国家神经系统疾病临床医学研究中心数据管理与共享系统
Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
Monocyte chemoattractant protein-1, inflammatory biomarkers and prognosis of ischemic stroke or TIA patients: findings from a nationwide registry study
基本信息
- 负责人：Qin Xu,Yuanliang Liu
- 数据来源： CNSR-Ⅲ
- 论文编号：CNSR-Ⅲ20230187
- 发表时间：2024-08-09
2024-08-09
已发表文章
主要研究背景及目的
Ischemic stroke, caused by reduced blood flow to the brain, is the leading cause of death and the most common cause of disability worldwide. The pathogenesis of acute ischemic stroke is complex, and inflammation is one of the important, but as yet unknown, mechanisms. Some previous epidemiology studies showed that the markers for systemic inflammation, such as interleukin-6 (IL-6), high sensitive C-reactive protein (hsCRP), and local vascular inflammation produced in atherosclerotic lesions, such as lipoprotein-associated phospholipase A2 mass (Lp-PLA2) and activity (Lp-PLA2-A) and YKL-40 were associated with first or subsequent stroke or functional outcome. In recent years, monocyte chemotactic protein (MCP-1), the first purified and best characterized human CC chemokine, has emerged as an novel new biomarker for vascular disease. Studies suggested MCP-1/CCR2 axis might be a potential additional target for reducing residual inflammatory risk. Experimental evidence and Mendelian randomization analyses suggested that MCP-1 plays a role in stroke. In observational studies, plasma levels of MCP-1 are elevated in ischemic stroke patients and are considered to be an early predictor of ischemic stroke. However, data regarding MCP-1 and the prognosis of stroke from large-scale observational studies remain scarce. Moreover, current evidence does not yet explore whether the relationships between MCP-1 and stroke prognosis would be mediated via elevated systemic inflammation. Therefore, the aims of this study were to investigate the association of MCP-1 with the prognosis of patients with ischemic stroke or transient ischemic attack and to assess whether systemic inflammation mediates the relationship between MCP-1 and the clinical outcomes.
方法
A total of 10700 patients from the Third China National Stroke Registry study were included in the study. Multivariable Cox regression was used for recurrent stroke and all-cause death, and logistic regression was used for poor functional outcome (a modified Rankin Scale score of 3 to 6). Mediation analyses were performed to clarify whether inflammation mediates the associations.
结论
Low plasma MCP-1 level was associated with decreased risk of all-cause mortality and poor functional outcome in patients with ischemic stroke or TIA. Inflammation partially mediated and jointly contributed to the associations.
主要结果
The median (interquartile range) MCP-1 was 260.3 (202.4–337.6) pg/ml. A total of 1052 (9.8%) patients experienced stroke recurrence, 1395 (13.0%) patients had poor functional outcome, and 357 (3.3%) died during the 1-year follow-up. After adjusting for potential confounders, low MCP-1 level (< 337.6 pg/ml) was associated with a reduced risk of all-cause death (hazards ratio [HR], 0.65; 95% confidence interval [CI], 0.51–0.82) and poor functional outcome (odds ratio, 0.81; 95% CI, 0.70–0.94), but was not associated with recurrent stroke (HR, 1.10; 95% CI, 0.95–1.27), compared with high MCP-1 level (≥337.6 pg/ml). The association between MCP-1 and all-cause death was partially mediated by highly sensitive C-reactive protein, interleukin-6, and YKL-40 (mediated proportion: 7.4%, 10.5%, and 7.4%, respectively). The corresponding mediated proportion for poor functional outcome was 9.9 %, 17.1%, and 7.1%, respectively. Patients with combined high levels of MCP-1 and inflammatory biomarkers had the highest risks of death and poor functional outcome.