Serum uric acid as an independent predictor of mortality in patients with angiographically proven coronary artery disease

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Abstract

It is a matter of controversy as to whether uric acid is an independent predictor of mortality in patients with coronary artery disease (CAD) or whether it represents only an indirect marker of adverse outcome by reflecting the association between uric acid and other cardiovascular risk factors. Therefore, we studied the influence of uric acid levels on mortality in patients with CAD. In 1,017 patients with angiographically proven CAD, classic risk factors and uric acid levels were determined at enrollment. A follow-up over a median of 2.2 years (maximum 3.1) was performed. Death from all causes was defined as an end point of the study. In CAD patients with uric acid levels <303 μmol/L (5.1 mg/dl) (lowest quartile) compared with those with uric acid levels >433 μmol/L (7.1 mg/dl) (highest quartile), the mortality rate increased from 3.4% to 17.1% (fivefold increase). After adjustment for age, both sexes demonstrated an increased risk for death with increasing uric acid levels (female patients: hazard ratio [HR] 1.30, 95% confidence intervals [CI] 1.14 to 1.49, p ≤0.001; male patients: HR 1.39 [95% CI 1.21 to 1.59], p ≤0.001). In multivariate Cox regression analysis performed with 12 variables that influence overall mortality—including diuretic use—elevated levels of uric acid demonstrated an independent, significant positive relation to overall mortality (HR 1.23 [95% CI 1.11 to 1.36], p <0.001) in patients with CAD. Thus, uric acid is an independent predictor of mortality in patients with CAD.

Section snippets

Study design and outcome events:

In all, 1,017 patients with angiographically proven CAD were included in the study (defined as the presence of any diameter stenosis >30% according to coronary angiography by visual assessment in a major coronary artery; 42 patients had a diameter stenosis <50% [exclusion of those patients did not influence the study results]). Of the 1,017 patients, 994 (97.7%) were followed up a median of 2.2 years (maximum 3.1). Patients either presented at our clinic (86.5%) or were interviewed by telephone

Serum uric acid levels:

Of all of the study patients, 270 (26.5%) were women and 747 (73.5%) were men. The mean age ± SD of the study patients was 62 ± 10 years, the minimal age was 26 years, and the maximum age was 79 years; men were significantly younger than women (60.9 ± 10.2 vs 66.0 ± 8.9 years, p <0.001). The median (25th/75th quartiles) uric acid levels of all study patients was 357 μmol/L (303/422), whereas the uric acid levels of women were significantly lower than those of men (333 μmol/L [266/400] vs 363

Discussion

Serum uric acid was first reported to be a risk factor of atherosclerosis nearly half a century ago.1 Most, but not all, epidemiologic studies have suggested that there is an association between serum uric acid and CAD.2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 Some studies only found this association in women8, 10, 15 or found no association between serum uric acid and CAD.11, 12, 13 Several mechanisms may be involved in the association between uric acid and atherosclerosis. Uric acid may

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