Link between muscle disorders, statins probed

The National Institutes of Health has awarded nearly $2.5 million in grants to determine the genes that make serious muscle problems more likely for patients taking statin drugs. The grants also will support efforts to develop tools physicians can use to identify those who are most at risk.

"We want to find what makes them different from people who take statins and have no problems," said Georgirene D. Vladutiu, PhD, head of the research group at the University at Buffalo in New York that received the grants. "And if people could be tested in advance of taking statins, it would lead to or contribute to personalized medicine. That's where we're headed."

This project, approved this summer and announced Oct. 2, is one of a handful seeking to investigate side effects associated with these medications. Physicians and researchers who focus on this area say such research is necessary. Statins have a track record and are considered safe, although myopathy is listed as a possibility on the label. The rates of the severe form of this adverse event are low, although lesser versions are more common. Also, the majority of symptoms resolve if patients stop taking the drug. But with so many people taking the medication at ever-higher doses, the actual number impacted is large.

"It's an important question, and I think that we should look at this," said Bruce R. Gordon, MD, director of the Rogosin Institute's Comprehensive Lipid Control Center in New York. "The statins are important drugs, and there's not a physician who doesn't have patients who complain about this." He also researches the genes that determine the variability of the cholesterol-lowering effect of these drugs as well as the chance of adverse events.

In recognition of the need for answers, the National Heart, Lung and Blood Institute awarded two grants to the University at Buffalo, including $2 million to study the association between various genes and statin-induced myopathy and $110,000 to determine the commercial viability of a product to identify them in patients. The National Institute of Arthritis and Musculoskeletal and Skin Diseases provided $383,000 for characterizing the genes associated with statin myopathy.

Researchers suspect that the genes most likely to be contributing factors are associated with other muscle disorders. Prior research has suggested various recessive variants that are somehow activated by these drugs.

"We think that there are a higher number of people who have an underlying muscle disease that's simply been triggered by the statins," said Vladutiu, a professor of pediatrics, neurology, pathology and anatomical sciences . Her previous studies have shown that certain genetic polymorphisms are more common among those with statin-induced myopathies.

Still, it's unknown whether those who carry these genes have a greater chance of developing this problem. "What we have not proven is: Are all carriers going to be at increased risk?" she said.

While this research has the potential for significant payoff, challenges exist. For example, a standard definition of statin-induced myopathy is lacking, making it difficult to compare one study to another. In response, Vladutiu is using part of the grant to establish a scoring system to make assessment more precise.

"We need to qualify and quantify what severe means," she said.

This potential side effect also can be tough to diagnose. These drugs are primarily used by older people, and it's not always clear whether a new ache or pain is due to initiating statin therapy or age. In addition, several studies have found that physicians may discount patient complaints of myalgia after starting these drugs.

"Patients who complain of muscle weakness are not all loopy. There really is something going on," said Paul D. Thompson, MD, director of preventive cardiology at Hartford Hospital in Connecticut. He also has NHLBI funding to investigate the effect of statins on muscle strength.