Multiple inflammatory biomarkers in predicting short-term and long-term mortality after stroke [Abstract]

Background: Inflammation plays an important role in atherosclerosis and its clinical sequelae, including stroke. Accumulating evidence suggests that inflammatory biomarkers predict adverse events aftercoronary event. The role of elevated concentrations of these biomarkers in predicting adverse events after stroke is less clear. Study Objectives: This study aimed to investigate the relationships of multiple inflammatory biomarkers of various pathophysiologic pathways including high-sensitivity C-reactive protein (hs-CRP), lipocalin-2 (LCN2), myeloperoxidase (MPO), matrix metalloproteinases 9 (MMP9) and their combinations with short-term and long-term mortality in stroke patients. Methods: Ninety-two stroke patients were recruited. The concentrations of hs-CRP, LCN2 and MPO in plasma were determined using sandwich enzyme-linked immunosorbent assays. The MMP9 mRNA concentrations in blood cells were determined using real-time quantitative reverse transcription-polymerase chain reaction. Results: Of the 92 patients recruited with a mean age of 70.7±11.6 years, there were 47 males (51.1%). Hemorrhagic stroke was diagnosed in 25 (27.2%) patients and ischemic stroke in 67 (72.8%) patients. There were 12 (13.0%) deaths at 6 months and 34(37.0%) deaths at 5 years. After adjusting for neutrophil count, white blood cell count, Glasgow Coma Scale (GCS), National Institutes of Health Stroke Scale (NIHSS), and time from stroke onset to blood taking, the independent predictors for 6-month mortality were hs-CRP [odd ratio (OR)=16.0; 95% CI 1.23 to 210; P=0.0343] and LCN2 (OR=16.9; 95% CI 1.81 to 158; P=0.0132). After adjusting for age, neutrophil count, white blood cell count, GCS and NIHSS, the independent predictor for 5-year mortality was hs-CRP (OR=5.56; 95% CI 1.79 to 17.3; P=0.0030). In Cox regression analysis, both unadjusted and adjusted HRs of 6-month (continuous pulse rate=6.79, P=0.0134; adjusted continuous pulse rate=11.4, P=0.0139) and 5-year mortality (continuous pulse rate=3.54, P=0.0006; adjusted continuous pulse rate=3.11, P=0.0086) increased significantly with hs-CRP >3.4 mg/L. For patients with an hs-CRP >3.4 mg/L, an increase in LCN2 was associated with more than 2.5-fold higher 6-month mortality, while an increase in normalized MMP9 mRNA was associated with 5.8-fold higher 6-month and 1.5-fold higher 5-year mortality respectively. Conclusion: hs-CRP was the most significant independent predictor of both short-term and long-term mortality in stroke patients,with LCN2 and MMP9 mRNA each adding further to the risk stratification