Plasma -Amyloid 1-40 Is Associated With the Diffuse Small Vessel Disease Subtype

Background and Purpose—The underlying mechanisms of small vessel disease (SVD) subtypes are diffuse arteriopathy (diffuse-SVD) or microatheroma (focal-SVD). Endothelial dysfunction by -amyloid peptide (A ) deposition has been associated with lacunar infarcts and leukoaraiosis, but its specific relationship with SVD subtypes is unknown. We hypothesized that plasma A levels can play a different role in SVD subtypes in patients with acute lacunar stroke. Methods—We studied 149 patients with acute ischemic stroke of SVD etiology according to Trial Of Org 10172 In Acute Stroke Treatment criteria and 25 age-matched control subjects. Patients were classified into focal-SVD: 39 patients with isolated lacunar infarct without leukoaraiosis and diffuse-SVD: 110 patients with an isolated lacunar infarct with leukoaraiosis or with multiple lacunar infarcts with or without leukoaraiosis. Baseline data included vascular risk factors and extensive laboratory tests, including plasma A levels. Results—Median [quartiles] A 1-40 levels (40.4 [35.1, 50.5] versus 55.1 [42.3, 69.6] pg/mL), but not A 1-42 levels, were significantly higher in the diffuse-SVD group than in focal-SVD group (P 0.001) and control subjects (P 0.001). No differences in A 1-40 levels were found between focal-SVD and control subjects. Logistic regression analysis showed that age (OR, 1.06; 95% CI, 1.01 to 1.12), history of hypertension (OR, 3.5; 95% CI, 1.3 to 9.2), and plasma -amyloid1-40 levels over the median value (OR, 17.3; 95% CI, 3.0 to 99 for the third quartile and OR, 6.0; 95% CI, 1.6 to 23 for the fourth quartile) were independently associated with the diffuse-SVD subtype. Conclusions—Plasma -amyloid1-40 levels are independently associated with the diffuse-SVD subtype. These results are consistent with the pathophysiological role of fraction A 1-40 in disrupting endothelial vascular function. (Stroke. 2009; 40:3197-3201.)