Long-Term Survival and Apolipoprotein A1 Level in Chronic Heart Failure: Interaction With Tumor Necrosis Factor α-308 G/A Polymorphism

Background: Apolipoprotein A1 (ApoA1), a major constituent of high-density lipoprotein (HDL), has antiinflammatory and antioxidative properties and plays a prognostic role in chronic heart failure (CHF). Despite increased tumor necrosis factor alpha (TNF alpha) levels being linked to worse outcome of HF, the results are ambiguous about the association of functionally active 308 promoter polymorphism of the TNF alpha gene. The aims of our study were to investigate the association of ApoA1 and TNF alpha levels with mortality and to evaluate potential interaction between these factors and TNF alpha -308 polymorphism. Methods: Together with several parameters ApoA1, TNF alpha levels and TNF alpha-308 polymorphism were determined in a cohort of 195 patients with CHF who were followed for 5 years. Results: Low ApoA1 and high TNF alpha levels were associated with more severe disease, and ApoA1 showed the strongest relationship with HDL, total cholesterol, C-reactive protein, and N-terminal pro B-type natriuretic peptide (NT-proBNP). TNF alpha 308 A carriers had significantly higher ApoA1 levels than wild type (GG) patients (1.41 +/- 0.268 vs 1.29 +/- 0.324 g/L; P=.007), whereas levels of TNF alpha were the same in these groups. Decreased ApoA1 levels were significant predictors of 5-year mortality (NT-proBNP adjusted HR for 1 decile decrease in ApoA1 level was 1.10 (P=.011). Interaction was found between the ApoA1 level and TNF alpha 308 polymorphism, because in patients with GG haplotype the adverse effect of low ApoA1 level on survival was more prevalent. Conclusions: Lower ApoA1 levels were strongly associated with adverse outcome in CHF patients in a TNF alpha-308 polymorphism dependent manner. These observations support the complex involvement of mal nutrition and inflammation in the pathogenesis of CHF.