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High Lipoprotein Levels Can Cause Heart Disease
Date:12/23/2009

Study shows it could be a new target for prevention and treatment

WEDNESDAY, Dec. 23 (HealthDay News) -- A genetic study proves that high blood levels of the fat-carrying molecule called lipoprotein(a) can cause heart disease.

"The case for lipoprotein(a) as a direct cause of coronary artery disease is now firm," said Martin Farrall, a professor of cardiovascular genetics at the University of Oxford in England and senior author of a report in the Dec. 24 issue of the New England Journal of Medicine.

Elevated blood levels of LPA, as it is often abbreviated, have been linked to an increased risk of heart disease and other cardiovascular problems for decades, but the evidence has not been definitive. So while an elevated low-density lipoprotein (LDL) cholesterol level remains the most clearly established indicator of coronary risk, "our paper, by genetic research, shows that LPA plays an important role as well," Farrall said.

"Our results will not perhaps surprise some researchers, but the scale of this project and confidence in our results mean that we can move forward to study the details of LPA and coronary risk," he added.

It is a pivotal finding, said Dr. Sekar Kathiresan, director of preventive cardiology at Massachusetts General Hospital, who wrote an accompanying editorial. "Many things in medicine are associated with an increased risk of heart attack. Almost all of these associations are not of a causal nature. This brings LPA into the domain of causal factors. And if it is causal, that gives hope that reducing it can reduce the risk of heart attack," he said. "

"We are now honing in on a potential therapeutic target," Kathiresan stated.

LPA is a member of the family of molecules that carry LDL cholesterol, the "bad" kind that clogs arteries, in the blood. The most common such molecule is lipoprotein(b), which consists of LDL with one protein attached. LPA is different because it has an additional protein attached.

The study done by Farrall and his colleagues looked in exquisite detail at the genetic makeup of 3,145 people with coronary artery disease and 3,352 free of coronary disease. The study of more than 48,000 variants of 2,100 genes found that two variants affecting LPA levels were strongly associated with coronary disease.

"We speculate and anticipate that our finding may carry over to other cardiovascular diseases, such as some kinds of stroke," Farrall said.

The reason for the harmful effects of LPA is unknown, he said. "A number of speculative mechanisms have been proposed," Farrall said. "Our study doesn't help resolve those."

One immediate impact of the research could be widened use of a blood test for LPA, which has been available for years, Kathiresan said. "This kind of study shows that people who carry a genetically determined high level of LPA have an increased risk, and this will likely increase enthusiasm for measuring LPA blood levels, particularly for people who have heart disease at an early age or have a strong family history of heart disease," he said.

And while at least one available drug, niacin, is known to reduce LPA levels to some extent, "we need a drug that selectively reduces LPA," Kathiresan said. "There is some effort to do that."

A major controlled trial will be needed to show that an LPA-lowering drug reduces the incidence of coronary disease, he added.

One odd sidelight is that while participants in the new study -- and most previous trials -- were white Europeans, elevated LPA levels are more common among people from Africa and southern Asia, Kathiresan noted. Studies of those populations are needed, he stressed.

More information

An introduction to the world of lipoproteins is provided by the American Heart Association.



SOURCES: Martin Farrall, professor, cardiovascular genetics, University of Oxford, England; Sekar Kathiresan, director, preventive cardiology, Massachusetts General Hospital, and assistant professor, medicine, Harvard Medical School, Boston; Dec. 24, 2009, New England Journal of Medicine


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