Abstract
Background/objectivesPericoronary 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.MethodsAn 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.ResultsThe 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.ConclusionPrediabetes 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
Highlights
Prediabetes affects more than 38% of people in adult population [1]
Prediabetic patients showed higher inflammatory tone and leptin to adiponectin ratio in pericoronary fat compared to normoglycemic patients (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)
Summary
Prediabetes affects more than 38% of people in adult population [1]. Without any intervention, prediabetes often progresses to diabetes mellitus and is associated with increased risk of cardiovascular disease [2]. Adipose tissue is an active endocrine organ secreting multiple metabolically active factors, such as leptin, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) [4] These factors are involved in metabolic and inflammatory processes and may act in a paracrine or endocrine manner, altering liver, pancreas, skeletal muscle and vascular system metabolism [5]. Is reasonable that inflammatory cytokines and adipokines released from pericoronary fat may be involved in the outcomes of prediabetic patients after cardiovascular events, including coronary artery diseases. It is conceivable that pericoronary fat in patients with prediabetes may release inflammatory factors leading to the development and destabilization of atherosclerotic plaques in coronary arteries In this setting, the aim of this study was to investigate the pro-inflammatory tone in pericoronary fat, by evaluating leptin to adiponectin ratio, TNF-α levels, and SIRT6 protein level [14]. Since metformin therapy regulates both leptin and adiponectin levels in plasma and in subcutaneous fat [15,16,17], here, its effect on leptin to adiponectin ratio and inflammatory tone in pericoronary fat was evaluated, as well as its correlation with 12-months prognosis in AMI-prediabetic patients
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