Short and medium chain acylcarnitines as markers of outcome in diabetic and non-diabetic subjects with acute coronary syndromes

Allan Davies; Florian A Wenzl; Xinmin S Li; Patric Winzap; Slayman Obeid; Roland Klingenberg; François Mach; Lorenz Räber; Olivier Muller; Christian M Matter; Reijo Laaksonen; Zeneng Wang; Stanley L Hazen; Thomas F Lüscher

doi:10.1016/j.ijcard.2023.131261

Short and medium chain acylcarnitines as markers of outcome in diabetic and non-diabetic subjects with acute coronary syndromes

Int J Cardiol. 2023 Oct 15:389:131261. doi: 10.1016/j.ijcard.2023.131261. Epub 2023 Aug 11.

Authors

Affiliations

¹ Royal Brompton and Harefield Hospitals, London, UK.
² Center for Molecular Cardiology, University of Zurich, Switzerland.
³ Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
⁴ Division of Cardiology, Department of Medicine, Aarau Cantonal Hospital, Aarau, Switzerland; Herzklinik Kreuzlingen, Kreuzlingen, Switzerland.
⁵ Kerckhoff Heart and Thorax Center, Department of Cardiology, Kerckhoff-Klinik, Bad Nauheim, Germany; Campus of the Justus Liebig University of Giessen, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Bad Nauheim, Germany.
⁶ Department of Cardiology, Hopital Universitaire de Geneve, Switzerland.
⁷ Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland.
⁸ Department of Cardiology, University Hospital of Lausanne, Lausanne, Switzerland.
⁹ University Heart Center, Cardiology, University Hospital Zurich, Zurich, Switzerland.
¹⁰ Zora Biosciences Oy, Espoo, Finland; Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Faculty of Medicine and Health Technology, Finnish Cardiovascular Research Center Tampere, Tampere University, Tampere, Finland.
¹¹ Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA.
¹² Royal Brompton and Harefield Hospitals, London, UK; Center for Molecular Cardiology, University of Zurich, Switzerland; National Heart and Lung Institute, Imperial College, London, UK; School of Cardiovascular Medicine and Sciences, Kings College London, London, UK. Electronic address: cardio@tomluescher.ch.

PMID: 37574027
DOI: 10.1016/j.ijcard.2023.131261

Abstract

Background: Carnitine metabolism produces numerous molecular species of short-, medium-, and long-chain acylcarnitines, which play important roles in energy homeostasis and fatty acid transport in the myocardium. Given that disturbances in the carnitine metabolism are linked to cardiometabolic disease, we studied the relationship of circulating acylcarnitines with outcomes in patients with acute coronary syndromes (ACS) and evaluated differences in circulating levels of these metabolites between diabetic and non-diabetic patients.

Methods: Harnessing a prospective multicentre cohort study (SPUM-ACS; NCT01000701), we measured plasma levels of acylcarnitines, carnitine, and carnitine metabolites to assess their relationship with adjudicated major adverse cardiac events (MACE), defined as composite of myocardial infarction, stroke, clinically indicated revascularization, or death of any cause. The SPUM-ACS study enrolled patients presenting with ACS to Swiss University Hospitals between 2009 and 2012. Acetylcarnitine, octanoylcarnitine, proprionylcarnitine, butyrylcarnitine, pentanoylcarnitine, hexanoylcarnitine, carnitine, γ-butyrobetaine, and trimethylamine N-oxide were measured in plasma using stable isotope dilution high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry.

Results: A total of 1683 patients with ACS were included in the study. All measured metabolites except γ-butyrobetaine and carnitine were higher in diabetic subject (n = 294) than in non-diabetic subjects (n = 1389). On univariate analysis, all metabolites, apart from octenoylcarnitine, were significantly associated with MACE at 1 year. After multivariable adjustment for established risk factors, acetylcarnitine remained an independent predictor of MACE at 1-year (quartile 4 vs. quartile 1, adjusted hazard ratio 2.06; 95% confidence interval 1.12-3.80, P = 0.020).

Conclusion: Circulating levels of acetylcarnitine independently predict residual cardiovascular risk in patients with ACS.

Keywords: Acute coronary syndromes; Diabetes; Microbiome; Mortality; Risk prediction - major cardiovascular and cerebrovascular events.

MeSH terms

Acetylcarnitine
Acute Coronary Syndrome* / diagnosis
Carnitine
Clinical Studies as Topic
Cohort Studies
Diabetes Mellitus* / diagnosis
Diabetes Mellitus* / epidemiology
Humans
Multicenter Studies as Topic
Prospective Studies

Substances

Acetylcarnitine
acylcarnitine
Carnitine
gamma-butyrobetaine

Associated data

ClinicalTrials.gov/NCT01000701