Aug 16, 2004 17:00 ET Benefit of 'Good' Cholesterol in Arteries Limited by Enzyme Linked to Heart Attack Risk, Clinic Study Shows

Findings Appear in Aug. 16 Issue of The Journal of Clinical Investigation

CLEVELAND, Aug. 16 /PRNewswire/ -- Researchers at The Cleveland Clinic have discovered that not all HDL, or "good" cholesterol, helps to protect arteries from becoming clogged with fatty deposits. Clinic researchers discovered a chemical signature for "dysfunctional" HDL, or HDL that does not protect against atherosclerosis in some individuals.


"This study helps explain why not all persons with high HDL levels are protected from getting heart disease," said Stanley Hazen, M.D., Ph.D., head of the Section of Preventive Cardiology and Rehabilitation at The Cleveland Clinic.


HDL becomes dysfunctional, Dr. Hazen said, when myeloperoxidase (MPO), an enzyme present in white blood cells, inhibits the HDL's ability to keep LDL, or "bad" cholesterol, from building up in artery walls.


Previous Cleveland Clinic research led by Dr. Hazen found that in patients seeking emergency care for chest pain, elevated MPO levels identified who was at risk for heart attack, bypass surgery or death within the next six months. A new test is being developed at the Clinic to measure MPO levels and determine heart-disease risk.


The present study shows for the first time a link among MPO, HDL and HDL's role in removing bad cholesterol from arteries. The study also describes the mechanism of how dysfunctional HDL is made.


Results of the study indicate that apolipoprotein A-I, or apoA-I, the primary protein found in HDL, is targeted for damage by MPO, disrupting HDL function. The new study suggests that MPO and apoA-I interactions play a significant role in a person's overall risk for cardiac disease.


A specific "chemical fingerprint" for MPO-damaged HDL was discovered in the blood of people with heart disease. Those with a high level of this marker showed a 16-fold increase in heart-disease risk. Thus, the study suggests this new test for dysfunctional HDL could be a 10-fold better predictor of heart- disease risk compared to cholesterol levels alone.


"Remarkably, up to 50 percent of the HDL recovered from atherosclerotic plaque in some subjects does not promote cholesterol removal," Dr. Hazen said. "This study also helps explain why MPO is predictive of atherosclerosis."


The study -- conducted by researchers at The Cleveland Clinic Lerner Research Institute and The Cleveland Clinic Heart Center, Section of Preventive Cardiology -- appears in the Aug. 16 issue of The Journal of Clinical Investigation, available online at http://www.jci.org/ .


The study's first author is Lemin Zheng, a graduate student at Cleveland State University who is completing his doctorate research in the Department of Cell Biology and the Center for Cardiovascular Diagnostics and Prevention at The Cleveland Clinic Lerner Research Institute. He worked on this study as part of his Ph.D. research. In addition, research groups led by Mike Kinter, Ph.D., and Jonathan Smith, Ph.D., in the Lerner Research Institute conducted research for this study.


The Lerner Research Institute, home to The Cleveland Clinic's basic research departments, houses approximately 130 principal investigators and their teams who are pursuing a wide range of biomedical questions. With total annual research expenditures exceeding $150 million from federal agencies, non-federal societies and associations, and endowment funds, the Lerner Research Institute is the fifth-largest research institute in the country. The Cleveland Clinic Heart Center, ranked No. 1 in the country for the past 10 years in a row by U.S. News & World Report, is comprised of internationally recognized physicians and scientists who investigate clinical and molecular aspects of cardiac disease diagnosis, treatment and prevention.


The Cleveland Clinic Foundation, located in Cleveland, Ohio, is a not-for- profit multispecialty academic medical center that integrates clinical and hospital care with research and education. The Cleveland Clinic was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. U.S. News & World Report consistently names The Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. Approximately 1,200 full-time salaried physicians at The Cleveland Clinic and Cleveland Clinic Florida represent more than 100 medical specialties and subspecialties. In 2003, patients came for treatment from every state and from nearly 90 countries. The Cleveland Clinic website address is http://www.clevelandclinic.org/ .


Source: The Cleveland Clinic Foundation