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Published on: December 1, 2020
Sodium-Glucose Cotransporter 2 Inhibitors Preceding ST-Segment Elevation Myocardial Infarction: Global Proteomics and
Jay S Shavadia1, Megan Tomilin2, Paulos Chumala3
1Department of Medicine, Division of Cardiology, College of Medicine, Royal University Hospital, Saskatoon, Saskatchewan, Canada.
Background:
While sodium-glucose cotransport 2 receptor inhibitors (SGLT2i) improve post infarction cardiovascular outcomes, limited understanding exists on how these agents influence pathophysiology preceding myocardial infarction.
Objectives:
The objective of this study was to explore how proteins are differentially regulated in patients on and not on an SGLT2i preceding ST-segment elevation myocardial infarction (STEMI).
Methods:
Between June 2021 and October 2023, blood was collected at the time of arterial sheath insertion from consecutive STEMI patients. We then identified patients with diabetes and created propensity-matched pairs of patients on and not on SGLT2i prior to STEMI (SGLT2i+ and SGLT2i-). Serum was separated, and following immunodepletion and enzymatic digestion, liquid chromatography-tandem mass spectrometry was performed to identify differentially regulated proteins between the 2 SGLT2i groups.
Results:
Of the 560 STEMI patients, 149 eligible patients had diabetes distributed by pre-existing SGLT2i use as: SGLT2i+ (n = 35) and SGLT2i- (n = 114). Both SGLT2i groups were comparable in their presenting demographics and reperfusion strategies, except for higher proportion of insulin use in SGLT2i+ patients. Thirty-three SGLT2i+/SGLT2i- propensity-matched pairs were created from which 21 differentially expressed proteins were identified; dominantly noted was up-regulation of proteins involved in heme-scavenging and nitric oxide transport in patients on SGLT2i+ compared with SGLT2i preceding STEMI.
Conclusions:
SGLT2i appears to predominantly associate with up-regulation of heme-scavenging and nitric oxide, and plausibly through a related reduction in infarct size also associates with the observed related improvement in post infarction heart failure.
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