Correlation of Serum Acylcarnitines with Clinical Presentation and Severity of Coronary Artery Disease

Abstract

Recent studies support that acylcarnitines exert a significant role in cardiovascular disease development and progression. The aim of this metabolomics-based study was to investigate the association of serum acylcarnitine levels with coronary artery disease (CAD) severity, as assessed via SYNTAX Score. Within the context of the prospective CorLipid trial (NCT04580173), the levels of 13 circulating acylcarnitines were accurately determined through a newly developed HILIC-MS/MS method in 958 patients undergoing coronary angiography in the AHEPA University Hospital of Thessaloniki, Greece. Patients presenting with acute coronary syndrome had significantly lower median acylcarnitine C8, C10, C16, C18:1 and C18:2 values, compared to patients with chronic coronary syndrome (p = 0.012, 0.007, 0.018, 0.011 and <0.001, respectively). Among CAD subgroups, median C5 levels were significantly decreased in unstable angina compared to STEMI (p = 0.026), while median C10, C16, C18:1 and C18:2 levels were higher in stable angina compared to STEMI (p = 0.019 p = 0.012, p = 0.013 and p < 0.001, respectively). Moreover, median C2, C3, C4 and C8 levels were significantly elevated in patients with diabetes mellitus (p < 0.001, <0.001, 0.029 and 0.011, respectively). Moreover, short-chain acylcarnitine C2, C4, C5 and C6 levels were elevated in patients with heavier calcification and lower left ventricular ejection fraction (LVEF) % (all p-values less than 0.05). With regard to CAD severity, median C4 and C5 levels were elevated and C16 and C18:2 levels were reduced in the high CAD complexity group with SYNTAX Score > 22 (p = 0.002, 0.024, 0.044 and 0.012, respectively), indicating a potential prognostic capability of those metabolites and of the ratio C4/C18:2 for the prediction of CAD severity. In conclusion, serum acylcarnitines could serve as clinically useful biomarkers leading to a more individualized management of patients with CAD, once further clinically oriented metabolomics-based studies provide similar evidence.

Keywords: CAD; CVD; HILIC; LC-MS; SYNTAX Score; acylcarnitines; cardiovascular disease; carnitine; coronary artery disease; diabetes mellitus; metabolic profiling; serum.

Figure 1

(A) Box plot with the respective medians for each of the important acylcarnitines for the CAD groups, (B) Box plot with the respective medians for each of the important acylcarnitines for the CAD groups in DM and non-DM patients, (C) ACS vs. CCS 2-D log scaled plots for C5, C8, C10, C16, C18:1, and C18:2 level distributions.

Figure 2

(A) SS Groups, log10 scaled 2-D plots for C4, C5, C16, and C18:2 level distributions. (B) Bar plots with the respective medians for each of the important acylcarnitines for the SS groups. (C) Log10 scaled grouped box plots with the respective medians for the C4/C18:2 carnitine ratio in each of the CAD groups for all three SS groups. (D) Linear relationship of the C4/C18:2 ratio to the continuous SS as identified by the linear regression model presented in text. (E) ROC analysis of the C4/C18:2 ratio for high risk SS Group > 22.