Abstract 14888: Plasma Eicosanoids are Potential Biomarkers for Muscle Weakness and Pain related to Statin Treatment
Background and aims: Statin users report muscle symptoms with frequency estimates ranging from 5-20%. At its worst such complaints may lead to the rare and full-blown rhabdomyolysis syndrome. Diagnostic tools are limited for accurate and sensitive diagnosis of myopathy. The current golden standard, creatine kinase (CK) measurement, is useful only after considerable damage to muscle. In the vast majority of cases the CK measurement remains uninformative despite true symptoms. An earlier detection would ensure that patients complaining of muscle symptoms would not be taken off vital treatments if their symptoms are not de facto drug related. In this study a comprehensive lipidomic analysis of statin patients was undertaken to identify better plasma biomarkers for statin adverse events.
Methods: First plasma samples obtained from subjects (n=40) with statin-induced muscle pain and 40 tolerant patients were analyzed. Direct infusion coupled to tandem mass spectrometry, i.e. shotgun lipidomics, and two liquid chromatography tandem mass spectrometry (LC-MS/MS) approaches were used to identify potential biomarkers. Then a targeted biomarker validation was performed with a larger sample set (n= 300).
Results: In the first analysis three hundred molecular lipids were quantified. Out of those two eicosanoids 12-Hydroxyeicosatetraenoic acid (12-HETE) and 8, 9-dihydroxyeicosatrienoic acid (8,9- DHET) appeared to separate well cases and controls with an AUC of 0.81, while plasma CK values remained normal and equivalent in both groups. In the validation study 12-HETE proved to be a prime biomarker candidate for muscle side effects. Plasma concentrations of 12-HETE were +236% (p<=0.0001) higher in cases with normal plasma CK than in asymptomatic control subjects.
Conclusion: Molecular lipid species proved to be excellent biomarker candidates for statin-induced myotoxicity allowing for more sensitive detection of muscular side effects. These new biomarker candidates are diagnostic even in patients with normal plasma CK and therefore provide valuable information for the majority of patients suffering from muscle pain and weakness while on statin therapy.
- © 2011 by American Heart Association, Inc.