Abstract
BackgroundA downwards secular trend in the incidence of cardiovascular disease (CVD) in England was identified through previous work and the literature. Risk prediction models for primary prevention of CVD do not model this secular trend, this could result in over prediction of risk for individuals in the present day. We evaluate the effects of modelling this secular trend, and also assess whether it is driven by an increase in statin use during follow up.MethodsWe derived a cohort of patients (1998–2015) eligible for cardiovascular risk prediction from the Clinical Practice Research Datalink with linked hospitalisation and mortality records (N = 3,855,660). Patients were split into development and validation cohort based on their cohort entry date (before/after 2010). The calibration of a CVD risk prediction model developed in the development cohort was tested in the validation cohort. The calibration was also assessed after modelling the secular trend. Finally, the presence of the secular trend was evaluated under a marginal structural model framework, where the effect of statin treatment during follow up is adjusted for.ResultsSubstantial over prediction of risks in the validation cohort was found when not modelling the secular trend. This miscalibration could be minimised if one was to explicitly model the secular trend. The reduction in risk in the validation cohort when introducing the secular trend was 35.68 and 33.24% in the female and male cohorts respectively. Under the marginal structural model framework, the reductions were 33.31 and 32.67% respectively, indicating increasing statin use during follow up is not the only the cause of the secular trend.ConclusionsInclusion of the secular trend into the model substantially changed the CVD risk predictions. Models that are being used in clinical practice in the UK do not model secular trend and may thus overestimate the risks, possibly leading to patients being treated unnecessarily. Wider discussion around the modelling of secular trends in a risk prediction framework is needed.
Highlights
A downwards secular trend in the incidence of cardiovascular disease (CVD) in England was identified through previous work and the literature
Data source A ‘CVD primary prevention cohort’ was defined from a Clinical Practice Research Datalink (CPRD) [7] dataset linked with Hospital Episode Statistics [8] (HES) and Office for National Statistics [9] (ONS) using the same criteria as QRISK3 [1]
The amount of missing data was lower in the validation cohorts compared to the development cohorts, and in the female cohorts compared to the male cohorts
Summary
A downwards secular trend in the incidence of cardiovascular disease (CVD) in England was identified through previous work and the literature. Downwards secular trends in the incidence of coronary heart disease, myocardial infarction, and stroke have been reported in the literature [3,4,5,6] Not including this trend in the prediction modelling could be resulting in the miscalibration of risk scores for patients in the present day, while including it would cause a large reduction in the predicted risks of these patients. It is important to clarify if the secular trend is being driven by an increase in statin use over time In this scenario it should not be modelled, as it would result in risks predictions becoming lower and patients would be subsequently advised not to initiate statin treatment, despite this being the cause for the drop in risk
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