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

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. 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-α, IL-6, IL-8, serum amyloid A, intercellular adhesion molecule 1 (ICAM-1), ceruloplasmin and haptoglobin]. After adjustment for traditional CVD risk factors, plasma uric acid (per s.d. of 81 μmol/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 (β = 0.024, 95% CI 0.007, 0.042) and slightly more strongly in individuals with NGM (β = 0.030, 95% CI 0.006, 0.054) than DGM (β = 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 (β = 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. 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.