Abstract

BackgroundElevated serum uric acid (SUA) is associated with poor prognosis in patients with cardiovascular disease, yet it is still not decided whether the role of SUA is causal or only reflects an underlying disease. The purpose of the study was to investigate if SUA was an independent predictor of 5-year all-cause mortality in a propensity score matched cohort of chronic heart failure (HF) outpatients. Furthermore, to assess whether gender or renal function modified the effect of SUA.MethodsPatients (n = 4684) from the Norwegian Heart Failure Registry with baseline SUA were included in the study. Individuals in the highest gender-specific SUA quartile were propensity score matched 1:1 with patients in the lowest three SUA quartiles. The propensity score matching procedure created 928 pairs of patients (73.4% males, mean age 71.4 ± 11.5 years) with comparable baseline characteristics. Kaplan Meier and Cox regression analyses were used to investigate the independent effect of SUA on all-cause mortality.ResultsSUA in the highest quartile was an independent predictor of all-cause mortality in HF outpatients (hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.03–1.37, p-value 0.021). Gender was found to interact the relationship between SUA and all-cause mortality (p-value for interaction 0.007). High SUA was an independent predictor of all-cause mortality in women (HR 1.65, 95% CI 1.24–2.20, p-value 0.001), but not in men (HR 1.06, 95% CI 0.89–1.25, p-value 0.527). Renal function did not influence the relationship between SUA and all-cause mortality (p-value for interaction 0.539).ConclusionsHigh SUA was independently associated with inferior 5-year survival in Norwegian HF outpatients. The finding was modified by gender and high SUA was only an independent predictor of 5-year all-cause mortality in women, not in men.

Highlights

  • Elevated serum uric acid (SUA) is associated with poor prognosis in patients with cardiovascular disease, yet it is still not decided whether the role of SUA is causal or only reflects an underlying disease

  • Survival analyses and outcomes based on SUA level SUA in the highest quartile was an independent predictor of all-cause mortality in heart failure (HF) outpatients (HR 1.19, 95% Confidence interval (CI) 1.03–1.37, p-value 0.021, Fig. 2)

  • High SUA was an independent predictor of all-cause mortality in women (HR 1.65, 95% confidential interval (95% CI) 1.24– 2.20, p-value 0.001) but not in men (HR 1.06, 95% CI 0.89–1.25, p-value 0.527)

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Summary

Introduction

Elevated serum uric acid (SUA) is associated with poor prognosis in patients with cardiovascular disease, yet it is still not decided whether the role of SUA is causal or only reflects an underlying disease. The relationship between elevated serum uric acid (SUA) and cardiovascular (CV) disease and mortality is well recognized [1, 2], yet it is still undecided whether the association reflects a causal inference or whether SUA is a risk marker reflecting the burden of the underlying disease. Gender, race, High SUA in heart failure (HF) may result from impaired oxidative metabolism causing accumulation of uric acid precursors and increased XO activation [5] as well as from decreased renal elimination as chronic kidney disease (CKD) is highly prevalent [6]. The association between SUA and CV disease outcomes appears to be more pronounced in women than in men [7, 27, 28] but the role of gender in the relationship between SUA and survival of HF patients is not yet clearly determined

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