Тhe link of T(–786)C аnd G894T polymorphisms of the endothelial NO-synthase gene with endothelial vasodilatory function and long-term clinical prognosis in patients with chronic heart failure and reduced left ventricular ejection fraction

Abstract

The aim – сhronic heart failure (CHF) is associated with endothelial dysfunction. The pivotal role of nitric oxide in the maintenance of endothelial function (EF) is well-known. But it is unknown whether endothelial nitric oxide synthase (eNOS) gene polymorphismis associated with both EF and clinical outcomes in systolic CHF.Materials and methods. 116 stable (NYHA II–III) ischemic CHF patients with left ventricular ejection fraction (LVEF) ≤ 45 % were examined. Flow-mediated vasodilation (FMVD) of a. brachialis was carried out by standard cuff test. Patients were followed-up for a median of twenty months to determine long-term outcomes. The frequency of T(–786)C genotypes was: TT – 40.5 % (n=47), TC – 43.1 % (n=50), CC – 16.4 % (n=19); the frequency of G894T genotypes was: GG 56.0 % (n=65), GT 33.6 % (n=39), ТТ 10.4 % (n=12). Results and discussion. FMVD in patients with TT genotype of T(–786)C polymorphisms was 7.2 [4.7; 8.3] %, in patients with TC – 6.6 [4.4; 9.1] %, where as FMVD in patients with genotype CC was 4.7 [2.8; 6.0] %, p=0.034 for TT vs. CC; p=0.046 for TC vs. CC. FMVD in patients with GG genotype of G894T polymorphisms was 7.1 [4.3; 9.4] %, in patients with GT – 6.2 [5.1; 8.1] %, in patients with genotype TT was 4.2 [2.5; 5.3] %. The difference between FMVD was significant only TT vs. CC – p=0.030. The patients with CC genotype demonstrated a significantly higher heart failure hospitalization rate (log-rank 5.304, p=0.021) and higher cardiovascular (CV) mortality rate (log-rank 4.011, p=0.045) as compared with the TT homozygote group. LVEF, FMVD, and CC genotype were the predictors of CV mortality in univariate Cox regression analysis, and only LVEF and FMVD in multivariate Cox model. Long-term outcomes were similar in patients with GG, GT and TT genotypes of G894T polymorphisms.Conclusion. In stable ischemic systolic CHF CC T(–786)C eNOS genotype is associated with worse FMVD response and worse long-term outcome versus TT T(–786)C eNOS genotype. TT G(984)T eNOS genotype is associated with worse FMVD response only, but not with long-term outcomes versus GG G(894)T eNOS genotype.