Genetics of Atherothrombotic and Lacunar Stroke

Abstract

Identifying new risk factors for ischemic stroke occurrence could help improve prevention strategies and identify new therapeutic targets. Genetic risk factors are particularly interesting, because they can offer a direct clue to the biological pathways involved. Ischemic stroke is a heterogeneous disorder, and this must be considered in the search for genetic susceptibility factors. In Western countries, most ischemic strokes can be attributed to large-artery atherosclerosis (atherothrombotic stroke) and small-artery occlusion (lacunar stroke), the rest being due to cardioembolism, vasculitis, monogenic disorders, undetermined causes, or rare etiologies such as cervical artery dissection. According to the Trial of Org 10172 in Acute Stroke Treatment criteria, an ischemic stroke is classified as atherothrombotic (or due to large-artery atherosclerosis) if it is associated with a >50% stenosis of an appropriate intracranial or extracranial artery1 and as lacunar (typically due to lipohyalinosis and microatheroma) if a brain stem or subcortical infarct of ≤1.5-cm diameter can be demonstrated and large-artery atherosclerosis and cardioembolism can be excluded.1 In the present study, we reviewed published data on the genetic risk factors underlying atherothrombotic and lacunar strokes. Our reasons for focusing on these 2 subtypes are that (1) extensive reviews exploring the genetic risk factors for total ischemic stroke already exist,2–4 (2) there is some evidence that genetic susceptibility factors may differ according to stroke subtype, and (3) atherothrombotic and lacunar stroke may have a greater genetic component than cardioembolic stroke.5–7 Several monogenic disorders can cause large-artery and small-vessel stroke. Overall, they are responsible for a very small proportion of these strokes, probably <1%,8 and should mainly be considered when stroke occurs at a young age in individuals with little or no exposure to conventional vascular risk factors. The mechanisms by which these monogenic disorders result in stroke are varied. ### Cerebral Autosomal Dominant Arteriopathy, Subcortical Infarcts, and Leukoencephalopathy Cerebral autosomal dominant …