Pericoronary fat inflammation and Major Adverse Cardiac Events (MACE) in prediabetic patients with acute myocardial infarction: effects of metformin

• Main Authors: Celestino Sardu, Nunzia D’Onofrio, Michele Torella, Michele Portoghese, Francesco Loreni, Simone Mureddu, Giuseppe Signoriello, Lucia Scisciola, Michelangela Barbieri, Maria Rosaria Rizzo, Marilena Galdiero, Marisa De Feo, Maria Luisa Balestrieri, Giuseppe Paolisso, Raffaele Marfella
• Format: Article
• Language: English
• Published: BMC 2019-09-01
• Series: Cardiovascular Diabetology
• Subjects: Prediabetes; Acute myocardial infarction; Metformin; Pericoronary fat; Inflammation; Adipokines
• Online Access: http://link.springer.com/article/10.1186/s12933-019-0931-0

Abstract Background/objectives Pericoronary adipose tissue inflammation might lead to the development and destabilization of coronary plaques in prediabetic patients. Here, we evaluated inflammation and leptin to adiponectin ratio in pericoronary fat from patients subjected to coronary artery bypass grafting (CABG) for acute myocardial infarction (AMI). Furthermore, we compared the 12-month prognosis of prediabetic patients compared to normoglycemic patients (NG). Finally, the effect of metformin therapy on pericoronary fat inflammation and 12-months prognosis in AMI-prediabetic patients was also evaluated. Methods An observational prospective study was conducted on patients with first AMI referred for CABG. Participants were divided in prediabetic and NG-patients. Prediabetic patients were divided in two groups; never-metformin-users and current-metformin-users receiving metformin therapy for almost 6 months before CABG. During the by-pass procedure on epicardial coronary portion, the pericoronary fat was removed from the surrounding stenosis area. The primary endpoints were the assessments of Major-Adverse-Cardiac-Events (MACE) at 12-month follow-up. Moreover, inflammatory tone was evaluated by measuring pericoronary fat levels of tumor necrosis factor-α (TNF-α), sirtuin 6 (SIRT6), and leptin to adiponectin ratio. Finally, inflammatory tone was correlated to the MACE during the 12-months follow-up. Results The MACE was 9.1% in all prediabetic patients and 3% in NG-patients. In prediabetic patients, current-metformin-users presented a significantly lower rate of MACE compared to prediabetic patients never-metformin-users. In addition, prediabetic patients showed higher inflammatory tone and leptin to adiponectin ratio in pericoronary fat compared to NG-patients (P < 0.001). Prediabetic never-metformin-users showed higher inflammatory tone and leptin to adiponectin ratio in pericoronary fat compared to current-metformin-users (P < 0.001). Remarkably, inflammatory tone and leptin to adiponectin ratio was significantly related to the MACE during the 12-months follow-up. Conclusion Prediabetes increase inflammatory burden in pericoronary adipose tissue. Metformin by reducing inflammatory tone and leptin to adiponectin ratio in pericoronary fat may improve prognosis in prediabetic patients with AMI. Trial registration Clinical Trial NCT03360981, Retrospectively Registered 7 January 2018