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Published on: April 17, 2021
Sex and Gender Differences in Heart Failure
Vera Regitz-Zagrosek1,2,3
1Berlin Institute for Gender in Medicine, Charité Universitätsmedizin, Berlin, Germany.
Insights
Sex significantly impacts heart failure (HF) presentation and treatment. Women experience different HF types and respond uniquely to therapies, highlighting the need for sex-specific research and care.
Area of Science:
- Cardiology
- Sex-based Medicine
- Translational Research
Background:
- Heart failure (HF) exhibits distinct sex-based phenotypes, with preserved ejection fraction (EF) more common in women and reduced EF (HFrEF) in men.
- Women with HF generally have better survival rates and lower risks of sudden death compared to men.
- Etiologies differ, with ischemia prevalent in men, while hypertension and diabetes are more significant contributors in women.
Purpose of the Study:
- To explore the sex-specific differences in heart failure pathophysiology, clinical presentation, and therapeutic responses.
- To emphasize the need for sex-disaggregated data in clinical trials and research.
- To highlight unique HF conditions in women, such as Takotsubo and peripartum cardiomyopathy.
Main Methods:
- Review of existing literature on sex differences in heart failure.
- Analysis of epidemiological data regarding HF prevalence and outcomes by sex.
- Examination of pharmacological responses to HF therapies based on sex.
Main Results:
- Women exhibit greater left ventricular stiffness and higher EF, potentially due to age-related fibrosis and hormonal influences.
- Estrogen's differential effect on collagen production in male and female cardiac fibroblasts noted.
- Metabolic profiles and responses to therapies like sacubitril-valsartan show significant sex-based variations.
Conclusions:
- Sex is a critical determinant in heart failure, influencing disease mechanisms, progression, and treatment efficacy.
- Current research and clinical trials inadequately report sex-specific outcomes, hindering personalized medicine.
- Further investigation into sex differences is essential for advancing heart failure management and improving patient outcomes.
Abstract:
Heart failure (HF) phenotypes differ according to sex. HF preserved ejection fraction (EF) has a greater prevalence in women and HF reduced EF (HFrEF) in men. Women with HF survive longer than men and have a lower risk of sudden death. Ischemia is the most prominent cause in men, whereas hypertension and diabetes contribute to a greater extent in women. Women with HF have a greater stiffness of the smaller left ventricle and a higher EF than men. This higher stiffness of women's hearts may be based on an increase in fibrosis at old age. In younger women estrogen reduces collagen production in female cardiac fibroblasts, but stimulates it in males. Lipid and energy metabolism is better maintained in female than in male stressed hearts. Pulse pressure is a key determinant of outcome in HF women but not in men. Takotsubo and peripartum cardiomyopathy are rare diseases affecting predominantly or exclusively women. Sudden cardiac arrest affects more men than women, but women are less adequately treated. New findings in HF therapy indicate that women with HFrEF need lower doses of beta-blockers and angiotensin-converting enzyme inhibitors than men for optimal effects. The combined neprilysin inhibitor/angiotensin II receptor blockers sacubitril-valsartan led to a significant reduction in event rate versus valsartan in women, which was not observed in men. Unfortunately, only less than 10% of recent randomized controlled trial report effects and adverse drug reactions for women and men separately. More research on sex differences in pathophysiology and therapy of HF is needed.
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