Association of Endometriosis with Incident Valvular Heart Disease: A UK Biobank Cohort Study

Objective: Endometriosis is associated with an increased risk of atherosclerotic cardiovascular disease. However, whether endometriosis is also associated with an increased risk of valvular heart disease (VHD) remains unclear. Methods: Using data from the UK Biobank, we used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between baseline endometriosis and incident VHD. Prespecified subgroup analyses were conducted to explore potential effect modification by demographic, clinical, and reproductive factors. Multivariable linear regression was used to identify metabolites significantly associated with endometriosis, and Cox proportional hazards regression was used to examine associations between these metabolites and incident VHD. Both types of models were adjusted for all potential confounders except high cholesterol. Results: A total of 256,284 women were included in this study. Of these, 8,166 had a diagnosis of endometriosis at baseline, and 248,118 did not. During a median follow-up of 14.1 years, 9,253 women developed VHD: 273 with endometriosis and 8,980 without endometriosis. After multivariable adjustment, endometriosis was associated with a significantly higher risk of incident VHD (HR = 1.17, 95% CI 1.04–1.32, P = 0.010). Subgroup and sensitivity analyses yielded consistent results. Metabolomic analyses identified 32 nuclear magnetic resonance (NMR)-derived metabolic measures that were significantly associated with both endometriosis and the risk of incident VHD. Conclusions: In this prospective cohort analysis of UK Biobank data, baseline endometriosis was associated with a modestly higher risk of incident VHD after adjustment for major demographic, lifestyle, clinical, and reproductive factors.