Impact of homocysteine-lowering vitamin therapy on long-term outcome of patients with coronary artery disease.
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.
Mager
Aviv
A
Department of Cardiology, Rabin Medical Center, Beilinson Campus, FMRC, Petah Tikva, Israel. avivmager@yahoo.com
Orvin
Katia
K
Koren-Morag
Nira
N
Lev
Israel Eli
IE
Assali
Abid
A
Kornowski
Ran
R
Shohat
Mordechai
M
Battler
Alexander
A
Hasdai
David
D
D000328:Adult; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D016019:Survival Analysis; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000008:administration & dosage*
D006710:Homocysteine; D014803:Vitamin B Complex; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)