Abstract 9602: Serum Proteomic Profiles Predict Coronary Artery Disease in Symptomatic Patients Referred for Coronary Angiography
Coronary angiography is a definitive assay for coronary artery disease (CAD). However, high rates of normals and exposure to ionizing radiation warrant development of tests to identify patients lacking significant CAD without cardiac catheterization. We hypothesized that combinatorial proteomic changes in patient sera correlated with coronary artery disease status.
Methods: We performed targeted immunoassay profiling of serum from 359 symptomatic patients undergoing coronary angiography. A cohort of 208 patients required stent, angioplasty or bypass graft for hemodynamically significant CAD based on angiography while 151 had no significant disease (No CAD). Both cohorts were comparable in gender, BSA, cholesterol, LDL, creatinine, hypertension and clinical symptoms with a slight difference in age (No CAD: 58+/-10; CAD: 63 +/-11 years, p<0.001). Forty one target proteins implicated in atherogenesis were tested across the 2 groups. Thirty-three proteins were screened among 56 samples, 24 analytes were tested across a 239 sample training set and 12 analytes were validated in 120 additional serum samples.
Results: Highly significant increases were detected (false detection level=0.018) in patients with CAD for Apo-B100, fibrinogen, VCAM-1, myeloperoxidase, CRP, resistin, osteopontin, IL-6, IL-1b, IL-10 and NT-pBNP. Apo-A1 fell significantly in this group. A scoring algorithm was derived for patient classification (CAD vs. No CAD) using signatures of 2 to 5 analytes from the 239 patient study. Discrimination of patients without CAD was achieved (86% Negative Predictive Value: NPV) while correctly classifying 95% (PPV) of patients with CAD. Osteopontin, resistin, MMP7 and interferon-g were the most frequent classification biomarkers among diagnostic signatures. Validation studies (120 samples) confirmed this signature plus ACRP30 as the strongest multiplex classifier.
Conclusions: A non-invasive serum biomarker test has been developed to discriminate between patients with angiographically-confirmed, significant CAD and those without it. The ability to exempt even a small percentage of patients from cardiac catheterization provides significant medical and economic benefits given the growing epidemic of coronary artery disease.
- © 2011 by American Heart Association, Inc.