Statin uses and skeletal muscle-related phenotypes: insights from epidemiological and Mendelian randomization analyses
Bibliographic record
Abstract
Abstract Background The association between statin use and skeletal muscle-related side effects is always controversial. This study aimed to comprehensively investigate the associations between statin use and muscle-related phenotypes including sarcopenia, sarcopenic obesity, serum lactate dehydrogenase (LDH), and musculoskeletal pain symptoms among adults with indications for statin use for secondary prevention (cardiovascular disease, diabetes, or hyperlipidemia). Methods This cross-sectional study included 22,549 patients aged ≥20 years with cardiovascular disease, diabetes, or hyperlipidemia. Weighted generalized linear regression analysis and propensity score matching methods were used to estimate the associations between the use of statins or other lipid-lowering agents and skeletal muscle-related phenotypes. Mendelian randomization (MR) analysis was additionally used to verify the causal relationship between statin use and skeletal muscle-related phenotypes. Results The weighted mean age was 59 years, 50.3% were male, and 37.6% (n=8,481) received statin treatment. In the unadjusted model, compared with adults without any lipid-lowering drugs, statin use was associated with a higher likelihood of sarcopenia (appendicular skeletal muscle mass [ASM]/Body mass index [BMI] OR 1.35 (95%CI 1.12 to 1.62, p < 0.001), ASM/weight [Wt] OR 1.86 (95%CI 1.62 to 2.13, p < 0.001), max HGS β -3.01 (95% CI -3.97 to -2.06, p < 0.001), relative HGS β -0.23 (95% CI -0.30 to -0.17, p < 0.001) and combined HGS β -5.90 (95% CI -7.86 to -3.93, p < 0.001)), sarcopenic obesity (ASM/height squared [Ht 2 ] and body fat percentage definition [OR 1.36 (95% CI 1.13 to 1.63, p < 0.001]). After multivariable adjustment or propensity score match, the independent associations of statin use with sarcopenia, sarcopenic obesity, HGS, LDH, and musculoskeletal pain became nonsignificant. Stepwise regression suggested that age was the predominant confounding factor for the associations. MR analysis also revealed no significant causality between statin use and skeletal muscle-related phenotypes. Conclusions Our epidemiological and MR analyses did not support the causality between statin use and skeletal muscle-related phenotypes. A higher likelihood of skeletal muscle-related adverse phenotypes in statin users may be attributed to age. Future studies should further explore the biological factors that may affect statin-related muscle phenotypes to provide evidence for the safety of statins.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.049 | 0.104 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.003 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".