An independent external validation of the QRISK3 cardiovascular risk prediction model applied to UK Biobank participants

Background The QRISK3 cardiovascular disease (CVD) risk prediction model was derived using primary care data; however, it is frequently used outside of clinical settings. The use of QRISK3 in epidemiological studies without external validation may lead to inaccurate results, however it has been used multiple times on data from UK Biobank. We aimed to externally evaluate the performance of QRISK3 for predicting 10-year risk of cardiovascular events in the UK Biobank cohort. Methods We used data from the UK Biobank, a large-scale prospective cohort study of 403,370 participants aged 40-69 years recruited between 2006 and 2010 in the United Kingdom (UK). We included participants with no previous history of CVD or statin treatment and the outcome was the first occurrence of coronary heart disease, ischaemic stroke or transient ischaemic attack, derived from linked hospital episode statistics (HES) and death registration data (DRD). Results Our study population included 233,233 females and 170,137 males, with 9295 and 13,028 incident cardiovascular events, respectively. The overall median follow-up time after recruitment was 11.7 years. The discrimination measure of QRISK3 in the overall population was reasonable (Harrell’s C-Index 0.722 in females and 0.697 in males), this was poorer in older participants (<0.62 in all participants aged 65 or older). QRISK3 had systematic over-prediction of CVD risk in UK Biobank, particularly in older participants, by as much as 20%. Conclusions QRISK3 had reasonable overall discrimination for the whole study population, which was best in younger participants. The observed CVD risk in UK Biobank participants was lower than that predicted by QRISK3, particularly for older participants. The UK Biobank cohort is known to be healthier than the general population and therefore it is necessary to recalibrate QRISK3 before using it to predict absolute CVD risk in the UK Biobank cohort. ### Competing Interest Statement D.A.C. declares academic grants from GlaxoSmithKline and personal fees from Oxford University Innovation, Biobeats and Sensyne Health, outside the context of this work. D.A.C is additionally supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. ### Funding Statement The UK Biobank study was supported by the Wellcome Trust, Medical Research Council, Department of Health, Scottish government, and Northwest Regional Development Agency. It has also received funding from the Welsh Assembly government and British Heart Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The UK Biobank study received ethical approval from the North West Multi-center Research Ethics Committee (REC reference: 11/NW/03820). All participants gave written informed consent before enrolment in the study, which was conducted in accordance with the principles of the Declaration of Helsinki. This study has been conducted under the UK Biobank application number 33952. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes UK Biobank data are available through a procedure described at [http://www.ukbiobank.ac.uk/using-the-resource/][1]. [1]: https://www.ukbiobank.ac.uk/using-the-resource/