title: Improved cardiovascular outcomes following temporal advances in lipid-lowering therapy in a genetically-characterised cohort of familial hypercholesterolaemia homozygotes.
abstract: OBJECTIVE
  There is a paucity of data concerning the influence of lipid-lowering therapy on cardiovascular (CV) outcomes in patients with homozygous familial hypercholesterolaemia (FH). To redress this a retrospective analysis was undertaken of the demographic features, lipid levels, low density lipoprotein receptor and Autosomal Recessive Hypercholesterolaemia gene mutations, CV outcomes and vital status of 44 FH homozygotes referred to a single centre in the UK between 1964 and 2014.
  
  
  METHODS
  Data were obtained from past publications, case records and death certificates. Differences in categorical and continuous variables between living and dead patients were analysed using Fisher's exact test and an independent t-test respectively.
  
  
  RESULTS
  During the 50 years covered by this survey 13 patients have died, 30 are still alive and 1 was lost to follow up. The mean age of Alive patients was 32.6 ± 11.5 versus 28.3 ± 14.9 years in Dead ones (P = 0.31) and they were born 18 years later (P = 0.0001). Pre-treatment serum total cholesterol (TC) was similar in Alive and Dead (20.2 ± 5.1 v 21.3 ± 4.4 mmol/l, P = 0.52) but on-treatment TC was lower in Alive than Dead (8.1 ± 2.8 v 14.5 ± 6.0 mmol/l, P = 0.0001) and CV adverse events were far less frequent (eg aortic stenosis, 33% v 77%, P = 0.02).
  
  
  CONCLUSIONS
  The lower on-treatment TC and fewer CV adverse events in FH homozygotes still living reflect advances in apheresis and drug therapy since the 1990s. Further improvements in prognosis can be expected with the impending introduction of novel lipid-lowering agents.
authors.affiliation: Imperial College London, London, UK. Electronic address: g.thompson@imperial.ac.uk.
authors.forename: Gilbert R
authors.initials: GR
authors.lastname: Thompson
authors.affiliation: Imperial College London, London, UK. Electronic address: drmaryseed@hotmail.com.
authors.forename: Mary
authors.initials: M
authors.lastname: Seed
authors.affiliation: Novartis Pharma AG, Basel, Switzerland. Electronic address: rossi.naoumova@hotmail.com.
authors.forename: Rossi P
authors.initials: RP
authors.lastname: Naoumova
authors.affiliation: Imperial College London, London, UK. Electronic address: Clare.neuwirth2@imperial.nhs.uk.
authors.forename: Clare
authors.initials: C
authors.lastname: Neuwirth
authors.affiliation: Hammersmith Hospital, London, UK. Electronic address: Shahenaz.Walji@imperial.nhs.uk.
authors.forename: Shahenaz
authors.initials: S
authors.lastname: Walji
authors.affiliation: University of Edinburgh, Edinburgh, UK. Electronic address: tim.aitman@ed.ac.uk.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Aitman
authors.affiliation: Imperial College London, London, UK. Electronic address: james.scott@imperial.ac.uk.
authors.forename: James
authors.initials: J
authors.lastname: Scott
authors.affiliation: Medical Research Council, UK.
authors.forename: Nicolas B
authors.initials: NB
authors.lastname: Myant
authors.affiliation: MRC Clinical Sciences Centre, London, UK. Electronic address: anne.soutar@csc.mrc.ac.uk.
authors.forename: Anne K
authors.initials: AK
authors.lastname: Soutar
mesh_terms: D000293:Adolescent; D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001024:Aortic Valve Stenosis / Q000188:drug therapy; D001781:Blood Component Removal; D002318:Cardiovascular Diseases / Q000150:complications / Q000235:genetics / Q000628:therapy*; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006720:Homozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006938:Hyperlipoproteinemia Type II / Q000150:complications* / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009154:Mutation; D011973:Receptors, LDL / Q000097:blood / Q000235:genetics; D012189:Retrospective Studies; D006113:United Kingdom; D055815:Young Adult
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011973:Receptors, LDL
keywords: ARH mutations; Aortic stenosis; Apheresis; LDLR mutations; Statins