Who does -- and doesn't -- need cholesterol-lowering drugs.

By Daniel DeNoon
WebMD Feature

Reviewed By Brunilda Nazario

The newest dance: the cholesterol limbo.

Step one: You get your bad LDL cholesterol down to normal levels. Whew! You're under the bar.
Step two: Your doctor says normal levels aren't low enough and sets the bar lower.
Step three: You get your cholesterol way down. You're under the bar again!
Step four: New research shows that even lower LDL cholesterol levels are better. The bar drops again.

How low must you go?

If you're starting to get obsessed with cholesterol, you aren't alone. Ernst J. Schaefer, MD, is director of the lipid metabolism laboratory at Boston's Tufts University. He's also head of the heart disease prevention clinic and the lipid research laboratory at New England Medical Center.

"My wife complains that all I do is dream about these particles," Schaefer tells WebMD.

That's because Schaefer's job is to keep people from dying of heart disease. This means improving the condition of people who already have heart disease. And it means preventing heart disease in people who don't yet have it.

Bad Cholesterol

When we talk about cholesterol, we're usually talking about bad cholesterol: low-density lipoprotein or LDL. A little too much LDL starts the heart-disease ball rolling.

When a person's blood is loaded with LDL cholesterol, the stuff builds up inside the walls of the large blood vessels known as arteries. This plaque irritates the blood vessel walls. The immune system gets involved and this only makes things worse. The blood vessel lining becomes fragile and unstable -- what doctors call inflammation. The artery narrows, and blood flow is restricted. And if the inflamed area of plaque bursts through the artery wall, the resulting clot can cause a fatal heart attack or stroke.

This is why your doctor's focus is on your LDL cholesterol level. The average American has an LDL level of about 130 mg/dL. About 25% of us have an LDL level higher than 150, and about 25% of us have an LDL level lower than 100.

Everybody, Schaefer says, should get their cholesterol level below 160 mg/dL -- at the very least. An LDL level below 130 is much better. And many of us -- especially those who have heart disease -- should have much lower LDL levels than that.

But LDL it isn't the whole story.

Good Cholesterol

You also have a kind of cholesterol called high-density lipoprotein, or HDL. HDL is the good guy.

"HDL is responsible for pulling LDL cholesterol out of the artery wall," Schaefer notes. Too little HDL -- less than 40 mg/dL -- raises heart disease risk . Plenty of HDL -- at least 60 mg/dL --- greatly lowers heart disease risk.

Pretty simple, right? Wrong, says UCLA professor Prediman K. Shah, MD, director of cardiology and the Atherosclerosis Research Center at Cedars-Sinai Medical Center in Los Angeles.

"It gets complicated very quickly," Shah tells WebMD. Inflammation in the artery in response to "bad" LDL cholesterol can vary from person to person, depending on factors of which we don't have a clue, says Shah. "This very simplistic notion that everybody's LDL is equally inflammatory cannot be true. This can explain why some people get heart disease at relatively low LDL levels, and some do not."

People differ in how well their HDL works, too.

"We know not only the quantity of HDL, but also the quality of HDL is important," Shah says. "If you have highly efficient HDL, good. If you have the poopy kind of HDL, it's not much help."

Your Cholesterol

LDL cholesterol isn't the whole story. But it's where you have to start, Schaefer and Shah agree. So what story does a person's LDL cholesterol level tell?

"To understand the significance of a person's LDL level, one would have to look at the entire risk profile for this patient," Shah says. "If it's a high-risk patient, we would want to lower LDL to 70-85 -- we don't know the precise ceiling. So the higher the risk, the lower we would want to go with LDL lowering. The severity of intervention should match the magnitude of risk, not just the risk factor."

What's a high risk? The main risk factor is age, Schaefer says. This means 45 or older for men and 55 or older for women. That counts as one risk factor. Two risk factors give a person a 20% chance of heart disease in the next 10 years. The risk factors are:

Age 45 or more for men, 55 or more for women
Cigarette smoking
High blood pressure -- greater than 140/90
Low HDL cholesterol -- less than 40 mg/dL
A close relative who had heart disease at an early age -- before 55 for a male relative and before 65 for a female relative.
A 20% risk of heart disease over 10 years based on the Framingham table, an estimate of risk based on age, blood pressure, cholesterol levels, and smoking.

But this list -- from the National Cholesterol Education Program -- is already outdated, says Laurence S. Sperling, MD, director of the Emory Heart Center risk reduction program.

"These are minimal guidelines," Sperling tells WebMD. "Right now those guidelines in clinical practice are already outdated."

Shah and Schaefer agree that other risk factors should be considered:

Insulin resistance
Obesity or a BMI of greater than 30
A waist size of more than 40 inches for a man and 35 inches for a woman
Signs of early, asymptomatic heart disease

And there's also a "very high risk" category. This includes people who already have heart disease and people who have diabetes.

"So the target is getting LDL cholesterol under 160 in everyone, to less than 130 in people who have two or more risk factors or who have a 10% to 20% risk of heart disease over 10 years, and then less than 100 in very high risk people," Schaefer says.

Recent studies show that very aggressive treatment -- getting LDL levels down to 70 or 80 -- reduces the risk of worsening disease or death in very high-risk patients.

Sperling notes that though it's easy to say who is at very low and very high risk of heart disease, it's not a simple thing to evaluate heart disease risk in the average middle-aged person. Shah agrees.

"Some day, we will really be able to determine each individual's risk and ferret out those who do not have risk of a heart attack," Shah says. "Unfortunately, right now our crystal ball is very fuzzy."

This means too many people get treated too aggressively, Shah says.

"We tend to treat a lot of people, out of whom only a few will benefit," he notes. "When we say a person is high risk, for example, we mean someone with a 20% chance of stroke or death in 10 years. That is 2% a year. So for 100 such patients, 98 will not have a problem, but we will give then intensive treatment anyway. Unfortunately, we are not good enough at picking out those two in 100 people who really need such treatment. That is a limitation of our ability to predict heart disease. The better we get at predicting which patients will have a heart attack, the better we can use these intensive lipid-lowering therapies."

In the meantime, Shah says, it's important to look beyond risk factors for physical signs of disease.

Cholesterol Lowering Drugs -- Not the Whole Answer

Americans spend more money on cholesterol lowering drugs -- known as statins -- than any other kind of medicine. The market is growing. And it will get larger, now that new drugs that increase HDL cholesterol are making their way through clinical trials.

These drugs save lives. But they aren't the only way to lower cholesterol. Getting more exercise, eating a low-fat/reduced-calorie diet, substituting plant-sterol products for fat, eating more soy, and getting plenty of fiber all reduce cholesterol. Add them all up, and the effect is similar to that seen with cholesterol-lowering drugs -- without the side effects or high cost.

And drugs can never be the answer to America's heart disease epidemic, Sperling notes.

"The average American may be fine with an LDL of 120, but when we're born we have an LDL of 25 or 30," he notes. "If we put statins in the drinking water, would it help public health? Yes, but public health endeavors would help more. Our obesity epidemic needs to be conquered not with medicine but with effective change for the whole population. If you're looking at cost-effectiveness, the time to teach people to eat right and exercise is when they are kids. We can do that -- or we can start throwing 10 medicines at them when they are 40 or 50 years old."

Published March 24, 2004.

SOURCES: Ernst J. Schaefer, MD, director, Lipid Metabolism Laboratory, Tufts University; director, heart disease prevention clinic and lipid research laboratory, New England Medical, Boston. Prediman K. Shah, MD, director, division of cardiology and the Atherosclerosis Research Center, Cedars-Sinai Medical Center; professor, UCLA School of Medicine. Laurence S. Sperling, MD, director, risk reduction program, Emory Heart Center, Atlanta. ATP III Guidelines, National Cholesterol Education Program. Topol, E.J., The New England Journal of Medicine, April 8, 2004 [early release downloaded March 22, 2004]; vol 350. Cannon, C.P. The New England Journal of Medicine, April 8, 2004 [early release downloaded March 22, 2004]; vol 350.

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