Around 1 in 250 people carry a genetic condition that spikes their cholesterol from birth, and doctors lack clear evidence on when to start them on statins as children. The problem is that national guidance recommends starting lipid-lowering treatment at age 10, but the evidence for that threshold is thin. Researchers don’t know whether starting earlier or later, or at different cholesterol levels, actually prevents heart disease decades later without causing side effects or harming adherence. This study will follow over 1,300 children on the national Paediatric Familial Hypercholesterolaemia Register, collect 3.5 years of prospective data, and interview 40 children and families plus 30 healthcare professionals. It will also build a cost-effectiveness model comparing different starting ages and cholesterol thresholds. If successful, the findings could directly update NHS guidelines on when to begin treatment, giving clinicians and families a clear, evidence-based answer. That would reduce the risk of premature heart attacks in these patients while avoiding unnecessary medication in children who may not benefit. The work also informs how the NHS configures paediatric lipid services, a quiet but critical piece of preventive infrastructure.
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BACKGROUND: Around 1 in 250 people have familial hypercholesterolaemia (FH) with raised low density lipoprotein-cholesterol (LDL-C) from birth, increasing the risk of premature cardiovascular disease. National guidance recommends starting lipid-lowering treatment (LLT) at age 10 years, yet evidence for the age and LDL-C thresholds at which to initiate LLT is limited, leading to the commissioned call for the RESEARCH QUESTIONS: What is the clinical and cost-effectiveness of LLT in children with FH in the UK? How are these affected by the age of commencing treatment and different thresholds of LDL-C for commencing treatment? OBJECTIVES to answer research questions: 1. Estimate absolute and relative reductions in LDL-C, and in cumulative LDL-C, achieved in current practice with LLT, and whether these vary by age and LDL-C at initiation of LLT 2. Estimate the incidence of side-effects and adverse events associated with LLT 3. Estimate LLT adherence at different ages and characterise reasons for variations in adherence 4. Understand the views of children and young people (CYP), their families and healthcare professionals, on information needs for starting LLT at different ages, and how these influence treatment acceptability, monitoring, and adherence 5. Estimate the impact of initiating LLT at different ages on the costs of managing FH over the short-term in CYP 6. Estimate long-term health outcomes and NHS costs of starting LLT at different ages and LDL-C thresholds to identify a cost-effective approach to management DESIGN & METHODS: Objectives 1 & 2: We will update the national Paediatric FH Register (PFHR) with new recruitment, retrospective clinical data and 3.5 years of prospective data, increasing the current 613 patients to over 1,300. We will also identify FH patients in the Clinical Practice Research Datalink (CPRD), and conduct evidence reviews for any remaining gaps. The Avon Longitudinal Study of Parents and Children (ALSPAC) cohort will provide average age-specific LDL-C levels across childhood in the general population that could be used as target LDL-C levels for treatment in FH. Objectives 3 & 4: Repeated questionnaires sent to CYP on the PFHR will characterise LLT adherence over time, inform healthcare utilisation (for Obj 5), and inform sampling for qualitative interviews (Obj 4). Interviewing 40 CYP with FH and their families and 30 healthcare professionals will inform LLT acceptability and information needed to support monitoring. Objectives 5 & 6: We will estimate the healthcare costs of managing FH in CYP and the impact of initiating LLT. Synthesising information compiled across the study, we will develop a new cost-effectiveness model estimating long-term reductions in cardiovascular disease risk given observed LDL-C reductions in childhood. The model will compare the benefit-risk, short- and long-term health outcomes and costs of starting LLT at different ages and LDL-C thresholds. PROJECT TIMELINE: CPRD/ALSPAC analyses [3-12mths]; PFHR and questionnaire analyses [9-54]; Systematic and pragmatic evidence reviews [6-12 & 36-42]; Interview analyses [10-30]; Estimate costs [39-44]; Build cost-effectiveness model [45-56] IMPACT & DISSEMINATION: We will establish 2 new patient/stakeholder groups for this study bringing direct experience of FH (CYP Advisory Group (CYPAG) and Parent Advisory Group (PAG)). In partnership with these groups, charities including Heart UK, and health care professionals involved in FH care, we will widely disseminate findings with presentations and publications for various audiences. Impact will include updating national FH guidelines and informing commissioners and policymakers on service configuration.
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