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Heart Research Targets Enzyme

Posted on: Tuesday, 8 March 2005, 15:00 CST

Measuring levels of a naturally occurring enzyme in blood may help physicians determine treatment for patients "in the gray area" for risk of heart disease, according to researchers at LDS Hospital.

They presented the results of their seven-year, 1,493-patient study to the American College of Cardiology scientific session in Orlando, Fla., Monday.

Their research indicates that elevated levels of the enzyme LpPLA2, shorthand for lipoprotein-associated phospholipase A2, significantly raises the risk of coronary artery disease, according to Dr. Jeffrey L. Anderson, associate chief of cardiology at LDS Hospital and the study's clinical investigator. It also predicts the long-term risk of dying from coronary artery blockages.

Detecting elevated levels of the enzyme could predict the risk even in those who have no standard risk factors for heart disease, he said.

The study used patients enrolled in the LDS Hospital Intermountain Heart Collaborative Study registry. Researchers measured levels of LpPLA2 and the better-known C-reactive protein (CRP), known to indicate inflammation in the blood vessels. All of those enrolled had heart angioplasty to diagnose possible coronary artery disease, then the angiogram results were compared to their LpPLA2 enzyme and CRP levels to see if the latter two factors indicated the presence of heart disease. They were subsequently followed for nearly seven years to see if those LpPLA2 and CRP levels predicted future cardiovascular problems, such as heart attacks, stroke and death from blockages in the coronary arteries.

Anderson said the results indicate particular potential benefit for those who have a moderate level of risk for heart disease, based on traditional risk factors.

It's clear that coronary artery disease is not a passive process but an active one, Anderson said, believed to be triggered by inflammation in the blood vessels.

The inflammation leads to plaque, ruptures and clots that damage and kill. The hope is the study will provide another tool to identify those living with heart-disease-promoting inflammation before a cataclysmic event like a heart attack. It could also tell physicians whether someone who has had such an event still has the dangerous inflammation so that treatment could be tailored to prevent further damage.

While CRP indicates inflammation and is used as a predictor of coronary artery disease, elevated levels can also be a sign of other conditions such as infections, rheumatoid arthritis, even a cold, he said.

Elevated LpPLA2 is different. The enzyme directly travels with low-density (LDL) cholesterol -- the "bad cholesterol" -- and is carried to the artery walls where it can kick off inflammation that promotes atherosclerosis. That's why researchers believe LpPLA2 levels might be a specific indicator of vascular inflammation and therefore a more specific predictor of heart disease than CRP.

Elevated LpPLA2 doubles the risk of coronary heart disease and, depending on how high it is, can quadruple risk of death from heart disease, Anderson said.

Further study is needed, he said. But he expects it to offer guidance when a patient has only one or two known risk factors for heart disease. In treating such patients, doctors wrestle with whether to prescribe lifestyle changes such as more exercise and better diet alone or whether more aggressive treatments such as medications are needed.

"It's a tie-breaker, so to speak," Anderson aid. "No test is so good we're going to use it alone." He added that it helps complete the picture.

Three-fourths of patients who have heart attacks do not have a lot of high-risk factors, so they "don't stand out" as being in particular danger. The new research may provide yet another type of information that can be evaluated to make good treatment choices, Anderson said.

Some factors by themselves clearly indicate the need for action, such as steps to lower high blood pressure or high cholesterol.

ARUP Laboratories is one of four in the country that have developed a plaque test that will detect levels of LpPLA2, he said.

In the search for a more specific predictor of coronary artery disease, the researchers teamed up with diaDexus, Inc.cq of San Francisco to determine if LpPLA2 could be used.

Other members of the LDS Hospital research team were Benjamin D. Horne, Robert L. Wolfert, Dr. Joseph "Brent" Muhlestein, Dr. Dale G. Renlund, Jessica L. Clarke, Heidi Thomas, Matthew J. Kolek, Tami L. Bair, Robert R. Pearson, Krishnankutty Sudhir and John F. Carlquist.

E-mail: lois@desnews.com

Source: Deseret News (Salt Lake City)

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