Effect of losartan on circulating TNFalpha levels and left ventricular systolic performance in patients with heart failure.

BACKGROUND: Tumor necrosis factor alpha (TNFalpha) 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 TNFalpha levels in heart failure has not yet been studied. We evaluated the effect of losartan on circulating TNFalpha levels and ejection fraction (EF) in patients with congestive heart failure. METHODS: Forty patients with heart failure and EF < or = 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 TNFalpha 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 TNFalpha (EF increased from 29.4 +/- 7.3% to 36.0 +/- 8.5%, P < 0.001, and TNFalpha decreased from 39.2 +/- 37.4 pg/ml to 27.0 +/- 30.0 pg/ml, P < 0.05). Changes in TNFalpha levels and EF were not found to be correlated (r=-0.28, P=0.24). However, in the control group, EF and TNFalpha levels were similar at baseline and at the fifteenth day (EF 31.4 + 8.1% vs 31.7 +/- 7.8%, P=0.1, and TNFalpha 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 TNFalpha level. The decreased TNFalpha level seems to be independent of EF.

Predictive value of mitral annular calcification for the diagnosis of coronary artery disease in patients with dilated cardiomyopathy.

Mitral annulus calcification (MAC) is an independent predictor of coronary artery disease (CAD). The present study was designed to determine whether an association exists between MAC and CAD in patients with dilated cardiomyopathy. Among the 286 patients with MAC on echocardiographic examination who underwent coronary angiography, 55 patients with echocardiographic findings of dilated cardiomyopathy (group I) were compared to 60 age-matched controls without MAC and an echocardiographic diagnosis of dilated cardiomyopathy (group II) who underwent coronary angiography during the same time. There were no differences in echocardiographic findings between two groups. The prevalence of CAD was higher in group I when compared to group II (74% vs 28%, p<0.001). With regard to severity of CAD, two-vessel, three-vessel, and left main coronary artery disease were found to be significantly frequent in group I (p<0.001). Multivariate analysis revealed that MAC (p=0.001), diabetes mellitus (p=0.048), and history of anginal chest pain (p=0.009) are the independent predictors for the presence of CAD in patients with dilated cardiomyopathy. In conclusion, MAC may be a marker for the presence of coronary artery disease in patients with dilated cardiomyopathy.

Hyperhomocysteinemia and restenosis.

OBJECTIVE: This study was undertaken to assess the effect of plasma homocysteine level on angiographic restenosis 6 months after coronary angioplasty. METHODS: The plasma homocysteine level was measured in 100 consecutive patients at the time of coronary angioplasty, 56 patients who attended a 6-month follow-up angiogram being enrolled to the study; the 44 patients without a control coronary angiogram were not enrolled. Patients with and without angiographic restenosis were designated as groups A (n = 34) and B (n = 22) respectively. RESULTS: The baseline demographic (groups A and B), angiographic (groups A and B) and procedural characteristics were similar in both groups. The mean plasma homocysteine level (SD) was 15.2 (7.7) and 11.1 (2.5) mumol/l in groups A and B respectively (P = 0.007; 95% CI -6.9 to -1.1). With respect to the plasma homocysteine level, the upper and the lower thirds were compared by binary logistic regression (the lower third homocysteine level being < 10.6 mumol/l and the upper third homocysteine level > 14.1 mumol/l). The angiographic restenosis rate for the lower and upper tertiles was 47.4% and 89.5% respectively (P = 0.01; OR = 9.4; 95% CI 1.6-52.7). After adjustment for age and sex, the statistical significance did not change (P = 0.013; OR = 9.43; 95% CI 1.6-54.9). Even after adjustment for age, sex, smoking, hypertension, hypercholesterolemia, and diabetes mellitus, there was a statistically significant difference between the upper and lower tertiles (P = 0.008; OR = 41.3; 95% CI 2.6-635). CONCLUSION: Increased plasma homocysteine level and diabetes mellitus were independent risk factors for angiographic restenosis after percutaneous transluminal coronary angioplasty and coronary stenting.