To the Editor,
We read with interest the article by Mert Er et al., “Physical activity and quality of life in statin users,”. The topic is clinically important given persistent concerns regarding statin-associated muscle symptoms (SAMS) and their potential impact on adherence and lifestyle behaviors. However, several conceptual and methodological considerations warrant closer examination.
The cross-sectional design substantially limits causal inference. Without pre-treatment baseline assessment or longitudinal follow-up, reduced physical activity or impaired quality of life cannot be confidently attributed to statin exposure rather than underlying cardiovascular risk, multimorbidity, or pre-existing functional limitations.
The study appears to rely predominantly on self-reported symptoms and physical activity. This is particularly relevant in the context of the well-documented nocebo effect in statin therapy. Randomized N-of-1 trials such as SAMSON and StatinWISE demonstrated that the majority of reported muscle symptoms during statin therapy were similarly reproduced with placebo, suggesting expectation-driven symptom attribution rather than pharmacologic causality. Failure to account for this phenomenon risks overestimating statin-related functional impairment.
The diagnostic framework for SAMS requires greater clarity. Contemporary consensus statements emphasize criteria such as temporal relationship to initiation, resolution on challenges recurrence on rechallenge, and creatine kinase evaluation. Without standardized SAMS diagnostic criteria, nonspecific musculoskeletal complaints may be misclassified as statin-induced, thereby biasing associations with reduced activity levels.
Furthermore, insufficient stratification by statin type, dose intensity, and treatment duration limits interpretability. Lipophilic versus hydrophilic statins may differ in tolerability profiles, and absence of such subgroup analyses may mask heterogeneity.
Finally, robust multivariable modeling is essential. Depression, frailty, obesity, diabetes, polypharmacy, and baseline sedentary behavior independently influence quality of life and activity patterns. Without comprehensive adjustment, residual confounding remains likely.
Given the substantial public health consequences of statin discontinuation, caution is warranted in drawing conclusions that may inadvertently reinforce nocebo-driven perceptions. Prospective designs incorporating standardized SAMS assessment, objective physical activity monitoring (e.g., accelerometry), and blinded rechallenge paradigms would more definitively clarify whether statins independently impair physical activity or quality of life.
Author Contributions
Credit: Vimal Tyagi (PhD Scholar) drafting of the manuscript; Critical review of the manuscript for important intellectual content.
Dr. Sajjan Pal contributed crucial Intellectual input, Supervision, and Article Correction.
Disclosure Statement
No potential conflicts of interest was reported by the author(s).
References
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