Not All ‘Good’ Cholesterol Is Good, Study Says

For almost 52 million Americans with high cholesterol, the complex causes of heart disease were long ago reduced to a simple formula of good cholesterol and bad cholesterol. The higher the ratio of good cholesterol to bad cholesterol, the greater the chances of staying healthy.

Now experiments with genetically engineered mice show that some high-density lipoproteins--the so-called good HDL cholesterol long thought to prevent heart disease--may cause it.

Researchers at UCLA have demonstrated that mice with high levels of a common HDL are more likely to develop atherosclerosis than normal mice.

Even mice on a low-fat diet had a higher incidence of heart disease if that specific HDL protein was present, the researchers determined.

Their finding, published today in the journal Science, calls into question the growing consensus among medical professionals that HDL is a key defense against coronary artery disease, which kills 500,000 Americans every year. It leaves many health-conscious people where they started when the cholesterol debate began: trying to decide how much of what is too much.

“What this study shows is that HDL proteins are not all alike,” said medical geneticist Aldons Lusis, one of five UCLA scientists who conducted the research, sponsored by the National Institutes of Health.

“Some may protect against atherosclerosis and some may not. Some may be associated with increased risk,” he said.

“This is probably something people don’t want to hear because it means that it all is more complicated and not so straightforward,” he said.

Cholesterol, a natural substance found in all body cells, is carried through the bloodstream in protein capsules. If it accumulates along artery walls, it can constrict the flow of blood and heighten the probability of a heart attack.

Low-density lipoproteins (LDL) carry cholesterol from the liver throughout the body. High LDL levels are regarded as a major risk factor for heart disease.

HDL proteins remove excess cholesterol from the bloodstream and carry it to the liver, where it is removed. Low levels of HDL have been associated with high risk of atherosclerosis.

In the effort to combat heart disease, HDL cholesterol has recently attracted considerable attention.

Earlier this year, a panel of experts convened by the National Heart, Lung and Blood Institute urged physicians to test for HDL as a “negative” risk factor that would reduce the chances of developing heart disease.

The National Cholesterol Education Program in June urged doctors treating patients with high cholesterol to select medications that raise HDL levels. Many popular drugs prescribed to treat high cholesterol benefit in part from their ability to increase levels of HDL blood proteins.

Several groups have been experimenting with synthetic HDL proteins in the hope that they can come up with an effective treatment for heart patients.

Some researchers even speculated that moderate drinking, which some studies suggest appears to reduce coronary disease, owed its beneficial effect to the ability of ethyl alcohol to increase levels of HDL in the bloodstream.

If borne out by additional research, the UCLA study adds an unexpected variable that may lead clinicians to reconsider the role of HDL in heart disease.

Scientists are not sure how the new findings on HDL proteins will affect the diets and clinical exercise regimens prescribed to lower blood cholesterol levels. It is too early, they say, for heart patients to ask what foods promote high levels of good HDL cholesterol or lower levels of bad HDL cholesterol.

“Eventually, there will probably be dietary and diagnostic implications. But we don’t know enough to apply it immediately,” Lusis said.

There are two common HDL proteins: apoA-I, which apparently does confer some resistance to coronary artery disease, and apoA-II, the subject of the UCLA study, which appears to do the opposite.

Earlier studies with genetically engineered mice at the Lawrence Berkeley Laboratory provided direct evidence that apoA-I can protect against heart disease.

To isolate the effects of the apoA-II protein, the UCLA team genetically engineered a breed of laboratory mice that produce unnaturally high levels of the protein in their blood.

The result was dramatic.

The animals showed significantly higher levels of HDL and otherwise had low cholesterol levels. Nonetheless, they had much higher levels of coronary artery disease, with a marked increase in the size and the number of lesions.

The reason, researchers said, was that levels of the apoA-II HDL protein were almost three times higher than the levels of apoA-I protein. Scientists do not know why apoA-II should be so harmful. It may be that HDL proteins play other, not yet understood roles in the human immune system and in blood circulation, they said.

“One has to be cautious extrapolating studies with mice to humans, but it is quite likely this has significance for our understanding of human cholesterol metabolism,” Lusis said.

Heart of the Matter

Cholesterol is carried through the blood stream in low-density capsules of special blood proteins called apoproteins. A new study shows that one type of apoprotein thought to prevent heart disease can cause it.

1. Low-density lipoproteins (LDL) carry cholesterol from the liver, where it is created, to the heart and throughout the rest of the body. Higher levels of LDL cholesterol indicate a greater risk of a heart attack.

2. High-density lipoprotein (HDL) binds with cholesterol in the bloodstream and carriy it back to the liver, where it is broken down. In this way, HDL reduces the cholesterol build-up on the artery wall.

HDL is primarily made up of two apoproteins, apoA-I and apoA-II. A new study by UCLA shows that apoA-II causes coronary heart disease in mice.

SOURCES: UCLA, Harvard Medical Schools