Risk factor profile of cerebral small vessel disease and its subtypes

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 78; no. 7; pp. 702 - 706
• Main Authors: Khan, Usman, Porteous, Linda, Hassan, Ahamad, Markus, Hugh S
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.07.2007; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Aged; Atherosclerosis; Bias; Biological and medical sciences; Blood Vessels - anatomy & histology; Blood Vessels - pathology; Cardiovascular disease; Case-Control Studies; Classification; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Diabetes; Diabetes Mellitus - epidemiology; Embolisms; Endothelium; Female; Glucose; Homocysteine; Humans; Hypercholesterolemia - epidemiology; Hypertension; Hypertension - epidemiology; ILA; ILI; Intracranial Arteriosclerosis - epidemiology; Intracranial Arteriosclerosis - pathology; ischaemic leukoaraiosis; isolated lacunar infarction; large vessel disease; Leukoaraiosis - epidemiology; LVD; Male; Medical imaging; Medical sciences; Middle Aged; myocardial infarction; Myocardial Infarction - epidemiology; Neurology; Odds Ratio; Pathogenesis; peripheral vascular disease; PVD; Recruitment; Risk Factors; small vessel disease; Stroke; Stroke - epidemiology; Stroke - pathology; Studies; SVD; TOAST; Trial of Org 10172 in Acute Stroke Treatment; Vascular diseases and vascular malformations of the nervous system; Veins & arteries; White people; Nervous system diseases; Subtype; Central nervous system; Risk factor; Encephalon
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp.2006.103549

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. Conclusion: 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.