Hyperhomocysteinemia in patients with symptomatic chronic heart failure: Prevalence and prognostic importance—pilot study

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] ≥ 14 μmol/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 μmol/L (range 2.3–28.3 μmol/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.