Investigating the Controversy Surrounding Statin Therapy and Achilles Tendinopathy Using Mendelian Randomization Analysis

Background: The relationship between statin therapy and tendon injuries, particularly Achilles tendinopathy, which is the body's largest and strongest tendon, remains controversial.

Aim: This study employed Mendelian Randomization (MR) analysis to explore the causal link between statin therapy and Achilles tendinopathy (ATP).

Method: Summary statistics were obtained from genome-wide association studies on statin medication and four specific statin drugs from public databases, as well as data related to two ATP phenotypes, namely Achilles tendinitis and Achilles tendon injury. Furthermore, a two-sample bidirectional MR analysis was conducted to investigate the association between statin therapy and ATP. The primary method used was the inverse variance weighted (IVW) method, supplemented by four other validation methods. Heterogeneity analysis, pleiotropy assessment, and leave-one-out sensitivity analysis were further conducted to validate the robustness of the results.

Results: Based on our comprehensive investigation, all MR analyses in this study found no significant causal relationship between statin therapy and ATP (IVW, p > 0.05). Notably, the MR findings regarding pravastatin, rosuvastatin, and ATP were limited by a small pool of instrumental variables, necessitating further research. Moreover, no association was observed between the two in the reverse MR analysis (IVW, p > 0.05). All results passed heterogeneity tests, pleiotropy tests, and sensitivity analyses.

Conclusion: Our results do not establish a causal connection between statin therapy and ATP, indicating that individuals with ATP should consider alternative pathogenic contributors. Moreover, these findings highlight the safety profile of statin medications.