Researchers work to harness power of good cholesterol

When it comes to cholesterol, doctors are sure of two things: High levels of the bad kind increase the risk of heart disease, and lowering those levels reduces the risk. So traditional treatments are aimed at cutting bad cholesterol through diet, exercise and drugs called statins.

Now cardiologists are trying to harness the power of good cholesterol to help stave off heart disease. Clinical trials of drugs designed to boost good cholesterol are underway. Meanwhile, scientists are learning more about how it contributes to health: A new study suggests it’s not just the total amount of good cholesterol that matters, but how efficiently it’s able to gobble up bad cholesterol.

“We’re getting very excited about good cholesterol,” says Dr. Christopher P. Cannon, a cardiologist at Brigham and Women’s Hospital in Boston. “That may become the next big thing.”

Cholesterol is a waxy substance produced naturally in the body. It circulates in the blood, where it is a necessary ingredient to coat nerve cells and keep cell membranes fluid and permeable, among other functions. We consume cholesterol when we eat animal-based fats such as those in dairy products, egg yolks and red meat. Genetics, body weight and exercise and other lifestyle choices also influence cholesterol levels.

But not all cholesterol is the same.

Low-density lipoprotein, or LDL, is Public Enemy No. 1 because it gloms up and gets trapped in the walls of blood vessels, leading to inflammation and a dangerous buildup of plaque in the artery wall. In addition to constricting the flow of blood, the plaque can rupture and cause clots to form, in some cases leading to a heart attack or stroke.

“Every 10% reduction in LDL cholesterol is translated to a 10% reduction in cardiovascular risk,” says Dr. Gregg C. Fonarow, a professor of cardiovascular medicine at UCLA. This is true for men and women, old and young, people who have never had a heart attack or stroke and people who have suffered multiple cardiovascular events, he says.

High-density lipoprotein, or HDL, can counteract LDL by removing it from the arteries and delivering it to the liver so it can be excreted. Studies show that people with high levels of HDL have a lower incidence of heart attacks and stroke, while those with low HDL have an increased risk of such events.

Based on the success of statins in lowering LDL, researchers are trying to create a new generation of drugs that will be just as effective at raising HDL. The strategy is based on the idea that the more HDL there is in the bloodstream, the more LDL it can clear from the body.

But direct evidence that using drugs to boost HDL actually improves heart health is still lacking.

A high-profile clinical trial of a Pfizer drug designed to raise good cholesterol was stopped prematurely in 2006 because the people who took it in combination with a statin had a 58% higher rate of death over 12 months than another group of people who took the statin alone. Those extra deaths occurred even though the drug raised HDL levels by 72%.

Still, experts say HDL remains a promising target. In November, researchers reported in the New England Journal of Medicine that the HDL-boosting drug anacetrapib raised good cholesterol by 138% — a “whopping increase” that is five times bigger than currently available treatments, says Cannon, who led the study. The drug, made by Merck & Co., also reduced bad cholesterol by 40% and showed no signs of increased cardiovascular side effects.

It’s not yet clear whether those improvements will mean fewer heart attacks and strokes. Cannon and his colleagues are beginning a study involving 30,000 patients to determine whether anacetrapib reduces the risk of heart disease and death from cardiovascular disease, the results of which are at least four years away.

Other researchers are examining whether more good cholesterol is always better or if something more subtle is going on.

Dr. Daniel Rader, director of preventive cardiovascular medicine at the University of Pennsylvania School of Medicine in Philadelphia, says good cholesterol isn’t all created equal. In a study published this month in the New England Journal of Medicine, he reported that HDL function might in fact trump HDL level when it comes to reducing the risk of heart disease. The finding could influence the development of therapies aimed at HDL.

Given these complexities, it’s no surprise that doctors keep changing their minds about whether LDL and HDL levels are most important for patients, or if what really matters is the ratio of the two.

“I talk to patients about both of them,” says Dr. John Saultz, chairman of the department of family medicine at Oregon Health and Science University in Portland.

At the moment, most doctors are emphasizing the need to control both good and bad cholesterol, and if either is out of healthful range they will recommend steps to correct it. “I don’t think many physicians in practice would withhold statin therapy from a patient simply because they also had a high HDL,” says Dr. John C. LaRosa, a cardiovascular specialist who studies statins at the State University of New York Health Science Center at Brooklyn.

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