Biomarkers for Identification of High-Risk Coronary Artery Plaques in Patients with Suspected Coronary Artery Disease

ABSTRACT Background Patients with atherosclerotic plaques containing high-risk features have an increased likelihood of events and a worse prognosis. Whether increased levels of Troponin I (TnI) and C-reactive protein (CRP) are associated with the presence of high-risk coronary atherosclerotic plaques (HRP) is not well described. We assessed the association between 1) TnI and 2) CRP with quantified coronary plaque burden, luminal diameter stenosis, and HRP in patients with low/intermediate pre-test probability of obstructive coronary artery disease (CAD) referred for coronary computed tomography angiography (CCTA). Methods The CCTA from 1,615 patients were analyzed using a semiautomatic software for coronary artery plaque characterization. Patients with high TnI (>6 ng/L) and high CRP (>2 mg/L) were identified. Associations of TnI and CRP with plaque burden, stenosis (≥50% luminal diameter stenosis on CCTA), and HRP were investigated. Results TnI and CRP were both positively correlated with total plaque burden (TnI r s =0.14, p<0.001; CRP r s =0.08, p<0.001). In multivariate logistic regression analyses, high TnI was associated with stenosis (OR 1.43, 95% confidence interval (CI) 1.03-1.99, p=0.034), the presence of HRP (OR 1.79, 95% CI: 1.17– 2.74, p=0.008), and the subtypes of HRP; low attenuation plaque (OR 1.93, 95% CI: 1.24–3.00, p=0.003), and positive remodeling (OR 1.51, 95% CI: 1.07–2.13, p=0.018). For CRP, only stenosis and napkin ring sign correlated significantly. Conclusion In patients with suspected CAD, TnI and CRP are associated with HRP features. These findings may suggest that inflammatory and particularly ischemic biomarkers might improve early risk stratification and affect patient management. ClinicalTrials.gov identifier: NCT02264717 CLINICAL PERSPECTIVE Using CCTA, our findings direct the focus toward plaque characteristics rather than just overall plaque burden, outlining that the presence of stenosis and specifically HRPs may be more important in CAD risk evaluation than the amount of atherosclerosis alone. Our findings suggest that biomarkers can help identify patients with HRP features, which previously were shown to increase the risk of future events. TnI may have a place in pre-test evaluation of patients with stable chest pain by introducing biomarkers to a pre-test clinical likelihood model, which may pave the way for more accurate risk stratification and, consequently, better-informed clinical decision-making. Still, trials on biomarker-guided diagnostic testing and medical therapy in de novo stable chest pain patients are warranted.