Federico Biscetti1,2,3, Pietro Manuel Ferraro4,5,6, William R Hiatt7, Flavia Angelini3, Elisabetta Nardella3, Andrea Leonardo Cecchini3, Angelo Santoliquido6,8, Dario Pitocco6,9, Raffaele Landolfi4,2,6, Andrea Flex4,3,10. 1. Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy f.biscetti@gmail.com. 2. UOC Clinica Medica e Malattie Vascolari, Rome, Italy. 3. Laboratorio di Biologia e Genetica Vascolare, Università Cattolica del Sacro Cuore, Rome, Italy. 4. Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 5. UOC Nefrologia, Rome, Italy. 6. Università Cattolica del Sacro Cuore, Rome, Italy. 7. Division of Cardiology, Department of Medicine, University of Colorado School of Medicine, and CPC Clinical Research, Aurora, CO. 8. UOS Angiologia CIC, Rome, Italy. 9. UOSA Diabetologia, Rome, Italy. 10. UOSA Medicina delle Malattie Vascolari Periferiche, Rome, Italy.
Abstract
OBJECTIVE: Peripheral artery disease (PAD) is one of the most relevant complications of diabetes. Although several pharmacological and revascularization approaches are available for treating patients with diabetes and PAD, an endovascular approach is often associated with postprocedural complications that can increase the risk for acute limb ischemia or amputation. However, no definitive molecular associations have been described that could explain the difference in outcomes after endovascular treatment in patients with diabetes, PAD, and chronic limb-threatening ischemia (CLTI). RESEARCH DESIGN AND METHODS: We evaluated the relationship between the levels of the main cytokines associated with diabetic atherosclerosis and the outcomes after endovascular procedures in patients with diabetes, PAD, and CLTI. RESULTS: A total of 299 patients with below-the-knee occlusive disease who were undergoing an angioplasty procedure were enrolled. The levels of key cytokines-osteoprotegerin (OPG), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP)-were measured, and major adverse limb events (MALE) and major adverse cardiovascular events (MACE) were assessed 1, 3, 6, and 12 months after the procedure. There was a linear trend from the lowest to the highest quartile for each cytokine at baseline and incident MALE. A linear association was also observed between increasing levels of each cytokine and incident MACE. Receiver operating characteristics models were constructed using clinical and laboratory risk factors, and the inclusion of cytokines significantly improved the prediction of incident events. CONCLUSIONS: We demonstrated that elevated OPG, TNF-α, IL-6, and CRP levels at baseline correlate with worse vascular outcomes in patients with diabetes, PAD, and CLTI undergoing an endovascular procedure.
OBJECTIVE:Peripheral artery disease (PAD) is one of the most relevant complications of diabetes. Although several pharmacological and revascularization approaches are available for treating patients with diabetes and PAD, an endovascular approach is often associated with postprocedural complications that can increase the risk for acute limb ischemia or amputation. However, no definitive molecular associations have been described that could explain the difference in outcomes after endovascular treatment in patients with diabetes, PAD, and chronic limb-threatening ischemia (CLTI). RESEARCH DESIGN AND METHODS: We evaluated the relationship between the levels of the main cytokines associated with diabetic atherosclerosis and the outcomes after endovascular procedures in patients with diabetes, PAD, and CLTI. RESULTS: A total of 299 patients with below-the-knee occlusive disease who were undergoing an angioplasty procedure were enrolled. The levels of key cytokines-osteoprotegerin (OPG), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP)-were measured, and major adverse limb events (MALE) and major adverse cardiovascular events (MACE) were assessed 1, 3, 6, and 12 months after the procedure. There was a linear trend from the lowest to the highest quartile for each cytokine at baseline and incident MALE. A linear association was also observed between increasing levels of each cytokine and incident MACE. Receiver operating characteristics models were constructed using clinical and laboratory risk factors, and the inclusion of cytokines significantly improved the prediction of incident events. CONCLUSIONS: We demonstrated that elevated OPG, TNF-α, IL-6, and CRP levels at baseline correlate with worse vascular outcomes in patients with diabetes, PAD, and CLTI undergoing an endovascular procedure.
Authors: J Husakova; R Bem; V Fejfarova; A Jirkovska; V Woskova; R Jarosikova; V Lovasova; E B Jude; M Dubsky Journal: J Diabetes Res Date: 2022-04-11 Impact factor: 4.061