P1753Novel biomarker algorithmic panel measuring permutations of immune response to cardiac endothelial injury and global risk factors identifies patients at risk of acute coronary syndrome (ACS)

Abstract

Abstract Background Global cardiovascular risk scores frequently underestimate risk in persons with underlying asymptomatic cardiac lesions who eventually experience cardiovascular events. The Get-With-The-Guidelines Initiative analysis revealed that over 70% of patients with a first cardiac event were well within guideline targets for lipid values. Most artery flow-disrupting events occur at locations with less than 50% lumen narrowing. From clinical studies published in the late 1990s using IVUS (in-the-artery-ultrasound) to visualize disease status, the typical heart attack occurs at locations with about 20% stenosis (narrowing), prior to sudden lumen closure and resulting ACS. This sudden lumen closure is caused by rupture of an unstable cardiac lesion causing a blood clot and occlusion in up to 75% of heart attacks. The role of multi-biomarker algorithms to identify vulnerable patients with these lesions at risk of short-term ACS events is of great interest. Methods We studied 725 adults (≥18 yrs) from Cardiology practices who received a 5-year modified Framingham Risk Score (mFRS), and a coronary artery disease predictive algorithm (CADPA) multi-biomarker score. CADPA incorporates 9 biomarkers (CTACK, Eotaxin, Fas Ligand, HGF, IL-16, MCP-3, sFas, HDL, and HbA1c) with age, sex, diabetes, and family history of myocardial infarction, previously shown to more accurately reclassify risk of cardiovascular events (cNRI=43%). Patients were classified into low (<3.5%), intermediate (3.5% - <7.5%), and high (≥7.5%) 5-year risk categories with both mFRS and CADPA. Patients low or intermediate risk by mFRS, but reclassified high by CADPA are reported and compared. Results Persons at low, intermediate, and high global risk categories were successively more likely to demonstrate high-risk scores with CADPA (Figure). However, 349 (65%) in the low mFRS risk group were reclassified into higher CADPA risk groups and 104 (70%) intermediate risk patients were reclassified into the high-risk group (p<0.0001 for CADPA vs. mFRS). Analysis demonstrated that 89% (309) of the low or intermediate mFRS [125 females (99%); 184 males (83%); p<0.0001] and, 86 below 65 years (93%) and 223 above 65 years (88%); p=0.26)] were classified as high-risk by CADPA, indicating that many persons who may be at high risk are not identified as such by global risk assessment. CADPA Risk Reclassification Conclusions We conclude that this novel multi-biomarker panel (CADPA) identifies many persons at increased risk of cardiac events due to asymptomatic cardiac lesions missed by traditional global risk methods. Further investigation of the value of such a test for prediction of near-term CVD events is required.