HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA IS ASSOCIATED WITH PATHOLOGICAL EXERCISE-INDUCED LEAKAGE OF MUSCLE PROTEINS, WHICH IS NOT AGGRAVATED BY SIMVASTATIN THERAPY

The objective of this study was to assess the relationship between the rapy with the HMG-CoA reductase inhibitor simvastatin and muscle damag e and the possible causal role of hypercholesterolaemia. The exercise- induced release of muscle proteins as a parameter of muscle damage was studied in two equicholesterolaemic groups of male patients with hete rozygous familial hypercholesterolaemia (FH); one group without treatm ent, the second group on simvastatin. To assess the role of cholestero l, a third group of healthy male volunteers was studied as well. The s tudy took place at the Lipid Clinic of an 800-bed University Hospital. One group of 21 male patients with heterozygous FH did not receive tr eatment, except for a lipid-lowering diet. A second group of 13 male F H patients were treated with 40 mg simvastatin day(-1) for at least 1 year and matched for cholesterol levels with the first group. A third group consisted of 25 normocholesterolaemic male controls. All subject s underwent a 45 min lean body mass (LBM) standardized ergometer muscl e provocation test (2 Watt/kg LBM). Levels of creatine kinase (CK) and myoglobin (Mb) were assessed before and 1 and 8 h after exercise and compared with baseline levels. The exercise-induced release of muscle proteins is reflected by peak CK and Mb levels expressed as a percenta ge of baseline levels. The exercise-induced increase in Mb and CK leve ls did not differ between untreated and simvastatin-treated FH patient s. However, the increase in Mb 1 h after exercise in untreated FH pati ents (181% of baseline level) and in simvastatin-treated patients (144 % of baseline level) differed significantly from controls (107% of bas eline level, P < 0.025, Mann-Whitney test). We conclude that hyperchol esterolaemia may be associated with muscle damage, and the CK rises ob served under therapy with HMG-CoA reductase inhibitors might be attrib uted to hypercholesterolaemia per se.