Sex versus gender-related differences in new-onset heart failure with preserved and reduced left ventricular ejection fraction

Abstract

Abstract Aims Sex refers to genetic and biological characteristics, whereas gender reflects psychosocial norms, roles and behaviors. Sex differences in new-onset heart failure are well described, but gender differences in new-onset heart failure with preserved (HFpEF) and reduced left ventricular ejection fraction (HFrEF) are unknown. Methods A total of 6830 participants (50.3% women, mean age of 54 years) from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) observational Dutch cohort were enrolled in the study. Gender-related characteristics were assessed using self-administered questionnaires. LASSO regression analysis selected the psychosocial variables related to sex, whose coefficient estimates were used to calculate the gender-related scores for each subject [1–2]. The participants were grouped by sex and further analyzed according to tertiles of the gender-related score. Competing-risk regression analysis was used to assess whether sex and gender were associated with new-onset HFrEF (LVEF ≤40%) and HFpEF (LVEF ≥50%). Results Women with predominantly masculine gender had lower BMI, were more often Caucasian and had higher total cholesterol and high-density lipoprotein (HDL) levels than women with a predominantly feminine gender. Men with predominantly feminine gender were less often Caucasian with lower total cholesterol and HDL cholesterol levels than men with a predominantly masculine gender. During a median follow-up of 8.3 years, 227 (3.3%) subjects were diagnosed with heart failure (57.3% HFrEF and 43.7% HFpEF). In the total population including both men and women, feminine gender was significantly and independently associated with a higher risk of new-onset HFpEF compared with masculine gender (HR per 10 point: 1.17, 95% CI: 1.06–1.30; p=0.003). However, sex was not associated with new-onset HFpEF (HR: 1.09, 95% CI: 0.73–1.62; p=0.670). Separately in men, feminine gender was associated with a higher risk of new-onset HFpEF (HR: 1.37, 95% CI: 1.06–1.78; p=0.017), but not in women (HR: 1.13, 95% CI: 0.90–1.41; p=0.310). Conclusions Gender and sex are different constructs and feminine gender was associated with an increased risk of new-onset HFpEF, whereas sex was not associated with new-onset HFpEF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Dutch Kidney Foundation