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Detection of Familial Hypercholesterolaemia in Cardiovascular Disease Registry

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ClinicalTrials.gov Identifier: NCT02778646
Recruitment Status : Completed
First Posted : May 20, 2016
Last Update Posted : May 20, 2016
Sponsor:
Collaborator:
Aegerion Pharmaceuticals, Inc.
Information provided by (Responsible Party):
University College, London

Brief Summary:

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.


Condition or disease
Familial Hypercholesterolemia Cardiac Event Percutaneous Coronary Intervention

Detailed Description:

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).


Study Type : Observational [Patient Registry]
Actual Enrollment : 1622948 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Target Follow-Up Duration: 10 Years
Official Title: Detection of Familial Hypercholesterolaemia Within United Kingdom Based National Disease Registries: A National Institute for Cardiovascular Outcomes Research (NICOR) Study
Study Start Date : January 2003
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine


Group/Cohort
MINAP Audit
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
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.



Primary Outcome Measures :
  1. Cholesterol (mmol/L) [ Time Frame: Within 24 hours of Hospital Admission ]

    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).


  2. Survival Following Hospital Admission for a Major Coronary Event [ Time Frame: Up to 10 years ]

    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.




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Ages Eligible for Study:   18 Years to 59 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
UK based clinical population (participating hospitals across England and Wales).
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02778646


Sponsors and Collaborators
University College, London
Aegerion Pharmaceuticals, Inc.
Investigators
Study Chair: Joy Ayemoba, MSc UCL
Principal Investigator: John Deanfield, MD UCL
Study Director: Owen Nicholas, PhD UCL
Study Chair: Riyaz Patel, MD UCL

Publications:
Nair, Devaki R., Mahtab Sharifi, and Khalid Al-Rasadi. 'Familial Hypercholesterolaemia : Current Opinion In Cardiology'. LWW. N.p., 2015. Web. 16 Apr. 2015.
Nice.org.uk,. 'Identification And Management Of Familial Hypercholesterolaemia | Guidance And Guidelines | NICE'. N.p., 2008. Web. 27 Apr. 2015.
Charniak, Eugene. 'Bayesian Networks Without Tears'. AI Magazine 12.4 (1991): 50-63. Print.
De Castro-Orós, Isabel, Miguel Pocoví, and Fernando Civeira. 'The Fine Line Between Familial And Polygenic Hypercholesterolemia'. Clinical Lipidology 8.3 (2013): 303-306. Web.
Spiegelhalter, D. J, K. R Abrams, and Jonathan P Myles. Bayesian Approaches To Clinical Trials And Health-Care Evaluation. Chichester: John Wiley & Sons, 2004. Print.
World Health Organization,. Familial Hypercholesterolaemia. Geneva, Switzerland: Human Genetics Programme, 1998. Print. Annex Progress Report.
Do R, Stitziel NO, Won HH, Jørgensen AB, Duga S, Angelica Merlini P, Kiezun A, Farrall M, Goel A, Zuk O, Guella I, Asselta R, Lange LA, Peloso GM, Auer PL; NHLBI Exome Sequencing Project, Girelli D, Martinelli N, Farlow DN, DePristo MA, Roberts R, Stewart AF, Saleheen D, Danesh J, Epstein SE, Sivapalaratnam S, Hovingh GK, Kastelein JJ, Samani NJ, Schunkert H, Erdmann J, Shah SH, Kraus WE, Davies R, Nikpay M, Johansen CT, Wang J, Hegele RA, Hechter E, Marz W, Kleber ME, Huang J, Johnson AD, Li M, Burke GL, Gross M, Liu Y, Assimes TL, Heiss G, Lange EM, Folsom AR, Taylor HA, Olivieri O, Hamsten A, Clarke R, Reilly DF, Yin W, Rivas MA, Donnelly P, Rossouw JE, Psaty BM, Herrington DM, Wilson JG, Rich SS, Bamshad MJ, Tracy RP, Cupples LA, Rader DJ, Reilly MP, Spertus JA, Cresci S, Hartiala J, Tang WH, Hazen SL, Allayee H, Reiner AP, Carlson CS, Kooperberg C, Jackson RD, Boerwinkle E, Lander ES, Schwartz SM, Siscovick DS, McPherson R, Tybjaerg-Hansen A, Abecasis GR, Watkins H, Nickerson DA, Ardissino D, Sunyaev SR, O'Donnell CJ, Altshuler D, Gabriel S, Kathiresan S. Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. Nature. 2015 Feb 5;518(7537):102-6. doi: 10.1038/nature13917. Epub 2014 Dec 10.

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT02778646     History of Changes
Other Study ID Numbers: NCR-15-07
First Posted: May 20, 2016    Key Record Dates
Last Update Posted: May 20, 2016
Last Verified: July 2015

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipoproteinemia Type II
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias