Sex differences in heart failure with preserved ejection fraction: From traditional risk factors to sex-specific risk factors

Heart failure with preserved ejection fraction has a higher prevalence in women versus men. There are several proposed mechanisms to explain this sex discrepancy including differences in cardiovascular adaptation to comorbidities and potential underlying etiologic mechanisms. In this review, we summarize sex differences in traditional risk factors, such as obesity, diabetes, hypertension, and coronary artery disease, which contribute to the development of heart failure with preserved ejection fraction in women. Furthermore, we explore female-specific risk factors, such as sex hormones, adverse pregnancy outcomes, and other reproductive factors, which may explain the predominance of heart failure with preserved ejection fraction in women. Beyond sex differences in risk factors, there are also significant sex differences in outcomes with women reporting lower quality of life but overall better survival versus men. Finally, while treatment options for patients with heart failure with preserved ejection fraction are still limited, sex differences have also been reported for the available therapies, with suggestion of preferential benefit of specific heart failure with preserved ejection fraction therapies in women. Further work is required to better understand sex differences in heart failure with preserved ejection fraction, including deeper understanding of pathophysiological mechanisms, derivation of more accurate risk stratification models, and increased representation of women in clinical trials.