Familial hypercholesterolaemia (FH) is a condition that runs in families and is thought to affect about 1 person in every 250. People with FH have raised blood cholesterol levels from birth. Cholesterol is a type of fat our bodies need but having raised levels over a long time causes heart disease, such as heart attacks. To prevent future heart disease, guidelines in the UK recommend starting cholesterol-reducing medication, usually statins, by age 10.
However, it is unclear what is the right age and cholesterol level at which to start statins to best prevent heart disease later in life. Trials of 1-2 years show these medications reduce cholesterol in children and are safe, but we need more information about taking them in the longer term. There are also newer cholesterol-reducing medications that have not been in trials in children and young people with FH so looking at how they are currently being used will give information on whether they are useful and safe.
This study will use electronic patient health records to assess how useful it is for children and young people with FH to start cholesterol-reducing medications at different ages from under 8 to 18 years. We will see how much cholesterol is reduced compared with not taking medications, whether children take the medication regularly, if there is any evidence that medications are unsafe, and if they affect growth at different ages.
Results will provide information for health professionals and families of children with FH to support their decision-making.
Background: Without treatment, individuals with familial hypercholesterolemia (FH) have a substantial risk of heart attack and premature death. Treatment of FH in childhood primarily uses lipid-lowering therapy (LLT), commonly statins, with National Institute for Health and Care Excellence (NICE) guidelines recommend considering LLT from 10 years of age. The guidelines acknowledge, however, the limited research evidence on the optimal age and low-density lipoprotein-cholesterol (LDL-C) concentration at which LLT should be started in children and young people (CYP). Clinical trials have shown LLT to be effective and safe in children; however, most trials last 6-12 months, with the longest trials being 2 years.
Aim: To describe the current use of LLT in children with FH in the UK and estimate the clinical effectiveness, adherence to treatment, and safety when LLT is commenced at different ages and thresholds of LDL-C for treatment initiation.
Design, Participants and Setting: Open cohort of all patients younger than 25 years of age with FH between 2000 and 2023 with prospectively recorded primary care data (CPRD GOLD and Aurum) from across the United Kingdom, and a sub-cohort from England with linked secondary care data (Hospital Episode Statistics).
Methods: We will estimate:
• absolute and relative reductions in LDL-C, and in cumulative LDL-C, achieved in current practice with LLT using linear mixed-effects models,
• LLT prescription possession ratios (proxy for adherence) and variation using the generalised method of moments (GMM),
• incidence of side-effects and adverse events and changes in growth whilst prescribed LLT and variation using Cox regression.
Models will assess variation by age and LDL-C at initiation of LLT, confounding and effect modification by sex, ethnicity, smoking, body mass index, socioeconomic deprivation, and comorbid conditions.
Public health benefits: Evidence will inform clinical guidelines on the management of FH in young people.
Change in Low Density Lipoprotein-Cholesterol concentration; Lipid-lowering therapy adherence; Lipid-lowering therapy discontinuation; Incidence of side-effects and adverse outcomes potentially related to lipid-lowering therapy.
Laila Tata - Chief Investigator - University of Nottingham
Yana Vinogradova - Corresponding Applicant - University of Nottingham
Nadeem Qureshi - Collaborator - University of Nottingham
Ralph Kwame Akyea - Collaborator - University of Nottingham
Steve Humphries - Collaborator - University College London ( UCL )
Yana Vinogradova - Collaborator - University of Nottingham
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation