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-FDGPET/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
