Methods: The GES is a validated quantitative diagnostic test for non-diabetic patients that measures expression levels of 23 genes from peripheral blood to determine the likelihood of a symptomatic patient having obstructive CAD, as defined by at least one vessel with > 50% coronary artery stenosis by quantitative coronary angiography or core-lab computed tomography (CT) angiography. The GES has a negative predictive value of 96% among low GES (≤ 15) patients. Between April 2012 to January 2013, a total of 344 stable patients presenting with symptoms suggestive of obstructive CAD at 6 community-based PCP practices had a peripheral blood sample drawn for gene expression measurement, which was sent to a central reference lab and reported within 2-3 days.The primary outcome is the association between GES results and referrals to noninvasive and invasive cardiac testing.
Results: Of the 342 evaluable patients, the median age was 55 years, 53% were female, the mean (SD) GES was 16 (±10), and 49% of patients had low GES. Patients presented with typical and atypical symptoms (93%), were asymptomatic with >3 risk factors (5%), or were asymptomatic with <3 risk factors for CAD (2%). After adjusting for age, gender, and type of chest pain, each 10-point decrease in the GES was associated with a 13 fold decrease in the likelihood of referral to further cardiac testing (p<0.0001). Additionally, patients with low GES had a 94% decrease in the likelihood of referral versus patients with non-low GES (p<0.0001). At 30 days of follow-up, no major adverse cardiac events were noted.
Conclusions: This novel genomic-based, personalized gene expression score was incorporated into medical decision making in primary care practice. The test demonstrated clinical utility as a rule-out test, with low GES patients being significantly less likely to be referred for further diagnostic evaluation to rule out obstructive CAD.