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SHR Neuro Cancer Cardio Lipid Metab Microb

Aziz, F; Tripolt, NJ; Pferschy, PN; Scharnagl, H; Abdellatif, M; Oulhaj, A; Benedikt, M; Kolesnik, E; von, Lewinski, D; Sourij, H.
Ketone body levels and its associations with cardiac markers following an acute myocardial infarction: a post hoc analysis of the EMMY trial.
Cardiovasc Diabetol. 2024; 23(1): 145 Doi: 10.1186/s12933-024-02221-2 [OPEN ACCESS]
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Leading authors Med Uni Graz: Aziz Faisal; Sourij Harald; von Lewinski Dirk
Co-authors Med Uni Graz: Abdellatif Mahmoud; Benedikt Martin; Kolesnik Ewald; Pferschy Peter; Scharnagl Hubert; Tripolt Norbert
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Abstract:: BACKGROUND: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been suggested to exert cardioprotective effects in patients with heart failure, possibly by improving the metabolism of ketone bodies in the myocardium. METHODS: This post hoc analysis of the EMMY trial investigated the changes in serum β-hydroxybutyrate (3-βOHB) levels after acute myocardial infarction (AMI) in response to 26-week of Empagliflozin therapy compared to the usual post-MI treatment. In addition, the association of baseline and repeated measurements of 3-βOHB with cardiac parameters and the interaction effects of Empagliflozin were investigated. Cardiac parameters included N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), left ventricle end-systolic volume (LVESV), left ventricle end-diastolic volume (LVEDV), and left ventricular filling pressure (E/é ratio). RESULTS: The mean 3-βOHB levels increased from baseline (46.2 ± 3.0 vs. 51.7 ± 2.7) to 6 weeks (48.8 ± 2.2 vs. 42.0 ± 2.3) and 26 weeks (49.3 ± 2.2 vs. 35.8 ± 1.9) in the Empagliflozin group compared to a consistent decline in placebo over 26 weeks (p_interaction < 0.001). Baseline and longitudinal measurements of 3-βOHB were not significantly associated with NT-proBNP and E/é ratio. Baseline 3-βOHB value was negatively associated with LVEF (coefficient: - 0.464, 95%CI - 0.863;- 0.065, p = 0.023), while an increase in its levels over time was positively associated with LVEF (0.595, 0.156;1.035, 0.008). The baseline 3-βOHB was positively associated with LVESV (1.409, 0.186;2.632, 0.024) and LVEDV (0.640, - 1.170;- 2.449, 0.488), while an increase in its levels over time was negatively associated with these cardiac parameters (LVESV: - 2.099, - 3.443;- 0.755, 0.002; LVEDV: - 2.406, - 4.341;- 0.472, 0.015). Empagliflozin therapy appears to modify the association between 3-βOHB, LVEF (p_interaction = 0.090), LVESV (p_interaction = 0.134), and LVEDV (p_interaction = 0.168), particularly at 26 weeks; however, the results were not statistically significant. CONCLUSION: This post hoc analysis showed that SGLT2i increased 3-βOHB levels after AMI compared to placebo. Higher baseline 3-βOHB levels were inversely associated with cardiac function at follow-up, whereas a sustained increase in 3-βOHB levels over time improved these markers. This highlights the importance of investigating ketone body metabolism in different post-MI phases. Although more pronounced effect of 3-βOHB on cardiac markers was observed in the SGLT2i group, further research is required to explore this interaction effect.
Find related publications in this database (using NLM MeSH Indexing): Humans - administration & dosage; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use, adverse effects; Biomarkers - blood; Male - administration & dosage; Female - administration & dosage; Benzhydryl Compounds - therapeutic use; Ventricular Function, Left - drug effects; Glucosides - therapeutic use; Middle Aged - administration & dosage; Time Factors - administration & dosage; Aged - administration & dosage; Treatment Outcome - administration & dosage; Natriuretic Peptide, Brain - blood; Peptide Fragments - blood; 3-Hydroxybutyric Acid - blood; Stroke Volume - drug effects
Find related publications in this database (Keywords): SGLT2 inhibitor; Empagliflozin; Ketone body; Beta-hydroxybutyrate; 3-beta OHB; Clinical Trial