Oxidized LDL Cholesterol Linked to Metabolic Syndrome

TUESDAY May 20, 2008 -- Higher levels of LDL cholesterol "packets" that have undergone oxidation are associated with an increased risk of developing metabolic syndrome, a constellation of conditions that can lead to heart attack and stroke, a new study finds.

Previous studies with animals and cell models have linked metabolic syndrome to oxidized LDL cholesterol, the "bad" kind that can build up and block blood vessels. However, this new long-term study shows the association in people, said David R. Jacobs Jr., a Mayo professor of public health at the University of Minnesota, and a member of the team reporting the findings in the May 21 issue of the Journal of the American Medical Association.

"Cholesterol in the blood is associated with the problem of atherosclerosis," or blockage of blood vessels, Jacobs explained. "It is important to the health of arteries that cholesterol be able to zip into and out of cells. If the particle is not oxidized, cholesterol does its stuff and comes out again, doing no damage. The thought is that what is happening in atherosclerosis is that minimal oxidation initiates damage to the artery wall."

What gets oxidized is not the cholesterol itself, but its protein coating, Jacobs explained. "Cholesterol is a fat and it is not soluble in water," he said. "It needs to be surrounded by proteins. Those particles which contain cholesterol float in the bloodstream and interact with the walls of blood vessels."

Cholesterol is a vital ingredient of all cells, so it must be able to enter and leave them quickly, Jacobs explained. Severely oxidized LDL cholesterol is quickly eliminated from the body, but the slightly oxidized version can linger to cause damage.

The oxidized version is only a minor fraction of all LDL cholesterol, ranging from almost none in healthy individuals to 5 percent in those who suffer acute coronary problems, the new study noted.

Researchers followed 1,889 people between the ages of 18 and 30 when first seen, looking for development of metabolic syndrome -- whose components include abdominal obesity, high fasting blood sugar levels and high blood fat levels -- over the next 20 years. The 20 percent of the people in the study with the highest oxidized LDL levels were 3.5 times more likely to develop metabolic syndrome than those with the lowest levels, the researchers found.

A similar relationship was found for the individual components of metabolic syndrome, with people with the highest oxidized LDL cholesterol levels twice as likely to develop abdominal obesity, high blood fat and high blood sugar levels, the study found.

It's not yet possible to say that high levels of oxidized LDL lead directly to metabolic syndrome, the researchers wrote, but "the strong association ... is consistent with a causal role."

"This highlights the potential of oxidized LDL to be a target in perhaps preventing metabolic syndrome," said Bret Goodpaster, an associate professor of medicine at the University of Pittsburgh School of Medicine, who has participated in previous studies of oxidized LDL.

"We have statin drugs that are very effective in treating high LDL levels," Goodpaster said. "The question now becomes, what kind of intervention can we deliver here?"

On a practical level, the new finding does nothing to affect the existing recommendations for prevention of cardiovascular disease, Jacobs said.

"What we can do to start with is not to smoke," he said. "Smoking is associated with higher oxidized LDL cholesterol. I would also recommend a healthy diet and physical activity. The diet should include plant foods with lots of antioxidants, which will probably help to keep the body in better balance."

Goodpaster said there's no evidence now that either lifestyle changes or drug treatment can affect oxidized LDL levels. "What we should be looking for is how these things change with interventions such as statin drugs or lifestyle changes," he said.

More information

Metabolic syndrome and its effects are described by the American Heart Association.

Posted: May 2008


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