title: Clinical Utility of a Precision Medicine Test Evaluating Outpatients with Suspected Obstructive Coronary Artery Disease.
abstract: BACKGROUND
  Identifying patients with obstructive coronary artery disease can be challenging for primary care physicians. Advances in precision medicine may help augment clinical tools and redefine the paradigm for evaluating coronary artery disease in the outpatient setting. A blood-based age/sex/gene expression score (ASGES) incorporating key features of precision medicine has shown clinical validity with a 96% negative predictive value and 89% sensitivity in estimating a symptomatic patient's current likelihood of obstructive coronary artery disease. To better characterize the clinical utility of the ASGES and measure its impact on clinician decision-making, a community-based registry was established.
  
  
  METHODS
  The prospective PRESET Registry (NCT01677156) enrolled stable, nonacute adult patients presenting with typical or atypical symptoms suggestive of obstructive coronary artery disease from 21 US primary care practices from August 2012 to August 2014. Demographics, clinical characteristics, and ASGES results (predefined as low [ASGES ≤15] or elevated [ASGES >15]) were collected, as were referrals to Cardiology or further functional/anatomic cardiac testing after ASGES testing. Patients were followed for 1 year post ASGES testing.
  
  
  RESULTS
  Among the 566-patient cohort (median age 56 years), clinicians referred 26/252 (10%) of patients with low scores vs 137/314 (44%) of patients with elevated scores to Cardiology or advanced cardiac testing for further evaluation (unadjusted odds ratio 0.15, P <.0001; adjusted odds ratio after accounting for clinical covariates = 0.18, P <.0001). Data on 84 patients referred for advanced cardiac testing showed abnormal findings in 0 of 13 (0%) low ASGES and 10 of 71 (14%) elevated ASGES patients. Major adverse cardiovascular events and revascularization were noted in 3/252 (1.2%) patients with low ASGES and 14/314 (4.5%) patients with elevated ASGES score (P <.03).
  
  
  CONCLUSIONS
  In this community-based cardiovascular registry, the ASGES demonstrated clinical utility in the evaluation of patients with suspected obstructive coronary artery disease. Low-score patients were less likely to undergo cardiac referral, were unlikely to have positive findings on further cardiac work-up, and had a low rate of adverse cardiovascular events in 1-year follow-up. Our work provides evidence supporting the value of using precision medicine in the delivery of cardiovascular care.
authors.affiliation: David Geffen School of Medicine at University of California at Los Angeles. Electronic address: jladapo@mednet.ucla.edu.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Ladapo
authors.affiliation: University of California at Los Angeles, Torrance.
authors.forename: Matt
authors.initials: M
authors.lastname: Budoff
authors.affiliation: Doctors for Health, Omaha, Neb.
authors.forename: David
authors.initials: D
authors.lastname: Sharp
authors.affiliation: CardioDx, Inc, Redwood City, Calif.
authors.forename: Michael
authors.initials: M
authors.lastname: Zapien
authors.affiliation: CardioDx, Inc, Redwood City, Calif.
authors.forename: Lin
authors.initials: L
authors.lastname: Huang
authors.affiliation: Bells Medical Clinic, Bells, Tex.
authors.forename: Bruce
authors.initials: B
authors.lastname: Maniet
authors.affiliation: Johns Creek Primary Care, Suwanee, Ga.
authors.forename: Lee
authors.initials: L
authors.lastname: Herman
authors.affiliation: CardioDx, Inc, Redwood City, Calif.
authors.forename: Mark
authors.initials: M
authors.lastname: Monane
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000553:Ambulatory Care / Q000379:methods*; D003324:Coronary Artery Disease / Q000175:diagnosis*; D020000:Decision Support Systems, Clinical; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D057285:Precision Medicine / Q000379:methods*; D011446:Prospective Studies; D012042:Registries; D015203:Reproducibility of Results; D012307:Risk Factors; D055815:Young Adult
keywords: Age/sex/gene expression score; Clinical decision-making; Clinical utility; Coronary artery disease; Diagnosis; Genomics; Precision medicine; Registry