Tiny molecules may tell big story about cardiovascular disease risk

Feb 19, 2010

(PhysOrg.com) -- Tiny bits of molecular "trash" found in circulating blood appear to be good predictors of cardiovascular disease and untimely death, say researchers at Duke University Medical Center.

The discovery, published online in the April issue of the journal Circulation Genetics, comes from the largest study of its kind for cardiovascular disease, and is the first to identify specific metabolic profiles associated with , heart attacks and death among patients who have undergone coronary catheterization.

The Duke study analyzed metabolites, the molecular debris left over after the body breaks food down into energy sources and building blocks of cells and tissues.

Scientists believe metabolites may be useful in diagnosing disease, said Svati Shah, M.D., M.H.S., a cardiologist in the Duke Heart Center, the Duke Center for and the lead author of the study. But the tiny molecules are notoriously hard to identify, quantify and characterize. Shah has been studying metabolic signatures in heart disease for several years and led earlier research showing that metabolic profiles associated with early-onset coronary artery disease can be inherited.

Shah and William Kraus, M.D., professor of medicine at Duke and the senior author of the study, wanted to know if they could isolate and identify particular metabolites associated with coronary artery disease. They began their investigation with information in Duke's CATHGEN biorepository which holds health records and blood samples from nearly 10,000 patients who had come to Duke over the past eight years for catheterization. Collaboration with Christopher B. Newgard, PhD., director of Duke's Sarah W. Stedman Center for Nutrition and Metabolism, allowed Shah, Kraus and others to accurately quantify and characterize the metabolites.

Researchers selected 174 patients who had experienced early-onset coronary artery disease (CAD) and compared them to 174 controls who had undergone catheterization but who were not found to have CAD. Using a panel of 69 metabolites previously identified as potentially involved in the development of CAD, they examined the metabolic profiles in both groups.

"We found two sets, or clusters of metabolites that seemed to differentiate between the two groups," says Shah.

Next, they tested the two sets of metabolites to see if they could differentiate between patients of any age who had CAD and those who did not. Again, the two sets of metabolites were able to discriminate between the two groups.

In order to evaluate the ability of the metabolites to predict risk of heart attack or death, the researchers also created an "event group" comprising 314 patients from all groups who suffered a heart attack or death during a follow-up period of almost three years. They compared metabolic profiles between those who suffered a heart attack or death with those who did not. Using multiple analytic and statistical methods, they found two factors that were clearly associated with coronary artery disease and one factor that predicted greater risk of or death among patients with coronary artery disease.

"When we added these biomarkers to traditional clinical risk models, we found that they increased the accuracy of projected risk," says Shah.

While earlier studies have suggested that certain metabolites are associated with the presence and severity of CAD, researchers have not been able to identify most of the individual molecules within those profiles, says Shah, "which in the end meant that these studies were not that clinically useful."

"Here, we specifically selected clusters of metabolites that we know are involved in multiple pathways of lipid, protein and glucose metabolism - pathways that are often disrupted in CAD -- and we showed that they are indeed associated with CAD and subsequent risk of cardiac events," says Kraus, "These metabolic profiles may be a way from routine clinical use, but we feel they are a good first step in that direction."

Explore further: Missing protein restored in patients with muscular dystrophy

add to favorites email to friend print save as pdf

Related Stories

Genetic variation may lead to early cardiovascular disease

Jan 03, 2009

Researchers from Duke University Medical Center have identified a variation in a particular gene that increases susceptibility to early coronary artery disease. For years, scientists have known that the devastating, early-onset ...

Toward a urine test for diagnosing heart disease

Feb 02, 2009

Researchers in Australia are reporting an advance toward the first urine test for diagnosing coronary artery disease (CAD), the condition responsible for most of the 1.5 million heart attacks that occur in the United States ...

Recommended for you

Student seeks to improve pneumonia vaccines

12 hours ago

Almost a million Americans fall ill with pneumonia each year. Nearly half of these cases require hospitalization, and 5-7 percent are fatal. Current vaccines provide protection against some strains of the ...

Seabed solution for cold sores

14 hours ago

The blue blood of abalone, a seabed delicacy could be used to combat common cold sores and related herpes virus following breakthrough research at the University of Sydney.

Better living through mitochondrial derived vesicles

Aug 19, 2014

(Medical Xpress)—As principal transformers of bacteria, organelles, synapses, and cells, vesicles might be said to be the stuff of life. One need look no further than the rapid rise to prominence of The ...

Zebrafish help to unravel Alzheimer's disease

Aug 19, 2014

New fundamental knowledge about the regulation of stem cells in the nerve tissue of zebrafish embryos results in surprising insights into neurodegenerative disease processes in the human brain. A new study by scientists at ...

User comments : 0