Elevated plasma homocysteine is a risk factor for coronary artery disease (CAD) and thromboembolic disorders that seems also to be associated with chronic heart failure. To evaluate the association between homocysteine and left ventricular dysfunction and to assess whether it is independent of CAD. A prospective study evaluated this relationship in 709 patients referred for diagnostic coronary angiography, including 515 CAD and 194 patients without evidence of coronary artery lesions. The homocysteine level was significantly higher in the 187 patients with a left ventricular ejection fraction (LVEF) dysfunction < 40% (P < 0.0001) than in those without ventricular dysfunction. LVEF, NYHA functional class II or III and CAD, stable angina and hypertension were clinical characteristics that influenced total homocysteine level in univariate analysis. Homocysteine was significantly associated with LVEF and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) in univariate regression (r = -0.267, 95% CI -0.33 to -0.19, P < 0.0001, and r = 0.381, 95% CI 0.28-0.47, P < 0.0001, respectively) and in multiple regression (P = 0.0022 and P = 0.0001, respectively). Other determinants were creatinine and vitamin B(12), but not folate. LVEF was a predictor of homocysteine > 15 micromol L(-1) in the whole population (P for trend < or = 0.0001) and in patients without documented CAD (P for trend = 0.0058). Our results showed an association of homocysteine with left ventricular systolic dysfunction and NT-pro-BNP that existed independently of documented CAD. Whether this association reflects a causative factor or a consequence of CHF and influences the prognosis of the disease remains an open question.
