Personalized Risk Evaluation and Diagnosis (Using Corus CAD or ASGES) in the Coronary Tree

Conditions

Angina Pectoris, CAD, Cardiovascular Diseases, CHD, Chest Pain, Coronary Artery Disease, Coronary Heart Disease, CVD

Keywords

Atherosclerosis, Biological Markers, Molecular Genetics, Gene Expression, GES, CAD, CVD, CHD, Clinical Validity, Precision Medicine, ASGES, CT Angiography, Corus CAD, Coronary angiorgram, Age/Sex/Gene expression Score, Coronary Artery Disease, Angina Pectoris, Chest Pain, Cardiovascular Disease, Coronary Heart Disease, CTA, PREDICT

Brief summary

The PREDICT study is to develop and validate a diagnostic blood ASGES (age, sex, gene expression score) or Corus CAD for atherosclerotic coronary artery disease (CAD). The Corus CAD (Age/Sex/Gene Expression score - ASGES) will use quantitative real-time PCR (RT-PCR) to quantify the expression of multiple genes from circulating peripheral blood cells to assess the presence of clinically significant CAD in a patient.

Detailed description

The purpose of the PREDICT study is to develop and validate a diagnostic blood ASGES (age, sex, gene expression score) or Corus CAD for atherosclerotic coronary artery disease (CAD). The Corus CAD (Age/Sex/Gene Expression score - ASGES) will use quantitative real-time PCR (RT-PCR) to quantify the expression of multiple genes from circulating peripheral blood cells to assess the presence of clinically significant CAD in a patient. This is a prospective, multi-center, observational study. Participation in the study does not alter clinical care. The only procedure required by the protocol is collection of a research blood sample. All other data collected will be in accordance with each participating institution's standard patient care. The study is divided into four sequential segments with unique subjects and goals: ASGES (Corus CAD) discovery (segment 1), ASGES (Corus CAD) development (segment 2), ASGES (Corus CAD) validation (segment 3), and additional ASGES (Corus CAD) testing (segment 4). The primary analysis will be performed during the third segment of the study using a subset of the enrolled subjects (primary subjects). Primary subjects will be defined by additional eligibility criteria beyond the general eligibility criteria required for enrollment in the overall study. The additional, post-enrollment eligibility criteria will be based on clinical and demographic factors that are found during the course of the study to affect the expression of genes used in the ASGES (Corus CAD). Such factors will be identified during gene discovery and algorithm development. The post-enrollment eligibility criteria will be defined prior to the beginning of the ASGES (Corus CAD) validation segment of the study. In addition, three substudies are planned and will enroll up to 1500 subjects. * The first substudy will include subjects undergoing cardiac CT angiography (CTA) and aims to determine how gene expression correlates with total coronary atheroma burden, as measured by CTA. * The second substudy examines sample handling and shipping conditions and does not affect the treatment of the subjects. * The third substudy will focus on additional algorithm development and validation in a non-diabetic female patient population.

Alexandra J. Lansky, John McPherson, Nic Chronos, Kari Schmitz, Jim Wingrove et al. (6 authors)

Circulation Cardiovascular Quality and Outcomes2017-03-01

10.1161/circoutcomes.10.suppl_3.214

Abstract 16357: Identification of Circulating Proteins that Predict the Presence of Obstructive Coronary Artery Disease in Symptomatic, Non-Diabetic Patients Referred for Invasive Coronary Angiography

James A. Wingrove, Karen Fitch, Phil Beineke, Steven Rosenberg

Circulation2015-11-10

10.1161/circ.132.suppl_3.16357

A peripheral blood gene expression score is associated with atherosclerotic Plaque Burden and Stenosis by cardiovascular CT-angiography: results from the PREDICT and COMPASS studies.

Voros S, Elashoff MR, Wingrove JA, Budoff MJ, Thomas GS, Rosenberg S.

2014-01-2019 citations

10.1016/j.atherosclerosis.2013.12.045

A whole blood gene expression-based signature for smoking status.

Beineke P, Fitch K, Tao H, Elashoff MR, Rosenberg S, Kraus WE, Wingrove JA, PREDICT Investigators.

2012-12-0367 citations

10.1186/1755-8794-5-58

Development of a blood-based gene expression algorithm for assessment of obstructive coronary artery disease in non-diabetic patients.

Elashoff MR, Wingrove JA, Beineke P, Daniels SE, Tingley WG, Rosenberg S, Voros S, Kraus WE, Ginsburg GS, Schwartz RS, Ellis SG, Tahirkheli N, Waksman R, McPherson J, Lansky AJ, Topol EJ.

2011-03-2899 citations

10.1186/1755-8794-4-26

Multicenter validation of the diagnostic accuracy of a blood-based gene expression test for assessing obstructive coronary artery disease in nondiabetic patients.

Rosenberg S, Elashoff MR, Beineke P, Daniels SE, Wingrove JA, Tingley WG, Sager PT, Sehnert AJ, Yau M, Kraus WE, Newby LK, Schwartz RS, Voros S, Ellis SG, Tahirkheli N, Waksman R, McPherson J, Lansky A, Winn ME, Schork NJ, Topol EJ, PREDICT (Personalized Risk Evaluation and Diagnosis in the Coronary Tree) Investigators.

2010-10-01128 citations

10.7326/0003-4819-153-7-201010050-00005

Interventions

DIAGNOSTIC_TESTCorus CAD (ASGES)

Age/Sex/Gene Expression Score - ASGES

Study design

Observational model

OTHER

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

21 Years to 99 Years

Healthy volunteers

No

Inclusion criteria

* Referral for a coronary angiogram (either invasive X-ray angiography or coronary CTA) * Any one of the following clinical syndromes: 1. chest pain syndrome, stable angina, or anginal equivalent suggesting myocardial ischemia 2. low-risk unstable angin, or 3. asymptomatic individuals with a high probability of CAD

Exclusion criteria

* History of myocardial infarction or known CAD * Current Myocardial Infarct (MI), acute coronary syndrome with high-risk features or unstable angina with high-risk features * New York Heart Association (NYHA) class III or IV congestive * Inability to give informed congestive heart failures * Severe left ventricular systolic dysfunction (LVEF\<35%) * Severe regurgitant or stenotic cardiac valve lesion * Active or chronic systemic infection * Rheumatologic, autoimmune or hematologic conditions * Any organ transplant * Immunosuppressive therapy * Chemotherapy in the preceding year * Major blood or blood product transfusion in the preceding 2 months

Design outcomes

Primary

Measure	Time frame	Description
Algorithm AUC >0.50	30days	The primary analysis will be performed during the third segment of the study using a subset of the enrolled subjects (primary subjects). The primary endpoint for the PREDICT study is a validated algorithm that can accurately classify subjects with and without any coronary artery lesion with a ≥50% diameter stenosis, as measured by Core Laboratory blinded quantitative coronary angiography. In evaluating this endpoint, subjects will be classified as either cases or controls. The endpoint will be assessed by calculating the area under the curve (AUC) for the algorithm score, and testing against an AUC = 0.50 to determine clinical utility, using an alpha level of 0.05 (two-sided).

Countries

United States

Outcome results

None listed