炎性细胞因子与缺血性卒中风险：REGARDS 队列研究。
Inflammatory cytokines and ischemic stroke risk: The REGARDS cohort.
机构信息
From the Departments of Pathology and Laboratory Medicine (N.S.J., N.A.Z., M.C.) and Medicine (N.A.Z., M.C.), University of Vermont Larner College of Medicine, Burlington; Department of Biometry (P.W.C.), University of Vermont, Burlington; Department of Biostatistics (S.E.J.), University of Alabama at Birmingham; Department of Epidemiology and Biostatistics (L.A.M.), Dornsife School of Public Health, Drexel University, Philadelphia, PA; and Department of Neurology and Rehabilitation Medicine (B.K.), University of Cincinnati College of Medicine, OH.
出版信息
Neurology. 2019 May 14;92(20):e2375-e2384. doi: 10.1212/WNL.0000000000007416. Epub 2019 Apr 19.
OBJECTIVE
We studied circulating interleukin (IL)-6, IL-8, and IL-10 concentrations and incident ischemic stroke risk in a biracial cohort, and determined if these cytokines mediated the racial disparity in stroke incidence affecting the black population.
METHODS
The Reasons for Geographic and Racial Differences in Stroke study enrolled 30,237 black and white men and women age ≥45 in 2003-2007. We measured baseline IL-6, IL-8, and IL-10 in a case-cohort study of 557 participants with incident stroke over 5.4 years and 951 participants in a cohort sample.
RESULTS
IL-6, but not IL-8 or IL-10, was higher in cases compared to the cohort sample (mean 4.5 vs 3.7 ng/mL; < 0.001). Only IL-6 was associated with stroke risk factors. Adjusting for age, sex, and race, the hazard ratio (HR; 95% confidence interval) for incident stroke for the highest vs lowest quartile of IL-6 was 2.4 (1.6-3.4). HRs for the highest vs lowest quartiles of IL-8 and IL-10 were 1.5 (1.0-2.1) and 1.4 (1.0-1.9), respectively. After additional adjustment for stroke risk factors, only higher IL-6 remained associated with stroke risk (HR 2.0; 1.2-3.1). Associations did not differ by race. Mediation analyses showed that IL-6 mediated the black-white disparity in stroke risk, but mediation was via IL-6 associations with stroke risk factors.
CONCLUSIONS
In this biracial population-based sample, IL-6 was strongly associated with risk of incident stroke and mediated the racial disparity in stroke via inflammatory effects of risk factors. Further study on the clinical utility of IL-6 measurement in stroke risk assessment would be helpful.
目的
我们研究了循环白细胞介素（IL）-6、IL-8 和 IL-10 浓度与非裔和白人两种族裔队列人群中缺血性卒中发病风险的关系，并确定这些细胞因子是否介导了影响黑人群体的卒中发病风险的种族差异。
方法
地理和种族差异导致的卒中研究（Reasons for Geographic and Racial Differences in Stroke study）于 2003-2007 年纳入了 30237 名年龄≥45 岁的黑人和白人男性和女性。我们在一项 557 名参与者的病例-队列研究中测量了基线 IL-6、IL-8 和 IL-10，这些参与者在 5.4 年内发生了卒中，以及在一项队列样本中测量了 951 名参与者的 IL-6、IL-8 和 IL-10。
结果
与队列样本相比，病例组的 IL-6 更高（平均 4.5 vs 3.7ng/mL；<0.001），而 IL-8 或 IL-10 则没有差异。只有 IL-6 与卒中危险因素相关。在校正年龄、性别和种族后，IL-6 最高四分位数与最低四分位数相比，发生卒中的风险比（HR；95%置信区间）为 2.4（1.6-3.4）。IL-8 和 IL-10 的最高四分位数与最低四分位数的 HR 分别为 1.5（1.0-2.1）和 1.4（1.0-1.9）。在进一步校正卒中危险因素后，只有较高的 IL-6 仍与卒中风险相关（HR 2.0；1.2-3.1）。各因素的相关性在不同种族间无差异。中介分析表明，IL-6 通过危险因素的炎症作用，介导了黑人和白人之间的卒中风险差异。进一步研究 IL-6 测量在卒中风险评估中的临床应用价值将有所帮助。
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