Biomarkers predict hemorrhagic transformation and stroke severity after acute ischemic stroke

J Stroke Cerebrovasc Dis. 2023 Jan;32(1):106875. doi: 10.1016/j.jstrokecerebrovasdis.2022.106875. Epub 2022 Nov 14.

Abstract

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.

Keywords: Acute ischemic stroke; Claudin-5; Hemorrhagic transformation; Matrix metalloproteinase-9; Stroke severity.

MeSH terms

  • Aged
  • Biomarkers
  • Brain Ischemia*
  • Claudin-5
  • Humans
  • Ischemic Stroke* / complications
  • Matrix Metalloproteinase 9
  • Middle Aged
  • Stroke* / complications

Substances

  • Matrix Metalloproteinase 9
  • Claudin-5
  • Biomarkers