About 1 in 250 people (0.4%) have familial hypercholesterolaemia (FH), characterized by elevated plasma low-density lipoprotein cholesterol (LDL-C) and early onset cardiovascular disease (CVD) which includes heart attacks. Despite increased risks of early heart disease, many patients are unaware of their condition, and there are no national screening programmes in England, although GP FH registers are currently under consideration.
To help address this, the recently published NHS Long Term Plan issued in January 2019, aims to improve FH detection to at least 25% over 5 years through the NHS Genomics Programme and management to reduce preventable CVD morbidity. NICE suggests treatment with high-dose cholesterol lowering medication, including statin medicines in adult patients, which reduces the risk of heart attacks by about 80% in patients with FH.
In considering our work on FH, we recognise ethnic disparities in access to diagnosis and treatment. This research using primary care electronic health records will examine ethnic and regional differences in FH diagnosis, management, and lipid clinic referrals to secondary care and how these change over time. This will help inform how patients from different sociodemographic backgrounds with FH will benefit from improved diagnosis, prevention, and management of CVD risk.
Familial hypercholesterolaemia (FH) is a common inherited disorder, causing lifelong elevated low-density lipoprotein cholesterol (LDL-C). Most individuals with FH remain undiagnosed, resulting in the lost opportunities for preventing premature heart disease and death. Ethnic differences in the diagnosis and management of familial hypercholesterolemia (FH) are poorly understood.
This study will use a cohort study design to assess ethnic differences in the diagnosis and management of FH, associated with key intersecting socio-economic (including patient level IMD and a practice level IMD measure), clinical factors, and our selected outcomes in the UK general population.
Linked primary care (both CPRD GOLD and Aurum) and hospitalisation records (HES Admitted Patient Care) in the UK will be used to define a cohort of patients aged 16 years and over with a cholesterol measurement recorded in their primary care records (either CPRD GOLD or Aurum) from 1 January 1997 to 31 December 2021.
The ethnic specific prevalence rates for the diagnosis of familial hypercholesterolaemia (based on both coded diagnosis and phenotypic characteristics) will be estimated. Multivariable Cox proportional hazard regression model will be used to assess the risk of mortality (CVD-related and all-cause) after FH diagnosis. A modified multilevel model [multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA)] will be used to explore inequalities at the intersection of socio-economic and clinical identities. Patient- and practice-level Index of Multiple Deprivation (IMD) information will be used to assess socio-economic inequalities on FH diagnosis at individual and practice level. Practice level IMD will be defined as the percentage of patients from the 4th and 5th lowest IMD.
This study will provide evidence on ethnic disparities in the diagnosis and management of FH in the adult general populations associated with key intersecting socio-demographic and clinical factors, as well as subsequent clinical outcomes.
Primary outcome: The diagnosis of familial hypercholesterolaemia
Secondary outcomes after FH diagnoses:
• Health care utilisation and management:
o Referral to lipid clinics
o Prescription of lipid-lowering medication (statins) and lifestyle advice (smoking cessation, weight reduction)
o Unscheduled hospital admissions
• Mortality:
o CVD-related mortality after a diagnosis of FH
o All-cause mortality after a diagnosis of FH
Mariam Molokhia - Chief Investigator - King's College London (KCL)
Ralph Kwame Akyea - Corresponding Applicant - University of Nottingham
Aya Ayoub - Collaborator - King's College London (KCL)
Divya Parmar - Collaborator - King's College London (KCL)
Nadeem Qureshi - Collaborator - University of Nottingham
Ralph Akyea - Collaborator - King's College London (KCL)
Riyaz Patel - Collaborator - Barts Health and UCLH NHS Trusts
Salma Ayis - Collaborator - King's College London (KCL)
Seeromanie Harding - Collaborator - University of Glasgow
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation