The improvement in muscle function following statin withdrawal might involve the repair of the neuromuscular junction

AIMS: The effects and relative mechanisms of statin usage and withdrawal on subjective and objective muscle functions are poorly known. We investigated the associations of neuromuscular junction (NMJ) degradation to muscle impairment in older adults taking statins. METHODS: We recruited male controls (n = 82) and statin users (n = 76) for measuring handgrip strength (HGS), body composition, gait speed, short physical performance battery (SPPB), statin-associated muscle symptoms (SAMS) and plasma c-terminal agrin fragment-22 (CAF22; a marker of NMJ degradation). The statin users were evaluated at baseline, 1 year after statin usage and 6 months after statin withdrawal. RESULTS: One year of statin usage was associated with lower HGS, gait speed, SPPB scores and higher SAMS scores and plasma CAF22 levels (all P < .05). Conversely, 6 months after statin withdrawal, gait speed and SPPB scores were restored with a concurrent reduction in SAMS and CAF22 levels (all P < .05). Correlation analysis revealed significant correlations of plasma CAF22 with HGS, SPPB and SAMS after statin usage and withdrawal (all P < .05). Lastly, statin withdrawal also reduced the plasma creatine kinase levels (P < .05). CONCLUSION: Altogether, statin usage was associated with muscle and physical decline and an increase in CAF22 and SAMS, which were partly restored after statin withdrawal. Our findings suggest a role for NMJ plasticity in muscle restoration following statin withdrawal.