Abstract

Abstract Background The incidence and characteristics of heart failure (HF) differ between men and women. However, evidence regarding sex differences in determinants and changes of cardiac function in association with incidence of HF remains scarce. Purpose To study the evolution and determinants of left ventricular ejection fraction (LVEF) over time and its association with incident mortality and HF among men and women. Methods From a population-based cohort, we included 7923 participants, 3319 men and 4604 women, free of heart failure (HF) and atrial fibrillation with up to 3 repeated echocardiographic measurements. Using joint models, we analyzed the evolution of LVEF and its associated traditional cardiovascular risk factors among men and women. Second, we studied the association of LVEF changes with incident HF and mortality as a composite outcome adjusted for age (time-varying covariate) and traditional cardiovascular risk factors. We then performed the analyses with HF and mortality as competing events. Results Mean (SD) age was 65.7 (9.6) in men and 66.5 (10) in women. During a median follow-up of 9 years, 988 events in men and 840 events in women occurred. LVEF had a one-directional nonlinear declining with increasing age among men and women (Figure). Up to age of 70, LVEF showed a sharper decline per year among men compared to women. Every unit increase in systolic blood pressure (SBP) was associated with 0.03% (0.05% to 0.02%) decrease in LVEF per year in men. Among women, SBP had an inverse J-shaped association with LVEF changes (P<0.001). Diastolic blood pressure (DBP) also showed a non-linear association with LVEF in both sexes. Prevalent diabetes was not associated with LVEF change. In the survival analysis, every 5% decrease in LVEF was associated with 35% and 30% increase in the risk of the composite outcome among men [HR (95% CI): 1.35 (1.26 to 1.43)] and women [HR (95% CI): 1.30 (1.22 to 1.40)]. Conclusion(s) Despite a similar risk of LVEF decline for the composite outcome, the evolution of LVEF, especially before 70 years of age, differ between men and women. Cardiovascular risk factors, especially blood pressure, play diverse roles in the evolution of left ventricular systolic function among men and women. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam.

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