Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Nov 15:12:777083.
doi: 10.3389/fphar.2021.777083. eCollection 2021.

Effects of Sodium-Glucose Transporter 2 Inhibitors (SGLT2-I) in Patients With Ischemic Heart Disease (IHD) Treated by Coronary Artery Bypass Grafting via MiECC: Inflammatory Burden, and Clinical Outcomes at 5 Years of Follow-Up

Celestino Sardu  1   2 , Massimo Massetti  2   3 , Nicola Testa  2 , Luigi Di Martino  2 , Gaetano Castellano  2 , Fabrizio Turriziani  1 , Ferdinando Carlo Sasso  1 , Michele Torella  4 , Marisa De Feo  4 , Gaetano Santulli  5   6   7 , Giuseppe Paolisso  1   8 , Raffaele Marfella  1   8
Affiliations

Effects of Sodium-Glucose Transporter 2 Inhibitors (SGLT2-I) in Patients With Ischemic Heart Disease (IHD) Treated by Coronary Artery Bypass Grafting via MiECC: Inflammatory Burden, and Clinical Outcomes at 5 Years of Follow-Up

Celestino Sardu et al. Front Pharmacol. .

Abstract

Introduction: Minimally invasive extracorporeal circulation (MiECC) reduced inflammatory burden, leading to best clinical outcomes in patients treated with coronary artery bypass grafting (CABG). Despite this, the patients with type 2 diabetes mellitus (T2DM) vs those without T2DM (non-T2DM) have a worse prognosis, caused by over-inflammation and modulated by sodium-glucose transporter 2 receptors. However, we evaluated the inflammatory burden and clinical outcomes in non-T2DM vs T2DM patients under sodium-glucose transporter 2 inhibitors (SGLT2-I users) vs non-SGLT2-I users at 5 years of follow-up post-CABG via MiECC. Materials and methods: In a multicenter study, we screened consecutive patients with indications to receive CABG. The study endpoints were the inflammatory burden (circulating serum levels of tumor necrosis factor-alpha (TNF-α), interleukin 1 and 6 (IL-1 and IL-6), C-reactive protein (CRP), and leucocytes count) and the clinical outcomes at follow-up of 5 years in non-T2DM vs SGLT2-I users, in non-T2DM vs non-SGLT2-I users, and SGLT2-I users vs non-SGLT2-I users. Results: At baseline, and at one year and 5 years of follow-up, the non-T2DM vs SGLT2-I users, non-T2DM vs non-SGLT2-I users, and SGLT2-I users vs non-SGLT2-I users had the lowest values of IL-1, IL-6, and TNF-α (p < 0.05). At one year of follow-up, SGLT2-I users vs non-T2DM and non-SGLT2-I users vs non-T2DM users had a higher rate of all deaths, cardiac deaths, re-myocardial infarction, repeat revascularization, and stroke, and of the composite endpoint (p < 0.05). In a multivariate Cox regression analysis, the composite endpoint was predicted by IL-1 [2.068 (1.367-3.129)], TNF-α [1.989 (1.081-2.998)], and SGLT2-I [0.504 (0.078-0.861)]. Conclusion: In T2DM patients, the SGLT2-I significantly reduced the inflammatory burden and ameliorated clinical outcomes at 5 years of follow-up post-CABG via MiECC.

Keywords: coronary artery bypass grafting; minimally invasive extracorporeal circulation; multi-vessel coronary stenosis; over-inflammation; sodium-glucose transporter 2 inhibitors; type 2 diabetes mellitus, coronary heart disease.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The representation of the study outcomes at 1 year of follow-up in patients without type 2 diabetes mellitus (non-T2DM; green color) vs T2DM under sodium-glucose transporter 2 inhibitors (SLGT2-I users; red color) vs T2DM patients without sodium-glucose transporter 2 inhibitors (non-SLGT2-I users; blue color). We reported the percentage of events for all deaths, cardiac deaths, re-myocardial infarction (re-MI), stroke, revascularization, and composite endpoint. For interleukin 1 (IL-1), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α), we used the values as mean ± standard deviation. * Is for statistical significant (p-value <0.05) vs T2DM; ** is for statistical significant (p value < 0.05) comparing SGLT2-I users vs non-SLGT2-I users.
FIGURE 2
FIGURE 2
The representation of the study outcomes at 5 years of follow-up in patients without type 2 diabetes mellitus (non-T2DM; green color) vs T2DM under sodium-glucose transporter 2 inhibitors (SLGT2-I users; red color) vs T2DM patients without sodium-glucose transporter 2 inhibitors (non-SLGT2-I users; blue color). We reported the percentage of events for all deaths, cardiac deaths, re-myocardial infarction (re-MI), stroke, revascularization, and composite endpoint. For interleukin 1 (IL-1), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α), we used the values as mean ± standard deviation. * Is for statistical significant (p-value < 0.05) vs T2DM; ** is for statistical significant (p value < 0.05) comparing SGLT2-I users vs non–SLGT2-I users.
FIGURE 3
FIGURE 3
Kaplan survival curves in non-diabetics (non-T2DM) vs type 2 diabetes mellitus (T2DM) patients under sodium-glucose transporter 2 inhibitors (SGLT2-I users) vs T2DM patients without SGLT2-I (non-SGLT2-I users) for study clinical outcomes. * is for statistical significant (p < 0.05).
See this image and copyright information in PMC

References

    1. American Diabetes Association (2020). 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2020. Diabetes Care 43 (Suppl. 1), S14–S31. 10.2337/dc20-S002 - DOI - PubMed
    1. Anastasiadis K., Murkin J., Antonitsis P., Bauer A., Ranucci M., Gygax E., et al. (2016). Use of Minimal Invasive Extracorporeal Circulation in Cardiac Surgery: Principles, Definitions and Potential Benefits. A Position Paper from the Minimal Invasive Extra-corporeal Technologies International Society (MiECTiS). Interact Cardiovasc. Thorac. Surg. 22 (5), 647–662. 10.1093/icvts/ivv380 - DOI - PMC - PubMed
    1. D'Onofrio N., Sardu C., Trotta M. C., Scisciola L., Turriziani F., Ferraraccio F., et al. (2021). Sodium-glucose Co-transporter2 Expression and Inflammatory Activity in Diabetic Atherosclerotic Plaques: Effects of Sodium-Glucose Co-transporter2 Inhibitor Treatment. Mol. Metab. 54, 101337. 10.1016/j.molmet.2021.101337 - DOI - PMC - PubMed
    1. Einarson T. R., Acs A., Ludwig C., Panton U. H. (2018). Prevalence of Cardiovascular Disease in Type 2 Diabetes: a Systematic Literature Review of Scientific Evidence from across the World in 2007-2017. Cardiovasc. Diabetol. 17 (1), 83. 10.1186/s12933-018-0728-6 - DOI - PMC - PubMed
    1. Gallinoro E., Paolisso P., Candreva A., Bermpeis K., Fabbricatore D., Esposito G., et al. (2021). Microvascular Dysfunction in Patients with Type II Diabetes Mellitus: Invasive Assessment of Absolute Coronary Blood Flow and Microvascular Resistance Reserve. Front. Cardiovasc. Med., 8. 10.3389/fcvm.2021.765071 - DOI - PMC - PubMed