TY - JOUR
T1 - Association of Circulating Ketone Bodies With Functional Outcomes After ST-Segment Elevation Myocardial Infarction
AU - de Koning, Marie-Sophie L Y
AU - Westenbrink, B Daan
AU - Assa, Solmaz
AU - Garcia, Erwin
AU - Connelly, Margery A
AU - van Veldhuisen, Dirk J
AU - Dullaart, Robin P F
AU - Lipsic, Erik
AU - van der Harst, Pim
N1 - Funding Information:
The GIPS-III trial was supported by grant 95103007 from the Netherlands Organization for Health Research and Development (ZonMw), The Hague, the Netherlands. Dr Westenbrink was supported by The Netherlands Organisation for Scientific Research (NWO VENI, grant 016.176.147) and the Netherlands Heart Foundation Senior Clinical Scientist Grant (2019T064), The Hague, the Netherlands. Drs Garcia and Connelly are employees of LabCorp. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Publisher Copyright:
© 2021 The Authors
PY - 2021/10/5
Y1 - 2021/10/5
N2 - BACKGROUND: 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.OBJECTIVES: 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).METHODS: 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.RESULTS: 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).CONCLUSIONS: 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).
AB - BACKGROUND: 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.OBJECTIVES: 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).METHODS: 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.RESULTS: 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).CONCLUSIONS: 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).
KW - ischemia/reperfusion
KW - ketone bodies
KW - metabolism
KW - metformin
KW - myocardial infarction
UR - http://www.scopus.com/inward/record.url?scp=85115151046&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2021.07.054
DO - 10.1016/j.jacc.2021.07.054
M3 - Article
C2 - 34593124
SN - 0735-1097
VL - 78
SP - 1421
EP - 1432
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 14
ER -