Uric acid and subclinical atherosclerosis: distinct associations across coronary and carotid arteries

BACKGROUND: Serum uric acid has been consistently associated with cardiovascular risk, yet whether this relationship reflects independent vascular pathology or cardiometabolic risk clustering remains unresolved. We examined associations of serum uric acid and hyperuricemia with imaging-defined subclinical coronary and carotid atherosclerosis in a large population-based cohort. METHODS: We analyzed data from the Paracelsus 10,000 study, a population-based cohort of adults aged 40-77 years recruited from the Austrian national population registry. Coronary artery calcium (CAC) was assessed by computed tomography in 1561 participants with available cardiac computed tomography and polygenic risk score data; carotid plaque burden was assessed by ultrasonography in 8970 participants. Associations were evaluated using ordinal logistic regression - with CAC categorized by Agatston score (0, 1-99, 100-299, ≥ 300) and carotid plaque burden categorized by total plaque area - with sequential adjustment for cardiovascular risk score (SCORE2), metabolic syndrome, polygenic cardiovascular risk, lipoprotein(a) and systemic inflammation. RESULTS: Higher serum uric acid levels were strongly associated with greater CAC burden in unadjusted analyses (OR 1.60 per 1 mg/dL, 95% CI 1.48-1.74). This association was attenuated but remained significant after adjustment for cardiovascular risk score, metabolic syndrome, polygenic risk, lipoprotein(a), and inflammatory markers (OR 1.26, 95% CI 1.14-1.38). Hyperuricemia was independently associated with higher CAC categories after adjustment (OR 1.67, 95% CI 1.20-2.32). Carotid plaque burden showed a strong unadjusted association with serum uric acid that was substantially attenuated after multivariable adjustment, although a weak association remained statistically significant (OR 1.06, 95% CI 1.01-1.10). CONCLUSIONS: Serum uric acid and hyperuricemia are independently associated with subclinical coronary atherosclerosis beyond established cardiovascular risk factors, genetic susceptibility and systemic inflammation. The attenuation of carotid plaque associations after full adjustment suggests that extracoronary plaque burden is largely driven by cardiometabolic risk clustering rather than urate-specific pathways. These findings position uric acid as a clinically accessible marker of subclinical coronary atherosclerosis and raise the question of whether systematic urate assessment should inform cardiovascular risk stratification beyond established risk scores.