Rafał Celiński, Anna Grzywa-Celińska, Wojciech Myśliński, Andrzej Dybała, Jerzy Mosiewicz rhabdomyolysis, the most commonly used criterion is a sudden increase of serum CK levels exceeding at least fivefold the upper normal limit after excluding myocardial infarction (CK-MB fraction < 5%) [13]. The risk of myotoxicity during hyperlipidaemia treatment with statins increases during simultaneous therapy with drugs impeding statin metabolism, which include itraconazole, erythromycin and nefazodone [14], or others which can cause muscle inflammation, such as cyclosporine, macrolide antibiotics, niacin, azole antimycotic drugs, protease inhibitors or calcium channel blockers [15]. The risk of statin-induced myopathy is also increased in electrolyte imbalance, severe infections, injuries and hypoxia [14], as well as in hepatic disorders and renal failure [15, 16]. In the last two pathologies, the risk is related to the dose of statins [17]. Hypothyroidism may also predispose to rhabdomyolysis [18]. The risk of myopathy also increases significantly in patients with congenital muscular defects, in patients with alcohol-related diseases, in people from the Mongoloid race and in people consuming large amounts of grapefruit juice [19]. A few articles provide information concerning life-threatening side effects of simvastatin therapy [20-22]. A recent topic of discussion is the role of genetic factors in the occurrence of statin-induced myopathy, which can influence the pharma- cokinetics of these drugs and play a part in causing metabolic muscular diseases. Gene mutations responsible for metabolic muscular diseases were found in 10% of patients with statin-induced myopathy but only in 3% of patients who tolerated statins well [23]. Finally, a crucial factor predisposing to rhabdo- myolysis in patients undergoing statin therapy is loading with physical effort [16, 24]. The study of Thompson et al. published in 1997 [25] analysed the hypothesis that physical effort in the course of statin treatment causes a higher increase of muscle damage factor activity (CK) than physical training in patients who were not taking these drugs. Fifty-nine men with LDL > 130 mg/dl in spite of dietary therapy were examined. These patients were given 40 mg of lovastatin or a placebo over a 5-week period. Moreover, after 4 weeks of therapy, they underwent a 45-min treadmill test in order to assess maximal expected heart rate. In the following week, the patients trained using a different set of exercises. The activity of CK was examined before and after physical effort. It was demonstrated that the activity of CK in the group taking lovastatin was higher by 62% to 77% than in the case of physical training. Therefore, it was hypothesized that statins intensify muscle damage connected to physical training. In the study published by Coen et al. [26], physically inactive patients with hypercholes- terolaemia were divided into 2 groups. Patients from both groups received 10 mg of rosuvastatin during a 20-week period. Additionally, patients from the first group attended a programme of physical training between the 10th and 20th week. A temporary increase of CK activity 48 h after the first round of exercise was noted in the exercise group, but these values returned to previous levels 48 h after the fifth round of exercise. Side effects such as muscular pain and stiffness were observed very early on, but their occurrence was not associated with the increase of CK. These results differ significantly from the results obtained by Thompson et al. [25], probably due to the smaller load with physical effort in the new study. In another study, professional sportsmen with familial hypercholesterolaemia, taking all sorts of statins (excluding cerivastatin), were analysed; 78% of them did not tolerate the suggested statin therapy because of muscular pain. However, an increase of CK activity higher than the acceptable levels for sportsmen was not observed [27]. There is no unambiguous answer in the litera- ture as to whether the treatment of physical exercise in the scheme of early cardiac rehabilitation is safe in patients undergoing therapy with statins. Does clinical practice offer any hints? Although there are almost no data from large clinical trials about the possible effect of statin therapy on the whole process of cardiac reha- bilitation, some clinical conclusions can be drawn from case reports. In 2009 we published an article reporting a case of severe myopathy during therapy with simvastatin in a patient undergoing early cardiac rehabilitation after PCI [28]. In the presented case, a high dose of simvastatin, together with too intensive physical training in the poorly trained patient, led to the development of life-threatening rhabdomyolysis. Our patient also presented with abnormal structure of the left kidney in ultrasonography (post-inflammatory changes? renal cirrhosis?) and abnormal kidney function. These abnormalities might have had a significant influence on statin metabolism and unfortunately had not been taken into consideration before the patient was qualified for the rehabilitation programme [28]. Conclusions The careful selection of patients for both treatment with statins and the gradual intensi- fication of physical training in the course of cardiac rehabilitation appears to be fundamentally impor- tant. The general condition and the previous physi- cal activity of the patient should be assessed, together with all the factors presented above that 758 Arch Med Sci 5, October / 2011