Statins are widely used lipid-lowering medications that reduce cardiovascular risk, but their use may be limited by statin-associated muscle symptoms (SAMS), which range from mild myalgia to significant elevations in creatine kinase (CK). The underlying biological mechanisms of SAMS are not fully understood. One proposed mechanism involves impaired mitochondrial fatty acid metabolism, which may lead to the accumulation of acylcarnitines-intermediate metabolites involved in fatty acid transport and oxidation within mitochondria.
This study aims to investigate whether statin-associated muscle symptoms are associated with disturbances in acylcarnitine metabolism in blood and skeletal muscle tissue. Specifically, the study will assess whether patients with SAMS have higher concentrations of acylcarnitines compared to statin users without muscle symptoms and individuals not receiving statin therapy, and whether these concentrations change after discontinuation or reduction of statin therapy.
This is a single-center observational case-control study conducted at the Latvian Cardiology Center of Pauls Stradiņš Clinical University Hospital. The study population includes three groups: (1) patients with elevated CK levels with or without muscle symptoms suggestive of statin-associated myopathy, (2) patients receiving stable high-dose statin therapy without muscle symptoms, and (3) control participants not using lipid-lowering therapy and without unexplained muscle symptoms.
All participants underwent a single study visit during which demographic data, medical history, medication use (including statins and other lipid-lowering therapies), and lifestyle factors (such as smoking, alcohol consumption, and physical activity) were recorded. Blood samples were collected for routine biochemical analyses (including CK, alanine aminotransferase, creatinine, and lipid profile) and for the measurement of plasma acylcarnitine concentrations. Plasma samples were processed and stored at -80°C for current and future analyses.
Participants were assessed for statin-associated muscle symptoms using the Statin-Associated Muscle Symptom Clinical Index (SAMS-CI). In a subset of participants who provided additional informed consent, a muscle biopsy was performed under local anesthesia from the non-dominant forearm muscle. Muscle tissue samples were used to evaluate acylcarnitine concentrations and mitochondrial fatty acid metabolism.
Participants in the SAMS group (Group A) who required discontinuation or dose reduction of statin therapy as part of routine clinical care underwent prospective follow-up. Repeat blood sampling was performed approximately 4 and 8 weeks after statin discontinuation or dose adjustment, and continued at 4-week intervals (up to 24 weeks) until CK levels normalized. In selected participants, a repeat muscle biopsy was performed within 4-8 weeks after statin discontinuation or dose reduction to assess changes in mitochondrial metabolism and acylcarnitine concentrations.
Data will be analyzed to compare acylcarnitine concentrations between groups and to evaluate changes over time in the SAMS group. Quantitative variables will be summarized using means and standard deviations or medians and interquartile ranges, depending on data distribution. Between-group comparisons will be performed using parametric or non-parametric statistical tests as appropriate, and repeated measurements will be analyzed using paired statistical methods. A p-value \<0.05 will be considered statistically significant.
The results of this study are expected to improve understanding of the pathophysiology of statin-associated muscle symptoms and may contribute to the development of better diagnostic and management strategies for patients experiencing statin intolerance.
