Sex Differences in Heart Failure Phenomena
Summary
Heart failure exhibits marked sex-related disparities in its epidemiology, pathophysiology, clinical presentation and outcomes. Women typically present at older ages, more often with preserved systolic function and microvascular or hypertensive phenotypes, whereas men are more prone to ischaemic injury, reduced ejection fraction and right-ventricular dysfunction. Underlying mechanisms include sex hormone modulation of vascular tone, inflammatory signalling and myocardial remodelling, as well as differential gene expression profiles that influence fibrosis and endothelial integrity. In clinical practice, women may report more dyspnoea and fatigue despite similar haemodynamic profiles, and standard diagnostic thresholds such as natriuretic peptides and New York Heart Association staging can under-estimate risk in female patients. Age-adjusted survival is generally superior in women, yet they are less likely to receive guideline-directed therapies and are under-represented in randomised trials. Recognition of these differences has global significance for tailored screening programmes, risk stratification and the design of sex-specific therapeutic trials in both heart failure with reduced ejection fraction and preserved ejection fraction.
Research from Nature Portfolio
Recent studies have characterised sex-specific phenotypes in heart failure with preserved ejection fraction. In a well-phenotyped cohort undergoing invasive haemodynamics and imaging, male patients exhibited more pronounced pulmonary vascular remodelling, higher diastolic pressure gradients and reduced right ventricular ejection fraction compared with female patients. Although men were at greater risk of cardiac death, overall mortality did not differ by sex, suggesting distinct mechanisms of disease progression and end-organ vulnerability. These findings underscore the need to refine diagnostic criteria and to investigate sex-tailored interventions for preserved-function heart failure.
Sex Differences in Heart Failure Phenomena publication trend
The graph below shows the total number of articles in sex differences in heart failure phenomena across all publications each year (not limited to Nature Index journals).
Technical terms
Heart failure with preserved ejection fraction (HFpEF): A form of heart failure in which ventricular contraction is normal but relaxation is impaired, leading to symptoms of congestion despite a normal ejection fraction.
Ejection fraction: The percentage of blood ejected from the left ventricle during each contraction, used to distinguish between preserved and reduced systolic function.
NT-proBNP: N-terminal pro-B-type natriuretic peptide, a blood biomarker released in response to ventricular wall stress and used in the diagnosis and prognostic assessment of heart failure.
New York Heart Association (NYHA) classification: A functional scale ranging from I (no symptoms) to IV (symptoms at rest) employed to grade the severity of heart failure based on patient-reported exertional limitation.
References
- Gender differences in the etiology of heart failure: A systematic review. Journal of Geriatric Cardiology (2011).
- Estrogen Contributions to Microvascular Dysfunction Evolving to Heart Failure With Preserved Ejection Fraction. Frontiers in Endocrinology (2019).
- Sex-based differences in myocardial gene expression in recently deceased organ donors with no prior cardiovascular disease. PLOS ONE (2017).
- Sex differences in early dyspnea relief between men and women hospitalized for acute heart failure: insights from the RELAX-AHF study. Clinical Research in Cardiology (2016).
- Should There Be Sex-Specific Criteria for the Diagnosis and Treatment of Heart Failure?. Journal of Cardiovascular Translational Research (2013).
- Age- and gender-specific risk of death after first hospitalization for heart failure. BMC Public Health (2010).
- Sex differences in the diagnostic algorithm of screening for heart failure by symptoms and NT-proBNP in patients with type 2 diabetes. Cardiovascular Diabetology (2024).
- Gender-related differences in heart failure with preserved ejection fraction. Scientific Reports (2018).
- Effects of Empagliflozin in Women and Men With Heart Failure and Preserved Ejection Fraction. Circulation (2022).
- National trends in heart failure mortality in men and women, United Kingdom, 2000–2017. European Journal of Heart Failure (2020).
About these summaries
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