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

• Published in: Atherosclerosis Vol. 239; no. 2; pp. 459 - 464
• Main Authors: Rizza, Stefano, Copetti, Massimiliano, Cardellini, Marina, Menghini, Rossella, Pecchioli, Chiara, Luzi, Alessio, Di Cola, Giovanni, Porzio, Ottavia, Ippoliti, Arnaldo, Romeo, Franco, Pellegrini, Fabio, Federici, Massimo
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.04.2015
• Subjects: ADAM Proteins - metabolism; ADAM17 Protein; Adult; Aged; Atherosclerosis; Atherosclerosis - blood; Atherosclerosis - diagnosis; Atherosclerosis - enzymology; Atherosclerosis - mortality; Atherosclerosis - surgery; Biomarkers - blood; Cardiovascular; Cardiovascular disease outcomes; Decision Support Techniques; Endothelium-derived factors; Enzyme-Linked Immunosorbent Assay; Female; Follow up study; Humans; Inflammation; Intercellular Adhesion Molecule-1 - blood; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction - mortality; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Receptors, Interleukin-6 - blood; Receptors, Tumor Necrosis Factor, Type I - blood; Recurrence; Risk Assessment; Risk Factors; Rome - epidemiology; Stroke - mortality; Substrate Specificity; Time Factors; Vascular Cell Adhesion Molecule-1 - blood; Cardiovascular disease outcomes; NRI; MACEs; PTCA; Inflammation; RCHD; AVD; IDI; Endothelium-derived factors; ADAM17; CV; Follow up study; RECPAM; Atherosclerosis; TIMP3; RIDI; OGTT; CEA; Net reclassification improvement; Recursive Partitioning and Amalgamation; Cardiovascular; Tissue inhibitor of metalloproteinase 3; Transluminal coronary angioplasty; Oral Glucose Tolerance Test; A Disintegrin and Metallo Protease Domain 17; Carotid endo-arterectomy; Major cardiovascular events; Relative Integrated Discrimination Improvement; Athero vascular diabetes; Integrated Discrimination Improvement; Recurrent Coronary Heart Disease
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2015.01.029

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, 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). 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. •ADAM17 substrates may help to predict major cardiovascular events.•A RECPAM model was used to create a quantitative risk score based on ADAM17 substrates.•Individuals with high ADAM17 score show increased risk for incident events in univariable and multivariable analysis.•Application of ADAM17 score led to a significant enhancement of the Framingham risk score.