Top

03-01-2024 | Cardiogenic Shock | Original Paper

GLP-1 in patients with myocardial infarction complicated by cardiogenic shock—an IABP-SHOCK II-substudy

Authors: Michael Lehrke, Georg Fuernau, Christian Jung, Florian Kahles, Julia Moellmann, Ingo Eitel, Nathalie Thelemann, Steffen Desch, Karl Werdan, Uwe Zeymer, Volker Adams, Nikolaus Marx, Holger Thiele

Published in: Clinical Research in Cardiology

Abstract

Background

Glucagon-like peptide-1 (GLP-1) is a gut-derived peptide secreted in response to nutritional and inflammatory stimuli. Elevated GLP-1 levels predict adverse outcome in patients with acute myocardial infarction or sepsis. GLP-1 holds cardioprotective effects and GLP-1 receptor agonists reduce cardiovascular events in high-risk patients with diabetes. In this study, we aimed to investigate the capacity of GLP-1 to predict outcome in patients with cardiogenic shock (CS) complicating myocardial infarction.

Methods

Circulating GLP-1 levels were serially assessed in 172 individuals during index PCI and day 2 in a prospectively planned biomarker substudy of the IABP-SHOCK II trial. All-cause mortality at short- (30 days), intermediate- (1 year), and long-term (6 years) follow-up was used for outcome assessment.

Results

Patients with fatal short-term outcome (n = 70) exhibited higher GLP-1 levels [86 (interquartile range 45–130) pM] at ICU admission in comparison to patients with 30-day survival [48 (interquartile range 33–78) pM; p < 0.001] (n = 102). Repeated measures ANOVA revealed a significant interaction of GLP-1 dynamics from baseline to day 2 between survivors and non-survivors (p = 0.04). GLP-1 levels above vs. below the median proved to be predictive for short- [hazard ratio (HR) 2.43; 95% confidence interval (CI) 1.50–3.94; p < 0.001], intermediate- [HR 2.46; 95% CI 1.62–3.76; p < 0.001] and long-term [HR 2.12; 95% CI 1.44–3.11; p < 0.001] outcome by multivariate Cox-regression analysis.

Conclusion

Elevated plasma levels of GLP-1 are an independent predictor for impaired prognosis in patients with myocardial infarction complicated by CS. The functional relevance of GLP-1 in this context is currently unknown and needs further investigations.

Trial registration

www.ClinicalTrials.gov Identifier: NCT00491036.

Graphical abstract

Thiele H, Ohman EM, de Waha-Thiele S et al (2019) Management of cardiogenic shock complicating myocardial infarction: an update 2019. Eur Heart J 40:2671–2683. https://doi.org/10.1093/eurheartj/ehz363CrossRefPubMed

Shimizu K, Ogura H, Goto M et al (2006) Altered gut flora and environment in patients with severe SIRS. J Trauma 60:126–133. https://doi.org/10.1097/01.ta.0000197374.99755.feCrossRefPubMed

Baggio LL, Drucker DJ (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132:2131–2157. https://doi.org/10.1053/j.gastro.2007.03.054CrossRefPubMed

Drucker DJ (2016) The Cardiovascular Biology of Glucagon-like Peptide-1. Cell Metab 24:15–30. https://doi.org/10.1016/j.cmet.2016.06.009CrossRefPubMed

Diebold S, Moellmann J, Kahles F et al (2018) Myocardial infarction is sufficient to increase GLP-1 secretion, leading to improved left ventricular contractility and mitochondrial respiratory capacity. Diabetes Obes Metab 20:2911–2918. https://doi.org/10.1111/dom.13472CrossRefPubMed

Kahles F, Ruckbeil MV, Mertens RW et al (2020) Glucagon-like peptide 1 levels predict cardiovascular risk in patients with acute myocardial infarction. Eur Heart J 41:882–889. https://doi.org/10.1093/eurheartj/ehz728CrossRefPubMed

Thiele H, Schuler G, Neumann FJ et al (2012) Intraaortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock: design and rationale of the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial. Am Heart J 163:938–945. https://doi.org/10.1016/j.ahj.2012.03.012CrossRefPubMed

Thiele H, Zeymer U, Neumann FJ et al (2012) Intraaortic balloon support for myocardial infarction with cardiogenic shock. NEnglJMed 367:1287–1296. https://doi.org/10.1056/NEJMoa1208410CrossRef

Thiele H, Zeymer U, Neumann FJ et al (2013) Intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock (IABP-SHOCK II): final 12 month results of a randomised, open-label trial. Lancet 382:1638–1645. https://doi.org/10.1016/S0140-6736(13)61783-3CrossRefPubMed

10.

Thiele H, Zeymer U, Thelemann N et al (2019) Intraaortic balloon pump in cardiogenic shock complicating acute myocardial infarction. Circulation 139:395–403. https://doi.org/10.1161/CIRCULATIONAHA.118.038201CrossRefPubMed

11.

Fuernau G, Poenisch C, Eitel I et al (2014) Growth-differentiation factor 15 and osteoprotegerin in acute myocardial infarction complicated by cardiogenic shock: a biomarker substudy of the IABP-SHOCK II-trial. Eur J Heart Fail 16:880–887. https://doi.org/10.1002/ejhf.117CrossRefPubMed

12.

Kahles F, Meyer C, Mollmann J et al (2014) GLP-1 secretion is increased by inflammatory stimuli in an IL-6-dependent manner, leading to hyperinsulinemia and blood glucose lowering. Diabetes 63:3221–3229. https://doi.org/10.2337/db14-0100CrossRefPubMed

13.

Lebherz C, Kahles F, Piotrowski K et al (2016) Interleukin-6 predicts inflammation-induced increase of Glucagon-like peptide-1 in humans in response to cardiac surgery with association to parameters of glucose metabolism. Cardiovasc Diabetol 15:21. https://doi.org/10.1186/s12933-016-0330-8CrossRefPubMedPubMedCentral

14.

Lebherz C, Schlieper G, Mollmann J et al (2017) GLP-1 levels predict mortality in patients with critical illness as well as end-stage renal disease. Am J Med 130(833–41):e3. https://doi.org/10.1016/j.amjmed.2017.03.010CrossRef

15.

Steven S, Hausding M, Kroller-Schon S et al (2015) Gliptin and GLP-1 analog treatment improves survival and vascular inflammation/dysfunction in animals with lipopolysaccharide-induced endotoxemia. Basic Res Cardiol 110:6. https://doi.org/10.1007/s00395-015-0465-xCrossRefPubMed

16.

Marsico F, Paolillo S, Gargiulo P et al (2020) Effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events in patients with Type 2 diabetes mellitus with or without established cardiovascular disease: a meta-analysis of randomized controlled trials. Eur Heart J 41:3346–3358. https://doi.org/10.1093/eurheartj/ehaa082CrossRefPubMed

Title: GLP-1 in patients with myocardial infarction complicated by cardiogenic shock—an IABP-SHOCK II-substudy
Authors: Michael Lehrke
Georg Fuernau
Christian Jung
Florian Kahles
Julia Moellmann
Ingo Eitel
Nathalie Thelemann
Steffen Desch
Karl Werdan
Uwe Zeymer
Volker Adams
Nikolaus Marx
Holger Thiele
Publication date: 03-01-2024
Publisher: Springer Berlin Heidelberg
Keywords: Cardiogenic Shock
Cardiogenic Shock
Intra-Aortic Balloon
Myocardial Infarction
Shock
Shock
Published in: Clinical Research in Cardiology
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI: https://doi.org/10.1007/s00392-023-02366-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

GLP-1 in patients with myocardial infarction complicated by cardiogenic shock—an IABP-SHOCK II-substudy

Abstract

Background

Methods

Results

Conclusion

Trial registration

Graphical abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Trial registration

Graphical abstract

Please log in to get access to this content