The association between statins and gait speed reserve in older adults: effects of concomitant medication

Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]). However, ACE inhibitors and aspirin significantly influenced this association. The GSR difference for statin users compared to non-users increased by 3.7 cm/s (from - 2.2 to 1.5 cm/s; 95% CI, 0.0 to 7.4) with concomitant ACE inhibitor use and by 5.8 cm/s (from - 3.4 to 2.3 cm/s; 95% CI, 2.5 to 9.1) with aspirin use. We found no statistically significant association between statin use and usual gait speed, the secondary outcome. In conclusion, ACE inhibitors and aspirin interacted with statins, reversing the negative association with GSR into a positive one when co-used. Future clinical trials are needed to determine causality and further investigate the impact of concomitant medication use on statin effects in aging populations. Meanwhile, our findings underscore the importance of considering concomitant medication use when assessing the effects of statins in older adults.