New test may identify cardiovascular disease earlier

DURHAM, N.C. -- By analyzing the "trash" left in blood by the body's metabolism, a team of cardiologists and geneticists at Duke University Medical Center has found what may be new markers for measuring cardiovascular health, to complement such traditional measures as cholesterol and triglycerides.

The markers also may prove useful as "early warning systems" for coronary artery disease, alerting physicians to patients who need preventive treatment to keep their disease from progressing to danger levels, according to the researchers.

The analysis is one of the first to use metabolomics -- that is, the systematic study of the unique chemical fingerprints that specific cellular processes leave behind -- to better understand the underlying biological pathways involved in families with coronary artery disease, the researchers said. They likened metabolomics to analyzing the contents of a trash can in order to learn about the people who filled the can.

The team measured minute amounts of metabolites, or byproducts of cellular metabolism, in the blood of people whose extended family members had a history of developing coronary artery disease at an early age. Using the measurements, the researchers generated "metabolite profiles" of each individual.

Based on these profiles, the researchers demonstrated that many of the metabolites have stronger heritabilities, a measure of genetic predisposition, than do conventional markers such as cholesterol. This finding suggests that it may be possible to identify people at an early age who would be most likely to develop coronary artery disease, the researchers said.

"The results of our studies may have significant clinical implications above and beyond the ability of identifying the genes that underlie the susceptibility to coronary artery disease," said cardiologist and study team leader Svati Shah, M.D., who reported the findings on Tuesday, Nov. 14, at the annual scientific sessions of the American Heart Association, in Chicago.

"The data from our study suggest that there is a strong genetic component to an individual's metabolomic profile," Shah said. "Furthermore, they suggest that changes in the metabolic profiles in the offspring of patients with coronary artery disease precede development of the disease. With this advance notice, we could then start strategies, such as drugs or lifestyle changes, to stop or slow down the disease process."

The study was supported by the National Institutes of Health and the American Heart Association.

The researchers studied 82 patients from five extended families with at least two siblings afflicted with coronary artery disease at an early age -- that is, at age 51 or younger for men and 56 or younger for women. The team chose to focus on families with histories of early cardiovascular because it is most likely that patients who have coronary artery disease at a young age have inherited it, rather than developed it over years.

The researchers took blood samples from all family members and performed detailed screening for more than 60 metabolites. According to Shah, the metabolites they were searching for are physically tiny and occur in small numbers. She said a colleague, Christopher Newgard, Ph.D., developed the technology necessary to make these exacting and detailed measurements.

The team found that certain metabolites were significantly different in the five families, and paralleled differences in the clinical characteristics of the families. The presence of the suspect metabolites may serve as an indicator that the body is not properly using certain fuel sources, and may represent a marker for cardiovascular risk, Shah said.

"We found clear evidence for a strong genetic component to metabolites in families heavily burdened with cardiovascular risk factors," Shah said. "Some of the metabolites we identified can aggravate the body's inflammatory response as well as insulin signaling in diseased arteries." Both such actions, she said, may play a role in cardiovascular disease.

Shah's group plans further studies to identify the genes responsible for the metabolomic profiles uncovered in the current study. She also plans to study the metabolite screening process in a much larger group of patients without family histories of cardiovascular disease to see if there are any similarities to the early-onset cardiovascular disease.

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Other researchers who participated in the study were James Bain, Robert Stevens, Brett Wenner, Michael Muehlbauer, Elaine Dowdy, Carol Haynes, Sarah Nelson, Geoffrey Ginsburg, Elizabeth Hauser and William Kraus.


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