Abstract TP223: Role of Plasma Biomarkers in Diagnosis of Ischemic Stroke Subtypes

Abstract

Objectives: Identifying underlying stroke etiology plays critical role in acute management and secondary prevention strategies. Despite advanced diagnostics, up to 35% of ischemic strokes (IS) remain undetermined. We sought to evaluate the association between IS subtypes and plasma levels of biomarkers as representative of distinct etiologies underlying stroke subtypes. Methods: We prospectively measured plasma high sensitivity-C reactive protein (hs-CRP), matrix metalloproteinase (MMP)-2 and MMP-9, F2-isoprostane (F2-isoP), Oxygen Radical Absorbance Capacity assay (ORAC), homocysteine and urinary 8-hydroxydeoxyguanosine (8OHdG), in patients presenting within 9 hours from acute ischemic stroke (AIS) onset. Stroke subtype was assigned by a stroke neurologist according to the Causative Classification of Stroke System (CCSS) criteria. Results: There were 489 AIS subjects enrolled in this study [mean (SD) age 70.1 (15.1) y; 43.4% female; median (IQR) NIHSS 6 (3-13); 40.7% received IV tPA]. Among these AIS, 51% were of cardioembolic (CE), 17% of atherothrombotic, 7% of lacunar, 5% of other, and 20% of undetermined subtype. Patients with CE stroke were older and more likely to be female, non-smokers, have atrial fibrillation and congestive heart failure, but not carotid stenosis (all p<0.05). CE stroke subtype was also associated with greater stroke severity, and baseline levels of MMP-2 (p= 0.001) and ORAC (p= 0.008), as compared to other CCSS subtypes. In multivariate logistic regression analysis including all univariate predictors with p<0.05 as well as treatment with IV t-PA, baseline MMP-2 (OR 2.8, 95% CI 1.3-5.8; p= 0.006) and ORAC (OR 2.6, 95% CI 1.3-5.1; p= 0.007) was independently associated with CE stroke subtype. Conversely, the “other” stroke subtype was associated with lower levels of MMP-2 (OR 0.1, 95% CI 0.02-0.3; p= 0.001), and homocysteine levels were independently correlated with undetermined subtype (OR 2.2, 95% CI 1.2-4.1; p= 0.008). Conclusions: In AIS patients, hyperacute plasma biomarkers are associated with specific stroke subtypes, reflective of the underlying pathophysiology. If validated in future studies, plasma biomarkers may play valuable role in early diagnosis and guide management of specific AIS subtypes.