Association of carnitine insufficiency with sarcopenia and dynapenia in patients with heart failure

Abstract

Aim L‐carnitine transports fatty acids into mitochondria and contributes to energy metabolism in skeletal muscles. However, the association between carnitine insufficiency and skeletal muscle weakness, namely sarcopenia and dynapenia, in patients with heart failure (HF) remains unclear. Methods In total, 124 patients with HF were enrolled in this study. Carnitine insufficiency was indicated by a decrease in serum free carnitine (FC) levels of less than 36 μmol/L or an elevated serum acylcarnitine (AC) to free carnitine (FC) ratio (AC/FC ratio) of 0.27 or higher. Skeletal muscle weakness was defined as reduced handgrip strength and classified into two phenotypes: sarcopenia (low muscle strength with low skeletal muscle mass) and dynapenia (low muscle strength with normal skeletal muscle mass). Results Patients with carnitine insufficiency had a significantly higher prevalence of muscle weakness and a lower 6‐min walk distance than those without carnitine insufficiency (P < 0.05). A machine learning model showed that older age (≥77 years) and, in patients aged 64–76 years, a higher AC/FC ratio (≥0.31) were associated with sarcopenia. However, there was only a week association between carnitine levels and dynapenia. The effect of carnitine insufficiency on skeletal muscle weakness was greater in patients with low skeletal muscle mass than in those with normal skeletal muscle mass (P < 0.05 for interaction). Conclusions Carnitine insufficiency is more closely associated with sarcopenia than with dynapenia in patients with HF, suggesting carnitine insufficiency as a potential therapeutic target for sarcopenia in these patients. Geriatr Gerontol Int 2023; 23: 524–530.

Pathophysiological roles of the serum acylcarnitine level and acylcarnitine/free carnitine ratio in patients with cardiovascular diseases

“…Serum AC might contribute to the worsening of HF through the promotion of arrhythmias, insulin resistance, adverse remodeling, and reduced energy production [19] . Previous studies have reported an association between the AC/FC and cardiac events in patients with HF, suggesting that the AC/FC may increase in patients with HF due to mitochondrial dysfunction, which is associated with impaired energy metabolism [13] , [14] . Yoshihisa et al [13] reported that patients with HF with an AC/FC ≥ 0.27 had the highest rate of cardiac events, including cardiac death and HF progression, and the AC/FC was a predictor of cardiac events.…”

“…Yoshihisa et al [13] reported that patients with HF with an AC/FC ≥ 0.27 had the highest rate of cardiac events, including cardiac death and HF progression, and the AC/FC was a predictor of cardiac events. Also, Kinugasa et al [14] found that in patients with HF, sarcopenia was associated with older age (>77 years) and a high AC/FC (>0.31) in patients aged 64–76 years, suggesting that carnitine deficiency is a potential therapeutic target against sarcopenia in patients with HF. The present study showed that the serum AC concentration, but not the AC/FC, is associated with echocardiographic findings and BNP in male patients undergoing cardiac surgery.…”

“…Diagnostic methods for carnitine deficiency include the liquid chromatography-mass spectrometry (LC-MS) detection and enzymatic cycling methods. While the LC-MS detection method is essential for the definitive diagnosis of congenital metabolic disorders [11] , the enzyme cycling method is an alternative method for follow-up, and in most cases, the enzyme cycling method is considered a viable alternative for the diagnosis of carnitine deficiency due to other causes [12] , [13] , [14] .…”