Renal Dysfunction Increases Mortality and Morbidity in Chronic Heart Failure Patients

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Decreased renal function has been found to be an independent risk factor for cardiovascular outcomes in patients with chronic heart failure (CHF) with markedly reduced left ventricular ejection fraction (LVEF). The aim of this analysis was to evaluate the prognostic importance of renal function in a broader spectrum of patients with CHF.


The Candesartan in Heart Failure—Assessment of Reduction in Mortality and Morbidity (CHARM) program consisted of three component trials that enrolled patients with symptomatic CHF, based on use of angiotensin-converting enzyme (ACE) inhibitors and reduced (≤40%) or preserved LVEF (>40%). Entry baseline creatinine was required to be below 3.0 mg/dL (265 μmol/L). Routine baseline serum creatinine assessments were performed in 2680 North American patients. An analysis of the estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease equation and LVEF on risk of cardiovascular death or hospitalization for heart failure, as well as on all-cause mortality, was conducted in these 2680 patients.


The proportion of patients with eGFR <60 mL/min/1.73 m2 was 36.0%,42.6%forCHARM-Alternative, 33.0% for CHARM-Added, and 34.7% for CHARM-Preserved. During the median follow-up of 34.4 months (total 6493 person-years), the primary outcome of cardiovascular death or hospital admission for worsening CHF occurred in 950 of 2680 subjects. Both reduced eGFR and lower LVEF were found to be significant independent predictors of worse outcome after adjustment for major confounding baseline clinical characteristics. The risk of cardiovascular death or hospitalization for worsening CHF as well as the risk for all-cause mortality increased significantly below an eGFR of 60 mL/min/1.73 m2 (adjusted hazard ratio, 1.54 for 45 to 60 mL/min/1.73 m2 and 1.86 for <45 mL/min/1.73 m2 for the primary outcome, both p<0.001, and hazard ratio of 1.50, p>=0.006, and 1.91, p=0.001, respectively, for all-cause mortality). The prognostic value of eGFR was not significantly different among the three component trials. There was no significant interaction between renal function, the effect of candesartan, and clinical outcome.


Impaired renal function is independently associated with heightened risk of death, cardiovascular death, and hospitalization for heart failure in patients with CHF with both preserved as well as reduced LVEF. There was no evidence that the beneficial effect of candesartan was modified by baseline eGFR.—Hillege HL, Nitsch D, Pfeffer MA, et al. Renal function as a predictor of outcome in a broad spectrum of patients with heart failure. Circulation. 2006;13:671–678.

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