Elevated Circulating Metalloproteinase 7 Predicts Recurrent Cardiovascular Events in Patients With Carotid Stenosis: A Prospective Cohort Study
David Moreno-Ajona (1), Pablo Irimia (2,3,4) , José Antonio Rodríguez (5,6,7) , María José García-Velloso (5,8), Jesús López-Fidalgo (9), Leopoldo Fernández-Alonso (5,10) , Lukasz Grochowitz (5,11) , Roberto Muñoz (5,12,13) , Pablo Domínguez (14), Jaime Gállego-Culleré (5,12,13) , Eduardo Martínez-Vila (1,5,12)
(1) Department of Neurology, Clínica Universidad de Navarra, Av. Pío XII 36, 31008, Pamplona, Navarra, Spain.
(2) Department of Neurology, Clínica Universidad de Navarra, Av. Pío XII 36, 31008, Pamplona, Navarra, Spain. firstname.lastname@example.org.
(3) Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain.
(4) Red de Investigación Cooperativa de Enfermedades Vasculares Cerebrales (INVICTUS PLUS), Madrid, Spain. email@example.com.
(5) Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain.
(6) Laboratory of Atherothrombosis, Program of Cardiovascular Diseases, CIMA-Universidad de Navarra, 31008, Pamplona, Spain.
(7) CIBERCV, Madrid, Spain.
(8) Department of Nuclear Medicine, Clínica Universidad de Navarra, 31008, Pamplona, Spain.
(9) Universidad de Navarra, ICS, Unidad de Estadística, 31008, Pamplona, Spain.
(10) Department of Vascular Surgery, Complejo Hospitalario de Navarra, 31008, Pamplona, Spain.
(11) Department of Vascular Surgery, Clínica Universidad de Navarra, 31008, Pamplona, Spain.
(12) Red de Investigación Cooperativa de Enfermedades Vasculares Cerebrales (INVICTUS PLUS), Madrid, Spain.
(13) Department of Neurology, Complejo Hospitalario de Navarra, 31008, Pamplona, Spain.
(14) Department of Radiology, Clínica Universidad de Navarra, 31008, Pamplona, Spain.
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.
CITA DEL ARTÍCULO BMC Cardiovasc Disord . 2020 Feb 26;20(1):93. doi: 10.1186/s12872-020-01387-3