Why is cardiac fatigue more common in women, especially those with a history of cardiovascular disease, such as heart failure or coronary artery disease?

Why Cardiac Fatigue is More Common in Women with Cardiovascular Disease

Cardiac fatigue disproportionately affects women due to a complex interplay of biological sex differences (genetic, epigenetic, and hormonal factors), distinct disease mechanisms more prevalent in women (microvascular dysfunction, spontaneous coronary artery dissection, Takotsubo cardiomyopathy), and systemic healthcare failures including delayed diagnosis and less aggressive treatment. 1

Biological and Physiological Mechanisms

Sex-specific cardiovascular differences create unique pathways to fatigue in women:

• Genetic, epigenetic, and sex hormone-mediated factors fundamentally alter cardiovascular physiology, homeostasis, and drug responses in ways that remain incompletely understood but clearly contribute to different disease presentations. 1

• Women experience higher rates of heart failure with preserved ejection fraction (HFpEF) rather than reduced ejection fraction, driven by sex differences in cardiac structure, metabolism, vascular aging, and myocardial adaptation to risk factors. 1 This type of heart failure is particularly associated with fatigue as a dominant symptom.

• Microvascular dysfunction and coronary microvascular disease occur more frequently in women, with endothelial dysfunction present in 80% of patients with angina and non-obstructive coronary arteries. 2 This causes myocardial ischemia despite normal-appearing epicardial vessels, leading to persistent fatigue.

Disease Entities Disproportionately Affecting Women

Women develop specific cardiovascular conditions that manifest prominently with fatigue:

• Spontaneous coronary artery dissection accounts for 20-35% of all acute coronary syndromes in women under 60 years, compared to only 4% of all acute coronary syndromes overall. 1

• Takotsubo cardiomyopathy affects 90% women (mean age 66.8 years), causing sudden severe left ventricular dysfunction with substantial long-term morbidity (5.6% death rate per patient-year). 1 Fatigue is a cardinal feature of this condition.

• Inflammatory and autoimmune conditions (systemic lupus erythematosus, rheumatoid arthritis) occur more frequently in postmenopausal women and are strongly associated with microvascular angina and fatigue. 2

Healthcare System Failures Amplifying Fatigue Burden

Systemic biases in cardiovascular care worsen outcomes for women:

• Women remain underrepresented in clinical trials (comprising less than 30% of studied populations), and preclinical studies are predominantly performed in male animals. 1 This knowledge gap means treatments are optimized for male physiology.

• Women experience delays in diagnosis, receive incorrect diagnoses more frequently, and are treated less aggressively than men with identical presentations. 1

• Clinical guidelines recommend identical diagnostic and management strategies for both sexes despite clear biological differences, because the evidence base is derived from predominantly male populations. 1

Gender-Specific Symptom Presentation

Women present differently than men, leading to missed diagnoses:

• Women with myocardial infarction are 8-10 years older than male counterparts and have higher prevalence of traditional risk factors (hypertension, hyperlipidemia, diabetes). 3 Older age correlates with greater fatigue burden.

• Women report fatigue as the most common prodromal myocardial infarction symptom and also as a common acute symptom, often accompanied by nausea, back pain, jaw pain, and palpitations rather than classic chest pain. 3, 4

• In stable coronary heart disease, women report higher fatigue intensity and more interference from fatigue compared to men (p = 0.003 and p = 0.007 respectively). 5

Psychosocial and Functional Dimensions

The experience and impact of fatigue differs by gender:

• Women with heart failure express clear household maintenance roles that amplify the functional impact of fatigue, whereas men describe fatigue differently in relation to their social roles. 6

• Depressive symptoms are the sole predictor of both fatigue intensity and interference in patients with stable coronary disease, and women have higher rates of depression comorbid with cardiovascular disease. 5

• Forty percent of patients with stable coronary disease report fatigue more than 3 days per week lasting more than half the day, with women experiencing significantly greater burden. 5

Critical Clinical Pitfall to Avoid

Never assume normal epicardial coronary arteries on angiography exclude significant coronary disease in women. 2 Coronary microvascular disease causes myocardial ischemia, fatigue, and adverse cardiovascular outcomes even with completely normal-appearing epicardial vessels—a pattern far more common in women than men. This leads to dismissal of women's cardiac symptoms as "non-cardiac" or psychosomatic, perpetuating undertreatment and worse outcomes. 1, 2