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Nonfasting Plasma Total Homocysteine Levels and Stroke Incidence in Elderly Persons: The Framingham Study

Andrew G. Bostom, MD, MS; Irwin H. Rosenberg, MD; Halit Silbershatz, PhD; Paul F. Jacques, ScD; Jacob Selhub, PhD; Ralph B. D'Agostino, PhD; Peter W.F. Wilson, MD; and Philip A. Wolf, MD
[+] Article and Author Information

From the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, and Boston University, Boston, Massachusetts; Memorial Hospital of Rhode Island, Providence, Rhode Island; and the National Heart, Lung, and Blood Institute's Framingham Study, Framingham, Massachusetts.


Grant Support: By U.S. Department of Agriculture contract 53-3K06-5-10; National Institutes of Health contract N01-HC-38038; National Heart, Lung, and Blood Institute grant RO1-HL-40423-05; and National Institute of Neurological Disorders and Stroke grant 2-RO1-NS-17950-17.

Requests for Reprints: Irwin H. Rosenberg, MD, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts New England Medical Center, 711 Washington Street, Boston, MA 02111; e-mail, rosenberg@hnrc.tufts.edu.

Current Author Addresses: Dr. Bostom: Memorial Hospital of Rhode Island, 111 Brewster Street, Pawtucket, RI 02860.

Drs. Rosenberg, Jacques, and Selhub: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts New England Medical Center, 711 Washington Street, Boston, MA 02111.

Drs. Silbershatz and D'Agostino: Boston University, 111 Cummington Street, Boston, MA 02215.

Dr. Wilson: National Heart, Lung, and Blood Institute, 5 Thurber Street, Framingham, MA 01701.

Dr. Wolf: Boston University School of Medicine, 715 Albany Street, B608, Boston, MA 02118.


Ann Intern Med. 1999;131(5):352-355. doi:10.7326/0003-4819-131-5-199909070-00006
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Background: Total homocysteine levels are associated with arteriosclerotic outcomes.

Objective: To determine whether total homocysteine levels predict incident stroke in elderly persons.

Design: Prospective population-based cohort study with 9.9 years of follow-up.

Setting: Framingham, Massachusetts.

Patients: 1947 Framingham Study participants (1158 women and 789 men; mean age ± SD, 70 ± 7 years).

Measurements: Baseline total homocysteine levels and 9.9-year stroke incidence.

Results: The quartiles of nonfasting total homocysteine levels were as follows: quartile 1, 4.13 to 9.25 µmol/L; quartile 2, 9.26 to 11.43 µmol/L; quartile 3, 11.44 to 14.23 µmol/L; quartile 4, 14.24 to 219.84 µmol/L. During follow-up, 165 incident strokes occurred. In proportional hazards models adjusted for age, sex, systolic blood pressure, diabetes, smoking, and history of atrial fibrillation and coronary heart disease, relative risk (RR) estimates comparing quartile 1 with the other three quartiles were as follows: quartile 2 compared with quartile 1—RR, 1.32 (95% CI, 0.81 to 2.14); quartile 3 compared with quartile 1—RR, 1.44 (CI, 0.89 to 2.34); quartile 4 compared with quartile 1—RR, 1.82 (CI, 1.14 to 2.91). The linear trend across the quartiles was significant (P < 0.001).

Conclusion: Nonfasting total homocysteine levels are an independent risk factor for incident stroke in elderly persons.

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