Familial hypercholesterolaemia (FH) is an inherited condition characterised by raised cholesterol levels from birth and associated heightened risk of heart disease. However, among those with FH there is variation in the extent to which both cholesterol and future heart disease risk are raised. This has consequences for treatment decisions, as the benefits conferred by cholesterol-lowering treatments are typically greater where future cardiovascular disease (CVD including heart disease) risk is higher, and individuals may feel that the risks and inconvenience of treatment are justified only when the expected benefit exceeds a particular threshold. Moreover, the cost of particular treatments may be considered justifiable only at particular levels of risk. As such, an ability to estimate individual future CVD risk among those with FH would be valuable, and help enable provision of new treatments to those that may benefit. Such a risk prediction method has recently been proposed, but requires testing in settings other than that in which it was derived (multiple centres across Spain), before wider use is recommended. We therefore aim here to test this model among those registered with UK primary care practices. In addition to assessing the tool per se, the study will aid understanding of whether it has clinical utility in UK primary care practice specifically.
Aim: an external validation of the SAFEHEART prognostic tool in predicting the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) events
Study design: historical open cohort study
Observational period: 2000-2017
Population: a routine UK primary care cohort of individuals with familial hypercholesterolaemia, >18 years and < 80 years at baseline
Outcome: first occurrence, post cohort entry, of myocardial infarction, coronary revascularisation, ischaemic stroke, carotid revascularisation, peripheral vascular disease, peripheral arterial revascularisation, or cardiovascular death
Predictors: age, sex, ASCVD history, hypertension, body mass index, current smoking, low density lipoprotein-cholesterol and lipoprotein(a) levels
Performance assessment: We will describe the risk factor distributions and outcome incidence for the validation cohort, and calculate the 10-year estimated ASCVD event risk for each individual using the SAFEHEART tool. We will assess model accuracy using standard measures of calibration and discrimination for censored data, including those reported for the derivation dataset, to enable comparison. We will assess the clinical utility of the tool across a range of vascular risk estimates/potential treatment decision thresholds, in a decision curve analysis.
Myocardial infarction
Coronary revascularisation
Ischaemic stroke
Carotid revascularisation
Peripheral vascular disease
Peripheral arterial revascularisation
Cardiovascular death
Kausik Ray - Chief Investigator - Imperial College London
Ailsa McKay - Corresponding Applicant - Imperial College London
Azeem Majeed - Collaborator - Imperial College London
Laura Gunn - Collaborator - Imperial College London
HES Admitted Patient Care;ONS Death Registration Data