Association between serum uric acid and atrial fibrillation: A systematic review and meta-analysis
Introduction
Atrial fibrillation (AF) is an important cause of morbidity and mortality. Along with the increased risk of death, AF can lead to stroke and decreased quality of life.1 The pathogenesis of AF remains incompletely understood.
Uric acid is produced by xanthine oxidase (XO), is the terminal breakdown product of purine nucleotides, and is a surrogate marker of oxidative stress. Recent studies have demonstrated that there is a strong association between serum uric acid (SUA) levels with an important AF mediator (such as heart failure mortality)2 and incident coronary artery disease.3
The key pathways implicated in the development of AF are neurohormonal activation,4 oxidative stress/nitroso–redox imbalance,5 and immune activation.6 There seems to be a common mechanism linking all 3 pathways since mechanical stretch mediated by neurohormones leads to oxidative stress and inflammation upregulates XO7, 8, 9; therefore, SUA may play a role in the etiology and persistence of AF. Identifying new associations and mechanisms of AF could lead to therapeutic targets in the future. Therefore, the purpose of this meta-analysis was to help define the relationship between SUA and AF in an effort to better understand the pathophysiology of the disease.
Section snippets
Search strategy
A search was conducted through the MEDLINE database by using PubMed, which contained articles from 1966 to July 2013. This search was conducted by filtering all articles except those containing key terms such as uric acid and AF. More specifically, the search was performed by entering the following: (“uric acid”[MeSH Terms] OR (“uric”[All Fields] AND “acid”[All Fields]) OR “uric acid”[All Fields]) AND (“atrial fibrillation”[MeSH Terms] OR (“atrial”[All Fields] AND “fibrillation”[All Fields]) OR
Literature search
Our search yielded 40 abstracts (Figure 1). We excluded 21 at the abstract level because they did not met our inclusion criteria and selected 19 for full-text review; of the19 selected for full-text review, we included 9 studies and excluded 10 for the following reasons: studies did not include data that could be abstracted for mathematical pooling (n = 4); editorials or review articles (n = 4); and studies included uric acid measurements that could not be replicated (n = 1).11 Interrater
Discussion
Our study reports that high SUA is associated with AF. This association was consistently seen in both cross-sectional and cohort studies, and it was also seen with different types of analyses that included univariate, multivariate, random effects mathematical pooling, and subgroup analyses. It was also seen consistently in multiple and diverse populations. The strengths that lend weight to this conclusion include the stratified analysis of the different study designs and the large sample size.
Conclusion
Despite its limitations, this study finds a clear and strong association between AF and elevated SUA. Future studies should focus on evaluating the mechanistic relationship between SUA and AF and determining whether modifying SUA on patients at risk for AF can decrease its incidence.
References (38)
- et al.
Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates
Am J Cardiol
(1998) - et al.
Hemodynamic and neurohormonal predictors and consequences of the development of atrial fibrillation in dogs with chronic heart failure
J Card Fail
(2006) - et al.
Oxidative stress in atrial fibrillation: an emerging role of NADPH oxidase
J Mol Cell Cardiol
(2013) - et al.
Inflammatory pathways underlying atrial fibrillation
Trends Mol Med
(2011) - et al.
Association of serum uric acid with incident atrial fibrillation (from the Atherosclerosis Risk in Communities [ARIC] study)
Am J Cardiol
(2011) - et al.
The association between hyperuricemia, left atrial size and new-onset atrial fibrillation
Int J Cardiol
(2013) - et al.
Relation of elevated serum uric acid levels to incidence of atrial fibrillation in patients with type 2 diabetes mellitus
Am J Cardiol
(2013) - et al.
Relation of multiple inflammatory biomarkers to incident atrial fibrillation
Am J Cardiol
(2009) - et al.
Development of a risk score for atrial fibrillation (Framingham Heart Study): a community-based cohort study
Lancet
(2009) - et al.
A clinical risk score for atrial fibrillation in a biracial prospective cohort (from the Atherosclerosis Risk in Communities [ARIC] study)
Am J Cardiol
(2011)