title: Intraplaque Expression of C-Reactive Protein Predicts Cardiovascular Events in Patients with Severe Atherosclerotic Carotid Artery Stenosis.
abstract: Serum c-reactive protein (CRP) was suggested for the assessment of intermediate cardiovascular (CV) risk. Here, systemic or intraplaque CRP levels were investigated as predictors of major adverse cardiovascular events (MACEs) in patients with severe carotid stenosis. CRP levels were assessed in the serum and within different portions (upstream and downstream) of carotid plaques of 217 patients undergoing endarterectomy. The association between CRP and intraplaque lipids, collagen, neutrophils, smooth muscle cells (SMC), and macrophage subsets was determined. No correlation between serum CRP and intraplaque biomarkers was observed. In upstream portions, CRP content was directly correlated with intraplaque neutrophils, total macrophages, and M1 macrophages and inversely correlated with SMC content. In downstream portions, intraplaque CRP correlated with M1 and M2 macrophages. According to the cut-off point (CRP > 2.9%) identified by ROC analysis in upstream portions, Kaplan-Meier analysis showed that patients with high CRP levels had a greater rate of MACEs. This risk of MACEs increased independently of age, male gender, serum CRP, and statin use. In conclusion, in patients with severe carotid artery stenosis, high CRP levels within upstream portions of carotid plaques directly and positively correlate with intraplaque inflammatory cells and predict MACEs at an 18-month follow-up period.
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132 Genoa, Italy.
authors.forename: Aldo
authors.identifier: 0000-0002-4747-5535
authors.initials: A
authors.lastname: Bonaventura
authors.affiliation: Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland.
authors.forename: François
authors.initials: F
authors.lastname: Mach
authors.affiliation: Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland.
authors.forename: Aline
authors.initials: A
authors.lastname: Roth
authors.affiliation: Unit of Toxicology, University Centre of Legal Medicine, Geneva-Lausanne, Rue Michel-Servet 1, 1211 Geneva, Switzerland.
authors.forename: Sébastien
authors.identifier: 0000-0002-4853-8163
authors.initials: S
authors.lastname: Lenglet
authors.affiliation: Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Burger
authors.affiliation: Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland.
authors.forename: Karim J
authors.identifier: 0000-0003-1042-5283
authors.initials: KJ
authors.lastname: Brandt
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132 Genoa, Italy; IRCCS AOU San Martino-IST, 10 Largo Benzi, 16132 Genoa, Italy.
authors.forename: Aldo
authors.identifier: 0000-0002-3804-918X
authors.initials: A
authors.lastname: Pende
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132 Genoa, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Bertolotto
authors.affiliation: Vascular and Endovascular Surgery Unit, Department of Surgery, IRCCS AOU San Martino-IST, 10 Largo Benzi, 16132 Genoa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Spinella
authors.affiliation: Vascular and Endovascular Surgery Unit, Department of Surgery, IRCCS AOU San Martino-IST, 10 Largo Benzi, 16132 Genoa, Italy.
authors.forename: Bianca
authors.initials: B
authors.lastname: Pane
authors.affiliation: Vascular and Endovascular Surgery Unit, Department of Surgery, IRCCS AOU San Martino-IST, 10 Largo Benzi, 16132 Genoa, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Palombo
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132 Genoa, Italy; IRCCS AOU San Martino-IST, 10 Largo Benzi, 16132 Genoa, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Dallegri
authors.affiliation: Clinic of Hematology, Department of Internal Medicine, University of Genoa, IRCCS AOU San Martino-IST, 10 Largo Benzi, 16132 Genoa, Italy.
authors.forename: Michele
authors.identifier: 0000-0002-1530-6729
authors.initials: M
authors.lastname: Cea
authors.affiliation: Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1205 Geneva, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vuilleumier
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132 Genoa, Italy; IRCCS AOU San Martino-IST, 10 Largo Benzi, 16132 Genoa, Italy; Centre of Excellence for Biomedical Research (CEBR), University of Genoa, 9 Viale Benedetto XV, 16132 Genoa, Italy.
authors.forename: Fabrizio
authors.identifier: 0000-0003-0823-8729
authors.initials: F
authors.lastname: Montecucco
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132 Genoa, Italy.
authors.forename: Federico
authors.identifier: 0000-0003-2957-4078
authors.initials: F
authors.lastname: Carbone
mesh_terms: D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D016893:Carotid Stenosis / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000378:metabolism; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D012372:ROC Curve; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein