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Eric B. Rimm, ScD; Walter C. Willett, MD, DrPH; Frank B. Hu, MD, PhD; Laura Sampson, MS; Graham A. Colditz, MB, BS, DrPH; JoAnn E. Manson, MD, DrPH; Charles Hennekens, MD, DrPH; Meir J. Stampfer, MD, DrPH

JAMA. 1998;279:359-364.

Context.— Hyperhomocysteinemia is caused by genetic and lifestyle influences, including low intakes of folate and vitamin B₆. However, prospective data relating intake of these vitamins to risk of coronary heart disease (CHD) are not available.

Objective.— To examine intakes of folate and vitamin B₆ in relation to the incidence of nonfatal myocardial infarction (MI) and fatal CHD.

Design.— Prospective cohort study.

Setting and Patients.— In 1980, a total of 80082 women from the Nurses' Health Study with no previous history of cardiovascular disease, cancer, hypercholesterolemia, or diabetes completed a detailed food frequency questionnaire from which we derived usual intake of folate and vitamin B₆.

Main Outcome Measure.— Nonfatal MI and fatal CHD confirmed by World Health Organization criteria.

Results.— During 14 years of follow-up, we documented 658 incident cases of nonfatal MI and 281 cases of fatal CHD. After controlling for cardiovascular risk factors, including smoking and hypertension and intake of alcohol, fiber, vitamin E, and saturated, polyunsaturated, and trans fat, the relative risks (RRs) of CHD between extreme quintiles were 0.69 (95% confidence interval [CI], 0.55-0.87) for folate (median intake, 696 µg/d vs 158 µg/d) and 0.67 (95% CI, 0.53-0.85) for vitamin B₆ (median intake, 4.6 mg/d vs 1.1 mg/d). Controlling for the same variables, the RR was 0.55 (95% CI, 0.41-0.74) among women in the highest quintile of both folate and vitamin B₆ intake compared with the opposite extreme. Risk of CHD was reduced among women who regularly used multiple vitamins (RR=0.76; 95% CI, 0.65-0.90), the major source of folate and vitamin B₆, and after excluding multiple vitamin users, among those with higher dietary intakes of folate and vitamin B₆. In a subgroup analysis, compared with nondrinkers, the inverse association between a high-folate diet and CHD was strongest among women who consumed up to 1 alcoholic beverage per day (RR =0.69; 95% CI, 0.49-0.97) or more than 1 drink per day (RR=0.27; 95% CI, 0.13-0.58).

Conclusion.— These results suggest that intake of folate and vitamin B₆ above the current recommended dietary allowance may be important in the primary prevention of CHD among women.

From the Departments of Epidemiology (Drs Rimm, Willett, Colditz, Manson, Hennekens, and Stampfer) and Nutrition (Drs Rimm, Willett, Hu, and Stampfer and Ms Sampson), Harvard School of Public Health, Boston, Mass; the Channing Laboratory (Drs Rimm, Willett, Colditz, Manson, Hennekens, and Stampfer) and the Division of Preventive Medicine (Drs Manson and Hennekens), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass; and the Department of Ambulatory Care and Prevention (Dr Hennekens) Harvard Medical School, Boston, Mass.

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