Shoamanesh Ashkan, Preis Sarah R, Beiser Alexa S, Vasan Ramachandran S, Benjamin Emelia J, Kase Carlos S, Wolf Philip A, DeCarli Charles, Romero Jose R, Seshadri Sudha
From McMaster University (A.S.), Hamilton, Canada; Harvard Medical School (A.S.), Boston; Boston University School of Public Health (S.R.P., A.S.B.); Boston University School of Medicine (A.S.B., R.S.V., E.J.B., C.S.K., P.A.W., J.R.R., S.S.), MA; and University of California (C.D.), Davis School of Medicine, Sacramento.
Neurology. 2015 Feb 24;84(8):825-32. doi: 10.1212/WNL.0000000000001279. Epub 2015 Jan 28.
We investigated the association between circulating biomarkers of inflammation and MRI markers of small vessel disease.
We performed a cross-sectional study relating a panel of 15 biomarkers, representing systemic inflammation (high-sensitivity C-reactive protein, interleukin-6, monocyte chemotactic protein-1, tumor necrosis factor α, tumor necrosis factor receptor 2, osteoprotegerin, and fibrinogen), vascular inflammation (intercellular adhesion molecule 1, CD40 ligand, P-selectin, lipoprotein-associated phospholipase A2 mass and activity, total homocysteine, and vascular endothelial growth factor), and oxidative stress (myeloperoxidase) to ischemic (white matter hyperintensities/silent cerebral infarcts) and hemorrhagic (cerebral microbleeds) markers of cerebral small vessel disease (CSVD) on MRI in 1,763 stroke-free Framingham offspring (mean age 60.2 ± 9.1 years, 53.7% women).
We observed higher levels of circulating tumor necrosis factor receptor 2 and myeloperoxidase in the presence of cerebral microbleed (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.1-4.1 and OR 1.5, 95% CI 1.1-2.0, respectively), higher levels of osteoprotegerin (OR 1.1, 95% CI 1.0-1.2), intercellular adhesion molecule 1 (OR 1.7, 95% CI 1.1-2.5), and lipoprotein-associated phospholipase A2 mass (OR 1.5, 95% CI 1.1-2.1), and lower myeloperoxidase (OR 0.8, 95% CI 0.7-1.0) in participants with greater white matter hyperintensity volumes and silent cerebral infarcts.
Our study supports a possible role for inflammation in the pathogenesis of CSVD, but suggests that differing inflammatory pathways may underlie ischemic and hemorrhagic subtypes. If validated in other samples, these biomarkers may improve stroke risk prognostication and point to novel therapeutic targets to combat CSVD.
我们研究了炎症循环生物标志物与小血管疾病MRI标志物之间的关联。
我们进行了一项横断面研究，将代表全身炎症（高敏C反应蛋白、白细胞介素-6、单核细胞趋化蛋白-1、肿瘤坏死因子α、肿瘤坏死因子受体2、骨保护素和纤维蛋白原）、血管炎症（细胞间黏附分子1、CD40配体、P选择素、脂蛋白相关磷脂酶A2质量和活性、总同型半胱氨酸和血管内皮生长因子）以及氧化应激（髓过氧化物酶）的15种生物标志物与1763名无卒中的弗雷明汉后代（平均年龄60.2±9.1岁，53.7%为女性）MRI上脑小血管疾病（CSVD）的缺血性（白质高信号/无症状脑梗死）和出血性（脑微出血）标志物相关联。
我们观察到，在存在脑微出血的情况下，循环肿瘤坏死因子受体2和髓过氧化物酶水平较高（优势比[OR]分别为2.2，95%置信区间[CI]为1.1 - 4.1和OR 1.5，95% CI为1.1 - 2.0）；在白质高信号体积较大和有无症状脑梗死的参与者中，骨保护素（OR 1.1，95% CI为1.0 - 1.2）、细胞间黏附分子1（OR 1.7，95% CI为1.1 - 2.5）和脂蛋白相关磷脂酶A2质量（OR 1.5，95% CI为1.1 - 2.1）水平较高，而髓过氧化物酶水平较低（OR 0.8，95% CI为0.7 - 1.0）。
我们的研究支持炎症在CSVD发病机制中可能起作用，但表明不同的炎症途径可能是缺血性和出血性亚型的基础。如果在其他样本中得到验证，这些生物标志物可能会改善卒中风险预测，并指向对抗CSVD的新治疗靶点。
