Detection of Familial Hypercholesterolaemia in Cardiovascular Disease Registry

NCT02778646 | Completed

• 1 other identifier: NCR-15-07
• Study Type: observational
• Target: 1,622,948
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Familial Hypercholesterolemia; Cardiac Event; Percutaneous Coronary Intervention

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (2)

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.

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

UK based clinical population (participating hospitals across England and Wales).

You may qualify if:

• Experienced a cardiac event and is therefore entered in CVD audit
• First registered event within audits

You may not qualify if:

• Under age 18
• Previous diagnosis of FH

Sponsors & Collaborators

• University College, London: lead
• Aegerion Pharmaceuticals, Inc.: collaborator

Related Publications (50)

• Bell DA, Kirke AB, Barbour R, Southwell L, Pang J, Burrows S, Watts GF. Can patients be accurately assessed for familial hypercholesterolaemia in primary care? Heart Lung Circ. 2014 Dec;23(12):1153-7. doi: 10.1016/j.hlc.2014.06.015. Epub 2014 Jul 5.

  PMID: 25065543 BACKGROUND

• Chen CX, Hay JW. Cost-effectiveness analysis of alternative screening and treatment strategies for heterozygous familial hypercholesterolemia in the United States. Int J Cardiol. 2015 Feb 15;181:417-24. doi: 10.1016/j.ijcard.2014.12.070. Epub 2014 Dec 24.

  PMID: 25569270 BACKGROUND

• Futema M, Kumari M, Boustred C, Kivimaki M, Humphries SE. Would raising the total cholesterol diagnostic cut-off from 7.5 mmol/L to 9.3 mmol/L improve detection rate of patients with monogenic familial hypercholesterolaemia? Atherosclerosis. 2015 Apr;239(2):295-8. doi: 10.1016/j.atherosclerosis.2015.01.028. Epub 2015 Jan 28.

  PMID: 25682026 BACKGROUND

• Goldberg AC, Hopkins PN, Toth PP, Ballantyne CM, Rader DJ, Robinson JG, Daniels SR, Gidding SS, de Ferranti SD, Ito MK, McGowan MP, Moriarty PM, Cromwell WC, Ross JL, Ziajka PE. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011 May-Jun;5(3):133-140. doi: 10.1016/j.jacl.2011.03.001. Epub 2011 Mar 11.

  PMID: 21600517 BACKGROUND

• Gray J, Jaiyeola A, Whiting M, Modell M, Wierzbicki AS. Identifying patients with familial hypercholesterolaemia in primary care: an informatics-based approach in one primary care centre. Heart. 2008 Jun;94(6):754-8. doi: 10.1136/hrt.2006.107391. Epub 2007 Jun 17.

  PMID: 17575326 BACKGROUND

• Haralambos K, Whatley SD, Edwards R, Gingell R, Townsend D, Ashfield-Watt P, Lansberg P, Datta DB, McDowell IF. Clinical experience of scoring criteria for Familial Hypercholesterolaemia (FH) genetic testing in Wales. Atherosclerosis. 2015 May;240(1):190-6. doi: 10.1016/j.atherosclerosis.2015.03.003. Epub 2015 Mar 6.

  PMID: 25797312 BACKGROUND

• Kirke AB, Barbour RA, Burrows S, Bell DA, Vickery AW, Emery J, Watts GF. Systematic detection of familial hypercholesterolaemia in primary health care: a community based prospective study of three methods. Heart Lung Circ. 2015 Mar;24(3):250-6. doi: 10.1016/j.hlc.2014.09.011. Epub 2014 Sep 30.

  PMID: 25445428 BACKGROUND

• Kirke A, Watts GF, Emery J. Detecting familial hypercholesterolaemia in general practice. Aust Fam Physician. 2012 Dec;41(12):965-8.

  PMID: 23210121 BACKGROUND

• Nair DR, Sharifi M, Al-Rasadi K. Familial hypercholesterolaemia. Curr Opin Cardiol. 2014 Jul;29(4):381-8. doi: 10.1097/HCO.0000000000000083.

  PMID: 24870549 BACKGROUND

• Nice.org.uk,. 'Identification And Management Of Familial Hypercholesterolaemia | Guidance And Guidelines | NICE'. N.p., 2008. Web. 27 Apr. 2015.

  BACKGROUND

• Watts GF, Shaw JE, Pang J, Magliano DJ, Jennings GL, Carrington MJ. Prevalence and treatment of familial hypercholesterolaemia in Australian communities. Int J Cardiol. 2015 Apr 15;185:69-71. doi: 10.1016/j.ijcard.2015.03.027. Epub 2015 Mar 3. No abstract available.

  PMID: 25791093 BACKGROUND

• Weng SF, Kai J, Andrew Neil H, Humphries SE, Qureshi N. Improving identification of familial hypercholesterolaemia in primary care: derivation and validation of the familial hypercholesterolaemia case ascertainment tool (FAMCAT). Atherosclerosis. 2015 Feb;238(2):336-43. doi: 10.1016/j.atherosclerosis.2014.12.034. Epub 2014 Dec 20.

  PMID: 25555265 BACKGROUND

• Arnold SV, Kosiborod M, Tang F, Zhao Z, McCollam PL, Birt J, Spertus JA. Changes in low-density lipoprotein cholesterol levels after discharge for acute myocardial infarction in a real-world patient population. Am J Epidemiol. 2014 Jun 1;179(11):1293-300. doi: 10.1093/aje/kwu060. Epub 2014 Apr 16.

  PMID: 24743066 BACKGROUND

• Austin MA, Hutter CM, Zimmern RL, Humphries SE. Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review. Am J Epidemiol. 2004 Sep 1;160(5):407-20. doi: 10.1093/aje/kwh236.

  PMID: 15321837 BACKGROUND

• Barth JH, Jackson BM, Farrin AJ, Efthymiou M, Worthy G, Copeland J, Bailey KM, Romaine SP, Balmforth AJ, McCormack T, Whitehead A, Flather MD, Nixon J, Hall AS; SPACE ROCKET Trial Group. Change in serum lipids after acute coronary syndromes: secondary analysis of SPACE ROCKET study data and a comparative literature review. Clin Chem. 2010 Oct;56(10):1592-8. doi: 10.1373/clinchem.2010.145631. Epub 2010 Aug 20.

  PMID: 20729301 BACKGROUND

• Besseling J, Kindt I, Hof M, Kastelein JJ, Hutten BA, Hovingh GK. Severe heterozygous familial hypercholesterolemia and risk for cardiovascular disease: a study of a cohort of 14,000 mutation carriers. Atherosclerosis. 2014 Mar;233(1):219-23. doi: 10.1016/j.atherosclerosis.2013.12.020. Epub 2014 Jan 11.

  PMID: 24529147 BACKGROUND

• Chakko S, Myerburg RJ. Cardiac complications of cocaine abuse. Clin Cardiol. 1995 Feb;18(2):67-72. doi: 10.1002/clc.4960180206.

  PMID: 7720292 BACKGROUND

• Charniak, Eugene. 'Bayesian Networks Without Tears'. AI Magazine 12.4 (1991): 50-63. Print.

  BACKGROUND

• 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.

  BACKGROUND

• de Ferranti SD, de Boer IH, Fonseca V, Fox CS, Golden SH, Lavie CJ, Magge SN, Marx N, McGuire DK, Orchard TJ, Zinman B, Eckel RH. Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association. Circulation. 2014 Sep 23;130(13):1110-30. doi: 10.1161/CIR.0000000000000034. Epub 2014 Aug 11. No abstract available.

  PMID: 25114208 BACKGROUND

• Gaziano JM, Hennekens CH, Satterfield S, Roy C, Sesso HD, Breslow JL, Buring JE. Clinical utility of lipid and lipoprotein levels during hospitalization for acute myocardial infarction. Vasc Med. 1999;4(4):227-31. doi: 10.1177/1358836X9900400404.

  PMID: 10613626 BACKGROUND

• Kasim S, O'Donabhain R, Mcfadden E. Cocaine-associated myocardial infarction: should they all be stented? Case Rep Cardiol. 2011;2011:347806. doi: 10.1155/2011/347806. Epub 2011 Jul 19.

  PMID: 24826216 BACKGROUND

• Mabuchi H, Higashikata T, Nohara A, Lu H, Yu WX, Nozue T, Noji Y, Katsuda S, Kawashiri MA, Inazu A, Kobayashi J, Koizumi J. Cutoff point separating affected and unaffected familial hypercholesterolemic patients validated by LDL-receptor gene mutants. J Atheroscler Thromb. 2005;12(1):35-40. doi: 10.5551/jat.12.35.

  PMID: 15725694 BACKGROUND

• Mittleman MA, Mintzer D, Maclure M, Tofler GH, Sherwood JB, Muller JE. Triggering of myocardial infarction by cocaine. Circulation. 1999 Jun 1;99(21):2737-41. doi: 10.1161/01.cir.99.21.2737.

  PMID: 10351966 BACKGROUND

• Mundal L, Sarancic M, Ose L, Iversen PO, Borgan JK, Veierod MB, Leren TP, Retterstol K. Mortality among patients with familial hypercholesterolemia: a registry-based study in Norway, 1992-2010. J Am Heart Assoc. 2014 Dec 2;3(6):e001236. doi: 10.1161/JAHA.114.001236.

  PMID: 25468658 BACKGROUND

• Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, Wiklund O, Hegele RA, Raal FJ, Defesche JC, Wiegman A, Santos RD, Watts GF, Parhofer KG, Hovingh GK, Kovanen PT, Boileau C, Averna M, Boren J, Bruckert E, Catapano AL, Kuivenhoven JA, Pajukanta P, Ray K, Stalenhoef AF, Stroes E, Taskinen MR, Tybjaerg-Hansen A; European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013 Dec;34(45):3478-90a. doi: 10.1093/eurheartj/eht273. Epub 2013 Aug 15.

  PMID: 23956253 BACKGROUND

• Orchard TJ, Costacou T, Kretowski A, Nesto RW. Type 1 diabetes and coronary artery disease. Diabetes Care. 2006 Nov;29(11):2528-38. doi: 10.2337/dc06-1161. No abstract available.

  PMID: 17065698 BACKGROUND

• Qureshi AI, Chaudhry SA, Suri MF. Cocaine use and the likelihood of cardiovascular and all-cause mortality: data from the Third National Health and Nutrition Examination Survey Mortality Follow-up Study. J Vasc Interv Neurol. 2014 May;7(1):76-82.

  PMID: 24920992 BACKGROUND

• Raal FJ, Pilcher GJ, Panz VR, van Deventer HE, Brice BC, Blom DJ, Marais AD. Reduction in mortality in subjects with homozygous familial hypercholesterolemia associated with advances in lipid-lowering therapy. Circulation. 2011 Nov 15;124(20):2202-7. doi: 10.1161/CIRCULATIONAHA.111.042523. Epub 2011 Oct 10.

  PMID: 21986285 BACKGROUND

• Schnell O, Cappuccio F, Genovese S, Standl E, Valensi P, Ceriello A. Type 1 diabetes and cardiovascular disease. Cardiovasc Diabetol. 2013 Oct 28;12:156. doi: 10.1186/1475-2840-12-156.

  PMID: 24165454 BACKGROUND

• Sijbrands EJ, Westendorp RG, Defesche JC, de Meier PH, Smelt AH, Kastelein JJ. Mortality over two centuries in large pedigree with familial hypercholesterolaemia: family tree mortality study. BMJ. 2001 Apr 28;322(7293):1019-23. doi: 10.1136/bmj.322.7293.1019.

  PMID: 11325764 BACKGROUND

• 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.

  BACKGROUND

• Stein EA, Raal FJ. Polygenic familial hypercholesterolaemia: does it matter? Lancet. 2013 Apr 13;381(9874):1255-7. doi: 10.1016/S0140-6736(13)60187-7. Epub 2013 Feb 22. No abstract available.

  PMID: 23433574 BACKGROUND

• Sterne JA, White IR, Carlin JB, Spratt M, Royston P, Kenward MG, Wood AM, Carpenter JR. Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls. BMJ. 2009 Jun 29;338:b2393. doi: 10.1136/bmj.b2393.

  PMID: 19564179 BACKGROUND

• Versmissen J, Oosterveer DM, Yazdanpanah M, Defesche JC, Basart DC, Liem AH, Heeringa J, Witteman JC, Lansberg PJ, Kastelein JJ, Sijbrands EJ. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ. 2008 Nov 11;337:a2423. doi: 10.1136/bmj.a2423.

  PMID: 19001495 BACKGROUND

• Wald DS, Bangash FA, Bestwick JP. Prevalence of DNA-confirmed familial hypercholesterolaemia in young patients with myocardial infarction. Eur J Intern Med. 2015 Mar;26(2):127-30. doi: 10.1016/j.ejim.2015.01.014. Epub 2015 Feb 11.

  PMID: 25682442 BACKGROUND

• Wattanasuwan N, Khan IA, Gowda RM, Vasavada BC, Sacchi TJ. Effect of acute myocardial infarction on cholesterol ratios. Chest. 2001 Oct;120(4):1196-9. doi: 10.1378/chest.120.4.1196.

  PMID: 11591560 BACKGROUND

• World Health Organization,. Familial Hypercholesterolaemia. Geneva, Switzerland: Human Genetics Programme, 1998. Print. Annex Progress Report.

  BACKGROUND

• Sun LY, Zhang YB, Jiang L, Wan N, Wu WF, Pan XD, Yu J, Zhang F, Wang LY. Erratum: Identification of the gene defect responsible for severe hypercholesterolaemia using whole-exome sequencing. Sci Rep. 2015 Aug 3;5:12656. doi: 10.1038/srep12656. No abstract available.

  PMID: 26237740 BACKGROUND

• Mortality in treated heterozygous familial hypercholesterolaemia: implications for clinical management. Scientific Steering Committee on behalf of the Simon Broome Register Group. Atherosclerosis. 1999 Jan;142(1):105-12.

  PMID: 9920511 BACKGROUND

• Moons KG, Donders RA, Stijnen T, Harrell FE Jr. Using the outcome for imputation of missing predictor values was preferred. J Clin Epidemiol. 2006 Oct;59(10):1092-101. doi: 10.1016/j.jclinepi.2006.01.009. Epub 2006 Jun 19.

  PMID: 16980150 BACKGROUND

• Medeiros AM, Alves AC, Bourbon M. Mutational analysis of a cohort with clinical diagnosis of familial hypercholesterolemia: considerations for genetic diagnosis improvement. Genet Med. 2016 Apr;18(4):316-24. doi: 10.1038/gim.2015.71. Epub 2015 May 28.

  PMID: 26020417 BACKGROUND

• McAllister KS, Ludman PF, Hulme W, de Belder MA, Stables R, Chowdhary S, Mamas MA, Sperrin M, Buchan IE; British Cardiovascular Intervention Society and the National Institute for Cardiovascular Outcomes Research. A contemporary risk model for predicting 30-day mortality following percutaneous coronary intervention in England and Wales. Int J Cardiol. 2016 May 1;210:125-32. doi: 10.1016/j.ijcard.2016.02.085. Epub 2016 Feb 17.

  PMID: 26942330 BACKGROUND

• Marks D, Thorogood M, Neil HA, Humphries SE. A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia. Atherosclerosis. 2003 May;168(1):1-14. doi: 10.1016/s0021-9150(02)00330-1.

  PMID: 12732381 BACKGROUND

• Do R, Stitziel NO, Won HH, Jorgensen 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.

  PMID: 25487149 BACKGROUND

• Damgaard D, Larsen ML, Nissen PH, Jensen JM, Jensen HK, Soerensen VR, Jensen LG, Faergeman O. The relationship of molecular genetic to clinical diagnosis of familial hypercholesterolemia in a Danish population. Atherosclerosis. 2005 May;180(1):155-60. doi: 10.1016/j.atherosclerosis.2004.12.001. Epub 2005 Jan 12.

  PMID: 15823288 BACKGROUND

• Civeira F, Ros E, Jarauta E, Plana N, Zambon D, Puzo J, Martinez de Esteban JP, Ferrando J, Zabala S, Almagro F, Gimeno JA, Masana L, Pocovi M. Comparison of genetic versus clinical diagnosis in familial hypercholesterolemia. Am J Cardiol. 2008 Nov 1;102(9):1187-93, 1193.e1. doi: 10.1016/j.amjcard.2008.06.056. Epub 2008 Aug 27.

  PMID: 18940289 BACKGROUND

• Benn M, Watts GF, Tybjaerg-Hansen A, Nordestgaard BG. Familial hypercholesterolemia in the danish general population: prevalence, coronary artery disease, and cholesterol-lowering medication. J Clin Endocrinol Metab. 2012 Nov;97(11):3956-64. doi: 10.1210/jc.2012-1563. Epub 2012 Aug 14.

  PMID: 22893714 BACKGROUND

• Al-Rasadi K, Al-Waili K, Al-Sabti HA, Al-Hinai A, Al-Hashmi K, Al-Zakwani I, Banerjee Y. Criteria for Diagnosis of Familial Hypercholesterolemia: A Comprehensive Analysis of the Different Guidelines, Appraising their Suitability in the Omani Arab Population. Oman Med J. 2014 Mar;29(2):85-91. doi: 10.5001/omj.2014.22.

  PMID: 24715932 BACKGROUND

• Cattle BA, Baxter PD, Greenwood DC, Gale CP, West RM. Multiple imputation for completion of a national clinical audit dataset. Stat Med. 2011 Sep 30;30(22):2736-53. doi: 10.1002/sim.4314. Epub 2011 Jul 22.

  PMID: 21786284 BACKGROUND

MeSH Terms

Conditions

Hyperlipoproteinemia Type II; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Joy Ayemoba, MSc

  UCL

  STUDY CHAIR

• John Deanfield, MD

  UCL

  PRINCIPAL INVESTIGATOR

• Owen Nicholas, PhD

  UCL

  STUDY DIRECTOR

• Riyaz Patel, MD

  UCL

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Target Duration: 10 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2016
• First Posted: May 20, 2016
• Study Start: January 1, 2003
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: May 20, 2016

Record last verified: 2015-07