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Cleveland Clinic-Led Research Uncovers New Mechanism That Heightens Risk of Heart Disease
Date:9/10/2007

Findings Appear in Sept. 9 Issue of the Journal Nature Medicine

CLEVELAND, Sept. 10 /PRNewswire/ -- Heart disease often hits with devastating effects in people with normal cholesterol levels, yet seemingly misses striking others who smoke, or have multiple risk factors. A new research discovery may help explain why one person suffers a heart attack and yet another doesn't.

Researchers at Cleveland Clinic's Lerner Research Institute have discovered a mechanism that contributes to the hardening of arteries and could explain why some individuals are at greater risk of developing heart disease than others.

In a study published in the Sept. 9 issue of the journal Nature Medicine, researchers identify a mechanism that is found in high-risk populations, including smokers and individuals with chronic kidney disease, as well as the general population, which heightens an individual's risk of developing heart disease. The researchers found that proteins in the bloodstream, when damaged by a process called carbamylation, change the way cells behave, promoting the accumulation of harmful substances in the arteries and raising the risk of heart disease.

"This is a breakthrough in explaining why some populations are at greater risk for developing heart disease," said the study's lead author, Stanley Hazen, M.D., Ph.D., Section Head of Preventive Cardiology at Cleveland Clinic and a researcher in the Lerner Research Institute. "To date, we have focused on cholesterol as the central linchpin of how cardiovascular disease occurs. However, the presence of heart disease in many high-risk groups has not been adequately explained by traditional risk factors, including elevated cholesterol levels. This study highlights a new mechanism that augments an individual's risk of heart disease."

Researchers began their work trying to understand why smokers are at increased risk for developing heart disease. In a study of 1000 patients and additional cell and animal studies, they discovered the new pathway that occurs during atherosclerosis to some extent in all individuals, but to a greater extent in smokers.

The researchers found that a blood test measuring systemic levels of homocitrulline, a molecular marker for the pathway, serve as the strongest, independent predictor of heart disease risk identified thus far. It could help further define who is at risk for the development and progression of heart disease, and to help monitor the effectiveness of heart disease therapies.

"Our studies demonstrate that protein carbamylation is a fundamental and intrinsic process to atherosclerosis," Dr. Hazen said. "They establish a foundation for designing targeted therapies that may block this pathway to prevent the development and progression of heart disease."

About Cleveland Clinic's Lerner Research Institute

The Lerner Research Institute is home to Cleveland Clinic's laboratory- based and translational biomedical research. Its mission is to understand the causes of human diseases and to develop new treatments and cures. The Lerner Research Institute's total annual research expenditures exceed $120 million from Federal agencies, non-Federal societies and associations, endowment funds and the Cleveland Clinic. More than 1,100 people (including about 160 investigators, 350 junior faculty and postdoctoral fellows, and 120 graduate students) work in research programs focusing on cardiovascular, cancer, neurologic, musculoskeletal, allergic and immunologic, eye, metabolic, and infectious disease. The Institute also is an integral part of the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University -- training the next generation of physician-scientists.

About Cleveland Clinic

Cleveland Clinic, located in Cleveland, Ohio, is a not-for-profit multispecialty academic medical center that integrates clinical and hospital care with research and education. 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 Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. Approximately 1,800 full-time salaried physicians and researchers at Cleveland Clinic and Cleveland Clinic Florida represent more than 100 medical specialties and subspecialties. In 2006, there were 3.1 million outpatient visits to Cleveland Clinic. Patients came for treatment from every state and from more than 80 countries. There were more than 53,000 hospital admissions to Cleveland Clinic in 2006. Cleveland Clinic's Web site address is http://www.clevelandclinic.org.


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