The message is loud and clear — when it comes to bad (LDL) cholesterol, aim low. But now researchers are finding that LDL represents only half of the story.

A recent study published in JAMA found that raising levels of one's "good" HDL cholesterol boasts significant benefits in halting the progression of atherosclerosis. In the study of 1,455 patients, the Cleveland Clinic team reaffirmed the benefit of cholesterol-lowering medication in reducing LDL cholesterol while highlighting the role of increasing one's HDL in preventing clogged arteries.

"This study provides further evidence to help us understand how statins work to prevent heart disease," explained lead investigator Dr. Stephen Nicholls, Cleveland Clinic cardiologist. "What the current findings tell us is that raising levels of HDL, even to a small degree, can result in important benefits for patients."

Exercise is one path to raising HDL. Another is to combine a statin with a drug that raises HDL. A promising newcomer was the cholesterol drug torcetrapib. heralded as a blockbuster that would lower LDL. raise HDL, and transform cardiovascular care. But the clinical trial was halted due to increased heart problems among the test participants.

The quest continues.

"If we can find the right way to raise HDL. the benefits to patients can be substantial," said Dr. Steven Nissen, senior author of the JAMA study. "Despite the failure of torcetrapib, we must continue to search for therapies that produce major elevations in the level of HDL."

The Post spoke with Dr. Nissen, current president of the American College of Cardiology, about steps that you can take to reduce your risk of cardiovascular disease, including the role of niacin — an effective HDL booster.

Post: Could you share findings from your recent study published in JAMA?

Dr. Nissen: The take-home message is: a little bit of HDL goes a long way. We've known for years that cholesterol-lowering statins raise HDL a little, but frankly most of us thought it wasn't very important. After all, statins lower bad LDL cholesterol by 30 percent or more, but raise HDL by about 8 percent, so this didn't seem an important fact.

But when we looked at the issue carefully by combining a number of trials, we saw that small elevations of HDL were almost as important a driver in determining the rate of progression of atherosclerosis as LDL reduction. The finding becomes particularly interesting in the wake of the recent failure of the torcetrapib. We know that torcetrapib raised HDL substantially, but exactly how you raise it may also be important.

Some maneuvers that patients engage in, such as exercise, can raise HDL 10 to 15 percent.

Post: How often should patients exercise to raise HDL?

Dr. Nissen: You need at least three sessions per week of 20 to 30 minutes — frankly, the more the better. A good vigorous 30- to 40-minute walk every day is optimal and will raise HDL. You can also raise HDL by losing abdominal fat. Reducing the waistline can have a huge impact on HDL by 20 to 25 percent. In our study, we showed that modest elevations of HDL confer substantial health benefits, which should prompt us to counsel our patients about the benefits of even modest exercise.

Post: When it comes to preventive measures, what role does niacin play?

Dr. Nissen: When you take a lot of niacin, you can raise HDL substantially — by 25 percent or more in some people. People get flushing and itching, but it works. In fact, many people in the wake of the failure of torcetrapib are returning to niacin. One important precaution is that I'm seeing more and more patients taking "no flush niacin" sold in health-food stores. The product is actually a fraud and offers no benefits in raising HDL levels.

Post: In your clinical practice, do you use niacin in combination with statins?

Dr. Nissen: I do, but I monitor its use and risks. When taking niacin, there is a higher likelihood of raising liver enzymes. Statins have a one or two percent risk of elevating liver enzymes, but if you add niacin, the risk goes up. You don't want to take niacin with a statin without a physician who is knowledgeable about its use and who monitors you closely. I talk to patients on the phone, if they have problems. Every three months or so, I get lab work to monitor liver enzymes. If they've been on the combo for a while and everything is going well, we schedule their visits less often.

By adding niacin, HDL goes up significantly, and patients can get some substantial benefits. Statins push down the LDL significantly and slightly raise the HDL. Niacin raises HDL a lot and lowers LDL some. The combination is pretty useful.

By the way, the combination is not that risky. But there's the Latin axiom, Primum non nocere, meaning "First, do no harm." It's important for the public to understand that all medications pose risks and that we have to be respectful.

Part of the equation is getting the right dose of statins and the right dose of niacin for the right patient. I use the lowest dosages that will get people to the goal that we've set. and I urge people to incorporate dietary and lifestyle measures so we don't have to use as many drugs.

If a person could lose a little weight and begin an exercise program, maybe we'll only need 10 mg of the statin instead of 20 or 40, which poses less risk of producing a side effect. This partnership between the patient and the physician combines lifestyle changes and medication.

Post: The FDA recently approved extended-release Niaspan to prevent recurrent heart attacks in patients with high cholesterol. Do the results compare favorably with those of statins in preventing heart attacks?

Dr. Nissen: There is substantially less data on Niaspan, which is a slow-release form of niacin. We have some reasonable evidence that it works, but there are no big, controlled, well-performed trials.

The NIH launched and is currently enrolling participants in a multicenter, randomized, controlled clinical trial to measure the independent effect of treating HDL and triglycerides with simvastatin (Zocor) alone or in combination with niacin. It will show whether the two together are better than one alone.

Post: Prescribing information on niacin indicates the drug may cause an increase in blood sugar levels. Is it safe for diabetics?

Dr. Nissen: It tends to raise blood sugar some. In susceptible individuals, it can provoke diabetes, so you have to be careful. I personally have not had trouble with that. A new drug in development called MK0524 is a combination of niacin with a second drug that blocks the flushing. It's under review with the FDA, and there is a large trial under way by the Oxford group in England — a very competent clinical trial center — to determine whether, in fact, it can reduce the risk of heart attack and stroke. It has promise but requires further study. It's not currently clinically available, but it is on the radar.

Post: Is there an optimal HDL level?

Dr. Nissen: We know so little about. HDL compared to LDL. Generally, it looks like higher HDL is better. In our report, it is clear that an HDL of 50 is better than 40. and 70 is better than 60. But there is much to learn about HDL. It's the great frontier in the lipid arena.

Post: Recently I heard that a low LDL of 70 confers protective benefits. Can lowering bad LDL cholesterol actually reverse the disease process?

Dr. Nissen: The finding is the result of a study called ASTEROID that we published in JAMA in 2006. In the study, we gave a very intensive cholesterol-lowering regimen with rosuvastatin and lowered mean LDL levels to 60. We saw a lot of regression of disease. But ASTEROID was not a mortality trial, so current guidelines don't necessarily recommend an LDL of less than 70 for all patients because we need the scientific evidence to support the recommendation.

Post: As a researcher and clinician in the field for many years, how do you think statins have changed cardiovascular medicine?

Dr. Nissen: Enormously. When I was in medical school, I was taught that a total cholesterol under 300 was normal. Now, we go lower and lower. Statins let us get there. Statins can lower cholesterol by 40 percent with very few side effects. While not completely innocuous, they are well tolerated and among the safer drugs that we use to get an edge on the disease. However, we're beginning to lose our edge because of another societal phenomenon — the diabetesobesity epidemic. Statins are not enough. They lower risk about a third. What are we going to do for the other two thirds of the patients? That's why we need new drugs and why there's a lot of research going on. I'm involved in research to push up HDL levels to block the atherosclerotic disease process.

Post: What other treatments appear promising?

Dr. Nissen: Many drugs are in development designed to interrupt the disease process at various points. It's still early. The public needs to know that those of us who work very, very hard in this area are engaged with industry in finding new drugs. There's a clear message here — statins are fabulous, but they're not enough. They still leave a number of patients unprotected, and we would like to get beyond the plateau we've been on. We've had statins in the U.S. since 1987, but there's been no big new class of drugs since. I'm impatient because I see these patients every day with heart attacks, and frankly, it can break your heart when you see somebody in the prime of life have a devastating event. We are working as fast as we can.

Post: What proactive steps do you recommend that people take to preserve heart health?

Dr. Nissen: Diet, exercise, and consider HDL-raising drugs. Physicians are somewhat less vigilant about monitoring and treating HDL than they are LDL. If you know you have low HDL, maybe you should talk to your doctor about it. It is important that we respect the public's intelligence and present the facts because, frankly, knowledge is power.

"By adding niacin, HDL goes up significantly, and patients can get some substantial benefits."