Statin-Induced Myopathy Reflects Structural Muscle Damage, New Study Shows

Persistent muscle pain in patients taking statins reflects structural muscle damage, and this microscopic damage can occur in the absence of elevated creatine phosphokinase levels, according to the results of a new study [1].

"It's clear that a patient with statin-induced myopathy can have microscopic muscle damage, but the damage is not sufficient to break the cell open, and that means that it doesn't release creatinine phosphokinase into the blood," said study investigator Dr Richard Karas (Tufts-New England Medical Center, Boston, MA). "So to say that the other way around, we have clear evidence that there is ongoing damage to the muscle at the microscopic level, but it's not revealed in the blood tests that we use to check for muscle damage."

Speaking with heartwire , Karas said that muscle-related adverse effects limit statin use, despite the drugs being part of the foundation of cardiovascular risk reduction. He added that although these muscular side effects are well documented, little is known about the mechanisms of myopathy.

In this study, which is published online July 7, 2009 in the Canadian Medical Association Journal, Karas, along with lead investigator Dr Marcus Mohaupt (University of Bern, Switzerland), obtained biopsy samples from the vastus lateralis muscle of 83 patients. Overall, 44 subjects had clinically diagnosed statin-associated myopathy, and of these, 29 were currently taking a statin, while 15 had discontinued statin therapy for at least three weeks. Among the 83 patients, 19 were currently taking a statin but had no myopathy and 20 patients served as healthy controls.

Among the 44 individuals with myopathy, 57% had muscle injury defined by structural abnormalities in the muscle fibers, as did one patient without clinically diagnosed myopathy. Interestingly, just one patient with structural muscle injury had circulating creatine phosphokinase levels that exceeded 10 times the upper limit of normal, or >1950 U/L.

"This is clinically relevant because when a patient is on a statin and they come in complaining that their muscles hurt, we check the blood test for creatinine phosphokinase," said Karas. "If it's normal we tell them not to worry about it, that it's not the statin. This study tells us that in this group of patients, that clinical assumption is not true."

Not Your Average Patient on a Statin

Karas stressed that the patients included in this study are not typical patients on statins, but rather individuals with clinically identified statin-related myopathy. This distinction is important because patients treated with statins who feel fine and who have normal creatine phosphokinase levels should not worry they are damaging their muscles with the LDL-cholesterol-lowering medications.

The researchers point out, however, that patients with clinically diagnosed statin-induced myopathy who had stopped their statins for at least three weeks also had persistent microscopic evidence of muscle damage. Although he is cautious in interpreting results, saying it needs further study, Karas said that muscle problems might not go away among individuals with persistent muscle pain.

The researchers also performed a gene-expression analysis in 57 patients to look for association between muscle damage and genes that encode proteins located in T-tubule membrane or the adjacent sarcoplasmic reticulum and that are involved in the release of intracellular calcium. One of those proteins, ryanodine receptor 3, was significantly upregulated among patients with structural muscle damage when compared with individuals without muscle damage.

"The problem is that we don't know if this was elevated in the first place, and then this makes people susceptible to statin-induced myopathy, or whether it is elevated as a result of them having statin-induced myopathy," Karas explained to heartwire . "This is the first step, as it tells us that it's a gene that should be focused on in studies going forward. What we'd like to do is take a huge group of people and get their levels of expression and see if it predicts them getting myopathy."

Source : http://www.medscape.com/viewarticle/705429?src=mpnews&spon=34&uac=133298AG