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Circulation. 2018 Jul 10;138(2):198-205. doi: 10.1161/CIRCULATIONAHA.118.034271.

Sex Differences in Cardiovascular Pathophysiology: Why Women Are Overrepresented in Heart Failure With Preserved Ejection Fraction.

Beale AL1,2,3, Meyer P3, Marwick TH1,2, Lam CSP4,5,6, Kaye DM7,2.

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Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (A.L.B., T.H.M., D.M.K.).
Department of Cardiology, Alfred Hospital, Melbourne, Victoria, Australia (A.L.B., T.H.M., D.M.K.).
Faculty of Medicine, Monash University, Melbourne, Victoria, Australia (A.L.B., D.M.K.).
National Heart Centre Singapore (C.S.P.L.).
Duke-National University of Singapore (C.S.P.L.).
University Medical Centre Groningen, The Netherlands (C.S.P.L.).
Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (A.L.B., T.H.M., D.M.K.).


Consistent epidemiological data demonstrate that patients with heart failure with preserved ejection fraction (HFpEF) are more likely to be women than men. Exploring mechanisms behind this sex difference in heart failure epidemiology may enrich the understanding of underlying HFpEF pathophysiology and phenotypes, with the ultimate goal of identifying therapeutic approaches for the broader HFpEF population. In this review we evaluate the influence of sex on the key domains of cardiac structure and function, the systemic and pulmonary circulation, as well as extracardiac factors and comorbidities that may explain the predisposition of women to HFpEF. We highlight the potential role of factors exclusive to or more prevalent in women such as pregnancy, preeclampsia, and iron deficiency. Finally, we discuss existing controversies and gaps in knowledge, as well as the clinical importance of known sex differences in the context of the potential need for sex-specific diagnostic criteria, improved risk stratification models, and targeted therapies.


heart failure; myocardium; sex factors; vascular stiffness; women

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