Hyperuricemia predicts adverse outcomes in patients with heart failure

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Abstract

Background

Hyperuricemia is associated with worse outcomes of patients with chronic heart failure (HF). However, it is unknown in an unselected HF patients encountered in routine clinical practice. We thus assessed the impact of hyperuricemia on long-term outcomes including mortality and rehospitalization among patients hospitalized with worsening HF.

Methods

The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) studied prospectively the characteristics and treatments in a broad sample of hospitalized HF patients and the outcomes were followed for 2.1 years after discharge. Study cohorts (n = 1869) were divided into 2 groups according to serum uric acid (UA) at discharge; ≥ 7.4 mg/dL (n = 908) and < 7.4 mg/dL (n = 961).

Results

Of the total cohort of HF patients, 56% had hyperuricemia defined as UA  7.0 mg/dl. Patients with UA  7.4 mg/dL had higher rates of all-cause death, cardiac death, rehospitalization, and all-cause death or rehospitalization due to worsening HF. After multivariable adjustment, higher UA levels were a significant and independent predictor for all-cause death (adjusted hazard ratio [HR] 1.413, 95% confidence interval [CI] 1.094–1.824, P = 0.008) and cardiac death (adjusted HR 1.399, 95% CI 1.020–1.920, P = 0.037).

Conclusions

Hyperuricemia was common in patients with HF encountered in clinical practice and higher UA was independently associated with long-term adverse outcomes in these patients.

Introduction

High serum uric acid (UA) or hyperuricemia has been well demonstrated to be associated with morbidity and mortality in general population [1], [2], [3] as well as in patients with coronary artery disease [4], [5]. It is also associated with poor outcomes in patients with mild to severe heart failure (HF) [6], [7], [8], [9]. Hyperuricemia in HF may be due to the upregulation of the xanthine oxidase (XO), a key enzyme in the generation of oxygen free radicals. Therefore, it may induce proinflammatory activation [10], impaired oxidative metabolism [11], vascular endothelial dysfunction [12], and exercise intolerance [13], [14] in HF. These conditions may well explain the association between hyperuricemia and poor outcome in chronic [6], [8] as well as acute HF [9]. However, previous studies enrolled small numbers of HF patients (n = 100–500) and were performed in a single center [6], [8], [9]. The impact of hyperuricemia on outcomes has not been assessed in a broad cohort of HF patients. Therefore, the purpose of this study was to examine the prevalence of hyperuricemia in HF patients encountered in routine clinical practice and to determine whether it is independently associated with the long-term outcomes. We analyzed the data from the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD), a prospective database of the clinical characteristics, treatments, and outcomes in a broad sample of patients hospitalized with worsening HF in Japan [15], [16], [17], [18], [19].

Section snippets

Study patients

The details of the JCARE-CARD have been described previously [15]. Briefly, eligible patients were those hospitalized due to worsening HF as the primary cause of admission. The patients with acute HF were excluded. For each patient, baseline data obtained at discharge included (1) demography; (2) causes of HF; (3) precipitating causes; (4) comorbidities; (5) complications; (6) clinical status; (7) electrocardiographic and echocardiographic findings; (8) plasma brain-type natriuretic peptide

Patient characteristics

Fig. 1 shows the distribution of serum UA among 1869 patients. Mean serum UA level in the study subjects was 7.3 ± 2.4 mg/dL, ranging from 0.3 to 22.5 mg/dL. 1041 (55.7%) patients had hyperuricemia defined as serum UA  7.0 mg/dL.

The mean age of the total cohort was 71.1 ± 12.9 years and 60.0% was men (Table 1). The causes of HF were ischemic in 32.5%, valvular in 28.5%, hypertensive in 25.9%, and dilated cardiomyopathy in 17.7%. The mean echocardiographic left ventricular ejection fraction (LVEF) was

Discussion

The present study demonstrated that hyperuricemia was seen in 56% of the patients hospitalized with HF. They had higher serum creatinine, higher plasma BNP, and lower LVEF and were prescribed more by loop diuretics and digitalis. Importantly, the risk of adjusted long-term adverse outcomes including all-cause death and cardiac death were significantly higher in patients with UA  7.4 mg/dl.

Even though the association between UA and cardiovascular diseases, including HF, has remained controversial

Acknowledgments

The JCARE-CARD investigators and participating cardiologists are listed in the Appendix of our previous publication [15]. This study could not have been carried out without the help, cooperation and support of the cardiologists in the survey institutions. We thank them for allowing us to obtain the data. The JCARE-CARD was supported by the Japanese Circulation Society and the Japanese Society of Heart Failure and by grants from Health Sciences Research Grants from the Japanese the Ministry of

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