From the Division of Epidemiology, School of Public Health (A.R.F.,
P.G.M.) and Department of Laboratory Medicine and Pathology (M.Y.T., J.H.E.),
University of Minnesota, Minneapolis; Department of Epidemiology, School of
Hygiene and Public Health (F.J.N.), Johns Hopkins University, Baltimore, Md;
Laboratory of Cardiovascular Diseases, Oregon Regional Primate Research Center
(M.R.M., D.L.H.), Beaverton, Ore; and Collaborative Studies Coordinating
Center (C.E.D.), Chapel Hill, NC.
Background—Elevated plasma total
homocysteine (tHcy), low B-vitamin intake, and genetic
polymorphisms related to tHcy metabolism may play roles
in coronary heart disease (CHD). More prospective studies
are needed.
Methods and Results—We used a prospective case-cohort design to
determine whether tHcy-related factors are associated with incidence of
CHD over an average of 3.3 years of follow-up in a biracial sample of
middle-aged men and women. Age-, race-, and field center–adjusted CHD
incidence was associated positively (P<0.05) with tHcy
in women but not men, and CHD was associated negatively
(P<0.05) with plasma folate (women only), plasma
pyridoxal 5'-phosphate (both sexes), and vitamin supplementation (women
only). However, after accounting for other risk factors, only plasma
pyridoxal 5'-phosphate was associated with CHD incidence; the relative
risk for the highest versus lowest quintile of pyridoxal 5'-phosphate
was 0.28 (95% CI=0.1 to 0.7). There was no association of CHD with the
C677T mutation of the
methylenetetrahydrofolate reductase
gene or with 3 mutations of the cystathionine ß-synthase gene.
Conclusions—Our prospective findings add uncertainty to
conclusions derived mostly from cross-sectional studies that tHcy is a
major, independent, causative risk factor for CHD. Our findings point
more strongly to the possibility that vitamin B6 offers
independent protection. Randomized trials, some of which are under way,
are needed to better clarify the interrelationships of tHcy, B
vitamins, and cardiovascular disease.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Prospective Study of Coronary Heart Disease Incidence in Relation to Fasting Total Homocysteine, Related Genetic Polymorphisms, and B Vitamins
The Atherosclerosis Risk in Communities (ARIC) Study
Key Words: : coronary disease • vitamins • homocysteine • polymorphism (genetics)
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