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(Stroke. 2000;31:1069.)
© 2000 American Heart Association, Inc.
Original Contributions |
Association Between High Homocyst(e)ine and Ischemic Stroke due to Large- and Small-Artery Disease but Not Other Etiologic Subtypes of Ischemic Stroke
From the Preventive Cardiology and Therapeutics Program, McMaster University, Hamilton, Canada (J.W.E., S.S.A.); the Stroke Unit, Department of Neurology, Royal Perth Hospital, Wellington St, Perth, Australia (G.J.H.); the Department of Medicine, McMaster University, Hamilton, Canada (S.S.A.); and the Clinical Thrombosis Unit, Department of Hematology, Royal Perth Hospital, Perth, Australia (E.L., N.S., R.I.B.).
Correspondence to Clinical Associate Professor Graeme J, Hankey, Stroke Unit, Department of Neurology, Royal Perth Hospital, PO Box X2213, Wellington St, Perth, Australia 6001. E-mail gjhankey{at}cyllene.uwa.edu.au
Background and Purpose—Elevated plasma homocyst(e)ine may be a causal and modifiable risk factor for ischemic stroke, but the results of previous studies have been conflicting. One possible explanation is that homocyst(e)ine may only be associated with certain pathophysiological subtypes of ischemic stroke.
Methods—We conducted a case-control study of 219 hospital cases with a first-ever ischemic stroke and 205 randomly selected community control subjects stratified by age, sex, and postal code. With the use of established criteria, cases of stroke were classified by etiologic subtype in a blinded fashion. The prevalence of conventional vascular risk factors, fasting plasma homocyst(e)ine levels, vitamin levels, and nucleotide 677 methylene tetrahydrofolate reductase (MTHFR) genotypes were determined in cases and controls.
Results—Increasing homocyst(e)ine was a strong and independent risk factor for ischemic stroke (adjusted OR 2.7, 95% CI 1.4 to 5.1 for a 5-µmol/L increase in fasting plasma homocyst(e)ine from 10 to 15 µmol/L). Compared with the lowest quartile, the highest quartile of homocyst(e)ine was associated with an adjusted OR of ischemic stroke of 2.2 (95% CI 1.1 to 4.2). Mean plasma homocyst(e)ine was significantly higher in cases of ischemic stroke due to large-artery disease (14.1 µmol/L, 95% CI 12.5 to 15.9, P<0.001) and small-artery disease (12.7 µmol/L, 95% CI 11.4 to 14.1, P=0.004) compared with control subjects (10.5 µmol/L; 95% CI 10.0 to 11.0) but not in cardioembolic or other etiologic subtypes of ischemic stroke. Compared with the lowest quartile of homocyst(e)ine, the upper 3 quartiles were associated with an adjusted OR of ischemic stroke due to large-artery disease of 3.0 (95% CI 0.8 to 10.8) for the second quartile, 5.6 (95% CI 1.6 to 20) for the third quartile, and 8.7 (95% CI 2.4 to 32) for the fourth quartile (P for trend=0.0005). However, despite a clear association between the TT MTHFR genotype and elevated fasting plasma homocyst(e)ine, there was no association between MTHFR genotype and ischemic stroke or subtype of ischemic stroke.
Conclusions—There is a strong, graded association between increasing plasma homocyst(e)ine and ischemic stroke caused by large-artery atherosclerosis and, to a much lesser extent, small-artery disease, but not cardioembolic or other etiologic subtypes of ischemic stroke. Our results are consistent with the hypothesis that the deleterious effect of high homocyst(e)ine is mediated primarily via a proatherogenic effect.
Key Words: arterial occlusive disease • homocyst(e)ine • ischemic risk • stroke
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