The cross-sectional association between uric acid and atherosclerosis and the role of low-grade inflammation: the CODAM study

Objectives. The aims of this study were to investigate (i) associations between uric acid and prevalent cardiovascular disease (CVD), ankle-arm blood pressure index (AAIx) and carotid intima-media thickness (CIMT) in the total population and in predefined subgroups according to glucose metabolism status and (ii) the extent to which these associations are explained by low-grade inflammation. Methods. Cross-sectional analyses were conducted among 530 individuals [60.6% men, mean age 58.9 years (S. D. 6.9), 52.6% normal glucose metabolism (NGM)] at increased risk of CVD from the Cohort of Diabetes and Atherosclerosis Maastricht study. A low-grade inflammation score was computed by averaging the z-scores of eight inflammation markers [CRP, TNF-alpha, IL-6, IL-8, serum amyloid A, intercellular adhesion molecule 1 (ICAM-1), ceruloplasmin and haptoglobin]. Results. After adjustment for traditional CVD risk factors, plasma uric acid (per S. D. of 81 mu mol/l) was associated with CVD in individuals with NGM [odds ratio (OR) = 1.66, 95% CI 1.06, 2.58] but not with disturbed glucose metabolism (DGM) (OR = 0.81, 95% CI 0.55, 1.19, P interaction = 0.165). Uric acid was associated with CIMT in the total population (beta = 0.024, 95% CI 0.007, 0.042) and slightly more strongly in individuals with NGM (beta = 0.030, 95% CI 0.006, 0.054) than DGM (beta = 0.018, 95% CI -0.009, 0.044, P interaction = 0.443). There was no association between uric acid and AAIx in any group (P interaction = 0.058). Uric acid was associated with low-grade inflammation in the total population (beta = 0.074, 95% CI 0.013, 0.134, P interaction = 0.737). Adding low-grade inflammation to the models did not attenuate any of the associations. Conclusion. The associations for uric acid with CIMT, and with CVD in NGM only, were not explained by low-grade inflammation. A difference in the strength of the associations between individuals with NGM and DGM was suggested.