Biomarkers predict hemorrhagic transformation and stroke severity after acute ischemic stroke.

OBJECTIVES: Hemorrhagic transformation (HT) is a complication occurring in patients with acute ischemic stroke (AIS) either spontaneously or post-thrombolysis leading to significant morbidity and mortality. We assessed circulating matrix metalloproteinase-9 (MMP-9), Claudin-5, and soluble serum stimulation-2 (sST2) in HT and stroke severity in AIS based on their temporal distribution. MATERIALS AND METHODS: We prospectively enrolled 111 AIS patients within 12 h from onset. Patient demographic, clinical, and imaging details were documented. Follow-up imaging was conducted 24-48 h after admission. Blood samples were taken at three time-points from stroke onset. HT was classified according to the European Co-operative Acute Stroke Study-III(ECASS-III). Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Multiple logistic regression and receiver operating characteristic curve were conducted to determine the discriminative capacity. RESULTS: Mean age was 62.3 ± 11.7 years and median baseline NIHSS was 12[IQR 8.0-18.0]. HT was detected in 30(27%) patients. Biomarker levels at 12 h were elevated with median MMP-9 concentration of 153.9 ng/mL[IQR 110.6-309 ng/mL] indicating a trend toward significant positive correlation with HT(P = 0.05). Claudin-5 levels at 12 h was elevated but was not statistically significant (43.1 pg/mL[IQR:26.7-72.6 pg/mL] vs 59.4 pg/mL[IQR:24.5-100.8 pg/mL];P = 0.4). Multiple logistic regression indicated Claudin-5 levels at 12 h (OR 9.46;95% CI:1.97-64.6;P = 0.010) and baseline low ASPECTS score(OR 20.3;95% CI:3.46-193; P = 0.003) independently predicted HT. MMP-9 at 12 h was significantly elevated in patients with moderate to severe strokes (P = 0.04). CONCLUSIONS: Claudin-5 and low ASPECTS independently predicted HT. MMP-9 was positively correlated with baseline stroke severity.

Soluble ST2 Predicts Poor Functional Outcome in Acute Ischemic Stroke Patients.

INTRODUCTION: There are very limited data on the role of biomarkers correlating with the outcome in acute ischemic stroke (AIS). We evaluated the predictive values of the plasma concentrations of soluble serum stimulation-2 (sST2), matrix metalloproteinase-9 (MMP-9), and claudin-5 in AIS. METHODS: The biomarker levels in the plasma samples of consecutive AIS patients collected at baseline, 12 h, and 24 h from stroke onset were quantified using immunoassays. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and functional outcome at 90 days using the modified Rankin Scale (mRS), with scores above 3 defined as poor outcome. Receiver operating characteristic curve analysis and multiple logistic regression were performed for evaluating the discriminative power of each marker. RESULTS: We included 108 patients in the study (mean age 62.3 ± 11.7 years). Median NIHSS score was 12 (interquartile range 8-18). High baseline glucose levels, systolic blood pressure, baseline NIHSS, low Alberta Stroke Program Early CT Score, and hemorrhagic transformation were associated with poor outcomes. Elevated sST2 at 12 h (50.4 ± 51.0 ng/mL; p = 0.047) and 24 h (81.8 ± 101.3 ng/mL; p = 0.001) positively correlated with poor outcomes. MMP-9 (p = 0.086) and claudin-5 (p = 0.2) were not significantly associated with the outcome, although increased expressions of both markers were observed at 12 h. Multiple logistic regression showed that sST2 levels ≥71.8 ng/mL at 24 h, with a specificity of 96.9%, emerged as an independent predictor of poor functional outcome (OR: 6.44; 95% CI: 1.40-46.3; p = 0.029). CONCLUSION: Evaluation of sST2 may act as a reliable biomarker of functional outcome in AIS.

Increased high­density lipoprotein­oxidant index in ischemic stroke patients.

High-density lipoprotein (HDL) is known to have atheroprotective properties which could become dysfunctional under certain disease conditions, particularly during the atherosclerotic progression. The present study sought to assess HDL functionality in acute ischemic stroke (AIS) patients in comparison with controls and the functional alteration among the ischemic stroke subtypes. The HDL functionality was evaluated in 71 statin-naïve, adult patients of South Indian descent, admitted with AIS and were compared with that of 25 age- and sex-matched healthy volunteers. Functional assay of HDL was based on its antioxidant ability to inhibit low-density lipoproteins (LDL) oxidation by air using a dichlorodihydrofluorescein-based fluorescent assay and expressed as HDL oxidant index (HOI). The HOI was higher in ischemic stroke patients as compared with controls (1.07±0.32 vs. 0.51±0.12; P<0.001) indicating high oxidative stress and dysfunctionality in HDL. Regarding the stroke subtypes, HOI was >1 in all stroke subtypes: 1.05±0.301 for Cardioembolic subtype, 1.15±0.41 for large vessel disease, and 1.01±0.25 for small vessel disease when compared with controls. However, no significant difference was noted in HOI values among the three stroke subtypes in the post hoc analysis. It was found that HDL in all ischemic stroke subtypes had less antioxidant capacity, indicating dysfunctional HDL. Functional alteration occurred in HDL of patients even in the presence of normal HDL-cholesterol levels suggesting that dysfunctionality in HDL is unrelated to cholesterol content.