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Multicenter Study

. 2023 Aug 1;8(8):755-764.

doi: 10.1001/jamacardio.2023.1729.

Coronary Atherosclerotic Plaque Activity and Future Coronary Events

Alastair Moss^{1

2

3}, Marwa Daghem^{1

2}, Evangelos Tzolos^{1

2}, Mohammed N Meah^{1

2}, Kang-Ling Wang^{1

2}, Anda Bularga^{1

2}, Philip D Adamson⁴, Jacek Kwiecinski⁵, Alison Fletcher^{1

2}, Dana Dawson⁶, Parthiban Arumugam⁷, Nikant Sabharwal⁸, John P Greenwood⁹, Jon N Townend¹⁰, Patrick A Calvert¹¹, James H F Rudd¹², Dan Berman¹³, Johan Verjans¹⁴, Piotr Slomka¹³, Damini Dey¹³, Laura Forsyth¹⁵, Lauren Murdoch¹⁵, Robert J Lee¹⁵, Steff Lewis¹⁵, Nicholas L Mills^{1

2

16}, Edwin J R van Beek^{1

2}, Michelle C Williams^{1

2}, Marc R Dweck^{1

2}, David E Newby^{1

2}; PREFFIR Investigators

Collaborators, Affiliations

Collaborators

PREFFIR Investigators:
Anny Briola, Ruth Armstrong, Alix Macdonald, Gill Scott, Garry Milne, Lynsey Milne, Claire Battison, Martin R Wilkins, Robert F Storey, Reza Razavi, Maja Wallberg, Rodney Mycock

Affiliations

¹ Edinburgh Imaging, The University of Edinburgh, Edinburgh, Scotland.
² British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, Scotland.
³ National Institute for Health and Care Research, Leicester Biomedical Research Centre, University of Leicester, Leicester, England.
⁴ Christchurch Heart Institute, University of Otago, Christchurch, New Zealand.
⁵ Department of Interventional Cardiology and Angiology, Institute of Cardiology, Warsaw, Poland.
⁶ Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen, Aberdeen, Scotland.
⁷ Manchester University, NHS Foundation Trust, Manchester, England.
⁸ Oxford University Hospitals, NHS Foundation Trust, Oxford, England.
⁹ Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, England.
¹⁰ Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, England.
¹¹ Royal Papworth Hospital, University of Cambridge, Cambridge, England.
¹² Department of Medicine, University of Cambridge, Cambridge, England.
¹³ Cedars-Sinai Medical Center, Los Angeles, California.
¹⁴ Adelaide Medical School, The University of Adelaide, Adelaide, Australia.
¹⁵ Edinburgh Clinical Trials Unit, Usher Institute, The University of Edinburgh, Edinburgh, Scotland.
¹⁶ Usher Institute, The University of Edinburgh, Edinburgh, Scotland.

PMID: 37379010
PMCID: PMC10308296
DOI: 10.1001/jamacardio.2023.1729

Multicenter Study

Coronary Atherosclerotic Plaque Activity and Future Coronary Events

Alastair Moss et al. JAMA Cardiol. 2023.

. 2023 Aug 1;8(8):755-764.

doi: 10.1001/jamacardio.2023.1729.

Authors

Alastair Moss^{1

2

3}, Marwa Daghem^{1

2}, Evangelos Tzolos^{1

2}, Mohammed N Meah^{1

2}, Kang-Ling Wang^{1

2}, Anda Bularga^{1

2}, Philip D Adamson⁴, Jacek Kwiecinski⁵, Alison Fletcher^{1

2}, Dana Dawson⁶, Parthiban Arumugam⁷, Nikant Sabharwal⁸, John P Greenwood⁹, Jon N Townend¹⁰, Patrick A Calvert¹¹, James H F Rudd¹², Dan Berman¹³, Johan Verjans¹⁴, Piotr Slomka¹³, Damini Dey¹³, Laura Forsyth¹⁵, Lauren Murdoch¹⁵, Robert J Lee¹⁵, Steff Lewis¹⁵, Nicholas L Mills^{1

2

16}, Edwin J R van Beek^{1

2}, Michelle C Williams^{1

2}, Marc R Dweck^{1

2}, David E Newby^{1

2}; PREFFIR Investigators

Collaborators

PREFFIR Investigators:
Anny Briola, Ruth Armstrong, Alix Macdonald, Gill Scott, Garry Milne, Lynsey Milne, Claire Battison, Martin R Wilkins, Robert F Storey, Reza Razavi, Maja Wallberg, Rodney Mycock

Affiliations

¹ Edinburgh Imaging, The University of Edinburgh, Edinburgh, Scotland.
² British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, Scotland.
³ National Institute for Health and Care Research, Leicester Biomedical Research Centre, University of Leicester, Leicester, England.
⁴ Christchurch Heart Institute, University of Otago, Christchurch, New Zealand.
⁵ Department of Interventional Cardiology and Angiology, Institute of Cardiology, Warsaw, Poland.
⁶ Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen, Aberdeen, Scotland.
⁷ Manchester University, NHS Foundation Trust, Manchester, England.
⁸ Oxford University Hospitals, NHS Foundation Trust, Oxford, England.
⁹ Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, England.
¹⁰ Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, England.
¹¹ Royal Papworth Hospital, University of Cambridge, Cambridge, England.
¹² Department of Medicine, University of Cambridge, Cambridge, England.
¹³ Cedars-Sinai Medical Center, Los Angeles, California.
¹⁴ Adelaide Medical School, The University of Adelaide, Adelaide, Australia.
¹⁵ Edinburgh Clinical Trials Unit, Usher Institute, The University of Edinburgh, Edinburgh, Scotland.
¹⁶ Usher Institute, The University of Edinburgh, Edinburgh, Scotland.

PMID: 37379010
PMCID: PMC10308296
DOI: 10.1001/jamacardio.2023.1729

Abstract

Importance: Recurrent coronary events in patients with recent myocardial infarction remain a major clinical problem. Noninvasive measures of coronary atherosclerotic disease activity have the potential to identify individuals at greatest risk.

Objective: To assess whether coronary atherosclerotic plaque activity as assessed by noninvasive imaging is associated with recurrent coronary events in patients with myocardial infarction.

Design, setting, and participants: This prospective, longitudinal, international multicenter cohort study recruited participants aged 50 years or older with multivessel coronary artery disease and recent (within 21 days) myocardial infarction between September 2015 and February 2020, with a minimum 2 years' follow-up.

Intervention: Coronary 18F-sodium fluoride positron emission tomography and coronary computed tomography angiography.

Main outcomes and measures: Total coronary atherosclerotic plaque activity was assessed by 18F-sodium fluoride uptake. The primary end point was cardiac death or nonfatal myocardial infarction but was expanded during study conduct to include unscheduled coronary revascularization due to lower than anticipated primary event rates.

Results: Among 2684 patients screened, 995 were eligible, 712 attended for imaging, and 704 completed an interpretable scan and comprised the study population. The mean (SD) age of participants was 63.8 (8.2) years, and most were male (601 [85%]). Total coronary atherosclerotic plaque activity was identified in 421 participants (60%). After a median follow-up of 4 years (IQR, 3-5 years), 141 participants (20%) experienced the primary end point: 9 had cardiac death, 49 had nonfatal myocardial infarction, and 83 had unscheduled coronary revascularizations. Increased coronary plaque activity was not associated with the primary end point (hazard ratio [HR], 1.25; 95% CI, 0.89-1.76; P = .20) or unscheduled revascularization (HR, 0.98; 95% CI, 0.64-1.49; P = .91) but was associated with the secondary end point of cardiac death or nonfatal myocardial infarction (47 of 421 patients with high plaque activity [11.2%] vs 19 of 283 with low plaque activity [6.7%]; HR, 1.82; 95% CI, 1.07-3.10; P = .03) and all-cause mortality (30 of 421 patients with high plaque activity [7.1%] vs 9 of 283 with low plaque activity [3.2%]; HR, 2.43; 95% CI, 1.15-5.12; P = .02). After adjustment for differences in baseline clinical characteristics, coronary angiography findings, and Global Registry of Acute Coronary Events score, high coronary plaque activity was associated with cardiac death or nonfatal myocardial infarction (HR, 1.76; 95% CI, 1.00-3.10; P = .05) but not with all-cause mortality (HR, 2.01; 95% CI, 0.90-4.49; P = .09).

Conclusions and relevance: In this cohort study of patients with recent myocardial infarction, coronary atherosclerotic plaque activity was not associated with the primary composite end point. The findings suggest that risk of cardiovascular death or myocardial infarction in patients with elevated plaque activity warrants further research to explore its incremental prognostic implications.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Sabharwal reported receiving grants from The University of Edinburgh during the conduct of the study. Dr Berman reported receiving personal fees for consulting from GE HealthCare outside the submitted work and having a patent for software with royalties paid from Cedars-Sinai Medical Center. Dr Slomka reported receiving personal fees for software royalties from Cedars-Sinai Medical Center and for consulting from Synektik and receiving grants from Siemens outside the submitted work. Dr Dey reported receiving fees for royalties from Cedars-Sinai Medical Center outside the submitted work. Dr Forsyth reported receiving grants from Wellcome Trust during the conduct of the study. Ms Murdoch reported receiving grants from The University of Edinburgh during the conduct of the study. Mr Lee reported receiving grants from Wellcome Trust during the conduct of the study. Prof Lewis reported receiving grants from the Wellcome Trust during the conduct of the study. Prof van Beek reported being founder and owner of Quantitative Clinical Trials Imaging Services, Inc, Ltd; being a member of the advisory board for Aidence NV; being a member of the steering committee of AstraZeneca; receiving consulting fees from Lunit IO and Contextflow; and receiving speaker fees from AstraZeneca outside the submitted work. Dr Williams reported receiving personal fees from Canon Medical Systems, Siemens Healthineers, and Novartis outside the submitted work. No other disclosures were reported.

Figures

Figure 1. — Figure 1.. Cumulative Incidence Plots of the Primary End Points
Low coronary atherosclerotic plaque activity was defined as coronary microcalcification activity [CMA] of 0; high coronary atherosclerotic plaque activity was defined as a CMA greater than 0. PET-CT indicates positron emission tomography–computed tomography.

Figure 2. — Figure 2.. Cumulative Incidence Plots of the Secondary End Points
Low coronary atherosclerotic plaque activity was defined as coronary microcalcification activity [CMA] of 0; high coronary atherosclerotic plaque activity was defined as a CMA greater than 0. PET-CT indicates positron emission tomography–computed tomography.

See this image and copyright information in PMC

Comment in

Can Noncalcified Plaques Contribute to Future Coronary Events?
Erbay MI, Susarla S, Budoff MJ. Erbay MI, et al. JAMA Cardiol. 2024 Jan 1;9(1):94. doi: 10.1001/jamacardio.2023.4390. JAMA Cardiol. 2024. PMID: 38019491 No abstract available.

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