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.
Highlights
Accurate predictors of cardio-metabolic diseases can contribute substantially to their prevention and provide the possibility for interventions aiming to avoid or delay their onset [1]
Several metabolomics-based studies have contributed to a better understanding of the metabolic changes that occur in heart failure and ischemic heart disease, and have identified new molecular markers and metabolic signatures of cardiovascular disease (CVD) risk [3,4]
Our study provided some novel findings, adding further evidence on the significance of serum acylcarnitines for the prediction of coronary artery disease (CAD) progression
Summary
Accurate predictors of cardio-metabolic diseases can contribute substantially to their prevention and provide the possibility for interventions aiming to avoid or delay their onset [1]. Such biomarkers can be timely recognized since metabolic perturbations. State of the art metabolomics technologies have the ability to monitor subtle changes in the metabolome that occur prior to the phenotypic changes reflecting the disease [2] These technologies have been recently proved capable of identifying sensitive biomarkers for the early detection or prevention of adverse cardiovascular events. Blood acylcarnitine levels are considered to be characteristic biomarkers describing the composition of cytoplasmic acylcarnitines in many severe pathological conditions such as CAD [11], heart failure [14], type 1 and 2 DM [15], as well as hereditary mitochondrial fatty acid (FA)
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