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

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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.

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Data availability

Data sharing maybe possible on a reasonable scientific request.

Abbreviations

CS:

Cardiogenic shock

ELISA:

Enzyme-linked immunosorbent assay

GLP-1:

Glucagon-like peptide-1

IABP:

Intra-aortic balloon counterpulsation

IQR:

Interquartile range

MODS:

Multiple organ failure

PCI:

Percutaneous coronary intervention

SIRS:

Systemic inflammatory response syndrome

TIMI:

Thrombolysis in myocardial infarction

IL-6:

Interleukin-6

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Funding

The IABP-SHOCK II trial was funded by grants from the German Research Foundation, the German Heart Research Foundation, the German Cardiac Society, Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte, and the Heart Center Leipzig at University of Leipzig, and by unrestricted grants from Maquet Cardiopulmonary and Teleflex Medical. This work was supported by the German Research Foundation (DFG) SFB/TRR219 (M-04 and M-05), Project-ID 403224013 and Interreg V-A grant EURlipids to ML as well as the CORONA Stiftung, Germany to NM.

Author information

Author notes

  1. Michael Lehrke, Georg Fuernau and Christian Jung contributed equally to the manuscript.

Authors and Affiliations

  1. Department of Internal Medicine I, University Hospital Aachen, Pauwelsstraße 30, 52074, Aachen, Germany

    Michael Lehrke, Florian Kahles, Julia Moellmann & Nikolaus Marx

  2. Clinic for Internal Medicine II, Staedtisches Klinikum Dessau, Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Auenweg 38, 06847, Dessau-Rosslau, Germany

    Georg Fuernau

  3. Lübeck and German Center for Cardiovascular Research (DZHK), University Heart Center Lübeck, Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany

    Georg Fuernau, Ingo Eitel & Nathalie Thelemann

  4. Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany

    Christian Jung

  5. Department of Internal Medicine/Cardiology, Heart Center Leipzig at University of Leipzig, Leipzig, Germany

    Steffen Desch & Holger Thiele

  6. Department of Medicine III, University Clinics of the Martin Luther University Halle-Wittenberg, Halle, Saale, Germany

    Karl Werdan

  7. Medizinische Klinik B, Klinikum Ludwigshafen and Institut Für Herzinfarktforschung, Ludwigshafen, Germany

    Uwe Zeymer

  8. Laboratory of Molecular and Experimental Cardiology, TU Dresden, Heart Center Dresden, Dresden, Germany

    Volker Adams

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  1. Michael Lehrke
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Corresponding authors

Correspondence to Michael Lehrke or Georg Fuernau.

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Conflict of interest

ML received grants and personal fees from Boehringer Ingelheim, grants and personal fees from MSD, grants and personal fees from Novo Nordisk, personal fees from Amgen, personal fees from Sanofi, personal fees from Astra Zeneca, personal fees from Bayer, personal fees from Lilly. FK has served as a speaker for Novo Nordisk, JM declares no conflict of interest, NM has served as speaker for Amgen, Bayer, Boehringer Ingelheim, Sanofi-Aventis, MSD, BMS, AstraZeneca, Lilly, NovoNordisk. All other authors declare no conflict of interests.

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Lehrke, M., Fuernau, G., Jung, C. et al. GLP-1 in patients with myocardial infarction complicated by cardiogenic shock—an IABP-SHOCK II-substudy. Clin Res Cardiol (2024). https://doi.org/10.1007/s00392-023-02366-2

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