Estudo da toxicidade muscular pelo uso de estatinas em pacientes hipercolesterolêmicos: avaliação pela espectroscopia do hidrogênio por ressonância magnética / Study of muscle toxicity by use of statins in hypercholesterolemic patients: evaluation by proton magnetic resonance spectroscopy

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

13/11/2012

RESUMO

Cardiovascular disease is the leading cause of death in the western world and statins are the most prescribed medications for prevention and treatment. Despite being the most prescribed drugs, they are still under-used. The main cause of interruption of statin treatment is myopathy. Among the mechanisms involved in the pathophysiology of myotoxicity, deficiency of coenzyme Q10 has been described as the main cause of this side effect. Creatine kinase (CK) is a biomarker for severity of muscle damage, but its levels may be normal or increased in patients on statin use and muscle symptoms. Thus, proton magnetic resonance spectroscopy (H-MRS) could assist in the diagnosis of muscle toxicity caused by statins, through a study of the metabolic changes. The aim of this study is to evaluate the concentrations of intramyocellular (IMCL) and extramyocellular lipids (EMCL), total creatine and trimethylamine (TMA), on tibialis anterior and soleus muscles in patients on statin use and muscle symptoms and compare with hypercholesterolemic subjects (LDL >= 160mg/dL) and normal subjects (LDL<160mg/dL), both without treatment. Also, the effect on LDL serum levels (after three month statin treatment), and concentrations of IMCL and EMCL lipids. In addition, make a correlation between the levels of CK and the variables of spectroscopy. Ninety-one patients (mean age=44, 54 women and 37 men) were submitted to blood sampling for evaluation of serum total cholesterol, LDL-C, HDL-C, triglycerides, AST, ALT, CK, glucose, TSH and creatinine, and H-MRS for evaluation of metabolites, IMCL and EMCL lipids, total creatine and TMA. Patients were divided in 3 groups: 1 (patients with LDL-C<160mg/dL, without statin use) n=49, 2 (patients on statin use and muscle symptoms) n=18 and 3 (patients with LDL-C>=160mg/dL, without statin use) n=24.Group 3 were subjected to blood sampling and the H-MRS on two occasions: before and three months after treatment with simvastatin 20 mg. The tests were carried out in a MRI SIGNA 1.5 Tesla (General Electric, Milwaukee, WI, USA) magnet and the images were processed automatically using the software LCModel version 6.2 (http://s-provencher.com/). From the 91 study subjects a total of 115 H-MRS scans were performed. Patients in group 2 (age 55.0 ± 9.0 years) were older, respectively, than in groups 3 (48.0 ± 9.0 years) and 1 (38.0 ± 11.0 years), p<0.001. There was a statistically significant difference between the groups before treatment in relation to the total cholesterol, LDL-cholesterol, triglycerides and AST (p<0.001). There were no significant differences on plasma CK levels, in patients presenting muscle symptoms (p=NS). In Group 3, there was significant reduction in levels of total cholesterol, LDL-C and triglycerides after treatment with statin (p<0.05).There were no significant differences regarding median IMCL variables, EMCL, total creatine and TMA, in the tibialis anterior and soleus muscles as well as their ratios among the three groups and after group 3 three month treatment (p=NS). A significant and positive correlation (r=0.253, p=0.018), was found in group 2 between serum CK and the ratio of intramyocellular and total creatine in tibialis anterior muscle. H-MRS is a feasible exam to be used in clinical practice; however it has not been possible to demonstrate changes in concentrations of the metabolites in the tibialis anterior and soleus muscles. The findings of correlations between CK and intramyocellular and total creatine may suggest an early manifestation of muscle toxicity caused by statins in patients with muscle symptoms.

ASSUNTO(S)

espectroscopia estatinas magnetic resonance miotoxicidade miotoxicity ressonância magnética spectroscopy statin

ACESSO AO ARTIGO

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