case study about cardiovascular disease

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• 10 February 2022

Heart-disease risk soars after COVID — even with a mild case

• Saima May Sidik

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Even a mild case of COVID-19 can increase a person’s risk of cardiovascular problems for at least a year after diagnosis, a new study 1 shows. Researchers found that rates of many conditions, such as heart failure and stroke, were substantially higher in people who had recovered from COVID-19 than in similar people who hadn’t had the disease.

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Nature 602 , 560 (2022)

doi: https://doi.org/10.1038/d41586-022-00403-0

Xie, Y., Xu, E., Bowe, B. & Al-Aly, Z. Nature Med . https://www.nature.com/articles/s41591-022-01689-3 (2022).

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Cardiovascular Diseases, Medications, and ALS: A Population-Based Case-Control Study

Affiliations.

• 1 Department of Epidemiology and Population Health, Stanford University, Stanford, California, USA, [email protected].
• 2 Stanford Center for Population Health Sciences, Stanford University School of Medicine, Stanford, California, USA, [email protected].
• 3 Department of Epidemiology and Population Health, Stanford University, Stanford, California, USA.
• 4 Department of Neurology, University of Kentucky, Lexington, Kentucky, USA.
• 5 Stanford Center for Population Health Sciences, Stanford University School of Medicine, Stanford, California, USA.
• PMID: 36481735
• PMCID: PMC9986836
• DOI: 10.1159/000526982

Introduction: We investigated the associations between antecedent all-cause CVD diagnoses, cause-specific CVD diagnosis, and CVD medication prescriptions with the risk of developing amyotrophic lateral sclerosis (ALS).

Materials and methods: We conducted a population-based case-control study of U.S. Medicare enrollees from 2006 to 2013. The final sample included 3,714 incident ALS cases and 18,570 controls (matched on age, sex, enrollment length, and county). Information was collected from Medicare Parts A, B, and D administrative claims data on hypertension, ischemic heart disease, heart failure, acute myocardial infarction, atrial fibrillation, prescriptions of angiotensin-converting enzyme inhibitors, angiotensin II receptors blockers, calcium channel blockers, beta blockers, and antiarrhythmics. Associations were evaluated using conditional logistic regression adjusting for age, sex, race/ethnicity, geographical location, alcohol and tobacco use, and socioeconomic status.

Results: The odds ratio (OR) for having one or more ICD-9 codes for any cardiovascular disease diagnosis at least 24 months prior to the date of ALS diagnosis was 0.85 (95% confidence interval [CI]: 0.78-0.92). Cardiovascular conditions that were inversely associated with ALS included heart failure (OR = 0.79; 95% CI 0.70-0.89), atrial fibrillation (OR = 0.81; 95% CI 0.77-0.92), and hypertension (OR = 0.91; 95% CI 0.84-0.98). Exposures to several classes of cardiovascular medications were inversely associated with ALS risk even after adjusting for confounding by indication, including ACE inhibitors (OR = 0.84, 95% CI 0.77-0.91), calcium channel blockers (OR = 0.64, 95% CI 0.59-0.70), and beta blockers (OR = 0.76, 95% CI 0.71-0.83).

Discussion/conclusion: These findings merit additional research, including animal studies and pilot clinical trials, to further evaluate and evidence the effects of ACEIs, CCBs, and BBs on the risk of developing and clinical expression of ALS.

Keywords: Amyotrophic lateral sclerosis; Angiotensin-converting enzyme inhibitors; Cardiovascular disease; Hypertension; Medications.

© 2022 The Author(s). Published by S. Karger AG, Basel.

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Chapter 4:  10 Real Cases on Valvular Heart Disease: Diagnosis, Management, and Follow-Up

Nikhitha Mantri; Puvanalingam Ayyadurai; Marin Nicu

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Case 1: Management of Patent Foramen Ovale

A 26-year-old woman presented to the emergency department (ED) with chest pain for 1 day. The chest pain started suddenly, was nonradiating, and was associated with arm movement. She did house cleaning 1 day prior to presentation. The pain was not relieved by taking over-the-counter medication. She denied palpitations, dizziness, shortness of breath, and trauma. Her family history and social history were unremarkable. On presentation to the ED, her vital signs were stable. On physical examination, she did not have any significant findings except chest wall tenderness. Her ECG showed first-degree atrioventricular block. Initial laboratory findings were unremarkable. She was given analgesics. The patient was transferred to the telemetry floor, where an echocardiogram was performed, which showed a normal left ventricular ejection fraction with no wall motion or valvular abnormality and a small patent foramen ovale (PFO). How would you manage this case?

This patient is a young asymptomatic woman who presented with musculoskeletal chest pain. Incidentally, she was noted to have a PFO, which is asymptomatic and does not require any treatment.

PFO is an opening in the atrial wall at the location of the fossa ovalis that remains open beyond 1 year of life. After birth, when the pulmonary circulation develops, the foramen ovale closes due to the increase in left atrial pressures, which takes up to 1 year.

PFO is usually asymptomatic and is often found incidentally. However, it carries a risk of paradoxical embolism in high-risk patients. Some patients present with systemic embolism causing organ infarcts and even myocardial infarction.

The diagnostic test of choice is echocardiography. PFO can be detected using color flow Doppler, contrast echocardiography, and transmitral Doppler.

Isolated PFO does not usually require any treatment unless it is associated with an unexplained neurologic event. Such conditions are treated with antiplatelet drugs and anticoagulation therapy. Percutaneous closure of the PFO is an option when there is contraindication to medical management and anticoagulant treatment, in the setting of paradoxical embolism or cryptogenic stroke. Surgical closure is indicated when the opening is >25 mm or when there is failure of a percutaneous device.

PFO is usually asymptomatic and is often found incidentally.

Isolated PFO does not usually require any treatment unless it is associated with an unexplained neurologic event.

Case 2: Management of Aortic Stenosis

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• v.105(5); 2015 Nov

Case 5/2015 – 88-Year-Old Female with Chronic Coronary Artery Disease, Upper Limb Thrombosis, Atrial Fibrillation and Cardiac Arrest

Magaly marçula.

Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP – Brazil

Vera Demarchi Aiello

An 88-year-old female was admitted due to pain and swelling of the left upper limb swelling (September 28, 2011).

She was first admitted to Instituto do Coração (InCor) at the age of 73 years (December 12, 1996), because of chest angina on great exertion for 8 months.

On that occasion, she reported arterial hypertension, glucose intolerance, hypercholesterolemia, hypertriglyceridemia, family history of sudden death, and smoking cessation at the age of 51 years.

Her physical examination evidenced heart rate of 60 bpm, blood pressure of 150/80 mmHg. Her heart, lung and abdomen examinations were normal. Her lower limbs showed no edema and her pulses were symmetrical.

The electrocardiogram (December 9, 1996) revealed sinus rhythm, an electrically inactive area in the inferodorsal wall, and ventricular repolarization changes with inverted T waves from V 1 to V 5 ( Figure 1 ).

ECG. Sinus rhythm, probable electrically inactive inferodorsal area and diffuse ventricular repolarization changes.

The laboratory tests (January 13, 1997) evidenced: glycemia, 115 mg/dL; creatinine, 1.4 mg/dL; total cholesterol, 295 mg/dL; high-density lipoprotein (HDL-cholesterol), 56 mg/dL; low-density lipoprotein (LDL-cholesterol), 183 mg/dL; and triglycerides, 179 mg/dL.

Her coronary angiography (December 12, 1996) showed obstructions of 90% in the right coronary and circumflex arteries, and of 70% in the anterior interventricular artery, in addition to normal left ventricular motility.

On January 20, 1997, the patient was submitted to successful coronary angioplasty with stent implantation in the circumflex artery, and unsuccessful coronary angioplasty of the right coronary artery, which was occluded. On January 29, 1997, she underwent coronary angioplasty with stent implantation in the anterior interventricular coronary branch.

The patient became asymptomatic. On August 8, 1997, control coronary angiography evidenced occlusion of the right coronary artery, irregularities in the interventricular and circumflex arteries, and a 70% obstruction in the first branch of the left marginal artery.

The laboratory assessment (March 25, 1998) showed: triglycerides, 338 mg/dL; total cholesterol, 294 mg/dL; LDL-cholesterol, 181 mg/dL; and HDL-cholesterol, 45 mg/dL. On January 27, 2000, a new laboratory assessment evidenced: triglycerides, 166 mg/dL; total cholesterol, 289 mg/dL; LDL-cholesterol, 210 mg/dL; and HDL-cholesterol, 46 mg/dL.

Simvastatin was added to the ongoing fenofibrate.

The laboratory assessment (December 14, 2001) revealed: triglycerides, 239 mg/dL; total cholesterol, 268 mg/dL; LDL-cholesterol, 160 mg/dL; and HDL-cholesterol, 60 mg/dL.

The new coronary angiography (December 18, 2001) showed a 90% obstruction in the right coronary artery, and complicated with injury and thrombosis of the right brachial artery. Thromboembolectomy and brachial-brachial graft with the ipsilateral basilic vein were performed.

The patient remained asymptomatic until 2011, with the diagnosis of diabetes mellitus since 2008, when metformin and glybenclamide were prescribed.

On August 2011, the patient sought medical care complaining of angina on moderate exertion, being then submitted to coronary angiography (August 22, 2011), which showed: in-stent restenosis of 90% associated with an 80% obstruction in the mid third of the anterior interventricular artery; an 80% obstruction in the first branch of the diagonal artery; a 90% distal obstruction of the circumflex artery with patent coronary stent; an obstruction in the ostium of the second branch of the left marginal artery; a 90% obstruction of the right coronary artery; and preserved left ventricular motility.

On September 15, 2011, the patient had prolonged chest pain at rest, and her laboratory assessment showed: hemoglobin, 12.1 g/dL; red blood cell count, 37%; platelets, 348,000/mm 3 ; creatinine, 1.11 mg/dL; potassium, 4 mEq/L; sodium, 140 mEq/L; triglycerides, 223 mg/dL; total cholesterol, 175 mg/dL; HDL-cholesterol, 47 mg/dL; LDL-cholesterol, 83 mg/dL; creatine kinase MB mass, 0.2 ng/mL; troponin, 0.064 ng/mL; activated prothrombin time (APT) according to International Normalized Ratio (INR), 1; and activated partial thromboplastin time ratio (APTT), 0.84.

The electrocardiography performed on September 15, 2011, revealed sinus rhythm, diffuse ventricular repolarization changes, and no changes of the special leads V 3r , V 4r , V 7 and V 8 ( Figures 2 and ​ and3 3 ).

ECG. Sinus rhythm, diffuse ventricular repolarization changes.

ECG. Right and dorsal leads, no evidence of ST-segment changes.

The sequential laboratory assessment on September 16, 2011, showed creatine kinase MB mass of 0.18 ng/mL and troponin of 0.34 ng/mL. On that same day, the patient underwent balloon angioplasty of the first diagonal branch, with stenting of the anterior interventricular artery. Bleeding, hemoglobin drop to 8.8 g/dL and pseudoaneurysm formation at the left femoral artery puncture site occurred.

On September 20 and 23, 2011, the pseudoaneurysm was injected with prothrombin, with resolution of local bleeding. The patient was discharged on September 26, 2011.

Two days after hospital discharge, she patient sought the emergency unit because of pain and left upper limb swelling.

The laboratory tests on September 28, 2011, showed: hemoglobin, 10.4 g/dL; red blood cell count, 32%; medium corpuscular volume (MCV), 103 fl; leukocytes, 102,310/mm 3 (band neutrophils 36%, segmented neutrophils 62%, lymphocytes 1%, monocytes 1%); platelets, 292,000/mm 3 ; creatine kinase MB mass, 0.27 ng/mL; troponin I, 0.126 ng/mL; creatinine, 2.52 mg/dL (glomerular filtration, 19 mL/min/1.73 m 2 ); aspartate aminotransferase (AST), 77 U/L; alanine aminotransferase (ALT), 75 U/L; gamma glutamyl transferase, 179 U/L; total bilirubin, 1.05 mg/dL; direct bilirubin, 0.55 mg/dL; sodium, 136 mEq/L; potassium, 4.6 mEq/L; APT (INR), 1.3; and APTT, 1.04.

Doppler ultrasound showed venous thromboses in the left upper limb, and anticoagulant therapy was initiated.

A few hours later, the patient had atrial fibrillation with rapid ventricular response. After amiodarone infusion, she had dyspnea, consciousness lowering, respiratory failure requiring orotracheal intubation for ventilatory support, and cardiac arrest with pulseless electrical activity. She recovered, but showed high-grade atrioventricular block, atrial fibrillation, severe bradycardia and right QRS axis deviation.

On September 29, 2011, the laboratory tests were as follows: hemoglobin, 10.5 g/dL; red blood cell count, 35%; MCV, 109 fl; leukocytes, 9,820/mm 3 (metamyelocytes 1%, band neutrophils 40%, segmented neutrophils 41%, eosinophils 1%, lymphocytes 14%, monocytes 3%); platelets, 202,000/mm 3 ; creatine kinase MB mass, 13.19 ng/mL; troponin I, 1.22 ng/mL; urea, 108 mg/dL; creatinine, 2.82 mg/dL (glomerular filtration, 12 mL/min/1.73m 2 ); sodium, 135 mEq/L; potassium, 5 mEq/L; AST, 756 U/L; ALT, 312 U/L; gamma glutamyl transferase, 136 U/L; total bilirubin, 1.19 mg/dL; direct bilirubin, 0.71 mg/dL; C-reactive protein, 209 mg/L; venous lactate, 105 mg/dL; APT (INR), 3.9; and APTT, 7.97. Venous blood gas analysis showed: pH, 6.55; pCO 2 , 33.9 mm Hg; pO 2 , 27.1 mm Hg; O 2 saturation, 21.4%; bicarbonate, 2.8 mEq/L; and base excess, (-) 29.8 mEq/L.

The patient underwent temporary pacemaker implantation, but the refractory shock persisted. She had a new cardiac arrest and no longer responded to resuscitation maneuvers, dying on September 29, 2011.

Clinical aspects

The patient is an 88-year-old female, who, because of chest angina, underwent percutaneous angioplasty with stenting, remaining asymptomatic for 13 years. The angina reappeared, and, after a new percutaneous intervention, she died. She underwent seven coronary angiographies, three of which with angioplasty and stenting. The fifth and seventh procedures had complications.

The first point of interest is the indication of intervention therapy with stenting to an elderly patient with chest angina. Published studies support that indication. The results of intervention therapy in patients older than 80 years (n = 983) have shown a four-year survival of 71.6% for stent implantation (n = 289), better than that achieved with isolated drug treatment (n = 561, survival of 60.3%) 1 . The good results of the intervention therapy were later confirmed in 79/276 patients (52%) aged 80 ± 4 years, whose four-year survival was 72% 2 . The clinical experience confirms those observations. Thus, in our patient, the percutaneous intervention therapy performed for the first time at the age of 74 years and followed by 13 asymptomatic years was again indicated, when she became symptomatic.

The patient underwent seven coronary angiographies in 15 years of follow-up, three of which (42.9%) with percutaneous coronary intervention via brachial and femoral punctures. Two of those revascularizations (66.7%) complicated with thrombosis, bleeding and pseudoaneurysm formation, requiring surgery for thromboembolectomy in the first event, and thrombin administration in the pseudoaneurysm and expectant management in the second event.

The second point of interest is performing coronary angiography in octogenarians, whose mortality is higher (0.8%) than that of the general elderly population (0.11%). In that age group, the risk of vascular complications, such as arterial occlusions requiring surgical correction or thrombectomy, retroperitoneal bleeding, formation of hematoma, pseudoaneurysm and arteriovenous fistula, as well as the risk of infection, is greater (5%). Studies have confirmed that the diagnosis of femoral pseudoaneurysm occurred in more than 0.2% of the cases, in 8% of the catheterization processes 3 , the risk of pseudoaneurysm formation being higher in cases whose compression of the femoral artery access was performed with a device (39 in 1768 events – 2.2%) as compared to those with manual compression (1720 events/1.7%) at the puncture site 4 . A meta-analysis has confirmed the risk of bleeding at the femoral artery puncture site, comparing compression with devices (n = 1700) to manual compression (n = 1500), the risks being 4.6% and 4.1%, respectively. The estimated risk of an intervention at the puncture site is 1.6-fold higher with compression with devices than with manual compression. The risks of blood transfusion and of arterial ischemia in the lower limb for compression with devices were, respectively, 1.2 and 2.1 times greater than those using manual compression. Despite the nonsignificant results, complications were more frequently found when using compression with devices (3.8%) at the arterial puncture site than when using manual compression (1.7%) 4 .

In the case discussed, the patient being of the female sex and submitted to therapeutic percutaneous coronary intervention increased the risk for pseudoaneurysm formation 5 . The expectant management of the femoral pseudoaneurysm assumes a vascular diameter smaller than 2 cm, and the reason for not using ultrasound-guided percutaneous injection of thrombin might have been the possibility of spontaneous thrombosis of the vascular content 5 .

The third point of interest is the treatment of elderly patients with coronary artery disease and its impact on survival. A study of 7472 octogenarians (mean age of 83 years) undergoing percutaneous coronary intervention has reported mortality ranging from 0 to 19%, being around 5% for patients older than 85 years, the mortality predictors being as follows: cardiogenic shock (31%); acute myocardial infarction (11%); lower ejection fraction (35%); kidney failure (7.2%); first coronary intervention (2.7%); patients older 85 years (1.8%); and diabetes mellitus (1.2%) 6 .

The recommendation of optimized drug treatment as the initial option for patients with chronic coronary artery disease is supported by a meta-analysis with 63 studies (1852 symptomatic and asymptomatic patients diagnosed with chronic coronary artery disease, mean age ranging from 56 to 65 years), comparing four possibilities of procedures (percutaneous coronary intervention versus drug treatment; angioplasty with stent versus conventional balloon angioplasty; angioplasty with stent versus drug treatment; angioplasty with drug eluting stent versus angioplasty with bare-metal stent), with no difference in mortality, acute myocardial infarction, coronary artery bypass graft surgery or need for a new procedure within 12 months 7 .

In the case discussed, 15 years after coronary disease stratification and percutaneous coronary intervention, the patient had angina on moderate exertion, suggesting that the therapeutic strategy with percutaneous and drug revascularization, to control risk factors, did not prevent disease progression.

Considering that the patient had coronary artery disease and diabetes mellitus, the clinical experience confirms the greater risk for restenosis and occlusion after revascularization procedures, via either percutaneous coronary intervention or coronary artery bypass graft surgery, as compared to nondiabetic patients with multivessel coronary disease. Hlatky et al. 8 have reported similar mortality for patients undergoing coronary artery bypass graft surgery (575/3889 patients) and for those (628/3923) undergoing percutaneous coronary intervention, 15% and 16%, respectively. In patients older than 65 years, however, treatment changed mortality. In patients with diabetes, the mortality of those undergoing coronary artery bypass graft surgery (615 patients) was substantially lower than that of those (618 patients) undergoing percutaneous coronary intervention, suggesting that coronary artery bypass graft surgery yields lower mortality in patients with diabetes older than 65 years 8 .

The controversy over the therapeutic option for the elderly is evident when assessing the result of two studies performed in patients older than 75 years with coronary artery disease. The Italian Elderly Acute Coronary Syndrome Trial Investigators has compared the survival of patients treated with an early invasive approach versus the clinical conservative approach, evidencing no advantage of the initial aggressive therapy 9 . Another recent study with patients diagnosed with non-ST-elevation acute coronary syndrome has estimated the presence of events (mortality, myocardial infarction, stroke, re-hospitalization due to cardiovascular cause, or bleeding) in the invasive treatment (86/182 patients; 47.3% females) as compared with that in the conservative approach (70/131 patients; 53.4% females). That study has shown those events in 24.7% of the patients undergoing early invasive therapy (45/182 patients) as compared to 40.5% (53/131 patients) of those undergoing the initial conservative treatment in a one-year follow-up. The patients undergoing invasive treatment had an improvement in survival with a reduction in death/nonfatal infarction (14.3% or 26 patients) and in new hospitalizations (9.9% or 18 patients) as compared to those undergoing conservative treatment (27.5% or 36 patients, and 16.8% or 22 patients, respectively) 10 .

It is worth noting that, although stents efficiently reestablish the vascular lumen by reducing 50% of the angiographic restenosis, they cause injure to the vascular wall, and, via repairing mechanisms, a healing response that, depending on the severity of the process, will lead to reobstruction of the vessel treated. The analysis of the composition of 40 coronary thrombi manually aspirated in the first 4 to 16.5 hours from chest pain onset, during primary percutaneous coronary intervention, has identified the presence of fibrin (49.1%), red blood cells (24.2%), platelets (11.6%) and leukocytes (3.7%) in the material studied 11 .

According to Montalescot et al., although current interventional treatments reduce the risk of restenosis by as much as 40% as compared to previous techniques, the introduction of conventional stent has not improved survival as compared to balloon angioplasty 12 . In addition, the use of drug-eluting stents has not improved survival as compared to conventional stents 13 .

The patient underwent new percutaneous coronary intervention with coronary stenting in the anterior interventricular artery and balloon angioplasty in the first branch of the diagonal artery, and had immediate and late, local and systemic complications of the procedure (bleeding at the puncture site with pseudoaneurysm formation in the left femoral artery and venous thrombosis in the left upper limb).

The acute drop in hemoglobin after the percutaneous intervention (the seventh procedure), as well as stent implantation with evidence of macrocytosis and elevation of the MCV can be associated with excessive regeneration of bone marrow or with altered DNA synthesis, probably related to post-hemorrhage anemia. The presence of leukocytosis with 36% of band neutrophils can be explained as stimulation by the inflammatory process, trauma or necrosis with release of interleukin-1, mobilization of the bone marrow reserve pool of band neutrophils and “shift to the left”. The absence of neutrophilia can be explained by the patient’s age group, suggesting the possibility of an infectious process.

Analyzing the laboratory tests, the increase in serum creatinine with a reduction in glomerular filtration (19 mL/min/1.73 m 2 ) and rapid progression with elevation in aminotransferases suggest renal injury with severe renal failure and acute liver failure due to ischemia/hypoxia and prolonged hypotension.

It is worth noting that, although the two sequential measurements of troponin (0.126 ng/mL and 1.22 ng/mL) performed at a 24-hour interval were within the normal range, a significant increase in the second value was observed, which can suggest an increased cardiovascular risk. That risk was confirmed in a study with 2285 patients diagnosed with stable coronary artery disease and diabetes mellitus (female sex, 34.9%; age range, 55 to 68 years; mean age, 61 years), and followed up for five years 14 . Cardiovascular death, non-fatal acute myocardial infarction or non-fatal stroke occurred in 12.9% (178/1388 patients) of those with normal troponin as compared to 27.1% (243/897 patients) of those with elevated troponin. An elevation in troponin concentration greater than 25% in a four-year follow-up proved to be an independent marker of cardiovascular risk 14 .

The patient had atrial fibrillation with rapid ventricular response and developed hemodynamic instability, respiratory instability and cardiac arrest after amiodarone intravenous infusion. Although the clinical experience confirms the efficacy of amiodarone to reverse atrial fibrillation in 80% of the cases, it should be carefully used in elderly patients, with special attention paid to its infusion velocity. Two authors have assessed the incidence of atrial fibrillation and the survival of patients with that arrhythmia. Reinel et al. have studied 310 episodes of arrhythmia in 133 severely ill patients, 29.8% of which (83/278 episodes of tachycardia) represented atrial fibrillation. Baine et al. have studied the incidence of types of arrhythmia in patients (144512) older than 65 years, atrial fibrillation being the most frequently found cardiac rhythm (44.8%) 15 . In another study of 4060 patients with atrial fibrillation and mean age of 69.7 years (range, 60.7 – 78.7), the mortality of those with controlled cardiac rhythm was 17.5% (356/2033 patients) as compared to 15.3% (310/2027 patients) among those with controlled heart rate 16 .

The fourth point of interest was the patient’s sudden clinical deterioration, suggesting the release of mediators, causing hypoxemia and hypotension requiring the differential diagnosis between sepsis and pulmonary thromboembolism. The rapid course with cardiac arrhythmia, hypotension, severe hypoxemia and cardiac arrest with pulseless electrical activity can be associated with massive pulmonary embolism 17 . A study has confirmed that 79% of the patients with pulmonary embolism had evidence of deep venous thrombosis of the lower limbs, and, of the hereditary or acquired risk factors, advanced age and antiphospholipid antibody syndrome increased the likelihood of acute episodes of repeated deep venous thrombosis and pulmonary embolism 18 .

The cause of death was pulmonary thromboembolism. The patient with chronic coronary artery disease and several cardiovascular risk factors, such as arterial hypertension, hypercholesterolemia and diabetes mellitus, showed progressive coronary atherogenesis. In one decade, she had repeated episodes of vascular thrombosis, the last thromboembolic event occurring at an uncommon site (upper limb), suggesting the need for thrombophilia assessment. The patient had cardiac arrhythmia, hemodynamic instability and refractory cardiogenic shock probably due to massive pulmonary embolism, and died. (Magaly Marçula, MD)

Diagnostic hypotheses: pulmonary thromboembolism, deep venous thrombosis at an uncommon site, chronic coronary artery disease. Cause of death: cardiogenic shock. (Magaly Marçula, MD)

The heart weighed 453 g (normal for the female sex: up to 350 g). Its opening revealed hypertrophy of the left ventricular walls and mottled aspect of the ventricular septum myocardium ( Figure 4 ). On microscopic examination, the mottled area corresponded to 2-to-3-week-old myocardial infarction ( Figure 5 ). Fibrotic or scarring foci and focal areas of extracellular amorphous substance accumulation with staining characteristics of amyloid (Congo red) were identified ( Figure 6 ). The microscopic study of the coronary arteries revealed recent partial thrombosis on the seventh cm of the right coronary artery, in addition to atherosclerosis with 80% obstruction. The anterior interventricular and circumflex branches of the left coronary artery had stents placed several years before and were submitted to special processing with resin inclusion, allowing for histological sections. These sections showed fibrous (anterior interventricular branch) or fatty (circumflex branch) atherosclerotic plaques in the coronary arteries causing in-stent occlusion ( Figures 7 and ​ and8 8 ).

Cross section of the ventricles showing mild left ventricular hypertrophy, in addition to irregularly mottled septal area and whitish area in the posteromedial papillary muscle (old healed infarction).

Photomicrographs of the ventricular myocardium showing: a) area of organizing infarction corresponding to the mottled ventricular septum area; b) fibrotic and scarring area in the inferior wall. Hematoxylin-Eosin, 20X and 5X, respectively.

Polarized light photomicrographs of the ventricular myocardium. Greenish areas correspond to amyloid substance deposits. Congo red under polarized light, 10X.

Photomicrographs of segments of the left coronary artery anterior interventricular branch, where signs of the old stent rods are seen (rectangular regions, usually empty due to artifactual detachment of the stent during the section, but sometimes partially filled with a dark residual material from the stent). There is fibrous neointimal thickening inside the old stent (neoatherosclerosis with fibrous plaque, marked with asterisks). In addition, residues of the older calcified plaque, external to the stent (yellow arrow in panel a) can be seen. Verhoeff stain for elastic fibers, 2.5X and 5X, respectively.

Photomicrographs of segments of the left coronary artery circumflex branch, where signs of the old stent rods are seen (rectangular regions, usually empty due to artifactual detachment of the stent during the section). Note, inside the stent (panel a), neoatherosclerosis with mixed plaque, fibrous (asterisks) and fatty, rich in xanthomatous histiocytes (detail in panel b). Hematoxylin-Eosin, 5X and 10X, respectively.

The lungs weighed together 860g, and their microscopic study showed areas of alveolar edema ( Figure 9 ). In addition, thromboemboli were identified in small intraparenchymal arteries with Gram-positive cocci. There was terminal bronchopneumonia, not related to the septic thromboembolism.

Photomicrographs of intra-alveolar edema in the lungs. Hematoxylin-Eosin, 5X.

Anatomopathological diagnoses: moderate systemic and coronary atherosclerosis with in-stent atheroma plaques; cardiovascular amyloidosis; pulmonary alveolar edema; terminal bronchopneumonia; and foci of septic pulmonary thromboembolism.

Cause of death: organizing myocardial infarction in the ventricular septum (Vera Demarchi Aiello, Prof. MD)

Coronary arteries submitted to stent implantation can develop late in-stent restenosis, due to neoatherosclerosis, which happened in the case reported. The resin inclusion technique allowed for sectioning and assessing the stented coronary segments. There were atherosclerotic plaques of varied composition (fibrous and fatty). That obstruction accounted for the recent septal infarction. Despite the occlusive lesions in the right coronary artery, which was not the dominant vessel in this case, no infarction was identified in that coronary artery territory.

A very recent study by Taniwaki et al. 19 has shown that in-stent neoatherosclerosis was more frequently found in patients with clinical and angiographic evidence of atherosclerosis progression in nontreated native coronary segments. Cardiovascular amyloidosis was an occasional finding, and, although not extensive, it might have contributed to the final myocardial dysfunction.

The lungs showed focal alveolar edema and terminal bronchopneumonia. The source of the septic thromboemboli was not identified. The gross examination of the heart evidenced no signs of infectious endocarditis that could explain that embolic event. According to clinical data, there were clinical signs of venous thrombosis of the left upper limb, which, if infected, could have been the embolic source. Usually the exposed areas are not inspected on the postmortem examination, explaining why that thrombosis was not studied. (Vera Demarchi Aiello, Prof. MD)

Editor da Seção: Alfredo José Mansur ( rb.psu.rocni@rusnamja )

Editores Associados: Desidério Favarato ( rb.psu.rocni@otaravaflcd )

Vera Demarchi Aiello ( rb.psu.rocni@arevpna )

Cardiac comorbidities in McArdle disease: case report and systematic review

• Review Article
• Open access
• Published: 27 May 2024

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• Domeniko Hoxhaj 1   na1 ,
• Gabriele Vadi   ORCID: orcid.org/0009-0002-3273-5362 1   na1 ,
• Lorenzo Bianchi 2 ,
• Lorenzo Fontanelli 1 ,
• Francesca Torri 1 ,
• Gabriele Siciliano 1 &
• Giulia Ricci 1  

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Introduction and methods

Myophosphorylase deficiency, also known as McArdle disease or Glycogen Storage Disease type V (GSD-V), is an autosomal recessive metabolic myopathy that results in impaired glycogen breakdown in skeletal muscle. Despite being labelled as a “pure myopathy,” cardiac involvement has been reported in some cases, including various cardiac abnormalities such as electrocardiographic changes, coronary artery disease, and cardiomyopathy. Here, we present a unique case of a 72-year-old man with GSD-V and both mitral valvulopathy and coronary artery disease, prompting a systematic review to explore the existing literature on cardiac comorbidities in McArdle disease.

Our systematic literature revision identified 7 case reports and 1 retrospective cohort study. The case reports described 7 GSD-V patients, averaging 54.3 years in age, mostly male (85.7%). Coronary artery disease was noted in 57.1% of cases, hypertrophic cardiomyopathy in 28.5%, severe aortic stenosis in 14.3%, and genetic dilated cardiomyopathy in one. In the retrospective cohort study, five out of 14 subjects (36%) had coronary artery disease.

Discussion and conclusion

Despite McArdle disease primarily affecting skeletal muscle, cardiac involvement has been observed, especially coronary artery disease, the frequency of which was moreover found to be higher in McArdle patients than in the background population in a previous study from a European registry. Exaggerated cardiovascular responses during exercise and impaired glycolytic metabolism have been speculated as potential contributors. A comprehensive cardiological screening might be recommended for McArdle disease patients to detect and manage cardiac comorbidities. A multidisciplinary approach is crucial to effectively manage both neurological and cardiac aspects of the disease and improve patient outcomes. Further research is required to establish clearer pathophysiological links between McArdle disease and cardiac manifestations in order to clarify the existing findings.

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Introduction

Myophosphorylase deficiency, also known as McArdle disease or Glycogen Storage Disease type V(GSD-V), is the most common metabolic myopathy and was firstly described in 1951 by Dr. Brian McArdle, who reported the case of a man with a history of exercise induced cramps [ 1 ]. This autosomal recessive disorder arises due to mutations in PYGM gene on chromosome 11q13, causing a deficiency of the myophosphorylase enzyme, which plays a crucial role in the breakdown of glycogen in skeletal muscle cells [ 2 ]. This rare condition leads to the impaired ability of affected individuals to access stored glycogen as an energy source during physical activity, resulting in a distinct set of clinical features. Although some individuals may remain asymptomatic until adulthood, symptoms onset generally occurs during adolescence, characterized by exercise intolerance which presents with fatigue, pain, and contractures after few minutes of exercise. Interestingly, individuals with McArdle disease may experience a remarkable characteristic known as the “second-wind” phenomenon, which refers to an improvement in exercise tolerance and a reduction in muscle symptoms after a brief period of rest during physical activity. CK levels are usually elevated in these patients and episodes of rhabdomyolysis may as well occur at some point in their lives [ 3 ].

Unlike many other myopathies, McArdle’s disease is not typically associated with multisystem involvement and some reviews have labelled this condition as a “pure myopathy”, since the muscle isozyme myophosphorylase is also present in other tissue such as the heart and the brain. However, in these tissues, the myophosphorylase deficiency is adequately compensated for by the substantially higher expression of the brain isozyme [ 4 ]. Nevertheless, a few cases of cardiological involvement have been described. In particular, reported cardiac manifestations of McArdle disease include electrocardiographic changes, coronary artery disease, and hypertrophic cardiomyopathy [ 5 ]. We report the case of a 72-year-old man with McArdle disease, early mitral and tricuspid valve disease and coronary artery disease, that is a rare combination of cardiac comorbidities, who underwent both tricuspid and mitral annuloplasty surgeries, as well as coronary angioplasty with the placement of four stents. Considering the limited number of reported cases of cardiological abnormalities in McArdle disease, we have opted to conduct a systematic review to analyse the existing findings in order to explore a possible link between the two conditions.

Illustrative case

A 72-year-old man with a history of mild hypertension and dyslipidaemia is regularly followed at Neuromuscular Unit of Santa Chiara Hospital in Pisa for the diagnosis of McArdle disease. He does not smoke and engages in regular physical activity. The patient's first evaluation at our clinic occurred when he reached 64 years of age, for a long-standing history of exercise intolerance that has been present since his adolescence. He never complained muscle weakness, nor he reported episodes of myoglobinuria or rhabdomyolysis. The "second-wind" phenomenon was clearly described by the patient since early adulthood. At that time we performed an ischemic forearm test that showed a blunted lactate response post-exercise and a muscle biopsy from quadriceps femoris that revealed a vacuolar myopathy with an increase of glycogen and absent myophosphorylase activity (Fig.  1 ). Genetic analysis confirmed the diagnosis of McArdle disease showing the common homozygous p.Arg50 stop codon mutation in PYGM gene. Over time, his muscle symptoms remained stable, and his average CK levels stayed within the range of 200–350 U/L, with a peak reaching 3500 U/L. A lower limbs muscular magnetic resonance imaging (MRI) showed signs of fatty infiltration in the anterior and posterior compartment of lower legs, in the posterior compartment of the thighs, gluteus, and paravertebral muscles (Fig.  2 ). During the last follow-up the neurological examination showed a hyperlordotic gait, a mild bilaterally deltoids hyposthenia (MRC 4), pectoral muscles hypotrophy, and preserved strength in all other muscle groups. His cardiological history begins at the age of 35, when a mitral valve prolapse with mild regurgitation was detected. Electrocardiogram was normal and blood pressure values showed only a mild hypertension. Since then, regular instrumental and clinical follow-up showed no significant changes until the age of 61, when he presented dyspnoea (New York Heart Association class 3) due to progression of mitral regurgitation from mild to severe, along with the concomitant finding of a mild tricuspid regurgitation. As a result, he underwent mitral and tricuspid annuloplasty surgery. During the procedure, a coronary angiography revealed significant stenosis in the marginal branch of the circumflex artery and multiple subcritical stenoses in the right coronary artery. Due to the absence of angina, coronary revascularization was not performed at that time. Subsequent cardiological follow-ups, including cycle ergometer exercise tests and myocardial scintigraphy, were periodically conducted without evidence of inducible myocardial ischemia. At 72 years of age, the patient was admitted for elective coronary angiography due to exertional dyspnea, which was interpreted as angina equivalent given the context of pre-existing two-vessel coronary artery disease. Echocardiography showed good overall systolic function with basal inferior wall akinesia and medio-basal posterolateral hypokinesia, a good functioning of the mitral and tricuspid valves, and mild aortic insufficiency. The coronary angiography revealed widespread atherosclerosis and identified two significant stenoses (80%) in the proximal and middle segments of the circumflex artery, as well as critical stenoses in the middle of the right coronary artery (80%) and its posterolateral branch (90%). Angioplasty was then performed, successfully placing two drug-eluting stents in the circumflex artery and an additional two in the right artery. No issues were reported during the percutaneous coronary intervention, performed under local anaesthesia with mepivacaine. As part of secondary prevention and given the presence of myopathy, the patient was prescribed alirocumab, a PCSK9 inhibitor. This therapy efficiently regulated his LDL cholesterol levels and was overall well-tolerated. Subsequent cardiological follow-ups have shown no concerning developments.

Muscle biopsy from our case (left quadriceps femori). A 10x, PAS staining; B 10x, Gomori's trichrome staining. Arrows indicating glycogen vacuoles

Ax IN/OUT MRI sequences of our case showing signs of fatty infiltration in the posterior compartment of the thighs ( A ) and in the anterior and posterior compartment of lower legs ( B )

The study was conducted following the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines [ 6 ]. A systematic literature search was conducted using PubMed/MEDLINE until July 2023. No language or country of publication filters were applied to retrieve all available literature. The complete search string was: ("McArdle Disease " OR "Glycogen Storage Disease Type V" OR "myophosphorylase deficiency" OR "GSD type V" OR "McArdle ") AND (''card'' or "cardiovascular diseases" or ''cardiac involvement '' or ''angina'' or ''valvulopathy'' or ''valvular heart disease'' or ''cardiomyopathy'' or ''coronaropathy'' or ''coronary artery disease'' or ''CAD”). Screening and eligibility assessment of articles was performed in Rayyan – a web and mobile app for systematic reviews ( https://www.rayyan.ai ).

Inclusion criteria were: studies (1) containing at least one well described case of McArdle disease with cardiac comorbidities, (2) discussing McArdle syndrome and its comorbidities, encompassing cardiac involvement or potential pathophysiological rationales for such associations.

Exclusion criteria were: (1) review on McArdle in general, (2) studies without detailed information about individual patients.

The articles were searched and extracted by two reviewers (D.H. and G.V.), and any discrepancies were solved by a third investigator (L.B.). We pulled out several variables including age, sex, clinical onset presentation, clinical neurological features, lactate test, CK level, muscle MRI, muscle biopsy, genetic mutation, cardiac comorbidity, electrocardiogram (ECG), echocardiogram (ECHO), cardiac MRI, coronary angiography, presence of other comorbidities. Continuous variables were presented as means ± standard deviations while categorical variables were presented as absolute values and percentages. Microsoft Excel was used to extract data and perform calculations. The collected results from the case reports were summarized in tables (Tables 1 and 2 ). The quality of the studies included was assessed using the Joanna Briggs Institute Critical Appraisal [ 7 ]. One reviewer (B.L) assessed each article and then assigned a consensus score to each. Score reports are provided in the supporting information: Tables S2–S3. Due to the heterogeneity in result description, study design, and participant selection, the available data were qualitatively described, and no meta-analysis was performed.

Case reports

The search identified 151 articles: among these, 140 were excluded due to their irrelevance to the topic, and from the remaining 11, after screening, 8 articles comprising 7 case reports and 1 retrospective cohort study were selected. The remaining articles were included in the discussion part (Fig.  3 ).

Flowchart showing the results of our literature search

Data from seven patients were described in the form of case reports (Tables 1 , 2 ). The average age of the patients was 54,3 ± 16,2 years (range: 29–69 years). Six patients (85.7%) were male, while only one patient was a female (14.3%). Four out of seven patients (57.1%) presented with significant acute or chronic coronary artery disease requiring percutaneous intervention (PCI) [ 5 , 11 ] or surgical revascularization by aorto-coronary bypass (CABG) [ 8 ], while in one case no specific treatment was mentioned [ 10 ]. Two patients had hypertrophic cardiomyopathy (28.5%), one being a severe obstructive form [ 9 ], while the other consisting of a non-obstructive form with concomitant significant coronary artery disease (CAD) and ECG abnormalities [ 5 ]. One patient had severe aortic stenosis in a bicuspid valve (14.3%) which required transcatheter valve replacement; the intervention was complicated two days later by a type 2 atrioventricular block necessitating a pacemaker insertion [ 13 ]. Lastly, one patient had a genetic (not otherwise specified) dilated cardiomyopathy, with clinical and functional deterioration during pregnancy, resulting in premature cesarean section performed under general anesthesia [ 12 ].

Among the examined case reports, the onset of cardiological symptoms in relation to the diagnosis of myopathy was not specified for one patient, while in three out of the six remaining patients, cardiological symptoms presented before the diagnosis of myopathy. In one patient the diagnosis of myopathy was made a few years after the diagnosis of dilated cardiomyopathy, both diseases occurring in young adulthood [ 12 ]. Interestingly, in two out of six patients, the diagnosis of GSD-V was made due to the appearance of muscular symptoms and/or an increase in CK levels triggered by the initiation of statin therapy following acute coronary syndrome [ 10 , 11 ].

Regarding the most frequent musculoskeletal symptoms, muscle fatigue and exercise intolerance, with or without cramps, were reported in all patients, while rhabdomyolysis with myoglobinuria was reported in one case only [ 10 ]. CPK levels, when available (six out of seven patients), were higher than the normal range in all patients (Tables 1 , 2 ).

Observational study

The retrospective Scottish cohort study included a total of 14 patients (8 males and 6 female) with GSD-V. Participants had a mean age at clinical presentation for myopathy of 43.8 ± 16.6 years with genetic diagnosis established at an average age of 47.7 ± 16.1. Five out of 14 subjects (36%) had coronary artery disease. However, clinical presentations, onset age, and information concerning any revascularization procedures were not specified. All 14 patients had exercise intolerance and muscle cramps, 12 patients (86%) suffered from myalgia, and 10 (71%) manifested the "second-wind" phenomenon. Episodes of rhabdomyolysis and myoglobinuria occurred in 10 patients (71%), and elevated CPK levels were observed in all patients [ 14 ].

McArdle disease is a metabolic myopathy that does not specifically affect cardiac muscle [ 4 ]. However, even though a sufficient myocardial myophosphorylase activity is expected to counterbalance the absence of the skeletal muscle isoenzyme, some cases of cardiac involvement have been reported as a manifestation of the disease itself [ 5 ]. To our knowledge, this is the first case of a double annuloplasty surgery with simultaneous finding of coronary artery disease in a patient with McArdle disease, which, a decade later, required an angioplasty procedure with the insertion of four drug eluting stents across distinct arteries. Both surgical procedures were well-tolerated by the patient and no specific anhestesia-related complications were reported. Only one case of hyperthermia, pulmonary oedema and rhabdomyolysis after protamine administration was reported in literature in occurrence with McArdle disease [ 15 ], however a later review concluded that such myopathy doesn’t seem to be related to severe perioperative problems in routine anaesthetic care [ 16 ]. Of note, after the angioplasty procedure, considering the presence of muscular disease, the patient was prescribed a PCSK9 inhibitor with an effective control over LDL levels and an excellent tolerability profile, confirming what has been previously reported concerning the safety of such drugs in McArdle patients [ 10 ].

In our revision of the literature, coronary heart disease (CHD) represented the most frequent findings among cardiac comorbidities (57.1%), while lower prevalence was detected for hypertrophic cardiomyopathy (28.5%) and valvular heart disease (14.3%). Indeed, a European registry study [ 17 ] reported a frequency of CHD of 8,3% in a large cohort of patients with McArdle disease, pointing out that such prevalence is higher than the background population, where it is estimated to be 2,8% in Europe [ 18 ]. However, so far, no study has compared the prevalence or incidence of such comorbidity across different age groups. The authors of the European registry study emphasized the importance of preventive screening for coronary artery disease, in light of their results. Our research supports this significant study, as CHD is the most prevalent cardiac abnormality observed in the available case reports. Interestingly, it has been hypothesised that some of the cardiological findings in McArdle disease may be related to the exaggerated autonomic cardiovascular responses occurring during submaximal exercise due to low concentrations of Na + /K + pumps in muscle and the resulting increase in extracellular K + concentration [ 19 ]. Earlier, an article reported the case of electrocardiographic alterations, including first-degree atrioventricular block and T-wave abnormalities, in a young man with McArdle disease, speculating a possible role of the impaired glycolytic metabolism in the conducting system [ 20 ]. However, no evidence of such an infiltration in the heart has been reported so far in literature. No specific electrocardiographic findings were mentioned among the examined case reports expect for one case that reported left axis deviation, inferolateral T-wave flattening, and late progression of QRS in the precordial leads [ 5 ], and another case with a type 2 atrioventricular block likely due to a post-operative complication [ 13 ].

Our patient was discovered with coronary artery disease at the age of 61, however it’s worth noting that his first signs of cardiac abnormalities dates back at the age of 35. The mean age of the available case reports is 54,3 ± 16,2 years and 43,8 ± 16,1 years for the retrospective study. While our case reports include younger patients with McArdle disease, we cannot conclude that the age of onset of cardiac abnormalities, although reported [ 17 ] more frequently in the general population, necessarily occurs at an earlier age compared to the general population. Of note, our patient reported regular physical activity but we can’t exclude that sedentary lifestyle related to pain experienced during exertion and exercise intolerance associated with McArdle disease might play a role in the development of coronary heart disease.

Regarding the possible role of biomarkers, in a review conducted by Molares-Vila et al. [ 21 ] no specific serum biomarker for McArdle disease, nor for a possible cardiological involvement were found.

While the pathophysiology of such involvement remains unproved, our work highlights the importance of a comprehensive cardiological screening in patients with McArdle disease given the variety of possible cardiological manifestations. Indeed, the proposed potential pathophysiological mechanisms linking the two conditions, and most importantly, the reported increased prevalence of coronary artery disease in McArdle patients, suggest a possible link between McArdle disease and cardiac involvement. Therefore, given our findings, we believe that considering a periodical check-up comprising electrocardiogram, transthoracic echocardiography, and cardiological examination would be beneficial in patients with McArdle disease, corroborating what previous research [ 17 ] highlighted concerning the importance of preventing comorbidities such as coronary artery disease in this condition.

Our study has several limitations. In particular, given the rarity of the disease, the available quantity of case reports and studies delving into the cardiac implications of McArdle disease remains limited. More extensive investigations involving larger cohorts of patients with a comprehensive cardiac evaluation should be conducted to gain deeper insights into the diverse phenotypic attributes of potential heart involvement. Additionally, the mechanisms underlying the connection between this cardiac involvement and glycogenosis remain largely unexplored. Preclinical research focusing on these aspects is therefore warranted and insights may be gleaned from larger and more detailed cohort studies.

This systematic review sheds light on the relatively rare but significant association between McArdle disease and cardiac comorbidities. The findings suggest that individuals with GSD-V may be at increased risk of developing coronary artery disease and other cardiac conditions, warranting close cardiac monitoring. A multidisciplinary approach that integrates neurologic and cardiac assessments is crucial for the comprehensive management of patients with McArdle disease, allowing for early detection and personalized interventions to improve their overall health and well-being.

Data Availability

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

McARDLE B (1951) Myopathy due to a defect in muscle glycogen breakdown. Clin Sci 10(1):13–35

CAS   PubMed   Google Scholar  

Lucia A, Nogales-Gadea G, Pérez M, Martín MA, Andreu AL, Arenas J (2008) McArdle disease: What do neurologists need to know? Nat Clin Pract Neurol 4(10):568–577. https://doi.org/10.1038/ncpneuro0913

Article   PubMed   Google Scholar  

Nogales-Gadea G, Santalla A, Brull A, de Luna N, Lucia A, Pinós T (2015) The pathogenomics of McArdle disease—genes, enzymes, models, and therapeutic implications. J Inherit Metab Dis 38(2):221–230. https://doi.org/10.1007/s10545-014-9743-2

Article   CAS   PubMed   Google Scholar  

Di Mauro S (2007) Muscle glycogenoses: an overview. Acta Myol 26(1):35–41. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC294932

Jones DM, Lopes L, Quinlivan R, Elliott PM, Khanji MY (2019) Cardiac manifestations of McArdle disease. Eur Heart J 40(4):397. https://doi.org/10.1093/eurheartj/ehy783 . Oxford University Press

Page MJ et al. (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372. https://doi.org/10.1136/BMJ.N71

Munn Z et al (2020) Methodological quality of case series studies: an introduction to the JBI critical appraisal tool. JBI Evid Synth 18:10. https://doi.org/10.11124/JBISRIR-D-19-00099

Article   Google Scholar  

Nicholls DP, Campbell NPS, Stevenson HP, Patterson VH (1996) Angina in McArdle’s disease. Heart 76(4):372–373. https://doi.org/10.1136/HRT.76.4.372

Article   CAS   PubMed   PubMed Central   Google Scholar  

Moustafa S, Patton DJ, Connelly MS (2013) Unforeseen cardiac involvement in McArdle’s disease. Heart Lung Circ 22(9):769–771. https://doi.org/10.1016/J.HLC.2012.12.004

Marco-Benedí V, Jarauta E, Pérez-Calahorra S, Bea AM, Civeira F (2019) Treatment of a high cardiovascular risk patient with McArdle’s disease with PCSK9 inhibitors. Clin Investig Arterioscler 31(2):89–92. https://doi.org/10.1016/J.ARTERI.2018.11.005

Vavouranakis I, Ganotakis ES, Manta P, Evangeliou A (2007) Elevated creatine kinase levels in a patient with coronary artery disease and asymptomatic McArdle’s disease. Int J Cardiol 115(1):114–115. https://doi.org/10.1016/j.ijcard.2005.12.027

Lepoivre T, Legendre E, Pinaud M (2002) Anesthesia for cesarean section in a patient with McArdle disease and hereditary dilated cardiomyopathy. Ann Fr Anesth Reanim 21(6):517–520. https://doi.org/10.1016/S0750-7658(02)00645-7

Wang LW, Granger EK, McCourt JA, Pye R, Kaplan JM, Muller DWM (2015) Late surgical explantation and aortic valve replacement after transcatheter aortic valve implantation. Ann Thorac Surg 99(4):1434–1436. https://doi.org/10.1016/J.ATHORACSUR.2014.06.099

Gandhi SE et al (2021) The phenotypic and genotypic features of a Scottish cohort with McArdle disease. Neuromuscul Disord 31(8):695–700. https://doi.org/10.1016/J.NMD.2021.05.009

Lobato EB, Janelle GM,  Urdaneta F, Malias MA (1999) W CASE REPORTS Noncardiogenic Pulmonary Edema and Rhabdomyolysis after Protamine Administration in a Patient with Unrecognized McArd le’s Disease. Available: http://pubs.asahq.org/anesthesiology/article-pdf/91/1/303/397584/0000542-199907000-00039.pdf

Bollig G, Mohr S, Ræder J (2005) McArdle’s disease and anaesthesia: Case reports. Review of potential problems and association with malignant hyperthermia. Acta Anaesthesiologica Scandinavica, Blackwell Munksgaard 49(8):1077–1083. https://doi.org/10.1111/j.1399-6576.2005.00755.x . Blackwell Munksgaard

Article   CAS   Google Scholar  

Scalco RS et al (2020) Data from the European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC). Orphanet J Rare Dis 15:1. https://doi.org/10.1186/s13023-020-01562-x

Safiri S et al (2022) Burden of ischemic heart disease and its attributable risk factors in 204 countries and territories, 1990–2019. Eur J Prev Cardiol 29(2):420–431. https://doi.org/10.1093/eurjpc/zwab213

Haller RG, Clausen T, Vissing J (1998) Reduced levels of skeletal muscle Na+K+-ATPase in McArdle disease

Book   Google Scholar  

Ratinov G, Baker WP, Swaiman KF. CASE STUDIES McArdle’s Syndrome with Previously Unreported Electrocardiographic and Serum Enzyme Abnormalities. Available: https://annals.org

Molares-vila A, Corbalán-rivas A, Carnero-gregorio M, González-cespón JL, Rodríguez-cerdeira C (2021) Biomarkers in glycogen storage diseases: an update. Int J Mol Sci 22:9. https://doi.org/10.3390/ijms22094381

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Acknowledgements

We extend our sincere gratitude to Dr. G. Alì for the histopathological analysis of the muscle sample. Additionally, we acknowledge the Unit of Radiology at Pisa Hospital for performing muscle MRI.

Open access funding provided by Università di Pisa within the CRUI-CARE Agreement. No funding was received for conducting this study.

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Domeniko Hoxhaj and Gabriele Vadi equally contributed to the study.

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Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Via Roma 67, 56100, Pisa, Italy

Domeniko Hoxhaj, Gabriele Vadi, Lorenzo Fontanelli, Francesca Torri, Gabriele Siciliano & Giulia Ricci

Department of Internal Medicine, University of Genova, Genoa, Italy

Lorenzo Bianchi

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Hoxhaj, D., Vadi, G., Bianchi, L. et al. Cardiac comorbidities in McArdle disease: case report and systematic review. Neurol Sci (2024). https://doi.org/10.1007/s10072-024-07600-x

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• Age-adjusted rate of death for Black fathers was lower than for nonfathers
• ‘Fatherhood may be protective for Black men’

CHICAGO --- Heart disease is the leading cause of death among men, and being a father may put men at an even greater risk of poor heart health later in life, reports a new study from scientists at Northwestern University and Ann & Robert H. Lurie Children’s Hospital of Chicago.

The study of 2,814 men between the ages of 45 and 84 found cardiovascular health in older age was worse for fathers compared to nonfathers. Study participants’ heart health was rated based on their diet, physical activity, smoking habits, weight, blood pressure, and level of lipids and glucose in their blood.

“The changes in heart health we found suggest that the added responsibility of childcare and the stress of transitioning to fatherhood may make it difficult for men to maintain a healthy lifestyle, such as a healthy diet and exercise,” said corresponding author Dr. John James Parker , an internist, pediatrician and assistant professor of pediatrics and general internal medicine at Northwestern University Feinberg School of Medicine.

“We really need to study fathers as a unique population and track men’s health outcomes as they become fathers. Cardiovascular health is especially important since the health behaviors and factors are all modifiable.”

The study was published as a peer-reviewed preprint earlier this month in the journal AJPM Focus with a more finalized version publishing soon. 

Fathers have worse heart health but lower death rates

Despite fathers in the study having worse heart health in older age, the study found they actually have lower rates of death than nonfathers. Parker said this conflicting association could be because fathers may have a more robust social support system, and social connectedness has been linked with lower mortality.

“Fathers may also be more likely to have someone as their future caretaker (i.e., their children) to help them attend medical appointments and manage medications and treatments as they get older,” Parker said. “We also found that fathers had lower rates of depressive symptoms than nonfathers, so mental health may be contributing to the lower age-adjusted death rates in fathers.”

The study included men who self-identified as Black, Chinese, Hispanic or White, and the age-adjusted rate of death for all Black fathers was lower than for Black nonfathers, the only racial and ethnic subgroup with this association.

“Fatherhood may be protective for Black men,” Parker said. “Maybe becoming a father helps promote a healthy lifestyle for Black men. Studying this association further could have important public health implications.”

Previous studies that evaluated fatherhood, cardiovascular health, cardiovascular disease and mortality have not included racially and ethnically diverse populations and lacked comprehensive cardiovascular health evaluation. This study is novel because it included men from the Multi-Ethnic Study of Atherosclerosis (MESA).

This study also examined influence of the age men transition to fatherhood on heart health and disease outcomes. Interestingly, men who became at younger ages (25 years old and younger) — especially Black and Hispanic men — had worse heart health and higher death rates and may benefit from focused clinical and public health attention.

“If you’re under 25, you may be less financially stable, your brain may be less mature, and, especially for racial and ethnic minorities, you may have lower-paying jobs with fewer benefits and limited leave policies,” Parker said. “All of this can make it harder to focus on your health. There are a lot of public health interventions for young mothers, but no one has ever really looked at young fathers in this way.”

‘A father’s health has a major influence on their family’

Since most men in the U.S. are fathers , identifying some of the explanations for the associations among health, disease and fatherhood could have important health implications for men, especially for men of color, the scientists said.

“A lot of times we focus on the health of mothers and children, and we don’t even think of fathers, but their health has a major influence on their family,” said Parker, citing previous research that found higher obesity rates among partners if their spouse was obese. “To improve the health of families, we need to consider the multi-directional relationship among mothers, fathers, other caregivers and children.”

The study also found a higher smoking rate among fathers, which Parker said is surprising because other studies have shown many fathers quit smoking when they have kids.

“This study looked at older fathers, so it’s possible men might quit smoking when they become fathers but then later, maybe they become more stressed and take up the habit again,” Parker said. “Either way, we should look at what’s happening with smoking rates because smoking is a leading cause of preventative death and if a father is smoking it will influence their families as well.”

The scientists defined study participants’ cardiovascular health using the American Heart Association Life's Essential 8 scores (excluding sleep). Men were categorized as either fathers (82% study participants) or nonfathers based on an interview in which participants were asked to list any children's ages and medical conditions. Men who did not list any children were categorized as nonfathers.

Other Northwestern study authors include Dr. Craig Garfield, Clarissa Simon, Laura Colangelo and Norrina Allen.

Funding for MESA was provided by the National Heart, Lung, and Blood Institute (grants N01-HC-95159, N01-HC- 95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01- HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169 and HHSN268201500003I) and the National Center for Research Resources (grants UL1-RR-024156 and UL1-RR-025005).

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Study reveals that gastric cancer surgery may reduce heart disease risk

by Korea University College of Medicine

Gastric cancer, also known as stomach cancer, is a highly prevalent and aggressive form of the disease that increases the risk of cardiovascular diseases. Depending on the stage of the cancer, treatment typically involves the surgical removal of cancer-affected tissue.

The surgical procedures include gastrectomy—a surgery to remove a portion or the entire stomach, and endoscopic resection —a non-invasive method that uses an endoscope to guide precise removal of the tumor. Both surgical procedures for gastric cancer treatment alter cardiovascular risk factors but differently. However, the impact of gastric cancer surgery on the incidence of cardiovascular events is ambiguous.

To fill this gap, a research team led by Assistant Professor Yeongkeun Kwon, from the Division of Foregut Surgery, Korea University College of Medicine conducted a nationwide cohort study to investigate the long-term risk of cardiovascular diseases in patients with gastric cancer who underwent surgical treatment. Their findings were made available online on March 28, 2024, in International Journal of Surgery .

The researchers analyzed the incidence of major adverse cardiovascular events (MACE) such as heart attack and stroke between patients who underwent surgical treatment for gastric cancer, and the general population, between 2004 and 2013. They observed that within a seven-year follow-up period, only 2.9% of patients who underwent gastrectomy developed MACE. In contrast, 5.4% of patients who were treated with endoscopic resection developed MACE within the same period.

Elaborating on the clinical importance of their research findings, Prof. Kwon explains, "There are concerns that the surgical modalities used to treat gastric cancer that remove a part of the stomach or the whole organ can result in other health hazards . Our study demonstrates that gastric cancer surgery has health benefits in terms of reduced cardiovascular risk."

Furthermore, statistical analysis revealed a significantly lowered risk of MACE in patients who underwent gastrectomy when compared to the general population. However, the risk of MACE in the endoscopic resection group was not significantly different than that of the general population. Further research into the specific risk factors that influence the incidence of cardiovascular disease is needed.

Sharing the long-term implications of their study, Prof. Yeongkeun concludes, "Korea has the highest long-term survival rate for gastric cancer in the world and, therefore, also has the largest amount of data available on long-term survivors of gastric cancer. If information on the health status of long-term stomach cancer survivors like our study is accumulated, health care professionals and gastric cancer patients will be able to make informed decisions that can greatly improve treatment outcomes."

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• Volume 3, Issue 1
• Regular use of fish oil supplements and course of cardiovascular diseases: prospective cohort study
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• Ge Chen 1 ,
• Zhengmin (Min) Qian 2 ,
• Junguo Zhang 1 ,
• Shiyu Zhang 1 ,
• http://orcid.org/0000-0002-7003-6565 Zilong Zhang 1 ,
• Michael G Vaughn 3 ,
• Hannah E Aaron 2 ,
• Chuangshi Wang 4 ,
• Gregory YH Lip 5 , 6 and
• http://orcid.org/0000-0002-3643-9408 Hualiang Lin 1
• 1 Department of Epidemiology , Sun Yat-Sen University , Guangzhou , China
• 2 Department of Epidemiology and Biostatistics, College for Public Health and Social Justice , Saint Louis University , Saint Louis , Missouri , USA
• 3 School of Social Work, College for Public Health and Social Justice , Saint Louis University , Saint Louis , Missouri , USA
• 4 Medical Research and Biometrics Centre , Fuwai Hospital, National Centre for Cardiovascular Diseases, Peking Union Medical College , Beijing , China
• 5 Liverpool Centre for Cardiovascular Science , University of Liverpool and Liverpool Heart and Chest Hospital , Liverpool , UK
• 6 Department of Clinical Medicine , Aalborg University , Aalborg , Denmark
• Correspondence to Dr Hualiang Lin, Department of Epidemiology, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China; linhualiang{at}mail.sysu.edu.cn

Objective To examine the effects of fish oil supplements on the clinical course of cardiovascular disease, from a healthy state to atrial fibrillation, major adverse cardiovascular events, and subsequently death.

Design Prospective cohort study.

Setting UK Biobank study, 1 January 2006 to 31 December 2010, with follow-up to 31 March 2021 (median follow-up 11.9 years).

Participants 415 737 participants, aged 40-69 years, enrolled in the UK Biobank study.

Main outcome measures Incident cases of atrial fibrillation, major adverse cardiovascular events, and death, identified by linkage to hospital inpatient records and death registries. Role of fish oil supplements in different progressive stages of cardiovascular diseases, from healthy status (primary stage), to atrial fibrillation (secondary stage), major adverse cardiovascular events (tertiary stage), and death (end stage).

Results Among 415 737 participants free of cardiovascular diseases, 18 367 patients with incident atrial fibrillation, 22 636 with major adverse cardiovascular events, and 22 140 deaths during follow-up were identified. Regular use of fish oil supplements had different roles in the transitions from healthy status to atrial fibrillation, to major adverse cardiovascular events, and then to death. For people without cardiovascular disease, hazard ratios were 1.13 (95% confidence interval 1.10 to 1.17) for the transition from healthy status to atrial fibrillation and 1.05 (1.00 to 1.11) from healthy status to stroke. For participants with a diagnosis of a known cardiovascular disease, regular use of fish oil supplements was beneficial for transitions from atrial fibrillation to major adverse cardiovascular events (hazard ratio 0.92, 0.87 to 0.98), atrial fibrillation to myocardial infarction (0.85, 0.76 to 0.96), and heart failure to death (0.91, 0.84 to 0.99).

Conclusions Regular use of fish oil supplements might be a risk factor for atrial fibrillation and stroke among the general population but could be beneficial for progression of cardiovascular disease from atrial fibrillation to major adverse cardiovascular events, and from atrial fibrillation to death. Further studies are needed to determine the precise mechanisms for the development and prognosis of cardiovascular disease events with regular use of fish oil supplements.

• Health policy
• Nutritional sciences
• Public health

Data availability statement

Data are available upon reasonable request. UK Biobank is an open access resource. Bona fide researchers can apply to use the UK Biobank dataset by registering and applying at http://ukbiobank.ac.uk/register-apply/ .

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:  https://creativecommons.org/licenses/by/4.0/ .

https://doi.org/10.1136/bmjmed-2022-000451

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WHAT IS ALREADY KNOWN ON THIS TOPIC

Findings of the effects of omega 3 fatty acids or fish oil on the risk of cardiovascular disease are controversial

Most previous studies focused on one health outcome and did not characterise specific cardiovascular disease outcomes (eg, atrial fibrillation, myocardial infarction, stroke, heart failure, and major adverse cardiovascular events)

Whether fish oil could differentially affect the dynamic course of cardiovascular diseases, from atrial fibrillation to major adverse cardiovascular events, to other specific cardiovascular disease outcomes, or even to death, is unclear

WHAT THIS STUDY ADDS

In people with no known cardiovascular disease, regular use of fish oil supplements was associated with an increased relative risk of atrial fibrillation and stroke

In people with known cardiovascular disease, the beneficial effects of fish oil supplements were seen on transitions from atrial fibrillation to major adverse cardiovascular events, atrial fibrillation to myocardial infarction, and heart failure to death

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE, OR POLICY

Regular use of fish oil supplements might have different roles in the progression of cardiovascular disease

Further studies are needed to determine the precise mechanisms for the development and prognosis of cardiovascular disease events with regular use of fish oil supplements

Introduction

Cardiovascular disease is the leading cause of death worldwide, accounting for about one sixth of overall mortality in the UK. 1 2 Fish oil, a rich source of omega 3 fatty acids, containing eicosapentaenoic acid and docosahexaenoic acid, has been recommended as a dietary measure to prevent cardiovascular disease. 3 The UK National Institute for Health and Care Excellence recommends that people with or at high risk of cardiovascular disease consume at least one portion of oily fish a week, and the use of fish oil supplements has become popular in the UK and other western countries in recent years. 4 5

Although some epidemiological and clinical studies have assessed the effect of omega 3 fatty acids or fish oil on cardiovascular disease and its risk factors, the findings are controversial. The Agency for Healthcare Research and Quality systematically reviewed 37 observational studies and 61 randomised controlled trials, and found evidence indicating the beneficial effects of higher consumption of fish oil supplements on ischaemic stroke, whereas no beneficial effect was found for atrial fibrillation, major adverse cardiovascular events, myocardial infarction, total stroke, or all cause death. 6 In contrast, the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) reported a decreased risk of major adverse cardiovascular events with icosapent ethyl in patients with raised levels of triglycerides, regardless of the use of statins. 7 Most of these findings, however, tended to assess the role of fish oil at a certain stage of cardiovascular disease. For example, some studies restricted the study population to people with a specific cardiovascular disease or at a high risk of cardiovascular disease, 8 9 whereas others evaluated databases of generally healthy populations. 10 All of these factors might preclude direct comparison of the effects of omega 3 fatty acids on atrial fibrillation events or on further deterioration of cardiovascular disease. Few studies have fully characterised specific cardiovascular disease outcomes or accounted for differential effects based on the complex disease characteristics of participants. Hence, in this study, we hypothesised that fish oil supplements might have harmful, beneficial, or no effect on different cardiovascular disease events in patients with varying health conditions.

Most previous studies on the association between fish oil and cardiovascular diseases generally focused on one health outcome. Also, no study highlighted the dynamic progressive course of cardiovascular diseases, from healthy status (primary stage), to atrial fibrillation (secondary stage), major adverse cardiovascular events (tertiary stage), and death (end stage). Clarifying this complex pathway in relation to the detailed progression of cardiovascular diseases would provide substantial insights into the prevention or treatment of future disease at critical stages. Whether fish oil could differentially affect the dynamic course of cardiovascular disease (ie, from atrial fibrillation to major adverse cardiovascular events, to other specific cardiovascular disease outcomes, or even to death) is unclear.

To deal with this evidence gap, we conducted a longitudinal cohort study to estimate the associations between fish oil supplements and specific clinical cardiovascular disease outcomes, including atrial fibrillation, major adverse cardiovascular events, and all cause death in people with no known cardiovascular disease or at high risk of cardiovascular disease for the purpose of primary prevention. We also assessed the modifying effects of fish oil supplements on the disease process, from atrial fibrillation to other outcomes, in people with known cardiovascular disease for the purpose of secondary prevention.

The UK Biobank is a community based cohort study with more than half a million UK inhabitants aged 40-69 years at recruitment. 11–13 Participants were invited to participate in this study if they were registered with the NHS and lived within 35 km of one of 22 Biobank assessment centres. Between 1 March 2006 and 31 July 2010, a baseline survey was conducted, based on a touch screen questionnaire and face-to-face interviews, to collect detailed personal, socioeconomic, and lifestyle characteristics, and information on diseases. 11–13

We excluded patients who had a diagnosis of atrial fibrillation (n=8326), heart failure (n=2748), myocardial infarction (n=11 949), stroke (n=7943), or cancer (n=48 624) at baseline; who withdrew from the study during follow-up (n=1299); or who had incomplete or outlier data for the main information (n=11 748). Because we focused only on a specific sequence of progression of cardiovascular disease (ie, from healthy status to atrial fibrillation, to major adverse cardiovascular events, and then to death), we excluded 1983 participants with other transition patterns. The remaining 415 737 participants were included in this analysis ( figure 1 ).

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Flowchart of selection of participants in study. The count of diagnosed diseases does not equate to the total number of individuals, because each person could have multiple diagnoses

Determining use of fish oil supplements

Information on regular use of fish oil supplements was collected from a self-reported touchscreen questionnaire during the baseline survey. 14 15 Each participant was asked whether they regularly used any fish oil supplement. Trained staff conducted a verbal interview with participants, asking if they were currently receiving treatments or taking any medicines, including omega 3 or fish oil supplements. Based on this information, we classified participants as regular users of fish oil supplements and non-users.

Follow-up and outcomes

Participants were followed up from the time of recruitment to death, loss to follow-up, or the end date of follow-up (31 March 2021), whichever came first. Incident cases of interest, including atrial fibrillation, heart failure, stroke, and myocardial infarction, were identified by linkage to death registries, primary care records, and hospital inpatient records. 11 Information on deaths was obtained from death registries of the NHS Information Centre, for participants in England and Wales, and from the NHS Central Register Scotland, for participants in Scotland. 11 Outcomes were defined by a three character ICD-10 (international classification of diseases, 10th revision) code. In this study, atrial fibrillation was defined by ICD-10 code I48, and major adverse cardiovascular events was determined by a combination of heart failure (I50, I11.0, I13.0, and I13.2), stroke (I60-I64), and myocardial infarction (I21, I22, I23, I24.1, and I25.2) codes.

We collected baseline data on age (<65 years and ≥65 years), sex (men and women), ethnic group (white and non-white), Townsend deprivation index (with a higher score indicating higher levels of deprivation), smoking status (never, previous, and current smokers), and alcohol consumption (never, previous, and current drinkers). Data for sex were taken from information in UK Biobank rather than from patient reported gender. Baseline dietary data were obtained from a dietary questionnaire completed by the patient or by an interviewer. The questionnaire was established for each nation (ie, England, Scotland, and Wales) to assess an individual's usual food intake (oily fish, non-oily fish, vegetables, fruit, and red meat). Diabetes mellitus was defined by ICD-10 codes E10-E14, self-reported physician's diagnosis, self-reported use of antidiabetic drugs, or haemoglobin A1c level ≥6.5% at baseline. Hypertension was defined by ICD-10 code I10 or I15, self-reported physician's diagnosis, self-reported use of antihypertensive drugs, or measured systolic and diastolic blood pressure ≥130/85 mm Hg at baseline. Information on other comorbidities (obesity (ICD-10 code E66), chronic obstructive pulmonary disease (J44), and chronic renal failure (N18)) was extracted from the first occurrence (UKB category ID 1712). Information on the use of drugs, including antihypertensive drugs, antidiabetic drug, and statins, was extracted from treatment and drug use records. Biochemistry markers were measured immediately at the central laboratory from serum samples collected at baseline. Binge drinking was defined as consumption of ≥6 standard drinks/day for women or ≥8 standard drinks/day for men. Detailed information on alcohol consumption and binge drinking in the UK Biobank was reported previously. 16

Statistical analysis

Characteristics of participants are summarised as number (percentages) for categorical variables and mean (standard deviation (SD)) for continuous variables. Comparisons between regular users of fish oil supplements and non-users were made with the χ 2 test or Student's t test.

We used a multi-state regression model to assess the role of regular use of fish oil supplements in the temporal disease progression from healthy status to atrial fibrillation, to major adverse cardiovascular events, and subsequently to death. The multi-state model is an extension of competing risks survival analysis. 17–19 The model allows simultaneous estimation of the role of risk factors in transitions from a healthy state to atrial fibrillation (transition A), healthy state to major adverse cardiovascular events (transition B), healthy state to death (transition C), atrial fibrillation to major adverse cardiovascular events (transition D), atrial fibrillation to death (transition E), and major adverse cardiovascular events to death (transition F) (transition pattern I, figure 2 ). The focus on these six transitions rather than on all possible health state transitions was preplanned and evidence based. If participants entered different states on the same date, we used the date of the theoretically previous state as the entry date of the latter state minus 0.5 days.

Numbers of participants in transition pattern I, from baseline to atrial fibrillation, major adverse cardiovascular events, and death

We further examined the effects of regular use of fish oil supplements on other pathways. For example, we divided major adverse cardiovascular events into three individual diseases (heart failure, stroke, and myocardial infarction), resulting in three independent pathways (transition patterns II, III, and IV, online supplemental figures S1–S3 ). All models were adjusted for age, sex, ethnic group, Townsend deprivation index, consumption of oily fish, consumption of non-oily fish, smoking status, alcohol consumption, obesity, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, chronic renal failure, and use of statins, antidiabetic drugs, and antihypertensive drugs.

Supplemental material

We conducted several sensitivity analyses for the multi-state analyses of transition pattern A: additionally adjusting for setting (urban and rural), body mass index (underweight, normal, overweight, and obese), and physical activity (low, moderate, and high) in the model; adjusting for binge drinking rather than alcohol consumption; additionally adjusting for other variables of dietary intake (consumption of vegetables, fruit, and red meat); calculating participants' entry date into the previous state with different time intervals (0.5 years, one year, and two years); excluding participants who entered different states on the same date; excluding events occurring in the first two years of follow-up; restricting the follow-up date to 31 March 2020 to evaluate the influence of the covid-19 pandemic; and the use of the inverse probability weighted method to deal with biases between the regular users and non-users of fish oil supplements. Also, we conducted grouped analyses for sex, age group, ethnic group, smoking status, consumption of oily fish, consumption of non-oily fish, hypertension, and drug use, to examine effect modification. The interactions were tested with the likelihood ratio test. All analyses were carried out with R software (version 4.0.3), and the multi-model analysis was performed with the mstate package. A two tailed P value <0.05 was considered significant.

Patient and public involvement

Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. Participants were involved in developing the ethics and governance framework for UK Biobank and have been engaged in the progress of UK Biobank through follow-up questionnaires and additional assessment visits. UK Biobank keeps participants informed of all research output through the study website ( https://www.ukbiobank.ac.uk/explore-your-participation ), participant events, and newsletters.

A total of 415 737 participants (mean age 55.9 (SD 8.1) years; 55% women), aged 40-69 years, were analysed, and 31.4% (n=1 30 365) of participants reported regular use of fish oil supplements at baseline ( figure 1 ). Table 1 shows the characteristics of regular users (n=130 365) and non-users (n=285 372) of fish oil supplements. In the group of regular users of fish oil supplements, we found higher proportions of elderly people (22.6% v 13.9%), white people (95.1% v 94.2%), and women (57.6% v 53.9%), and higher consumption of alcohol (93.1% v 92.0%), oily fish (22.1% v 15.4%), and non-oily fish (18.0% v 15.4%) than non-users. The Townsend deprivation index (mean −1.5 (SD 3.0) v −1.3 (3.0)) and the proportion of current smokers (8.1% v 11.4%) were lower in regular users of fish oil supplements. Online supplemental table S1 provides more details on patient characteristics and online supplemental table S2 compares the basic characteristics of included and excluded people.

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Baseline characteristics of study participants grouped by use of fish oil supplements

Over a median follow-up time of of 11.9 years, 18 367 participants had atrial fibrillation (transition A) and 17 826 participants had major adverse cardiovascular events (transition B); 14 902 participants died without having atrial fibrillation or major adverse cardiovascular events (transition C). Among patients with incident atrial fibrillation, 4810 developed major adverse cardiovascular events (transition D) and 1653 died (transition E). Among patients with incident major adverse cardiovascular events, 5585 died during follow-up (transition F, figure 2 ). In separate analyses for individual diseases (transition patterns II, III, and IV, online supplemental figures S1–S3 ), in patients with atrial fibrillation, 3085 developed heart failure, 1180 had a stroke, and 1415 had a myocardial infarction. During follow-up, 2436, 2088, and 2098 deaths occurred in patients with heart failure, stroke, and myocardial infarction, respectively.

Multi-state regression results

Table 2 shows the different roles of regular use of fish oil supplements in transitions from healthy status to atrial fibrillation, to major adverse cardiovascular events, and then to death. For individuals in the primary stage (healthy status), we found that the use of fish oil supplements had a harmful effect on the transition from health to atrial fibrillation, with an adjusted hazard ratio of 1.13 (95% CI 1.10 to 1.17, transition A). The hazard ratio for transition B (from health to major adverse cardiovascular events) was 1.00 (95% CI 0.97 to 1.04) and for transition C (from health to death) was 0.98 (0.95 to 1.02).

Hazard ratios (95% confidence intervals) for each transition, for different transition patterns for progressive cardiovascular disease by regular use of fish oil supplements

For individuals in the secondary stage (atrial fibrillation) at the beginning of the study, regular use of fish oil supplements decreased the risk of major adverse cardiovascular events (transition D, hazard ratio 0.92, 95% CI 0.87 to 0.98), and had a borderline protective effect on the transition from atrial fibrillation to death (transition E, 0.91, 0.82 to 1.01). For transition F, from major adverse cardiovascular events to death, after adjusting for covariates, the hazard ratio was 0.99 (0.94 to 1.06, transition pattern I, table 2 ).

We divided major adverse cardiovascular events into three individual diseases (ie, heart failure, stroke, and myocardial infarction) and found that regular use of fish oil supplements was marginally associated with an increased risk of stroke in people with a healthy cardiovascular state (hazard ratio 1.05, 95% CI 1.00 to 1.11), whereas a protective effect was found in transitions from healthy cardiovascular states to heart failure (0.92, 0.86 to 0.98). For patients with atrial fibrillation, we found that the beneficial effects of regular use of fish oil supplements were for transitions from atrial fibrillation to myocardial infarction (0.85, 0.76 to 0.96), and from atrial fibrillation to death (0.88, 0.81 to 0.95) for transition pattern IV. For patients with heart failure, we found a protective effect of regular use of fish oil supplements on the risk of mortality (0.91, 0.84 to 0.99) (transition patterns II, III, and IV, table 2 ).

Stratified and sensitivity analyses

We found that age, sex, smoking, consumption of non-oily fish, prevalent hypertension, and use of statins and antihypertensive drugs modified the associations between regular use of fish oil supplements and the transition from healthy states to atrial fibrillation ( online supplemental figure S4 ). We found that the association between regular use of fish oil supplements and risk of transition from healthy states to major adverse cardiovascular events was greater in women (hazard ratio 1.06, 95% CI 1.00 to 1.11, P value for interaction=0.005) and non-smoking participants (1.06, 1.06 to 1.11, P value for interaction=0.001) ( online supplemental figure S4 ). The protective effect of regular use of fish oil supplements on the transition from healthy states to death was greater in men (hazard ratio 0.93, 95% CI 0.89 to 0.98, P value for interaction=0.003) and older participants (0.91, 0.86 to o 0.96, P value for interaction=0.002) ( online supplemental figures S5 and S6 ). The results were not substantially changed in the sensitivity analyses ( online supplemental table S3 ).

Principal findings

Our study characterised the regular use of fish oil supplements on the progressive course of cardiovascular disease, from a healthy state (primary stage), to atrial fibrillation (secondary stage), major adverse cardiovascular events (tertiary stage), and death (end stage). In this prospective analysis of more than 400 000 UK adults, we found that regular use of fish oil supplements could have a differential role in the progression of cardiovascular disease. For people with a healthy cardiovascular profile, regular use of fish oil supplements, a choice of primary prevention, was associated with an increased risk of atrial fibrillation. For participants with a diagnosis of atrial fibrillation, however, regular use of fish oil supplements, as secondary prevention, had a protective effect or no effect on transitions from atrial fibrillation to major adverse cardiovascular events, atrial fibrillation to death, and major adverse cardiovascular events to death. When we divided major adverse cardiovascular events into three individual diseases (ie, heart failure, stroke, and myocardial infarction), we found associations that could suggest a mildly harmful effect between regular use of fish oil supplements and transitions from a healthy cardiovascular state to stroke, whereas potential beneficial associations were found between regular use of fish oil supplements and transitions from atrial fibrillation to myocardial infarction, atrial fibrillation to death, and heart failure to death.

Comparison with other studies

Primary prevention.

The cardiovascular benefits of regular use of fish oil supplements have been examined in numerous studies but the results are controversial. Extending previous reports, our study estimated the associations between regular use of fish oil supplements and specific clinical cardiovascular disease outcomes in people with no known cardiovascular disease. Our findings are in agreement with the results of several previous randomised controlled trials and meta-analyses. The Long-Term Outcomes Study to Assess Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridaemia (STRENGTH) reported that consumption of 4 g/day of marine omega 3 fatty acids was associated with a 69% higher risk of new onset atrial fibrillation in people at high risk of cardiovascular disease. 20 A meta-analysis of seven randomised controlled trials showed that users of marine omega 3 fatty acids supplements had a higher risk of atrial fibrillation events, with a hazard ratio of 1.25 (95% CI 1.07 to 1.46, P=0.013). 21 The Vitamin D and Omega-3 Trial (VITAL Rhythm study), a large trial of omega 3 fatty acids for the primary prevention of cardiovascular disease in adults aged ≥50 years, however, found no effects on incident atrial fibrillation, major adverse cardiovascular events, or cardiovascular disease mortality among those treated with 840 mg/day of marine omega 3 fatty acids compared with placebo. 10 22

One possible explanation for the inconsistent results in these studies is that adverse effects might be related to dose and composition. Higher doses of omega 3 fatty acids used in previous studies might have had an important role in causing an adverse effect on atrial fibrillation. 21 One study found that high concentrations of fish oil altered cell membrane properties and inhibited Na-K-ATPase pump activity, whereas a low concentration of fish oil minimised peroxidation potential and optimised activity. 23 In another study, individuals with atrial fibrillation or flutter had higher percentages of total polyunsaturated fatty acids, and n-3 and n-6 polyunsaturated fatty acids, on red blood cell membranes than healthy controls. 24

In terms of composition of omega 3 fatty acids, a recent meta-analysis showed that eicosapentaenoic acid alone can be more effective at reducing the risk of cardiovascular disease than the combined effect of eicosapentaenoic acid and docosahexaenoic acid. 25 Similar outcomes were reported in the INSPIRE study, which showed that higher levels of docosahexaenoic acid reduced the cardiovascular benefits of eicosapentaenoic acid when given as a combination. 26 Another possible explanation is that age, sex, ethnic group, smoking status, dietary patterns, and use of statins and antidiabetic drugs by participants might modify the effects of regular use of fish oil supplements on cardiovascular disease events. Despite these differences in risk estimates, our findings do not support the use of fish oil or omega 3 fatty acid supplements for the primary prevention of incident atrial fibrillation or other specific clinical cardiovascular disease events in generally healthy individuals. Caution might be warranted when fish oil supplements are used for primary prevention because of the uncertain cardiovascular benefits.

Secondary prevention

Our large scale cohort study assessed the role of regular use of fish oil supplements on the disease process, from atrial fibrillation to more serious cardiovascular disease stages, to death, in people with known cardiovascular disease. Contrary to the observations for primary prevention, we found associations that could suggest beneficial effects between regular use of fish oil supplements and most cardiovascular disease transitions. No associations were found between regular use of fish oil supplements and transitions from atrial fibrillation to death, or from major adverse cardiovascular events to death.

Consistent with our hypothesis, the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI) Prevenzione study reported an association between administration of low dose prescriptions of n-3 polyunsaturated fatty acids and reduced cardiovascular events in patients with recent myocardial infarction. 27 A meta-analysis of 16 randomised controlled trials also reported a tendency towards a greater beneficial effect for secondary prevention in patients with cardiovascular disease. 28 Why patients with previous atrial fibrillation benefit is unclear. These findings indicate that triglyceride independent effects of omega 3 fatty acids might in part be responsible for the benefits in cardiovascular disease seen in previous trials. 29–31 No proven biological mechanism for this explanation exists, however, and the dose and formulation of omega 3 fatty acids used in clinical practice are not known.

For the disease process, from cardiovascular disease to death, our findings are consistent with the results of secondary prevention trials of omega 3 fatty acids, which have mostly shown a weak or neutral preventive effect in all cause mortality with oil fish supplements. The GISSI heart failure trial (GISSI-HF), conducted in 6975 patients with chronic heart failure, reported that supplemental omega 3 fatty acids reduced the risk of all cause mortality by 9% (hazard ratio 0.91, 95% CI 0.833 to 0.998, P=0.041). 32 Zelniker et al showed that omega 3 fatty acids were inversely associated with a lower incidence of sudden cardiac death in patients with non-ST segment elevation acute coronary syndrome. 33 A meta-analysis found that use of omega 3 supplements of ≤1 capsule/day was not associated with all cause mortality, but among participants with a risk of cardiovascular disease, taking a higher dose was associated with a reduction in cardiac death and sudden death. 28 Individuals who might benefit the most from fish oil or omega 3 fatty acid supplements are possibly more vulnerable individuals, such as those with previous cardiovascular diseases and those who can no longer live in the community. How fish oil supplements stop further deterioration of cardiovascular disease is unclear, but the theory that supplemental omega 3 fatty acids might protect the coronary artery is biologically plausible, suggesting that omega 3 fatty acids have anti-inflammatory and anti-hypertriglyceridaemia effects, contributing to a reduction in thrombosis and improvement in endothelial function. 34–41 Nevertheless, the effects of omega 3 fatty acids vary according to an individual's previous use of statins, which might partly explain the different effects of fish oil supplements in people with and without cardiovascular disease.

Many studies of omega 3 fatty acids, including large scale clinical trials and meta-analyses, have not produced entirely consistent results. 21 25 42 Our study mainly explored the varied potential effects of regular use of fish oil supplements on progression of cardiovascular disease, offering an initial overview of this ongoing discussion. Our findings suggest caution in the use of fish oil supplements for primary prevention because of the uncertain cardiovascular benefits and adverse effects. Further studies are needed to determine whether potential confounders modify the effects of oil fish supplements and the precise mechanisms related to the development and prognosis of cardiovascular disease events.

Strengths and limitations of this study

The strengths of our study were the large sample size, long follow-up period, which allowed us to analyse clinically diagnosed incident diseases, and complete data on health outcomes. Another strength was our analytical strategy. The multi-state model gives less biased estimates than the conventional Cox model, and distinguished the effect of regular use of fish oil supplements on each transition in the course of cardiovascular disease.

Our study had some limitations. Firstly, as an observational study, no causal relations can be drawn from our findings. Secondly, although we adjusted for multiple covariates, residual confounding could still exist. Thirdly, information on dose and formulation of the fish oil supplements was not available in this study, so we could not evaluate potential dose dependent effects or differentiate between the effects of different fish oil formulations. Fourthly, the use of hospital inpatient data for determining atrial fibrillation events could have excluded some events triggered by acute episodes, such as surgery, trauma, and similar conditions, resulting in underestimation of the true risk because undiagnosed atrial fibrillation is a common occurrence. 43 Fifthly, most of the participants in this study were from the white ethnic group and whether the findings can be generalised to other ethnic groups is not known. Finally, our study did not consider behavioural changes in populations with different cardiovascular profiles because of limited information, and variations in outcomes for different cardiovascular states merits further exploration.

Conclusions

This large scale prospective study of a UK cohort suggested that regular use of fish oil supplements might have differential roles in the course of cardiovascular diseases. Regular use of fish oil supplements might be a risk factor for atrial fibrillation and stroke among the general population but could be beneficial for disease progression, from atrial fibrillation to major adverse cardiovascular events, and from atrial fibrillation to death. Further studies are needed to determine whether potential confounders modify the effects of oil fish supplements and the precise mechanisms for the development and prognosis of cardiovascular disease events.

Ethics statements

Patient consent for publication.

Consent obtained directly from patients.

Ethics approval

The UK Biobank study obtained ethical approval from the North West Multicentre Research ethics committee, Information Advisory Group, and the Community Health Index Advisory Group (REC reference for UK Biobank 11/NW/0382). Participants gave informed consent to participate in the study before taking part.

Acknowledgments

This study was conducted with UK Biobank Resource (application No: 69550). We appreciate all participants and professionals contributing to UK Biobank.

• Mensah GA ,
• Johnson CO , et al
• Gao MM , et al
• Saravanan P ,
• Davidson NC ,
• Schmidt EB , et al
• National Institute for Health and Care Excellence
• Lichtenstein AH ,
• Vadiveloo M , et al
• Djuricic I ,
• Miller M , et al
• Kesse-Guyot E ,
• Czernichow S , et al
• Klemsdal TO ,
• Sandvik L , et al
• Manson JE ,
• Lee I-M , et al
• Gallacher J ,
• Allen N , et al
• Littlejohns TJ ,
• Sudlow C , et al
• Allen NE , et al
• Zhong W-F ,
• Liu S , et al
• Wu Z , et al
• Gallagher C ,
• Elliott AD , et al
• Qian SE , et al
• Nicholls SJ ,
• Lincoff AM ,
• Garcia M , et al
• Djousse L ,
• Al-Ramady OT , et al
• Bassuk SS ,
• Cook NR , et al
• Cazzola R ,
• Della Porta M ,
• Castiglioni S , et al
• Viviani Anselmi C ,
• Ferreri C ,
• Novelli V , et al
• Khan MS , et al
• Knowlton K , et al
• Marchioli R ,
• Bomba E , et al
• Olmastroni E ,
• Gazzotti M , et al
• Al Rifai M , et al
• Tavazzi L ,
• Maggioni AP ,
• Marchioli R , et al
• Zelniker TA ,
• Morrow DA ,
• Scirica BM , et al
• Limonte CP ,
• Zelnick LR ,
• Ruzinski J , et al
• Nelson JR ,
• Miller PE ,
• Van Elswyk M ,
• Alexander DD
• Mozaffarian D ,
• Bornfeldt KE
• Harris WS ,
• Ginsberg HN ,
• Arunakul N , et al
• Markozannes G ,
• Tsapas A , et al
• Svennberg E ,
• Engdahl J ,
• Al-Khalili F , et al

Supplementary materials

Supplementary data.

This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

• Data supplement 1
• Data supplement 2

GYL and HL are joint senior authors.

Contributors HL supervised the whole project and designed the work. GC and HL directly accessed and verified the underlying data reported in the manuscript. GC contributed to data interpretation and writing of the report. ZQ, SZ, JZ, ZZ, MGV, HEA, CW, and GYHL contributed to the discussion and data interpretation, and revised the manuscript. All authors had full access to all of the data in the study and had final responsibility for the decision to submit for publication. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. HL is the guarantor. Transparency: The lead author (guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Funding This work was supported by the Bill and Melinda Gates Foundation (grant No INV-016826). Under the grant conditions of the foundation, a creative commons attribution 4.0 generic license has already been assigned to the author accepted manuscript version that might arise from this submission. The funder had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication.

Competing interests All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from Bill and Melinda Gates Foundation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Provenance and peer review Not commissioned; externally peer reviewed.

Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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• Frontiers in Cardiovascular Medicine
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Telemedicine in Cardiology

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In the rapidly evolving healthcare field, telemedicine and remote monitoring have emerged as transformative tools, reshaping the cardiology landscape by enabling continuous and comprehensive patient care outside traditional clinical settings. This Research Topic seeks to explore the integration, impact, and future directions of telemedicine and remote monitoring technologies in cardiology, inviting submissions highlighting innovative research, case studies, and review articles on this pivotal topic. As cardiovascular disease remains the leading cause of mortality globally, the adoption of Telemedicine has become critical in preemptive care strategies, patient management, and post-procedural monitoring. This Research Topic aims to showcase the latest advancements in telemedicine technologies, from wearable devices that track cardiac rhythms to sophisticated platforms that facilitate real-time data analysis and patient-doctor interactions. Contributions may include but are not limited to, studies on the efficacy of remote monitoring tools in managing chronic conditions like hypertension and heart failure, evaluations of teleconsultation for cardiac care, and the development of AI-driven diagnostic algorithms. We are particularly interested in research that assesses the impact of these technologies on patient outcomes, healthcare costs, and access to care, especially in underserved populations. The collection will also consider critical analyses of telemedicine's challenges, including data privacy, the digital divide, regulatory hurdles, and integration into existing healthcare systems. This Research Topic will serve as a comprehensive repository of contemporary insights and advancements in telemedicine in cardiology, providing clinicians, researchers, and policymakers with valuable information to drive further innovation and adoption of these technologies. Through rigorous peer review, we aim to curate a collection of high-quality papers that reflect current practices and guide future developments in remote cardiac care.

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When’s the last time you were angry? Just recalling the experience may be detrimental to your heart health, study says

Losing your temper from time to time is part of the human experience, and it’s well documented that chronic anger is linked to cardiovascular disease . New research, however, suggests the mere recollection of a time you were angry may be harmful to your heart.

Spending several minutes ruminating on a past situation that made you angry can interfere with your blood vessels’ ability to relax, thereby impeding blood flow, according to a study published in May in the Journal of the American Heart Association . 

“Impaired vascular function is linked to an increased risk of heart attack and stroke ,” lead author Dr. Daichi Shimbo , a professor in the Division of Cardiology at Columbia University Irving Medical Center , said in a news release . “Observational studies have linked feelings of negative emotions with having a heart attack or other cardiovascular disease events. The most common negative emotion studied is anger, and there are fewer studies on anxiety and sadness , which have also been linked to heart attack risk.”

Shimbo and his colleagues explored the effects of anger, anxiety, and sadness on blood vessel function. The 280 people in the randomized controlled study were assigned one of these emotional tasks for eight minutes: 

• Anger: Recalling a personal memory that evoked anger
• Anxiety: Recalling a personal memory that evoked anxiety
• Sadness: Reading a series of depressing sentences
• Neutral: Repeatedly counting to 100

Prior to beginning their respective assignments, participants were instructed to relax for 30 minutes—in comfortable chairs in a temperature-controlled room—without talking or using their phones. They also weren’t allowed to read or sleep. Next, researchers collected blood samples and measured participants’ heart rate, blood pressure, and blood vessel dilation. Finger probes helped assess arterial blood flow.

Immediately after the emotional task, researchers examined the cells lining participants’ blood vessels, keeping an eye out for increased cell injury, impaired blood vessel dilation, and reduced cell repair capacity. The team repeated these assessments after three, 40, 70, and 100 minutes.

Negative emotions not tied to heart disease risk the same way

People in the anger group showed impaired blood vessel dilation up to 40 minutes after recalling a time they were enraged. Previous research shows such impairment may increase risk of atherosclerosis —a condition where plaque builds up in the arteries, heightening chances of stroke and heart disease . In this study, though, the damage was no longer detected after 40 minutes.

“We saw that evoking an angered state led to blood vessel dysfunction, though we don’t yet understand what may cause these changes,” Shimbo said. “Investigation into the underlying links between anger and blood vessel dysfunction may help identify effective intervention targets for people at increased risk of cardiovascular events.”

People in the anxiety and sadness groups didn’t demonstrate any statistically significant changes in their blood vessel linings. Shimbo and his team stressed that future research shouldn’t group negative emotions together in their associations with higher heart disease risk.

All participants were adults residing in the New York City area, with an average age of 26. They self-identified as 50% female, 40% white, 29% Hispanic/Latino, 19% Asian, and 14% Black. All were “healthy,” here meaning free of certain medical conditions including stroke, heart disease, high blood pressure, Type 2 diabetes, and mental illness. They were also nonsmokers who weren’t taking any prescription medications or dietary supplements. 

Because of these factors, it’s “unclear whether the results would apply to older adults with other health conditions, who would most likely be taking medications,” Shimbo said. Another limitation is the study was conducted in a controlled health care environment, as opposed to a real-world setting. Future research may study longer-term effects of anger, anxiety, sadness, and other negative emotions.

The National Heart, Lung, and Blood Institute (NHLBI) funded the study. Its findings fill a longstanding knowledge gap in how anger negatively impacts the heart, NHLBI psychologist Laurie Friedman Donze, PhD , said in another news release .

“It also opens the door to promoting anger management interventions as a way to potentially help stave off heart disease, the leading cause of death in this country,” Donze said.

Tips to manage your anger

If you’re aware your anger is frequent, severe, and negatively impacting your relationships and quality of life, a licensed mental health care provider can help you get back on the right track. In addition, the American Psychological Association recommends these and other anger management tips :

• Relax: Calming activities such as deep breathing, visualization exercises, and yoga-like movements can defuse tense moments.
• Change your environment: Your immediate surroundings can weigh down or irritate you. Be sure to schedule some quiet time to yourself in a relaxing atmosphere.
• Use humor: A good laugh can often take the edge off.
• Communicate better: If you’re in an argument, slow down and think before you speak. Don’t forget to actively listen to what others are saying.

For more on heart health: 

• Reddit cofounder Alexis Ohanian calls this ‘the highest ROI $100 you can spend on your health.’ Here’s what to know about the calcium score test’s benefits
• One secret to preventing dementia, diabetes, and heart disease may lie in your oral health habits. Here’s the dental routine to follow
• Work stress has scary implications for your heart health—especially if you’re a man
• 2 simple strategies can help control your high blood pressure without medication

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Risk of heart failure in inflammatory bowel disease: a swedish population-based study.

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Jiangwei Sun, Jialu Yao, Ola Olén, Jonas Halfvarson, David Bergman, Fahim Ebrahimi, Annika Rosengren, Johan Sundström, Jonas F Ludvigsson, Risk of heart failure in inflammatory bowel disease: a Swedish population-based study, European Heart Journal , 2024;, ehae338, https://doi.org/10.1093/eurheartj/ehae338

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Dysregulation of inflammatory and immune responses has been implicated in the pathogenesis of heart failure (HF). But even if inflammation is a prerequisite for inflammatory bowel disease (IBD), little is known about HF risk in IBD.

In this Swedish nationwide cohort, patients with biopsy-confirmed IBD were identified between 1969 and 2017 [n = 81,749, Crohn’s disease (CD, n = 24,303), ulcerative colitis (UC, n = 45,709), and IBD-unclassified (IBD-U, n = 11,737)]. Each patient was matched with up to five general population reference individuals (n = 382,190) and IBD-free full siblings (n = 95,239) and followed until 31 December 2019. Flexible parametric survival models estimated the adjusted hazard ratio (aHR) and standardized cumulative incidence for HF, with 95% confidence intervals (CI).

There were 5,582 incident HF identified in IBD patients (incidence rate [IR]: 50.3/10,000 person-years) and 20,343 in reference individuals (IR: 37.9) during a median follow-up of 12.4 years. IBD patients had a higher risk of HF than reference individuals (aHR 1.19, 95% CI 1.15 to 1.23). This increased risk remained significant ≥20 years after IBD diagnosis, leading to one extra HF case per 130 IBD patients until then. The increased risk was also observed across IBD subtypes: CD (IR: 46.9 vs. 34.4; aHR 1.28 [1.20 to 1.36]), UC (IR: 50.1 vs. 39.7; aHR 1.14 [1.09 to 1.19]), and IBD-U (IR: 60.9 vs. 39.0; aHR 1.28 [1.16 to 1.42]). Sibling-controlled analyses showed slightly attenuated association (IBD: aHR 1.10 [1.03 to 1.19]).

Patients with IBD had a moderately higher risk of developing HF for ≥20 years after IBD diagnosis than the general population.

• heart failure
• inflammatory bowel disease

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• Human Immunology of Heart Failure: Deconstructing Inflammatory Risk

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