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Previous Volume 332:286-291 February 2, 1995 Number 5 Next

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ABSTRACT

Background Epidemiologic studies have identified hyperhomocysteinemia as a possible risk factor for atherosclerosis. We determined the risk of carotid-artery atherosclerosis in relation to both plasma homocysteine concentrations and nutritional determinants of hyperhomocysteinemia.

Methods We performed a cross-sectional study of 1041 elderly subjects (418 men and 623 women; age range, 67 to 96 years) from the Framingham Heart Study. We examined the relation between the maximal degree of stenosis of the extracranial carotid arteries (as assessed by ultrasonography) and plasma homocysteine concentrations, as well as plasma concentrations and intakes of vitamins involved in homocysteine metabolism, including folate, vitamin B₁₂, and vitamin B₆. The subjects were classified into two categories according to the findings in the more diseased of the two carotid vessels: stenosis of 0 to 24 percent and stenosis of 25 to 100 percent.

Results The prevalence of carotid stenosis of >25 percent was 43 percent in the men and 34 percent in the women. The odds ratio for stenosis of >25 percent was 2.0 (95 percent confidence interval, 1.4 to 2.9) for subjects with the highest plasma homocysteine concentrations (>14.4 µmol per liter) as compared with those with the lowest concentrations (<9.1 µmol per liter), after adjustment for sex, age, plasma high-density lipoprotein cholesterol concentration, systolic blood pressure, and smoking status (P<0.001 for trend). Plasma concentrations of folate and pyridoxal-5'-phosphate (the coenzyme form of vitamin B₆) and the level of folate intake were inversely associated with carotid-artery stenosis after adjustment for age, sex, and other risk factors.

Conclusions High plasma homocysteine concentrations and low concentrations of folate and vitamin B₆, through their role in homocysteine metabolism, are associated with an increased risk of extracranial carotid-artery stenosis in the elderly.

Source Information

From the U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston (J.S., P.F.J., E.J.S., I.H.R.); the Framingham Heart Study, Framingham, Mass. (A.G.B., P.W.F.W.); the Department of Mathematics, Statistics and Consulting Unit, Boston University, Boston (R.B.D., A.J.B.); the Department of Radiology, Geisinger Medical Center, Danville, Pa. (D.H.O.); and the Department of Neurology, Boston University School of Medicine, and the Section of Preventive Medicine and Epidemiology, Evans Memorial Department of Clinical Research and Department of Medicine, University Hospital, Boston (P.A.W.).

Address reprint requests to Dr. Selhub at the USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St., Boston, MA 02111.

Full Text of this Article

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Plasma Homocyst(e)ine or Homocysteine?
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N Engl J Med 1995; 333:325, Aug 3, 1995. Correspondence

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• Federman, D. G., Kirsner, R. S. (2001). An Update on Hypercoagulable Disorders. Arch Intern Med 161: 1051-1056 [Abstract] [Full Text]  
• Roest, M., van der Schouw, Y. T., Grobbee, D. E., Tempelman, M. J., de Groot, P. G., Sixma, J. J., Banga, J. D. (2001). Methylenetetrahydrofolate Reductase 677 C/T Genotype and Cardiovascular Disease Mortality in Postmenopausal Women. Am J Epidemiol 153: 673-679 [Abstract] [Full Text]  
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• Meiklejohn, D. J., Vickers, M. A., Dijkhuisen, R., Greaves, M. (2001). Plasma Homocysteine Concentrations in the Acute and Convalescent Periods of Atherothrombotic Stroke. Stroke 32: 57-62 [Abstract] [Full Text]  
• Delvin, E. E, Rozen, R., Merouani, A., Genest, J. Jr, Lambert, M. (2000). Influence of methylenetetrahydrofolate reductase genotype, age, vitamin B-12, and folate status on plasma homocysteine in children. Am. J. Clin. Nutr. 72: 1469-1473 [Abstract] [Full Text]  
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• McKay, D. L., Perrone, G., Rasmussen, H., Dallal, G., Blumberg, J. B. (2000). Multivitamin/Mineral Supplementation Improves Plasma B-Vitamin Status and Homocysteine Concentration in Healthy Older Adults Consuming a Folate-Fortified Diet. J. Nutr. 130: 3090-3096 [Abstract] [Full Text]