Mathilde Nativel1, Fabrice Schneider2,3, Pierre-Jean Saulnier3,4,5, Elise Gand6, Stéphanie Ragot3,4,5, Olivier Meilhac7,8, Philippe Rondeau7, Elena Burillo7, Maxime Cournot7,9, Louis Potier10,11,12, Gilberto Velho12, Michel Marre10,11,12, Ronan Roussel10,11,12, Vincent Rigalleau1,13,14, Kamel Mohammedi15,13,14, Samy Hadjadj3,5,16,17. 1. Département d'Endocrinologie, Diabétologie, Nutrition, Hôpital Haut-Lévêque, Pessac, Bordeaux, France. 2. Département de Chirurgie Vasculaire, CHU de Poitiers, Poitiers, France. 3. UFR de Médecine et Pharmacie, Université de Poitiers, Poitiers, France. 4. Centre d'Investigation Clinique, CHU de Poitiers, Poitiers, France. 5. CIC 1402, INSERM, Poitiers, France. 6. Pôle Dune, CHU de Poitiers, Poitiers, France. 7. UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), INSERM, Université de La Réunion, Saint Denis de La Réunion, France. 8. CHU de La Réunion, Saint Denis de La Réunion, France. 9. Service de cardiologie, Centre Hospitalier Gabriel Martin, Saint-Paul, France. 10. DHU FIRE, Département d'Endocrinologie, Diabétologie, Nutrition, Assistance Publique Hôpitaux de Paris, Bichat Hospital, Paris, France. 11. UFR de Médecine, Université Paris Diderot, Sorbonne Paris Cité, Paris, France. 12. UMRS 1138, Centre de Recherche des Cordeliers, INSERM, Paris, France. 13. Faculté de Médecine, Université de Bordeaux, Bordeaux, France. 14. Centre de Recherche INSERM-Université de Bordeaux U1219 "Bordeaux Population Health," Bordeaux, France. 15. Département d'Endocrinologie, Diabétologie, Nutrition, Hôpital Haut-Lévêque, Pessac, Bordeaux, France km.mmohammedi@gmail.com. 16. Département d'Endocrinologie, Diabétologie, Nutrition, CHU de Poitiers, Poitiers, France. 17. Research Unit 1082, INSERM, Poitiers, France.
Abstract
OBJECTIVE: Inflammation and oxidative stress play an important role in the pathogenesis of lower-extremity artery disease (LEAD). We assessed the prognostic values of inflammatory and redox status biomarkers on the risk of LEAD in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: Plasma concentrations of tumor necrosis factor-α receptor 1 (TNFR1), angiopoietin-like 2, ischemia-modified albumin (IMA), fluorescent advanced glycation end products, protein carbonyls, and total reductive capacity of plasma were measured at baseline in the SURDIAGENE (Survie, Diabete de type 2 et Genetique) cohort. Major LEAD was defined as the occurrence during follow-up of peripheral revascularization or lower-limb amputation. RESULTS: Among 1,412 participants at baseline (men 58.2%, mean [SD] age 64.7 [10.6] years), 112 (7.9%) developed major LEAD during 5.6 years of follow-up. High plasma concentrations of TNFR1 (hazard ratio [95% CI] for second vs. first tertile 1.12 [0.62-2.03; P = 0.71] and third vs. first tertile 2.16 [1.19-3.92; P = 0.01]) and of IMA (2.42 [1.38-4.23; P = 0.002] and 2.04 [1.17-3.57; P = 0.01], respectively) were independently associated with an increased risk of major LEAD. Plasma concentrations of TNFR1 but not IMA yielded incremental information, over traditional risk factors, for the risk of major LEAD as follows: C-statistic change (0.036 [95% CI 0.013-0.059]; P = 0.002), integrated discrimination improvement (0.012 [0.005-0.022]; P < 0.001), continuous net reclassification improvement (NRI) (0.583 [0.294-0.847]; P < 0.001), and categorical NRI (0.171 [0.027-0.317]; P = 0.02). CONCLUSIONS: Independent associations exist between high plasma TNFR1 or IMA concentrations and increased 5.6-year risk of major LEAD in people with type 2 diabetes. TNFR1 allows incremental prognostic information, suggesting its use as a biomarker for LEAD.
OBJECTIVE: Inflammation and oxidative stress play an important role in the pathogenesis of lower-extremity artery disease (LEAD). We assessed the prognostic values of inflammatory and redox status biomarkers on the risk of LEAD in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: Plasma concentrations of tumor necrosis factor-α receptor 1 (TNFR1), angiopoietin-like 2, ischemia-modified albumin (IMA), fluorescent advanced glycation end products, protein carbonyls, and total reductive capacity of plasma were measured at baseline in the SURDIAGENE (Survie, Diabete de type 2 et Genetique) cohort. Major LEAD was defined as the occurrence during follow-up of peripheral revascularization or lower-limb amputation. RESULTS: Among 1,412 participants at baseline (men 58.2%, mean [SD] age 64.7 [10.6] years), 112 (7.9%) developed major LEAD during 5.6 years of follow-up. High plasma concentrations of TNFR1 (hazard ratio [95% CI] for second vs. first tertile 1.12 [0.62-2.03; P = 0.71] and third vs. first tertile 2.16 [1.19-3.92; P = 0.01]) and of IMA (2.42 [1.38-4.23; P = 0.002] and 2.04 [1.17-3.57; P = 0.01], respectively) were independently associated with an increased risk of major LEAD. Plasma concentrations of TNFR1 but not IMA yielded incremental information, over traditional risk factors, for the risk of major LEAD as follows: C-statistic change (0.036 [95% CI 0.013-0.059]; P = 0.002), integrated discrimination improvement (0.012 [0.005-0.022]; P < 0.001), continuous net reclassification improvement (NRI) (0.583 [0.294-0.847]; P < 0.001), and categorical NRI (0.171 [0.027-0.317]; P = 0.02). CONCLUSIONS: Independent associations exist between high plasma TNFR1 or IMA concentrations and increased 5.6-year risk of major LEAD in people with type 2 diabetes. TNFR1 allows incremental prognostic information, suggesting its use as a biomarker for LEAD.
Authors: Kamel Mohammedi; Stephen Harrap; Giuseppe Mancia; Michel Marre; Neil Poulter; John Chalmers; Mark Woodward Journal: Cardiovasc Diabetol Date: 2021-01-04 Impact factor: 9.951