A New Risk Factor for Heart Disease

The finding could lead to new ways of preventing heart disease. An ordinarily benign fat that coats blood vessels can turn into a risk factor for heart disease when it combines with oxygen, researchers report.

A first-ever study shows that high blood levels of the molecules, called oxidized phospholipids, are associated with increased blockage of heart arteries, the study found. Phospholipids are just one of the many families of fats found in the body, and normally they are harmless, said Dr. Sotirios Tsimikas, director of vascular medicine at the University of California, San Diego, and the lead author of the report.

But when they are oxidized, he added, they trigger inflammation that damages blood vessel walls and accelerates the formation of fatty plaques that eventually can stop blood flow, causing a heart attack.

Tsimikas and his colleagues measured blood levels of oxidized phospholipids and Lp(a) lipoprotein, another fat that has been linked to heart disease, in 504 people who underwent coronary angiography, which measures the extent of blood vessel blockage. Those with the highest levels of both molecules had 16 times more artery blockage than those with the lowest levels, Tsimikas said. "They are perfect partners in crime," he added.

As for oxidized phospholipids, "this is the first time we have shown that a small amount circulating in the blood stream correlates with the extent of coronary artery disease," Tsimikas said.

The finding helps solve a mystery about Lp(a) lipoprotein, an unusual molecule that is found only in humans, monkeys and apes, he said. Studies have shown that it is associated with the deterioration of blood vessels that leads to heart disease, but the way it does the damage has not been known.

"We argue that binding with phospholipids causes Lp(a) to be toxic," Tsimikas said.

The finding could lead to new ways of preventing heart disease, said Dr. Andrew W. Watson, assistant professor of medicine/cardiology at the University of California, Los Angeles’ David Geffen School of Medicine, and co-author of an accompanying editorial.

"There are a couple of ideas," he said. "One of them is to prevent formation of these molecules, which involves preventing oxidation." But the value of antioxidants such as beta carotene is far from certain, Watson said. "The whole antioxidant hypothesis has been thrown into doubt," he said. "There are a number of questions that have been raised by recent studies."
Another approach would be to use enzymes to break down the toxic phospholipids, Watson said. A couple of promising enzymes have been found in HDL cholesterol, the "good" kind that carries fat out of the blood. But research with them so far has been limited to animal studies, he said.
New England Journal of Medicine. July 7, 2005

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