Homocysteine and progression of generalized small-vessel disease The SMART-MR Study

Objectives: Assuming the involvement of homocysteine in a generalized small-vessel disease, we investigated the association of homocysteine levels with progression of white matter lesions, lacunar infarcts, and kidney disease. Methods: Within the SMART-MR (Second Manifestations of ARTerial disease–Magnetic Resonance) Study, a prospective cohort study on brain aging in patients with symptomatic atherosclerotic disease, 663 patients (aged 57 ± 9 years) had vascular screening and 1.5-tesla MRI at baseline and after a mean follow-up of 3.9 years. Multiple regression analysis was used to estimate the longitudinal association between total homocysteine level, defined as a continuous variable and as hyperhomocysteinemia (the highest quintile of homocysteine), and progression of white matter lesion volume, lacunar infarcts, and estimated glomerular filtration rate. Results: After adjusting for age, sex, follow-up time, and vascular risk factors, hyperhomocysteinemia was significantly associated with increased risk of white matter lesion progression (odds ratio 2.4, 95% confidence interval [CI] 1.5–4.1) and lower estimated glomerular filtration rate at follow-up (B = −3.4 mL/min, 95% CI −5.9 to −0.9) and borderline significantly associated with new lacunar infarcts (odds ratio 1.8, 95% CI 0.9–3.4). Conclusions: Our findings implicate a role for homocysteine in the development of a generalized small-vessel disease in which both brain and kidney are affected.