Intermountain Press Release

Salt Lake City—In a major new study to be presented to the nation's cardiologists on Monday, LDS Hospital cardiology researchers have identified a naturally occurring enzyme that may predict a person's risk of developing, and even dying, from coronary artery disease - even if they have no standard risk factors.

These findings will be reported at the annual scientific session of the American College of Cardiology held March 6-9 in Orlando, Florida.

"Our findings may allow these individuals to be better classified as to their true risk level by this new method. Those at lower risk, for example, could be treated with lifestyle changes alone," says Dr. Jeffrey L. Anderson, associate chief of cardiology at LDS Hospital and clinical investigator of the study. "Patients with a higher suspected risk would be candidates for medications to lower cholesterol. Given the huge impact of coronary heart disease, and the large numbers of individuals who suffer heart attacks, strokes, or cardiovascular death undiagnosed and untreated, these findings could have important health implications"

The seven-year study of 1,493 patients enrolled in the registry of LDS Hospital's Intermountain Heart Collaborative study showed that elevated levels of the enzyme, known as LpPLA2, significantly increased risk of coronary artery disease. In addition, LpPLA2 levels, unlike other known markers, such as CRP levels, were also predictive of a long-term risk of death due to blockages in the coronary arteries.

Levels of both the enzyme, LpPLA2, and CRP were measured in all patients. They also underwent coronary angiography for diagnosis of possible coronary artery disease. The measured LpPLA2 and CRP levels in each patient were then compared to their angiograms to see if the levels were predictive of heart disease already present. Patients were then followed for almost seven years to see if the measured LpPLA2 and CRP levels were predictive of future cardiovascular problems, including future heart attacks, strokes and death from blockages in the coronary arteries.

"The significance of these results may be most important to those individuals who face a moderate level of risk for coronary heart disease based on traditional risk factors in which the appropriate course of action is unclear, said Dr Anderson.

The study Cardiac researchers at LDS Hospital have played a key role in the identification and understanding of markers to predict a patients risk of heart disease. Cardiovascular inflammation is a precursor of coronary artery disease. The amount of a specific protein in the blood is called C-reactive protein (CRP). CRP is an indicator of inflammation and is currently used as a predictor of coronary artery disease. However, elevated CRP levels are also present in other inflammatory conditions such as infections and arthritis.

In order to find a more specific predictor of coronary artery disease, LDS Hospital researchers collaborated with diaDexus, Inc., of San Francisco to determine whether levels of the naturally occurring enzyme, Lipoprotein-associated phospholipase A2 (LpPLA2) could be used for this purpose.

Dr. Anderson explained that LpPLA2 associates in the blood with low-density lipoproteins (LDL), popularly known as "bad cholesterol". LpPLA2 is carried to the wall of arteries in the heart and elsewhere with the LDL, where it can activate an inflammatory response, promoting atherosclerosis. Because of this, the level of LpPLA2 might serve as a specific indicator of vascular inflammation and, therefore, as a more specific predictor of coronary artery disease than CRP.

Though a future study needs to be conducted to independently validate these findings before they can be incorporated into clinical practice, the present results are very encouraging, particularly considering the large numbers of patients studied, says Dr. Anderson.

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