Atherosclerosis quantification and cardiovascular risk: the ISCHEMIA trial

Author:

Nurmohamed Nick S123ORCID,Min James K4,Anthopolos Rebecca5ORCID,Reynolds Harmony R5,Earls James P46,Crabtree Tami4,Mancini G B John7,Leipsic Jonathon7,Budoff Matthew J8,Hague Cameron J7,O'Brien Sean M9,Stone Gregg W10ORCID,Berger Jeffrey S5,Donnino Robert5,Sidhu Mandeep S11,Newman Jonathan D5,Boden William E12,Chaitman Bernard R13,Stone Peter H14,Bangalore Sripal5,Spertus John A15,Mark Daniel B9,Shaw Leslee J16,Hochman Judith S5,Maron David J17

Affiliation:

1. Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam , De Boelelaan 1117, 1081 HV Amsterdam , The Netherlands

2. Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam , Meibergdreef 9, 1105 AZ Amsterdam , The Netherlands

3. Division of Cardiology, The George Washington University School of Medicine , 2150 Pennsylvania Avenue NW, Washington, DC 20037 , USA

4. Cleerly, Inc , Denver, CO, USA

5. New York University Grossman School of Medicine , New York, NY , USA

6. Department of Radiology, The George Washington University School of Medicine , Washington, DC , USA

7. Centre for Cardiovascular Innovation, University of British Columbia , Vancouver, British Columbia , Canada

8. Lundquist Institute , Torrance, CA , USA

9. Duke Clinical Research Institute , Durham, NC , USA

10. Icahn School of Medicine at Mount Sinai , New York, NY , USA

11. Albany Medical College , Albany, NY , USA

12. VA New England Healthcare System, Boston University School of Medicine , Boston, MA , USA

13. St Louis University School of Medicine Center for Comprehensive Cardiovascular Care , St Louis, MO , USA

14. Brigham and Women’s Hospital , Boston, MA , USA

15. University of Missouri—Kansas City’s Healthcare Institute for Innovations in Quality and Saint Luke’s Mid America Heart Institute , Kansas City, MO , USA

16. Bronfman Department of Medicine (Cardiology), Icahn School of Medicine at Mount Sinai , New York, NY , USA

17. Department of Medicine, Stanford University School of Medicine , Stanford, CA , USA

Abstract

Abstract Background and Aims The aim of this study was to determine the prognostic value of coronary computed tomography angiography (CCTA)–derived atherosclerotic plaque analysis in ISCHEMIA. Methods Atherosclerosis imaging quantitative computed tomography (AI-QCT) was performed on all available baseline CCTAs to quantify plaque volume, composition, and distribution. Multivariable Cox regression was used to examine the association between baseline risk factors (age, sex, smoking, diabetes, hypertension, ejection fraction, prior coronary disease, estimated glomerular filtration rate, and statin use), number of diseased vessels, atherosclerotic plaque characteristics determined by AI-QCT, and a composite primary outcome of cardiovascular death or myocardial infarction over a median follow-up of 3.3 (interquartile range 2.2–4.4) years. The predictive value of plaque quantification over risk factors was compared in an area under the curve (AUC) analysis. Results Analysable CCTA data were available from 3711 participants (mean age 64 years, 21% female, 79% multivessel coronary artery disease). Amongst the AI-QCT variables, total plaque volume was most strongly associated with the primary outcome (adjusted hazard ratio 1.56, 95% confidence interval 1.25–1.97 per interquartile range increase [559 mm3]; P = .001). The addition of AI-QCT plaque quantification and characterization to baseline risk factors improved the model’s predictive value for the primary outcome at 6 months (AUC 0.688 vs. 0.637; P = .006), at 2 years (AUC 0.660 vs. 0.617; P = .003), and at 4 years of follow-up (AUC 0.654 vs. 0.608; P = .002). The findings were similar for the other reported outcomes. Conclusions In ISCHEMIA, total plaque volume was associated with cardiovascular death or myocardial infarction. In this highly diseased, high-risk population, enhanced assessment of atherosclerotic burden using AI-QCT-derived measures of plaque volume and composition modestly improved event prediction.

Publisher

Oxford University Press (OUP)

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