Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women

Background: Elevated fasting total homocysteine (tHcy) levels were recently shown to confer an independent risk for all-cause and cardiovascular disea se (CVD) mortality among selected Norwegian patients with confirmed coronar y heart disease. We examined whether elevated fasting plasma tHcy levels we re predictive of all-cause and CVD mortality in a large, population-based s ample of elderly US women and men. Methods: Nonfasting plasma tHcy levels were determined in 1933 elderly part icipants (mean age, 70 +/- 7 years; 58.9% women) from the original Framingh am Study cohort, examined between 1979 and 1982, with follow-up through 199 2. Unadjusted and adjusted (ie, for age, sex, diabetes, smoking, systolic b lood pressure, total and high-density lipoprotein cholesterol, and creatini ne) relative risk estimates (with 95% confidence intervals [CIs]) for total and CVD mortality were generated by proportional hazards modeling, with tH cy levels (quartiles) as the independent variable. Results: There were 653 total deaths and 244 CVD deaths during a median fol low-up of 10.0 years. Proportional hazards modeling revealed that tHcy leve ls of 14.26 mu mol/L or greater (the upper quartile), vs less than 14.26 mu mol/L (the lower three quartiles), were associated with relative risk esti mates of 2.18 (95% CI, 1.86-2.56) and 2.17 (95% CI, 1.68-2.82) for all-caus e and CVD mortality, respectively. The relative risk estimates after adjust ment for age, sex, systolic blood pressure, diabetes, smoking, and total an d high-density lipoprotein cholesterol levels attenuated these associations , but they remained significant: 1.54 (95% CI, 1.31-1.82) for all-cause mor tality; 1.52 (95%;, CI, 1.16-1.98) for CVD mortality. Conclusion: Elevated nonfasting plasma tHcy levels are independently associ ated with increased rates of all-cause and CVD mortality in the elderly.