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

Arch Intern Med. 1999;159:1077-1080.

Background  Elevated fasting total homocysteine (tHcy) levels were recently shown to confer an independent risk for all-cause and cardiovascular disease (CVD) mortality among selected Norwegian patients with confirmed coronary heart disease. We examined whether elevated fasting plasma tHcy levels were predictive of all-cause and CVD mortality in a large, population-based sample of elderly US women and men.

Methods  Nonfasting plasma tHcy levels were determined in 1933 elderly participants (mean age, 70 ± 7 years; 58.9% women) from the original Framingham Study cohort, examined between 1979 and 1982, with follow-up through 1992. Unadjusted and adjusted (ie, for age, sex, diabetes, smoking, systolic blood pressure, total and high-density lipoprotein cholesterol, and creatinine) relative risk estimates (with 95% confidence intervals [CIs]) for total and CVD mortality were generated by proportional hazards modeling, with tHcy levels (quartiles) as the independent variable.

Results  There were 653 total deaths and 244 CVD deaths during a median follow-up of 10.0 years. Proportional hazards modeling revealed that tHcy levels of 14.26 µmol/L or greater (the upper quartile), vs less than 14.26 µmol/L (the lower three quartiles), were associated with relative risk estimates of 2.18 (95% CI, 1.86-2.56) and 2.17 (95% CI, 1.68-2.82) for all-cause and CVD mortality, respectively. The relative risk estimates after adjustment for age, sex, systolic blood pressure, diabetes, smoking, and total and high-density lipoprotein cholesterol levels attenuated these associations, but they remained significant: 1.54 (95% CI, 1.31-1.82) for all-cause mortality; 1.52 (95% CI, 1.16-1.98) for CVD mortality.

Conclusion  Elevated nonfasting plasma tHcy levels are independently associated with increased rates of all-cause and CVD mortality in the elderly.

From Tufts Jean Mayer USDA Human Nutrition Research Center on Aging, Boston, Mass (Drs Bostom, Rosenberg, Selhub, and Jacques); Division of General Internal Medicine, Memorial Hospital of Rhode Island, Providence (Dr Bostom); Department of Mathematics, Boston University (Drs Silbershatz, D'Agostino, and Wolf); and The National Heart, Lung, and Blood Institute Framingham Study, Framingham, Mass (Dr Wilson).

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