Detection of Familial Hypercholesterolaemia in Cardiovascular Disease Registry

Study Overview
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Brief Summary
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Familial hypercholesterolaemia (FH) is an autosomal dominant somatic mutation commonly located on the LDL-receptor, APOB, and PCKS9 gene. The estimated prevalence of homozygous FH is estimated at 1 in a million, whereas the prevalence of heterozygous FH ranges from 1/500-1/200 (0.2-0.5%) of the general population. The majority of individuals suffering from FH remain undiagnosed and without treatment. Using preexisting clinical guidelines, this study scored patients within national cardiovascular disease (CVD) registries for FH with the aim of evaluating prevalence of FH among individuals suffering from premature cardiac events within the UK. Following scoring of the registry, this study also examined the relationship between cholesterol and survival after a premature event in order to understand the possible ramifications of untreated FH on patient survival.

Detailed Description
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Familial Hypercholesterolaemia (FH) is a genetic disorder caused by a mutation in the low-density lipoprotein receptor (LDL-R) gene. Individuals suffering from FH experience elevated cholesterol levels that are outside of the accepted range of healthy cholesterol levels. When left untreated FH may cause complications in cardiovascular health and may cause premature cardiac events. Current screening methods for this disease do not successfully diagnose the majority of FH cases. This study applies three clinical diagnostic tools--Dutch Lipid Clinic Network Criteria (DLCN-Criteria), Make Early Diagnosis to Prevent Early Deaths (MEDPED) criteria, and the Simon Broome Register Criteria--within national registries in order to define possible, probable, and definite cases of FH. The national registries used for this study are the Myocardial Ischaemia National Audit Project (MINAP) and National Audit of Percutaneous Coronary Intervention (BCIS) audit. Following scoring of patients, a one-year and 30-day survival model were created in order to assess the effect of elevated cholesterol on survival, as suspected FH patients will have elevated cholesterol levels. Data within MINAP ranges from 2003-2013 and data from BCIS ranges from 2007-2014. Patient information within the audits was collected following admission to English and Welsh hospitals following a coronary event or percutaneous coronary intervention (PCI). Information related to survival and mortality was collected annually within each audit. Participants for this study were those experiencing a premature cardiovascular event or coronary intervention (men <55 and women<60).

Official Title
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Detection of Familial Hypercholesterolaemia Within United Kingdom Based National Disease Registries: A National Institute for Cardiovascular Outcomes Research (NICOR) Study

Conditions
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Familial Hypercholesterolemia, Cardiac Event, Percutaneous Coronary Intervention

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Experienced a cardiac event and is therefore entered in CVD audit First registered event within audits Exclusion Criteria: Under age 18 Previous diagnosis of FH

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MINAP Audit<br>Individuals within this group are those that have been admitted into a United Kingdom (UK) based hospital following a major cardiac event. The FH status of individuals within this group is unknown. | |
| BCIS Audit<br>Individuals within this group are those who have undergone percutaneous coronary intervention in the United Kingdom (UK). The FH status of individuals within this group is unknown. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cholesterol (mmol/L) | The primary outcome of this study is elevation of cholesterol due to suspected FH. Patients within either audit have experienced a major coronary event which is defined as: Myocardial Infarction (NSTEMI/STEMI), coronary artery bypass graft (CABG), aortic surgery, valve replacements/repairs, and percutaneous coronary intervention (PCI). This study is interested in detection of familial hypercholesterolaemia (FH) amongst patients experiencing a premature cardiac event. One of the key indicators of familial hypercholesterolaemia is elevated cholesterol. After hospital admission, a patient's cholesterol measurements will be taken within the first 24 hours. This is the only cholesterol measurement that is collected within the audit, as it does not fluctuate due to cholesterol depression post-event, and is potentially more indicative or a patient's cholesterol history (especially in situations where a patient has no prior history of statins). | Within 24 hours of Hospital Admission | 
| Survival Following Hospital Admission for a Major Coronary Event | Untreated familial hypercholesterolaemia--and as a result elevated cholesterol--may lead to premature death from coronary heart disease (CHD). Another primary outcome of this study is patient survival following hospital admission for a premature cardiac event. | Up to 10 years |