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Levels of Gene Expression a New Noninvasive Way to Identify Obstructive CAD

Value-Based Care in Cardiometabolic Health May 2012, Vol 1, No 1 - Cardiometabolic Health
Wayne Kuznar

Chicago, IL—A noninvasive whole blood test developed from the expression levels of 23 genes can identify patients unlikely to have coronary artery disease (CAD) events or require revas cularization procedures over the next 12 months, reported Robert S. Schwartz, MD, FACC, Professor of Medicine at the University of Minnesota Medical School, Medical Director at Minnesota Cardiovascular Research Institute, and a cardiologist at the Minneapolis Heart Institute, at the 2012 American College of Cardiology meeting.

Use of a score based on the blood test (the peripheral blood gene-expression score) may eventually represent a personalized risk evaluation for the noninvasive diagnosis of atherosclerotic CAD, which is precipitated by an interaction of genetic and environmental factors.

“Better diagnostic methods are needed to stratify patients for elec - tive invasive angiography,” said Dr Schwartz. Most patients undergoing first-time angiography do not have obstructive CAD: more than 60% of patients with risk factors or symptoms of CAD who are referred for elective cardiac catheterization for evaluation do not have significant CAD, and 40% have minimal to no CAD.

Unlike genetic tests, gene-expression testing assesses a dynamic process, integrating both genetic predisposition and behavioral and environmental influences on the current disease state, according to the test’s developer, CardioDx.

“Changes in gene expression have been observed in diseased arterial wall samples,” said Dr Schwartz. The study followed more than 1100 nondiabetic patients for 1 year who were clinically indicated for invasive angiography and who had their peripheral blood gene-expression score calculated. The gene-expression score considers age and sex in addition to the expression of the 23 genes.

Of the 1166 patients, 850 were eligible for subsequent analysis. Over the 12 months of follow-up, 14 patients had a revascularization procedure (percutaneous coronary intervention or coronary artery bypass graft), and 11 had a major adverse cardiac event (MACE), including myocardial infarction, stroke/transient ischemic attack, or all-cause mortality; 825 of the 850 had no events or procedures.

The likelihood of procedures and events was higher with increasing gene-expression score. At a threshold gene-expression score of ≤15, the negative predictive value of the gene-expression score was 91% for procedures within 30 days and 91% at 12 months. The negative predictive value was 99% for MACE within 30 days and at 12 months.

Patients with low gene-expression scores (approximately 35% of the study population) were at very low risk for subsequent MACE and revascularization, Dr Schwartz noted. Only 3 of 1160 patients with a geneexpression score <15 had events at 12 months.

Of the 8 patients who underwent late revascularization, 7 had a gene- expression score >15. Of those with high geneexpression scores (28-40), 39% had procedures or MACE; 28% of those with medium scores (16-27) had MACE or revascularization procedures.

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Last modified: July 16, 2012
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