Department of Neurology, Clínica Universidad de Navarra, Av. Pío XII 36, 31008, Pamplona, Navarra, Spain.
Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain.
BMC Cardiovasc Disord. 2020 Feb 26;20(1):93. doi: 10.1186/s12872-020-01387-3.
Major adverse cardiovascular events are the main cause of morbidity and mortality over the long term in patients undergoing carotid endarterectomy. There are few reports assessing the prognostic value of markers of inflammation in relation to the risk of cardiovascular disease after carotid endarterectomy. Here, we aimed to determine whether matrix metalloproteinases (MMP-1, MMP-2, MMP-7, MMP-9 and MMP-10), tissue inhibitor of MMPs (TIMP-1) and in vivo inflammation studied by F-FDG-PET/CT predict recurrent cardiovascular events in patients with carotid stenosis who underwent endarterectomy.
This prospective cohort study was carried out on 31 consecutive patients with symptomatic (23/31) or asymptomatic (8/31) severe (> 70%) carotid stenosis who were scheduled for carotid endarterectomy between July 2013 and March 2016. In addition, 26 healthy controls were included in the study. Plasma and serum samples were collected 2 days prior to surgery and tested for MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, high-density lipoprotein, low-density lipoprotein, high-sensitivity C-reactive protein and erythrocyte sedimentation rate. F-FDG-PET/CT focusing on several territories' vascular wall metabolism was performed on 29 of the patients because of no presurgical availability in 2 symptomatic patients. Histological and immunohistochemical studies were performed with antibodies targeting MMP-10, MMP-9, TIMP-1 and CD68.
The patients with carotid stenosis had significantly more circulating MMP-1, MMP-7 and MMP-10 than the healthy controls. Intraplaque TIMP-1 was correlated with its plasma level (r = 0.42 P = .02) and with F-FDG uptake (r = 0.38 P = .05). We did not find any correlation between circulating MMPs and in vivo carotid plaque metabolism assessed by F-FDG-PET. After a median follow-up of 1077 days, 4 cerebrovascular, 7 cardiovascular and 11 peripheral vascular events requiring hospitalization were registered. Circulating MMP-7 was capable of predicting events over and above the traditional risk factors (HR = 1.15 P = .006). When the model was associated with the variables of interest, the risk predicted by F-FDG-PET was not significant.
Circulating MMP-7 may represent a novel marker for recurrent cardiovascular events in patients with moderate to severe carotid stenosis. MMP-7 may reflect the atherosclerotic burden but not plaque inflammation in this specific vascular territory.
在接受颈动脉内膜切除术的患者中，主要不良心血管事件是长期内发病率和死亡率的主要原因。关于炎症标志物与颈动脉内膜切除术后心血管疾病风险之间的关系，评估其预后价值的报道很少。在这里，我们旨在确定基质金属蛋白酶（MMP-1、MMP-2、MMP-7、MMP-9 和 MMP-10）、基质金属蛋白酶抑制剂（TIMP-1）和通过 F-FDG-PET/CT 研究的体内炎症是否可预测颈动脉狭窄患者接受内膜切除术后复发性心血管事件。
这项前瞻性队列研究纳入了 2013 年 7 月至 2016 年 3 月期间接受颈动脉内膜切除术的 31 例有症状（23/31）或无症状（8/31）严重（>70%）颈动脉狭窄的连续患者。此外，还纳入了 26 名健康对照者。在手术前 2 天采集血浆和血清样本，并检测 MMP-1、MMP-2、MMP-7、MMP-9、MMP-10、TIMP-1、高密度脂蛋白、低密度脂蛋白、高敏 C 反应蛋白和红细胞沉降率。由于 2 例有症状患者术前不可用，29 例患者进行了 F-FDG-PET/CT 检查，重点评估多个区域的血管壁代谢。进行了 MMP-10、MMP-9、TIMP-1 和 CD68 抗体的组织学和免疫组织化学研究。
颈动脉狭窄患者的循环 MMP-1、MMP-7 和 MMP-10 明显高于健康对照组。斑块内 TIMP-1 与其血浆水平相关（r=0.42，P=0.02）和 F-FDG 摄取相关（r=0.38，P=0.05）。我们没有发现循环 MMPs 与 F-FDG-PET 评估的体内颈动脉斑块代谢之间存在任何相关性。中位随访 1077 天后，记录了 4 例脑血管事件、7 例心血管事件和 11 例需要住院的外周血管事件。循环 MMP-7 可预测事件，且超过传统危险因素（HR=1.15，P=0.006）。当将模型与相关变量相关联时，FDG-PET 预测的风险并不显著。
循环 MMP-7 可能是中重度颈动脉狭窄患者复发性心血管事件的新标志物。MMP-7 可能反映了特定血管区域的动脉粥样硬化负担，但不是斑块炎症。
