Eur Heart J Qual Care Clin Outcomes. 2025 Dec 16:qcaf156. doi: 10.1093/ehjqcco/qcaf156. Online ahead of print.
ABSTRACT
BACKGROUND AND AIMS: Mitral valve prolapse (MVP) is common, with higher prevalence in women. We hypothesized that sex hormones and regulatory protein sex hormone binding globulin (SHBG) play a pivotal role in development and prognosis of MVP.
METHODS: We prospectively study 472,178 participants in the UK Biobank. Univariable and multivariable regression analyses estimated associations of SHBG and sex hormones (including testosterone and estradiol) with incidence and prognosis of MVP, and differences between sexes. Mendelian randomization (MR) further assessed the causal relationship between SHBG and MVP.
RESULTS: Out of 472,178 participants, 970 patients without a baseline MVP diagnosis developed MVP over a median follow-up of 13.67 years. Serum SHBG and testosterone were positively associated with MVP incidence. In the multivariable model adjusted for confounders, SHBG remained significantly associated with MVP risk [hazard ratio (HR)=1.440, 95% confidence interval (CI): 1.201-1.726]. Compared to individuals with the lowest quintile of SHBG level, those in the second, third, and fourth quintiles had an 8.1%, 39.1%, and 49.3% higher risk of incident MVP. The association between SHBG and incident MVP was consistent across sexes (P for interaction=0.4434). Elevated SHBG level was also significantly associated with all-cause mortality (HR=2.223, 95% CI: 1.430-3.457) in MVP patients. One-sample and two-sample MR using European-ancestry GWAS data supported a causal relationship between genetically predicted SHBG levels and increased MVP risk in both females and males.
CONCLUSIONS: Elevated serum SHBG levels are associated with increased risk and adverse prognosis of MVP, providing insights into sex-related differences, risk stratification, and potential therapeutic targets.
PMID:41401193 | DOI:10.1093/ehjqcco/qcaf156