Familial hypercholesterolemia (FH) is the most common inherited cause of raised cholesterol, affecting 1 in 270 people in the UK. It leads to premature heart disease and death if untreated. Unfortunately, the majority of people with FH remain undiagnosed. A recent study has shown that even with a diagnosis of FH in primary care, individuals had a 2-fold higher risk of heart disease than the general population of people without FH.
While there is a pressing need to improve FH awareness and diagnosis among clinicians, no research has explored whether there is a difference in treatment and health outcomes between patients identified with FH in primary care and those under specialist management. It is unknown whether FH patients are more closely managed in specialist compared to primary care, and if this has an impact on future health outcomes and the risk of death.
To help answer this question, the proposed research aims to assess the treatment and health outcomes of patients with FH in primary care in comparison with patients in a specialist FH disease register. These two groups of patients will be compared and assessed in terms of differences in treatments, if they develop heart disease, and causes of death. The research findings will indicate if these FH patients need to be better managed in primary care.
Background: Early identification and treatment of familial hypercholesterolaemia (FH) can reduce the risk of premature heart disease and death. Current evidence suggests that individuals with a diagnosis of FH in primary care have a 2-fold higher risk of coronary heart disease (CHD) than individuals without FH. It is unknown whether there are significant gaps in treatment and clinical outcomes between individuals with a diagnosis of FH in primary care, and those who have been referred to lipid clinics and under specialist management.
Aim: To explore the difference in clinical management, cardiovascular health and mortality outcomes in individuals with FH in primary care compared with FH patients in the Simon Broome FH register.
Study design: Observational cohort study
Settings:
a. General practices in England providing data to the CPRD database
b. Lipid clinics in England which contribute data to the Simon-Broome FH register
Study population:
a. CPRD population: Individuals aged 18 to 80 years, documented FH diagnosis and registered at the general practice for at least a year after the earliest date that the practice started contributing quality-assured data to CPRD.
b. Simon-Broome study population: FH patients aged 18 to 80 years.
Main outcome measures:
Primary outcomes: cardiovascular disease (defined as composite of CHD, stroke, transient ischaemic attack, peripheral vascular disease); statin-prescribing rates, coronary revascularisation interventions
Secondary outcomes: Low-density-lipoprotein (LDL) cholesterol response to statins, cardiovascular death, all-cause mortality
Statistical analyses:
- Survival analyses to determine the incidence rates of cardiovascular disease (CVD), cardiovascular-mortality and all-cause mortality in both FH cohorts.
- Assessment of statin prescribing rates, and proportion of FH patients in primary care, who attain the treatment goal of 50% LDL-cholesterol reduction, 12 months after initiating statins
- Multivariate Cox regression analyses to estimate the hazards ratios of CVD and mortality: (a) associated with LDL-cholesterol treatment response and (b) associated with coronary-revascularisation interventions.
- Incidence of cardiovascular disease
- Statin-prescribing rates
- Coronary revascularisation
- Change in LDL-cholesterol, 12 months after initiation of statins
- Cardiovascular mortality and all-cause mortality rates
Barbara Iyen - Chief Investigator - University of Nottingham
Barbara Iyen - Corresponding Applicant - University of Nottingham
Joe Kai - Collaborator - University of Nottingham
Nadeem Qureshi - Collaborator - University of Nottingham
Stephen Weng - Collaborator - University of Nottingham
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation