Effect of Losartan on Circulating TNFα Levels and Left Ventricular Systolic Performance in Patients with Heart Failure

Abstract

Background Tumor necrosis factor alpha (TNFα) plays an important role in the pathophysiology of heart failure. Recent studies have shown a beneficial effect of losartan in these patients. However, the effect of losartan on TNFα levels in heart failure has not yet been studied. We evaluated the effect of losartan on circulating TNFα levels and ejection fraction (EF) in patients with congestive heart failure.

Methods Forty patients with heart failure and EF ≤ 40% were enrolled into the study. All of the patients have been given diuretic and digitalis therapy. Twenty patients were given losartan (50 mg/d) (Group I, 10 women, 10 men, 12 dilated cardiomyopathy, 8 ischemic heart disease, mean age 64.9 ± 8.9), and another 20 patients were not given losartan because of hypotension or renal dysfunction (Group II, 13 men, 7 women, 10 dilated cardiomyopathy, 10 ischemic heart disease, mean age 61.2 ±10.5). EF was measured at the initial evaluation and on the fifteenth day of the therapy by echocardiographic examination using an acoustic quantification method. Circulating TNFα levels were also measured at the initial evaluation and on the fifteenth day of therapy by the ELISA method.

Results Losartan significantly increased EF and decreased TNFα (EF increased from 29.4 ± 7.3% to 36.0 ± 8.5%, P < 0.001, and TNFα decreased from 39.2 ± 37.4 pg/ml to 27.0 ± 30.0 pg/ml, P < 0.05). Changes in TNFα levels and EF were not found to be correlated (r=−0.28, P=0.24). However, in the control group, EF and TNFα levels were similar at baseline and at the fifteenth day (EF 31.4 ± 8.1% vs 31.7 ± 7.8%, P=0.1, and TNFα 91.5 ± 86.0 pg/ml vs 110.0 ± 80.7 pg/ml, P=0.1, respectively).

Conclusions Losartan improves left ventricular systolic function and decreases TNFα level. The decreased TNFα level seems to be independent of EF.