High C-Reactive Protein, MMP-9 Increase Poststroke Death and Disability

Researchers observed an obvious gradient association between numbers of elevated novel biomarkers and risk for major disability, mortality, and vascular events in patients with ischemic stroke.

Increased levels of elevated high-sensitive C-reactive protein (CRP), complement C3, matrix metalloproteinase-9 (MMP-9), hepatocyte growth factor, and antiphosphatidylserine antibodies (aPS) increase the risk for death and major disability 3 months after ischemic stroke, according to study results published in Neurology.

Data from people who had ischemic stroke and were enrolled in the multicenter, randomized China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) trial were included (N=3405). Patients had biomarker data available for analysis, including information on blood pressure, high-sensitive CRP, complement C3, MMP-9, and hepatocyte growth factor measures. These data were used to assess the associations of circulating biomarkers with the combination of death and major disability (modified Rankin Scale score ≥3) at 3 months. Additional outcomes were major disability, death, and vascular events.

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The primary outcome of 3-month major disability or death was recorded in 25.4% of patients with ischemic stroke. Biomarkers associated with a higher risk for the primary outcome included increased elevated high-sensitive CRP ≥2.5 mg/L (odds ratio [OR] 1.57; 95% CI, 1.32-1.88), complement C3 ≥1.4 g/L (OR 1.25; 95% CI, 1.04-1.50), MMP-9 ≥812.2 ng/mL (OR 1.31; 95% CI, 1.08-1.58), hepatocyte growth factor ≥1648.4 pg/mL (OR 1.41; 95% CI, 1.17-1.70), and aPS ≥11 immunoglobulin G aPS units (OR 1.35; 95% CI, 1.06-1.72). Compared with patients with no elevated biomarkers, patients with all 5 elevated biomarkers had an increased risk for combined death and disability (OR 3.88; 95% CI, 2.05-7.36), major disability (OR 2.81; 95% CI, 1.49-5.33), death (OR 5.67; 95% CI, 1.09-29.52), and vascular events (OR 4.00; 95% CI, 1.22-13.14).

A limitation of the study was the lack of additional biomarkers that may have potentially greater prognostic implication for patients with ischemic stroke.

The researchers suggested that the inclusion of high-sensitive CRP, complement C3, MMP-9, hepatocyte growth factor, and aPS in “a model with established risk factors substantially improved the risk stratification for major disability, death, and vascular events in patients with ischemic stroke.”


Zhong C, Zhu Z, Wang A, et al. Multiple biomarkers covering distinct pathways for predicting outcomes after ischemic stroke. Neurology. 2019;92:e295-e304.