炎症生物标志物与脑小血管病：一项基于社区的队列研究。
Inflammatory biomarkers and cerebral small vessel disease: a community-based cohort study.
机构信息
Central Research Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
出版信息
Stroke Vasc Neurol. 2022 Aug;7(4):302-309. doi: 10.1136/svn-2021-001102. Epub 2022 Mar 8.
BACKGROUND AND PURPOSE
Although inflammation has been proposed to be a candidate risk factor for cerebral small vessel disease (CSVD), previous findings remain largely inconclusive and vary according to disease status and study designs. The present study aimed to investigate possible associations between inflammatory biomarkers and MRI markers of CSVD.
METHODS
A group of 15 serum inflammatory biomarkers representing a variety of those putatively involved in the inflammatory cascade was grouped and assessed in a cross-sectional study involving 960 stroke-free subjects. The biomarker panel was grouped as follows: systemic inflammation (high-sensitivity C reactive protein (hsCRP), interleukin 6 and tumour necrosis factor α), endothelial-related inflammation (E-selectin, P-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1 (VCAM-1), CD40 ligand, lipoprotein-associated phospholipase A2, chitinase-3-like-1 protein and total homocysteine (tHCY)) and media-related inflammation (matrix metalloproteinases 2, 3 and 9, and osteopontin). The association(s) between different inflammatory groups and white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs), enlarged perivascular space (PVS) and the number of deep medullary veins (DMVs) were investigated.
RESULTS
High levels of serum endothelial-related inflammatory biomarkers were associated with both increased WMH volume (R=0.435, p=0.015) and the presence of lacunes (R=0.254, p=0.027). Backward stepwise elimination of individual inflammatory biomarkers for endothelial-related biomarkers revealed that VCAM-1 was significant for WMH (β=0.063, p=0.005) and tHCY was significant for lacunes (β=0.069, p<0.001). There was no association between any group of inflammatory biomarkers and CMBs or PVS. Systemic inflammatory biomarkers were associated with fewer DMVs (R=0.032, p=0.006), and backward stepwise elimination of individual systemic-related inflammatory biomarkers revealed that hsCRP (β=-0.162, p=0.007) was significant.
CONCLUSION
WMH and lacunes were associated with endothelial-related inflammatory biomarkers, and fewer DMVs were associated with systemic inflammation, thus suggesting different underlying inflammatory processes and mechanisms.
背景与目的
尽管炎症已被提出是脑小血管病（CSVD）的候选风险因素，但先前的研究结果仍存在很大的不确定性，并且因疾病状态和研究设计而异。本研究旨在调查炎症生物标志物与 CSVD 的 MRI 标志物之间可能存在的关联。
方法
在一项涉及 960 例无中风的受试者的横断面研究中，将代表炎症级联中多种假定涉及的炎症生物标志物的一组 15 种血清炎症生物标志物进行分组和评估。生物标志物组分为以下几类：全身性炎症（高敏 C 反应蛋白（hsCRP）、白细胞介素 6 和肿瘤坏死因子 α）、内皮相关炎症（E-选择素、P-选择素、细胞间黏附分子 1、血管细胞黏附分子 1（VCAM-1）、CD40 配体、脂蛋白相关磷脂酶 A2、壳聚糖-3 样蛋白 1 和总同型半胱氨酸（tHCY））和中膜相关炎症（基质金属蛋白酶 2、3 和 9 以及骨桥蛋白）。研究了不同炎症组与脑白质高信号（WMH）、腔隙、脑微出血（CMBs）、扩大的血管周围空间（PVS）和深髓静脉（DMVs）数量之间的关联。
结果
高水平的血清内皮相关炎症生物标志物与 WMH 体积增加（R=0.435，p=0.015）和腔隙存在相关（R=0.254，p=0.027）。内皮相关生物标志物的逐步向后消除单个炎症生物标志物的分析表明，VCAM-1 对 WMH 有显著影响（β=0.063，p=0.005），tHCY 对腔隙有显著影响（β=0.069，p<0.001）。炎症生物标志物的任何一组与 CMB 或 PVS 均无关联。全身性炎症生物标志物与较少的 DMVs 相关（R=0.032，p=0.006），逐步向后消除单个系统性炎症相关生物标志物表明，hsCRP（β=-0.162，p=0.007）具有显著意义。
结论
WMH 和腔隙与内皮相关炎症生物标志物相关，而 DMVs 较少与全身炎症相关，因此表明存在不同的潜在炎症过程和机制。
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