A score including ADAM17 substrates correlates to recurring cardiovascular event in subjects with atherosclerosis

Autor: Massimiliano Copetti, Arnaldo Ippoliti, Stefano Rizza, Chiara Pecchioli, F Romeo, Marina Cardellini, Ottavia Porzio, Alessio Luzi, Fabio Pellegrini, Rossella Menghini, Massimo Federici, Giovanni Di Cola
Rok vydání: 2015
Předmět:
Male
Time Factors
Rome
Myocardial Infarction
Endothelium-derived factors
Settore MED/09
Kaplan-Meier Estimate
Disease
Substrate Specificity
Recurrence
Risk Factors
Medicine
Myocardial infarction
Settore MED/49 - Scienze Tecniche Dietetiche Applicate
Cardiovascular disease outcomes
Stroke
Settore BIO/12
Middle Aged
Intercellular Adhesion Molecule-1
Prognosis
Receptors
Tumor Necrosis Factor
Type I
Cardiology
Female
Follow up study
Cardiology and Cardiovascular Medicine
Adult
Cardiovascular event
medicine.medical_specialty
Vascular Cell Adhesion Molecule-1
Enzyme-Linked Immunosorbent Assay
ADAM17 Protein
Risk Assessment
Decision Support Techniques
Cardiovascular death
Predictive Value of Tests
Diabetes mellitus
Internal medicine
Humans
Atherosclerosis
Inflammation
Aged
Proportional Hazards Models
business.industry
medicine.disease
Receptors
Interleukin-6
Clinical method
Surgery
ADAM Proteins
Increased risk
Multivariate Analysis
business
Biomarkers
Zdroj: Atherosclerosis. 239:459-464
ISSN: 0021-9150
DOI: 10.1016/j.atherosclerosis.2015.01.029
Popis: Atherosclerosis disease is a leading cause for mortality and morbidity. The narrowing/rupture of a vulnerable atherosclerotic plaque is accountable for acute cardiovascular events. However, despite of an intensive research, a reliable clinical method which may disclose a vulnerable patient is still unavailable.We tested the association of ADAM17 (A Disintegrin and Metallo Protease Domain 17) circulating substrates (sICAM-1, sVCAM-1, sIL6R and sTNFR1) with a second major cardiovascular events [MACEs] (cardiovascular death, peripheral artery surgeries, non-fatal myocardial infarction and non-fatal stroke) in 298 patients belonging to the Vascular Diabetes (AVD) study. To evaluate ADAM17 activity we create ADAM17 score through a RECPAM model. Finally we tested the discrimination ability and the reclassification of clinical models. At follow-up (mean 47 months, range 1-118 months), 55 MACEs occurred (14 nonfatal MI, 14 nonfatal strokes, 17 peripheral artery procedures and 10 cardiovascular deaths) (incidence = 7.8% person-years). An increased risk for incident events was observed among the high ADAM17 score individuals both in univariable (HR 19.20, 95% CI 15.82-63.36, p0.001) and multivariable analysis (HR 3.42, 95% CI 1.55-7.54, p0.001). Finally we found that ADAM17 score significantly increases the prediction accuracy of the Framingham Recurring-Coronary-Heart-Disease-Score, with a significant improvement in discrimination (integrated discrimination improvement = 9%, p = 0.012) and correctly reclassifying 10% of events and 41% of non-events resulting in a cNRI = 0.51 (p = 0.005).We demonstrated a positive role of ADAM17 activity to predicting CV events. We think that an approach that targets strategies beyond classic cardiovascular risk factors control is necessary in individuals with an established vascular atherosclerosis.
Databáze: OpenAIRE
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