Association of Circulating Ketone Bodies With Functional Outcomes After ST-Segment Elevation Myocardial Infarction

• Published in: Journal of the American College of Cardiology 2021-10, Vol.78 (14), p.1421-1432
• Main Authors: de Koning, Marie-Sophie L Y, Westenbrink, B Daan, Assa, Solmaz, Garcia, Erwin, Connelly, Margery A, van Veldhuisen, Dirk J, Dullaart, Robin P F, Lipsic, Erik, van der Harst, Pim
• Format: Article
• Language: English
• Subjects: Aged; Biomarkers - blood; Female; Humans; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Ketone Bodies - blood; Male; Metformin - pharmacology; Metformin - therapeutic use; Middle Aged; Myocardium - pathology; Natriuretic Peptide, Brain - blood; Peptide Fragments - blood; Recovery of Function; ST Elevation Myocardial Infarction - blood; ST Elevation Myocardial Infarction - drug therapy; ST Elevation Myocardial Infarction - pathology; Stroke Volume - drug effects
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2021.07.054

Circulating ketone bodies (KBs) are increased in patients with heart failure (HF), corresponding with increased cardiac KB metabolism and HF severity. However, the role of circulating KBs in ischemia/reperfusion remains unknown. This study sought to investigate longitudinal changes of KBs and their associations with functional outcomes in patients presenting with ST-segment elevation myocardial infarction (STEMI). KBs were measured in 369 participants from a randomized trial on early metformin therapy after STEMI. Nonfasting plasma concentrations of KBs (β-hydroxybutyrate, acetoacetate, and acetone) were measured by nuclear magnetic resonance spectroscopy at presentation, at 24 hours, and after 4 months. Myocardial infarct size and left ventricular ejection fraction (LVEF) were determined by cardiac magnetic resonance imaging at 4 months. Associations of circulating KBs with infarct size and LVEF were determined using multivariable linear regression analyses. Circulating KBs were high at presentation with STEMI (median total KBs: 520 μmol/L; interquartile range [IQR]: 315-997 μmol/L). At 24 hours after reperfusion, KBs were still high compared with levels at 4-month follow-up (206 μmol/L [IQR: 174-246] vs 166 μmol/L [IQR: 143-201], respectively; P < 0.001). Increased KB concentrations at 24 hours were independently associated with larger myocardial infarct size (total KBs, per 100 μmol/L: β = 1.56; 95% confidence interval: 0.29-2.83; P = 0.016) and lower LVEF (β = -1.78; 95% CI: (-3.17 to -0.39; P = 0.012). Circulating KBs are increased in patients presenting with STEMI. Higher KBs at 24 hours are associated with functional outcomes after STEMI, which suggests a potential role for ketone metabolism in response to myocardial ischemia. (Metabolic Modulation With Metformin to Reduce Heart Failure After Acute Myocardial Infarction: Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III): a Randomized Controlled Trial; NCT01217307).