Infarct size, inflammatory burden, and admission hyperglycemia in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: a multicenter international registry

Pasquale Paolisso, Luca Bergamaschi, Gaetano Santulli, Emanuele Gallinoro, Arturo Cesaro, Felice Gragnano, Celestino Sardu, Niya Mileva, Alberto Foà, Matteo Armillotta, Angelo Sansonetti, Sara Amicone, Andrea Impellizzeri, Gianni Casella, Ciro Mauro, Dobrin Vassilev, Raffaele Marfella, Paolo Calabrò, Emanuele Barbato, Carmine Pizzi, Pasquale Paolisso, Luca Bergamaschi, Gaetano Santulli, Emanuele Gallinoro, Arturo Cesaro, Felice Gragnano, Celestino Sardu, Niya Mileva, Alberto Foà, Matteo Armillotta, Angelo Sansonetti, Sara Amicone, Andrea Impellizzeri, Gianni Casella, Ciro Mauro, Dobrin Vassilev, Raffaele Marfella, Paolo Calabrò, Emanuele Barbato, Carmine Pizzi

Abstract

Background: The inflammatory response occurring in acute myocardial infarction (AMI) has been proposed as a potential pharmacological target. Sodium-glucose co-transporter 2 inhibitors (SGLT2-I) currently receive intense clinical interest in patients with and without diabetes mellitus (DM) for their pleiotropic beneficial effects. We tested the hypothesis that SGLT2-I have anti-inflammatory effects along with glucose-lowering properties. Therefore, we investigated the link between stress hyperglycemia, inflammatory burden, and infarct size in a cohort of type 2 diabetic patients presenting with AMI treated with SGLT2-I versus other oral anti-diabetic (OAD) agents.

Methods: In this multicenter international observational registry, consecutive diabetic AMI patients undergoing percutaneous coronary intervention (PCI) between 2018 and 2021 were enrolled. Based on the presence of anti-diabetic therapy at the admission, patients were divided into those receiving SGLT2-I (SGLT-I users) versus other OAD agents (non-SGLT2-I users). The following inflammatory markers were evaluated at different time points: white-blood-cell count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-platelet ratio (NPR), and C-reactive protein. Infarct size was assessed by echocardiography and by peak troponin levels.

Results: The study population consisted of 583 AMI patients (with or without ST-segment elevation): 98 SGLT2-I users and 485 non-SGLT-I users. Hyperglycemia at admission was less prevalent in the SGLT2-I group. Smaller infarct size was observed in patients treated with SGLT2-I compared to non-SGLT2-I group. On admission and at 24 h, inflammatory indices were significantly higher in non-SGLT2-I users compared to SGLT2-I patients, with a significant increase in neutrophil levels at 24 h. At multivariable analysis, the use of SGLT2-I was a significant predictor of reduced inflammatory response (OR 0.457, 95% CI 0.275-0.758, p = 0.002), independently of age, admission creatinine values, and admission glycemia. Conversely, peak troponin values and NSTEMI occurrence were independent predictors of a higher inflammatory status.

Conclusions: Type 2 diabetic AMI patients receiving SGLT2-I exhibited significantly reduced inflammatory response and smaller infarct size compared to those receiving other OAD agents, independently of glucose-metabolic control. Our findings are hypothesis generating and provide new insights on the cardioprotective effects of SGLT2-I in the setting of coronary artery disease.

Trial registration: Data are part of the ongoing observational registry: SGLT2-I AMI PROTECT.

Clinicaltrials: gov Identifier: NCT05261867.

Keywords: Acute myocardial infarction; Hyperglycemia; Infarct size; Inflammation; SGLT2-I.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Box plot and Dot plot comparing the distribution of White Blood Cells (A and C) and Neutrophil-Lymphocyte Ratio (NLR) (B and D) at admission and discharge in SGLT2-I users vs. non-SGLT2-I users (blue box and red box respectively)
Fig. 2
Fig. 2
Density Plot showing the neutrophils (A and C) and lymphocytes (B and D) distribution at admission and after 24 h in SGLT2-I versus non-SGLT2-I users. Blue curve denotes non-SGLT2-I users; red curve represents patients receiving SGLT2-I. The dotted arrow shows how the peak of the neutrophil’s distribution in non SGLT2-I users moved towards higher values after 24 h
Fig. 3
Fig. 3
Correlations between neutrophils values measured at 24 h and the admission glucose levels (A) and peak troponin values (B), in the overall study population (n = 583)
Fig. 4
Fig. 4
Correlation between neutrophils at 24 h and discharge LVEF in SGLT2-I versus non-SGLT2-I users (red and blue lines respectively). An inverse correlation was found between the inflammatory burden (represented by neutrophils at 24 h) and the LVEF at discharge. Conversely, in SGLT2-I users, the higher inflammatory burden was not accompanied by a reduction in LVEF at discharge

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