Dose-response association between plasma homocysteine and white matter lesions in patients with hypertension: a case-control study.

White matter lesions (WMLs) are common MRI changes that are indicative of cerebral small vessel disease (CSVD). Elevated plasma homocysteine (Hcy) levels are related to an increased risk of vascular disease. We aimed to analyze the relationship between Hcy levels and WMLs in patients with hypertension. A total of 1961 patients with WMLs and 15,463 patients without WMLs were matched at a 1:1 ratio by age and sex. Hyperhomocysteinemia (HHcy) was defined as an abnormally high level (>15 µmol/l) of Hcy in a plasma sample. In total, 1888 (WML group) and 1888 (No-WMLs group) patients were enrolled, with 51.6% of the sample being male and a mean age of 63 years. Multivariate logistic regression analysis showed a significant association between a higher level of plasma Hcy and a higher prevalence of WMLs (OR 1.03 95% CI, 1.02-1.04) when the Hcy level was used as a continuous variable. Patients with Hcy levels of 15-20 µmol/l (OR 1.54, 95% CI 1.31-1.81) and >20 µmol/l (OR 1.51, 95% CI 1.26-1.82) also had a significantly higher risk of WMLs than patients with Hcy levels <15 µmol/l. Multivariable-adjusted spline regression models showed that the risk of WMLs started to increase only in patients with Hcy levels above 13.85 µmol/l (P < 0.001). In subgroup analyses of WMLs, there was no significant interaction between the Hcy group and subgroup heterogeneity for the prevalence of WMLs (P > 0.05). Our study found a dose-response association between plasma homocysteine levels, especially a Hcy level >13.85 µmol/l, and the prevalence of WMLs, implying that lowering Hcy levels might be a target for prevention.