Association Between Serum C1q Tumor Necrosis Factor-Related Protein 9 and the Clinical Characteristics and Prognosis of Ischemic Stroke

Introduction: C1q tumor necrosis factor (TNF)-related protein 9 (CTRP9) is a novel member of the C1q/TNF superfamily. According to our previous review, CTRP9 plays a vital role in the process of cardiovascular diseases, including regulating energy metabolism, modulating vasomotion, protecting endothelial cells, inhibiting platelet activation, inhibiting pathological vascular remodeling, stabilizing atherosclerotic plaques, and protecting the heart. We proposed that CTRP9 could play multiple positive and beneficial roles in vascular lesions in ischemic stroke (IS). Here, we aimed to study the relationship between serum CTRP9 and the etiology, severity, and prognosis of IS patients. Methods: A total of 302 patients with IS and 173 non-stroke controls were selected from the same hospital, and all patients with IS were followed up 12 months after stroke onset. Stroke etiology was classified according to the Trial of ORG 10172 in Acute Stroke Treatment classification. Symptomatic severity was determined using the National Institutes of Health Stroke Scale score. The lesion volume of acute cerebral ischemia was measured using magnetic resonance imaging (MRI). The unfavorable functional outcome was a combination of death or major disability 12 months after stroke onset. Receiver operating characteristic (ROC) curves and integrated discrimination improvement (IDI) and net reclassification improvement (NRI) statistics were applied in the statistical analysis. Results: We found that serum CTRP9 levels and the ratios of CTRP9/total cholesterol (TC), CTRP9/triglyceride (TG), CTRP9/low-density lipoprotein cholesterol (LDL-C), and CTRP9/high-density lipoprotein cholesterol (HDL-C) were associated with the presence of IS. Moreover, the serum CTRP9 concentration was positively associated with the severity of IS. Incorporation of CTRP9/LDL-C levels into a fully adjusted model for IS-cardioembolic (CE) improved discrimination and calibration, and significantly improved reclassification. In addition, CTRP9 was a predictor of unfavorable functional outcomes. Conclusions: All the findings indicated that serum CTRP9 could be a promising blood-derived biomarker for the early evaluation and prognosis assessment of IS. Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800020330.