Age-related sex differences in the outcomes of patients with hypertrophic cardiomyopathy

BACKGROUND: We aimed to clarify the sex differences in various cardiovascular and non-cardiovascular outcomes, and to investigate whether sex differences in outcomes are affected by age in hypertrophic cardiomyopathy (HCM). METHODS: A cohort of 835 patients with HCM initially evaluated during 2007–2019 were followed for a median of 6.4 years. Study outcomes were all-cause death, cardiovascular and non-cardiovascular death, sudden cardiac death (SCD)/SCD equivalent events, heart failure (HF) events, and the composite cardiovascular outcome including cardiovascular death, SCD/SCD equivalent events, admission for HF, and heart transplantation. RESULTS: Women were 5 years older (women 59.9±13.5 vs. men 54.9±11.4 years), had worse dyspnea, and greater left ventricular (LV) diastolic dysfunction and obstructive physiology at presentation. Women compared to men had higher all-cause mortality and cardiovascular event rates, driven by more cardiovascular deaths and heart failure (HF) events. Conversely, non-cardiovascular mortality was not different between the sexes. Female sex was independently associated with all-cause death (HR 1.88, 95% CI 1.11–3.20) and composite cardiovascular events (HR 3.60, 95% CI 2.00–6.49), independent of age, body mass index, New York Heart Association class, SCD risk score, and LV ejection fraction. When stratified by the age of 60, sex differences were not significant at <60 years; however, at ≥60 years, women had worse LV diastolic function, greater obstructive physiology, as well as worse survival and composite cardiovascular outcomes. Sex differences in outcomes remained consistent after propensity score matching for age and other clinical characteristics. CONCLUSIONS: Women with HCM have worse cardiovascular prognosis than men, driven by higher cardiovascular mortality and HF events. The negative impact of female sex on cardiac function and cardiovascular outcome became prominent at age ≥60 years, suggesting age-related sex differences in the prognosis of HCM.