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

Michael P Gray; Yemima Berman; Giordano Bottà; Stuart M Grieve; Amy Ho; Jessica Hu; Karice Hyun; Jodie Ingles; Garry Jennings; Gary Kilov; Jean-Frederic Levesque; Peter Meikle; Julie Redfern; Tim Usherwood; Stephen T Vernon; Stephen J Nicholls; Gemma A Figtree; PPP-CAD Collaborators

doi:10.1016/j.ahj.2023.06.009

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

Am Heart J. 2023 Oct:264:163-173. doi: 10.1016/j.ahj.2023.06.009. Epub 2023 Jun 25.

Authors

Michael P Gray¹, Yemima Berman², Giordano Bottà³, Stuart M Grieve⁴, Amy Ho⁵, Jessica Hu¹, Karice Hyun⁶, Jodie Ingles⁷, Garry Jennings⁸, Gary Kilov⁹, Jean-Frederic Levesque¹⁰, Peter Meikle¹¹, Julie Redfern¹², Tim Usherwood¹³, Stephen T Vernon¹⁴, Stephen J Nicholls¹⁵, Gemma A Figtree¹⁶; PPP-CAD Collaborators

Collaborators

Affiliations

¹ Faculty of Medicine & Health, University of Sydney, Camperdown, NSW, Australia; Cardiovascular Discovery Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia.
² Faculty of Medicine & Health, University of Sydney, Camperdown, NSW, Australia; Department of Clinical Genetics, Royal North Shore Hospital, St Leonards, NSW, Australia.
³ Center for Genomic Medicine, Allelica Srl, Rome Italy.
⁴ Department of Radiology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Imaging and Phenotyping Laboratory, Charles Perkins Centre, University of Sydney, Camperdown, NSW, Australia.
⁵ Our Medical Crows Nest, Crows Nest, NSW, Australia.
⁶ Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Westmead, NSW, Australia; ANZAC Research Institute, Faculty of Medicine & Health, University of Sydney, Concord West, NSW, Australia.
⁷ Faculty of Medicine & Health, University of Sydney, Camperdown, NSW, Australia; Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, Camperdown, NSW, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Centre for Population Genomics, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; Murdoch Children's Research Institute, Parkville, VIC, Australia.
⁸ Faculty of Medicine & Health, University of Sydney, Camperdown, NSW, Australia.
⁹ Launceston Diabetes Clinic, Launceston, TAS, Australia; Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia.
¹⁰ NSW Agency for Clinical Innovation, St Leonards, NSW, Australia; Centre for Primary Health Care and Equity, University of New South Wales, Sydney, NSW, Australia.
¹¹ Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; Department of Cardiovascular Research Translation and Implementation, La Trobe University, Melbourne, VIC, Australia.
¹² The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; Sydney School of Health Sciences, Faculty of Medicine & Health, University of Sydney, Camperdown, NSW, Australia.
¹³ Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Westmead, NSW, Australia.
¹⁴ Faculty of Medicine & Health, University of Sydney, Camperdown, NSW, Australia; Department of Cardiology, Royal North Shore Hospital, St Leonards, NSW, Australia.
¹⁵ Victorian Heart Institute, Monash University, Clayton, VIC, Australia.
¹⁶ Faculty of Medicine & Health, University of Sydney, Camperdown, NSW, Australia; Cardiovascular Discovery Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia; Department of Cardiology, Royal North Shore Hospital, St Leonards, NSW, Australia. Electronic address: [email protected].

PMID: 37364748
DOI: 10.1016/j.ahj.2023.06.009

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Australien
Calcium
Cardiovascular Diseases*
Coronary Angiography / methods
Coronary Artery Disease* / diagnosis
Coronary Artery Disease* / genetics
Humans
Middle Aged
Multicenter Studies as Topic
Prospective Studies
Quality of Life
Risk Assessment
Risk Factors
Triage

Substances

Calcium