Stroke, Vol 25, 1924-1930, Copyright © 1994 by American Heart Association
P Verhoef, CH Hennekens, MR Malinow, FJ Kok, WC Willett and MJ Stampfer
BACKGROUND AND PURPOSE: Several studies have reported elevated circulating
homocyst(e)ine levels in subjects with cerebral atherosclerosis. We
assessed prospectively whether high plasma levels of homocyst(e)ine affect
risk of ischemic stroke and evaluated whether high blood pressure modifies
any such effect. METHODS: The study sample was drawn from the Physicians'
Health Study, a randomized, double- blind, placebo-controlled trial of
aspirin and beta-carotene in 22,071 US male physicians. A total of 14,916
subjects 40 to 84 years old with no prior history of stroke, transient
ischemic attack, or myocardial infarction provided blood samples at
baseline and were followed for 5 years, with 99.7% morbidity and 100%
mortality follow-up. Using a nested case-control design, we assayed
homocyst(e)ine in samples from 109 subjects who subsequently developed
ischemic stroke and 427 control subjects. RESULTS: The mean plasma
concentration of homocyst(e)ine was slightly higher in subjects with stroke
(11.1 +/- 4.0 [+/- SD] nmol/mL) than in control subjects (10.6 +/- 3.4
nmol/mL), but the difference was not statistically significant (P = .12).
The crude odds ratio of ischemic stroke for subjects in the upper 20% (>
12.7 nmol/mL) compared with those in the bottom 80% of homocyst(e)ine
levels was 1.4 (95% confidence interval, 0.8 to 2.2). The odds ratio was
1.2 (95% confidence interval, 0.7 to 2.0) after controlling for several
risk factors and other potential confounders. In subgroup analyses,
elevated homocyst(e)ine levels appeared to be more strongly predictive of
ischemic stroke in normotensive subjects and in men 60 years or younger.
Although not statistically significant, in these subgroups increases in
risks of 100% and 70%, respectively, were observed for men in the upper 20%
of homocyst(e)ine values. CONCLUSIONS: In this study, the data were
compatible with a small but nonsignificant association between elevated
plasma homocyst(e)ine and risk of ischemic stroke. However, since the
sample size is small and the confidence intervals are wide, either no
association or a moderate increase in risk cannot be excluded, particularly
in subgroups otherwise at low risk, eg, younger men and those with normal
blood pressure.
ARTICLES
A prospective study of plasma homocyst(e)ine and risk of ischemic stroke
Department of Epidemiology and Public Health, Agricultural University, Wageningen, Netherlands.
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R. W. Evans, B. J. Shaten, J. D. Hempel, J. A. Cutler, and L. H. Kuller Homocyst(e)ine and Risk of Cardiovascular Disease in the Multiple Risk Factor Intervention Trial Arterioscler Thromb Vasc Biol, October 1, 1997; 17(10): 1947 - 1953. [Abstract] [Full Text]
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S. Evers, H.-G. Koch, K.-H. Grotemeyer, B. Lange, T. Deufel, and E.-B. Ringelstein Features, Symptoms, and Neurophysiological Findings in Stroke Associated With Hyperhomocysteinemia Arch Neurol, October 1, 1997; 54(10): 1276 - 1282. [Abstract] [PDF]
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K. Sutton-Tyrrell, A. Bostom, J. Selhub, and C. Zeigler-Johnson High Homocysteine Levels Are Independently Related to Isolated Systolic Hypertension in Older Adults Circulation, September 16, 1997; 96(6): 1745 - 1749. [Abstract] [Full Text]
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H. S. Markus, N. Ali, R. Swaminathan, A. Sankaralingam, J. Molloy, and J. Powell A Common Polymorphism in the Methylenetetrahydrofolate Reductase Gene, Homocysteine, and Ischemic Cerebrovascular Disease Stroke, September 1, 1997; 28(9): 1739 - 1743. [Abstract] [Full Text]
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O. Nygard, J. E. Nordrehaug, H. Refsum, P. M. Ueland, M. Farstad, and S. E. Vollset Plasma Homocysteine Levels and Mortality in Patients with Coronary Artery Disease N. Engl. J. Med., July 24, 1997; 337(4): 230 - 237. [Abstract] [Full Text] [PDF]
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I. M. Graham, L. E. Daly, H. M. Refsum, K. Robinson, L. E. Brattstrom, P. M. Ueland, R. J. Palma-Reis, G. H. J. Boers, R. G. Sheahan, B. Israelsson, et al. Plasma Homocysteine as a Risk Factor for Vascular Disease: The European Concerted Action Project JAMA, June 11, 1997; 277(22): 1775 - 1781. [Abstract] [PDF]
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P. M. Ridker, C. H. Hennekens, J. Selhub, J. P. Miletich, M. R. Malinow, and M. J. Stampfer Interrelation of Hyperhomocyst(e)inemia, Factor V Leiden, and Risk of Future Venous Thromboembolism Circulation, April 1, 1997; 95(7): 1777 - 1782. [Abstract] [Full Text]
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C. Schmitz, K. Lindpaintner, P. Verhoef, J. M. Gaziano, and J. Buring Genetic Polymorphism of Methylenetetrahydrofolate Reductase and Myocardial Infarction: A Case-Control Study Circulation, October 15, 1996; 94(8): 1812 - 1814. [Abstract] [Full Text]
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M. van den Berg, C. D.A. Stehouwer, E. Bierdrager, and J. A. Rauwerda Plasma Homocysteine and Severity of Atherosclerosis in Young Patients With Lower-Limb Atherosclerotic Disease Arterioscler Thromb Vasc Biol, January 1, 1996; 16(1): 165 - 171. [Abstract] [Full Text]
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C. J. Boushey, S. A. A. Beresford, G. S. Omenn, and A. G. Motulsky A Quantitative Assessment of Plasma Homocysteine as a Risk Factor for Vascular Disease: Probable Benefits of Increasing Folic Acid Intakes JAMA, October 4, 1995; 274(13): 1049 - 1057. [Abstract] [PDF]
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W. H. Giles, S. J. Kittner, R. F. Anda, J. B. Croft, and M. L. Casper Serum Folate and Risk for Ischemic Stroke : First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study Stroke, July 1, 1995; 26(7): 1166 - 1170. [Abstract] [Full Text]
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A. Lindgren, L. Brattstrom, B. Norrving, B. Hultberg, A. Andersson, and B. B. Johansson Plasma Homocysteine in the Acute and Convalescent Phases After Stroke Stroke, May 1, 1995; 26(5): 795 - 800. [Abstract] [Full Text]
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