(Circulation. 1999;99:2383-2388.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Hyperhomocysteinemia but Not the C677T Mutation of Methylenetetrahydrofolate Reductase Is an Independent Risk Determinant of Carotid Wall Thickening
The Perth Carotid Ultrasound Disease Assessment Study (CUDAS)
Presented in part at the 70th Scientific Sessions of the American Heart Association, Orlando, Fla, November 9–12, 1997, and published in abstract form (Circulation. 1997;96[suppl I]:I-655).
From the Sir Charles Gairdner Hospital Campus of the Heart Research Institute of Western Australia (B.McQ., M.N., P.L.T., J.H.); the Department of Clinical Biochemistry, PathCentre, QEII Medical Centre (J.P.B.); and the Department of Medicine, University of Western Australia (J.H.), Nedlands.
Correspondence to A/Prof Joseph Hung, University Department of Medicine, QEII Medical Centre, Nedlands, Western Australia, Australia 6009. E-mail jhung{at}cyllene.uwa.edu.au
Background—Hyperhomocysteinemia has been identified as a potential risk factor for atherosclerosis. This study examined whether a modest elevation of plasma total homocysteine (tHcy) was an independent risk factor for increased carotid artery intimal-medial wall thickness (IMT) and focal plaque formation in a large, randomly selected community population. We also examined whether vitamin cofactors and the C677T genetic mutation of the methylenetetrahydrofolate reductase (MTHFR) enzyme were major contributors to elevated plasma tHcy and carotid vascular disease.
Methods and Results—In 1111 subjects (558 men, 553 women) 52±13 years old (mean±SD; range, 27 to 77 years) recruited from a random electoral roll survey, we measured fasting tHcy and performed bilateral carotid B-mode ultrasound. For the total population, mean tHcy was 12.1±4.0 µmol/L. Plasma tHcy levels were correlated with IMT (Spearman rank rs=0.31, P=0.0001). After adjustment for age, sex, and other conventional risk factors, subjects in the highest versus the lowest quartile of tHcy had an odds ratio of 2.60 (95% CI, 1.51 to 4.45) for increased IMT and 1.76 (95% CI, 1.10 to 2.82) for plaque. Serum and dietary folate levels and the C677T mutation in MTHFR were independent determinants of tHcy (all P=0.0001). The mutant homozygotes (10% of the population) had higher mean tHcy than heterozygotes or those without the mutation (14.2 versus 12.3 versus 11.6 µmol/L, respectively, P=0.0001). The inverse association of folate levels with tHcy was steeper in the mutant homozygotes. Despite this, the C677T MTHFR mutation was not independently predictive of increased carotid IMT or plaque formation.
Conclusions—Mild hyperhomocysteinemia is an independent risk factor for increased carotid artery wall thickness and plaque formation in a general population. Lower levels of dietary folate intake and the C677T mutation in MTHFR are important causes of mild hyperhomocysteinemia and may therefore contribute to vascular disease in the community.
Key Words: homocysteine • genes • folate • atherosclerosis • ultrasonics
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