Jagiellonian University Department of Cardiac and Vascular Diseases, Krakow, Poland. ; John Paul II Hospital, Krakow, Poland.
J Clin Neurol. 2013 Jul;9(3):165-75. doi: 10.3988/jcn.2013.9.3.165. Epub 2013 Jul 1.
Several circulating biomarkers have been implicated in carotid atherosclerotic plaque rupture and thrombosis; however, their clinical utility remains unknown. The aim of this study was to determine the role of a large biomarker panel in the discrimination of symptomatic (S) vs. asymptomatic (A/S) subjects in a contemporary population with carotid artery stenosis (CS).
Prospective sampling of circulating cytokines and blood lipids was performed in 300 unselected, consecutive patients with ≥50% CS, as assessed by duplex ultrasound (age 47-83 years; 110 with A/S and 190 with S) who were referred for potential CS revascularization.
CS severity and pharmacotherapy did not differ between the A/S and S patients. The median values of total cholesterol, low-density lipoprotein cholesterol, and lipoprotein(a) did not differ, but high-density lipoprotein (HDL) cholesterol was significantly higher (p<0.001) and triglycerides were lower (p=0.03) in the A/S-CS group than in the S-CS group. Interleukin-6 (IL-6) and high-sensitivity C-reactive protein were higher (p=0.04 and p=0.07, respectively) in the S-CS group. Circulating visfatin, soluble CD 40 receptor ligand, soluble vascular cell adhesion molecule, leptin, adiponectin, IL-1β, IL-8, IL-18, monocyte chemoattractant protein-1, myeloperoxidase, matrix metalloproteinases-8, -9, and -10, and fibrinogen were similar, but tissue inhibitor of matrix metalloproteinases-1 (TIMP) was reduced in S-CS compared to A/S-CS (p=0.02). Nevertheless, incorporation of TIMP and IL-6 did not improve the HDL-cholesterol receiver operating characteristics for S-CS status prediction. S-CS status was unrelated to angiographic stenosis severity or plaque burden, as assessed by intravascular ultrasound (p=0.16 and p=0.67, respectively). Multivariate logistic regression analysis revealed low HDL-cholesterol to be the only independent predictor of CS symptoms, with an odds ratio of 1.81 (95% confidence interval=1.15-2.84, p=0.01) for HDL <1.00 mmol/L (first quartile) vs. >1.37 (third quartile). In S-CS, osteoprotegerin and lipoprotein-associated phospholipase A2 (Lp-PLA2) were elevated in those with recent vs. remote symptoms (p=0.01 and p=0.02, respectively).
In an all-comer CS population on contemporary pharmacotherapy, low HDL-cholesterol (but not other previously implicated or several novel circulating biomarkers) is an independent predictor of S-CS status. In addition, an increase in circulating osteoprotegerin and Lp-PLA2 may transiently indicate S transformation of the carotid atherosclerotic plaque.
已有几种循环生物标志物被认为与颈动脉粥样硬化斑块破裂和血栓形成有关；然而，其临床应用价值尚不清楚。本研究的目的是确定一个大型生物标志物组在区分当代颈动脉狭窄（CS）患者中有症状（S）与无症状（A/S）方面的作用。
前瞻性采集 300 例未经选择的、连续的、有症状（年龄 47-83 岁，110 例 A/S，190 例 S）的患者的循环细胞因子和血脂，这些患者的 CS 程度为 50%以上，通过双功能超声（CS 严重程度和药物治疗在 A/S 和 S 患者之间无差异。总胆固醇、低密度脂蛋白胆固醇和脂蛋白（a）的中位数无差异，但高密度脂蛋白（HDL）胆固醇显著升高（p<0.001），甘油三酯水平较低（p=0.03），A/S-CS 组高于 S-CS 组。S-CS 组的白细胞介素-6（IL-6）和高敏 C 反应蛋白较高（p=0.04 和 p=0.07）。循环内脂素、可溶性 CD40 配体、可溶性血管细胞黏附分子、瘦素、脂联素、白细胞介素-1β、白细胞介素-8、白细胞介素-18、单核细胞趋化蛋白-1、髓过氧化物酶、基质金属蛋白酶-8、-9 和 -10 相似，但基质金属蛋白酶组织抑制剂-1（TIMP）在 S-CS 中低于 A/S-CS（p=0.02）。然而，TIMP 和 IL-6 的纳入并不能改善 HDL-胆固醇对 S-CS 状态预测的接收者操作特征。S-CS 状态与血管内超声评估的血管造影狭窄严重程度或斑块负荷无关（p=0.16 和 p=0.67）。多变量逻辑回归分析显示，低 HDL-胆固醇是 CS 症状的唯一独立预测因素，HDL<1.00mmol/L（第一四分位数）的优势比为 1.81（95%置信区间=1.15-2.84，p=0.01），而>1.37（第三四分位数）。在 S-CS 中，骨保护素和脂蛋白相关磷脂酶 A2（Lp-PLA2）在近期症状与远期症状患者中升高（p=0.01 和 p=0.02）。
在接受当代药物治疗的所有 CS 患者中，低 HDL-胆固醇（而非其他先前涉及或几种新型循环生物标志物）是 S-CS 状态的独立预测因素。此外，循环骨保护素和 Lp-PLA2 的增加可能暂时表明颈动脉粥样硬化斑块的 S 转化。
