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

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 rs=0.14, p<0.001; CRP rs=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][1] identifier: [NCT02264717][2] 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. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT02264717 ### Funding Statement This study was financed by the Novo Nordisk Foundation Clinical Emerging Investigator grant (NNF21OC0066981) and the Independent Research Fund Denmark (1149-00015B). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Patients provided informed consent. The study was approved by The Danish Data Protection Agency and the Central Denmark Regional Committee on Health Research Ethics and registered at ClinicalTrials.gov. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the results of this study are available from the corresponding author upon reasonable request. * CAD : Coronary artery disease CCTA : Coronary computed tomography angiography HRP High-risk plaque TnI : Troponin I CRP : C-reactive protein FFR : Fractional flow reserve CACS : Coronary artery calcium score HU : Hounsfield units PAV : Percentage atheroma volume [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02264717&atom=%2Fmedrxiv%2Fearly%2F2023%2F09%2F16%2F2023.09.14.23295593.atom