title: Effects of statins on the progression of cerebral white matter lesion: Post hoc analysis of the ROCAS (Regression of Cerebral Artery Stenosis) study.
abstract: Arteriosclerotic related cerebral white matter lesion (WML) is associated with increased risk of death, stroke, dementia, depression, gait disturbance, and urinary incontinence. We investigated the effects of statins on WML progression by performing a post hoc analysis on the ROCAS (Regression of Cerebral Artery Stenosis) study, which is a randomized, double-blind, placebo-controlled study evaluating the effects of statins upon asymptomatic middle cerebral artery stenosis progression among stroke-free individuals. Two hundreds and eight randomized subjects were assigned to either placebo (n = 102) or simvastatin 20 mg daily (n = 106) for 2 years. Baseline severity of WML was graded visually into none, mild, and severe. Volume (cm3) of WML was determined quantitatively at baseline and at end of study using a semi-automated method based on MRI. Primary outcome was the change in WML volume over 2 years. After 2 years of follow-up, there was no significant change in WML volume between the active and the placebo group as a whole. However, stratified analysis showed that for those with severe WML at baseline, the median volume increase in the active group (1.9 cm3) was less compared with that in the placebo group (3.0 cm3; P = 0.047). Linear multivariate regression analysis identified that baseline WML volume (beta = 0.63, P < 0.001) and simvastatin treatment (beta = -0.214, P = 0.043) independently predicted change in WML volume. Our findings suggest that statins may delay the progression of cerebral WML only among those who already have severe WML at baseline.
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China. vctmok@cuhk.edu.hk
authors.forename: Vincent C T
authors.initials: VC
authors.lastname: Mok
authors.forename: Wynnie W M
authors.initials: WW
authors.lastname: Lam
authors.forename: Yu Hua
authors.initials: YH
authors.lastname: Fan
authors.forename: Adrian
authors.initials: A
authors.lastname: Wong
authors.forename: Ping Wing
authors.initials: PW
authors.lastname: Ng
authors.forename: Tak Hon
authors.initials: TH
authors.lastname: Tsoi
authors.forename: Vincent
authors.initials: V
authors.lastname: Yeung
authors.forename: Ka Sing
authors.initials: KS
authors.lastname: Wong
mesh_terms: D000368:Aged; D001931:Brain Mapping; D002536:Cerebral Arteries / Q000187:drug effects* / Q000473:pathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D015140:Dementia, Vascular / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D007091:Image Processing, Computer-Assisted; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002537:Intracranial Arteriosclerosis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000473:pathology; D010919:Placebos; D012720:Severity of Illness Index; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010919:Placebos; D019821:Simvastatin