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

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.

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%).

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).

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.

Type of funding sources: Foundation. Main funding source(s): Dutch Kidney Foundation