Elevated serum uric acid levels in outpatients with chronic heart failure: side effect or marker of myocardial damage?

Abstract

Background: High serum uric acid level is a marker of impaired oxidative metabolism, a possible mechanism of myocardial damage, and it reflects the degree of xantine oxidasa activation in patients with chronic heart failure (CHF). However, hyperuricemia is frequently found in subjects treated with diuretics or with renal impairment. Objectives: We sought to determine clinical variables associated with hyperuricemia (Uric) in outpatients (pt) with chronic heart failure (CHF) as well as the relationship with elevated cardiac troponin-T levels (cTnT) and long-term prognosis. Methods: One hundred and eighty outpatients from Heart Failure Program were prospectively included. Clinical, echocardiographic, 6 minute walk test distance, and laboratory data were obtained. Serum uric acid level >7 mg/dL, in male and >5.7 mg/dL in female was considered abnormal. Baseline, 3-months and 6 months blood samples were assayed for cTnT with a 3rd generation immunoassay. Minimal myocardial damage was defined as cTnT ≥0.02 ng/mL. Results: The mean age was 63±12 years and 68% were male. Hyperuricemia was found in 92 (51%) patients. In Uric and non-Uric patients NYHA Class was 2.3±0.8 vs 2.5±0.8 (p = ns), ejection fraction was 34±16 vs 38±15% (p = ns) and 6-min walked distance was 368±84 vs 383±91 m(p = ns). In multiple regression analysis, the variables significantly associated with Uric were: sinus rhythm (OR = 0.40, p = 0.026), heart rate (OR = 1.05, p<0.001), aspirin user (OR = 2.9, p = 0.01) and serum creatinine level (OR = 3.1, p = 0.034). In patients with or without Uric, baseline, 3 and 6 months high cTnT levels were detected in 31 vs 19%, 37 vs 16%, 19 vs 7% (all p<0.05), respectively. The rate of worsening heart failure was 48 vs. 21% (p<0.001) in patients with or without Uric, and 8-months free-CHF hospitalization survival was 61 vs. 83% (p = 0.047), respectively. Conclusion: Hyperuricemia was detected in a half of patients with CHF and it was associated with aspirin intake, impaired renal function, tachycardia and absence of sinus rhythm. Higher rate of minimal myocardial damage and worse prognosis suggest that high uric acid levels should be considerer a manifestation of myocite toxicity, probably secondary to release of oxygen free radicals, instead of side effect.