Background/Purpose: Uric acid may be involved in the atherosclerotic process by increasing the level of low-grade inflammation. The aims of this study were: 1) to investigate if uric acid was associated with ankle-brachial index (AAIx), carotid intima media thickness (c-IMT), and prevalent cardiovascular disease (CVD); 2) the extent to which any such association(s) could be explained by low-grade inflammation; and 3) whether these associations were different in subjects with normal (NGM) compared to disturbed (DGM) glucose metabolism. A difference between these subgroups may exist because of the influence of insulin and glucose on uric acid excretion.

Methods: We studied 530 subjects (60.6% men; mean age 58.9 ± 6.9 yrs; 52.6% NGM) with an increased risk of CVD from the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) Study. Cross-sectional associations between uric acid and CVD, AAIx and c-IMT, and the mediating role of low-grade inflammation therein, were analyzed with logistic and linear regression analyses in the total population and stratified according to glucose metabolism status. Inflammation markers (hs-CRP, TNF-α, IL-6, IL-8, SAA, sICAM-1, haptoglobin, ceruloplasmin) were standardized and combined into an average inflammation score.  

Results: After adjustment for potential confounders (gender, age, BMI, waist, alcohol, smoking, physical activity, hypertension, total:HDL cholesterol, triglycerides , fasting glucose and insulin, eGFR, diuretics) plasma uric acid concentration, expressed per SD (81.3 µmol/L), was positively associated with CVD in subjects with NGM (OR=1.66, 95%CI 1.06-2.58), but not with DGM (OR=0.82, 0.56-1.22; p for interaction=0.065). Uric acid was positively associated with c-IMT in the total population (β=0.027, 95%CI 0.010-0.045) and in subjects with NGM (β=0.030, 95%CI 0.007-0.054). Although the beta coefficient was similar, uric acid was not significantly associated with c-IMT in subjects with DGM (β=0.023, 95%CI -0.004-0.050; p for interaction=0.164). There was no association between uric acid and AAIx in any of the groups. Uric acid was positively associated with low-grade inflammation in the total population (β=0.073, 95%CI 0.012-0.133) and in DGM (β=0.115, 95%CI 0.026-0.203), but not in NGM (β=0.042, 95%CI -0.044-0.128, p for interaction=0.975). The significant associations between uric acid and CVD or c-IMT were not attenuated when adding low-grade inflammation to the models. 

Conclusion: We found evidence of modest associations between uric acid and CVD and c-IMT, but these were not explained by low-grade inflammation. The data suggest the effect of uric acid may be different in subjects with NGM and DGM.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-role-of-low-grade-inflammation-in-the-association-between-uric-acid-and-atherosclerosis-the-codam-study/