N Engl J Med 1997, 337(4): 230-236
Nygard,O.; Nordrehaug,J.E.; Refsum,Helga; Ueland,Per Magne; Farstad,M.; Vollset,S.E.
BACKGROUND: Elevated plasma homocysteine levels are a risk factor for coronary
heart disease, but the prognostic value of homocysteine levels in patients with established coronary artery
disease has not been defined.
METHODS: We prospectively investigated the relation between plasma total
homocysteine levels and mortality among 587 patients with angiographically confirmed coronary artery disease.
At the time of angiography in 1991 or 1992, risk factors for coronary disease, including homocysteine levels,
were evaluated. The majority of the patients subsequently underwent coronary-artery bypass grafting (318
patients) or percutaneous transluminal coronary angioplasty (120 patients); the remaining 149 were treated
medically.
RESULTS: After a median follow-up of 4.6 years, 64 patients (10.9 percent) had died.
We found a strong, graded relation between plasma homocysteine levels and overall mortality. After four
years, 3.8 percent of patients with homocysteine levels below 9 micromol per liter had died, as compared
with 24.7 percent of those with homocysteine levels of 15 micromol per liter or higher. Homocysteine levels
were only weakly related to the extent of coronary artery disease but were strongly related to the history
with respect to myocardial infarction, the left ventricular ejection fraction, and the serum creatinine
level. The relation of homocysteine levels to mortality remained strong after adjustment for these and
other potential confounders. In an analysis in which the patients with homocysteine levels below 9 micromol
per liter were used as the reference group, the mortality ratios were 1.9 for patients with homocysteine
levels of 9.0 to 14.9 micromol per liter, 2.8 for those with levels of 15.0 to 19.9 micromol per liter,
and 4.5 for those with levels of 20.0 micromol per liter or higher (P for trend=0.02). When death due to
cardiovascular disease (which occurred in 50 patients) was used as the end point in the analysis, the
relation between homocysteine levels and mortality was slightly strengthened.
CONCLUSIONS: Plasma total homocysteine levels are a strong predictor of
mortality in patients with angiographically confirmed coronary artery disease