Barnabas Gellen1, Nathalie Thorin-Trescases2, Eric Thorin2,3, Elise Gand4, Philippe Sosner4,5,6, Sonia Brishoual4, Vincent Rigalleau7, David Montaigne8,9, Vincent Javaugue4,10, Yann Pucheu11, Philippe Gatault12, Xavier Piguel13, Samy Hadjadj12,14, Pierre-Jean Saulnier4. 1. ELSAN, Polyclinique de Poitiers, 1 Rue de la Providence, F-86000, Poitiers, France. barnabas.gellen.cardio@gmail.com. 2. Research Center, Montreal Heart Institute, Montreal, QC, Canada. 3. Department of Surgery, Faculty of Medicine, Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada. 4. INSERM, Centre d'Investigation Clinique CIC1402, Université de Poitiers, CHU de Poitiers, Poitiers, France. 5. Laboratoire MOVE (EA 6314), Université de Poitiers, Poitiers, France. 6. Centre Médico-Sportif Mon Stade, Paris, France. 7. Endocrinology - Diabetology - Nutrition, CHU de Bordeaux, Hôpital Haut-Lévêque, Pessac, France. 8. Department of Clinical Physiology - Echocardiography, CHU Lille, Lille, France. 9. INSERM U1011, EGID, Institut Pasteur de Lille, University of Lille, Lille, France. 10. Nephrology, CHU de Poitiers, Poitiers, France. 11. Cardiology, CHU de Bordeaux, Pessac, France. 12. Transplantation, Immunology and Inflammation (T2I) - EA4245, CHRU de Tours, Nephrology-Hypertension, Dialysis and Renal Transplantation, FHU SUPORT, Université de Tours, Tours, France. 13. Endocrinology-Diabetology, CHU de Poitiers, Poitiers, France. 14. L'Institut du Thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France.
Abstract
AIMS/HYPOTHESIS: Tenascin-C (TN-C) is an extracellular matrix glycoprotein highly expressed in inflammatory and cardiovascular (CV) diseases. Serum TN-C has not yet been specifically studied in individuals with type 2 diabetes, a condition associated with chronic low-grade inflammation and increased CV disease risk. In this study, we hypothesised that elevated serum TN-C at enrolment in participants with type 2 diabetes would be associated with increased risk of death and major adverse CV events (MACE) during follow-up. METHODS: We used a prospective, monocentric cohort of consecutive type 2 diabetes participants (the SURDIAGENE [SUivi Rénal, DIAbète de type 2 et GENEtique] cohort) with all-cause death as a primary endpoint and MACE (CV death, non-fatal myocardial infarction or stroke) as a secondary endpoint. We used a proportional hazard model after adjustment for traditional risk factors and the relative integrated discrimination improvement (rIDI) to assess the incremental predictive value of TN-C for these risk factors. RESULTS: We monitored 1321 individuals (58% men, mean age 64 ± 11 years) for a median of 89 months. During follow-up, 442 individuals died and 497 had MACE. Multivariate Cox analysis showed that serum TN-C concentrations were associated with an increased risk of death (HR per 1 SD: 1.27 [95% CI 1.17, 1.38]; p < 0.0001) and MACE (HR per 1 SD: 1.23 [95% CI 1.13, 1.34]; p < 0.0001). Using TN-C concentrations on top of traditional risk factors, prediction of the risk of all-cause death (rIDI: 8.2%; p = 0.0006) and MACE (rIDI: 6.7%; p = 0.0014) improved significantly, but modestly. CONCLUSIONS/ INTERPRETATION: In individuals with type 2 diabetes, increased serum TN-C concentrations were independently associated with death and MACE. Therefore, including TN-C as a prognostic biomarker could improve risk stratification in these individuals.
AIMS/HYPOTHESIS: Tenascin-C (TN-C) is an extracellular matrix glycoprotein highly expressed in inflammatory and cardiovascular (CV) diseases. Serum TN-C has not yet been specifically studied in individuals with type 2 diabetes, a condition associated with chronic low-grade inflammation and increased CV disease risk. In this study, we hypothesised that elevated serum TN-C at enrolment in participants with type 2 diabetes would be associated with increased risk of death and major adverse CV events (MACE) during follow-up. METHODS: We used a prospective, monocentric cohort of consecutive type 2 diabetesparticipants (the SURDIAGENE [SUivi Rénal, DIAbète de type 2 et GENEtique] cohort) with all-cause death as a primary endpoint and MACE (CV death, non-fatal myocardial infarction or stroke) as a secondary endpoint. We used a proportional hazard model after adjustment for traditional risk factors and the relative integrated discrimination improvement (rIDI) to assess the incremental predictive value of TN-C for these risk factors. RESULTS: We monitored 1321 individuals (58% men, mean age 64 ± 11 years) for a median of 89 months. During follow-up, 442 individuals died and 497 had MACE. Multivariate Cox analysis showed that serum TN-C concentrations were associated with an increased risk of death (HR per 1 SD: 1.27 [95% CI 1.17, 1.38]; p < 0.0001) and MACE (HR per 1 SD: 1.23 [95% CI 1.13, 1.34]; p < 0.0001). Using TN-C concentrations on top of traditional risk factors, prediction of the risk of all-cause death (rIDI: 8.2%; p = 0.0006) and MACE (rIDI: 6.7%; p = 0.0014) improved significantly, but modestly. CONCLUSIONS/ INTERPRETATION: In individuals with type 2 diabetes, increased serum TN-C concentrations were independently associated with death and MACE. Therefore, including TN-C as a prognostic biomarker could improve risk stratification in these individuals.
Entities:
Keywords:
Cardiovascular risk; MACE; Tenascin-C; Type 2 diabetes
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