Plasma B vitamins and their relation to the severity of chronic heart failure

Background: Total homocysteine (tHcy) has been linked to the severity of chronic heart failure (CHF). Elevated tHcy concentrations are mainly caused by folate and vitamin B-12 deficiencies. Objective: We hypothesized that folate and vitamin B-12 deficiencies can explain the relation between tHcy and the severity of CHF. Design: We investigated 987 CHF patients. All subjects underwent a physical examination and blood sampling. Cardiac catheterization was performed in 929 patients and echocardiography in 460 patients. Serum tHcy, folate, vitamin B-12, and N-terminal pro-B-type natriuretic-peptide (NT-proBNP) were measured and renal and hepatic function were studied. Results: tHcy increased with increasing New York Heart Association (NYHA) classes of heart failure (P < 0.001) and correlated with the left ventricular ejection fraction (EF; r = -0. 150, P < 0.00 1). Contrary to the hypothesis, vitamin B-12 (P < 0.00 1) increased with NYHA class (P < 0.00 1) and was negatively correlated with EF (r = -0.080, P = 0.015). Folate showed no relation with NYHA class or EF. Comparable results were obtained for NT-proBNP (tHcy: r = 0.27, P < 0.001; vitamin B-12: r = 0.091, P = 0.004; folate: r = -0.045, P = 0.169). The correlations between tHcy, EF, and NT-proBNP were significantly stronger in patients without coronary artery disease (CAD) than in those with CAD. Regression analysis showed that tHcy, but not B vitamins, is a strong predictor of EF and NT-proBNP. Conclusions: This study showed that tHcy, but not folate and vitamin B-12, is related to clinical, echocardiographic, and laboratory variables of CHF, which indicates a relation between tHcy and the severity of CHF. This relation is stronger in patients without CAD . The lack of association of folate and the paradoxical relation of vitamin B-12 with CHF can possibly be explained by a disturbance in hepatic homeostasis.