BACKGROUND 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 18F-FDG-PET/CT predict recurrent cardiovascular events in patients with carotid stenosis who underwent endarterectomy. METHODS 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. 18F-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. RESULTS 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 18F-FDG uptake (r = 0.38 P = .05). We did not find any correlation between circulating MMPs and in vivo carotid plaque metabolism assessed by 18F-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 18F-FDG-PET was not significant. CONCLUSIONS 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.

中文翻译：

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循环金属蛋白酶7升高可预测颈动脉狭窄患者的复发性心血管事件：一项前瞻性队列研究。

背景技术重大不良心血管事件是长期接受颈动脉内膜切除术的患者发病率和死亡率的主要原因。很少有报道评估炎症标志物与颈动脉内膜切除术后心血管疾病风险的预后价值。在这里，我们旨在确定是否通过18F-FDG-F研究了基质金属蛋白酶（MMP-1，MMP-2，MMP-7，MMP-9和MMP-10），MMPs的组织抑制剂（TIMP-1）和体内炎症。 PET / CT可预测接受内膜切除术的颈动脉狭窄患者的复发性心血管事件。方法这项前瞻性队列研究针对计划在2013年7月至2016年3月间接受颈动脉内膜切除术的有症状（23/31）或无症状（8/31）严重（> 70％）颈动脉狭窄的31例患者进行。此外，该研究还包括26个健康对照。手术前2天收集血浆和血清样品，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，敏感性C反应蛋白和红细胞沉降率。由于2例有症状患者没有术前可利用性，因此对29例患者进行了聚焦于多个区域血管壁代谢的18F-FDG-PET / CT。使用针对MMP-10，MMP-9，TIMP-1和CD68的抗体进行了组织学和免疫组化研究。结果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与血浆水平（r = 0.42 P = .02）和18F-FDG摄取（r = 0.38 P = .05）相关。我们没有发现循环的MMP与18F-FDG-PET评估的体内颈动脉斑块代谢之间有任何相关性。在中位随访1077天后，记录了4例需要住院的脑血管，7例心血管疾病和11例外围血管事件。循环中的MMP-7能够预测超出传统危险因素的事件（HR = 1.15 P = .006）。当模型与目标变量相关联时，18F-FDG-PET预测的风险并不显着。结论循环中的MMP-7可能代表中度至重度颈动脉狭窄患者复发性心血管事件的新标志。MMP-7可能反映该特定血管区域的动脉粥样硬化负担，但不反映斑块炎症。