Risk of Sarcopenia Following Long-Term Statin Use in Community-Dwelling Middle-Aged and Older Adults in Japan

Background: Inconsistent results have been reported concerning the association between statin administration and muscle health, specifically its potential to increase the risk of sarcopenia. Given the widespread long-term use of statins among the elderly population, the exploration of this association remains a crucial yet insufficiently examined matter. This study aimed to assess the association between the prolonged administration of statins and the risk of sarcopenia, diminished muscle strength, reduced skeletal muscle mass and impaired physical performance.

Methods: This population-based cohort study was conducted in Japan utilizing data derived from the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA). The study participants, enlisted from the 2nd to the 6th waves (spanning from April 2000 to July 2010) of NILS-LSA, were those who aged 40 years or older and had initiated statin therapy (n = 348, age: 64.1 years, female: 63.5%). Individuals who were not administered statins (n = 2559, age: 55.5 years, female: 48.4%) were arbitrarily chosen using a combined approach of propensity score (PS) matching and risk set sampling to form the control group (with a 1:4 matching ratio). The primary outcome of this study was the occurrence of sarcopenia, as defined by the 2019 consensus of the Asian Working Group for Sarcopenia (AWGS). The secondary outcomes included low muscle mass (< 7.0 kg/m² for men and below 5.4 kg/m² for women by DXA), reduced skeletal muscle strength (handgrip strength < 28 kg in men and < 18 kg in women) and subpar physical performance (6-min walking speed < 1.0 m/s). The relationship between the use of statins and the outcomes was estimated using a Cox proportional hazard model with time-varying covariates, which included the status of statin use and other variables (two-tailed p < 0.05 was considered statistically significant). Stratification based on age and sex, along with five sensitivity analyses-including propensity score overlap weighting and a negative control-was conducted.

Results: After applying PS matching, we identified 342 statin initiators and 1294 non-statin users, with well-balanced baseline characteristics between the groups. The use of statins was not associated with an increased risk of incident sarcopenia (adjusted hazard ratio [aHR], 1.43 [95% CI, 0.86, 2.36]), diminished muscle strength (aHR, 1.11 [95% CI, 0.80, 1.54]), reduced muscle mass (aHR, 1.09 [95% CI, 0.66, 1.82]) or impaired physical performance (aHR, 0.73 [95% CI, 0.46, 1.17]). These findings were consistent across age and sex stratifications, as well as all sensitivity analyses.

Conclusions: Statin use was not associated with an elevated risk of sarcopenia or impaired muscle health among community-dwelling middle-aged and older adults in Japan.