Serum Acylcarnitines and Risk of Cardiovascular Death and Acute Myocardial Infarction in Patients With Stable Angina Pectoris

Abstract

BackgroundExcess levels of serum acylcarnitines, which are intermediate products in metabolism, have been observed in metabolic diseases such as type 2 diabetes mellitus. However, it is not known whether acylcarnitines may prospectively predict risk of cardiovascular death or acute myocardial infarction in patients with stable angina pectoris.Methods and ResultsThis study included 4164 patients (median age, 62 years; 72% men). Baseline serum acetyl‐, octanoyl‐, palmitoyl‐, propionyl‐, and (iso)valerylcarnitine were measured using liquid chromatography/tandem mass spectrometry. Hazard ratios (HRs) and 95% CIs for quartile 4 versus quartile 1 are reported. The multivariable model included age, sex, body mass index, fasting status, current smoking, diabetes mellitus, apolipoprotein A1, apolipoprotein B, creatinine, left ventricular ejection fraction, extent of coronary artery disease, study center, and intervention with folic acid or vitamin B6. During median 10.2 years of follow‐up, 10.0% of the patients died of cardiovascular disease and 12.8% suffered a fatal or nonfatal acute myocardial infarction. Higher levels of the even‐chained acetyl‐, octanoyl‐, and palmitoyl‐carnitines were significantly associated with elevated risk of cardiovascular death, also after multivariable adjustments (HR [95% CI]: 1.52 [1.12, 2.06]; P=0.007; 1.73 [1.23, 2.44]; P=0.002; and 1.61 [1.18, 2.21]; P=0.003, respectively), whereas their associations with acute myocardial infarction were less consistent.ConclusionsAmong patients with suspected stable angina pectoris, elevated serum even‐chained acylcarnitines were associated with increased risk of cardiovascular death and, to a lesser degree with acute myocardial infarction, independent of traditional risk factors.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00354081.

Untargeted high-resolution plasma metabolomic profiling predicts outcomes in patients with coronary artery disease

“…Acylcarnitines are lipid intermediates that shuttle fatty acids into mitochondria for β-oxidation, [43] and several prior studies have demonstrated that impaired carnitine shuttle function and elevated acylcarnitine levels predict adverse cardiovascular outcomes and death in CAD patients. [44][45][46][47] We were able to validate these findings in our cohort in addition to other novel metabolites.…”

High-coverage plasma lipidomics reveals novel sex-specific lipidomic fingerprints of age and BMI: Evidence from two large population cohort studies

“…In a mice model, Bodil and colleagues have reported an increase in plasma acylcarnitine levels caused by inhibition of mitochondrial fatty acid oxidation [ 42 ]. In clinical studies, elevated plasma acylcarnitine levels have been shown to be associated with age-related cardiometabolic conditions such as the risk of T2D and CVD, independently of age [ 43 – 46 ]. Notwithstanding these observations, other explanations are possible, and further studies are required to validate our findings.…”

Dissecting Cellular Mechanisms of Long-Chain Acylcarnitines-Driven Cardiotoxicity: Disturbance of Calcium Homeostasis, Activation of Ca2+-Dependent Phospholipases, and Mitochondrial Energetics Collapse

“…According to recent data, serum LCAC represents an independent risk factor of acute myocardial infarction in patients with angina pectoris, etc. [ 62 ]. Mitochondria isolated from ischemic areas of myocardium accumulate LCAC and respective long-chain acyl-CoA, which are known to suppress oxidative phosphorylation [ 15 ].…”