Effects of hyperhomocysteinemia on ischemic cerebral small vessel disease and analysis of inflammatory mechanisms

Purpose: Hyperhomocysteinemia is closely related to, but is not a confirmed risk factor of, cerebral small vessel disease (CSVD). This study aimed to determine whether hyperhomo-cysteinemia is correlated significantly with CSVD. Materials and methods: This cross-sectional study compared the homocysteine (Hcy) levels of patients with and without CSVD. High-sensitivity C-reactive protein (hs-CRP) levels were compared according to white matter lesion (WML) severity, which was classified using the Fazekas system. Risk factors for ischemic CSVD were analyzed through multivariate unconditional logistic regression analysis. Results: Hcy levels were significantly higher in patients with lacunar infarction (LI) than in controls (p=.0438), in patients with Fazekas 2-3 than in patients with Fazekas 0-1 WMLs (p=.0192), in patients with Fazekas 4-6 than in patients with Fazekas 2-3 WMLs (p=.0207), and in patients with LI than in patients without LI (p=.0043). hs-CRP levels were significantly higher in patients with LI than in patients without LI (p=.0068) and in patients with Fazekas 4-6 than in patients with Fazekas 0-1 WMLs (p=.0031). Three multivariate unconditional logistic regression analyses showed that hyperhomocysteinemia is a risk factor for LI (p=.006; odds ratio [OR], 27.668), severe WML (p=.028; OR, 1.984), and high hs-CRP level (p=.016; OR, 3.956). Conclusions: The assessment of Hcy levels is important for ischemic CSVD. Hyperhomocysteinemia is a risk factor for LI and severe WML. Further, hyperhomocysteinemia is associated with high hs-CRP levels, and this may involve an inflammatory mechanism; however, further studies are needed in this regard.