title: Risk factor profile of cerebral small vessel disease and its subtypes.
abstract: BACKGROUND
  The mechanisms of cerebral small vessel disease (SVD) are unclear. Both atherosclerosis and a non-atherosclerotic diffuse arteriopathy have been reported pathologically. Two pathological and radiological subtypes have been suggested: localised atherosclerotic disease in larger perforating arteries causing larger lacunar infarcts without leukoaraiosis, and diffuse disease in smaller arterioles causing multiple smaller lacunar infarcts with leukoaraiosis. If atherosclerosis were important in SVD as a whole or in one particular subtype, one would expect the risk factor profile to be similar to that of cerebral large vessel disease (LVD).
  
  
  METHODS
  Risk factor profiles were compared in Caucasian stroke patients with SVD (n = 414), LVD (n = 471) and 734 stroke-free Caucasian population controls. Patients with SVD were subdivided according to the presence or absence of confluent leukoaraiosis, into isolated lacunar infarction (ILI) and ischaemic leukoaraiosis (ILA).
  
  
  RESULTS
  Hypertension was commoner in SVD than LVD (odds ratio (OR) 3.43 (2.32 to 5.07); p<0.001) whereas hypercholesterolaemia (OR 0.34 (0.24 to 0.48); p<0.001), smoking (OR 0.63 (0.44 to 0.91); p = 0.012), myocardial infarction (OR 0.35 (0.20 to 0.59); p<0.001) and peripheral vascular disease (OR 0.32 (0.20 to 0.50); p<0.001) were commoner in LVD. Among SVD patients, age (OR 1.11 (1.09 to 1.14); p<0.001) and hypertension (OR 3.32 (1.56 to 7.07); p = 0.002) were associated with ILA and hypercholesterolaemia (OR 0.45 (0.28 to 0.74); p = 0.002), diabetes (OR 0.42 (0.21 to 0.84); p = 0.014) and myocardial infarction (OR 0.18 (0.06 to 0.52); p = 0.001) with ILI.
  
  
  CONCLUSIONS
  SVD has a different risk factor profile from the typical atherosclerotic profile found in LVD, with hypertension being important. There are differences in the risk factor profile between the SVD subtypes; the association of ILI with hypercholesterolaemia, diabetes and myocardial infarction may be consistent with a more atherosclerotic aetiology.
authors.affiliation: Centre for Clinical Neuroscience, St George's University of London, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: Usman
authors.initials: U
authors.lastname: Khan
authors.forename: Linda
authors.initials: L
authors.lastname: Porteous
authors.forename: Ahamad
authors.initials: A
authors.lastname: Hassan
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Markus
mesh_terms: D000368:Aged; D001808:Blood Vessels / Q000033:anatomy & histology / Q000473:pathology; D016022:Case-Control Studies; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000453:epidemiology; D006973:Hypertension / Q000453:epidemiology; D002537:Intracranial Arteriosclerosis / Q000453:epidemiology* / Q000473:pathology*; D049292:Leukoaraiosis / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D016017:Odds Ratio; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000473:pathology*