Sex differences in the association of uric acid to HDL-cholesterol ratio (UHR) with subclinical cardiovascular damage

Abstract

Cardiovascular diseases remain the leading cause of global mortality, with risk increasing significantly in women post-menopause. Identifying accessible biomarkers for subclinical risk stratification is a clinical priority. The uric acid to HDL-cholesterol ratio (UHR) has emerged as a composite marker reflecting metabolic burden and reduced vascular protection. This study investigates the independent association between UHR and subclinical organ damage, exploring sex-specific differences. We analyzed 1,198 Caucasian subjects. Subclinical cardiovascular damage was evaluated via carotid intima-media thickness (c-IMT) and left ventricular mass index (LVMI). Multivariate linear regression and formal interaction analyses were employed to assess the independent association of UHR with organ damage, adjusting for traditional cardiometabolic risk factors. UHR correlated significantly with adiposity, insulin resistance, blood pressure, and lipid profiles. In the total population, UHR was independently associated with both c-IMT (β = 0.093, p  = 0.003) and LVMI (β = 0.194, p  < 0.0001). A significant sex-UHR interaction was observed for LVMI ( p  = 0.024). Sex-stratified analyses revealed that UHR was linked to LVMI in women, particularly those postmenopausal, but not in males. In postmenopausal women, UHR remained an independent determinant of LVMI (β = 0.164, p  = 0.033). UHR is independently associated with subclinical cardiovascular damage, displaying a sex-specific relationship with myocardial remodeling after menopause. As an inexpensive and easily accessible biomarker, UHR may represent a practical tool to combat clinical inertia and improve the early selection of postmenopausal women warranting targeted diagnostic workups.