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Homocysteine, small-vessel disease, and atherosclerosis

Objective: We evaluated the relationship between hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and small-vessel disease (SVD) and atherosclerotic large-vessel disease (LVD) in stroke patients. Methods: A total of 825 noncardioembolic ischemic stroke patients whose plasma concentrations of total homocysteine were measured and whose MTHFR C677T polymorphism status was identified were included in this retrospective study. MRI of the brain and magnetic resonance angiography of the intracranial and extracranial cerebral arteries had been performed. SVD and LVD were assessed by the Scheltens scale (the SVD score) and by the number of atherosclerotic steno-occlusive arteries (the LVD score), respectively. Results: The TT genotype of the MTHFR C677T polymorphism was associated with hyperhomocysteinemia (p < 0.001), but not with SVD (p = 0.182) or LVD (p = 0.988) scores. Multiple logistic regression analysis showed that hyperhomocysteinemia was associated with SVD (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.01–1.07; p = 0.005) and LVD (OR 1.02; 95% CI 1.00–1.05; p = 0.041) scores. Hyperhomocysteinemia was related to the LVD score of extracranial arteries (p = 0.008), but not to the LVD score of intracranial arteries (p = 0.730). In multiple logistic regression analysis, however, hyperhomocysteinemia was not related to the LVD score of extracranial arteries (p = 0.255). Conclusions: Hyperhomocysteinemia was associated with SVD of the brain and LVD of cerebral arteries. The MTHFR C677T polymorphism was not related to SVD and LVD, although the TT genotype was an important determinant of hyperhomocysteinemia.