Elsevier

Atherosclerosis

Volume 231, Issue 1, November 2013, Pages 61-68
Atherosclerosis

Review
Baseline serum uric acid level as a predictor of cardiovascular disease related mortality and all-cause mortality: A meta-analysis of prospective studies

https://doi.org/10.1016/j.atherosclerosis.2013.08.023Get rights and content

Abstract

Objective

Serum uric acid (SUA) levels have been used to predict cardiovascular and all-cause mortality event, but the data have yielded conflicting results. We investigated whether SUA was an independent predictor for cardiovascular or all-cause mortality with prospective studies by meta-analysis.

Methods

Pubmed and Embase were searched without language restrictions for publications available till April 2013. Only prospective studies on cardiovascular or all-cause mortality related to SUA levels were included. Pooled adjust relative risk (RR) and corresponding 95% confidence intervals (CI) were calculated separately for the highest vs. lowest category or the lowest vs. middle category.

Results

For the highest SUA, eleven studies with 172,123 participants were identified and analyzed. Elevated SUA increased risk of all-cause mortality (RR 1.24; 95% CI 1.09–1.42) and cardiovascular mortality (RR 1.37; 95% CI 1.19–1.57). Subgroup analyses showed that elevated SUA significantly increase the risk of all-cause mortality among men (RR 1.23; 95% CI 1.08–1.42), but not in women (RR 1.05; 95% CI 0.79–1.39). Risk of cardiovascular mortality appeared to be more pronounced among women (RR 1.35; 95% CI 1.06–1.72). The association between extremely low SUA and mortality was reported in three studies; we did not perform a pooled analysis because of high degree of heterogeneity in these studies.

Conclusions

Baseline SUA level is an independent predictor for future cardiovascular mortality. Elevated SUA appears to significantly increase the risk of all-cause mortality in men, but not in women. Whether low SUA levels are predictors of mortality is still inconclusive.

Introduction

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Many traditional risk factors have been for CVD, such as hyperlipidemia, hypertension, diabetes, uric acid levels, smoking, etc. Early detection of high-risk subjects is likely to aid in the prevention of CVD and further lower CVD mortality.

Uric acid is the end product of purine metabolism in humans. The available evidence indicates that elevated serum uric acid (SUA) is related to the development and progression of hypertension [1], coronary heart disease (CHD) [2], myocardial infarction [3], stroke [4], and cardiovascular disease (CVD) [5]. Furthermore, elevated SUA are also predictors of all-cause mortality among heart failure patients [6]. Many studies have indicated [7], [8], [9], [10], [11], [12] that higher SUA is a predictor of cardiovascular or all-cause mortality in the general population. A gender specific association with mortality was found only for women in one study [13], whereas other studies [14], [15], [16], [17] showed that higher SUA could not predict the development of cardiovascular or all-cause mortality. In addition, there is some evidence that suggests that lower SUA levels are also associated with an accelerated rate of mortality [18], [19], [20]. Therefore, studies that evaluated the role of SUA levels as an independent risk factor for cardiovascular or all-cause mortality produced conflicting results. These inconsistent results are possibly related to the differences in the populations that were studied, duration of follow-up, outcomes studied and the statistical adjustments.

To the best of our knowledge, no meta-analysis has been conducted to evaluate the association between baseline SUA and the risk of cardiovascular or all-cause mortality. The aim of this study was to systematically evaluate the association between baseline SUA levels and cardiovascular or all-cause mortality risk in the general population through a meta-analysis.

Section snippets

Methods

The meta-analysis was conducted according to the checklist of the Meta-Analysis of Observational Studies in Epidemiology [21]. Electronic literature databases (Pubmed and Embase) were searched for relevant prospective observational studies published prior to April 2013. Studies assessed baseline SUA levels and subsequent cardiovascular or all-cause mortality events in the general population without language restrictions. Potentially relevant studies were identified by various combinations of

Results

A detailed description of how the studies were selected is presented in Fig. 1. Briefly, from the preliminary literature search, a total of 567 potentially relevant citations were identified. After screening the abstracts or titles, 525 studies were excluded. After reviewing the full texts, fourteen prospective studies [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20] representing data from 584,771 participants were finally included in this meta-analysis.

The

Discussion

The findings of the current meta-analysis provided evidence that elevated SUA led to 24% greater risk of all-cause mortality and substantially increased to 37% greater risk for cardiovascular mortality. Subgroup analyses showed that elevated SUA appeared to significantly increase the risk of all-cause mortality in men but not in women. Risk of cardiovascular mortality appeared to more pronounce in the case of women.

In the subgroup analysis of cardiovascular mortality, all the results indicated

Conclusions

In conclusion, our meta-analysis of published prospective studies suggests that elevated SUA levels are associated with an increased risk of cardiovascular and all-cause mortality. However, high SUA appears to increase the risk of all-cause mortality for men but not for women. It is still inconclusive whether extremely low SUA level is an independent risk factor for mortality. There is a need for more well designed trials that focus on the role of urate-lowering therapy while monitoring

Conflict of interest

The authors declare that there are no conflicts of interest.

Acknowledgments

We gratefully thank Shijun Wang for his assistance in proofreading.

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