Degradation of neuromuscular junction contributes to muscle weakness but not physical compromise in chronic obstructive pulmonary disease patients taking lipids-lowering …

Abstract

The relevant data about the effects and the associated mechanisms of statins on muscle strength and physical capacity is inconsistent. We investigated the potential contribution of neuromuscular junction (NMJ) degradation to muscle weakness and physical compromise in patients with chronic obstructive pulmonary disease (COPD) on statins. We recruited male COPD patients (age range = 63–75 years, n = 150) as nonusers (n = 71) and users of statin medications (n = 79) along with age-matched controls (n = 76). The COPD patients were evaluated at baseline and one year later. The data about handgrip strength (HGS), body composition, short physical performance battery (SPPB), and plasma c-terminal agrin fragment-22 (CAF22) as a marker of NMJ disintegration was collected at two time points. We observed lower HGS, SPPB scores, and higher CAF22 levels in all COPD patients than controls, irrespective of the treatment status (all p < 0.05). Statins further reduced HGS and elevated CAF22 in COPD patients (both p < 0.05). The decline in SPPB was relatively modest in statin users (≈3.7%, p = 0.032) than in nonusers (≈8.7%, p = 0.002). The elevated plasma CAF22 exhibited robust negative correlations with a reduction in HGS but not with SPPB in COPD patients taking statins. We also found a reduction in markers of inflammation and no increase in oxidative stress markers following statin use in COPD patients. Altogether, statin-induced NMJ degradation exacerbates muscle decline but does not contribute to physical compromise in COPD patients.