Homocysteine and progression of generalized small-vessel disease: the SMART-MR Study.
OBJECTIVE
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.
From the Department of Neurology (R.P.K., M.V., P.J.N.), Academic Medical Center, Amsterdam; and Departments of Neurology (R.P.K.), Internal Medicine (F.L.V.), and Radiology (W.P.T.M.M.), and Julius Center for Health Sciences and Primary Care (R.P.K., M.I.G., Y.v.d.G.), University Medical Center Utrecht, the Netherlands.
Raoul P
RP
Kloppenborg
Mirjam I
MI
Geerlings
Frank L
FL
Visseren
Willem P T M
WP
Mali
M
M
Vermeulen
Yolanda
Y
van der Graaf
Paul J
PJ
Nederkoorn
D000367:Age Factors; D000368:Aged; D001284:Atrophy / Q000097:blood / Q000150:complications / Q000473:pathology; D001921:Brain / Q000473:pathology*; D002561:Cerebrovascular Disorders / Q000097:blood* / Q000150:complications / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications / Q000473:pathology*; D007674:Kidney Diseases / Q000097:blood* / Q000150:complications / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors
D006710:Homocysteine