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VAP Cholesterol Test Helps In Search For New Heart Disease Drugs

Peer-reviewed journal, Science, reports that advanced cholesterol test aids in identifying connection between improved lipid profile and heart protection

BIRMINGHAM, Ala., Feb. 16 /PRNewswire/ -- Using the VAP Cholesterol Test from Atherotech, Inc., University of Maryland researchers have found an association between a rare gene mutation and heart protection. The information reported in a recent study could help in the development of heart disease risk-lowering drugs and also demonstrates the value of advanced lipid profile testing in the identification of individuals at increased risk of heart disease.

The genome-wide association study (GWAS) of fasting and postprandial triglyceride levels was performed as part of the Heredity and Phenotype Intervention (HAPI) Heart Study. The results, published in the highly respected journal, Science, identified a specific gene mutation (APOC3 R19X) present in 5 percent of a Lancaster County, Pa., Amish community. This rare genetic occurrence prevents the production of a protein (apoC-III) that leads to increased rates of atherosclerosis.

Toni I. Pollin, Ph.D., assistant professor of medicine at the University of Maryland School of Medicine and the triglyceride study's lead investigator, said participants who were carriers of the mutation had one of their inherited APOC3 genes "switched off," apparently resulting in several cardiovascular benefits. The benefits included low triglycerides and LDL (bad cholesterol) levels, high HDL (good cholesterol) levels and protection against heart disease as evidenced by decreased levels of coronary artery calcification.

The association between these improved lipid profiles and decreased coronary artery calcification - an underlying indicator of coronary heart disease - was confirmed using the expanded cholesterol profiling capabilities of the VAP (Vertical Auto Profile) Test.

"Using the VAP profile, we were able to demonstrate that mutation carriers have extraordinarily low levels (less than 50 percent of normal) of remnant lipoproteins, which are highly atherogenic particles generated during the absorption and clearance of triglycerides derived from dietary fat," Dr. Pollin noted.

Lipid-lowering fibrates actually work in part through decreased APOC3 expression. Other lipid-lowering therapies such as statins, niacin, ezetimibe, fish oil and weight loss have also been associated with decreases in apoC-III protein levels. Dr. Pollin believes the next step is the discovery of new therapies aimed specifically at blocking apoC-III expression, improving lipid profiles and decreasing the risk of heart attack and stroke.

Dr. Pollin's study was conducted on 809 Old Order Amish individuals as part of the University of Maryland School of Medicine's HAPI Heart Study, which was designed to identify genetic factors in response to short-term interventions related to cardiovascular risk. The GWAS allowed researchers to rapidly scan 500,000 markers in the DNA of the participants to find variations that are associated with triglyceride levels in the blood.

HAPI study participants drank a 782-calorie per m(2) body surface area milkshake and were then monitored for the next six hours with blood tests - including the VAP Test - plus ultrasound tests of the brachial artery to determine how they were reacting to the high-fat meal. Results showed that Amish who were carriers of the gene mutation - only one copy of the APOC3 gene instead of two - would rapidly break down triglycerides, the fat particles in the blood associated with an increased risk of coronary artery disease. Those with the gene abnormality also had lower triglycerides both before and after the fat load and better lipid profiles overall.

"This is a brilliant GWAS study that beautifully illustrates the value of advanced lipid profiling, direct LDL determination and the value of postprandial measurement of remnant lipoproteins," said James Ehrlich, M.D., Atherotech's Chief Medical Officer and an expert in coronary calcification imaging. And beyond research, the accurate identification of lipid profiles and subclasses can have a major impact on proper individualized therapy and improved cardiac risk assessment, which may also include imaging tests and endothelial function testing, as in this research."

The improved lipid profile of mutation carriers included: significantly lower levels of non-HDL, very low density lipoprotein (VLDL), VLDL3 (the most-dense VLDL subfraction), intermediate density lipoprotein (IDL), real LDL, and remnant lipoprotein cholesterol. Higher (cardioprotective) levels of both HDL2 and HDL3 cholesterol were also reported along with apparent cardioprotection as measured by decreased prevalence of coronary artery calcification.

The VAP Test, which is covered by most insurance carriers and Medicare, provides physicians with direct measurement of LDL, HDL and all relevant cholesterol subclasses. These important but often overlooked subclasses include non-HDL, particle number as determined by accurate apoB, and emerging risk factors such as Lp(a), low-density lipoprotein remnants and small dense LDL.

VAP technology has been used in more than 100 clinical trials and will continue to play an important role in clinical practice and as a valuable analytical research tool. The VAP Test is available nationwide.

About Atherotech, Inc.

Atherotech is a cardio-diagnostic company focusing on direct measurement of the comprehensive lipid panel using the company's patented VAP technology, which directly measures the cholesterol content of all lipids, components and subclasses. The VAP Test is the first cholesterol profile to comply with updated National Cholesterol Education Program ATP III recommendations for LDL measurement and the only commercially available advanced lipid profile that routinely reports all three lipoprotein parameters considered necessary by the American Diabetes Association and American College of Cardiology expert consensus guidelines. The VAP Cholesterol Test is available through national and regional diagnostic laboratories and is reimbursed by many of the largest private insurers as well as Medicare. For more information, visit

SOURCE Atherotech, Inc.
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