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Revolutionizing Heart Disease Risk Assessment
New Assay Determines Functional Quality of HDL

July 28, 2013 – In a ground-breaking, proof-of-principle study just published in PLoS ONE [Borja MS, Zhao L, Hammerson B, Tang C, Yang R, et al. (2013) HDL-apoA-I Exchange: Rapid Detection and Association with Atherosclerosis. PLoS ONE 8(8): e71541.], CHORI Associate Scientist Michael Oda, PhD, reports that his novel assay, site directed spin-label electron paramagnetic resonance (SDSL-EPR), provides a precise and accurate measure of an individual's high density lipoprotein (HDL) functional capacity. The assay is quick, highly accurate, and affordable, and has the potential to revolutionize heart disease risk assessment.

"Our assay can test a person's HDL functional capacity with a drop of blood and 15 minutes," says Dr. Oda. "This is the first test ever to be able to categorically and consistently identify people's risk for heart disease. Other tests work in men but this is a superior analyte that works equally well in women and men, a very important distinction."

“This is the first test ever to be able to categorically and consistently identify people's risk for heart disease.”



Traditional risk assessments for coronary artery disease (CAD) – the hardening of the arteries that is a precursor to heart disease and exponentially increases one’s risk of heart attacks – measure the amount of an individuals “good” HDL cholesterol (HDL-C). This is because research has always shown a clear association between increased HDL-C levels and reduced CAD risk in longitudinal population studies, which follow individuals over time. But research has also shown that large numbers of patients with normal or high HDL-C still had heart disease or high risk for heart disease. Dr. Oda's test is capable of identifying a large portion of these patients, who have been identified as carrying "silent risk" for CAD.

“What this means,” says Dr. Oda, “is that while there may be a general trend for higher HDL-C to be associated with reduced CAD, on a patient-by-patient basis, HDL-C levels are not a good predictor of a given individual’s predisposition for CAD.”

The reason for this is that measuring the amount of HDL-C alone doesn’t tell you how well the HDL is actually functioning.

“When your HDL is dysfunctional, you can have a very high amount of HDL-C in your blood stream, but have very low HDL functional capacity,” explains Dr. Oda.
“Because our test works on the functionality of HDL, not the amount of HDL-C, it is both utterly unique and potentially the best marker out there of cardiovascular health.”

The EPR-based assay is founded on nearly a decade of research in Dr. Oda’s lab on apolipoprotein A-I (apoA-I), the main protein on HDL that is responsible for nearly 90 percent of HDL’s functionality. Dr. Oda recently verified the structure of apoA-I in a Federation of European Biosciences Journal publication (2013 Jul;280(14):3416-24), providing the first comprehensive apoA-I model for the field. The structural information provided key information for the development of the EPR-based HDL function assay.

As Dr. Oda explains, “If you can understand the structure of apoA-I, you have a structural foundation for the majority of HDL’s function.”

The new assay actually measures HDL-apoA-I exchange, or HAE, which is a measure of how malleable or adaptable apoA-I is to its lipid environment.

"HAE is essentially a proxy for the ability of HDL to transport cholesterol to the liver for removal," Dr. Oda says. "Thus, the greater the plasticity of apoA-I, the greater the ability of the HDL to transport cholesterol out of the body."

The new study confirms that the EPR-based HAE assay is a clear biomarker of cardiovascular disease and can detect dysfunctional HDL in subjects both prior to and following a cardiovascular event.

Because it is simple, affordable, precise and accurate, the assay has the potential to become the new gold standard for cardiovascular disease risk assessment.

In addition to determining heart disease risk, the assay can be used as a measure of how well a particular drug is working to increase HDL functionality, both in tracking patients' treatment responses and in identifying potential study participants for drugs aimed at increasing HDL functionality. The assay can also be used as an early detector for type 2 diabetes and metabolic syndrome. Finally, other disorders such as Alzheimer's disease, chronic inflammation or arthritis, for example, are associated with HDL dysfunction, which means Dr. Oda's assay could have impacts beyond the area of cardiovascular disease.

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Thursday, August 29, 2013 6:49 AM

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