Eyelid Xanthelasma and Cardiovascular Outcomes: A Propensity-Matched Analysis

Xanthelasma palpebrarum (XP) is a common periocular lesion often regarded as benign. However, its potential association with systemic lipid dysregulation and cardiovascular disease remains controversial. This study aimed to evaluate the relationship between XP, dyslipidemia, and major cardiovascular outcomes using a large-scale, electronic health record dataset.

This retrospective propensity score-matched cohort study used de-identified electronic health record data from TriNetX, a global federated research network. Adults aged 20 to 85 years with and without XP were identified between August 5, 2005, and August 5, 2025. XP cases were matched 1:1 to controls without XP based on age, sex, comorbidities, and other covariates. Primary outcomes included the incidence of hyperlipidemia and major adverse cardiovascular events. Secondary measures included lipid profile values and use of lipid-lowering medications. Cox proportional hazards models estimated hazard ratios (HRs) for outcomes, adjusted for demographics and comorbidities.

A total of 40,096 patients (20,048 with XP; 20,048 controls) were included in the analysis. The mean age at index was 53.7 years in both groups. Male sex accounted for 28.3% of the XP cohort and 28.4% of the control group. Lipid profiles differed significantly between groups. Compared with controls, patients with XP had higher rates of hyperlipidemia (32.2% vs. 27.6%; p < 0.0001) and major adverse cardiovascular event (13.0% vs. 11.4%; p < 0.0001), while all-cause mortality was not significantly different in unadjusted comparisons (3.1% vs. 3.3%; p = 0.27). In Cox proportional hazards models, XP was associated with increased risk of hyperlipidemia (HR: 1.38; 95% CI: 1.35-1.41; p < 0.0001), major adverse cardiovascular event (HR: 1.26; 95% CI: 1.22-1.31; p < 0.0001), and a statistically significant but small elevation in all-cause mortality (HR: 1.09; 95% CI: 1.01-1.17; p = 0.0324).

XP is significantly associated with atherogenic lipid profiles, greater use of lipid-lowering medications, and increased risk of cardiovascular events. Recognition of XP during routine ophthalmic examinations may provide an opportunity for early cardiovascular risk stratification.