Published Online
on September 2, 2004

A more recent version of this article appeared on October 1, 2004

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Submitted on June 2, 2004
Revised on July 27, 2004
Accepted on July 30, 2004

Homocysteine and the Risk of Ischemic Stroke in a Triethnic Cohort. The Northern Manhattan Study

Ralph L. Sacco MD, MS^*; Kishlay Anand MD, MS; Hye-Seung Lee MS; Bernadette Boden-Albala DrPH; Sally Stabler MD; Robert Allen MD; and Myunghee C. Paik PhD

From the Department of Neurology (R.L.S., B.B.-A., H.-S.L.), the Sergievsky Center (R.L.S., K.A.), the Department of Socio-Medical Science (B.B.-A.), and the Department of Biostatistics (H.-S.L., M.C.P.), Columbia University College of Physicians and Surgeons and the Mailman School of Public Health, New York, NY; and the Department of Medicine (S.S., R.A.), School of Medicine, University of Colorado, Denver, Colo.

^* To whom correspondence should be addressed. E-mail: rls1{at}columbia.edu.

Background and Purpose--The level of total homocysteine (tHcy) that confers a risk of ischemic stroke is unsettled, and no prospective cohort studies have included sufficient elderly minority subjects. We investigated the association between mild to moderate fasting tHcy level and the incidence of ischemic stroke, myocardial infarction, and vascular death in a multiethnic prospective study.

Methods--A population-based cohort was followed for vascular events (stroke, myocardial infarction, and vascular death). Baseline values of tHcy and methylmalonic acid were measured among 2939 subjects (mean age, 69±10; 61% women, 53% Hispanics, 24% blacks, and 20% whites). Cox proportional models were used to calculate hazard ratios (HRs) and 95% CIs in tHcy categories after adjusting for age, race, education, renal insufficiency, B₁₂ deficiency, and other risk factors.

Results--The adjusted HR for a tHcy level 15 µmol/L compared with <10 µmol/L was greatest for vascular death (HR=6.04; 95% CI, 3.44 to 10.60), followed by combined vascular events (HR=2.27; 95% CI, 1.51 to 3.43), ischemic stroke (HR=2.01; 95% CI, 1.00 to 4.05), and nonvascular death (HR=2.02; 95% CI, 1.31 to 3.14). Mild to moderate elevations of tHcy of 10 to 15 µmol/L were not significantly predictive of ischemic stroke, but increased the risk of vascular death (2.27; 95% CI, 1.44 to 3.60) and combined vascular events (1.42; 95% CI, 1.06 to 1.88). The effect of tHcy was stronger among whites and Hispanics, but not a significant risk factor for blacks.

Conclusions--Total Hcy elevations above 15 µmol/L are an independent risk factor for ischemic stroke, whereas mild elevations of tHcy of 10 to 15 µmol/L are less predictive. The vascular effects of tHcy are greatest among whites and Hispanics, and less among blacks.

Key words: cerebrovascular disorders • ethnic groups • homocyst(e)ine • risk factors • women

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