EFFECTS OF STRESS HYPERGLYCEMIA ACCORDING TO DIABETICSTATUS IN PATIENTS WITH ST-ELEVATION MYOCARDIALINFARCTION AND ITS RELATIONSHIP WITH CARDIAC CELL INJURYAND MITOCHONDRIAL DAMAGE: A TRANSLATIONAL APPROACH

Background: Acute hyperglycemia (AH) is common in ST-elevation myocardial infarction (STEMI) and predicts outcomes. AH is a more powerful prognostic predictor in patients without diabetes mellitus (DM) than with DM, emphasizing the role of an acute glucose rise compared to chronic elevations. Moreover, AH may exacerbate, thorough mitochondrial dysfunction, infarct size (IS). We investigated the association between AH and chronic glycemia, considered separately or in combination, with mitochondrial injury and myocardial IS in STEMI patients with or without DM. Methods: We measured admission serum glucose (AH), cytochrome c and mitochondrial DNA levels (mitochondrial biomarkers), and estimated chronic glucose in all patients. We calculated the acute on chronic (A/C) glycemic ratio. The primary endpoint was IS at cardiac magnetic resonance. The composite of in hospital mortality, acute-pulmonary-edema, and shock was the secondary endpoint. Results: 100 STEMI patients with DM and 100 without were included. IS was 25gr and 19gr and the secondary endpoint occurred in 21% and 8% of patients with and without DM, respectively (p=0.02 and p=0.01, respectively). The A/C ratio only significantly correlated with cytochrome c and mitochondrial DNA levels in DM patients. However, at reclassification analyses, A/C glycemic ratio showed the best prognostic power in predicting the primary and secondary endpoints as compared to AH in DM (net-reclassification-index 28% and 31%, respectively) but not in non DM patients (net-reclassification-index 1% and 2%, respectively). In DM patients, A/C glycemic ratio, but not AH, significantly predicted 1-year mortality, after adjustment for major confounders. 4 Conclusions: In STEMI patients with DM, A/C glycemic ratio seems to be a better predictor of IS and in-hospital and 1-year outcome than AH. This study highlights the prognostic role of A/C ratio, its impact on mitochondrial impairment and outcomes, and may pave the way to interventional trials targeting AH according to A/C ratio in DM patients with STEMI.