循环酮体与 ST 段抬高型心肌梗死患者功能结局的关系。

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

机构信息

Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

出版信息

J Am Coll Cardiol. 2021 Oct 5;78(14):1421-1432. doi: 10.1016/j.jacc.2021.07.054.

DOI:10.1016/j.jacc.2021.07.054

PMID:34593124

Abstract

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).

摘要

背景

心力衰竭（HF）患者的循环酮体（KBs）增加，相应地，心脏 KB 代谢和 HF 严重程度也增加。然而，循环 KBs 在缺血/再灌注中的作用尚不清楚。

目的

本研究旨在探讨 ST 段抬高型心肌梗死（STEMI）患者中循环 KBs 的纵向变化及其与功能结局的关系。

方法

对一项关于 STEMI 后早期二甲双胍治疗的随机试验中的 369 名参与者进行了 KB 测量。通过磁共振波谱法在发病时、24 小时和 4 个月时测量非空腹状态下的 KBs（β-羟丁酸、乙酰乙酸和丙酮）浓度。在 4 个月时通过心脏磁共振成像确定心肌梗死面积和左心室射血分数（LVEF）。使用多变量线性回归分析来确定循环 KBs 与梗死面积和 LVEF 的关系。

结果

STEMI 患者发病时循环 KBs 水平较高（中位总 KBs：520μmol/L；四分位间距[IQR]：315-997μmol/L）。再灌注后 24 小时，KBs 水平仍高于 4 个月随访时的水平（206μmol/L[IQR：174-246]与 166μmol/L[IQR：143-201]；P<0.001）。24 小时 KB 浓度升高与更大的心肌梗死面积独立相关（每 100μmol/L 总 KBs：β=1.56；95%置信区间：0.29-2.83；P=0.016）和较低的 LVEF（β=-1.78；95%CI：-3.17 至-0.39；P=0.012）。

结论

STEMI 患者的循环 KBs 增加。24 小时时更高的 KBs 与 STEMI 后的功能结局相关，这表明酮体代谢在心肌缺血反应中可能发挥作用。（二甲双胍代谢调节以减少急性心肌梗死后心力衰竭：糖代谢干预作为 ST 段抬高型心肌梗死的辅助治疗（GIPS-III）：一项随机对照试验；NCT01217307）。