Hyperuricemia as risk factor for coronary heart disease incidence and mortality in the general population: a systematic review and meta-analysis

Abstract

Previous meta-analyses reported no significant or weak association between hyperuricemia (HU) and coronary heart disease (CHD). We updated the literature search, systematically reviewing retrieved papers. The peer-reviewed literature published from 1965 to December 2014 was searched using Medline and Embase. We included prospective cohort studies involving adults (sample size ≥ 100) with no cardiovascular disease (CVD) and a follow-up of at least 1 year. Studies were excluded if they considered as outcome the CVD incidence/mortality without separately reporting data on CHD, did not adjusted for major confounders and if the 95% confidence interval (CI) for risk ratio (RR) was not available. Relative risk or hazard ratio estimates, with the corresponding CIs, were obtained. For CHD incidence 12 populations were included (457,915 subjects [53.7% males]). For CHD mortality seven populations were included (237,433 subjects [66.3% males]). The overall combined RR were 1.206 (CI 1.066-1.364, p = 0.003) for CHD incidence and 1.209 (CI 1.003-1.457, p = 0.047) for CHD mortality, respectively. Subgroup analysis showed a marginal (incidence) and not significant (mortality) association between HU and CHD in men, but an increased risk for CHD incidence and mortality in hyperuricemic women (RR 1.446, CI 1.323-1.581, p < 0.0001, and RR 1.830, CI 1.066-3.139, p = 0.028, respectively). The risk markedly increases for urate concentrations > 7.0 mg/dL. HU appears to increase the risk of CHD events in the general population, mainly in adult women. This finding requires, however, further investigation.

Hyperuricemia does not seem to be an independent risk factor for coronary heart disease

“…In our opinion, the contribution of Braga and colleagues [1] does not help to resolve the clinical dilemma. A potentially serious problem of the meta-analysis of Braga et al [1] is the lack of any (explicit) assessment of the validity of the trials included.…”

“…age, BMI, total cholesterol or LDL-cholesterol or presence of dyslipidemia, blood pressure values or presence of hypertension, smoke, glucose values or presence of diabetes) selected by each multivariate regression model exploring the relation between hyperuricemia and log risk of CHD. That number ranged from x = 3 to x = 6 between trials considered by the meta-analysis of Braga et al [1]. The graph shows that adding one more covariate to a multivariate regression model produces in the new model a -0.144 lowering of the log-risk ratio of CHD (t = −2.16, p = 0.056).…”

“…A potentially serious problem of the meta-analysis of Braga et al [1] is the lack of any (explicit) assessment of the validity of the trials included. Even well-conducted observational studies can in fact be subject to important and insidious biases: about this, the quality of the trials of Braga et al [1] appears very far from excellent: 89% have missed adjustments for cointerventions, which is for an important prognostic factor for CVD, and 100% were burdened by moderate/serious bias due to confounding. Also taking into account this qualitative approach, it seems very difficult to have full confidence in its [1] conclusions.…”

“…That message seems to be of great importance: if it is true, the treatment of hyperuricemia should be included in the landscape of the therapeutic strategies to reduce the coronary risk. To ascertain the methodologic validity and robustness of that work, we considered it as a critical appraisal of some methodological aspects.In our approach, (a) we evaluated the overall quality of that systematic review through the AMSTAR checklist [2]; (b) we recovered the nine studies selected by Braga and colleagues [1] in order to repeat the meta-analysis and quantified the heterogeneity through I 2 statistic [3]; (c) we launched new subgroup and sensitivity and metaregression analyses in order to better explore the heterogeneity, considering the following as potential effect modifiers: gender, number of CHD covariates used in the adjustment models (i.e. age, BMI, total cholesterol or LDL-cholesterol or presence of dyslipidemia, blood pressure values or presence of hypertension, smoke, glucose values or presence of diabetes) and lack of nutritional information; (d) we estimated the prevalence of metabolic syndrome in single-trial samples using an Italian epidemiological research as reference sample [4]; (e) we investigated the quality of included trials and their risk of bias through the ACROBAT Cochrane checklist [5]; and (f) we used a generalized least-squares regression model to inspect some dose-response effect [6] both at trial level and with a doseresponse meta-analysis; the goodness of fit was explored with a χ 2 -test [7].…”

“…To the Editor, Federica Braga and coworkers [1] stated recently that hyperuricemia shows to be an independent predictor of coronary heart disease (CHD) risk (RR CHD = 1.206 [1.066-1.364]; RR CHD death = 1.209 [1.003-1.457]), mainly for the results found in women. That message seems to be of great importance: if it is true, the treatment of hyperuricemia should be included in the landscape of the therapeutic strategies to reduce the coronary risk.…”