Incorporating a polygenic risk score-triaged coronary calcium score into cardiovascular disease examinations to identify subclinical coronary artery disease (ESCALATE): Protocol for a prospective, nonrandomized implementation trial - 13/09/23

Doi : 10.1016/j.ahj.2023.06.009

Michael P. Gray, MPH ^a,^b, Yemima Berman, PhD ^a,^c, Giordano Bottà, PhD ^d, Stuart M. Grieve, DPhil ^e,^f, Amy Ho, MBBS ^g, Jessica Hu, BSc ^a,^b, Karice Hyun, PhD ^h,ⁱ, Jodie Ingles, PhD ^a,^j,^k,^l,^m, Garry Jennings, MD ^a, Gary Kilov, MBBCh ^n,^o, Jean-Frederic Levesque, PhD ^p,^q, Peter Meikle, PhD ^r,^s, Julie Redfern, PhD ^t,^u, Tim Usherwood, PhD ^h, Stephen T. Vernon, PhD ^a,^v, Stephen J. Nicholls, PhD ^w, Gemma A. Figtree, DPhil ^a,^b,^v,^⁎
On behalf of the
PPP-CAD Collaborators
John E. Barlow, Denis Bauer, DanaYemima BradfordBerman, Giordano Bottá, Gemma A. Figtree, Andrew Gilbert, Michael P. Gray, Stuart M. Grieve, Amy Ho, Jessica Hu, Karice Hyun, Garry Jennings, Gary Kilov, Jean-Frederic Levesque, Peter Meikle, Stephen J. Nicholls, Julie Redfern, Bill Stavreski, Graeme Suthers, Tim Usherwood, Andrew Wilson, Stephen Thackway, Caroline Rogers

^a Faculty of Medicine & Health, University of Sydney, Camperdown, NSW, Australia
^b Cardiovascular Discovery Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia
^c Department of Clinical Genetics, Royal North Shore Hospital, St Leonards, NSW, Australia
^d Center for Genomic Medicine, Allelica Srl, Rome Italy
^e Department of Radiology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
^f Imaging and Phenotyping Laboratory, Charles Perkins Centre, University of Sydney, Camperdown, NSW, Australia
^g Our Medical Crows Nest, Crows Nest, NSW, Australia
^h Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Westmead, NSW, Australia
ⁱ ANZAC Research Institute, Faculty of Medicine & Health, University of Sydney, Concord West, NSW, Australia
^j Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, Camperdown, NSW, Australia
^k Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
^l Centre for Population Genomics, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
^m Murdoch Children's Research Institute, Parkville, VIC, Australia
ⁿ Launceston Diabetes Clinic, Launceston, TAS, Australia
^o Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia
^p NSW Agency for Clinical Innovation, St Leonards, NSW, Australia
^q Centre for Primary Health Care and Equity, University of New South Wales, Sydney, NSW, Australia
^r Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
^s Department of Cardiovascular Research Translation and Implementation, La Trobe University, Melbourne, VIC, Australia
^t The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
^u Sydney School of Health Sciences, Faculty of Medicine & Health, University of Sydney, Camperdown, NSW, Australia
^v Department of Cardiology, Royal North Shore Hospital, St Leonards, NSW, Australia
^w Victorian Heart Institute, Monash University, Clayton, VIC, Australia

^⁎Reprint requests: Gemma A. Figtree, MBBS, DPhil, The University of Sydney, Interventional Cardiologist, Royal North Shore Hospital, Kolling Institute of Medical Research, Level 12, Kolling Institute, Reserve Road, St Leonards NSW 2065, Australia.The University of Sydney, Interventional CardiologistRoyal North Shore HospitalKolling Institute of Medical Research, Level 12, Kolling Institute, Reserve RoadSt LeonardsNSW2065Australia

Résumé

Background

Identifying and targeting established modifiable risk factors has been a successful strategy for reducing the burden of coronary artery disease (CAD) at the population-level. However, up to 1-in-4 patients who present with ST elevation myocardial infarction do so in the absence of such risk factors. Polygenic risk scores (PRS) have demonstrated an ability to improve risk prediction models independent of traditional risk factors and self-reported family history, but a pathway for implementation has yet to be clearly identified. The aim of this study is to examine the utility of a CAD PRS to identify individuals with subclinical CAD via a novel clinical pathway, triaging low or intermediate absolute risk individuals for noninvasive coronary imaging, and examining the impact on shared treatment decisions and participant experience.

Trial Design

The ESCALATE study is a 12-month, prospective, multicenter implementation study incorporating PRS into otherwise standard primary care CVD risk assessments, to identify patients at increased lifetime CAD risk for noninvasive coronary imaging. One-thousand eligible participants aged 45 to 65 years old will enter the study, which applies PRS to those considered low or moderate 5-year absolute CVD risk and triages those with CAD PRS ≥80% for a coronary calcium scan. The primary outcome will be the identification of subclinical CAD, defined as a coronary artery calcium score (CACS) >0 Agatston units (AU). Multiple secondary outcomes will be assessed, including baseline CACS ≥100 AU or ≥75th age-/sex-matched percentile, the use and intensity of lipid- and blood pressure-lowering therapeutics, cholesterol and blood pressure levels, and health-related quality of life (HRQOL).

Conclusion

This novel trial will generate evidence on the ability of a PRS-triaged CACS to identify subclinical CAD, as well as subsequent differences in traditional risk factor medical management, pharmacotherapy utilization, and participant experience.

Trial Registration

Australian New Zealand Clinical Trials Registry, ACTRN12622000436774. Trial was prospectively registered on March 18, 2022. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383134

Le texte complet de cet article est disponible en PDF.

Abbreviations : ACS, ANZCTR, AU, AUC, CACS, CAD, CCS, CRF, CT, CVD, ECG, GPAQ, GWAS, HRQOL, MACE, MBS, MESA, MI, NHMRC, PBS, PPP-CAD, PRO, PRS, SC, SCT, SNP, TMC

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Vol 264

P. 163-173 - octobre 2023 Retour au numéro

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Incorporating a polygenic risk score-triaged coronary calcium score into cardiovascular disease examinations to identify subclinical coronary artery disease (ESCALATE): Protocol for a prospective, nonrandomized implementation trial - 13/09/23

Résumé

Background

Trial Design

Conclusion

Trial Registration

Plan

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