Combined hyperlipidemia is associated with increased exercise-induced muscle protein release which is improved by triglyceride-lowering intervention

Although myopathy is considered an adverse effect of treatment with 3-hydro xy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors and fibrates in combined hyperlipidemia, the present study was performed to investigate whether combined hyperlipidemia itself is associated with skeletal muscle p athology and whether lipid-lowering intervention has beneficial effects. To investigate whether combined hyperlipidemia is associated with skeletal mu scle pathology 10 male patients and 15 normolipidemic controls underwent a 45-minute standardized bicycle ergometer test at a load of 2 W/kg lean body mass (parallel study). One- and 8-hour postexercise increments in the plas ma level of the muscle proteins creatine kinase (CK), myoglobin (Mb), and f atty acid-binding protein (FABP) were assessed as parameters for (subclinic al) skeletal muscle pathology. The 8-hour postexercise increments in CK and Mb and 1-hour postexercise increment in Mb were significantly higher in pa tients than in controls, thus indicating increased exercise-induced muscle membrane permeability in combined hyperlipidemia. To investigate the effect s of lipid-lowering intervention on skeletal muscle in combined hyperlipide mia, 21 subjects with combined hyperlipidemia were randomized double-blindl y to receive 6 weeks of treatment with fluvastatin 40 mg/d, gemfibrozil 600 mg twice daily, or combination therapy. All subjects underwent an ergomete r test before and after treatment. Gemfibrozil treatment alone reduced the CK increments 8 hours postexercise by 47% and the FABP increments 1 and 8 h ours postexercise by 83% and 101%, respectively tall P <.05). Combined trea tment reduced Mb increments 1 hour postexercise by 54% and FABP increments 8 hours postexercise by 44% tall P <.05). A highly significant correlation existed between therapy-induced changes in plasma triglycerides and changes in postexercise increments of FABP and Mb. In conclusion, combined hyperli pidemia is associated with an increased exercise-induced release of muscle proteins, which is ameliorated by triglyceride-lowering intervention. As FA BP is an indicator for ischemia-induced skeletal muscle pathology, a possib le explanation is the impaired muscle blood flow during hypertriglyceridemi a, which may be reversed by triglyceride-lowering intervention. The mechani sm and clinical relevance of these findings remain to be investigated. Copy right (C) 1999 by W.B. Saunders Company.