Hg, and/or current use of antihypertensive medication) was 31.1% (95% CI 30.0–32.2%). 3 The age-standardized prevalence of hypertension was slightly higher in men (31.9%) than in women (30.1%) ( Table 1 ) 3 and was lower in HICs (28.5%) than in LMICs (31.5%) ( Figure 2 ). 3 The lowest prevalence of hypertension in men was found in South Asia (26.4%), whereas the highest prevalence was in Eastern Europe and Central Asia (39.0%). In women, the prevalence of hypertension was lowest in HICs (25.3%) and highest in Sub-Saharan Africa (36.3%). The reasons for these disparities in hypertension prevalence across regions are not fully understood but are likely influenced by differences in the prevalence of risk factors for hypertension, including unhealthy diet, lack of physical activity and obesity. 3 , 8

Prevalence of hypertension defined as systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg or use of antihypertensive medication in A. Men and B. Women. Data obtained from reference 3 .

Estimated prevalence of hypertension in high-income and low and middle-income countries in 2000 and 2010

Data obtained from reference 3

The Prospective Urban Rural Epidemiology (PURE) study included 153,996 adults aged 35–70 years from 628 rural and urban communities in 17 geographically and economically diverse countries who were recruited between 2003 and 2009. 11 This study included 142,042 participants with BP data at baseline, providing a unique opportunity to compare hypertension prevalence between rural and urban populations in different world regions. The PURE study found that 40.8% (95% CI 40.5–41.0%) of participants had hypertension with a higher prevalence in men (41.4%) than in women (37.7%). 11 Residents of rural areas had a higher prevalence of hypertension than urban residents in HICs and middle-income countries (MICs), but the opposite was true in low-income countries (LICs). 11

We estimated that between 2000 and 2010, the global age-standardized prevalence of hypertension in adults aged ≥20 years increased by 5.2%. 3 This estimate is consistent with a 2015 Global Burden of Disease analysis that found that the prevalence of elevated systolic BP (≥140 mmHg) increased 3.2% from 17.3% in 1990 to 20.5% in 2015. 12 The global increase in prevalence of hypertension was consistent by sex (5.5% in men and 5.0% in women) but varied by economic development. 3 From 2000 to 2010, the prevalence of hypertension increased in LMICs and decreased in HICs ( Table 1 ). 3 LMICs experienced a sharp increase in hypertension prevalence from 23.8% in 2000 to 31.5% in 2010. By contrast, HICs experienced a decrease in hypertension prevalence from 31.1% to 28.5% in the same ten-year period. 3 Hypertension prevalence was therefore higher in LMICs (31.5%) than in HICs (28.5%) in 2010. Similar to the trends observed for BP change, population ageing, urbanization and related lifestyle changes (such as unhealthy diet and lack of physical activity) might explain the increased prevalence of hypertension in LMICs. 8 , 10

As mentioned above, an estimated 1.39 billion adults worldwide had hypertension in 2010 with an approximately even distribution between men and women ( Table 1 ). 3 Among those with hypertension, approximately 75% (1.04 billion) lived in LMICs and 25% (349 million) lived in HICs. By contrast, in 2000 an estimated 921 million people had hypertension comprising 322 million (34%) in HICs and 599 million (66%) in LMICs. 3 , 13 Between 2000 and 2010, the absolute burden of hypertension (total number of individuals with hypertension) increased by 440 million in LMICs and only 27 million in HICs. 3 In 2010, the highest absolute burden of hypertension was in East Asia and the Pacific, which had more individuals with hypertension than all HICs combined. 3 The absolute burden of hypertension in men and women increased in all world regions between 2000 and 2010, except for in the Middle East and North Africa where the absolute burden in women decreased slightly. 3 The Global Burden of Disease study estimated that in 2015 around 3.5 billion adults worldwide had systolic BP of at least 110–115 mmHg, a level that is associated with increased risk of ischaemic heart disease (IHD), stroke, and kidney disease. 4 This prevalence represents a marked increase from 1990 when 1.87 billion people had a systolic BP of at least 110–115 mmHg. 4

In 2017, the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines redefined hypertension in adults as systolic BP ≥130 mmHg and/or diastolic BP ≥80 mmHg. 14 This change was based on findings from a number of large-scale, prospective observational studies that reported significant increases in risk of CVD with increasing BP even from levels as low as systolic BP 115 mmHg, as well as the results of randomized clinical trials including the SPRINT trial (discussed further below) that showed that intensive BP lowering (target systolic BP <120 mmHg) reduces CVD and all-cause mortality to an even greater extent than does standard BP lowering (target systolic BP ≤140 mmHg). 15 – 18 When the new definition was applied to the US general population, hypertension prevalence increased from 32.0% (based on the traditional criteria) to 45.4% ( Table 2 ). 19 , 20 In the Chinese general population, the increase was even greater from 23.2% to 46.4%. 19 , 20 These findings suggest that if the new criteria were applied worldwide, the difference in hypertension prevalence between LMICs and HICs would be much greater than previously reported. 3 Full implementation of the new guidelines would require a greater proportion of adults to be treated with antihypertensive medications but could prevent an estimated 610,000 CVD events and 334,000 deaths per year in the US alone. 19

Estimated prevalence of hypertension in the general populations of the US in 2013–2016 and China in 2012–2015

Data obtained from references 19 and 20

Valid estimation of global BP levels and hypertension prevalence is highly dependent on the availability and quality of BP data from population-based studies around the world. Many factors, such as the representativeness of study populations (e.g. sampling methods and response rates), BP measurement methods (e.g. calibration of BP measuring devices, appropriate BP cuff sizes, and preparation of participants), and number of BP measurements can affect the quality of prevalence data. 21 In many countries, population-based BP studies have not been conducted or BP data are not publicly available. In addition, the number of studies and the quality of the available data varies substantially between regions. As a result, BP estimates for some countries are based entirely on modelling in several pooling projects. 4 , 12 , 22 This problem is particularly apparent in Sub-Saharan Africa for which BP data are sparse. 23 High-quality, population-based studies that accurately measure BP in all countries worldwide, particularly in LMICs, are required to enable accurate assessment of the global burden of hypertension.

BLOOD PRESSURE, CVD, CKD AND MORTALITY

Elevated BP is associated with a large global burden of CVD and premature death. In 2015, the estimated number of all-cause deaths that were associated with systolic BP ≥110–115 mmHg was 10.7 million (19.2% of all deaths) and with systolic BP ≥140 mm Hg was 7.8 million (14.0% of all deaths). 12 The largest numbers of deaths that were related to systolic BP ≥110–115 mmHg were attributed to IHD (4.9 million or 54.5% of IHD deaths), ischaemic stroke (1.5 million or 50.0% of ischaemic stroke deaths), and haemorrhagic stroke (2.0 million or 58.3% of haemorrhagic stroke deaths) ( Figure 3 ). The corresponding numbers of deaths related to systolic BP ≥140 mmHg were 3.6 million (40.1% of IHD deaths), 1.1 million (38.1% of ischemic stroke deaths) and 1.4 million (42.5% of hemorrhagic stroke deaths). 12 Consistent with trends in hypertension prevalence, the estimated numbers of BP-related all-cause and CVD deaths increased substantially from 1990 to 2015, especially in LMICs. 12 Scaling up effective antihypertensive interventions to reduce BP-related morbidity and mortality should be a global public health priority.

A. Estimated numbers of deaths attributed to systolic blood pressure (SBP) ≥110–115 mmHg and B. SBP ≥140 mmHg by cause of death. Data obtained from reference 12 .

Observational epidemiological studies have shown a strong, independent and linear association between BP and the risk of CVD without any evidence of a BP threshold. 15 , 24 – 26 For example, the Prospective Studies Collaboration examined the association between BP and cause-specific mortality in approximately 1 million adults aged 40–89 years with no previous history of CVD at baseline using data from 61 prospective observational studies. 15 During 12.7 million person-years of follow-up, around 56,000 CVD deaths (12,000 stroke, 34,000 IHD, and 10,000 other CVD) and 66,000 deaths owing to other causes were reported. Meta-analyses that corrected for regression dilution showed that the proportional difference in risk of CVD death that was associated with a given absolute difference in usual BP for each decade of age was similar for increases in BP from levels as low as 115 mmHg systolic and 75 mmHg diastolic. 15 In those aged 40–69 years, a difference in usual systolic BP of 20 mmHg or usual diastolic BP of 10 mmHg was associated with a more than twofold difference in the rate of stroke deaths and a twofold difference in the rate of death owing to IHD and other CVD causes. The proportional difference in CVD mortality that was associated with a given absolute difference in usual blood pressure in adults aged 80–89 years was about half that of adults aged 40–49 years, but the annual absolute differences in risk were greater in old age. 15

In adults who are middle aged or older (≥35 years), systolic BP is a more important determinant of CVD risk than diastolic BP. 24 – 26 Among 347,978 men aged 35 to 57 years who were screened in the US for entry into the Multiple Risk Factor Intervention Trial (MRFIT) and had not previously been hospitalized for CVD, 7,150 deaths from IHD and 733 deaths from stroke were identified during an average of 11.6 years of follow-up. 25 In every decile of BP, systolic BP was more strongly associated with risk of IHD and stroke than was diastolic BP. When the highest deciles were compared with the lowest deciles, the relative risks associated with increased systolic and diastolic BP were 3.7 and 2.8, respectively, for IHD, and 8.2 and 4.4, respectively, for stroke.

Several large prospective cohort studies have reported that elevated BP is also a strong independent risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD). 27 – 29 The increase in risk that was associated with higher BP was dose-response and continuous throughout the distribution of BP levels above 120 mmHg. 27 – 29 Among 332,544 men aged 35 to 57 years who were screened for entry into the MRFIT trial and did not have ESRD at baseline, a strong independent linear relationship between both systolic and diastolic BP and incidence of ESRD was identified during an average of 16 years of follow-up. 28 Compared with normotensive men who had a systolic BP <120 mmHg and diastolic BP <80 mmHg, the relative risk of ESRD for men with hypertension who had a systolic BP >210 mmHg or diastolic BP >120 mmHg was 22.1 (P<0.001). A similar association between BP and risk of ESRD was reported in a cohort of 158,365 Chinese men and women aged ≥40 years. 29 In addition, BP was significantly and independently associated with progression to ESRD among patients with CKD. 27 Among 3,708 patients with CKD in the Chronic Renal Insufficiency Cohort Study in the US, multivariable-adjusted relative risk (95% CI) for ESRD was 2.37 (CI, 1.48 to 3.80) and 3.37 (CI, 2.26 to 5.03) among those with systolic BP of 130–139 and ≥140 mmHg, respectively, compared with systolic BP <120 mmHg. 27

Randomized clinical trials have demonstrated that BP lowering with commonly used regimens, such as diuretics, angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, and calcium channel blockers reduces the risk of CVD and all-cause mortality. 30 , 31 A large meta-analysis of 123 clinical trials with 613,815 participants showed that relative risk reductions of CVD and all-cause mortality were proportional to the magnitude of achieved BP reductions. 31 For example, every 10 mmHg reduction in systolic BP significantly reduced the risk of major CVD events by 20% (relative risk 0.80, 95% CI 0.77–0.83), IHD by 17% (relative risk 0.83, 0.78–0.88), stroke by 27% (relative risk 0.73, 0.68–0.77), heart failure by 28% (relative risk 0.72, 0.67–0.78), and all-cause mortality by 13% (0.87, 0.84–0.91). 31 This study provided no clear evidence that proportional risk reductions in major CVD events differed by baseline BP levels or comorbidities, except for patients with diabetes and CKD, for whom the risk reductions were smaller but still statistically significant.

The Systolic Blood Pressure Intervention Trial (SPRINT) randomly assigned 9,361 patients with systolic BP ≥130 mmHg and increased CVD risk to a systolic BP target of <120 mmHg (intensive treatment) or <140 mmHg (standard treatment). 17 Increased CVD risk was defined as clinical or subclinical CVD, CKD, a 10-year risk of CVD of ≥15% according to the Framingham risk score, or an age of ≥75 years. At 1 year, mean systolic BP was 121.4 mmHg in the intensive treatment group and 136.2 mmHg in the standard-treatment group. Moreover, intensive treatment was associated with a 25% reduction in CVD events (hazard ratio 0.75, 95% CI 0.64–0.89, P<0.001) and a 27% reduction in all-cause mortality (hazard ratio 0.73, 95% CI 0.60–0.90, P=0.003) compared to standard treatment over a median follow-up of 3.26 years. The number needed to treat (NNT) to prevent one CVD event during the follow-up period was 61, and the NNT to prevent one death from any cause was 90. 17 The SPRINT trial demonstrates that intensive BP lowering treatment with a systolic BP target of <120 mmHg is beneficial for patients with hypertension who are at high risk of CVD. The SPRINT trial prompted the revision of the definition of hypertension and BP antihypertensive treatment goals. 14

The results of meta-analyses of randomized controlled trials that compared the efficacy of different BP targets or treatment intensities to reduce the risk of CVD and mortality in patients with hypertension are consistent with the SPRINT findings. 18 , 31 , 32 For example, a 2015 network meta-analysis of 42 trials that included 144,220 patients with hypertension, reported linear associations between mean achieved systolic BP and risk of CVD and mortality, with the lowest risk among those who achieved a systolic BP of 120–124 mmHg. 18 In these trials, study groups that achieved mean systolic BPs of 120–124 mm Hg had hazard ratios for major CVD of 0.71 (95% CI, 0.60–0.83), 0.58 (95% CI, 0.48–0.72), 0.46 (95% CI, 0.34–0.63), and 0.36 (95% CI, 0.26–0.51), compared with study groups that achieved systolic BPs of 130–134 mmHg, 140–144 mmHg, 150–154 mmHg and ≥160 mmHg, respectively. 18 Network meta-analyses offer a unique advantage over traditional meta-regression methods by enabling the simultaneous comparison of the effects of multiple interventions or treatment targets on clinical outcomes while preserving trial-level treatment randomization and its associated protection against bias.

Despite the findings from SPRINT and related meta-analyses, some concerns remain about the appropriateness and effectiveness of intensive BP reduction in certain subgroups, including patients with CKD, diabetes or stroke and older adults (≥65 years). A pre-specified subgroup analysis of outcomes in SPRINT trial participants with CKD found that intensive BP treatment resulted in significant reductions in the risk of CVD and death but no significant increase in the incidence of serious adverse events compared to standard BP treatment. 33 The rate of continuous eGFR decline was higher in the intensive BP treatment group but there was no significant difference in risk of CKD progression (defined as incident ESRD or halving of eGFR) between the two groups. 33 In addition, a subgroup analysis of 978 SPRINT participants (519 in the intensive and 459 in the standard treatment group) showed that while eGFR was lower in the intensive treatment compared to standard treatment group, urine biomarkers of tubule function, injury, inflammation, and repair were not different over 4 years of follow-up. These findings suggest that observed eGFR declines in the intensive treatment group predominantly reflect hemodynamic changes rather than intrinsic damage to kidney tubule cells. 34 An additional SPRINT subgroup analysis in patients aged ≥75 years reported that intensive BP treatment significantly reduced the incidence of CVD and mortality with no increase in serious adverse events compared with standard BP-lowering treatment. 35

As patients with diabetes or stroke were not included in the SPRINT trial, questions regarding the risks and benefits of intensive BP lowering remain in these subgroups. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study reported that intensive BP treatment aimed at achieving a systolic BP target of <120 mmHg did not significantly reduce the risk of CVD events compared with standard BP treatment (systolic BP target of <140 mmHg) in patients with type 2 diabetes (hazard ratio 0.88; 95% CI 0.73–1.06). 36 However, a subgroup analysis suggested a significant reduction in CVD events in the intensive BP treatment group compared to standard treatment group (hazard ratio 0.74, 95% CI 0.55 to 1.00, p=0.049) among participants who received standard glycaemic treatment. 37 In addition, a meta-analysis of four randomized clinical trials with 4,895 participants reported that intensive BP control reduced the risk of recurrent stroke compared with standard BP control (relative risk 0.78; 95% CI 0.64–0.96; P = 0.02). 38 On-going clinical trials (such as the OPTIMAL-DIABETES trial [ {"type":"clinical-trial","attrs":{"text":"NCT04040634","term_id":"NCT04040634"}} NCT04040634 ], the OPTIMAL Stroke trial [ {"type":"clinical-trial","attrs":{"text":"NCT04036409","term_id":"NCT04036409"}} NCT04036409 ], the BPROAD trial [ {"type":"clinical-trial","attrs":{"text":"NCT03808311","term_id":"NCT03808311"}} NCT03808311 ], and the IBIS Trial [ {"type":"clinical-trial","attrs":{"text":"NCT03585595","term_id":"NCT03585595"}} NCT03585595 ]) will likely provide definite answers regarding optimum BP treatment goals for patients with diabetes or stroke. However, the currently available evidence supports a more intensive BP treatment target. 14

RISK FACTORS FOR HYPERTENSION

BP levels and hypertension prevalence increase with age in both sexes. 39 Men have higher BP at younger ages than women, but BP increase per decade is higher in women than in men. By the age of 60 years, women have a higher mean BP and hypertension prevalence than men. Race and ethnicity is also a significant risk factor for hypertension. For example, a study that analyzed National Health and Nutrition Examination Survey (NHANES) 2015–2016 data for 4,821 US adults aged ≥20 years, reported a significantly higher age-standardized prevalence of hypertension in non-Hispanic Black individuals (57.3%) than in non-Hispanic White individuals (43.8%) and Hispanic-Americans (44.7%). 40 There is no evidence that racial and ethnic disparities in risk of hypertension are explained by genetic factors. 41 , 42 Sociodemographic, environmental and behavioral factors are therefore likely to be the main contributors to racial and ethnic differences in mean BP and prevalence of hypertension. 42 In addition, several modifiable risk factors, including high sodium intake, low potassium intake, alcohol consumption, obesity, lack of physical activity, and unhealthy diet are associated with increased risk of hypertension

High sodium intake

The PURE study estimated that in 2010, global sodium intake was 3,950 mg per day, which is considerably higher than the recommended amounts of 2,300 mg or less per day in all published guidelines. 44 , 45 In addition, sodium consumption varied considerably by world region from >4,200 mg per day in East Asia, Central Asia, and Eastern Europe to <3,300 mg per day in Latin America and Sub-Saharan Africa. 44

Animal experiments, observational epidemiologic studies, and randomized clinical trials have demonstrated a causal relationship between sodium intake and elevated BP. 46 The majority of the observational studies were cross-sectional and reported a positive, linear, and significant association of either dietary intake or 24-hour urinary excretion of sodium with BP or hypertension. 47 , 48 For example, the Intersalt study investigated the association between 24-hour urinary sodium excretion and BP among 10,074 men and women aged 20–59 from 52 population samples in 32 countries. 47 In within population analyses, a 100 mmol higher individual 24-hour urinary sodium excretion was associated with a 6.0 mmHg higher average systolic BP and a 2.5 mmHg higher average diastolic BP. In across population analyses, a 100 mmol higher median 24-hour sodium excretion was associated with a median 4.5 mmHg higher systolic and 2.3 mmHg higher diastolic BP. 47 When four remote populations with extremely low urinary sodium excretion were excluded from the across population analyses, a 100 mmol increase in median 24-hour sodium excretion was associated with a 2.5 mmHg increase in systolic BP. 47 The Intersalt study showed consistent patterns of regional differences in salt intake and BP levels. A positive and significant association between spot urinary sodium excretion and BP was also observed in the PURE study. 49

In the DASH-Sodium trial, 412 people with an average systolic BP of 120–159 mmHg and diastolic BP of 80–95 mmHg were randomly assigned to high sodium (mean urinary excretion of 142 mmol per day), intermediate sodium (mean urinary excretion of 107 mmol per day) and lower sodium diets (mean urinary excretion of 65 mmol per day) for 30 days in a cross-over design. 50 The results showed that reducing sodium intake from a high to an intermediate level lowered systolic BP by 2.1 mmHg (P<.001) during consumption of a usual American control diet and by 1.3 mm Hg (P = 0.03) during consumption of a Dietary Approaches to Stop Hypertension (DASH) diet. Further reducing sodium intake from an intermediate to a lower level resulted in an additional reduction in systolic BP of 4.6 mmHg during consumption of the control diet (P<0.001) and a 1.7 mmHg reduction during consumption of the DASH diet (P<0.01). 50

Several meta-analyses of clinical trials have shown that sodium reduction significantly lowers BP in hypertensive and normotensive individuals. 51 – 55 An Agency for Healthcare Research and Quality (AHRQ) meta-analysis that included 48 randomized control trials found a significant BP-lowering effect of dietary sodium reduction in adults both with and without hypertension. 55 In this study, a 42 mmol decrease in the weighted mean sodium intake was associated with a 3.23 mmHg (95% CI 2.41–4.06) reduction in systolic BP and a 2.24 mmHg (95% CI 1.61–2.96) reduction in diastolic BP. 55

Despite the strong positive association between dietary sodium intake, BP and risk of hypertension, the associations of sodium intake with risk of CVD, CKD, and mortality are inconsistent. 55 Some studies have found a positive association between dietary sodium intake and these clinical outcomes, whereas others have found inverse, J-shaped or U-shaped associations. 56 – 65 These conflicting findings can likely be partly explained by methodological limitations, such as systematic and random error in sodium measurements, reverse causality, insufficient statistical power, residual confounding, and inadequate follow-up duration. 55 , 64 , 66 In summary, dietary sodium reduction should be recommended to lower population BP levels and risk of hypertension. More research is needed, however, to determine optimal dietary sodium intake for the prevention of CVD, CKD and mortality.

Low potassium intake

Similar to sodium, considerable regional variation exists in 24-hour urinary potassium excretion (the best available measure of potassium intake) with the highest levels in Europe (e.g., Finland 2,995 mg, Netherlands 2,835 mg, Germany 2,825 mg, Belgium 2,618 mg, and Spain 2,629 mg) and South America (e.g., Brazil 2,940 mg, and Colombia 2,803 mg), and the lowest levels in Asia (e.g., China 1,249 mg and Japan 1,792 mg) and Africa (e.g., Kenya 1,306 mg and Zimbabwe 1,466 mg). 67 , 68 Observational epidemiological studies have reported an inverse association of dietary potassium intake with BP levels and hypertension. In the Intersalt study, a 50 mmol per day higher level of urinary potassium excretion was associated with a 3.4 mmHg (95% CI 1.5–5.2) lower level of systolic BP and 1.9 mmHg (95% CI 0.7–3.0) lower level of diastolic BP after adjustment for important confounding factors, including age, sex, BMI, alcohol consumption, and urinary sodium excretion, and correction for regression dilution bias. 69

Randomized clinical trials have shown that potassium supplementation lowers BP in hypertensive and normotensive individuals. 70 – 73 In a meta-analysis of 33 randomized controlled trials with 2,609 participants, potassium supplementation was associated with significant reductions in mean systolic and diastolic BP of 3.11 mmHg (95% CI 1.91–4.31) and 1.97 mmHg (95% CI 0.52–3.42), respectively. 71 In 31 trials with urinary potassium measurements, the median net increase in potassium excretion in the potassium supplementation group versus the control group was 50 mmol per day; in 21 (68%) of these trials, the net difference in potassium excretion was ≥40 mmol per day. 71 The effects of potassium supplementation seemed to be greater in black individuals and in those eating a high sodium diet. An AHRQ meta-analysis that included 18 randomized controlled trials also reported that potassium supplementation was associated with a significant reduction in systolic (6.43 mmHg; 95% CI 1.80–11.1) and diastolic BP (3.50 mmHg; 95% CI 0.89–6.10). 55 Increasing potassium intake, especially from fruits and vegetables, is therefore recommended for the prevention and treatment of hypertension. 14 , 43

Alcohol consumption

Globally, alcohol consumption varies considerably, with the lowest consumption in North African and the Middle East (most countries <1 L per-capita annually), and the highest consumption in Central and Eastern Europe (many countries >12 L per-capita annually). Global annual alcohol consumption increased from 5.9 L per-capita in 1990 to 6.5 L in 2017. 74 Numerous observational epidemiologic studies have reported that high alcohol consumption is a risk factor for elevated BP. 75 , 76 The Atherosclerosis Risk in Communities Study reported a J-shaped association between alcohol consumption and risk of hypertension. 76 Light to moderate alcohol drinkers were at lower risk of incident hypertension than nondrinkers, whereas heavy drinkers were at higher risk than both light to moderate drinkers and nondrinkers. This pattern was observed in all race and gender groups except for black men, for whom risk was similarly elevated in light to moderate and heavy drinkers compared to nondrinkers. 76 In a large prospective cohort study of over 500,000 Chinese adults, however, self-reported usual alcohol intake and genotype-predicted alcohol intake were both positively and linearly associated with BP. Genetic epidemiological data showed that the observed protective effects of moderate alcohol intake against hypertension and CVD were largely non-causal. 77

A meta-analysis of 15 randomized control trials with a total of 2,234 participants reported that a reduction in alcohol intake (median: 76%, range: 16%–100%) was associated with significant reductions in mean systolic BP (3.31 mmHg, 95% CI 2.52–4.10) and diastolic BP (2.04 mmHg, 95% CI 1.49–2.58). 78 A dose-response relationship was observed between mean percentage reduction in alcohol intake and mean reduction in BP. Moreover, the effects of reducing alcohol intake on BP were enhanced in those with higher BP at baseline. A recent meta-analysis of 36 trials with 2,865 participants showed that a reduction in alcohol intake was not associated with a significant reduction in BP in individuals who drank two or fewer drinks per day. However, a 50% reduction in alcohol intake was significantly associated with a 5.50 (95% CI 4.30 to 6.70) mmHg lower systolic BP and a 3.97 (3.25 to 4·70) mmHg lower diastolic BP in participants who drank six or more drinks per day. 79 These findings suggest that reducing alcohol intake should be recommended as an important component of lifestyle modification for the prevention and treatment of hypertension in people who are heavy drinkers.

Lack of physical activity

Global age-adjusted prevalence of insufficient physical activity (less than 150 min of moderate-intensity, or 75 min of vigorous-intensity physical activity per week, or any equivalent combination of the two) was 27.5% with a higher prevalence in women (31.7%) than in men (23.4%). The highest levels were in women in Latin America and the Caribbean (43.7%), south Asia (43.0%), and high-income Western countries (42.3%), whereas the lowest levels were in men from Oceania (12.3%), east and southeast Asia (17.6%), and sub-Saharan Africa (17.9%). Prevalence of insufficient physical activity was much higher in urbanized populations in high-income countries. 80

Epidemiological studies have reported an inverse relationship between physical activity, BP and hypertension. 81 Even modest levels of physical activity (such as walking to work) are associated with a decrease in the risk of incident hypertension. 82 Randomized controlled trials and meta-analyses have demonstrated that physical activity lowers BP in hypertensive and normotensive individuals. 83 – 85 For example, a meta-analysis of 54 randomized controlled trials with 2,419 participants reported that aerobic exercise was associated with a significant reduction in mean systolic BP of 3.84 mmHg (95% CI 2.72–4.97) and diastolic BP of 2.58 mmHg (95% CI 1.81–3.35). 83 Aerobic exercise-induced BP reductions were consistent in hypertensive and normotensive participants and in overweight and normal-weight participants. These findings indicate that physical activity is an effective lifestyle intervention for the prevention and treatment of hypertension.

Overweight and obesity

The prevalence of obesity has increased rapidly worldwide over the past several decades. From 1975 to 2014, global age-standardized prevalence of obesity increased from 3.2% to 10.8% in men, and from 6.4% to 14.9% in women. During the same period, global age-standardized mean body mass index (BMI) increased from 21.7 kg/m 2 to 24.2 kg/m 2 in men and from 22.1 kg/m 2 in 1975 to 24.4 kg/m 2 in women. BMI varied significantly by world region, from 21.4 kg/m 2 in central Africa and south Asia to 29.2 kg/m 2 in the Pacific Islands for men and from 21.8 kg/m 2 in south Asia to 32.2 kg/m 2 in the Pacific Islands for women in 2014. 86

Epidemiological studies have consistently identified a direct relationship between BMI and BP that is continuous and almost linear, with no evidence of a threshold. 87 , 88 The relationship between BP and waist-to-hip ratio or computed tomographic measures of central fat distribution is even stronger than the relationship between BP and BMI. 89 Attributable risk estimates from the Nurses’ Health Study suggest that obesity is responsible for about 40% of hypertension 80 , whereas the Framingham Offspring Study suggested that obesity is responsible for 78% of hypertension in men and 65% of hypertension in women. 90 , 91 In a meta-analysis of 25 randomized controlled trials with 4,874 participants, a net reduction in body weight of 5.1 kg (95% CI 4.25–6.03) owing to calorie restriction, increased physical activity, or both, reduced systolic BP by 4.44 mmHg (95% CI 2.95–5.93) and diastolic BP by 3.57 mmHg (95% CI 2.25–4.88). BP reductions were 1.05 mmHg (95% CI 0.66–1.43) systolic and 0.92 mmHg (95% CI 0.55–1.28) diastolic when expressed per kilogram of weight loss. 92

Unhealthy diet

In addition to sodium and potassium, several macronutrients are associated with BP, including dietary fiber, 93 , 94 protein, 95 , 96 and fat. 97 , 98 The Global Burden of Diseases Nutrition and Chronic Diseases Expert Group examined two different dietary patterns worldwide: one based on relatively high consumption of ten healthy items (fruits, vegetables, beans and legumes, nuts and seeds, whole grains, milk, total polyunsaturated fatty acids, fish, plant omega-3s, and dietary fiber); and another based on relatively low consumption of seven unhealthy items (unprocessed red meats, processed meats, sugar sweetened beverages, saturated fat, trans fat, dietary cholesterol, and sodium). Diets and their trends were very heterogeneous across world regions. For example, both types of dietary patterns improved in high-income countries but worsened in some low-income countries in Africa and Asia. Middle-income countries showed the largest improvement in dietary patterns based on healthy items but the largest deterioration in dietary patterns based on unhealthy items. 99

The efficacy of dietary interventions for blood pressure lowering has been investigated in randomized controlled trials. For example, in the DASH trial, 459 adults with systolic BP <160 mmHg and diastolic BP of 80–95 mm Hg were randomly assigned to 8 weeks of a control diet low in fruits, vegetables, and dairy products with a fat content typical of the average diet in the US, a diet rich in fruits and vegetables or a DASH diet rich in fruit, vegetables and low-fat dairy products with a total fat and saturated fat content lower than the typical US diet. 100 Sodium intake and body weight were maintained at constant levels. Compared to the control diet, the DASH diet significantly reduced systolic and diastolic BP by 5.5 mmHg and 3.0 mmHg (both P<0.001), respectively, whereas the fruit and vegetable diet reduced systolic and diastolic BP by 2.8 mmHg (P<0.001) and 1.1 mm Hg (P=0.07), respectively. In participants with hypertension, the DASH diet reduced systolic and diastolic BP by 11.4 mmHg and 5.5 mmHg compared with the control diet (both P<0.001). The DASH diet was also effective in reducing BP in normotensive participants, but the BP reductions were smaller than those seen in hypertensive participants [(3.5 mmHg (P<0.001) and 2.1 mmHg (P=0.003) compared with the control diet]. 100 These data indicate that the DASH diet provides an effective nutritional approach to prevent and treat hypertension.

Vegetarian and Mediterranean dietary patterns are also associated with BP reduction. 101 , 102 A meta-analysis of 7 randomized controlled trials with a total of 311 participants reported that vegetarian diets (defined as diets that never or rarely included meat) were associated with a mean reduction in systolic BP of 4.8 mmHg (95% CI 3.1–6.6) and diastolic BP of 2.2 mmHg (95% CI 1.1–3.5). 101 Mediterranean diets are characterized by moderate fat intake (primarily from olive oil and nuts), low consumption of red meat, and high consumption of vegetables. 102 A meta-analysis of 6 trials with a total of 2,650 participants reported a modest but significant reduction in systolic BP of 1.7 mmHg (95% CI 0.1–3.4) and diastolic BP of 1.5 mmHg (95% CI 0.8–2.1) in Mediterranean diets compared to low-fat diets. 102

In summary, numerous lifestyle risk factors are associated with BP levels and hypertension. These risk factors vary by world region and this heterogeneity likely underlies some of the disparities in hypertension trends and prevalence worldwide. Lifestyle interventions that target these risk factors could therefore play an important role in reducing global disparities in hypertension. 22 Implementing lifestyle interventions in HICs has contributed to reductions in hypertension prevalence and BP levels. 43 However, there is limited data on implementing lifestyle intervention programs in LMIC communities.

Other potential risk factors

Several other potential risk factors for hypertension have been proposed, including cigarette smoking, air pollution, psychological stress, sleep disorders and noise exposure. 103 – 114 Cigarette smoking has been shown to be associated with an immediate acute increase in BP, mainly through stimulation of the sympathetic nervous system. 103 , 104 , 107 However, its long-term effects on BP and incidence of hypertension are inconclusive. 107 , 108 , 115 Several prospective cohort studies have reported a weak positive association between cigarette smoking and risk of hypertension. For example, in 13,529 men from the Physicians’ Health Study, former and current smoking were significantly associated with an 8% (RR 1.08, 95% CI 1.01 to 1.15) and 15% (RR 1.15, 95% CI 1.03 to 1.27) increase in the risk of incident hypertension, respectively, compared with never smoking over a median follow-up of 14.5 years. 107 In a prospective cohort study of 28,236 women from the Women’s Health Study, multiple-adjusted hazard ratios of developing hypertension among former smokers and current smokers of 1–14 and ≥15 cigarettes per day were 1.03 (95% CI 0.98 to 1.08), 1.02 (95% CI 0.92 to 1.13), and 1.11 (95% CI 1.03 to 1.21), respectively, compared to never smokers. 108 However, direct causality between cigarette smoking and hypertension cannot be established because cessation of chronic smoking does not lower BP. 116

The association between exposure to ambient air pollutants and risk of hypertension has been investigated in epidemiological studies. 109 , 110 A meta-analysis that examined the effects of a 10 μg/m 3 increase in exposure to air pollutants on hypertension, reported that short-term exposure over several days to sulfur dioxide (OR=1.046, 95% CI 1.012–1.081), particulate matter with a diameter of ≤2.5 μm (PM 2.5 ) (OR=1.069, 95% CI 1.003–1.141), and particulate matter with a diameter of ≤10 μm (PM 10 ) (OR=1.024, 95% CI 1.016–1.032) were all significantly associated with hypertension (based on data from 7 studies). 109 Long-term exposure over years to nitrogen oxide (OR=1.034, 95% CI 1.005–1.063) and PM 10 (OR=1.054, 95% CI 1.036–1.072) were also significantly associated with hypertension (based on data from 11 studies). These results suggest that short-term and long-term exposure to air pollutants might increase the risk of hypertension. Future studies are needed to assess the impacts of chronic exposure to air pollution on global disparities of hypertension. 117 , 118

Psychosocial stress and rotating shift work have also been reported to be associated with risk of hypertension. 111 , 112 In a meta-analysis of two observational studies with 622 participants, mental stress was associated with an increased risk of hypertension (OR 2.40, 95% CI 1.65–3.49, p < 0.001). 111 However, a meta-analyses of 15 trials with 902 participants testing the effects of different stress-reduction techniques, such as biofeedback, relaxation or combined interventions, on BP concluded that the benefit of stress reduction on BP remains unproven. 119 The meta-analysis identified methodological shortcomings in these trials and significant heterogeneity of BP changes: from −12 to 10 mmHg for systolic and from −10 to 1 mmHg for diastolic. In addition, a meta-analysis of 9 cohort studies with a total of 172,824 individuals reported a pooled OR of hypertension in shift workers of 1.31 (95% CI, 1.07–1.60). 112 In addition, ambient noise from road, rail, and air traffic has a modest association with hypertension prevalence but not incidence in cohort studies. 113 , 114 An inconsistent relationship between sleep duration and risk of hypertension has also been reported. 105 Obstructive sleep apnea is a very common risk factor for hypertension, and continuous positive airway pressure was shown to reduce systolic BP by 2.46 mm Hg (95% CI 0.62–4.31) and diastolic BP by 1.83 mm Hg (95% CI 0.61–3.05) in a meta-analysis of 16 randomized clinical trials with 818 participants. 106

In summary, observational studies have reported weak or moderate associations between these potential risk factors (i.e., cigarette smoking, air pollution, psychological stress, sleep disorders and noise exposure) and risk of hypertension. However, there is insufficient evidence from randomized clinical trials to support causal relationships between these potential risk factors and risk of hypertension. Overall, the currently available data suggest that these potential risk factors have limited effect on BP in the general population.

HYPERTENSION CONTROL IN THE COMMUNITY

As discussed above, antihypertensive treatment and lifestyle modifications have been shown to lower BP and CVD risk in randomized clinical trials. 30 , 31 , 120 , 121 Despite these effective interventions, hypertension control remains unacceptably low, particularly in LMICs. 3 The most recent global estimates suggest that in 2010, only 45.6% of people with hypertension were aware of their condition, only 36.9% were receiving treatment, and only 13.8% had achieved BP control (defined as systolic BP <140 mmHg and diastolic BP <90 mmHg. 3 Moreover, HICs had approximately twice the proportion of hypertension awareness and treatment and four times the proportion of hypertension control than that of LMICs, in which the proportion of BP control was only 7.7% in 2010. 3 Between 2000 and 2010, HICs experienced substantial improvements in the proportions of hypertension awareness, treatment, and control. In the same period, awareness and treatment increased much more modestly in LMICs and the proportion of patients with hypertension and controlled BP decreased slightly ( Table 3 ). 3 Similar patterns were observed in the baseline data from the PURE study in which hypertension awareness, treatment, and control were lower in communities in low-income countries (LICs) than in those in HICs. 11

Hypertension control in high income and low and middle income countries in 2000 and 2010

Large-scale screening programs in communities or health facilities could be an effective way to address the lack of BP awareness in LMICs. For example, May Measurement Month (MMM) 2017 was a BP screening program aimed at raising global awareness of hypertension. 122 The MMM 2017 program screened over 1.2 million individuals in 80 countries who had not had their BP measured in the past year and found that 34.9% had hypertension, 17.3% of those with hypertension were not receiving treatment, and 46.3% of those with hypertension who were receiving treatment did not have controlled BP (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg). This program demonstrated that BP screening in convenience samples can be cost-effective and can identify large numbers of individuals who could benefit from initiation or enhancement of antihypertensive treatment. 122

Barriers to hypertension control exist at multiple levels: patients, healthcare providers, health systems, and communities. 123 – 125 A meta-analysis of randomized controlled trials that assessed the comparative effectiveness of 8 implementation strategies for BP control in patients with hypertension found that multilevel, multicomponent strategies were most effective for systolic BP reduction. 125 These multicomponent strategies included team-based care with medication titration by a nonphysician mean change −7.1 mmHg, 95% CI −8.9 to −5.2 mmHg]), team-based care with medication titration by a physician (−6.2 mmHg 95% CI, −8.1 to −4.2 mmHg), and multilevel strategies without team-based care (−5.0 mmHg, 95% CI, −8.0 to −2.0 mmHg). Patient-level strategies resulted in systolic BP reductions of −3.9 mmHg (95% CI, −5.4 to −2.3 mm Hg) for health coaching and −2.7 mmHg (95% CI, −3.6 to −1.7 mm Hg) for home BP monitoring. Similar trends were reported for diastolic BP reductions. Strategies that targeted provider-level barriers only, including provider training, audit and feedback, and electronic decision support systems, did not result in significant BP reductions.

Most trials of implementation strategies to overcome barriers to BP control have been conducted in HICs. Whether the same strategies will be effective in LMICs is unclear. A cluster-randomized trial published in 2017 showed that a multifaceted intervention, which included a community health worker-led home intervention (health coaching, home BP monitoring, and BP audit and feedback), a physician intervention, and a text-messaging intervention over 18 months, significantly lowered systolic BP by 6.6 mmHg (95% CI, 4.6–8.6; P <0.001) and diastolic BP by 5.4 mmHg (95% CI, 4.0–6.8 mmHg; P <0.001) in low-income patients in Argentina. 126 This trial indicated that a community health worker-led multifaceted intervention was effective for improving patients’ adherence to antihypertensive medication and physicians’ adherence to clinical guidelines resulting in a significant reduction in BP and an increase in hypertension control among low-income patients with hypertension. Widespread scale-up of this proven effective intervention in LMICs should result in a substantial reduction in uncontrolled hypertension and related CVD and premature death.

Increased use of out-of-office BP measurements for confirmation of hypertension diagnosis and titration of antihypertensive medications could also play an important role in improving BP control. A meta-analysis of 11 prospective cohort studies showed that ambulatory BP measurements (ABPM) predicted long-term CVD outcomes independently of office BP (hazard ratio range, 1.28 to 1.40). 127 An international pooling project with 11,135 participants reported that higher 24-hour and night-time BP measurements using ABPM were significantly associated with greater risks of death and CVD outcomes after adjustment for office BP. 128 However, the incremental improvement in predictive values of clinical outcomes with these measurements compared with office BP was small. Adding 24-hour or nighttime systolic BP to base models that included other BP measures resulted in incremental improvements in the area under the curve (AUC) of 0.0013 to 0.0027 for mortality and 0.0031 to 0.0075 for CVD. 128 However, base models that included single systolic BP measure already had an AUC of 0.83 for mortality and 0.84 for CVD. Home BP measurements (HBPM) are a more economical option than ABPM and are a useful strategy to overcome patient-level barriers to BP control by empowering patients. 129 Use of self HBPM resulted in a significant reduction in systolic and diastolic BP among patients with hypertension in randomized clinical trials. 125 , 130 Out-of-office BP measurements are recommended for diagnostic confirmation to avoid white coat hypertension and masked hypertension and for optimal titration of medications to overcome therapeutic inertia. 130

The prevention and control of hypertension in communities requires a life-course approach. 131 Epidemiological studies have shown that elevated BP in childhood promotes subclinical organ damage (i.e. early vascular ageing) and leads to increased risk of hypertension, CVD, and CKD later in life. 132 – 134 To reduce BP-related risks of CVD, CKD, and premature death over the lifespan, preventive efforts should start in early childhood. Innovative strategies for early detection and optimal treatment of hypertension, such as a multifaceted intervention approach, should be implemented in communities to reduce the burden of this condition.

THE FINANCIAL BURDEN OF HYPERTENSION

Hypertension is associated with a substantial financial burden. Costs include direct healthcare expenditures associated with BP management, such as medications, laboratory tests, and clinic visits, as well as costs associated with hospitalizations for BP-related complications and indirect costs associated with lost productivity resulting from premature mortality and disability owing to hypertension-related cardiovascular and kidney diseases. 135 The global financial burden of high BP in 2001 was estimated to be around 370 billion US dollars or about 10% of the world’s overall healthcare expenditure. 135 However, large regional variations in healthcare costs were observed. For example, high BP accounted for 22.6% of all healthcare expenditures in Eastern Europe and Central Asia but only 7.2% in East Asia and Pacific. 135 To the best of our knowledge, no more recent estimates of the global financial burden of hypertension are available.

More recent national and regional estimates of the financial burden of hypertension are available for some HICs, although they are not always consistent owing to methodologic differences. 136 – 139 A study that used a nationally representative database, the Medical Expenditure Panel Survey, estimated that the average annual adjusted incremental expenditure for patients with hypertension was $1,920 higher compared to individuals without hypertension in the US between 2003 and 2014. Based on an average annual number of individuals with hypertension in the US (n= 68,420,747) from NHANES during this period, the estimated adjusted annual incremental cost is $131 billion higher for the hypertensive adult population compared with the non-hypertensive population.. 136 Using the same database, another study analyzed changes in medical expenditures associated with hypertension between 2000 and 2013. Estimated annual medical expenditures per person associated with hypertension in 2000–2001 ($1,399) were not significantly different from those in 2012–2013 ($1,494), but annual national spending for patients with hypertension increased significantly from US$58.7 billion in 2000–2001 to US$109.1 billion in 2012–2013, mainly owing to an increase in the number of treated patients. 137 In addition to lower estimates of medical costs per patient, the underestimated prevalence of hypertension in the Medical Expenditure Panel Survey which used self-reported history of hypertension to define hypertension might also contribute to the conservative estimates of medical expenditure for hypertension in this study. 121

Payments for prescription medications account for a large proportion of the medical expenditures associated with hypertension. The cost of hypertension medication expenditures in the US in 2007 was estimated to be $68 billion based on an analysis of data for 21,782 adults (aged ≥18 years) who participated in the Medical Expenditure Panel Survey. 139 A study that used data from the National Hospital Discharge Survey reported that annual costs for hypertension-related hospitalizations in the US increased from $40 billion (5.1% of total hospital costs) during 1979–1982 to $113 billion (15.1% of total hospital costs) during 2003–2006. 138 The American Heart Association projected that by 2030, the direct costs of hypertension in the US population would increase to $200 billion and the indirect costs to $40 billion. 140

In a study of 314, 622 beneficiaries of the medical insurance system in Japan, inpatient medical expenditure attributable to hypertension represented 7.2% and 6.9% of the total medical expenditure for men and 2.8% and 3.8% of the total medical expenditure for women aged 40–54 years and 55–69 years, respectively. 141 Estimates from Mexico suggest that combined direct and indirect costs attributable to hypertension amounted to nearly $2.5 billion in 2007, which was between 6% and 8% of the healthcare budget. 122 The economic burden of hypertension in Mexico grew by 24% between 2010 and 2012, and the total direct and indirect costs of hypertension in 2011 were estimated to exceed $5.7 billion. 123

The financial implications of hypertension in LICs are of particular concern because of the rapid increase in the prevalence and absolute burden of hypertension and the low current and projected healthcare spending in these regions. 4 , 124 In 2016, only 0.4% of global health spending was in LICs even though these countries comprise 10% of the global population. 124 Projections suggest that by 2050, only 0.6% of health spending will occur in countries that are currently classed as LICs although these countries will comprise 15.7% of the global population. 124 Many LICs currently rely on development assistance for health spending from international agencies and private philanthropy, which is primarily focused on infectious diseases and could be less sustainable for chronic disease control. 124 Large-scale studies using standardized methods are needed to improve understanding of the economic costs of hypertension, particularly in LMICs.

In general, interventions are considered to be reasonably cost-effective if they cost less than US$50,000–75,000 per quality-adjusted life year (QALY); however, payers routinely cover treatments that cost >$100,000 per QALY. 145 Several analyses have concluded that all antihypertensive medications are cost effective compared with no treatment (placebo). 146 In a meta-analysis of 14 studies, the incremental cost-effectiveness ratio (ICER) of all antihypertensive medications adjusted to 2015 US dollars was $19,945 per QALY gained. 146 The SPRINT trial reported an ICER of $28,000 per QALY gained for the intensive BP intervention compared to the standard intervention if the treatment effects persisted for the remaining lifetime of the patient. 147 Antihypertensive treatment might be even more cost effective in LMICs than in HICs. For example, treating all adults with hypertension and prior CVD for secondary prevention was projected to be cost saving in China with an ICER in 2015 of Int$9,000 per QALY gained in those with BP ≥160/100 mmHg and Int$13,000 per QALY gained in those with BP ≥140/90 mm Hg. 148 Moreover, patient-centered values, such as health-related quality of life, productivity, severity of disease, and equity, are important to factor into analyses when determining the financial burden associated with hypertension and weighing the costs of prevention and treatment versus the costs associated with BP-related CVD. 149 , 150

FUTURE PERSPECTIVES

Without intervention, the prevalence and absolute burden of hypertension is expected to continue to increase, particularly in LMICs. 3 , 4 , 12 , 13 Consequentially, BP-related cardiovascular and kidney disease will become even greater health and financial burdens worldwide. 2 Economic development and urbanization have resulted in rapid epidemiological and nutrition transitions, i.e., decreasing infant mortality and infectious diseases and increasing life expectancy and chronic diseases, in many LMICs, including China and India. 151 – 153 The prevalence of hypertension is high and increasing in these countries, whereas the rates of awareness, treatment and control are low. 3 , 20 Lifestyle risk factors for hypertension, such as obesity, high dietary sodium intake, low dietary potassium intake, alcohol consumption, lack of physical activity and unhealthy diet have reached epidemic proportions in LMICs. 154 , 155 National programs for the prevention, detection, and treatment of hypertension in LMICs are needed to slow and reverse the current trends in the hypertension epidemic. In addition, community-based intervention programs are needed to reduce health disparities and improve hypertension prevention and control in low-income and ethnic minority populations in HICs. 42 To accurately estimate the global burden of hypertension, worldwide prevalence surveys using standardized methodology for sampling of participants, BP measurement, and data quality control and analysis are needed, especially in under-represented regions. 3 Research to develop and test the effective, equitable, and sustainable interventions for implementing evidence-based clinical guidelines and public health policies worldwide are critically important for reducing the global burden of hypertension. 3

CONCLUSIONS

Although the estimated global mean BP appears to be fairly stable, the prevalence and absolute burden of hypertension is increasing globally, especially in LMICs. In 2010, an estimated 1.39 billion adults worldwide had hypertension of whom 1.04 billion were in LMICs and 349 million in HICs. 3 Elevated BP is strongly, independently, and linearly associated with the risk of CVD, CKD, and all-cause mortality. Although effective lifestyle modifications and pharmaceutical treatments are available, proportion of hypertension awareness, treatment, and control are low. Hypertension, therefore, remains a global public health challenge. Few comprehensive assessments of the economic impact of hypertension in global populations exist. It was estimated that the global financial burden of hypertension was about 10% of the world’s overall healthcare expenditures, varying from about 22.6% of all healthcare expenditures in Eastern Europe and Central Asia to 7.2% in East Asia and Pacific. Future studies are warranted to develop multifaceted implementation strategies for hypertension prevention and control, especially in LICs and low-income populations, and to accurately assess the financial burden of hypertension worldwide.

• Hypertension is the leading modifiable risk factor for cardiovascular disease and premature death worldwide.
• The prevalence and absolute burden of hypertension is rising globally, especially in low and middle-income countries (LMICs).
• Awareness, treatment, and control of hypertension are unacceptably low worldwide, particularly in LMICs.
• Reductions in risk factors, including high sodium intake, low potassium intake, obesity, alcohol consumption, physical inactivity and unhealthy diet, are recommended for the prevention and control of hypertension.
• Multifaceted implementation strategies for hypertension prevention and control are needed to address barriers at the patient, provider, system, and community levels.
• Comprehensive assessments are needed to evaluate the economic impact of hypertension worldwide.

Acknowledgements

The authors’ work is supported by the National Institute of General Medical Sciences of the National Institutes of Health (NIH) under Award Number P20GM109036 and by the National Heart, Lung, and Blood Institute of NIH under Award Number R01HL133790. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH.

Glossary of Terms

Competing interest statement

The authors declare no competing interests.

• Open access
• Published: 07 August 2021

Prevalence of hypertension in Ghanaian society: a systematic review, meta-analysis, and GRADE assessment

• Fidelis Atibila 1 ,
• Gill ten Hoor 2 ,
• Emmanuel Timmy Donkoh 3 ,
• Abdul Iddrisu Wahab 4 &
• Gerjo Kok 5  

Systematic Reviews volume  10 , Article number:  220 ( 2021 ) Cite this article

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Hypertension has become an important public health concern in the developing world owing to rising prevalence and its adverse impact on ailing health systems. Despite being a modifiable risk factor for cardiovascular disease, hypertension has not received the needed attention in Ghana as a result of various competing interests for scarce health resources. This systematic review and meta-analysis provides a comprehensive and updated summary of the literature on the prevalence of hypertension in Ghana.

Major databases such as MEDLINE, EMBASE, and Google Scholar and local thesis repositories were accessed to identify population-based studies on hypertension among Ghanaians. Data extracted from retrieved reports were screened independently by two reviewers. The quality of eligible studies was evaluated and reported. A reliable pooled estimate of hypertension prevalence was calculated utilizing a random-effects model and reported according to the GRADE framework. Additionally, a meta-regression analysis was performed to analyze the contribution of study-level variables to variance in hypertension prevalence.

In general, a total of 45,470 subjects ( n  = 22,866 males and 22,604 females) were enrolled from urban ( n  = 12), rural ( n  = 8), and mixed populations ( n  = 7). Blood pressure (BP) was measured across studies according to a validated and clinically approved protocol by trained field workers or healthcare workers including nurses and physicians. A combined total of 30,033 participants across twenty studies reporting on the population prevalence of hypertension were pooled with 10,625 (35.4%) identified to satisfy study criteria for elevated BP. The pooled prevalence across 24 studies was 30.3% (95% CI 26.1–34.8%) after fitting a random effects model. Prevalence of hypertension was 30.1% (95% CI 25.6–36.0%) among females and 34.0% (95% CI 28.5–40.0%) among males. Significant differences in pooled estimates across regions emerged from subgroup comparisons of regional estimates with an increasing trend in the north-to-south direction and with increasing age. Compared to rural settings, the burden of hypertension in urban populations was significantly higher. Age structure and population type accounted for 65.0% of the observed heterogeneity in hypertension estimates.

Conclusions

The prevalence of hypertension in Ghana is still high. The gap in hypertension prevalence between rural and urban populations is closing especially in elderly populations. These findings must claim the attention of public health authorities in Ghana to explore opportunities to reduce rural hypertension.

Systematic review registration

The protocol for this review has been published previously with PROSPERO ( CRD42020215829 ).

Peer Review reports

Introduction

Hypertension or elevated blood pressure (BP) represents a significant cause of avoidable cardiovascular debility and early death in less-developed countries with inadequately resourced healthcare systems [ 1 , 2 ]. Suboptimal control of BP in the growing hypertensive population is a major contributory factor to the rising burden of non-communicable diseases (NCDs) in low- and middle-income countries [ 3 , 4 ]. Whereas hypertension is a well-known cause of cardiovascular disease and related deaths in the advanced nations, the importance of hypertension in low-resource health settings is less emphasized but believed to be on the ascendancy [ 1 , 5 , 6 , 7 ]. In developing nations, healthcare resources are stretched by a double burden of communicable diseases such as malaria, HIV AIDS, and tuberculosis and non-communicable diseases such as hypertension and diabetes [ 8 ]. In spite of this double burden of diseases, a disproportionate fraction of health resources is allotted to combat and prevent infectious diseases, leaving little to invest in interventions to prevent non-communicable diseases [ 9 ].

In Ghana, available records indicate that hypertension prevalence has been rising with the spate of rural–urban migration and associated changes to lifestyle and dietary choices [ 10 , 11 ]. A number of factors such as positive perception of obesity, more sedentary lifestyles, excessive consumption of high-calorie diets, genetic predisposition, high intake of salt, and increasing life-expectancy have been cited for this disturbing trend [ 12 , 13 ]. Without urgent attention, the current epidemic of hypertension in the country is expected to worsen [ 14 ].

From an adult hypertension prevalence of less than 5% a generation ago, currently, approximately 50% of all adults have hypertension [ 15 ]. The incidence of outpatient hypertension in health facilities increased 11-fold from an estimated 60,000 reported cases in 1990 to approximately 700,000 reported cases in 2010 [ 15 ]. Prevalence estimates of hypertension based on population studies range between 19 and 48% depending on the study protocol and diagnostic criteria used to detect hypertension [ 16 , 17 , 18 , 19 ]. Furthermore, close to half of diagnosed hypertension manifest clinical signs of organ damage, as a consequence of late presentation/detection by the existing health system and suboptimal BP control [ 15 , 20 ].

Several attempts have been made in the past decade to better understand the burden of hypertension in Ghana [ 4 , 19 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. These studies extended the scope of preliminary work undertaken in the previous decade and began to dispel popular myths and misconceptions still held from the earliest studies [ 30 , 31 , 32 ]. As a result of their nature, observational studies have several inherent flaws that limit their impact. Systematic reviews have become one way to circumvent these limitations and provide concrete epidemiological data [ 33 ]. The last systematic review focussing exclusively on the prevalence of hypertension in Ghanaians dates back to 2012 [ 34 ]. Since then, a few large continental studies have reported aggregated evidence on a handful of datasets from Ghana [ 8 , 35 , 36 , 37 , 38 ]. Otherwise, population data on hypertension prevalence is sparse. High-quality nationally representative, population-based data on hypertension in the country are needed to monitor trends in disease epidemiology across socioeconomic strata, population demographics, time, and space [ 13 ]. The aim of this review was to identify new observational studies reporting on the prevalence of elevated BP in Ghanaian populations and to consolidate their findings with previous studies to generate high-impact evidence to inform health planning in this setting.

This review was guided by internationally Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for undertaking systematic reviews and the Meta-analyses of Observational Studies in Epidemiology (MOOSE) approach [ 39 , 40 ]. In addition, the protocol for this review has been published previously with PROSPERO (CRD42020215829).

Literature search strategy and terms

The major electronic archives for published research, Medline/PubMed, Web of Science, Embase (via Ovid), CINAHL, and African journals online (AJOL) were queried for publications reporting population estimates of hypertension in Ghana. For grey literature, the authors perused the first 200 results in an advanced Google Scholar search as well as local thesis repositories. In addition, a snowballing technique of scrutinizing bibliographies of all eligible studies was employed to identify additional potential reports. A modified approach with search terms specifying and targeting the defined population, intervention (defined appropriately for non-experimental scenarios), defined outcome of interest, and required setting for studies was used to screen all study titles and abstracts [ 39 ]. Terms specifying the intervention concept were “prevalence”, “proportion”, “survey”, “descriptive”, “cross-sectional”, “cohort”, “longitudinal”, “attributable fraction”, and “incidence”. Outcome of interest was coded in the search strategy as “hypertension”, “blood pressure”, “cardiovascular”, and “cardiometabolic”. Those for the settings were “Ghana” and “Ghanaians”. Search terms were framed with the “OR” and “AND” operators as previously described [ 35 ].

Exclusion and inclusion criteria

The main outcome was the prevalence of elevated BP in the general and various strata of the population. Published articles on studies and follow-up studies published before October 2019 with hypertension, risk factors, management practices, and control in the Ghanaian population as an outcome were eligible for inclusion in this review. An additional search for the period spanning October 2019 to November 2020 yielded an additional 2 studies. Conference abstracts reporting adequately detailed information regarding the population, definition of hypertension, sample size, blood pressure data collection, and a point estimate of hypertension were also included for screening. Population-based studies involving individuals living in Ghana or with well-defined data analysis of Ghanaian cohorts were considered for inclusion. Multicenter studies that include Ghanaian participants were included if there was adequate statistical detail on data pertaining to Ghana. Reports fulfilling inclusion criteria were eligible for the initial screening (Fig.  1 ). Studies that failed to satisfy conditions for inclusion were excluded in this review to prevent impact of related confounding variables. These included case reports, reviews, expert commentaries, and data on Ghanaians living in foreign territories. Although reviews were not included in this work, a manual search of references found in review articles was performed. Additionally, the findings of this work were compared to previous work and in order to build upon existing knowledge. Clinical studies reporting on organ-specific elevated blood pressure such as pulmonary hypertension and studies that were based on hospitalized patients, pregnant women, or utilized hospital-based sampling protocols were excluded on grounds that they do not adequately represent the national population. Studies that did not report absolute population or sub-population estimates on hypertension were further excluded from the quantitative synthesis or meta-analysis.

Flow diagram illustrating sequence of important actions

Selection of studies

Citations returned in the database query were imported to Mendeley Desktop 1.19.4, and duplicate reports from multiple sources were identified and removed. The titles and abstracts of articles returned in database queries using the above search strategy were accessed and pre-screened by two co-authors who worked independently to flag non-suitable or extraneous reports for exclusion. Subsequently, full-text reports of the pre-screened and promising studies were accessed and perused by two co-authors who worked independently to ascertain conformity to stated inclusion criteria. A checklist was used for this purpose. Only articles published in the English language were considered. Detected discrepancies in the outcome of independent screening was resolved by consensus of reviewers. Relevant information from selected studies was extracted into a standardized Microsoft Excel template. In accordance with the PRISMA guidelines, the basis for excluding any article during the extensive screening stage was documented and reported (see Additional file 1 ) [ 40 ].

Data extraction

Relevant data was retrieved from selected full-text manuscripts using a standardized extraction form [ 35 ]. Details of publication such as manuscript title, author names, date of publication, digital object identifiers (DOIs), and other vital variables were extracted. In addition, informative variables such as study size, target population, time period of data collection, geographical location, study objective, eligible participants, and other elements of design were captured into format. Furthermore, explanatory and outcome variables, details of data analysis, and the major findings were retrieved as well. Additional data on participant sociodemographic characteristics, anthropometrics, and blood pressure measurement protocols were also extracted. The overall prevalence as well as age-specific prevalence based on the classification of hypertension were of interest. In instances of replicate data reporting affecting the same study population and setting, relevant information was retrieved from the most informative manuscript(s). All such reports were regarded as one unique study report. Also, in such instances, the earliest year of publication was reported.

Definition of hypertension and classification

Studies were scrutinized for and organized according to compliance to the JNC VII criteria which defines elevated BP or hypertension as having either a systolic BP greater or equal to 140 mmHg or concurrent with a diastolic BP greater or equal to 90 mmHg or prescription use of antihypertensive medication [ 41 ]. The three grades of hypertension were all reported as one category: hypertension.

Appraisal of selected studies for risk

All studies were appraised for potential risk of bias according to a suitably validated tool [ 42 ]. The tool concerns itself with assessments of both the internal and external validity of reports from cross-sectional studies. Two independent assessors conducted this appraisal and scored the manuscripts as high, low, or very low for bias based on the presence or absence of each construct being assessed. Specific issues probed included whether participants were adequately representative of the defined population, randomly sampled, and were drawn from an adequate sampling frame with low non-response bias (external validity). Internal validity was assessed from impressions about instrument reliability and validity, uniform administration of instrument, definition of hypertension, primary data collection, and exposure bias. All disagreements were resolved by discussion and regular consultations with more experienced team members. Reports with scanty detail were classified as “limited,” and the primary investigators were contacted for particular information.

Meta-analysis procedures: data analysis

Meta-analysis was conducted in the R computing software using the “meta” package [ 43 , 44 ] (Additional file 2 ). A random intercept logistic regression model, which is a form of generalized linear mixed model (GLMM), was utilized to estimate pooled estimates of hypertension prevalence in Ghana based on available studies [ 45 ]. The proportion of hypertensive individuals in each study was transformed using the logit transformation in order to stabilize the variances of the prevalence estimates. The choice of the logit transformation was made after a thorough review and consideration of the merits and demerits of the various transformation methods of proportions, including the arcsine and Freeman-Tukey double arcsine transformations. Schwarzer et al. [ 46 ] recommended “the use of inverse variance method with the arcsine or logit transformations for the meta-analysis of single proportions that require individual study weights, after reporting seriously misleading results in a meta-analysis with very different sample sizes due to problems with the back-transformation of the Freeman-Tukey transformation.” Gender-, age-, and region-specific estimates were presented.

The I 2 statistic is a measure of variability in pooled estimate attributed to heterogeneity of studies while the Q statistic is a check for homogeneity in effect estimates. Higgins and Thompson’s I 2 statistic [ 47 ] and Cochran’s Q statistic [ 48 ] were used to assess heterogeneity between the included studies. Subgroup analysis was performed by BP measurement device, year of publication, nature of study population, region, and geographical location of study site in order to determine whether prevalence of hypertension was modified by subgroup membership.

Meta-regression was performed in R to determine the extent to which study characteristics could explain the heterogeneity among prevalence estimates of hypertension between studies. Codes for the procedure are shown in Additional file 3 . Whereas σ 2 is typically used to represent within study variance, τ 2 is used to represent the between study variance, also called study heterogeneity [ 49 ]. The estimate of τ 2 in meta-regression analysis with covariate in comparison to τ 2 when the covariate is omitted allows for the calculation of the proportion of study heterogeneity explained by the covariate [ 50 ]. Attention was also given to the R 2 value which indicates the percentage of the variance in the dependent variable that the independent variables explain collectively.

Description of selected studies

The database queries returned 381 hits which were screened down to 344 studies after exclusion of duplicates ( n  = 37). An initial screening of titles for relevance narrowed this number down to 132 reports. A further 105 were removed following abstract ( n  = 63) and full manuscript review ( n  = 42) for a number of reasons stated in Fig.  1 . These reasons include false hits, failure to meet eligibility criteria, reporting on secondary data, hospital-based studies involving convenient samples, small sample size, unexpected definition of hypertension or self-reports, systematic reviews or letters to the editor, duplicate analyses on previous samples, and other risks of bias. The remaining 27 eligible reports retained for analysis represent unique population-based studies on Ghanaian subjects conducted from 1977 to 2020.

At the time of compiling this report, new administrative regions of the country were created out of existing ones. To facilitate comprehension among international audiences and avoid confusion in future, the administrative map used here has been given in Fig.  2 . Most of these studies ( n  = 15) were conducted in the Greater Accra ( n  = 8 studies) and the Greater Kumasi ( n  = 8 studies) areas. There were 3 studies from the Upper East, 2 nationwide reports and one international study. In addition, the Bono, Bono East, Eastern, and Volta regions were represented by a study each. Details of the specific locations and identities of these studies are given in Fig.  2 and Additional file 4 . Data collection ranged from 2 to 36 months. The earliest sampling was conducted in 1972 by Pobee et al. [ 30 ], and the latest was from November 2017 by Acheampong et al. [ 51 ]. There were more published studies available in the past decade (2010–2020) than the two decades (1990–2010) prior. A total of sixteen (16) studies were published after year 2010, and eleven (11) studies were published before this year. The year with the most included studies was 2017 with 5 studies.

Regional map of Ghana showing distribution of included studies. *Included in one of two (2) nationwide surveys, one (1) multi-city study, and one (1) international study

All studies included in the review were original articles capturing cross-sectional studies and baseline surveys of prospective studies [ 52 , 53 ]. Hypertension prevalence was reported as a primary outcome in all 24 studies included in the meta-analysis. A number of studies also reported on risk factors ( n  = 15), awareness ( n  = 9), management ( n  = 9), and control ( n  = 9).

Although a number of reports published on the same dataset were identified, all selected studies reported on unique datasets. These clusters of publications emerged from datasets generated by large-scale multinational population-based cardiovascular risk studies such as the modeling epidemiologic transition study (METS) [ 27 , 54 ] and the WHO SAGE project [ 22 , 23 , 55 ]. One study also [ 21 ] reported results from the University of Witwatersrand’s INDEPTH collaboration with the US National Institutes for Health (NIH) [ 56 ] and H3Africa Consortium [ 57 ]. Six study sites in four sub-Saharan African countries, namely, South Africa, Kenya, Ghana, and Burkina Faso, are involved in the African genomics partnership (AWI-Gen) [ 21 ].

Other smaller, localized datasets informing selected studies included the Accra urban poverty project (UPHS) which examined associations between health and developmental indices from urban poor populations in the capital of Ghana [ 53 , 58 ] and the second phase of the Women’s Health Survey (WHSA-2) conducted in Accra [ 52 , 59 , 60 ]. The WHSA was designed to measure the burden of tropical diseases among adult women. Notably, the Time Use and Health Study of Accra (TUHS) [ 61 ] was not selected on account of using 87% of data reported in the WHSA [ 52 ].

In general, a total of 45,470 subjects ( n  = 22,866 males and 22,604 females) enrolled from urban ( n  = 12) and rural populations ( n  = 8), as well as mixed populations ( n  = 7), were captured in this review. Studies from populations designated as mixed covered both urban and rural populations. The definition of “urban” and “rural” given by the original authors were applied. In cases where this was not stated, the entry category used for the location in question in the Ghana Demographic Heath Survey 2010 by the Ghana Statistical Service was used to classify the study. Two studies sampled female subjects exclusively [ 51 , 52 ], and one study reported on males exclusively [ 62 ].

Measurement of blood pressure

In general, BP was measured across studies according to a validated and clinically approved protocol by trained field workers or healthcare workers including nurses and physicians (Additional file 5 ). Mostly, all subjects had their BP readings taken by protocols that were standardized across study sites. Only a handful of studies reported partial fractions of study subjects evaluated for blood pressure. Some studies, per the definition of hypertension given, admitted patients who were on medication into this category [ 63 , 64 ]. Most studies reportedly used the JNC VII criteria which defines elevated BP or hypertension as having either a systolic BP greater or equal to 140 mmHg or concurrent with a diastolic BP greater or equal to 90 mmHg or prescription use of antihypertensives [ 41 ], irrespective of BP [ 28 ]. However, a few studies conducted before this definition was published used the old WHO definition (BP greater or equal 160/95) [ 30 , 65 ]. One study refrained from explicitly providing a prevalence of hypertension but reported the mean systolic and diastolic BP values [ 66 ].

In most studies ( n  = 21), participants were seated during the BP measurement, usually in a quiet place. Two (2) reports had patients in the supine position [ 52 , 67 ], and five (5) did not report on posture. In general, study subjects were required to take at least 5 min rest prior to BP measurement, and in one instance, investigators insisted on avoidance of smoking [ 68 ]. One study reported an initial resting period of 3–5 min [ 21 ].

Half of the selected studies ( n  = 13, 52%), usually the more recent, reportedly used electronic BP monitors. Commonly, models of the Omron digital brand were employed. In addition, the Boso Medistar Wrist BP Monitor Model S and the semi-automated Microlife Watch BP home were also used. Two studies did not specify the BP measurement apparatus used, and up to 10 (40%) included studies also used manual sphygmomanometers. In such cases, the systolic and diastolic BPs were noted to coincide with the first and the fourth or fifth [ 30 , 68 ] Korotkoff phase sounds heard during auscultation, respectively.

The preferred anatomical site for BP measurement was the upper arm. A dozen studies ( n  = 12) indicated using either large or small cuffs depending on which was appropriate for the subject. The Danfa study used a 14-cm large cuff size for all subjects [ 30 ] while the SAGE WAVE 1 used a wrist BP monitor [ 23 ]. BP measurements were performed by teams of trained study staff with varying degrees of experience. Teams were variously constituted with clinical and community health nurses, general field staff/research assistants, allied health workers, and students. Teams were usually supervised by medical officers or research officers. In line with national and international guidelines, most studies measured participant’s blood pressure from the arm, mostly the right upper arm. Minicuci et al. used a device that had to be worn around the wrist to measure the BP. In most cases, participants were seated in a quiet area. Koopman et al. reported blood pressure readings from supine individuals, while Hill et al. had some participants seated and some supine [ 52 ].

Except for four studies [ 20 , 65 , 69 , 70 ], all studies performed one-time BP readings. Studies using BP protocols based on multiple visits performed secondary readings within 24 h [ 65 ], 3 weeks [ 20 ], or 1 month [ 60 ] to confirm an initial BP reading exceeding 140/90 mmHg [ 20 , 60 ]. In Kunutsor et al., BP readings were replicated after 2 weeks for participants ( n  = 89 (16%)) in order to adjust for the phenomenon of regression dilution in BP studies where baseline/initial BP measurements are noted to underestimate the actual BP leading to underestimation of cardiovascular risk [ 69 ]. A regression dilution ratio may be calculated from repeat readings for the purpose of correcting for this error and to estimate the actual BP [ 71 ].

On sampling days, with the exception of one study in which BP was measured a minimum of three times [ 19 ], most studies conducted BP readings up to three times to allow confirmation of elevated BP readings [ 65 , 69 , 72 ]. In general, the intervening time between repeat BP measurements was not less than 1 min but less than 1 h in most studies and up to a full day in one study [ 72 ]. Majority of studies ( n  = 23) reported the nature of BP statistic used in classifying participants. Most studies computed an average BP from two readings [ 20 , 21 , 23 , 26 , 27 , 28 , 51 , 66 , 68 , 69 , 72 , 73 , 74 , 75 ] or three [ 19 , 30 , 53 , 70 , 76 ]. Frequently, studies would discard the initial reading and rely on the mean of the latter readings [ 11 , 20 , 21 , 23 , 73 ] or the fifth and sixth [ 27 ]. One study, Pobee et al. [ 65 ], used only one BP reading with confirmation for high-for-age readings.

Prevalence of hypertension

Reported prevalence estimates on hypertension ranged from a low of 4.5% in a rural population from the Ashanti Region [ 27 ] to a high of 54.3% in adults above 65 years in the same Region [ 70 ]. A combined total of 30,033 participants across twenty studies reporting on the population prevalence of hypertension were pooled with 10,625 (35.4%) identified to satisfy study criteria for elevated BP. A few studies reporting only mean systolic and diastolic BP were excluded from pooled analysis. After fitting a random effects model to 24 representative studies, the composite prevalence of elevated BP in the general population of Ghanaians stood at 30.3% (95% CI 26.1–34.8%) (Fig.  3 ). Two nationwide studies (9195 participants) in adults above 50 years gave rise to a higher pooled estimate of hypertension of 49.5% (46.2–52.7%) [ 23 , 25 ]. The pooled estimate did not change significantly between studies using manual [32.2% (95% CI 26.1–38.9%)] and electronic measuring devices [29.5% (24.5–35.1%)] ( p  = 0.527).

Pooled prevalence of hypertension in Ghana

After fitting a random effects model to 17 exclusive studies with sex-stratified rates, the prevalence of elevated BP was 30.6% (95% CI 25.6–36.0%) among females ( n  = 15 data points) and 34.0% (95% CI 28.5–40.0%) among males ( n  = 16 data points) (Fig.  4 ). In general, hypertension prevalence was higher in males (see Additional file 6 ) [ 19 , 20 , 23 , 26 , 53 , 67 , 70 , 72 , 74 , 76 , 77 , 78 ]. This trend was reversed in two studies which reported narrowly higher hypertension prevalence in females [ 21 , 68 ].

Prevalence of hypertension in males and females

Regionally, hypertension prevalence from studies in the Greater Accra region (30.7%; 95% CI 24.7–37.5%) did not vary significantly from the estimate from the Ashanti Region (29.2%; 95% CI 21.6–37.5%). However, significant differences in pooled estimates across regions emerged from subgroup comparisons of regional estimates in the general population ( p  < 0.001).

Temporal variations in the prevalence estimates were not statistically significant ( p  = 0.624). Two identical studies were published in 2000–2005 with a combined estimate of 28.0% (95% CI 25.9–30.3%) [ 74 , 78 ]. A further six studies were included from the next 5-year period (2006–2010), giving a pooled estimate of 29.3% (95% CI 23.9–35.3%). In the next 5-year window (2011–2015), another 6 published studies gave a pooled estimate of 35.5% (95% CI 24.5–46.1%). Similarly, there was no significant time-trend when the earliest year of sampling was considered instead of the publication year in the random effects model ( p  = 0.829). The pooled estimate for eleven studies conducted in the past decade (2010–2019) was 30.4% (95% CI 24.4–37.2%). For comparison, another eleven studies were conducted before the 2010 population and housing census giving a pooled prevalence of 31.5% (95% CI 25.0–38.9%).

In terms of the developmental indices of populations studied, the highest pooled prevalence of hypertension was seen in studies comprised of a mix of urban and rural dwellers (38.7%; 95% CI 31.4–46.7%). The prevalence of elevated BP in urban populations (31.7%; 95% CI 28.1–35.5%) was significantly higher than in rural populations (23.4%; 95% 18.6–28.9%) (Fig.  5 ). Most of the studies in rural areas were among the general population: just one study in eight recruited participants who are above 50 years [ 67 ] with the potential of skewing the result.

Prevalence of hypertension in rural and urban areas

Prevalence of hypertension increased in the north-to-south direction. The highest prevalence of hypertension was (30.7%; 95% CI 25.8–36.2%) observed for southern Ghana. This was significantly higher than that in the other northern belt 22.9% (95% CI 20.3–25.9%) of Ghana and only marginally higher than that for the middle-belt 30.1% (95% CI 25.4–35.4%).

There was a distinguishable age pattern of hypertension in which prevalence of elevated bp increased with age, peaking in middle-aged individuals [ 51 , 53 , 76 ]. Statistics on the age distribution of participants were extracted to classify studies based on the following criteria: (1) retirees where selection criteria specifying advanced age > 50 or > 65 was used, and (2) senior citizens where the mean ages range from 67.2 to 74.4 years, and (3) studies in the general population with mean ages ranging from 31 to 54.7 years. The pooled prevalence of hypertension from studies focussing on adults was 43.9% (95% CI 36.2–51.9%) while general population studies that recruited younger participants on average gave an estimated prevalence of 27.4% (95% CI 24.5–30.6%). In addition to overall prevalence estimates, some studies also provided age-specific prevalence rates for hypertension. In general, the prevalence of hypertension was always lower in the youngest age group than in the oldest age group [ 51 , 53 , 76 ].

A weighted regression technique was performed to understand systematic differences among studies that potentially explained the heterogeneity between study results (see Additional file 7 ). In univariate analysis, type of study population (rural vs. urban) ( R 2  = 31.4%, p  < 0.05) and age structure of the population ( R 2  = 47.2%, p  < 0.05) accounted for significant variability in the estimated prevalence of hypertension. All other study characteristics were not responsible for significant variation in hypertension prevalence. A multivariate model based on significant determinants of hypertension in preliminary analysis across studies accounted for 65% of the variability in hypertension prevalence across studies ( p  < 0.05).

Risk appraisal of selected studies

A total of 69 full-text articles were perused for eligibility and assessment of bias according to a suitably validated tool [ 42 ]. Available articles were rated as having “low,” “moderate,” “high,” and “very high” risk of bias by consensus of two investigators. The results of this appraisal are presented in supplementary file (Additional file 1 ). Forty-two (42) full-text articles were adjudged to have a very high risk of bias and were discarded, leaving 27 for the meta-analysis. Out of this number, 7 studies [ 23 , 51 , 69 , 70 , 73 , 74 , 76 ] were rated low risk of bias, 18 studies [ 19 , 20 , 21 , 25 , 26 , 27 , 28 , 30 , 52 , 53 , 65 , 67 , 72 , 75 , 77 , 78 , 79 ] were rated moderate risk, and two studies [ 62 , 68 ] were rated high risk of bias.

GRADE assessment of quality of pooled estimate

In terms of quality, the pooled estimate presented here can be adjudged to have a bias rating of 3 + on a scale ranging from 1 + representing an estimate with a low quality and 4 + representing the highest quality. This rating reflects that all the included studies were observational studies. Although some level of bias may arise from the lack of blinding, concealment, and randomization to treatment, selected studies presented adequate sample sizes and simple/systematic random sampling to mitigate bias to moderate levels. In addition, most of the samples were sufficiently representative of the study populations from which they were obtained. In terms of consistency, we assign a low rating based on the elevated I 2 statistic. An elevated I 2 statistic and low Q statistic were indicative of a high proportion of variability in the pooled estimate attributable to heterogeneity of reported estimates. A relatively small confidence interval indicated a moderate level of precision in the effect estimate. In terms of the risk of the influence of publication bias from included studies, after examination of funnel plots and based on the results of Egger’s tests, a moderate level of confidence may be exercised when interpreting the pooled prevalence. The authors have provided subgroup analyses to supplement the interpretation of the pooled prevalence by circumventing some degree of heterogeneity in the composite value.

There is a surge in non-communicable diseases in the developing world, driven by a high prevalence of cardiometabolic risk factors such as hypertension. We have systematically reviewed the available literature on population-based studies in order to present an accurate and updated synthesis on the state of the epidemic in Ghana. The inclusion of a meta-analysis unifies the available literature on hypertension over the longest time span: it includes studies from the 1970s to date conducted in rural and urban settings in both youthful and advanced age groups. A key finding is the high prevalence of hypertension in vulnerable groups such as rural women, urban poor folk, and aged individuals with limited access to healthcare services which has persisted over the last decade in contrast to most regions of the world [ 80 ].

The pooled prevalence of hypertension of 30.3% (95% CI 26.1–34.8%) established in this study coincides with the findings of most studies conducted in the general population of Ghanaians in the past decade [ 51 , 72 , 81 ]. This estimate is higher than estimates reported on the general population of Ghanaians at the beginning of the last decade [ 32 ] and may indicate the worsening in the epidemic of hypertension first recognized and reported by Pobee et al. [ 65 ] and several others much later [ 32 ]. However, it coincides with prevalence of hypertension established for younger adults in Africa or sub-Saharan Africa [ 82 ]. This may be explained by the age dynamics of studies included in the meta-analysis and may reflect general population studies in the region [ 82 ]. An analysis of secondary data from the Ghana demographic and health survey gave the prevalence of hypertension as 13.0% (12.1% for males and 13.4% for females) [ 4 ]. In addition, there was a 22% prevalence of high-risk pre-hypertensives [ 4 ]. The GDHS examined the prevalence of hypertension among Ghanaian’s aged 15–49 years with approximately 90% of participants between 15 and 44 years and mostly women (71%). Exclusion of aged individuals may account for the much lower prevalence.

There have been a few systematic reviews of prevalence studies on hypertension in Ghana [ 32 , 34 , 83 ] and a few nationally representative surveys [ 10 , 23 , 25 ]. According to Bosu, after reviewing 15 unique population-based reports and two academic dissertations, the prevalence estimates ranged from 19 to 48% between studies [ 32 ]. Addo et al. later published a similar review of 11 population-based surveys with an estimated hypertension prevalence of 19.3% in rural areas and 54.6% in urban areas [ 34 ]. Neither of these studies provided a pooled estimate of hypertension making the present study the first to report a pooled prevalence of hypertension in Ghana.

According to study area, the prevalence of hypertension in urban versus rural areas follows the familiar pattern of higher rates of blood pressure and hypertension in urban areas [ 77 ]. However, up to a quarter of rural Ghanaians were estimated to have high blood pressure. There is evidence that the problem of hypertension in rural settings deserves as much attention as in urban settings [ 32 , 77 ]. In a few decades, hypertension has transitioned from being almost unheard of among the rural poor into a genuine public health concern. The principal factors driving this trend need to be investigated. Systemic disparities in healthcare between rural and urban areas are typical in Ghana and need to be addressed. Factors such as shortage of qualified health workforce, low access to care, insurance coverage, and inconsistent supply of medication have been identified [ 84 , 85 ].

An ambiguity in the gender variation in the distribution of blood pressure and prevalence of hypertension has been recognized in most studies in the country and in the sub-region [ 38 ]. This review confirms that in the general population, the prevalence of hypertension may be higher for males compared to females. However, a reversal of this order can be seen in older populations, where females show higher blood pressure on the average [ 35 ]. These variations may reflect differences in obesity between older males and females [ 17 , 24 , 25 ] and may result in a reversal of the trend seen for even younger populations with a high prevalence of female obesity [ 86 ].

During this review, Bosu et al. published a meta-analysis of hypertension in older adults in Africa. The high prevalence of hypertension reported for older adults was confirmed by this study. Furthermore, the detection of higher blood pressure with age is consistent with previous reports [ 4 , 35 , 38 ]. This trend is evident in both the urban and rural settings [ 77 ] and has been attributed to changes in renal sodium metabolism and the renin-aldosterone pathway, oxidative stress resulting in microvascular injury and chronic inflammation, loss of arterial and arteriolar elasticity, suppressed baroreceptor sensitivity, and increased sensitivity to sympathetic nervous system stimuli [ 87 , 88 , 89 ]. Acheampong et al. found a significant age-related trend among a small sample of women in the capital, suggesting that elderly women are not spared. The accumulated data on age-related hypertension supports the assertion that as the life expectancy in Ghana rises, there is the need for practical and effective hypertension management strategies that target the aging population [ 51 ]. However, the large fraction of younger individuals exhibiting high blood pressure warrants equal attention since they are likely to live with the condition long enough to develop complications unchecked.

The spatiotemporal aspects of disease epidemiology have become a topic of interest in recent discourse. We compared studies conducted in the past decade to previous work in an attempt to appreciate trends across time. In consonance with most studies across Africa, the epidemic of hypertension does not seem to have eased up over the past decade [ 80 ]. This has implications for the healthcare system and calls for more innovative and impact-driven public health strategies to curb the trend [ 90 ]. Home-grown strategies that have shown promising results will need to be identified and aggressively scaled up in the general population [ 8 , 14 , 19 , 24 ]. Commonly held myths about the distribution of hypertension in the population need to be dispelled [ 32 ]. The socioeconomic patterning and regional disparities in access to healthcare services will need to be addressed as well.

Strengths and limitations

We have successfully provided a comprehensive update on the prevalence of hypertension from the best available studies providing estimates of hypertension in the general population. This review featured a large number of studies from the population with a good data distribution across all 10 regions of the country, across the longest time span, and across both young and elderly age groups as shown in Fig.  2 . The consolidation of studies with large sample sizes improved the generalizability of findings by making the sample representative of the larger population. In addition, all included studies were assessed for risk of bias. Most studies adopted measures for ensuring the quality of blood pressure measurements such as training of field staff prior to deployment and the use of unified protocols. Adherence to the MOOSE validates the methodology of the meta-analysis against international benchmarks, and the use of the PRISMA approach for reporting standardizes the review process. Furthermore, we have included a GRADE assessment of the quality of evidence provided by the meta-analysis (see Additional file 8 ) [ 91 ].

In spite of these, there are a number of important caveats to bear in mind when interpreting findings enumerated here. By design, the review attracted a number of observational studies reporting on hypertension prevalence in the general population with a few instances of confirmatory screening: the classification of subjects based on a single visit falls short of the recommended protocol for diagnosing hypertension [ 41 ]. It is therefore likely to overestimate the true prevalence of hypertension in the general population by an inclusion of false-positive diagnoses. As has been previously indicated in similar pooled studies [ 12 , 32 , 34 ], there was also evidence of heterogeneity in the pooled estimate, possibly as a result of systematic variations in populations and study protocols [ 82 , 92 ]. This point has been conceded in rating the quality of evidence presented here. Additionally, unlike prospective studies, the absence of participant follow-up reduces the strength of the review for monitoring time-related trends and other changes over time.

Conclusion and recommendations

The results presented in this systematic review indicate that hypertension is an important problem in the country, requiring urgent public health attention. The pooled prevalence of hypertension among the Ghanaian populace was 30.3% or approximately one in every three individuals. Most authors of articles perused were supportive of this conclusion and recommended large-scale intervention to curtail the rising trend of hypertension especially in rural populations. The national health insurance scheme may be relevant in this regard to deal with socioeconomic disparities and providing affordable access to healthcare providers. Also, since hypertension is a known risk factor for cardiovascular complications, measures taken to reduce the level of hypertension will improve quality-of-life for affected individuals and reduce the burden on an already constrained healthcare system. This is especially significant for populations where higher than average prevalence of hypertension was observed such as elderly/senior citizens and urban centers. There was also indication of rising rates in rural areas previously considered to be hypertension safe havens. In general, our findings are corroborated by other reviews and large-scale studies from sub-Saharan Africa.

Availability of data and materials

The data that support the findings of this study are shown in the manuscript or attached as supplementary material. In addition, all data has been lodged with the institutional ethical review board and is fully accessible to the public on reasonable request without the permission of the authors.

Abbreviations

Acquired immune deficiency syndrome

African Journals Online

• Blood pressure

Committee on Human Research, Publication and Ethics, Kwame Nkrumah University of Science and Technology, School of Medical Sciences

Cumulative Index to Nursing & Allied Health

Diastolic blood pressure

Digital object identifier

Generalized linear mixed model

Grading of Recommendations Assessment, Development, and Evaluations

Human Heredity and Health

Human immunodeficiency virus

International Network for the Demographic Evaluation of Populations and Their Health

Joint National Committee

Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

Millennium Development Goals

Modelling the Epidemiological Transition Study

Ministry of Health

Meta-analyses Of Observational Studies in Epidemiology

Non-communicable diseases

Participants, interventions, comparators, and outcomes

Preferred Reporting Items for Systematic review and Meta-Analysis Protocols

International prospective register of systematic reviews

Study on Global Ageing and Adult Health

Systolic blood pressure

Time Use and Health Study

Urban Poverty and Health Study

World Health Organization

Women’s Health Study of Accra

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Acknowledgements

The authors are particularly grateful to authors of included studies for making full text articles available for review and providing additional data when called upon. Special thanks go to Prof. William Kofi Bosu and Prof. Juliet Addo for their contribution to the subject.

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FA, ETD, GH, and GK are credited with conceptualizing the idea for an updated and comprehensive review of the literature on the prevalence of hypertension in the Ghanaian context. FA contributed the foundational draft of the paper, reviewed abstracts and full articles, and retrieved data on studies for data analysis. GH contributed conceptually to the paper and reviewed, effected changes, and provided feedback on all drafts, and also gave approval for submission. ETD contributed conceptually to the paper, reviewed abstracts and full articles, planned and performed statistical analysis with AIW, and approved the final manuscript for submission. GK contributed conceptually to the paper and reviewed and provided feedback on all drafts as well as final approval for submission. AIW contributed conceptually to the paper, carried out statistical analysis, and approved the final version. The author(s) read and approved the final manuscript.

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Supplementary Information

Additional file 1..

Summary of findings table for eligibility assessment of full-text articles retrieved indicating reasons for exclusion.

Additional file 2.

R codes for meta-analysis.

Additional file 3.

R codes for meta-regression.

Additional file 4.

Characteristics of selected studies.

Additional file 5.

Blood pressure measurement protocols from selected studies.

Additional file 6.

Full results of meta-analysis

Additional file 7.

Meta regression output.

Additional file 8.

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Atibila, F., Hoor, G.t., Donkoh, E.T. et al. Prevalence of hypertension in Ghanaian society: a systematic review, meta-analysis, and GRADE assessment. Syst Rev 10 , 220 (2021). https://doi.org/10.1186/s13643-021-01770-x

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Interventions in hypertension: systematic review and meta-analysis of natural and quasi-experiments

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Hypertension is an urgent public health problem. Consistent summary from natural and quasi-experiments employed to evaluate interventions that aim at preventing or controlling hypertension is lacking in the current literature. This study aims to summarize the evidence from natural and quasi-experiments that evaluated interventions used to prevent or control hypertension.

We searched PubMed, Embase and Web of Science for natural and quasi-experiments evaluating interventions used to prevent hypertension, improve blood pressure control or reduce blood pressure levels from January 2008 to November 2018. Descriptions of studies and interventions were systematically summarized, and a meta-analysis was conducted.

Thirty studies were identified, and all used quasi-experimental designs including a difference-in-difference, a pre-post with a control group or a propensity score matching design. Education and counseling on lifestyle modifications such as promoting physical activity (PA), promoting a healthy diet and smoking cessation consultations could help prevent hypertension in healthy people. The use of computerized clinical practice guidelines by general practitioners, education and management of hypertension, the screening for cardiovascular disease (CVD) goals and referral could help improve hypertension control in patients with hypertension. The educating and counseling on PA and diet, the monitoring of patients’ metabolic factors and chronic diseases, the combination of education on lifestyles with management of hypertension, the screening for economic risk factors, medical needs, and CVD risk factors and referral all could help reduce blood pressure. In the meta-analysis, the largest reduction in blood pressure was seen for interventions which combined education, counseling and management strategies: weighted mean difference in systolic blood pressure was − 5.34 mmHg (95% confidence interval [CI], − 7.35 to − 3.33) and in diastolic blood pressure was − 3.23 mmHg (95% CI, − 5.51 to − 0.96).

Conclusions

Interventions that used education and counseling strategies; those that used management strategies; those that used combined education, counseling and management strategies and those that used screening and referral strategies were beneficial in preventing, controlling hypertension and reducing blood pressure levels. The combination of education, counseling and management strategies appeared to be the most beneficial intervention to reduce blood pressure levels.

Cardiovascular diseases (CVD) represent the leading cause of death, accounting for one in three deaths in the United States (US) and worldwide [ 1 , 2 , 3 ]. One of their most potent risk factors, hypertension (also known as high blood pressure), is a common risk factor for CVD [ 3 , 4 ]. Approximately 40% of adults aged 25 and over had elevated blood pressure in 2008 [ 3 ]. What is more, hypertension is responsible for at least 45% of deaths due to heart diseases and 51% of deaths due to stroke worldwide [ 3 , 4 ]. In the US alone, the direct medical and indirect expenses from CVDs were estimated at approximately $329 billion in 2013 to 2014 [ 5 ]. Effective large-scale interventions to prevent or treat hypertension are therefore urgently needed to reverse this trend. Yet, as new and promising interventions are surfacing every day, the need for rigorous evaluation of these interventions to inform evidence-based policies and clinical practice is ever growing.

To this effect, several randomized clinical trials (RCT) have been conducted to evaluate interventions used to prevent hypertension or improve its control [ 6 , 7 , 8 ]. However, although RCTs represent the gold standard for evaluating the efficacy (i.e., impact under ideal conditions) of most health interventions because of their high internal validity [ 9 , 10 ], they are not always feasible, appropriate or ethical for the evaluation of certain types of interventions. Furthermore, results from RCTs are not always generalizable to populations or settings of interest due to the highly selected sample and because the intervention is generally conducted under more stringent conditions ( low external validity ) [ 11 ]. To evaluate the effectiveness of an intervention (i.e., impact under real conditions) and to increase the uptake and implementation of evidence-based health interventions in the communities of interests, other types of experimental designs have been proposed. One such example is natural and quasi-experiments. The terms “natural experiments” and “quasi-experiments” are sometimes used interchangeably. In this study, and as described by others [ 12 ], we will distinguish these two concepts. Natural and quasi-experiments are similar in that, in both cases, there is no randomization of treatments or exposures (i.e., no random assignment). They differ, however, in that, natural experiments are those that involve naturally occurring or unplanned events (e.g., a national policy, new law), while quasi-experiments involve intentional or planned interventions implemented (typically for the purpose of research/evaluation) to change a specific outcome of interest (e.g., a community intervention program). Furthermore, in natural experiments, the investigator does not have control over the treatment assignment whereas in quasi-experiments, the investigator has control over the treatment assignment [ 12 ]. These experiments include difference-in-difference (DID) designs, synthetic controls and regression discontinuity designs to name a few [ 13 , 14 , 15 ].

As utilization of natural and quasi-experiments is increasing in public health and in the biomedical field [ 13 , 14 , 15 ], more natural and quasi-experiments are being conducted to evaluate interventions targeted to prevent or control hypertension [ 16 , 17 , 18 , 19 ]. This could be due to recent development or the reframing of classical approaches for determining causality in natural and quasi- experiments [ 13 , 14 , 15 , 20 ]. However, unlike RCTs of interventions aiming to prevent hypertension or improve its control [ 6 , 7 , 8 ], consistent summary and synthesis of evidence from natural and quasi- experiments is lacking in the current literature. The primary aim of the current systematic review is to summarize the evidence from natural and quasi-experiments that have evaluated interventions used to prevent, control hypertension or reduce blood pressure levels. A secondary aim of this study is to conduct a meta-analysis to summarize intervention effectiveness.

Data sources and strategy

We searched PubMed, Embase and Web of Science from January 2008 to November 2018. This time frame was selected to encompass studies that would have likely benefited from recent development and improvement in natural and quasi- experiments [ 13 , 20 ]. Briefly, the search strategy consisted in intersecting keywords related to the study methods (e.g., natural experiments, quasi-experiments, DID, synthetic control, interrupted time series, etc.) with the environment or settings (e.g., community, nation, organization, etc.) and the outcome (e.g., hypertension, elevated blood pressure, etc.). The full search strategy is described in Table S 1 . This systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement [ 21 ] (Fig. 1 ).

Study search and selection flow

Study selection

Two trained members (TX, FZ) screened abstracts and full-text articles. Disagreements were decided by a third member (RN). We included studies that used natural and quasi-experiments to evaluate interventions aimed at preventing hypertension, controlling hypertension or reducing blood pressure levels. The outcome measures were prevalence of hypertension and changes in mean blood pressure. Studies were excluded if they were not in English, were not a natural experiment or a quasi-experimental design, did not include a control group (as it has higher risk to internal validity due to the absence of comparison to adjust for time trends and confounding) [ 22 ], did not include blood pressure or hypertension as their outcome or included participants that were 13 years old or younger. In addition, we excluded studies that were not original research articles (e.g., study protocol, books, commentary, dissertations, conference proceedings, comments, systematic reviews, modeling and simulation studies), or had no full text available.

Data extraction and quality assessment

The following information was extracted: study design, sample size, study duration, data source, geographic location, participants’ socio-demographic characteristics, intervention types, intervention levels (e.g., individuals, community, school, clinic and national levels as suggested by the socio-ecological model [ 23 ]), behavior targeted and outcome measures (prevalence of hypertension or mean blood pressure change) (Table 1 , Table S 2 ).

The interventions were classified by strategies into four types:

Education and counseling: This subcategory includes strategies that aim at educating and providing knowledge and counseling to participants on lifestyle modifications (e.g., increasing physical activity (PA), eating better, avoiding or stopping smoking, etc.).

Management: This subcategory includes strategies that aim at monitoring patients’ metabolic factors and chronic diseases (e.g., blood pressure, cholesterol level, etc.) as well as patients’ adherence to medication. These strategies are generally done or facilitated by physicians, general practitioners (e.g., by assessing computerized clinical guidelines in the electronic health record management system), nurses, other staffs, or patients themselves.

Education, counseling and management: This subcategory combines education and counseling strategies with management strategies as described above.

Screening and referral for management: This subcategory includes strategies that aim at screening for (i.e., checking for the presence of) economic risk factors, medical needs, and CVD risk factors, followed by the referral of participants who screened positive to professionals who specialize in the management of those needs.

We also classified the interventions by settings into (1) community level; (2) health center level (i.e., primary care center or general practices), (3) organization level and (4) nationwide. In addition, we have classified the intervention by duration of the study into short-term (i.e., participants were followed for less than 12 months) and long-term (i.e., participants were followed for longer than or equal to 12 months).

We implemented the Cochrane Risk of Bias Tool for risk of bias and used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the quality of the evidence for mean blood pressure change outcome [ 50 ], since the meta-analysis focused on this outcome. The risk of bias for studies included in this review could be found in Table S 3 and the quality of studies has also been summarized in Table S 4 .

Meta-analysis

To summarize the effectiveness of interventions on mean blood pressure changes, we also conducted a meta-analysis. Due to the high heterogeneity in the studies and interventions, we undertook a random-effects model and only summarized the effectiveness of intervention strategies by subgroup defined by intervention types, settings and duration. We estimated the weighted mean difference (WMD) of blood pressure and 95% confidence intervals (CIs). The studies included in the meta-analysis were only those whose outcomes were mean differences (MDs) in blood pressure ( n = 27) [ 16 , 19 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ] as these studies provided the data needed for performing the meta-analysis. Three studies [ 38 , 39 , 43 ] were excluded as they did not provide enough information to compute the standard errors (SEs). To estimate the average effect of the intervention when not directly provided, we subtracted the before-and-after change in the intervention group from that in the control group or subtracted the intervention-to-control difference at follow-up to that at baseline (pre-post design with a control group). Methods to calculate intervention impact and SEs were outlined in the appendix (Figs. S 1 , S 2 , Table S 5 ).

We presented the meta-analysis results using forest plots (Table 2 , Fig. 2 , Figs. S 3 , S 4 ). We assessed the heterogeneity by using the I 2 (Table 2 , Fig. 2 , Figs. S 3 , S 4 ). We did not perform meta-regression as it is not recommended when the number of studies is small (< 10 studies per covariate) [ 51 ]. We assessed publication bias by using funnel plots of SEs (Figs. S 5 , S 6 , S 7 ). To test the robustness of our results, we performed sensitivity analyses by removing one study at a time from the pool of studies to assess its impact on the findings (Tables S 6  , S 7 , S 8 , Figs. S 8 , S 9 , S 10 ). Data were analyzed with Stata 15.1 (StataCorp LLC, College Station, TX, USA).

Forest plot stratified by intervention types for blood pressure. A Forest plot stratified by intervention types for systolic blood pressure (SBP). B Forest plot stratified by intervention types for diastolic blood pressure (DBP)

Overall, 788 titles of potentially relevant studies were identified and screened. In total, 545 were excluded and 243 full papers were retrieved, then 30 studies were included in the final sample ( Fig. 1 ) .

Study characteristics

Of the 30 studies included in this review [ 16 , 17 , 18 , 19 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ], three studies reported changes in hypertension prevalence, among which one study reported preventing hypertension in the general population [ 24 ] and two studies reported blood pressure control in patients with hypertension [ 17 , 18 ]; 25 studies reported mean blood pressure changes [ 16 , 19 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ]; two studies reported both outcome measures (changes in hypertension prevalence and mean blood pressure changes) [ 25 , 26 ]. Thirteen studies used education and counseling intervention strategies [ 24 , 25 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]; four studies used management intervention strategies [ 18 , 19 , 38 , 39 ]; seven studies combined education, counseling and management intervention strategies [ 26 , 40 , 41 , 42 , 43 , 44 , 45 ]; and six studies used screening and referral for management intervention strategies [ 16 , 17 , 46 , 47 , 48 , 49 ]. Fourteen studies followed participants for less than 12 months (i.e., short-term interventions) [ 17 , 26 , 27 , 29 , 30 , 32 , 33 , 34 , 36 , 40 , 41 , 42 , 43 , 45 ]. Twelve studies were conducted in the US [ 16 , 17 , 19 , 24 , 27 , 28 , 32 , 33 , 39 , 41 , 43 , 46 ] and most studies included both genders [ 16 , 17 , 18 , 19 , 24 , 25 , 26 , 28 , 29 , 30 , 31 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ] and all racial/ethnic groups [ 16 , 17 , 18 , 19 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ]. We found no natural experiments according to the definition used in this study (Table 1 , Table S 2 ).

Quality ratings

According to the Cochrane Risk of Bias Tool, most studies included in this review were found to have a high risk of bias ( Table S 3 ). This was so because the Cochrane Risk of Bias Tool was mostly designed for RCTs. Studies included in this review only used quasi-experiment designs and as such did not use randomization, allocation concealment, blinding of participants and personnel, and blinding of outcome assessment. Using the GRADE approach, the quality of evidence was deemed of low quality for the mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) change outcome (Table S 4 ).

Studies that reported prevalence of hypertension in the general population or changes in the prevalence of controlled blood pressure in hypertension patients after intervention

Outcome of interest: prevention of hypertension in healthy people, education and counseling intervention strategies.

Two studies evaluated the education and counseling intervention strategies, and both found that those strategies could help prevent hypertension in healthy people [ 24 , 25 ]. One study in the US found that nutritional education and giving access to fruits and vegetables through community gardens helped reduce hypertension prevalence (61.0% vs. 45.0%; P < 0.01), whereas the prevalence of hypertension in the control group did not change (46.7% vs. 49.8%; P = 0.39) [ 24 ]. The other study in Africa showed that an education strategy which promoted PA and healthy diet and combined with free smoking cessation consultations could help reduce the prevalence of hypertension (22.8% vs. 16.2%; P = 0.01), compared to that in control group (14.0% vs. 15.1%; P = 0.52) [ 25 ].

Outcome of interest: improvement of hypertension control in patients with hypertension

Management intervention strategies.

A study in the US showed that patients whose general practitioners accessed the computerized clinical practice guideline at least twice a day improved their hypertension control compared to the patients whose general practitioners never accessed the computerized clinical practice guideline ( P < 0.001) [ 18 ].

Education, counseling and management intervention strategies

A study in the US found that patients who received education about hypertension and did home blood pressure monitoring had a better control of their hypertension compared to the control group ( P = 0.03) [ 26 ].

Screening and referral for management intervention strategies

A study in the US showed that for White patients, interventions which involved a coordinator who identified and reached out to patients not meeting CVD goals and linked them to management programs could improve the odds of blood pressure control (odds ratio, 1.13; 95% CI, 1.05 to 1.22) compared to no intervention [ 17 ].

Studies that reported mean blood pressure changes after intervention

Outcome of interest: reduction in mean blood pressure.

Seven [ 25 , 27 , 28 , 29 , 30 , 34 , 35 ] of twelve [ 25 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ] (58.3%) studies showed that the education and counseling intervention strategies could help reduce mean blood pressure compared to the control group. Education and counseling interventions targeting lifestyle modifications (e.g., diet and PA) have been found effective in reducing blood pressure in the workplace. A study in US female nursing assistants found that combining education and continuing motivation (e.g., counseling on questions of interventions and receiving feedback) on diet and PA led to more reduction in DBP compared to the control group who only received the education (MD, − 6.70 mmHg; 95% CI, − 13.35 to − 0.05) [ 27 ]. Two other studies also found that multi-component lifestyle interventions in the workplace including sharing health information by messages, putting up posters, using pedometers, and giving education on PA could help healthy employees or employees with hypertension lower blood pressure [ 28 , 29 ]. Besides the workplace, interventions implemented in a community setting also appeared to work in reducing blood pressure. A study that included participants age 55 years or more in Asia found that people who attended 60-min Tai Chi three times per week for 12 weeks had a larger reduction in SBP (MD, − 14.30 mmHg; 95% CI, − 19.20 to − 9.40) and in DBP (MD, − 7.02 mmHg; 95% CI, − 10.62 to − 3.42) compared to people maintaining usual daily activities [ 30 ]. Another study among patients with hypertension in Asia found that education about the nutritional behavior and guidelines from dietary approaches to stop hypertension (DASH) approach could help reduce blood pressure more in the intervention group compared to the control group who only received the instruction booklets used in intervention group (SBP: MD, − 13.50 mmHg; 95% CI, − 16.15 to − 10.85; DBP: MD, − 6.60 mmHg; 95% CI, − 8.17 to − 5.03) [ 34 ]. One study in Africa also showed that education on promoting PA and healthy diet, combined with free smoking cessation consultations could help reduce SBP in the intervention group [ 25 ].

Two [ 19 , 39 ] of three [ 19 , 38 , 39 ] (66.7%) studies showed that the management intervention strategies could help reduce mean blood pressure compared to the control group. A study in the US showed that supporting diabetes patients’ self-management of hypertension by team-based chronic models (e.g., proactive patient outreach, depression screening, and health coaching) could decrease more DBP over a 6-month period compared to the usual care (MD, − 1.13 mmHg; 95% CI, − 2.23 to − 0.04) [ 19 ]. A study among hypertension patients in Asia showed that improving the social health insurance system by increasing outpatient expenditure reimbursement ratio could help reduce more SBP (MD, − 2.9 mmHg; P = 0.01) compared to outpatient expense not covered [ 38 ]. The other study among diabetes patients in the US also showed that team-based treatment with trained staff on medical management and self-management helped lower SBP (MD, − 0.88 mmHg; P = 0.01), but it did not compare the MD between treatment and control group [ 39 ].

Six [ 26 , 40 , 42 , 43 , 44 , 45 ] of seven [ 26 , 40 , 41 , 42 , 43 , 44 , 45 ] (85.7%) studies showed that the combination of education, counseling and management intervention strategies led to more blood pressure reduction compared to the control group. One study among hypertension patients in Europe found that management of stress by biofeedback-assisted relaxation and lifestyle counseling on diet and PA reduced more SBP (MD, − 2.62 mmHg; 95% CI, − 3.96 to − 1.29) and DBP (MD, − 1.00 mmHg; 95% CI, − 1.90 to − 0.93) compared to the control group [ 40 ]. One study among hypertension patients in the US also found that education about hypertension and home blood pressure monitoring could help reduce more SBP (MD, − 4.70 mmHg; 95% CI, − 7.14 to − 2.26) and DBP (MD, − 2.20 mmHg; 95% CI, − 3.80 to − 0.60) compared to controls [ 26 ]. A study among 65-year-and-older hypertension patients in Asia found that the intervention group who received education on hypertension management, community-based eHealth monitoring, and monthly telephone counseling had more reduction in SBP (MD, − 10.80 mmHg; 95% CI, − 14.99 to − 6.61) compared to the control group who only received a poster about hypertension management [ 42 ]. A study among hypertension patients in the US also showed that interventions on lifestyle modifications, and nutritional, pharmacological therapies as well as medication adherence lowered SBP and DBP compared to the control group [ 43 ]. A study among hypertension patients in Asia found that integration of preventive-curative services delivery and cooperation among village-town-county physicians for education on lifestyle modifications, taking blood pressure drugs regularly and monitoring the blood pressure could help reduce blood pressure more in the intervention group [ 44 ]. The other study in Asia also found that integrated program with health education on home blood pressure monitoring and hypertension measurement skills could help reduce blood pressure more in the intervention group [ 45 ].

Four [ 16 , 46 , 47 , 48 ] of five [ 16 , 46 , 47 , 48 , 49 ] (80.0%) studies showed that the screening and referral for management intervention strategies could help reduce more blood pressure compared to the control group. Screening for medical or economic needs followed by offering treatment and resources has been found helpful. One study in the US found that screening for unmet needs in primary care and offering those who screened positive some resources could reduce SBP (MD, − 2.6 mmHg; 95% CI, − 3.5 to − 1.7]) and DBP (MD, − 1.4 mmHg; 95% CI, − 1.9 to − 0.9) in patients [ 16 ]. The other study among patients with serious mental illness in the US also found that using registry for general medical needs and outcomes, screening and referral for general medical illness prevention and treatment could help reduce more DBP compared to controls (MD, − 3.00 mmHg; 95% CI, − 4.96 to − 1.04) [ 46 ]. Assessing and screening CVD risk followed by a management program has also been found beneficial to reduce blood pressure. A study in Europe showed that participating in CVD risk assessment and management program, including screening and tailored strategies for lifestyle advice on CVD risk factors could reduce more SBP (MD, − 2.51 mmHg; 95% CI, − 2.77 to − 2.25) and DBP (MD, − 1.46 mmHg; 95% CI, − 1.62 to − 1.29) compared to controls [ 47 ]. A study among hypertension patients in Asia also found that a standardized CVD-risk assessment, a hypertension complication screening and adherence to medications could help reduce more blood pressure compared to the usual care [ 48 ].

Meta-analysis of the effectiveness of interventions on mean blood pressure change

Intervention type sub-group analysis.

The largest blood pressure reduction (SBP: WMD, − 5.34 mmHg; 95% CI, − 7.35 to − 3.33; DBP: WMD, − 3.23 mmHg; 95% CI, − 5.51 to − 0.96) was seen for interventions that combined education, counseling and management intervention strategies (Table 2 , Fig. 2 ).

Intervention setting sub-group analysis

Participants who experienced interventions implemented in community settings (WMD, − 3.77 mmHg; 95% CI, − 6.17 to − 1.37) and in health center settings (WMD, − 3.77 mmHg; 95% CI, − 5.78 to − 1.76) had large SBP reduction. Participants experienced interventions implemented in organization settings had large DBP reduction (WMD, − 3.92 mmHg; 95% CI, − 5.80 to − 2.04) (Table 2 , Fig. S 3 ).

Intervention duration sub-group analysis

Participants who were followed for less than 12 months (i.e., short-term interventions) had a large reduction in blood pressure (SBP: WMD, − 6.25 mmHg; 95% CI, − 9.28 to − 3.21; DBP: WMD, − 3.54 mmHg; 95% CI, − 5.21 to − 1.87) and participants who were followed for longer than or equal to 12 months (i.e., long-term interventions) had a moderate reduction in blood pressure (SBP: WMD, − 1.89 mmHg; 95% CI, − 2.80 to − 0.97; DBP: WMD, − 1.33 mmHg; 95% CI, − 2.11 to − 0.55) (Table 2 , Fig. S 4 ).

We summarized the evidence from quasi-experiments that have evaluated interventions used to (1) prevent hypertension in the general population, (2) improve hypertension control in patients with hypertension or (3) reduce blood pressure levels in both the general population and patients.

In this systematic review, we found that the intervention strategies such as (1) education and counseling, (2) management, (3) education, counseling and management and (4) screening and referral for management were beneficial in preventing, controlling hypertension or reducing blood pressure levels. In particular, we found that education and counseling on lifestyle modifications (i.e., promoting PA, healthy diet, smoking cessation consultations) could help prevent hypertension in healthy people. The use of computerized clinical practice guidelines by general practitioners, education and management of hypertension, screening for CVD goals and referral to management could help improve hypertension control in patients with hypertension. The education and counseling on lifestyle modifications, the monitoring of patients’ metabolic factors and chronic diseases (e.g., blood pressure, cholesterol level, etc.) as well as patients’ adherence to medication, the combined education and management of hypertension, the screening for economic risk factors, medical needs, and CVD risk factors, followed by the referral to management all could help reduce blood pressure levels. Our study is one of the few systematic reviews that have summarized the evidence from quasi-experiments on hypertension prevention and control. A previous systematic review [ 52 ] which summarized evidence from cluster-randomized trials and quasi-experimental studies had been conducted and found that education, counseling and management strategies were also beneficial in controlling hypertension and reducing blood pressure. It showed that educating healthcare providers and patients, facilitating relay of clinical data to providers, promoting patients’ accesses to resources were associated with improved hypertension control and decreased blood pressure [ 52 ]. Another systematic review which summarized evidence from RCTs found that several interventions including blood pressure self-monitoring, educational strategies, improving the delivery of care, and appointment reminder systems could help control hypertension and reduce blood pressure [ 6 ]. Another study also found that community-based health workers interventions including health education and counseling, navigating the health care system, managing care, as well as giving social services and support had a significant effect on improving hypertension control and decreasing blood pressure [ 53 ]. A review from observational studies and RCT evidence from the US Preventive Services Task Force found that office measurement of blood pressure could effectively screen adults for hypertension [ 7 ].

Our review did not find natural experiments studies according to the definition used in this study. Quasi-experimental designs included DID, propensity score matching and pre-post designs with a control group (PPCG). While PPCG designs generally involve two groups (intervention and control) and two different time points (before and after the intervention), DID designs generally involve two or more intervention and control groups and multiple time points [ 13 ]. In this review, we did not include pre-post without a control group design because of its higher risk to internal validity due to the absence of comparison to adjust for time trends and confounding [ 22 ]. The findings in this review, highlight that, quasi-experiments are increasingly used to evaluate the effectiveness of health interventions for hypertension management when RCTs are not feasible or appropriate. For instance, several studies included in our systematic review often indicated that RCTs would have been difficult to be implemented given that the intervention was conducted in a particular setting such as a pragmatic clinical setting [ 16 , 43 , 45 , 48 ], a community setting [ 24 , 35 , 36 , 42 ], or a real-world organizational setting [ 33 ] because of ethical concerns and human resources issues. Another reason why quasi-experiments were chosen had to do with the need for translation and generalizability of the evidence in a specific community setting [ 32 ]. In fact, RCTs are not always generalizable to the communities or settings of interests [ 11 ]. The growing interest in and hence the increase in the use of natural and quasi-experiments in public health may be due to the recognition and realization of its usefulness in evaluating health interventions [ 14 , 54 ].

Given that there was high heterogeneity in the studies included in this systematic review, we have performed a random effects model and have only presented the subgroup analysis by intervention types, settings and duration of the study. Overall, our study suggested that interventions that combined education, counseling and management strategies appeared to show a relatively large beneficial effect for reducing blood pressure. However, our finding should be interpreted with caution due to the high-risk of bias and lower quality of evidence given the quasi-experimental nature of the designs (as opposed to evidence from randomized experiments). Nevertheless, the findings here can give us some insights on the benefit of interventions such as education, counseling and management, especially given that our findings are in line with previous studies [ 6 , 8 , 52 , 55 ]. Given that RCTs are not always feasible or appropriate, scientists should develop more rigorous methods to increase the internal validity of non-randomized studies. Compared to previous studies, one systematic review with meta-analysis including cluster-randomized trials and quasi-experiment studies showed that multi-component interventions which incorporated education of health care providers and patients, facilitating relay of clinical data to providers, and promoting patients’ accesses to resources could reduce more blood pressure compared to controls [ 52 ]. A recent systematic review with meta-analysis of RCTs also reported that interventions which included blood pressure self-monitoring, appointment reminder systems, educational strategies, and improving the delivery of care showed beneficial effects on lowering blood pressure [ 6 ]. Another systematic review and meta-analysis of RCTs also showed that self-measured blood pressure monitoring lowered SBP by 3.9 mmHg and DBP by 2.4 mmHg at 6 months compared to the usual care group [ 8 ]. One systematic review and meta-analysis of RCTs found that diet improvement, aerobic exercise, alcohol and sodium restriction, and fish oil supplements reduced blood pressure as well [ 55 ].

Limitations

This review has some limitations. First, the definition of natural and quasi-experiments is not consistent across fields. Second, the main limitation in most if not all the quasi-experimental study designs noted in this review was the potential for unobserved and uncontrolled confounding, which is a threat to internal validity and could lead to biased findings. Third, our findings may not be generalizable to all countries and settings as we only included studies published in the English language in this review. Fourth, as is the case in most other reviews, we could have missed relevant studies despite our best attempt to conduct a thorough search of the literature. Fifth, we found that most studies included in this study had a high risk of bias. It might be because we used the Cochrane Risk of Bias Tool to assess bias which was designed for examining RCTs. Studies in this review only used quasi-experiment designs and did not have randomization, allocation concealment, blinding of participants and personnel, and blinding of outcome assessment. Sixth, studies generally reported the measure of intervention impact differently across studies, making it difficult to combine the findings. In addition, studies were highly heterogeneous in terms of the types of individuals included in the study (e.g., healthy individuals and patients). We conducted the subgroup meta-analysis to reduce the heterogeneity, but the high heterogeneity still existed. Therefore, the results from meta-analysis need to be interpreted with caution. The individual impact reported for each individual study and the results from systematic review should be given more consideration.

In this systematic review, interventions that used education and counseling strategies; those that used management strategies; those that combined education, counseling and management strategies and those that used screening and referral for management strategies were beneficial in preventing, controlling hypertension and reducing blood pressure levels. The combination of education, counseling and management strategies appeared to be the most beneficial intervention to reduce blood pressure levels. The findings in this review, highlight that, a number of interventions that aim at preventing, controlling hypertension or reducing blood pressure levels are being evaluated through the use of quasi-experimental studies. Given that RCTs are not always feasible or appropriate, scientists should develop more rigorous methods to increase the internal validity of such quasi-experimental studies.

Availability of data and materials

The data supporting the conclusions of this article is included within the article and the additional file.

Abbreviations

Confidence interval

Cardiovascular disease

Dietary approaches to stop hypertension

Diastolic blood pressure

Difference-in-difference

Grading of Recommendations, Assessment, Development, and Evaluation

Mean difference

Physical activity

Pre-post designs with a control group

Randomized clinical trial

Systolic blood pressure

Standard error

United States

Weighted mean difference

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Additional file 1: table s1..

Search words. Table S2. Summary of the characteristics of the studies included in this review ( n = 30). Table S3. Risk of Bias Tool Assessments Across Studies (n = 30). Table S4. GRADE Evidence Profiles Across Studies in Meta-analysis ( n = 24). Table S5. Estimates and parameters in studies that reported on the mean difference in blood pressure ( n = 27). Table S6. Sensitivity analysis for systolic blood pressure (SBP) and diastolic blood pressure (DBP) in meta-analysis stratified by intervention type. Table S7. Sensitivity analysis for systolic blood pressure (SBP) and diastolic blood pressure (DBP) in meta-analysis stratified by intervention setting. Table S8. Sensitivity analysis for systolic blood pressure (SBP) and diastolic blood pressure (DBP) in meta-analysis stratified by intervention duration. Fig. S1. Methods to calculate mean differences (MD). Fig. S2. Methods to calculate standard errors (SE). Fig. S3. Forest plot stratified by intervention settings for blood pressure. (A) Forest plot stratified by intervention settings for systolic blood pressure (SBP). (B) Forest plot stratified by intervention settings for diastolic blood pressure (DBP). Fig. S4. Forest plot stratified by intervention duration for blood pressure. ( A) Forest plot stratified by intervention duration for systolic blood pressure (SBP). ( B) Forest plot stratified by intervention duration for diastolic blood pressure (DBP). Fig. S5. Funnel plot of systolic blood pressure (SBP), diastolic blood pressure (DBP) stratified by intervention types. Fig. S6. Funnel plot of systolic blood pressure (SBP), diastolic blood pressure (DBP) stratified by intervention settings. Fig. S7. Funnel plot of systolic blood pressure (SBP), diastolic blood pressure (DBP) stratified by intervention duration. Fig. S8. Sensitivity analysis of systolic blood pressure (SBP), diastolic blood pressure (DBP) stratified by intervention types. Fig. S9. Sensitivity analysis of systolic blood pressure (SBP), diastolic blood pressure (DBP) stratified by intervention settings. Fig. S10. Sensitivity analysis of systolic blood pressure (SBP), diastolic blood pressure (DBP) stratified by intervention duration

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Prevalence of metabolic syndrome and associated factors among patient with type 2 diabetes mellitus in Ethiopia, 2023: asystematic review and meta analysis

• Betelhem Mesfin Demissie 1 ,
• Fentaw Girmaw 2 ,
• Nimona Amena 3 &
• Getachew Ashagrie 2  

BMC Public Health volume  24 , Article number:  1128 ( 2024 ) Cite this article

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Metabolic syndrome is a complex pathophysiologic state which characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidaemia. The Adult Treatment Panel III report (ATP III) of the National Cholesterol Education Programme identified the metabolic syndrome as a serious public health issue in the modern era. In Western and Asian nations, the frequency of metabolic syndrome is rising, especially in developing regions experiencing rapid socio-environmental changes, in Sub-Saharan Africa; metabolic syndrome may be present in more than 70% of people with type 2 diabetes mellitus. Therefore the objective of our study was to estimate the pooled prevalence of metabolic syndrome and associated factors among type II diabetes mellitus patient.

This systematic review and meta-analysis included original articles of cross sectional studies published in the English language. Searches were carried out in PubMed, Web of Science, Google Scholar, and grey literature Journals from 2013 to June 2023. A random-effects model was used to estimate the pooled prevalence of metabolic syndrome among type II Diabetes mellitus patient in Ethiopia. Heterogeneity was assessed using the I 2 statistic. Subgroup analysis was also conducted based on study area. Egger’s test was used to assess publication bias. Sensitivity analysis was also conducted.

Out of 300 potential articles, 8 cross sectional studies were included in this systematic review and meta-analysis study. The pooled prevalence of metabolic syndrome among patient with type II diabetes mellitus in Ethiopia was found to be 64.49% (95% CI: 62.39, 66.59) and 52.38% (95% CI: 50.05, 54.73) by using NCEP/ATP III and IDF criteria, respectively. The weighted pooled prevalence of metabolic syndrome among type II diabetes mellitus patients by sub group analysis based on the study region was 63.79% (95% CI: 56.48, 71.11) and 52.23% (95%CI: 47.37, 57.22) by using NCEP/ATP III and IDF criteria, respectively. Being female and increased body mass index were factors associated with metabolic syndrome among type II diabetes mellitus patients.

The prevalence of metabolic syndrome among type II patient is high. Therefore, policymakers, clinicians, and concerned stakeholders shall urge effective strategies in the control, prevention, and management of metabolic syndrome among type II diabetes mellitus.

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Introduction

The complicated pathophysiologic condition known as the metabolic syndrome is characterised by insulin resistance, hypertension, hyperlipidaemia, and abdominal obesity and which originate primarily from an imbalance between energy expenditure and calorie intake [ 1 ]. Even though the NCEP-ATPIII, IDF, and WHO criteria are the most often utilised clinical criteria for the diagnosis of metabolic syndrome, there are numerous similarities between them, there are also notable differences in the perspectives on the underlying causes of the metabolic syndrome [ 2 ]. The prevalence of metabolic syndrome is increasing in Western and Asian countries, particularly in emerging areas that are undergoing fast socio-environmental change. Numerous studies have demonstrated that metabolic syndrome is a major risk factor for type 2 diabetes mellitus, cardiovascular disease (CVD), and overall mortality [ 3 ].

Global estimates suggest that about one-third of the world’s population, primarily in developing countries, may have metabolic syndrome [ 4 ]. The National Cholesterol Education Programme’s Adult Treatment Panel III report (ATP III) recognised metabolic syndrome as a significant contemporary public health concern. It is a multiplex risk factor for cardiovascular disease (CVD) that requires more therapeutic care, and it also raises the risk of cancer, mental problems, renal illness, and early mortality [ 2 , 5 ].

Compared to those in Western countries, the urban population in several developing nations has a greater prevalence of metabolic syndrome. The two main causes of this disease’s growth are the increase in fast food consumption—high-calorie, low-fiber foods—and the decline in physical activity brought on by sedentary leisure activities and the use of automated transportation [ 1 ].

In Sub-Saharan Africa, metabolic syndrome may be present in more than 70% of people with type 2 diabetes mellitus. According to research which is done in two rural clinics of Ghana, the prevalence of metabolic syndrome among type II diabetes mellitus patients was 68.6% (95% CI: 64.0-72.8), and having diabetes for more than five years, being female, and being overweight are significantly associated with metabolic syndrome [ 4 ]. A study done by Lira Neto JCG et al., Stated that among 201 study participants, 50.7% were diagnosed with metabolic syndrome [ 5 ].

A cross sectional study conducted in Ethiopia reported that the prevalence of metabolic syndrome was 20.3% among 325 study participants [ 6 ]. A Systematic Review and Meta-analysis study conducted in Ethiopia stated that the pooled prevalence of metabolic syndrome in Ethiopia was found to be 34.89% (95% CI: 26.77, 43.01) and 27.92% (95% CI: 21.32, 34.51) by using NCEP/ATP III and IDF criteria, respectively. Subgroup analysis based on the study subjects using NCEP/ATP III showed that the weighted pooled prevalence was 63.78%(95% CI: 56.17, 71.40) among type 2 Diabetes Mellitus patients [ 7 ].

Even though this topic has been studied before, our work is unique since we look at aspects outside prevalence. Thus, our study’s goal was to analyse the pooled prevalence of metabolic syndrome and associated factors among patients with type II diabetes mellitus. How much is the prevalence of metabolic syndrome among Ethiopian patients with type II diabetes mellitus? And what variables are associated with metabolic syndrome patients with type II diabetes in Ethiopian?

Protocol and search strategy

The systematic review and meta-analysis was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guideline (Fig.  1 ). The study protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (CRD42023442704). An inclusive literature search was conducted to identify studies about the prevalence of metabolic syndrome among patients with type II diabetes mellitus reported among the Ethiopian population of various study subjects. Both electronic and gray literature searches were carried out systematically. PubMed, Web of Science, Google Scholar, and grey literature, were searched for material between 2013 and 2023. The search terms were used separately and in combination using Boolean operators like “OR” or “AND.” An example of keywords used in PubMed to select relevant studies was as follows: (((“Metabolic Syndrome“[Mesh] OR Metabolic syndrome*[tiab]) AND (“Diabetes Mellitus, Type 2“[Mesh] OR “Diabetes Mellitus, Type 2*“[tiab])) AND (“Prevalence“[Mesh] OR “Magnitude*“[tiab])) AND (“Ethiopia“[Mesh] OR “Ethiopia*“[tiab]). Moreover, each database’s specific search parameters were customized accordingly.

Study selection (inclusion and exclusion criteria)

Inclusion criteria.

Studies were selected according to the following criteria: study design, participants, exposures and condition or outcome(s) of interest. Eligible studies were only quantitative full- text, and observational studies (cross-sectional) reporting prevalence and associated factors in terms of the odds ratio. Only articles written in English were retrieved for review. We included studies involving only type II diabetes mellitus patients aged greater than 30.

The primary outcome was the prevalence of metabolic syndrome. We used author reported definitions (according ATP III &IDF) (Table  1 ). Secondary outcome was factors associated with metabolic syndrome among type 2 diabetes mellitus patients. We were used unpublished articles to identify any potential studies that might have been missed from our search.

Exclusion criteria

We excluded reviews, case reports, case series, qualitative studies, and opinion articles. We were exclude abstract-only papers.

Data extraction and quality assessment

Data extraction was done independently by the two reviewers in a pre-piloted data extraction form created in MS Excel. Any discrepancies in the extracted data were resolved by consensus or discussion with a third reviewer. The following details will be extracted from each study:- details of the study (first author’s last name, year of publication), study region, study design, sample size, Prevalence of metabolic syndrome, associated factors.

The Joanna Brigg Institute’s quality evaluation criteria’s (JBI) were used to evaluate the studies’ quality. We assessed each of the chosen publications using the JBI assessment checklist. Research with a quality score of at least 50% was deemed to be of high quality.

Data analysis

Version 17 of STATA was used to analyse the retrieved data after they were imported into Microsoft Excel. To get a general summary estimate of the prevalence across trials, a random-effects model was employed. We employed point estimate with a 95% confidence interval. Sensitivity analysis was used to evaluate each study’s contribution to the outcome by eliminating each one individually. Using Egger’s test, the existence of publication bias was evaluated. The Cochran’s Q statistic and I2 statistics were used to assess the heterogeneity of the studies. Moreover, meta-regression has been conducted that represents linear predictions for the metabolic syndrome among type 2 diabetes mellitus patients prevalence as a function of published year. Subgroup analysis was performed based on study region and study subjects since there was unexplained significant heterogeneity.

Publication bias

Funnel plot and Egger’s test was used to assess publication bias and a P-value of less than 0.05 was used to declare the publication bias. The included studies were assessed for potential publication bias and separate analyses were done based on IDF and NCEP/ATPIII criteria (p values were 0.58 and 0.88, respectively) which indicated the absence of publication bias (Figs.  2 and 3 ).

PRISMA flow diagram of study selection for systematic review and meta-analysis of prevalence of metabolic syndrome among type II Diabetes mellitus patients in Ethiopia [ 11 ]

Forest plot showing the pooled prevalence of metabolic syndrome among type II Diabetes mellitus patients in Ethiopia (according to NCEP ATP III Criteria)

Forest plot showing the pooled prevalence of metabolic syndrome among type II Diabetes mellitus patients in Ethiopia (according to IDF Criteria)

Characteristics of included studies

The title and abstract screening of 300 potential articles yielded 102 that were included relevant to the topic of interest; the full-text screening of 50 of these articles indicated their eligibility for full-text assessment; 8 of these articles, involving 2375 study participants, were found to be eligible for systematic review and meta-analysis. Based on the NCEP/ATPIII and IDF criteria, the prevalence of metabolic syndrome in patients with type 2 diabetes mellitus was assessed among the Ethiopian population of different study participants. Five studies reported the prevalence of metabolic syndrome among type 2 diabetes mellitus based on both IDF and NCEP/ATPIII criteria, whereas seven studies based on NCEP/ATPIII criteria only and six studies by IDF criteria only (Table  2 ).

Prevalence of metabolic syndrome among type 2 diabetes mellitus patients using IDF and NCEP ATP III Criteria

The random-effects model was applied since the heterogeneity index of the studies were significant. The pooled prevalence of metabolic syndrome was found to be 64.49% (95% CI: 62.39, 66.59) by using NCEP/ATP III (Figs.  4 ) and 52.38% (95% CI: 50.05, 54.73) by using IDF criteria (Fig.  5 ). Subgroup analysis based on the study region using NCEP/ ATP III showed that the weighted pooled prevalence was 63.79% (95% CI: 56.48, 71.11) among type 2 diabetes patients (Fig.  6 ). Using IDF criteria, subgroup analysis based on the study region showed that the weighted pooled prevalence was 52.23% (95%CI: 47.37, 57.22).

Sub group analysis based on study region using NCEP ATP III Criteria

the pooled odds ratio of the association between sex and prevalence of metabolic syndrome among type II diabetes mellitus patients

The pooled odds ratio of the association between BMI and prevalence of metabolic

Factors associated with metabolic syndrome among type II DM

Association between sex and prevalence of metabolic syndrome.

The association between being female and prevalence of metabolic syndrome was examined based on the finding from five studies ( 1 , 2 , 4 , 5 and 7 ). The pooled odds ratio (AOR: 0.5, 95% CI: -0.32-1.31) showed that prevalence of metabolic syndrome associated with being female. The studies showed very high heterogeneity (I²=86.3% and P  = 0.00) (Fig.  7 ). Hence, a random effects model was employed to do the final analysis.

Funnel plot for prevalence of metabolic syndrome according to NCE ATPIII

Association between BMI and prevalence of metabolic syndrome

The association between BMI and prevalence of metabolic syndrome was examined based on the finding from four studies ( 1 , 2 , 4 and 8 ). The pooled odds ratio (AOR: 3.86, 95% CI: 2.57–5.15) showed that prevalence of metabolic syndrome associated with BMI. The studies showed high heterogeneity (I²= 68.2% and P  = 0.034) (Fig.  8 ). Hence, a random effects model was employed to do the final analysis.

Funnel plot for prevalence of metabolic syndrome according to IDF

Sensitivity analysis

Sensitivity analysis was carried out by gradually removing each research from the analytic process according to the two provided diagnostic criteria (NCEP/ATP III and IDF) in order to evaluate the impact of each study on the pooled estimated prevalence of metabolic syndrome among type II diabetes mellitus patients. The result showed that excluded studies led to significant changes in the shared estimation of the prevalence of metabolic syndrome (Figs.  9 and 10 ).

Sensitivity analysis based on NCEP/ATP III diagnostic criteria

Sensitivity analysis based on IDF diagnostic criteria

This systematic review and meta- analysis study provides evidence of an estimated pooled prevalence of metabolic syndrome among type II diabetes mellitus patients of the Ethiopian population. According to this review, the combined pooled prevalence of Metabolic syndrome among type II diabetes mellitus patients were 64.49% (95% CI: 62.39, 66.59) and 52.38% (95% CI: 50.05, 54.73) by using NCEP/ATP III and IDF criteria, respectively.

The finding of this study similar with the study conducted in African populations, which reported that the prevalence of metabolic syndrome among type 2 diabetes mellitus was 66.9%(95%CI: 60.3–73.1) [ 9 ]. In addition, the study which was done in sub-Saharan African countries in line with this finding which reports that prevalence of metabolic syndrome among type II diabetes melituse patients were 64.8% (95% CI: 54.74, 74.86) and 57.15% by using NCEP/ATP III and IDF criteria, respectively.

Furture more, the study which was done in Sub-Saharan Africa reported that, among others sub-Saharan Africa countries the prevalence of metabolic syndrome was highest in Ethiopia, (61.14%, 95% CI: 51.74, 70.53), which is almost similar with our study findings [ 8 ].

Similarly the study conducted in Ethiopian population showed that the weighted pooled prevalence of metabolic syndrome among type II diabetes mellitus patient was 63.78% (95% CI: 56.17, 71.40) [ 7 ].

This study result supported by the fact that metabolic syndrome has been associated with type 2 diabetes due to its high prevalence worldwide since it is both related to the increase in obesity and a sedentary lifestyle. Several studies suggest that individuals with Metabolic syndrome are 5 times more likely to develop type 2 diabetes [ 10 ].

This meta-analysis assessed factors determining metabolic syndrome among type II diabetes mellitus patients. The current meta-analysis demonstrated that the prevalence rate of metabolic syndrome was higher in females compared to that in males. This has been shown in all the Middle Eastern countries, and the prevalence was much higher among women than men [ 6 ]. The prevalence rate of metabolic syndrome associated with the individual’s body mass index.

This study has implications for clinical practice. Determining the prevalence of metabolic syndrome among type 2 diabetic patients is critical to guide healthcare professionals to minimize the risk of metabolic syndrome by providing guidance to the patient who has undergone diabetic care follow up. Moreover, it gives information about the burden and public health impact of metabolic syndrome for possible consideration during routine diabetic patient care.

This meta-analysis study has its own limitations that should be considered in the future research. Few studies are included due to limited research in Ethiopia which makes it difficult to generalize the findings to all type 2 diabetic patients in the countery and which makes the discussion part more shallow.

In conclusion, according to this systematic review the prevalence of metabolic syndrome among type II patient is high in Ethiopia and recommends an urgent attention from both the clinical and public health viewpoint Therefore, policymakers, clinicians, and concerned stakeholders shall urge effective strategies in the control, prevention, and management of metabolic syndrome among type II diabetes mellitus. In addition country context-specific preventive strategies should be developed to reduce the burden of metabolic syndrome.

Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

Abbreviations

Cardiovascular Disease

National Cholesterol Education Program–Adult Treatment Panel III

International diabetes federation

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

World Health Organization

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Department of Nursing, School of Nursing, College of Health Sciences, Woldia University, North Wollo, Amhara, Ethiopia

Betelhem Mesfin Demissie

Department of Pharmacy, College of Health Sciences, Woldia University, North Wollo, Amhara, Ethiopia

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“B.M involved in the entire work of the manuscript which is a design of the study, review of literature, and data analysis, “F.G.” was involved in, design of the study, review of the literature, data extraction, and statistical analysis. “N.A”. and “G.A” were involved in data analysis and interpretation and drafting of the manuscript. All authors critically revised the paper, and they agreed to be accountable for all aspects of the work.

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Correspondence to Betelhem Mesfin Demissie .

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Demissie, B.M., Girmaw, F., Amena, N. et al. Prevalence of metabolic syndrome and associated factors among patient with type 2 diabetes mellitus in Ethiopia, 2023: asystematic review and meta analysis. BMC Public Health 24 , 1128 (2024). https://doi.org/10.1186/s12889-024-18580-0

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Self-Monitoring and Managing Medications Improved High Blood Pressure

• Original Investigation Home BP Self-Monitoring Plus Self-Titration for Patients With Hypertension Patricia Martínez-Ibáñez, PhD; Irene Marco-Moreno, PhD; Aníbal García-Sempere, PhD; Salvador Peiró, PhD; Lucia Martínez-Ibáñez, MD; Ignacio Barreira-Franch, MD; Laura Bellot-Pujalte, MD; Eugenia Avelino-Hidalgo, MD; Marina Escrig-Veses, MD; María Bóveda-García, MD; Mercedes Calleja-del-Ser, MD; Celia Robles-Cabaniñas, BBioTech; Isabel Hurtado, PhD; Clara L. Rodríguez-Bernal, PhD; Margarita Giménez-Loreiro, MD; Gabriel Sanfélix-Gimeno, PhD; José Sanfélix-Genovés, PhD; ADAMPA Research Group; Joaquín Abad Carrasco; Maria Virginia Agudo Escagüés; Jorge Navarro-Perez; Rosa Maria  Bartual Penella; Rosa Carrión Villanueva; Ana Costa Alcaraz; Isabel Cristófol López; Rosario González Candelas; Ricardo González Espadas; Luis González Luján; Victoria Gosalbes; Enrique Guinot Martínez; Emilio Luis López Torres; Silvia Molla LLosa; Víctor Moreno Comins; Miriam Moreno Prat; Mª José Puchades Company; Ángela Ramos García; Paloma Ramos Ruiz; Pilar Roca Navarro; Rosa Saiz Rodriguez; Julia Lorena Salanova Chilet; Ana Tchang Sanchez; Francisca Torres Asensi; Ruth Uribes Fillol; Cristina Valle García; Macarena Villar Ruiz; Marta Alcocer Escribano; Laura Almudever Campo; Lorena Cruz Bautista; Mª Begoña Fuertes Fernandez; Victor García Olivencia; Carmen Molla Orts; María José Muñoz Sanchíz; Francisca Osuna Sabariego; Emilia Ramón Carretero; Pilar  Roca Roda; Esther Rodriguez García; Maria Rosa Serrada Iranzo; Eva Sierra García; Adina A Iftimi; Andreu Ferrero-Gregori JAMA Network Open

People who monitored their blood pressure at home and modified their medications based on the readings lowered their blood pressure more than those in a control group who received routine blood pressure management from a physician, according to results from a randomized clinical trial involving 219 patients in Spain. The participants were aged 40 years or older and had a systolic blood pressure of more than 145 mm Hg, a diastolic blood pressure of more than 90 mm Hg, or both. Both groups also received an educational booklet on reducing blood pressure.

Without consulting a clinician, participants titrated their medications if their daily readings were over the target range for 4 or more consecutive days. At the 2-year follow-up, they’d experienced an average 3.4-mm Hg decrease in systolic blood pressure and an average 2.5-mm Hg decrease in diastolic blood pressure relative to those in the control group. About 39% increased their medication dose during the trial and 55% added a new drug at least once. There was no difference in adverse events between groups.

The findings suggest that “simple, inexpensive, and easy-to-implement self-management interventions have the potential to improve the long-term control of hypertension in routine clinical practice,” the researchers wrote in JAMA Network Open .

Published Online: June 7, 2024. doi:10.1001/jama.2024.10331

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Harris E. Self-Monitoring and Managing Medications Improved High Blood Pressure. JAMA. Published online June 07, 2024. doi:10.1001/jama.2024.10331

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• Review Article
• Published: 11 October 2023

Endocrine causes of hypertension: literature review and practical approach

• Jean-Baptiste de Freminville 1 , 2 ,
• Laurence Amar 1 , 2 ,
• Michel Azizi 1 , 2 &
• Julien Mallart-Riancho 1 , 2  

Hypertension Research volume  46 ,  pages 2679–2692 ( 2023 ) Cite this article

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Hypertension (HTN) affects more than 30% of adults worldwide. It is the most frequent modifiable cardiovascular (CV) risk factor, and is responsible for more than 10 million death every year. Among patients with HTN, we usually distinguish secondary HTN, that is HTN due to an identified cause, and primary HTN, in which no underlying cause has been found. It is estimated that secondary hypertension represents between 5 and 15% of hypertensive patients [ 1 ]. Therefore, routine screening of patients for secondary HTN would be too costly and is not recommended. In addition to the presence of signs suggesting a specific secondary cause, screening is based on specific criteria. Identifying secondary HTN can be beneficial for patients in certain situations, because it may lead to specific treatments, and allow better control of blood pressure and sometimes even a cure. Besides, it is now known that secondary HTN are more associated with morbidity and mortality than primary HTN. The main causes of secondary HTN are endocrine and renovascular (mainly due to renal arteries abnormalities). The most frequent endocrine cause is primary aldosteronism, which diagnosis can lead to specific therapies. Pheochromocytoma and Cushing syndrome also are important causes, and can have serious complications. Other causes are less frequent and can be suspected on specific situations. In this article, we will describe the endocrine causes of HTN and discuss their treatments.

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de Freminville, JB., Amar, L., Azizi, M. et al. Endocrine causes of hypertension: literature review and practical approach. Hypertens Res 46 , 2679–2692 (2023). https://doi.org/10.1038/s41440-023-01461-1

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The psychological impact, risk factors and coping strategies to COVID-19 pandemic on healthcare workers in the sub-Saharan Africa: a narrative review of existing literature

• Freddy Wathum Drinkwater Oyat 1 ,
• Johnson Nyeko Oloya 1 , 2 ,
• Pamela Atim 1 , 3 ,
• Eric Nzirakaindi Ikoona 4 ,
• Judith Aloyo 1 , 5 &
• David Lagoro Kitara   ORCID: orcid.org/0000-0001-7282-5026 1 , 6 , 7  

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The ongoing COVID-19 pandemic has significantly impacted the physical and mental health of the general population worldwide, with healthcare workers at particular risk. The pandemic's effect on healthcare workers' mental well-being has been characterized by depression, anxiety, work-related stress, sleep disturbances, and post-traumatic stress disorder. Hence, protecting the mental well-being of healthcare workers (HCWs) is a considerable priority. This review aimed to determine risk factors for adverse mental health outcomes and protective or coping measures to mitigate the harmful effects of the COVID-19 crisis among HCWs in sub-Saharan Africa.

We performed a literature search using PubMed, Google Scholar, Cochrane Library, and Embase for relevant materials. We obtained all articles published between March 2020 and April 2022 relevant to the subject of review and met pre-defined eligibility criteria. We selected 23 articles for initial screening and included 12 in the final review.

A total of 5,323 participants in twelve studies, predominantly from Ethiopia (eight studies), one from Uganda, Cameroon, Mali, and Togo, fulfilled the eligibility criteria. Investigators found 16.3–71.9% of HCWs with depressive symptoms, 21.9–73.5% with anxiety symptoms, 15.5–63.7% experienced work-related stress symptoms, 12.4–77% experienced sleep disturbances, and 51.6–56.8% reported PTSD symptoms. Healthcare workers, working in emergency, intensive care units, pharmacies, and laboratories were at higher risk of adverse mental health impacts. HCWs had deep fear, anxious and stressed with the high transmission rate of the virus, high death rates, and lived in fear of infecting themselves and families. Other sources of fear and work-related stress were the lack of PPEs, availability of treatment and vaccines to protect themselves against the virus. HCWs faced stigma, abuse, financial problems, and lack of support from employers and communities.

The prevalence of depression, anxiety, insomnia, and PTSD in HCWs in sub-Saharan Africa during the COVID-19 pandemic has been high. Several organizational, community, and work-related challenges and interventions were identified, including improvement of workplace infrastructures, adoption of correct and shared infection control measures, provision of PPEs, social support, and implementation of resilience training programs. Setting up permanent multidisciplinary mental health teams at regional and national levels to deal with mental health and providing psychological support to HCWs, supported with long-term surveillance, are recommended.

Peer Review reports

Introduction

When coronavirus disease 2019 (COVID-19) was declared a pandemic in March 2020, healthcare workers (HCWs) globally and in sub-Saharan Africa (SSA) were unprepared for the scale of the physical and mental health devastation that was to follow [ 1 ]. The impact of the COVID-19 pandemic on healthcare workers has been profound, characterized by death, disability, and untenable burden on mental health and well-being [ 2 ]. Factors impacting their mental health include high risks of exposure and infection, financial insecurity, separation from loved ones, stigma, difficult triage decisions, stressful work environment, scarcity of supplies including personal protective equipment (PPEs), exhaustion, traumatic experiences due to regular witnessing of deaths among patients and colleagues [ 2 , 3 ]. Greenberg et al. [ 4 ] observed that the COVID-19 pandemic put healthcare professionals worldwide in an unprecedented situation, making difficult decisions to provide care for many severely ill patients with constrained or inadequate resources.

In almost all WHO regions, data indicates that infection rates among healthcare workers are higher than in the general population [ 5 ]. Scholars suggest that the end of the COVID-19 pandemic is not yet in sight. Neither are they sure about the virulence of the following variant when it appears as caseloads are still rising, with more than 621 million infections and 6.5 million deaths reported worldwide by 19th October 2022 [ 6 ]; mainly driven by the newer omicron variants. However, recently in October 2022, we received with gratitude a reassuring message from US President Biden declaring the end of the COVID-19 pandemic in the United States of America.

Meanwhile, previous studies found high levels of depression, anxiety, and PTSD in survivors among the general population and healthcare workers (HCWs) one-to-three years after the control of the SARS epidemic [ 7 ] and the 2014–2016 Ebola epidemic in West Africa [ 8 ]. In addition, recent surveys [ 9 , 10 , 11 , 12 , 13 , 14 ], reviews, and meta-analyses [ 15 , 16 , 17 , 18 ] are pointing to early evidence that a considerable proportion of healthcare workers have experienced stress, anxiety, depression, and sleep disturbances during the COVID-19 pandemic, raising concerns about risks to their long-term mental health.

Studies from the global north countries [ 19 , 20 ], UK [ 21 ], USA [ 22 ], and in India [ 23 ], and China [ 24 , 25 ] have shed light on the vulnerability that characterizes frontline healthcare workers during this pandemic, especially regarding their mental health and well-being. However, evidence in sub-Saharan Africa is scanty, and the pattern and prevalence of psychological disorders are not well understood.

Evidence from a systematic review by Pappa S et al. on 33,062 Chinese HCWs in April 2020 found a pooled prevalence rate of mental health problems among respondents; anxiety 23.2%, depression 22.8%, and insomnia 38.9% [ 26 ]. Similarly, Singapore study, Tan et al . [ 27 ], Li et al . [ 28 ], BMA [ 29 ] and in China [ 31 ] found high levels of psychological disorders among health workers.

Since the beginning of the pandemic, we found one systematic review involving 919 frontline HCWs, 3928 general HCWs, and 2979 medical students conducted in Africa from December 2019 to April 2020 [ 31 ]. The study by Chen J et al . reported a high prevalence of depression, anxiety, and insomnia among frontline HCWs in sub-Saharan Africa (SSA) at 45%, 51%, and 28%, respectively. In comparison, the prevalence of depression, anxiety, and insomnia among the general population was much lower at 30%, 31%, and 24%, respectively [ 31 ]. Furthermore, we found that only a few studies investigated protective and coping measures, given the many uncertainties surrounding the evolution of the COVID-19 pandemic [ 32 ]. Adequate data are needed to equip frontline HCWs and healthcare managers in sub-Saharan Africa to mitigate the medium and long-term adverse effects of the COVID-19 pandemic [ 33 ].

This review aimed to answer three questions (1) What is the psychological impact of the COVID-19 pandemic on HCWs in Sub-Saharan Africa?

(2) What are the associated risk factors during the COVID-19 pandemic?

(3) What interventions (mitigating and coping strategies) protect and support the mental health and well-being of HCWs during the ongoing crises and after the pandemic?

Methodology

Search methodology and article selection.

This current article is a mixed-method narrative review of existing literature on mental health disorders, risk factors, and interventions relevant to the COVID-19 pandemic on HCWs in sub-Saharan. A search on the PubMed electronic database was undertaken using the search terms "novel coronavirus", "COVID-19", "nCoV", "mental health", "psychiatry", "psychology", "anxiety", "depression" and "stress" in various permutations and combinations.

Search processes

We conducted a comprehensive literature search on original articles published from March 2020 to 30 April 2022 in electronic databases of Embase, PubMed, Google Scholar, and the daily updated WHO COVID-19 database. Our search terms included but were not limited to ('COVID-19'/exp OR COVID-19 OR 'coronavirus'/exp OR coronavirus) AND ('psychological'/exp OR psychological OR 'mental'/exp OR mental OR 'stress'/exp OR stress OR 'anxiety' OR anxiety OR 'depression' OR depression OR 'post-traumatic' OR 'post-traumatic'/exp OR 'trauma' OR 'trauma'/exp) OR Health care workers, medical workers of health care professionals, sub-Saharan Africa, for Embase. ("COVID-19" [All Fields] OR "coronavirus" [All Fields]) AND ("Stress, Psychological" [Mesh] OR "mental" OR "anxiety" OR "depression" OR "stress" OR "post-traumatic" OR "trauma") for PubMed, for the WHO COVID-19 database, and ("COVID-19" OR "coronavirus") AND ("Psychological" OR "mental" OR "anxiety" OR "depression" OR "stress" OR "post-traumatic" OR "trauma") for Google Scholar. On reviewing the above citations, twelve articles met the inclusion criteria relevant for this review and are in Table 1 . All twelve articles were cross-sectional, with one qualitative and the others quantitative observational studies.

Eligibility criteria

We included original qualitative and quantitative studies examining the risk factors, psychological impact of COVID-19 and coping strategies of healthcare workers (HCWs) in sub-Saharan Africa during the COVID-19 pandemic. We excluded studies if they were.

1. Not reported in the English language 2. Studies which were not primary research 3. Studies that had not been published in a peer-reviewed journal 4. Studies that did not include data on HCWs’ mental health or psychological well-being 5. Duplicate studies 6. not using validated instruments to measure the risks and psychological impact.

FWDO performed the search of articles. DLK reviewed the articles involving screening of titles, followed by examination of abstracts. The potential articles identified were further reviewed in full text to examine their eligibility. In addition, four of the authors independently reviewed the full articles to abstract the relevant data required for the review. Thereafter, a meeting to harmonise findings were done and presented in a report.

Data extraction and appraisal of the study

We extracted information from each study, including author, study population, year of publication, country, socio-demographic characteristics, sample size, response rate, gender proportion, age, and study time, areas assessed, the validated instrument used and the prevalence. The appraisal involved assessing the research design, recruitment of respondents, inclusion and exclusion criteria, reliability of outcome determination, statistical analyses, ethical compliance, strengths, limitations, and clinical implications of the articles.

Our review protocol was not registered on PROSPERO because of the significant variation in the methodologies of the articles used in the review. The results precluded using a meta-analytic approach and made a narrative review the most suitable for this work. In addition, we did not use the Cochrane Collaboration GRADE method to assess the quality of evidence of outcomes included in this narrative review. Instead, we used the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) 22 items checklist to gauge the quality of the twelve articles included in this review. We qualitatively validated the articles based on additional considerations namely study design, sample sizes, sampling procedures, response rates, statistical methods used, measures taken by the authors to deal with bias and confounding factors and ethical consideration.

Definition of healthcare worker (HCW)

For this narrative review, we adhered to the Centres for Disease Control and Prevention (CDC) definition of HCWs, which includes physicians, nurses, emergency medical personnel, dental professionals and students, medical and nursing students, laboratory technicians, pharmacists, hospital volunteers, and administrative staff [ 34 ].

Search results

The search found twenty-three studies of interest. Full texts of potentially relevant studies underwent eligibility assessment, and twelve articles met the inclusion criteria for this narrative review.

Study characteristics

The twelve articles comprised eleven quantitative and one qualitative study. The common mental health conditions assessed were depression, anxiety, perceived stress, and post-traumatic stress disorder (PTSD). The coping strategy, perceived health status, health distress (including burnout), insomnia, and perceived stigma were also assessed [ 35 , 36 ]. The total number of respondents in these studies was 5,323. The qualitative study had fifty respondents [ 35 ], while the most significant number of participants, 420 was recorded in one of the quantitative studies from Ethiopia [ 37 ]. The questionnaire response rates varied between 90%-100%, with most studies dominated by male respondents at 51.9%-69.2% [ 38 ]. Nurses were the commonest study population, followed by doctors, pharmacists, and laboratory technicians, and no study involved non-HCWs of facilities. Most papers utilized probability sampling procedures, and four quantitative studies used non-random sampling procedures limiting generalizability of their findings and increasing the risk of selection bias. Eight studies were from Ethiopia, and one was from Cameroon, Uganda, Mali, and Togo, respectively (Table 1 ). Most studies were conducted in urban tertiary public hospitals, university teaching hospitals, and rural and urban general hospitals, including primary care facilities operated by Non-Governmental Organizations (NGOs) for example in Mali [ 39 ]. Several validated tools assessed depression, anxiety, insomnia, stress, and PTSD (Table 1 ).

Table 1 provides an overview of the studies selected and validated instruments used to measure psychological disorders.

Table 2 provides comparisons with studies conducted outside of sub-Saharan Africa.

Table 3 provides information on studies showing the classification of psychological outcomes.

Table 4 are studies showing risk factors associated with psychological disorders.

Table 5 are studies that identified protective factors for psychological disorders.

Risks of bias and confounding factors

Most articles selected were cross-sectional studies that employed probability sampling procedures (Table 1 ). Cross-sectional study design minimized selection biases, but many used structured questionnaires, including online self-administered questionnaires, which increased bias due to social desirability. It was not clear how confounding variables were controlled in five papers reviewed [ 38 , 39 , 40 , 43 , 45 ] leading to excessive and perhaps inappropriate determination of associations.

Socio-demographic factors

In this review, the mean age of the respondents ranged between 23 and 35 years, and predominantly males. Age was associated with anxiety, and stress symptoms in 6(50%) of all the studies reviewed [ 35 , 37 , 40 , 41 , 42 , 44 ]. An age of over 40 years was associated with moderate to severe symptoms of PTSD. Two studies concluded that respondents aged over 40 years were more likely to develop PTSD symptoms than their younger counterparts [ 37 , 41 ].

Female gender was significantly associated with depression, anxiety, and stress symptoms among HCWs in seven studies reviewed [ 36 , 37 , 38 , 41 , 42 , 43 ]. Many studies found that being female, married, and a nurse were independent predictors of stress symptoms. Moreover, sex, age, marital status, type of profession, and working environment were significant factors for PTSD symptoms [ 37 , 41 ]. However, one study in Ethiopia found that the odds of depression were twice higher among male healthcare providers than among female healthcare providers [ 35 ].

Psychological impact on healthcare workers

Most studies reviewed directly assessed the prevalence of depression, anxiety, stress, insomnia, and PTSD in HCWs. Common causes of anxiety, fear, or psychological distress that health professionals reported were: lack of access to PPEs and other equipment, being exposed to COVID-19 at work and taking the infection home to their families, uncertainties that their organization will support/take care of their personal and family needs if they got infection, long working hours, death of colleagues, lack of social support, stigmatization, high rates of transmission and poor income [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. However, the prevalence of mental health symptoms exhibited great variations for example depressive symptoms were examined in nine studies [ 35 , 36 , 37 , 39 , 43 , 44 , 45 , 46 ], and varied between 16.3% and 71.9% among HCWs [ 38 , 39 ].

In addition, nine other studies reported high prevalence of anxiety symptoms among HCWs [ 35 , 36 , 37 , 40 , 43 , 44 , 45 , 46 , 47 ] which varied between 21.9% and 73.5% [ 36 , 39 ]. Five studies investigated HCWs' perceived stress during the pandemic; 15.5%-63.7% of HCWs reported high levels of work-related stress [ 35 , 36 , 37 , 43 , 45 ]. Three studies reported 12.4–77% of HCWs experienced sleep disturbances during the COVID-19 pandemic [ 37 , 39 , 40 ].

Post-traumatic stress disorder (PTSD) was in three studies [ 38 , 41 , 42 ], and the prevalence of PTSD-like symptoms varied between 51.6 and 56.8% in HCWs [ 38 , 41 ]. A qualitative study from Uganda reported high symptoms of depression, anxiety, and PTSD among HCWs [ 35 ]. Additionally, factors that increased the risk of PTSD symptoms were for example, working in emergency units and being frontline workers. Furthermore, many studies found that frontline HCWs had increased symptoms of mental disorders and being a frontline worker was an independent risk factor for depression, anxiety, and PTSD [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ].

Risk factors associated with adverse mental health outcomes

The qualitative study from Uganda reported the factors associated with mental disorder symptoms among HCWs. These were long working hours, lack of equipment (PPEs, testing kits), lack of sleep, exhaustion, high death rates, death of colleagues, and a high COVID-19 transmission rate among HCWs [ 35 ]. Lack of equipment (PPEs, ventilators, and testing kits), overworking, and lack of logistic support were in Ethiopian studies [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 45 ]. Most studies identified several risk factors for adverse mental health outcomes among respondents for example those with medical and mental illnesses, contacts with confirmed COVID-19 patients, and poor social support which were significantly associated with depression [ 42 , 43 ]. Other factors were females, nurses, married, frontline workers, ICU, emergency units, living alone, and lack of social support [ 35 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. Too, participants’ families with chronic illnesses, had contacts with confirmed COVID-19 cases, and poor social support were significantly associated with anxiety. Other risk factors associated with anxiety include exhaustion, long working hours, frontline workers, emergencies, nurses, pharmacists, laboratory technicians, married, older, younger, living alone, being female, working at general and referral hospitals, and perceived stigma. In addition, participants’ families with chronic illnesses, those who had contacts with confirmed COVID-19 cases, and those with poor social support were predictors of stress during the COVID-19 pandemic [ 37 , 38 , 40 , 41 , 42 , 43 , 45 ]. Other stress symptoms include having a medical illness, a mental illness, being a frontline worker, married, nurse, female, pharmacist, laboratory technician, physician, older age, lack of standardized PPE supply, low incomes, and living with a family [ 36 , 37 , 40 , 41 , 42 , 43 , 44 , 45 ]. Healthcare providers with low monthly incomes were significantly more likely to develop stress than those with high monthly incomes [ 38 ]. In addition, participants living alone, living with a family, and being married were associated with symptoms of psychological disorders among HCWs [ 36 , 37 , 38 , 45 ]. Overall, the risk factors for adverse psychological impacts are categorized in three thematic areas (i) occupational, (ii) psychosocial, and (iii) environmental aspects.

Occupational factors

Most studies showed that frontline HCWs, nurses, doctors, pharmacists, and laboratory technicians had significantly higher levels of mental health risks compared to non-frontline HCWs [ 35 , 36 , 37 , 38 , 40 , 42 , 43 , 45 ]. They experienced higher frequency of insomnia, anxiety, depression, and somatization than non-frontline medical HCWs. In contrast, Mali [ 39 ] and Cameroon [ 46 ] studies found a higher prevalence of depression, anxiety, and PTSD in non-frontline HCWs [ 39 , 46 ]. However, among HCWs, physicians were 20% less likely to develop mental health disorders than nurses, pharmacists, and laboratory technicians [ 39 ]. In addition, healthcare workers with low monthly incomes had higher symptoms of depression, anxiety, stress, and insomnia [ 37 ].

Healthcare groups

Five studies found that being a nurse was associated with worse mental disorders than doctors [ 36 , 37 , 40 , 44 , 45 ].

Frontline staff with direct contact with COVID-19

Most papers in the review found that being in a “frontline” position or having direct contact with COVID-19 patients was associated with higher level of psychological distress [ 35 , 36 , 37 , 38 , 40 , 42 , 43 , 45 ]. In addition, studies found that contact with COVID-19 patients was independently associated with an increased risk of sleep disturbances [ 40 , 46 ]. Moreover, HCWs who had contact with confirmed COVID-19 cases were more likely to develop depression, anxiety, and stress symptoms than those who had no contact with COVID-19 patients [ 36 , 37 , 38 , 43 , 45 ].

Lack of personal protective equipment (PPEs)

Most studies reported that the lack of PPEs was associated with higher symptoms of depression, anxiety, stress, and insomnia, while its availability was associated with fewer mental disorder symptoms [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. In Mali, workers from centres that provided facemasks were 51% less likely to suffer from depression, 62% less likely to develop anxiety, and 45% less likely to develop insomnia [ 39 ]. In Ethiopia, the odds of developing post-traumatic stress disorder were much higher among HCWs who did not receive standardized PPEs supplies than those who had [ 38 , 41 , 42 ]. In Uganda, the lack of PPEs was associated with depression, anxiety, and PTSD [ 35 ].

Heavy workload

Longer working hours, increased work intensity, increased patient load, and exhaustion were risk factors in Ugandan [ 35 ] and Ethiopian studies [ 36 ].

Psychosocial factors: perceived stigma and fear of infection

The fear of infection was in the qualitative study from Uganda [ 35 ], one quantitative study from Cameroon [ 47 ] and seven cross-sectional studies from Ethiopia [ 36 , 37 , 38 , 41 , 42 , 43 , 44 ]. Poor social support was associated with PTSD symptoms, depression, anxiety, and stress [ 35 , 36 , 37 , 38 , 42 , 43 ]. Two studies reported that HCWs with perceived stigmatization were more likely to suffer from depression, anxiety, stress, and PTSD [ 37 , 42 ].

family concerns

This came up as one of the main risk factors of stress in almost all studies, especially among those HCWs in direct contact with confirmed COVID-19 cases [ 35 , 36 , 37 , 38 , 40 , 41 , 42 , 43 , 44 , 45 ]. A family member suffering from COVID-19 was associated with poor mental health outcomes in HCWs [ 36 , 37 ].

Protective psychosocial factors

Two studies suggest a reduction of perceived stigma can be achieved by sensitization of communities about COVID-19 [ 37 , 42 ], and four studies recommend solid social support [ 36 , 37 , 42 , 43 ].

Safety of family

Family safety had the most significant impact in reducing stress. Safety from COVID-19 infection and financial protection of families were essential coping strategies for HCWs [ 35 , 36 ].

Underlying illnesses

We found three studies that reported an underlying medical and mental illness as an independent risk factor for poor psychological outcomes [ 42 , 43 , 45 ].

Protective factors against adverse mental health outcomes

The review identified protective factors to adverse mental health outcomes during COVID-19. The qualitative study from Uganda and four quantitative cross-sectional studies from Ethiopia identified some protective factors [ 35 , 38 , 41 , 42 , 45 ]. The protective factors are grouped under three thematic areas (i) occupational, (ii) psychosocial, and (iii) environmental aspects.

The qualitative study identified many social coping strategies among respondents, including family networks, community networks, help from family, responsibility to society, assistance from community members, availability of assistance from strangers, and the symbiotic nature of assistance in the community [ 35 ].

Protective occupational factors

Studies suggest that physicians suffered fewer mental health disorders partly because of their experience with previous epidemics [ 37 , 42 , 45 ].

Some necessary coping measures include good hospital guidance and ongoing training of frontline HCWs [ 37 , 42 , 45 ].

Adequate supply of PPEs

As mentioned above, PPE was a protective factor when adequate and a risk factor for poor mental health outcomes when deemed inadequate [ 35 , 36 , 37 , 42 , 43 ].

The COVID-19 pandemic has been an ongoing global public health emergency that has burdened healthcare workers' physical and mental well-being (HCWs) [ 1 , 5 ]. Our review confirms the enormous magnitude of mental health impact of COVID-19 on healthcare workers in sub-Saharan Africa, and it is widespread, with significant levels of depression, anxiety, distress, and insomnia; especially those working directly with COVID-19 patients at particular risk [ 34 , 35 , 36 , 37 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. Out of the twelve articles reviewed, eight studies (66%) came from Ethiopia, and this has implications on the results (Table 1 ). This finding indicates few research published to date on the psychological impact of the pandemic on the mental health of HCWs in sub-Saharan Africa; a subregion that the COVID-19 pandemic has severely impacted.

Overview of the study sites

Studies in this review were conducted predominantly in hospital settings. We found only one study relating to primary healthcare workers or facilities [ 38 ]. This finding is of concern, as there is increasing evidence that many non-frontline HCWs continue to suffer psychological symptoms long after the conclusion of infectious disease epidemics [ 7 , 8 ]. In addition, a significant mortality due to COVID-19 was due to excess morbidity, some of which were from primary care facilities. Given that this study is the first narrative review in sub-Saharan Africa, it would be helpful to briefly compare our findings with some published reviews and surveys from other regions (Table 2 ).

High prevalence of psychological disorders among participants

Investigators in this review found 16.3–71.9% HCWs with depressive symptoms, 21.9–73.5% had anxiety symptoms, 15.5–63.7% experienced work-related stress symptoms, 12.4–77% experienced sleep disturbances, and 51.6–56.8% PTSD symptoms [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. This high prevalence of mental health symptoms among HCWs in our review is consistent with previous reviews conducted early in the pandemic in sub-Saharan Africa [ 31 ], Asia [ 17 , 18 , 26 , 28 ], USA & Europe [ 15 , 16 ], and supported by a batch of cross-sectional studies globally [ 11 , 12 , 13 , 14 , 19 , 27 , 30 ]. We found mixed results with significant variations within and among regions and countries, as depicted in Tables 1 and 2 .

Risk factors of psychological disorders among participants

Studies established that HCWs responding to the COVID-19 pandemic in sub-Saharan Africa were exposed to long working hours, overworking, exhaustion, high risk of infection, and shortage of personal protective equipment (Tables 3 and 4 ). In addition, HCWs had deep fear, were anxious and stressed with the high transmission rate of the virus among themselves, high death rates among themselves and their patients, and lived under constant fear of infecting themselves and their families with obvious consequences [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. Some HCWs were deeply worried about the lack of standardized PPEs, known treatments and vaccines to protect against the virus. Many health workers had financial problems, lacked support from families and employers if they contracted the virus [ 34 , 35 , 36 , 37 , 39 , 40 , 41 , 42 , 44 ]. An additional source of fear and anxiety was the perceived stigma attached to being infected with COVID-19 by the public [ 36 , 41 ]. Studies found that HCWs, especially those working in emergency, intensive care units, infectious disease wards, pharmacies, and laboratories, were at higher risk of developing adverse mental health impacts compared to others [ 34 , 35 , 36 , 37 , 39 , 40 , 41 , 42 , 43 , 44 ]. This is supported by previous reviews [ 15 , 16 , 17 , 18 , 26 , 28 ] and cross-sectional studies [ 10 , 11 , 12 , 13 , 14 , 20 , 21 , 23 , 25 , 30 ]. However, findings were inconsistent on the impact of COVID-19 on frontline health workers, with ten studies [ 35 , 36 , 37 , 39 , 40 , 41 , 42 , 44 , 45 ] suggesting they are at higher risk than peers and two studies showing no significant difference in psychological disorders relating to the departments [ 38 , 43 ].

The Mali’s study was conducted exclusively in primary care facilities among HCWs not involved in treating COVID-19 cases but still registered a very high prevalence of depression 71.9%, anxiety 73.6%, and insomnia 77.0% [ 39 ]. In contrast, two studies conducted among HCWs at COVID-19 treatment facilities in Ethiopia [ 36 , 38 ] registered much lower prevalence of depression 20.2%, anxiety 21.0%, and insomnia12.4% [ 36 ], and 16.3%, 30.7% and 15.9% respectively, in the second study [ 38 ]. These findings show that not only frontline HCWs experienced mental health disorders during this pandemic but highlight the need for direct interventions for all HCWs regardless of occupation or workstation during this and future pandemics. The significant disparity in the studies could be due to structural, occupational, and environmental issues for example challenges faced by Mali's healthcare systems, characterized by acute equipment shortages, lack of PPEs, human resources, lack of trained and experienced HCWs, ongoing nationwide insecurity, and terrorism compared to Ethiopia. Therefore, local context needs to be considered as contributing factor to mental health disorders among HCWs.

Regional variations of psychological disorders

Tan et al . found a higher prevalence of anxiety among non-medical HCWs in Singapore [ 27 ]. As previously noted, the prevalence of poor psychological outcomes varied between countries. Compared to sub-Saharan Africa and China, data from India [ 23 ] and Singapore [ 27 ] revealed an overall lower prevalence of anxiety and depression than similar cross-sectional data from sub-Saharan Africa [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ] and China [ 9 , 25 , 30 ]. This finding suggests that different contexts and cultures may reveal different psychological findings and that, it is possible that being at different countries’ outbreak curve may play a part, as there is evidence that it is influential.

Tan et al . suggests that medical HCWs in Singapore had experienced a SARS outbreak and thus were well prepared for COVID-19 psychologically and infection control measures [ 27 ]. What can be deduced is that context and cultural factors play a role, not just the cadre or role of healthcare workers [ 16 ]. It also highlights the importance of reviewing evidence regularly as more data emerge from other countries.

One hospital in Ethiopia found that the thought of resignation was associated with higher chances of mental health disorders and that pharmacists and laboratory technicians who did not receive prior training exhibited higher symptoms of mental health disorders compared to others [ 36 ]. Work shift arrangement, considering a dangerous atmosphere presented by working in COVID-19 wards, was one which exacerbated or relieved mental health symptoms among HCWs, with shorter exposure periods being most beneficial [ 36 ]. Meanwhile, studies found that financial worries caused by severe lockdowns and erratic payment of salaries and allowances were also major stressors [ 35 ]. This finding is like studies in Pakistan [ 13 ] and China [ 30 , 32 ].

In this review, HCWs who had contact with confirmed COVID-19 patients were more affected by depression, anxiety, and stress than their counterparts who had not [ 35 , 36 , 37 , 40 , 41 , 43 , 45 ]. This finding is like previous reviews [ 15 , 16 , 17 , 18 , 26 , 28 , 31 ] and cross-sectional studies [ 9 , 10 , 11 , 12 , 13 , 14 , 21 , 23 , 24 , 25 , 27 , 30 ], which reported higher depression, anxiety, and psychological symptoms of distress in HCWs who were in direct contact with confirmed or suspected COVID-19 patients.

A study in Pakistan showed that 80% of participants expected the provision of PPE from authority [ 13 ], and 86% were anxious. Some respondents alluded to forced deployment, while in Mali, 73.3% were anxious, with the majority worrying about the shortage of nurses [ 39 ]. Therefore, prospects of being deployed at a workstation where one had not been trained or oriented contributed to fear among health workers. In the sub-Saharan African context, this scenario can best be represented in HCWs involved in internship who must endure hard work during their training. Tan et al . found that junior doctors were more stressed than nurses in Singapore [ 27 ].

Socio-demographic characteristics

Nearly all studies in our review suggest that socio-demographic variables for example age, gender, marital status, and living alone or with families contribute to the high mental disorder symptoms [ 35 , 36 , 37 , 39 , 40 , 41 , 42 , 43 , 44 ]. We, the authors suggest that these observations are handled cautiously as several investigators of these reviewed articles did not entirely control the influence of confounding variables. An alternative explanation for this study's findings may be the more significant risks of frontline exposure amongst women and junior HCWs, predominantly employed in lower-status roles, many of whom lacked experience and appropriate training within healthcare system globally. It is also important to note that respondents to all studies, when disaggregated by gender, and age, were predominantly younger or female, which may have impacted the outcomes of these findings [ 16 ]. In addition, the consistently higher mortality rates, and risk of severe COVID-19 disease amongst men would suggest that the complete picture regarding gender and mental health during this pandemic is still incomplete [ 16 ]. Moreover, in several studies, both younger and older age groups were equally affected by mental health symptoms but for different reasons. Cai et al . [ 32 ] in a Chinese study on HCWs for example observed that irrespective of age, colleagues' safety, self and families' safety, the lack of treatment for COVID-19 was a factor that induced stress in HCWs. Similarly, in our review, the lack of PPEs, high infection transmission rates, high death rates among HCWs, and the fear of infecting their families were the factors that induced stress in all HCWs [ 34 , 35 , 36 , 37 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ].

We, the authors propose that paying close attention to concerns of HCWs by employers would greatly relieve some stressors and contribute to increased mental well-being of participants. Compared with physicians, our review showed that nurses were more likely to suffer from depression, anxiety, insomnia, PTSD, and stress [ 35 , 37 , 39 , 40 , 41 , 44 , 45 ]. Workloads and night shifts in healthcare facilities, as well as contacts with risky patients, enhanced nurses' mental distress risks [ 15 , 16 , 17 , 18 , 26 , 27 , 28 ]. In addition, nursing staff have more extended physical contacts and closer interactions with patients than other professionals, providing round-the-clock care required by patients with COVID-19 and thus the increased risk [ 15 ]. On the one hand, we posit that most senior physicians are experienced and always keep well-informed with emerging medical emergencies. The majority become aware of emerging epidemic early and actively protect themselves from infections through regular scientific literature updates compared to their junior counterparts. Senior physicians also spend less time in emergency wards unless there is a need to conduct specific procedures which cannot be undertaken by senior housemen or general medical officers. Cai et al . [ 32 ] concluded that it is essential to have a high level of training and professional experience for healthcare workers engaging in public health emergencies, especially for the new staff. As a result, these findings highlight the importance of focusing on all the frontline HCWs sacrificing to contain the COVID-19 pandemic.

Regular monitoring of high-risk groups

There is a need to continue monitoring the high-at-risk groups, including nursing staff, interns, support staff, and all deployed in emergency wards. These high-at-risk groups should be encouraged to undertake screening, treatment, and vaccination to avoid the medium and long-term consequences of such epidemics [ 15 , 16 , 35 , 37 , 40 , 44 ].

Social support and coping mechanisms

The effect of social support and coping measures is in the qualitative study [ 34 ] and three other quantitative studies [ 36 , 41 , 42 ] which concluded that respondents with good social support were less likely to suffer from severe depression, anxiety, work-related stress, and PTSD. The qualitative study identified several coping measures, including community and organizational support, family, and community networks, help from family, responsibility to society, and assistance from community members and strangers, including the symbiotic nature of assistance in the community [ 35 ]. Other measures include providing accommodation and food to employees [ 35 ].

Interestingly, no study examined the association of resilience and self-efficacy with sleep quality, degrees of anxiety, depression, PTSD, and stress. However, a Chinese study by Cai et al. [ 32 ] suggests that the social support given to HCWs causes a reduction in anxiety and stress levels and increases their self-efficacy. In divergence, Xiao et al . [ 46 ] found no relationship between social support and sleep quality.

Only two studies in our review examined the effects of stigma on the mental health of HCWs [ 36 , 41 ] and found that HCWs with perceived stigma were more likely to be depressed, anxious, stressed, and prone to poor sleep quality [ 36 , 41 ]. We, the authors suggest that better community sensitization by creating public awareness involving appropriate local community structures and networks are essential. The broader community in sub-Saharan Africa may have suffered severely from infodemics with severe consequences on their mental health, especially during the difficult lockdowns. In addition, removing discrimination/inequalities at the workplace based on race and other social standings have a powerful influence on the mental health outcomes of HCWs. Also, because emotional exhaustion is long associated with depression, anxiety, and sleep disturbances, none of the studies in our review examined burnout as an essential component of mental health disorders in HCWs in sub-Saharan Africa.

Protective and coping measures

In this review we have provided evidence about personal, occupational, and environmental factors that were important protective and coping measures against psychological disorders. Based on these factors we suggest some protective and coping measures which can help to reduce the negative effects of the pandemic on mental health of HCWs in sub-Saharan Africa. Organizations and healthcare managers need to be aware that primary prevention is key to any successful interventions to contain and control any epidemic. This should take the form of planned regular training, orientation and continuing medical education grounded on proven infection control measures. These measures need to be backed up by timely provision of protective equipment, drugs, testing facilities, vaccines, isolation facilities, clinical and mental health support, and personal welfare of HCWs [ 35 , 36 , 37 , 42 , 45 ]. The effect of community and organizational support and coping measures was shown by the qualitative study [ 35 ] and five other quantitative studies [ 36 , 37 , 41 , 42 , 43 ] indicating that respondents who had good social and organizational support were less likely to suffer from severe depression, anxiety, work related stress and PTSD. Prior experience with comparable pandemics and training are suggested as beneficial coping strategies for healthcare workers during this pandemic but also local social structural and geopolitical conditions appear to determine the pattern and evolution of mental health symptoms among HCWs [ 14 , 15 , 31 , 32 , 47 ]. In our case the high prevalence of all mental health symptoms in non-frontline primary health care facilities in Mali [ 39 ] which was already plagued with instability and weak healthcare systems prior to the pandemic is a case in point. Results are particularly consistent in showing that provision of PPEs, testing kits, orientation training of workers, work shift arrangements, provision of online counselling, provision of food and accommodation and prompt payment of allowances by employers were important protective measures [ 35 , 36 , 37 , 38 , 39 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. The feeling of being protected is associated with higher work motivation with implication for staff turnover [ 35 , 38 , 43 , 45 ]. Hence, physical protective materials [ 14 ], together with frequent provision of information, should be the cornerstone of any interventions to prevent deterioration in mental health of HCWs (Table 5 ). Finally, provision of rest rooms, online consultation with psychologists/psychiatrists, protection from financial hardships, access to social amenities and religious activities are some important coping measures [ 35 , 36 , 38 , 42 , 45 ]. In this era of digital health care with plentiful internet and smartphones, organization can conduct online trainings, online mental health education, online psychological counselling services, and online psychological self-help intervention tailored to the needs of their HCWs [ 35 , 37 , 42 ]. In addition, it is essential to understand and address the sources of anxiety among healthcare professionals during this COVID-19 pandemic, as this has been one of the most experienced mental health symptoms [ 48 ]. Adequate protective equipment provided by health facilities is one of the most important motivational factors for encouraging continuation of work in future outbreaks. Furthermore, availability of strict infection control guidelines, specialized equipment, recognition of their efforts by facility management, government, and reduction in reported cases of COVID-19 provide psychological benefits [ 15 , 32 ]. Finally, we call upon Governments (the largest employers of HCWs) in sub-Saharan Africa to do what it takes to improve investments in the mental health of HCWs and plan proactively in anticipation of managing infectious disease epidemics, including other expected and unexpected disasters.

Future research direction

There was no study that examined the association of resilience and self-efficacy with sleep quality, degrees of anxiety, depression, PTSD, and stress. Although emotional exhaustion has long been associated with depression, anxiety, and sleep disturbances, no study in our review examined burnout as an important component of mental health disorders in HCWs in sub-Saharan Africa. The impacts of infodemics, stringent lockdown measures, discrimination/inequalities at workplaces based on race, and other social standings on mental health outcomes of HCWs need to be investigated.

Future studies are needed on the above including other critical areas like suicidality, suicidal ideations, and substance abuse during the COVID-19 pandemic. In addition, there is a significant variation of related literature calling for more rigorous research in future. More systematic studies will be required to clarify the full impact of the pandemic so that meaningful interventions can be planned and executed at institutional and national levels in the Sub-Saharan Africa.

Limitations of this study

There are some limitations to this study. First, most of the studies are from one country, limiting the generalizability of the results to the whole African continent. Second, all the studies were cross-sectional and only looked at associations and correlations. There is a need for prospective or retrospective cohort or case–control studies on this subject matter. Longitudinal research studies on the prevalence of mental disorders in the COVID-19 pandemic in the sub-Saharan Africa are urgently required. Third, most studies reviewed did not adequately examine protective factors or coping measures of the health workers in their settings. In addition, most studies did not pay strict attention to confounding variables which could have led to inappropriate results and conclusions. Fourth, most sample sizes were small and unlikely representative of the population and yet larger sample sizes would better identify the extent of mental health problems among health workers in the region. Fifth, depression, anxiety, and stress were assessed solely through self-administered questionnaires rather than face-to-face psychiatric interviews. Sixth, these studies employed various instruments and different cut-off thresholds to assess severity. Notably, the magnitude and severity of reported mental health outcomes may vary based on the validity and sensitivity of the measurement tools. Seventh, there was no mention of mental baseline information among the studied population and therefore it was unknown if the studied population had pre-existing mental health illnesses that decompensated during the pandemic crisis. Eight, investigators did not give much attention to stigma, burnout, resilience, and self-efficacy among study participants.

Furthermore, our review did not employ systematic reviews or meta-analyses methods for the information generated. This narrative review paper precluded deeper insight into the quality of reviewed articles for this paper. Still, our observation was that investigators did not consider the strict lockdown measures, quarantine, and isolation imposed by many countries in sub-Saharan Africa as possible risk factors for mental health disorders among HCWs.

Based on the articles reviewed, the prevalence of depression, anxiety, insomnia, and PTSD in HCWs in the sub-Saharan Africa during the COVID-19 pandemic is high. We implore health authorities to consider setting up permanent multidisciplinary mental health teams at regional and national levels to deal with mental health issues and provide psychological support to patients and HCWs, always supported with sufficient budgetary allocations.

Long-term surveillance is essential to keep track of insidiously rising mental health crises among community members. There is a significant variation of related literature thus calling for more rigorous research in the future. More systematic studies will be needed to clarify the full impact of the pandemic so that meaningful interventions can be planned better and executed at institutional and national levels in sub-Saharan Africa.

Availability of data and materials

Datasets analysed in the current study are available from the corresponding author at a reasonable request.

Abbreviations

Coronavirus disease 2019

Healthcare workers.

Mental health

Public health emergency

Personal protective equipment

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We thank Uganda Medical Association Acholi-branch members for the financial assistance which enabled the team to conduct this study successfully.

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Freddy Wathum Drinkwater Oyat, Johnson Nyeko Oloya, Pamela Atim, Judith Aloyo & David Lagoro Kitara

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Oyat, F.W.D., Oloya, J.N., Atim, P. et al. The psychological impact, risk factors and coping strategies to COVID-19 pandemic on healthcare workers in the sub-Saharan Africa: a narrative review of existing literature. BMC Psychol 10 , 284 (2022). https://doi.org/10.1186/s40359-022-00998-z

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Obstructive sleep apnea and acute lower respiratory tract infections: a narrative literature review.

1. Introduction

2. literature search strategy, 3. obstructive sleep apnea and community-acquired pneumonia, 4. obstructive sleep apnea and influenza pneumonia, 5. obstructive sleep apnea and covid-19 pneumonia, 6. obstructive sleep apnea and lower respiratory tract infections: pathophysiology, 6.1. altered immunity, 6.2. risk of aspiration, 6.3. the role of obesity and other comorbidities, 7. obstructive sleep apnea and lower respiratory tract infections: treatment, 7.1. settings of care and empiric antibiotics, 7.2. specific risks guiding empiric antibiotic therapy, 7.3. antibiotic pharmacokinetics, side effects, and resistance, 8. discussion, 9. conclusions, supplementary materials, author contributions, institutional review board statement, informed consent statement, data availability statement, acknowledgments, conflicts of interest.

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Nemet, M.; Vukoja, M. Obstructive Sleep Apnea and Acute Lower Respiratory Tract Infections: A Narrative Literature Review. Antibiotics 2024 , 13 , 532. https://doi.org/10.3390/antibiotics13060532

Nemet M, Vukoja M. Obstructive Sleep Apnea and Acute Lower Respiratory Tract Infections: A Narrative Literature Review. Antibiotics . 2024; 13(6):532. https://doi.org/10.3390/antibiotics13060532

Nemet, Marko, and Marija Vukoja. 2024. "Obstructive Sleep Apnea and Acute Lower Respiratory Tract Infections: A Narrative Literature Review" Antibiotics 13, no. 6: 532. https://doi.org/10.3390/antibiotics13060532

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