title: Combined hyperlipidemia is associated with increased exercise-induced muscle protein release which is improved by triglyceride-lowering intervention.
abstract: Although myopathy is considered an adverse effect of treatment with 3-hydroxy-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 pathology and whether lipid-lowering intervention has beneficial effects. To investigate whether combined hyperlipidemia is associated with skeletal muscle 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 plasma level of the muscle proteins creatine kinase (CK), myoglobin (Mb), and fatty acid-binding protein (FABP) were assessed as parameters for (subclinical) skeletal muscle pathology. The 8-hour postexercise increments in CK and Mb and 1-hour postexercise increment in Mb were significantly higher in patients than in controls, thus indicating increased exercise-induced muscle membrane permeability in combined hyperlipidemia. To investigate the effects of lipid-lowering intervention on skeletal muscle in combined hyperlipidemia, 21 subjects with combined hyperlipidemia were randomized double-blindly to receive 6 weeks of treatment with fluvastatin 40 mg/d, gemfibrozil 600 mg twice daily, or combination therapy. All subjects underwent an ergometer test before and after treatment. Gemfibrozil treatment alone reduced the CK increments 8 hours postexercise by 47% and the FABP increments 1 and 8 hours postexercise by 83% and 101%, respectively (all P < .05). Combined treatment reduced Mb increments 1 hour postexercise by 54% and FABP increments 8 hours postexercise by 44% (all 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 hyperlipidemia is associated with an increased exercise-induced release of muscle proteins, which is ameliorated by triglyceride-lowering intervention. As FABP is an indicator for ischemia-induced skeletal muscle pathology, a possible explanation is the impaired muscle blood flow during hypertriglyceridemia, which may be reversed by triglyceride-lowering intervention. The mechanism and clinical relevance of these findings remain to be investigated.
authors.affiliation: Department of Internal Medicine, University Hospital, Utrecht, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Smit
authors.forename: T W
authors.initials: TW
authors.lastname: De Bruin
authors.forename: E M
authors.initials: EM
authors.lastname: Eekhoff
authors.forename: J
authors.initials: J
authors.lastname: Glatz
authors.forename: D W
authors.initials: DW
authors.lastname: Erkelens
mesh_terms: D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use; D005260:Female; D000077340:Fluvastatin; D015248:Gemfibrozil / Q000627:therapeutic use; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use; D007231:Infant, Newborn; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D012016:Reference Values; D014280:Triglycerides / Q000037:antagonists & inhibitors* / Q000097:blood
chemical_list: D005229:Fatty Acids, Monounsaturated; D000960:Hypolipidemic Agents; D007211:Indoles; D008055:Lipids; D009124:Muscle Proteins; D014280:Triglycerides; D000077340:Fluvastatin; D015248:Gemfibrozil