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Published in: Homocysteine Metabolism: From Basic Science to Clinical Medicine, ed. Ian Graham, Helga Refsum, Irwin H. Rosenberg, Per Magne Ueland, & Jill M. Shuman (Boston: Kluwer Academic Publishers, 1997).


This article is a U.S. government work, and is not subject to copyright in the United States.


Recent epidemiologic studies suggest that elevated homocysteine concentrations in plasma represent a risk factor for vascular disease and stroke. In the present study, we analyzed plasma samples from the 20th biannual examination of the Framingham Heart Study cohort to determine distribution of plasma homocysteine concentrations, with emphasis on relationships to vitamins that are involved in homocysteine metabolism and prevalence of carotid artery stenosis. Results showed that homocysteine was positively correlated with age. After controlling for age and sex, homocysteine exhibited strong inverse correlation with plasma folate, and weaker correlations with plasma vitamin B12 and pyridoxal- 5' -phosphate. Homocysteine was also inversely correlated with intakes of folate and vitamin B6, but not vitamin Bl2 • Prevalence of high homocysteine (>14 μmol/L) was 29.3% in this cohort, and inadequate plasma concentrations of one or more B vitamins appeared to contribute to 67% of the cases of high homocysteine. After adjustment for sex, age, HDL cholesterol, systolic blood pressure, and cigarette smoking, the prevalence of carotidartery stenosis ≥25% was 43% in men and 34% in women with an odds ratio of 2.0 for individuals in the highest homocysteine quartile, compared with those in the lowest quartile (p < 0.001). Plasma concentrations of folate and pyridoxal-5'-phosphate and folate intake were inversely associated with extracranial carotid stenosis after adjustment for age, sex, and other risk factors. These data indicate that hyperhomocysteinemia is prevalent (30%) in this aged population, and that it is associated with increased risk of extracranial carotid-artery stenosis. Insufficient levels of folate, and, to a lesser extent, vitamin B6, appear to predict part of this elevated risk through their role in homocysteine metabolism.

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