Statin Use Is Associated With a Decline in Muscle Function and Mass Over Time, Irrespective of Statin Pharmacogenomic Score.

BACKGROUND: Statins are cholesterol-lowering drugs widely prescribed for preventing cardiovascular diseases. They may cause adverse effects on skeletal muscle, but it remains unclear whether they affect muscle function and mass. We aimed to evaluate the association between statin use and muscle function and mass, and whether the pharmacogenomic score (PGS) of statin response modifies these associations. METHODS: We included 297 977 participants from the UK Biobank. Grip strength was measured using a Jamar J00105 hydraulic hand dynamometer, and the appendicular lean mass (ALM) was estimated using bioelectrical impedance analysis. We performed linear regression to evaluate the cross-sectional and longitudinal associations between statin use and (changes in) grip strength or ALM, adjusting for demographic, lifestyle and health factors. We tested the interaction with the PGS and stratified the analysis by PGS tertile. RESULTS: Participants averaged 56.4 (± 8) years, and 46% were male. Statin use was associated with lower baseline grip strength (β = -0.68 kg [-0.89, -0.48]) and ALM (β = -0.19 kg [-0.22, -0.16]). Among 35 557 participants with follow-up data (10 ± 5 years), continuous statin use was associated with an accelerated decline in grip strength (β = -0.32 kg/year [-0.49, -0.14]) and ALM (β = -0.06 kg/year [-0.08, -0.03]) compared with never users. The PGS showed a potential modifying effect at baseline (p = 0.058 for grip strength and p = 0.068 for ALM) but did not significantly influence the rate of decline over time. CONCLUSIONS: Continuous statin use is associated with a decline in muscle function and mass over time (25% decline in grip strength and 73% decline in ALM compared to never-users), irrespective of genetic susceptibility to statin response. This study emphasizes the importance of monitoring musculoskeletal health in statin users and supports further research into the potential role of a healthy diet and regular physical activity in preserving muscle function, which may also reinforce the cardiovascular benefits of statin therapy.