Hyperuricaemia, chronic kidney disease, and outcomes in heart failure: potential mechanistic insights from epidemiological data

Abstract

Aim: To determine if the association between hyperuricaemia and poor outcomes in heart failure (HF) varies by chronic kidney disease (CKD).

Methods and results: Of the 2645 systolic HF patients in the Beta-Blocker Evaluation of Survival Trial with data on baseline serum uric acid, 1422 had hyperuricaemia (uric acid ≥6 mg/dL for women and ≥8 mg/dL for men). Propensity scores for hyperuricaemia, estimated for each patient, were used to assemble a matched cohort of 630 pairs of patients with and without hyperuricaemia who were balanced on 75 baseline characteristics. Associations of hyperuricaemia with outcomes during 25 months of median follow-up were examined in all patients and in those with and without CKD (estimated glomerular filtration rate of <60 mL/min/1.73 m(2)). Hyperuricaemia-associated hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause mortality and HF hospitalization were 1.44 (1.12-1.85, P = 0.005) and 1.27 (1.02-1.58, P = 0.031), respectively. Hazard ratios (95% CIs) for all-cause mortality among those with and without CKD were 0.96 (0.70-1.31, P = 0.792) and 1.40 (1.08-1.82, P = 0.011), respectively (P for interaction, 0.071), and those for HF hospitalization among those with and without CKD were 0.99 (0.74-1.33, P = 0.942) and 1.49 (1.19-1.86, P = 0.001), respectively (P for interaction, 0.033).

Conclusion: Hyperuricaemia has a significant association with poor outcomes in HF patients without CKD but not in those with CKD, suggesting that hyperuricaemia may predict poor outcomes when it is primarily a marker of increased xanthine oxidase activity, but not when it is primarily due to impaired renal excretion of uric acid.

Figure 1

Absolute standardized differences before and after propensity score matching comparing covariate values for patients with normal and high levels of uric acid. ACE, angiotensin-converting enzyme; ARB, angiotensin-receptor blocker; NYHA, New York Heart Association.

Figure 2

Kaplan–Meier plots for (A) all-cause mortality and (B) heart failure hospitalization. CI, confidence interval; HR, hazard ratio.

Figure 3

Association of hyperuricaemia and heart failure hospitalization in subgroups of matched patients. CI, confidence interval; HR, hazard ratio.

Figure 4

Association of hyperuricaemia and all-cause mortality in subgroups of matched patients. CI, confidence interval; HR, hazard ratio.