Taron J, Foldyna B, Mayrhofer T, Osborne MT, Meyersohn N, Bittner DO, Puchner SB, Emami H, Lu MT, Ferencik M, Pagidipati NJ, Douglas PS, and Hoffmann U
Objectives: The purpose of this study was to develop a risk prediction model for patients with nonobstructive CAD., Background: Among stable chest pain patients, most cardiovascular (CV) events occur in those with nonobstructive coronary artery disease (CAD). Thus, developing tailored risk prediction approaches in this group of patients, including CV risk factors and CAD characteristics, is needed., Methods: In PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) computed tomographic angiography patients, a core laboratory assessed prevalence of CAD (nonobstructive 1% to 49% left main or 1% to 69% stenosis any coronary artery), degree of stenosis (minimal: 1% to 29%; mild: 30% to 49%; or moderate: 50% to 69%), high-risk plaque (HRP) features (positive remodeling, low-attenuation plaque, and napkin-ring sign), segment involvement score (SIS), and coronary artery calcium (CAC). The primary end point was an adjudicated composite of unstable angina pectoris, nonfatal myocardial infarction, and death. Cox regression analysis determined independent predictors in nonobstructive CAD., Results: Of 2,890 patients (age 61.7 years, 46% women) with any CAD, 90.4% (n = 2,614) had nonobstructive CAD (mean age 61.6 yrs, 46% women, atherosclerotic cardiovascular disease [ASCVD] risk 16.2%). Composite events were independently predicted by ASCVD risk (hazard ratio [HR]: 1.03; p = 0.001), degree of stenosis (30% to 69%; HR: 1.91; p = 0.011), and presence of ≥2 HRP features (HR: 2.40; p = 0.008). Addition of ≥2 HRP features to: 1) ASCVD and CAC; 2) ASCVD and SIS; or 3) ASCVD and degree of stenosis resulted in a statistically significant improvement in model fit (p = 0.0036; p = 0.0176; and p = 0.0318; respectively). Patients with ASCVD ≥7.5%, any HRP, and mild/moderate stenosis had significantly higher event rates than those who did not meet those criteria (3.0% vs. 6.2%; p = 0.007)., Conclusions: Advanced coronary plaque features have incremental value over total plaque burden for the discrimination of clinical events in low-risk stable chest pain patients with nonobstructive CAD. This may be a first step to improve prevention in this cohort with the highest absolute risk for CV events., Competing Interests: Funding Support and Author Disclosures The PROMISE trial was supported by grants from the National Heart Lung and Blood Institute, Bethesda, Maryland: R01HL098237, R01HL098236, R01HL098305, and R01HL098235. Dr Taron is funded by the Deutsche Forschungsgemeinschaft (German Research Foundation; TA 1438/1-2); and is on the Speakers Bureau for Siemens Healthcare, unrelated to this work. Dr Osborne has received grant support from the National Institutes of Health (KL2TR002542) and Intrinsic Imaging, for unrelated work. Dr Meyersohn has received support from the National Institutes of Health/National Heart, Lung, and Blood Institute (T32 HL076136). Dr Lu has received consulting fees with PQBypass, a research grant from the Nvidia Corporation Academic Program, work as a co-investigator on research funded by AstraZeneca and Kowa, and grant support from the American Heart Association Precision Medicine Institute (18UNPG34030172) and the Harvard University Center for AIDS Research (NIH/NIAID 5P30AI060354-14). Dr Ferencik has received grant support from the American Heart Association (13FTF16450001). Dr Pagidipati has received research grants from Amgen, AstraZeneca, Baseline Study, Boehringer Ingelheim, Duke Clinical Research Institute, Eli Lilly & Company, Novo Nordisk Pharmaceutical Company, Regeneron Pharmaceuticals, Sanofi, and Verily Sciences Research Company; and consulting fees from AstraZeneca, Boehringer Ingelheim, Esperion Therapeutics, Eli Lilly & Company, and Novo Nordisk Pharmaceutical Company. Dr Douglas has received a research grant from HeartFlow. Dr Hoffmann has received a grant from the National Institutes of Health (K24HL113128), research support on behalf of the Massachusetts General Hospital from Duke University, HeartFlow, Kowa Company, and MedImmune/AstraZeneca; and consulting fees from Duke University and Recor Medical unrelated to this research. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)