Serum uric acid and coronary heart disease in 9,458 incident cases and 155,084 controls: prospective study and meta-analysis

Abstract

Background: It has been suggested throughout the past fifty years that serum uric acid concentrations can help predict the future risk of coronary heart disease (CHD), but the epidemiological evidence is uncertain.

Methods and findings: We report a "nested" case-control comparison within a prospective study in Reykjavik, Iceland, using baseline values of serum uric acid in 2,456 incident CHD cases and in 3,962 age- and sex-matched controls, plus paired serum uric acid measurements taken at baseline and, on average, 12 y later in 379 participants. In addition, we conducted a meta-analysis of 15 other prospective studies in eight countries conducted in essentially general populations. Compared with individuals in the bottom third of baseline measurements of serum uric acid in the Reykjavik study, those in the top third had an age- and sex-adjusted odds ratio for CHD of 1.39 (95% confidence interval [CI], 1.23-1.58) which fell to 1.12 (CI, 0.97-1.30) after adjustment for smoking and other established risk factors. Overall, in a combined analysis of 9,458 cases and 155,084 controls in all 16 relevant prospective studies, the odds ratio was 1.13 (CI, 1.07-1.20), but it was only 1.02 (CI, 0.91-1.14) in the eight studies with more complete adjustment for possible confounders.

Conclusions: Measurement of serum uric acid levels is unlikely to enhance usefully the prediction of CHD, and this factor is unlikely to be a major determinant of the disease in general populations.

Figure 1. Associations between Serum Uric Acid and CHD in 2,456 cases and 3,962 Controls in the Reykjavik Study at Different Levels of Established Risk Factors

Squares indicate odds ratios, with the size of the square proportional to the effective sample size.

Figure 2. Meta-Analysis of Prospective Observational Studies of Serum Uric Acid and CHD in Essentially General Populations, Subdivided by Sex

Conventions are the same as in Figure 1. Combined odds ratios and their CIs are indicated by unshaded diamonds for subtotals and shaded diamonds for grand totals. +, adjustment reported only for age and sex; ++, adjustment for these plus smoking; +++, adjustment for these plus some additional established risk factors; ++++, adjustment for these plus existing cardiovascular disease. Study abbreviations: ARIC, Atherosclerosis Risk in Communities; BIRNH, Belgium Interuniversity Research on Nutrition and Health; BRHS, British Regional Heart Study; CHA, Chicago Heart Association Detection Project in Industry; GRIPS, Göttingen Risk Incidence and Prevalence Study; IIHDS, Israeli Ischemic Heart Disease Study; MONICA, World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease; NHANES, National Health and Nutrition Examination Survey; NHEFS, NHANES I Epidemiologic Follow-Up Study; PROCAM, Prospective Cardiovascular Munster Study.

Figure 3. Prospective Studies of the Association of Serum Uric Acid and CHD, Grouped by Various Characteristics

Conventions are the same as in Figure 1. *, each sex-specific estimate was treated as a “study”; †, two studies (6 and 13) were drawn from general practice registers; §, risk factors adjusted for included: smoking, blood pressure, total cholesterol, triglycerides, alcohol consumption, obesity, use of cardiovascular medication, history of hypertension, and history of diabetes. PTA, phosphotungstic acid.