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(Circulation. 1999;99:2361-2363.)
© 1999 American Heart Association, Inc.

Editorial

Homocysteine and Arteriosclerosis

Subclinical and Clinical Disease Associations

Andrew G. Bostom, MD, MS; Jacob Selhub, PhD

From the Division of General Internal Medicine, Memorial Hospital of Rhode Island (A.G.B.), Providence, and Vitamin Bioavailability Laboratory, Jean Mayer USDA Human Nutrition Research Center (A.G.B., J.S.), Boston, Mass.

Correspondence to Andrew G. Bostom, MD, General Internal Medicine, Memorial Hospital of Rhode Island, 111 Brewster St, Pawtucket, RI 02860. E-mail abostom@loa.com

Key Words: Editorials • arteriosclerosis • homocysteine • risk factors

In 1969, the clinical observations of McCully¹ first linked marked hyperhomocysteinemia (ie, equivalent to total homocysteine [tHcy] levels of 100 to 450 µmol/L by current assays) to precocious arteriosclerotic disease in autopsied children who died from distinct metabolic forms of homocystinuria. Intermittent reports of severe thrombotic outcomes specifically involving the extracranial carotid arteries in homocystinuric patients have been reported dating back at least 20 years.^{2 3 4} Excepting 2 small but notable studies,^{5 6} overall a rather consistent body of published data has emerged linking plasma tHcy levels to extracranial carotid artery wall thickening in young adults homozygous⁷ or heterozygous⁸ for cystathionine synthase deficiency, among young heterozygotes for familial hypercholesterolemia,⁹ and in general population samples of middle-aged, asymptomatic individuals free of clinical cardiovascular disease (CVD).^{10 11 12 13} In addition, tHcy levels have also been associated with more advanced extracranial carotid artery arteriosclerosis (ie, percentage of luminal stenosis) in elderly subjects^{14 15 16 17} and those with prevalent cerebrovascular disease.¹⁸

Thirty years after McCully's initial report,¹ a burgeoning amount of clinical evidence has accumulated that indicates that mild to moderate fasting, nonfasting, or post–methionine loading (PML) hyperhomocysteinemia (ie, tHcy levels 12 to 100 µmol/L fasting or nonfasting or 50 to 140 µmol/L 6 hours PML) is an independent risk factor for hard, arteriosclerotic outcomes. A recent series of pooled observational studies examining the relationship between homocysteine and CVD^{19 20 21} has been updated through the end of 1998 (Dr S.A.A. Beresford, personal communication). These meta-analyses indicated that the best estimate for the increased risk of arteriosclerotic coronary heart disease morbidity and . . . [Full Text of this Article]

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