Background: Patients with chronic heart failure (CHF) may be particularly susceptible to unfavorable effects of hyperhomocysteinemia (HHcy). The aim of this study was to assess the prevalence of HHcy (plasma homocysteine [Hcy]>or=14 micromol/L) in an unselected cohort of CHF patients, its clinical determinants, and prognostic implications.
Methods and results: In 108 consecutive CHF patients (81 men, age: 66+/-11 years) with mean plasma Hcy level 12.5+/-5.5 micromol/L (range 2.3-28.3 micromol/L), 38 (35%) patients demonstrated HHcy. Among clinical and metabolic parameters, in multivariable regression models, advanced NYHA class (P<0.0001), plasma NT-proBNP (P<0.001), peak oxygen consumption (P<0.05), reduced glomerular filtration rate (P<0.0001) and elevated serum uric acid (P<0.05) predicted high plasma Hcy level. HHcy was related to increased mortality (HR=3.26, 95% CI: 1.78-5.98, P=0.0001), also when adjusted for conventional prognosticators in multivariable models (all P<0.01). In patients with HHcy, a 3-year survival was 37% (95% CI: 22-52%) as compared to 73% (95% CI: 63-83%) in those with normal Hcy levels (P<0.0001).
Conclusions: HHcy is common in CHF, is related to the disease severity, depicts generalized metabolic imbalance (evidenced by hyperuricaemia), and independently predicts poor long-term prognosis.