Higher serum uric acid levels may be associated with subclinical coronary atherosclerosis but not carotid plaque burden. Researchers found that the association between serum uric acid and coronary artery calcium persisted following adjustment, whereas the association with carotid plaque burden was largely attenuated.
The researchers analyzed data from the Paracelsus 10,000 study, a population-based cohort of adults aged 40 to 77 years recruited from the Austrian national population registry between April 2013 and March 2020. The analysis included 8,970 participants who underwent carotid ultrasonography and 1,561 participants with polygenic cardiovascular risk score data who underwent computed tomography for coronary artery calcium assessment. Hyperuricemia was defined as a serum uric acid concentration of at least 6.8 mg/dL. The researchers evaluated coronary artery calcium burden with the Agatston score and carotid plaque burden with total plaque area.
In unadjusted analyses, higher serum uric acid levels were associated with greater coronary artery calcium burden and greater carotid plaque burden. Following sequential adjustment for traditional cardiovascular risk factors, metabolic syndrome, genetic susceptibility, lipoprotein(a), systemic inflammation, alcohol consumption, and statin use, the association with coronary artery calcium remained. Each 1 mg/dL increase in serum uric acid was associated with 1.26 times the odds of a higher coronary artery calcium category, and hyperuricemia was associated with 1.67 times the odds of greater coronary artery calcium burden. Coronary artery calcium was present in 67% of the participants with hyperuricemia compared with 39% of those without hyperuricemia.
However, despite higher serum uric acid levels being associated with greater carotid plaque burden in unadjusted analyses, the association was no longer statistically significant following multivariable adjustment, suggesting that the observed relationship was largely explained by cardiometabolic risk clustering rather than urate-specific pathways. Additional analyses restricted to participants who underwent both imaging studies yielded similar results, indicating that the attenuation was not explained by differences in the study population.
The researchers evaluated potential subgroup differences, finding a significant interaction by sex for carotid plaque burden, with a stronger unadjusted association among female patients. No interaction by sex was observed for coronary artery calcium. In separate genetic sensitivity analyses, polygenic risk scores for serum uric acid were not associated with coronary artery calcium or carotid plaque burden, consistent with previous studies questioning a direct causal role of uric acid in atherosclerotic cardiovascular disease.
The study had several limitations. The cross-sectional design precluded causal inference, residual confounding could not be excluded, serum uric acid was measured at a single time point, and analyses involving patients receiving urate-lowering therapy were exploratory because of the small number of treated participants.
Overall, the findings suggested that serum uric acid may serve as a clinically accessible marker of subclinical coronary atherosclerosis, although additional longitudinal and interventional studies are needed to clarify whether it has a causal role in disease development.
"Higher serum uric acid levels and hyperuricemia are independently associated with subclinical coronary atherosclerosis, whereas associations with carotid plaque burden appear to be largely explained by cardiometabolic risk clustering," wrote lead study author Mathias Ausserwinkler, of the Department of Internal Medicine I at the University Hospital Salzburg at the Paracelsus Medical University in Austria, and colleagues.
The study received open-access funding from Paracelsus Medical University. Full disclosures of the study authors can be found in the study.
Source: Clinical Research in Cardiology