At present, the diagnosis of atrial fibrillation mainly relies on conventional electrocardiogram and ambulatory electrocardiogram, and there are no clear biochemical predictors. The search for new biomarkers is of great clinical importance for the early diagnosis of atrial fibrillation and the prediction of its occurrence. In recent years, more and more small molecule metabolites have been detected in the development of cardiovascular diseases, namely the so-called metabolomics[5]. Carnitine has been extensively tested and analyzed as an indicator of metabolic disorders in various diseases, and studies have confirmed that short-, medium- and long-chain acylcarnitine averages are associated with increased risk of cardiovascular death and acute myocardial infarction[6]. Circulating levels of long-chain acylcarnitine are also associated with maladaptive left ventricular remodeling[7]. With the application of metabolomics in atrial fibrillation, Alonso et al.[8] found that eight metabolites were significantly associated with the risk of atrial fibrillation, in addition to several studies comparing the metabolomic profile of patients with atrial fibrillation with that of controls without atrial fibrillation[9, 10] However, whether carnitine levels are associated with the development of AF remains controversial.
In this study, we found that plasma free carnitine CO and a total of nine other carnitine levels were significantly higher in patients with atrial fibrillation than in the non-atrial fibrillation group, with free carnitine CO being an independent correlate of atrial fibrillation, suggesting that our dynamic monitoring of changes in plasma carnitine levels in patients, especially free carnitine CO, has some value in predicting atrial fibrillation. This is similar to Smith et al.[11] study, which found that altered carnitine metabolism was associated with an increased risk of AF.[12] Seo et al. found that medium-chain acylcarnitine was associated with cardiogenic stroke, which may be caused mainly by atrial fibrillation. harskamp et al.[13] In a 2.8-year follow-up of 1892 patients who underwent coronary angiography, a total of 233 cases developed atrial fibrillation during follow-up. Increased peripheral blood carnitine levels were associated with new-onset atrial fibrillation in patients with atrial fibrillation compared with patients without atrial fibrillation, suggesting that carnitine metabolism is altered several years before the onset of atrial fibrillation and that metabolic disturbances that occur years before the diagnosis of atrial fibrillation may be a target for future medical or lifestyle interventions.
L-carnitine is present in the body as a transporter of energy substances and is an important component in the beta-oxidation of fatty acids in mitochondria.[3, 14] L-carnitine has been shown to promote mitochondrial β-oxidation, triggering cardioprotection by reducing oxidative stress, inflammation and necrosis in cardiomyocytes[15]. Free carnitine may contribute to the development of arrhythmias by affecting oxidative stress and cell membrane stability in cardiac myocytes[16]L-carnitine is divided into free carnitine and acyl carnitine based on whether it is bound to fatty acids, and free carnitine is bound to fatty acids to form acyl carnitine.[17] The free carnitine combines with fatty acids to form acylcarnitine. Changes in circulating carnitine levels are considered to be indirect evidence of altered mitochondrial metabolism, and accumulation of carnitine can be considered a marker of poor metabolic status[3]. Under physiological conditions, cardiomyocyte energy produced in mitochondria is derived mainly from free fatty acids (60%) and to a lesser extent from carbohydrates (35%), amino acids and ketone bodies (5%)[13]. In atrial fibrillation, stress cardiomyocytes shift from a fatty acid-dominated metabolism to a more glycolytic state or protein and amino acid metabolism[13, 18] The decrease in fatty acid metabolism leads to the accumulation of free carnitine, which may explain the elevated plasma carnitine levels in patients with atrial fibrillation.
We also found that plasma levels of acetylcarnitine C2 and a total of four other carnitines, all of which were acylcarnitines, were significantly higher in patients in the persistent AF group than in the paroxysmal AF group. Although different from Lind et al.[19] s study found that increased plasma levels of acylcarnitine were associated with paroxysmal AF, but all suggest that there are metabolic differences in acylcarnitine in patients with different types of AF.
Based on the correlation between carnitine and atrial fibrillation, Dastan et al.[20] by evaluating the effect of carnitine administration on atrial fibrillation after coronary artery bypass grafting (CABG), found that L-carnitine given before CABG reduced the incidence of atrial fibrillation after CABG. Similarly Shingu et al.[21] found by retrospective analysis of 30 patients undergoing aortic valve surgery that the incidence of postoperative atrial fibrillation was significantly lower in 15 patients who received oral levocarnitine for 9 days (daily dose of 3 g) than in the control group (20% and 60%, respectively; P = 0.025). However, some studies have reached the opposite conclusion, Ko et al.[22] concluded that plasma metabolites did not significantly correlate with the risk of new-onset AF by following 2458 subjects for 10 years. Since patients with atrial fibrillation often take drugs that may have an impact on metabolomics, for example, when patients with atrial fibrillation are often combined with hypertension for anti-hypertensive therapy, the application of lipid-lowering drugs can affect metabolites and the risk of developing atrial fibrillation[22] In addition, some carnitine has been found to be associated with visceral obesity[23], and intentional weight loss can affect blood carnitine levels[24], making such studies difficult to interpret.