Impact of Homocysteine-Lowering Vitamin Therapy on Long-Term Outcome of Patients With Coronary Artery Disease

Abstract

Elevated homocysteine levels are associated with increased risk for mortality in patients with coronary artery disease (CAD). However, the benefit of homocysteine-lowering therapy remains controversial. The aim of this study was to examine the impact of homocysteine-lowering therapy on the long-term outcomes of patients with CAD and its interaction with the methylenetetrahydrofolate reductase genotype. The study sample included 492 patients with early-onset CAD who were genotyped for the C677T mutation in the methylenetetrahydrofolate reductase gene or screened for elevated homocysteine from January 1997 to December 2002. Folic acid > or =400 microg/day with or without additional B vitamins was administered at the attending physicians' discretion. There was no difference between treated (n = 140) and untreated patients in age, gender, or prevalence of coronary risk factors. Forty-six patients (9%) died during a median follow-up period of 115 months. Treatment was associated with significantly lower all-cause mortality in patients with homocysteine levels >15 micromol/L (4% vs 32%, p <0.001) but not in patients with lower levels (5% vs 7%, p >0.05). On Cox regression analysis, the following factors were independently associated with all-cause mortality: vitamin therapy (hazard ratio 0.33, 95% confidence interval 0.11 to 0.98, p = 0.046), elevated homocysteine level (hazard ratio 3.5, 95% confidence interval 1.31 to 9.43, p = 0.013), and older age (hazard ratio 1.1, 95% confidence interval 1.04 to 1.14, p <0.0001 for an increment of 5 years). The methylenetetrahydrofolate reductase genotype was not associated with outcomes. In conclusion, long-term folate-based vitamin therapy was independently associated with lower all-cause mortality in patients with CAD and elevated homocysteine levels. This association was not observed in patients with lower homocysteine levels.