Factors associated with creatine kinase variability among statin users in routine outpatient care: a retrospective cross-sectional study

Background Statin therapy is frequently associated with concerns regarding creatine kinase (CK) elevation and potential muscle toxicity. Although clinically significant statin-associated muscle injury is uncommon, the interpretation of routine CK variability during outpatient statin therapy remains uncertain. Objectives To evaluate CK variability among outpatient statin users and identify patient-and treatment-related factors associated with CK levels. Methods A retrospective cross-sectional study was conducted among adult outpatient attending cardiology, endocrinology, or internal medicine clinics at a tertiary care center in Saudi Arabia between January-2020 to December-2021. Demographic characteristics, comorbidities, statin exposure, statin intensity, concomitant medications, renal function, and laboratory parameters were extracted from electronic medical records. Multivariable linear regression analyses were performed to identify factors independently associated with CK levels. Results A total of 6,517 patients were included, of whom 3,223 (49.5%) received statin therapy. Statin users had higher CK levels than non-users (112 vs. 80 IU/L, p < 0.001). CK values were generally distributed within a narrow range, with a median of 94 IU/L (IQR 68–121) and 95% of measurements below 157 IU/L. In the fully adjusted model, statin use ( β = 31.84, 95% CI 29.98–33.69; p < 0.001) and male sex ( β = 13.95, 95% CI 12.36–15.53; p < 0.001) were independently associated with higher CK levels. Thyroid disorder demonstrated a modest association with CK levels ( β = 2.60, 95% CI 0.32–4.88; p = 0.026). Conclusion Statin use and male sex were the primary factors associated with CK variability in this outpatient population. Despite modestly higher CK concentrations among statin users, most measurements remained within a relatively narrow range, and no dose-response relationship was observed according to statin intensity or statin type. These findings provide real-world evidence to support the interpretation of routine CK measurements during outpatient statin therapy.