title: A score including ADAM17 substrates correlates to recurring cardiovascular event in subjects with atherosclerosis.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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, p < 0.001) and multivariable analysis (HR 3.42, 95% CI 1.55-7.54, p < 0.001). 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).
  
  
  CONCLUSIONS
  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.
authors: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; Center for Atherosclerosis, Policlinico Tor Vergata, Rome, Italy.
authors: Stefano
authors: S
authors: Rizza
authors: Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors: Massimiliano
authors: M
authors: Copetti
authors: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; Center for Atherosclerosis, Policlinico Tor Vergata, Rome, Italy.
authors: Marina
authors: M
authors: Cardellini
authors: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors: Rossella
authors: R
authors: Menghini
authors: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; Center for Atherosclerosis, Policlinico Tor Vergata, Rome, Italy.
authors: Chiara
authors: C
authors: Pecchioli
authors: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; Center for Atherosclerosis, Policlinico Tor Vergata, Rome, Italy.
authors: Alessio
authors: A
authors: Luzi
authors: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; Center for Atherosclerosis, Policlinico Tor Vergata, Rome, Italy.
authors: Giovanni
authors: G
authors: Di Cola
authors: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors: Ottavia
authors: O
authors: Porzio
authors: Department of Biopathology and Diagnostic Imaging, University of Rome Tor Vergata, Italy.
authors: Arnaldo
authors: A
authors: Ippoliti
authors: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors: Franco
authors: F
authors: Romeo
authors: Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors: Fabio
authors: F
authors: Pellegrini
authors: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; Center for Atherosclerosis, Policlinico Tor Vergata, Rome, Italy. Electronic address: federicm@uniroma2.it.
authors: Massimo
authors: M
authors: Federici
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000175:diagnosis / Q000201:enzymology* / Q000401:mortality / Q000601:surgery; D015415:Biomarkers / Q000097:blood; D003661:Decision Support Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000401:mortality; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D019947:Receptors, Interleukin-6 / Q000097:blood*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D012384:Rome / Q000453:epidemiology; D020521:Stroke / Q000401:mortality; D013379:Substrate Specificity; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; C573420:ICAM1 protein, human; C508603:IL6R protein, human; D019947:Receptors, Interleukin-6; D047888:Receptors, Tumor Necrosis Factor, Type I; C506235:TNFRSF1A protein, human; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human
keywords: Atherosclerosis; Cardiovascular disease outcomes; Endothelium-derived factors; Follow up study; Inflammation