Association between statin use and longitudinal changes in skeletal muscle mass: A population-based cohort study

Statins are widely prescribed for cardiovascular risk reduction, yet concerns remain regarding their effects on skeletal muscle. Evidence on the longitudinal relationship between statin use and muscle mass remains inconsistent, particularly in population-based settings. Therefore, this study investigated the longitudinal association between statin use and changes in total and region-specific skeletal muscle mass in a population-based adult cohort. This single-center retrospective cohort study analyzed adults with repeated health examinations from 2021 to 2023. Skeletal muscle mass was assessed using bioelectrical impedance analysis, including upper limb lean mass (ULM), lower limb lean mass (LLM), appendicular lean mass (ALM), and skeletal muscle index (SMI). Statin use was determined from medical records and self-reported medication histories. Linear mixed-effects models with random intercepts helped evaluate longitudinal changes in muscle mass according to statin use. Models were sequentially adjusted for age and sex, and further for body mass index and diabetes mellitus. Among 2,300 participants, 334 (14.5%) were continuous statin users, who were older and had a higher prevalence of metabolic comorbidities than non-users. In unadjusted analyses, statin users exhibited significantly greater declines in LLM and ALM than non-users. These differences remained significant after adjustment for age and sex. However, after further adjustment for body mass index and diabetes mellitus, associations between statin use and changes in all muscle mass indices were no longer significant. No significant differences were observed for ULM or SMI in any model. In this longitudinal cohort, statin use was not independently associated with accelerated skeletal muscle mass decline after adjustment for key metabolic confounders. These findings suggest that underlying metabolic and clinical characteristics, rather than statin exposure, may play a more important role in longitudinal muscle mass changes.