Introduction

Despite overwhelming evidence for the benefits of statin therapy, a considerable proportion of patients with a high cholesterol concentration, including those at a very high cardiovascular risk, do not take any statin.^1,2 The major reason for statin therapy discontinuation and, consequently, an increased risk for cardiovascular disease are statin‑associated muscle symptoms, defined as all muscle‑related complaints, such as muscle pain and strength or function decline.³ Reduced muscle strength, leading to decreased physical activity, is one of the most frequent complaints reported by older patients, who are often burdened by multimorbidity.⁴ At the same time, it is still under debate whether statin therapy is related to decreased muscle strength among older patients with multimorbidity.⁵

The aim of this study was to assess the relationship between statin therapy and physical performance in consecutive patients hospitalized in a department of internal medicine and geriatric cardiology.

Patients and methods

This cross‑sectional study was conducted between June 2022 and February 2025, and included 219 consecutive patients aged 65 years and older who were hospitalized in an internal medicine and geriatrics department. Patients with severe functional decline (with terminal frailty according to the Clinical Frailty Scale), who could not perform any physical performance test, were excluded from the study (≤3%). Individuals taking a statin within at least 1 month preceding the hospitalization were considered statin takers (continuous statin use; data obtained from the patient, caregiver, or medical records).

The research questionnaires included demographic and medical data. Frailty was evaluated using the frailty phenotype based on the Fried criteria,⁶ and physical performance tests were carried out in the following sequence: muscle strength (in kg), that is, the grip strength measured with a dynamometer (Jamar FS658, Patterson Medical, Warrenville, Illinois, United States; the measurement was performed twice for each hand and average measurement was annualized); the back scratch test (BST; in cm), the timed up and go test (TUGT; in s), performed with assistive devices, if necessary, and the 5‑times sit‑to‑stand test (5 × SST; in s), performed without assistive devices. The TUGT was prespecified as primary.

The Fried criteria included 5 components: 1) unintentional weight loss of 4.5 kg or at least 5% of body mass in the last year (data obtained from the patient, caregiver, or medical records); 2) weakness (assessment based on the handgrip strength measurement, according to cutoff points for sarcopenia⁷); 3) exhaustion (based on 2 questions from the Centre for Epidemiological Studies Depression scale ranging from 1 to 4, with a score of 1 point indicating fatigue or exhaustion felt rarely or not at all, and 4 points indicating fatigue or exhaustion felt most of the time; a score of ≥3 points indicates a positive test result); 4) slow gait speed (<⁠0.8 m/s measured over a distance of 4 m); and 5) low physical activity (weekly energy expenditure rate). The patients who fulfilled at least 3 criteria were classified as frail.⁶ Physical performance of the study participants was assessed when their health status was optimized, 1 day before discharge.

The study was approved by the Bioethics Committee at the Centre of Postgraduate Medical Education of Warsaw (73/2022), and all patients provided written informed consent to participate.

Results

The study population comprised 219 patients (141 women) hospitalized due to exacerbation of chronic diseases, infections, electrolyte abnormalities, or for health status evaluation. Of those, 106 individuals were taking a statin (65 women and 41 men) and 113 were not taking any statin (78 women and 35 men). Sex distribution was comparable in both groups (women, 61.3% vs 69%; P = 0.23). The median (IQR) age was 82 (76–85) years vs 83 (78–87) years in the statin takers vs nontakers, respectively (P = 0.07). Altogether, 58 patients (54.7%) were taking atorvastatin (median dose, 20 [10–20] mg once daily; the highest dose was 40 mg in 6 patients [5.6%]), 43 (40.6%) were taking rosuvastatin (median dose, 10 [10–20] mg once daily; the highest dose was 40 mg in 2 patients (1.8%), and 5 (4.7%) were on simvastatin (median dose, 10 [10–20] mg once daily; the highest dose was 20 mg in 2 patients [1.8%]). There were 61 patients (57.5%) with frailty (according to the Fried criteria) in the statin group and 67 (59.3%) in the nonstatin group. The median number of medications used was 6 (5–8) among the statin takers and 5 (3–6) among the patients not taking any statin (P <⁠0.001). The median number of comorbidities (including cardiovascular diseases, metabolic diseases, thyroid dysfunction, or kidney failure) was 3 (2–4) in both groups. The patients taking a statin significantly more often had hypertension (90.6% vs 78.8%; P = 0.02), obesity (49.1% vs 34.5%; P = 0.03), diabetes (48.1% vs 34.5%; P = 0.04), and coronary heart disease (37.7% vs 23.9%; P = 0.03) than the individuals not taking a statin. The median creatinine, glycated hemoglobin, and serum glucose concentrations were significantly higher in the statin group (95.5 [75.1–115.8] vs 83.1 [67.2–101.7] µmol/l; P = 0.003; 6.4% [5.9%–7.3%] vs 6% [5.6%–6.3%]; P = 0.001; and 5.7 [5.2–7.5] vs 5.5 [5.1–6.1] mmol/l; P = 0.03, respectively), while total and low‑density lipoprotein cholesterol levels were significantly lower in the statin group (3.5 [3.1–4.3] vs 4.2 [3.4–4.9] mmol/l; P <⁠0.001; 1.9 [1.5–2.5] vs 2.5 [1.9–3] mmol/l; P <⁠0.001, respectively). The patients taking a statin had greater grip strength than those not taking a statin (20.7 [15.5–26.8] vs 17.6 [12.8–25.1] kg; P = 0.049). The difference was also noted between sexes, with median grip strength of 16.6 (12.56–19.95) kg in women and 28.5 (21.11–34.29) kg in men (P <⁠0.001). Additionally, there were differences in median grip strength between the women taking and not taking a statin (17.4 [13.4–21.2] vs 15.62 [11.6–18.7] kg, respectively; P = 0.001) and between the men taking and not taking a statin (27.6 [23.1–32] vs 28.6 [19.1–34.5], respectively; P = 0.008).

No significant differences were found between the groups with or without statin therapy with respect to BST, TUGT, 5 × SST results, and the presence of frailty (Table 1). No physical performance test was associated with statin use when adjusted for age, sex, New York Heart Association class, frailty syndrome, coronary artery disease, renal function, obesity, diabetes mellitus, and polypharmacy. In the multivariable analysis, age (β = –0.01; 95% CI, –0.02 to 0.01), female sex (β = –0.22; 95% CI, –0.26 to 0.19]), and frailty (β = –0.13; 95% CI, –0.15 to 0.1), but not statin use (β = –0.03; 95% CI, –0.06 to 0.01), were independently related to muscle grip strength. Additionally, age (β = 0.03; 95% CI, 0.01–0.05) and frailty (β = 0.15; 95% CI, 0.06–0.25), but not statin use (β = 0.09; 95% CI, –0.04 to 0.22) or female sex (β = –0.07; 95% CI, –0.19 to 0.05) were independently related to the BST. With respect to the TUGT, age (β = 0.03; 95% CI, 0.02–0.04) and frailty (β = 0.17; 95% CI, 0.11–0.24) were identified as independent predictors, whereas statin use (β = –0.07; 95% CI, –0.16 to 0.01) or female sex (β = 0.07; 95% CI, –0.02 to 0.15) were not. Finally, only frailty (β = 0.14; 95% CI, 0.09–0.19) was found to be independently related to the 5 × SST, whereas statin use (β = 0.06; 95% CI, –0.02 to 0.14), female sex (β = 0.02; 95% CI, –0.05 to 0.1), or age (β = 0.01; 95% CI, 0–0.02) were not.

Discussion

Statin therapy can impact the musculoskeletal system, with the most common symptoms including localized muscle pain or reduced physical activity, which become the main reasons for treatment discontinuation.⁸ However, this issue remains under debate, as statin‑related muscle problems reported in some observational studies have not been confirmed by randomized controlled trials.⁹ This inconsistency could originate from inadequate control of bias in nonrandomized studies or from an efficacy–effectiveness gap, which occurs when an intervention that appears safe in a clinical trial fails to produce the same results in a more heterogeneous or less controlled population, especially in the oldest patients.¹⁰ Moreover, randomized controlled trials may underestimate the incidence of adverse musculoskeletal events by excluding individuals with a personal or family history of muscle disorders or patients with a higher multimorbidity index, and by underestimating milder symptoms. In our study, we found no significant differences in muscle strength or function between the patients taking and not taking statins.

According to a recent meta‑analysis, the benefits of engaging in physical activity while on statin therapy clearly outweigh the risks.¹¹ Furthermore, the heterogeneity of the study methods, outcomes, and reporting does not allow for unequivocal synthesis of the results.¹² In our study, no physical performance test assessing muscle function was independently related to statin use, which is consistent with previous reports.¹³ We found associations between muscle strength and function measured with simple physical performance tests, and age, sex, and frailty. However, these associations were unaffected by statin use. This study may contribute to the application of lipid‑lowering treatment recommendations also in the oldest groups of patients, as well as to individualizing treatment in this population. This area undoubtedly requires further research, considering multimorbidity and including larger patient groups.

A limitation of our study is the lack of serum creatine phosphokinase concentration measurement and myalgia symptoms assessment, which could have broadened the scope of the research. However, we aimed to focus on the measurement of muscle strength and function.

Conclusions

Physical performance was not significantly associated with statin use in older, hospitalized patients with multimorbidity.