Serum Uric Acid Levels and Risk of Metabolic Syndrome: A Dose-Response Meta-Analysis of Prospective Studies

Context: An excess circulating uric acid level, even within the normal range, is always comorbid with metabolic syndrome (MS), several of its components, and nonalcoholic fatty liver disease (NAFLD), which was regarded as hepatic manifestation of MS; however, these associations remain controversial. Objective: This study aimed to quantitatively assess the relationship between the serum uric acid (SUA) levels and the MS/NAFLD risk. Design: We searched for related prospective cohort studies including SUA as an exposure and MS/NAFLD as a result in MEDLINE (PubMed) and EMBASE databases up to January 31, 2015 and July 28, 2015, respectively. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) were extracted. A random-effects model was used to evaluate dose-response relationships. Main Outcomes: On the basis of 11 studies (54 970 participants and 8719 MS cases), a combined RR of 1.72 (95% CI, 1.45-2.03; P < .0001) was observed for the highest SUA level category compared with the lowest SUA level category. Furthermore, based on nine studies (51 249 participants and 8265 MS cases), dose-response analysis suggested that each 1 mg/dL SUA increment was roughly linearly associated with the MS risk (RR, 1.30; 95% CI, 1.22-1.38; P < .0001). Beyond that, SUA level increased NAFLD risk (RR, 1.46; 95% CI, 1.31-1.63). Each 1 mg/dL SUA level increment led to 21% increase in the NAFLD risk. Conclusions: This meta-analysis suggests that higher SUA levels led to an increased risk of MS regardless of the study characteristics, and were consistent with a linear dose-response relationship. In addition, SUA was also a causal factor for the NAFLD risk.