Abstract
BackgroundThe predictive value of serum uric acid (SUA) for adverse cardiovascular events among obese and overweight patients is not known, but potentially important because of the relation between hyperuricaemia and obesity.MethodsThe relationship between SUA and risk of cardiovascular adverse outcomes (nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death) and all-cause mortality, respectively, was evaluated in a post-hoc analysis of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial. Participants enrolled in SCOUT were obese or overweight with pre-existing diabetes and/or cardiovascular disease (CVD). Cox models were used to assess the role of SUA as an independent risk factor.Results9742 subjects were included in the study; 83.6% had diabetes, and 75.1% had CVD. During an average follow-up time of 4.2 years, 1043 subjects had a primary outcome (myocardial infarction, resuscitated cardiac arrest, stroke, or cardiovascular death), and 816 died. In a univariate Cox model, the highest SUA quartile was associated with an increased risk of cardiovascular adverse outcomes compared with the lowest SUA quartile in women (hazard ratio [HR]: 1.59; 95% confidence interval [CI]: 1.20–2.10). In multivariate analyses, adjusting for known cardiovascular risk factors the increased risk for the highest SUA quartile was no longer statistically significant among women (HR: 0.99; 95% CI: 0.72–1.36) nor was it among men. Analyses of all-cause mortality found an interaction between sex and SUA. In a multivariate Cox model including women only, the highest SUA quartile was associated with an increased risk in all-cause mortality compared to the lowest SUA quartile (HR: 1.51; 95% CI: 1.08–2.12). No relationship was observed in men (HR: 1.06; 95% CI: 0.82–1.36).ConclusionSUA was not an independent predictor of cardiovascular disease and death in these high-risk overweight/obese people. However, our results suggested that SUA was an independent predictor of all-cause mortality in women.
Highlights
The association of gout with cardiovascular disease, first described in the 19th century was thought to be an association, rather than a cause, of cardiovascular disease
Of the 9,804 subjects who were randomised, 9,742 had serum uric acid concentration measured at baseline and formed the population used in the present analyses
Further adjustment for baseline values of cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), body-mass index (BMI), glucose, triglycerides, history of congestive heart failure, history of cardiovascular disease, history of diabetes, systolic blood pressure, diastolic blood pressure, waist-hip ratio, tobacco use, alcohol use, and randomized treatment attenuated these findings further; i.e. among women the second lowest quartile no longer exhibited reduced risk (HR: 0.73; 95% confidence intervals (CI): 0.52–1.01) while the highest quartile exhibited similar risk (HR: 0.99; 95% CI: 0.72–1.36) to the reference group
Summary
The association of gout with cardiovascular disease, first described in the 19th century was thought to be an association, rather than a cause, of cardiovascular disease. More recent evidence from cohort studies suggests a causal relationship between hyperuricaemia and risk of adverse cardiovascular events [1,2,3,4]. Elevated uric acid might merely represent an indirect marker of the metabolic syndrome. To examine this question several studies have tested the effect of allopurinol treatment on the risk of adverse cardiovascular events, and high dose allopurinol seems to be associated with better survival than low dose allopurinol, both in patients with congestive heart failure [11] and in a general hospital patient population [12]. The predictive value of serum uric acid (SUA) for adverse cardiovascular events among obese and overweight patients is not known, but potentially important because of the relation between hyperuricaemia and obesity
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