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 ≥400 μg/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 μmol/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.
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Article info
Publication history
Accepted:
May 2,
2009
Received in revised form:
May 2,
2009
Received:
February 21,
2009
Footnotes
This study was supported in part by an institutional research grant from Rabin Medical Center, Petah Tikva, Israel.
Identification
Copyright
© 2009 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
