Statin‐induced Myopathy and Ubiquinone Levels in Serum – Results from a Prospective, Observational Study

Abstract

It has been suggested that an impaired ubiquinone (Q10) synthesis may be responsible for muscular side effects caused by statins. The primary aim of this study was to investigate whether low Q10 levels in serum could be used as a marker to predict the risk of developing statin-induced myopathy. The secondary aim was to compare the change in Q10 levels during statin treatment and differences between men and women. Serum samples from a prospective, observational study in statin-treated patients who were thoroughly followed regarding muscular symptoms were used. In this cohort, 16 developed myopathy and 126 had no muscular symptoms related to statin treatment. Q10 levels were measured with a novel LC-MS method at baseline and after 2 months of statin treatment. Q10 levels showed no correlation with the risk of developing statin-induced myopathy. Individuals with low levels, Q10 < 200 ng/ml, at baseline had no increased risk of developing myopathy. In consistence with earlier reports, we showed that Q10 levels were reduced by 30% during statin treatment. There was no significant difference in the reduction between patients with or without myopathy. Women had approximately 30% lower Q10 levels compared to men both before and after treatment. In this study, there was no association between Q10 levels at baseline and statin-induced muscular side effects during a 2-month follow-up period, and our results indicate that Q10 levels in serum is not a useful marker to predict statin-induced myopathy.Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are used for treatment of hypercholesterolaemia and have a pronounced, preventive effect on serious cardiovascular events and mortality [1,2]. Today, statins are some of the most prescribed drugs in the Western world, and the consumption is steadily increasing [3]. However, several reports have demonstrated that statin-induced muscular side effects such as myalgia are more common than first demonstrated in clinical trials. In fact, 10-15% of patients prescribed statins may experience muscle symptoms [4][5][6]. The statin-induced myopathy is considered to be dose dependent [7] but independent of the cholesterol-lowering effect [8].Statins affect not only the synthesis of cholesterol but also all products in the cholesterol biosynthesis pathway.Ubiquinone (Q10) is one of these products. The major part of the intracellular Q10 is present in the inner mitochondrial membrane as an essential part of the electron transport chain [9,10]. A smaller fraction is present in the cytosol where it has antioxidative functions [9,11]. Q10 is also present in the blood and is mainly bound to low-density lipoprotein (LDL) and also, to some extent, to high density lipoprotein (HDL) and very low-density lipoprotein (VLDL) [12].It has been suggested that the decreased synthesis of Q10 may be involved in statin-induced myopathy [13,14]. In particular, the reduction of mitochondrial Q10 has been suggested to cause myopathy, and statin treatments have been shown to negatively a...

miRNA‐27b levels are associated with CYP3A activity in vitro and in vivo

“…The study is described in detail in another article (Skilving et al. ). From the original study, 28 patients were analyzed for 4 β ‐hydroxycholesterol levels in their baseline blood samples taken at study inclusion.…”

“…The study was approved by the local Ethics Committee (Dnr: 2006/431-31/2) and was performed in accordance with the declaration of Helsinki. The study is described in detail in another article (Skilving et al 2015). From the original study, 28 patients were analyzed for 4b-hydroxycholesterol levels in their baseline blood samples taken at study inclusion.…”

Effect of Statin Treatment on Plasma 4β‐Hydroxycholesterol Concentrations

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Low Vitamin D Levels and Genetic Polymorphism in the Vitamin D Receptor are Associated with Increased Risk of Statin‐Induced Myopathy

“…We analysed serum from a previously performed observational clinical study in which 180 patients starting on statin treatment (n = 120) or switching from one statin to another (n = 60) were followed for 1 year regarding onset of muscular symptoms with questionnaires (described in ref. and in Skilving et al ., Manuscript 2015 ). The questionnaires included 25 questions covering muscular symptoms, daily life activities, statin compliance, educational level and lifestyle factors, for example alcohol and tobacco use and exercise.…”