Abstract TP214: Hyperacute Plasma F2-Isoprostanes Predict Infarct Growth in Acute Ischemic Stroke
Objectives: Oxidative stress occurs as part of the earliest response to ischemia and is likely to play an important role in the pathogenesis of ischemic cerebral injury. We sought to evaluate whether hyperacute plasma concentrations of F2-isoprostane (F2-isoP), a biomarker of lipid peroxidation, predict infarct growth (IG), as a mediator of brain damage.
Methods: We prospectively measured plasma F2-isoP, high sensitivity-C reactive protein, matrix metalloproteinase-2 and -9, Oxygen Radical Absorbance Capacity assay, and urinary 8-hydroxydeoxyguanosine in acute ischemic stroke (AIS) patients presenting within 9 h of symptom onset. Patients with a baseline DWI MRI and a 48-h DWI or CT scan were included to evaluate the final infarct volume (FIV). Baseline DWIV and FIV were analyzed using semi-automated volumetric method. IG was defined as the difference between FIV and baseline DWIV.
Results: Of 489 AIS subjects, 220 [mean (SD) age 70.1 (15.1) y; 43.4% female; 40.5% treated with IV tPA] had both baseline DWI and follow-up imaging. Of these, 170 had IG of any size, and they were more likely to be male (p=0.032), to have prior transient ischemic attack (p=0.035) or diabetes mellitus (p=0.026), higher NIHSS score (p=0.001) and blood glucose levels (p=0.003) at admission, and higher median (IQR) baseline levels of F2-isoP [56.2 (36.4-75.3) vs. 42.0 (27.0-61.8) pg/mL, p=0.009]. Baseline F2-isoP and FIV (Spearman’s rho=0.19, p=0.009) as well as absolute IG volume (IGV) (Spearman’s rho=0.20, p=0.005) were significantly correlated. In a multivariable logistic regression model including all variables associated with IG at univariate p-value <0.05, as well as age and IV tPA, baseline F2-isoP emerged as an independent predictor of IG (OR 2.57, 95% CI 1.37-4.83; p=0.003). In linear regression model, baseline F2-isoP was independently associated with IGV (p=0.004). Inclusion of other biomarkers did not change the significance of F2-isoP in predicting IG (Bonferroni p <0.005).
Conclusions: Elevated hyperacute plasma F2-isoP concentrations independently predict IG and IGV in AIS patients. If validated in future studies, measuring plasma F2-isoP might be helpful in the acute setting to stratify AIS patients for progression and relative severity of ischemic injury.
- © 2012 by American Heart Association, Inc.