Michael Lauer, M.D., is the director of the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute (NHLBI). Recently, he discussed progress on high cholesterol research.
As our nation gets heavier and older, what does recent research on cholesterol and heart health tell us that Americans need to understand?
We are making progress. A newly released survey from the Centers for Disease Control and Prevention (CDC) shows that only 13 percent of Americans have elevated cholesterol levels, down 27 percent over the past 10 years. We think this is because of better diet and greater use of statins. Americans need to understand that the "cholesterol hypothesis" is for real—there no longer is any question that elevated cholesterol causes atherosclerosis, and that, in appropriate settings, reducing cholesterol is the way to go.
What is the current status of treatment for very high cholesterol? And how effective is that treatment?
We treat very high cholesterol levels with a combination of diet and drugs, mostly statins, sometimes in combination with other medications. There is clear evidence that statins reduce the risk of major clinical events—such as heart attack and stroke—in people with very high cholesterol.
Does research hold promise that someday we can better treat cholesterol problems?
Yes. There is now evidence that a monoclonal antibody to the enzyme PCSK9 can substantially reduce cholesterol levels, both in healthy volunteers and in people with familial hypercholesterolemia (a genetic cause of very high cholesterol).
Do gene-based challenges like familial hypercholesterolemia perhaps hold a key to how we understand cholesterol in all people?
Yes. Our understanding of the role of the LDL-receptor contributed to the eventual discovery of statins and their potential role in preventing heart attacks and strokes. Current work on PCSK9, which binds to and degrades the LDL-receptor is, in a way, a continuation of the same theme.
What would you say are areas of promising research related to high cholesterol and blood fat?
There are a number of exciting avenues, in addition to the PCSK9-based treatment:
- Determining the role, if any, of niacin (a vitamin) and ezetimibe (a drug that inhibits the absorption of cholesterol by the small intestine) as complementary agents to statins.
- Determining the role of anti-inflammatory therapies on top of statins, which themselves have anti-inflammatory properties. NHLBI is funding a large-scale trial of the drug methotrexate in high-risk patients with vascular disease. We have come to appreciate that hypercholesterolemia (gene-based high cholesterol) and chronic inflammation are tightly intertwined.
- Determining whether it's possible to "transform" fat from primarily white (energystoring) to primarily brown (energy-burning) forms, thereby correcting the metabolic abnormalities associated with obesity.
- Evaluating the "local effects" of fat. For example, Dr. Caroline Fox and her colleagues at the Framingham Heart Study are finding that fat collections in the pericardium (the sack around the heart) may have direct toxic effects on the coronary arteries.