Sex Differences in Cardiovascular-Kidney-Metabolic Risk Factors Associated with Degenerative Valvular Heart Disease

Abstract Aims The cardiovascular-kidney-metabolic (CKM) health approach emphasizes the importance of multidisciplinary early-stage disease prevention. This study aimed to explore sex differences in CKM risk factors associated with common degenerative valvular heart disease (VHD). Methods A total of 436,184 participants (54.4% women; mean age, 58 years) free of VHD or heart failure at baseline and with complete information about CKM risk factors were included from the UK Biobank cohort. We assessed sex differences in hazard ratios (HRs) and population-attributable risk (PAR) for incident VHD and VHD-related interventions or mortality, focusing on five CKM risk factors: hypertension, diabetes, obesity, hypertriglyceridemia, and chronic kidney disease (CKD). Results At baseline, 81.06% of participants had one or more CKM risk factors: 75.61% had hypertension, 4.80% had diabetes, 24.14% had obesity, 22.26% had hypertriglyceridemia, and 2.32% had CKD. Over a median follow-up period of 13.80 years, incidences of aortic valve stenosis (AS), aortic valve regurgitation (AR), and mitral valve regurgitation (MR) were 11.18 and 5.42, 3.64 and 2.19, and 10.39 and 6.94 events per 10,000 person-years for men and women, respectively. Hypertension was consistently the largest attributable risk factor for incident VHD in both sexes, with PARs of 29.07% and 25.17% for AS, 24.21% and 16.51% for AR, and 19.55% and 13.01% for MR in women and men, respectively. Compared to men, women had higher risks of AS with obesity (HR: 1.17 [1.04–1.32]), AR with CKD (1.59 [1.01–2.49]), and MR with either hypertension (1.25 [1.07–1.47]) or hypertriglyceridemia (1.22 [1.07–1.39]). Conclusions Tailoring the prioritization of CKM risk factors based on gender has the potential to enhance the effectiveness of VHD prevention strategies.