Department of Neurology, Vagelos College of Physicians and Surgeons (D.Y., M.L., M.S.V.E., J.G.), Columbia University, New York, NY.
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL (D.Y.).
Stroke. 2023 Dec;54(12):3030-3037. doi: 10.1161/STROKEAHA.123.044237. Epub 2023 Nov 1.
Inflammation contributes to atherosclerosis but is incompletely characterized in intracranial large artery stenosis (ICAS). We hypothesized that immune markers would be associated with ICAS and modify the risk ICAS confers on future vascular events.
This study included a subsample of stroke-free participants in the prospective NOMAS (Northern Manhattan Study), who had blood samples analyzed with a 60-plex immunoassay (collected from 1993 to 2001) and ICAS assessment with time-of-flight magnetic resonance angiography (obtained from 2003 to 2008). We dichotomized ICAS as either ≥50% stenosis or not (including no ICAS). We ascertained post-magnetic resonance imaging vascular events. We used least absolute shrinkage and selection operator procedures to select immune markers independently associated with ICAS. Then, we grouped selected immune markers into a derived composite score. Using proportional odds regression, we quantified the association of the composite immune marker score, ICAS, and risk of vascular events.
Among 1211 participants (mean age, 71±9 years; 59% women; 65% Hispanic participants), 8% had ≥50% ICAS. Using least absolute shrinkage and selection operator regression, we identified CXCL9 (C-X-C motif chemokine ligand 9), HGF (hepatocyte growth factor), resistin, SCF (stem cell factor), and VEGF-A(vascular endothelial growth factor A) to have the strongest positive relationships with ≥50% ICAS in fully adjusted models. Selected markers were used to derive a composite immune marker score. Over an average follow-up of 12 years, we found that each unit increase in immune marker scores was associated with an 8% (95% CI, 1.05-1.11), 11% (95% CI, 1.06-1.16), and 5% (95% CI, 1.01-1.09) increased hazard of death, vascular death, and any vascular event, respectively, in adjusted models. We did not find a significant interaction between immune marker scores and ICAS in their relationship with any longitudinal outcome.
Among a diverse stroke-free population, selected serum immune markers were associated with ICAS and future vascular events. Further study is needed to better understand their role in the pathogenesis of ICAS and as a potential therapeutic target in stroke prevention.
炎症是动脉粥样硬化的一个促成因素，但在颅内大动脉狭窄（ICAS）中并未得到充分描述。我们假设免疫标志物与 ICAS 相关，并改变 ICAS 对未来血管事件的风险。
本研究纳入了前瞻性 NOMAS（北曼哈顿研究）中无卒中的参与者的亚组，他们的血液样本采用 60 plex 免疫分析进行分析（1993 年至 2001 年采集），并采用时飞磁共振血管造影术（2003 年至 2008 年采集）评估 ICAS。我们将 ICAS 分为≥50%狭窄或非狭窄（包括无 ICAS）。我们确定了磁共振成像后血管事件。我们使用最小绝对收缩和选择算子程序独立选择与 ICAS 相关的免疫标志物。然后，我们将选定的免疫标志物分为衍生的综合评分。使用比例优势比回归，我们量化了综合免疫标志物评分、ICAS 和血管事件风险之间的关联。
在 1211 名参与者（平均年龄 71±9 岁；59%为女性；65%为西班牙裔参与者）中，8%的人存在≥50%的 ICAS。使用最小绝对收缩和选择算子回归，我们在完全调整的模型中发现，CXCL9（C-X-C 基序趋化因子配体 9）、HGF（肝细胞生长因子）、抵抗素、SCF（干细胞因子）和 VEGF-A（血管内皮生长因子 A）与≥50%的 ICAS 具有最强的正相关关系。选定的标志物用于推导综合免疫标志物评分。在平均 12 年的随访期间，我们发现免疫标志物评分每增加一个单位，与调整后的模型中死亡、血管死亡和任何血管事件的风险分别增加 8%（95%CI，1.05-1.11）、11%（95%CI，1.06-1.16）和 5%（95%CI，1.01-1.09）相关。我们没有发现免疫标志物评分与 ICAS 之间存在显著的相互作用，它们与任何纵向结局的关系。
在一个多样化的无卒中人群中，选定的血清免疫标志物与 ICAS 和未来的血管事件相关。需要进一步研究以更好地了解它们在 ICAS 发病机制中的作用以及作为预防卒中的潜在治疗靶点。
