From the Divisions of Cancer Epidemiology (L.P.-B., M.G., A.H., M.-L.G., T.J., S.G.M., R.K., T.K.) and Clinical Epidemiology and Aging Research (M.H.), German Cancer Research Center (DKFZ), Heidelberg; Medical Faculty (L.P.-B., M.G.), Heidelberg University; Department of Preventive Oncology (M.-L.G.), National Center for Tumor Diseases, Heidelberg; Department of Neurology (M.K.), Heidelberg University; Institute of Transfusion Medicine and Immunology (P.B.), Medical Faculty Mannheim, Heidelberg University; and German Red Cross Blood Service Baden-Württemberg-Hessen (P.B.), Mannheim, Germany.
Neurology. 2020 Jun 2;94(22):e2337-e2345. doi: 10.1212/WNL.0000000000009391. Epub 2020 May 5.
Because little is known about associations between biomarkers of vascular injury and stroke risk, we evaluated associations between plasma concentrations of 6 novel biomarkers of vascular injury and stroke risk in a population-based study.
A case-cohort subset of EPIC-Heidelberg (European Prospective Investigation for Cancer and Nutrition-Heidelberg) including incident stroke cases (n = 335) and a random subcohort (n = 2,418) was selected. Concentrations of intercellular adhesion molecule 3 (ICAM3), soluble E-selectin and P-selectin, soluble thrombomodulin (sTM), thrombopoietin, and glycoprotein IIb/IIIa were measured in baseline plasma samples. Weighted Cox regression analyses were used to assess associations between biomarker levels and stroke risk.
Median follow-up in the subcohort and among cases was 9.8 (range, 0.1-12.5) years and 6.2 (range, 0.01-12.1) years, respectively. ICAM3 levels were associated with increased risk of incident stroke after multivariable adjustment (hazard ratio, highest vs lowest quartile: 1.64 [95% confidence interval, 1.15-2.32]; < 0.001). This association was more apparent for ischemic (1.65 [1.12-2.45]; < 0.01) than for hemorrhagic stroke (1.29 [0.60-2.78]; = 0.3). We further observed a borderline significant trend for a positive association between sTM and overall stroke risk (1.47 [0.99-2.19]; = 0.05).
In this population-based study, circulating levels of ICAM3, an adhesion molecule shed by leukocytes, were associated with increased risk of incident stroke. Further mechanistic studies are needed to elucidate the pathophysiology underlying this association.
This study provides Class II evidence that plasma levels of ICAM3 are associated with increased stroke risk.
由于血管损伤生物标志物与卒中风险之间的关联知之甚少，我们在一项基于人群的研究中评估了 6 种新型血管损伤生物标志物的血浆浓度与卒中风险之间的关联。
从 EPIC-Heidelberg（欧洲癌症前瞻性调查和营养-海德堡）中选择了一个病例-队列亚组，包括首发卒中病例（n=335）和一个随机亚队列（n=2418）。在基线血浆样本中测量了细胞间黏附分子 3（ICAM3）、可溶性 E-选择素和 P-选择素、可溶性血栓调节蛋白（sTM）、血小板生成素和糖蛋白 IIb/IIIa 的浓度。使用加权 Cox 回归分析评估了生物标志物水平与卒中风险之间的关联。
在亚队列和病例中，中位随访时间分别为 9.8（范围：0.1-12.5）年和 6.2（范围：0.01-12.1）年。经多变量调整后，ICAM3 水平与新发卒中风险增加相关（风险比，最高四分位比最低四分位比：1.64[95%置信区间：1.15-2.32]；<0.001）。这种关联在缺血性卒中（1.65[1.12-2.45]；<0.01）中比在出血性卒中（1.29[0.60-2.78]；=0.3）中更为明显。我们还观察到 sTM 与总体卒中风险之间存在正相关的趋势（1.47[0.99-2.19]；=0.05）。
在这项基于人群的研究中，循环白细胞脱落的黏附分子 ICAM3 水平与新发卒中风险增加相关。需要进一步的机制研究来阐明这种关联的病理生理学基础。
这项研究提供了 II 级证据，表明 ICAM3 的血浆水平与卒中风险增加相关。
