Abstract

ObjectivesWe examined the association of the coronary thrombus microbiota and relative metabolites with major adverse cardiovascular events (MACE) in hyperglycemic patients with ST segment elevation myocardial infarction (STEMI). BackgroundHyperglycemia during STEMI may affect both development and progression of coronary thrombus via gut and thrombus microbiota modifications. MethodsWe undertook an observational cohort study of 146 first STEMI patients treated with primary percutaneous coronary intervention (PPCI) and thrombus-aspiration (TA). Patients were clustered, based on admission blood glucose levels, in hyperglycemic (≥140 mg/dl) and normoglycemic (<140 mg/dl). We analyzed gut and thrombus microbiota in all patients. Moreover, we assessed TMAO, CD40L and von Willebrand Factor (vWF) in coronary thrombi. Cox regressions were used for the association between Prevotellaspp. and TMAO terziles and MACE. MACE endpoint at 1 year included death, re-infarction, unstable angina. ResultsIn fecal and thrombus samples, we observed a significantly different prevalence of both Prevotellaspp. and Alistipesspp. between patients with hyperglycemia (n = 56) and those with normal glucose levels (n = 90). The abundance of Prevotella increased in hyperglycemic vs normoglycemic patients whereas the contrary was observed for Alistipes. Interestingly, in coronary thrombus, the content of Prevotella was associated with admission blood glucose levels (p < 0.01), thrombus dimensions (p < 0.01), TMAO, CDL40 (p < 0.01) and vWF (p < 0.01) coronary thrombus contents. Multivariate Cox-analysis disclosed a reduced survival in patients with high levels of Prevotella and TMAO in coronary thrombus as compared to patients with low levels of Prevotella and TMAO, after 1-year follow up. ConclusionsHyperglycemia during STEMI may increase coronary thrombus burden via gut and thrombus microbiota dysbiosis characterized by an increase of Prevotella and TMAO content in thrombi.Clinical Trial Registration: NCT03439592. September 30, 2016.Ethic Committee Vanvitelli University: 268/2016.

Highlights

  • Hyperglycemia during ST-elevation myocardial infarction (STEMI) may affect both development and progression of coronary thrombus via gut and thrombus microbiota modifications

  • In coronary thrombus, the content of Prevotella was associated with admission blood glucose levels (p

  • Hyperglycemia during STEMI may increase coronary thrombus burden via gut and thrombus microbiota dysbiosis characterized by an increase of Prevotella and TMAO content in thrombi

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Summary

Introduction

Hyperglycemia during STEMI may affect both development and progression of coronary thrombus via gut and thrombus microbiota modifications. The potential role of admission hyperglycemia in modulating the gut microbiota effects in coronary thrombus development remains unclear, and only small studies with diverse methods and findings have been reported so far [2,3,4]. Evidence about the possibleinteraction between hyperglycemia, microbiota and its metabolitesin the development and progression of coronary thrombus in ST-elevation myocardial infarction (STEMI) patients is lacking. To define a more robust evidence of gut microbiota signature and TMAO in coronary thrombus development and progression during AMI, we assessed both gut and thrombus microbiota in hyperglycemic (blood glucose levels >140 mg/dl at admission) and normoglycemic patients with STEMI. We explored associations between thrombus microbiota and TMAO levels, and composite endpoints (MACE= death, re-infarction, unstable angina) in cohorts at 1-year

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