Cholesterol-Lowering Drugs: Can They Do More?

How well do statins lower cholesterol?
Statins increase the activity of the LDL receptor on the surface of the liver, which makes most of the body's cholesterol, and promote the removal of LDL, the bad cholesterol, from circulation. The level of reduction varies, depending on what statin is used and the statin dose, but they generally reduce LDL cholesterol anywhere between 25 percent and 50 percent.

Can statins help prevent cardiovascular disease in people who do not have high cholesterol?
A number of trials have shown that statins reduce the risk for heart disease in patients who have average or only moderately elevated cholesterol levels. The Anglo-Scandinavian Cardiac Outcomes Trial recently showed that using statins in patients who had hypertension, another risk factor for heart disease, but did not have a particularly high cholesterol, significantly reduced the risk of major coronary events and stroke.

What role can statins play in preventing or treating complications of diabetes?
Because people with diabetes have a high risk for developing heart disease, the major role that statins can play is to help reduce a diabetic person's risk for heart attacks. Clinical trials suggest that statins are effective for this purpose in this group. More controversial are some very preliminary data that suggest that statins can possibly reduce the risk for developing diabetes, perhaps through a process that reduces inflammatory processes in the body. More research is definitely needed on this subject.

What are some theories about the benefit statins in Alzheimer's, MS and osteoporosis?
Much of the interesting data in regard to this could also have to do with the anti-inflammatory effects of statins. We know that the immune system is critical for helping the human body fight off infections, but certain diseases like arthritis are associated with inflammation in the body, perhaps because of an abnormal immune response. In experiments, statins can reduce the presence of some markers of inflammation, and these data suggest that statins may exert an anti-inflammatory action that is poorly understood, right now.

We have very little information about the situation with MS, but I would speculate that if the finding is borne out and confirmed, it might be on the basis of an anti-inflammatory effect. In Alzheimer's disease, the benefit could have to do with improvement of blood vessel function, as well as a reduction in carotid blockage. Statins also increase bone density and they may increase the formation of one of the proteins that forms a matrix of the bone. So this would be beneficial in conditions with bone thinning such as osteoporosis.

There are conflicting data from clinical studies: Some suggest benefit, others don't. We have to await the outcome of a large, controlled clinical trial in order to determine whether there's a significant beneficial effect of statins in diseases such as osteoporosis, Alzheimer's or multiple sclerosis.

What are some side effects of statins?
The most important side effect is myopathy, which is weakness, pain or tenderness in the muscle. Fortunately, this is relatively uncommon. When taking statins alone, the risk of myopathy is about 1 in 1,000 or 1 in 10,000. More common but of less clinical importance are the changes in liver tests. There may be an increase in liver function tests in 1 percent to 2 percent of patients taking statins. And there may be some nonspecific other complaints, such as headache, gastrointestinal disturbance, musculoskeletal aches and pains. In the large clinical trials, there usually are no differences between these side effects in the placebo group and the statin group.

Do you think the role of statins will continue to evolve?
The statins have now been studied in hundreds of thousands of patients and have proved to be remarkably safe and effective. They changed the way we treat and prevent coronary disease and cardiovascular disease in the 20th century and are at the forefront of cardiovascular drug therapies in the 21st century.

For now, it is not likely that statins will be used for conditions other than risk reduction for cardiovascular disease. However, laboratory and other data suggesting effects on Alzheimer's, multiple sclerosis and osteoporosis are interesting and deserve further investigation.

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