title: Effectiveness of genetic cascade screening for familial hypercholesterolaemia using a centrally co-ordinated clinical service: an Australian experience.
abstract: BACKGROUND
  Familial hypercholesterolaemia (FH) is a co-dominantly inherited disorder of low-density lipoprotein (LDL) catabolism, causing elevated LDL-cholesterol and premature coronary artery disease (CAD). Several guidelines recommend genetic cascade screening relatives of probands (index cases) with genetically proven FH, but experience in a clinical service setting is limited.
  
  
  METHODS
  Relatives from 100 index cases with genetically confirmed FH underwent genetic and lipid testing via a centralised screening program in Western Australia. The program's effectiveness was evaluated as the number of newly diagnosed relatives with FH per index case and the proportional reduction in LDL-cholesterol after treatment.
  
  
  RESULTS
  Of 366 relatives tested for FH, 188 (51.4%) were found to have a pathogenic mutation. On average, 2 cases were detected per index case. Affected relatives were younger and less likely to have physical stigmata of FH and premature CAD than index cases (p < 0.001). Of the new cases, 12.8% had hypertension, 2.7% had diabetes and 16.0% were smokers; 48.4% were already on statin therapy and these were older (p < 0.001) and had more vascular risk factors and CAD (p < 0.01) than those not on therapy. Significant reductions in LDL-cholesterol (-24.3%, p < 0.001) were achieved overall, with previously untreated new cases of FH attaining a maximal average reduction of 42.5% in LDL-cholesterol after drug therapy. Over 90% of subjects were satisfied with screening and care.
  
  
  CONCLUSIONS
  Genetic cascade screening co-ordinated by a centralised service is an effective and acceptable strategy for detecting FH in an Australian setting. A significant proportion of new cases exhibit other CAD risk factors and are already on statins, but have not received a prior diagnosis of FH.
authors.affiliation: Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, Perth, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth, Australia.
authors.forename: Damon A
authors.initials: DA
authors.lastname: Bell
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: Jing
authors.initials: J
authors.lastname: Pang
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: Sally
authors.initials: S
authors.lastname: Burrows
authors.affiliation: Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, Perth, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Bates
authors.affiliation: Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth, Australia; School of Surgery, University of Western Australia, Perth, Australia; School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
authors.forename: Frank M
authors.initials: FM
authors.lastname: van Bockxmeer
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth, Australia; School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Hooper
authors.affiliation: Faculty of Health Sciences, Curtin University, Perth, Australia; School of Women's and Infants' Health, University of Western Australia, Perth, Australia; PathWest Laboratory Medicine WA, Perth, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: O'Leary
authors.affiliation: Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, Perth, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth, Australia.
authors.forename: John R
authors.initials: JR
authors.lastname: Burnett
authors.affiliation: Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, Perth, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth, Australia. Electronic address: gerald.watts@uwa.edu.au.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
mesh_terms: D000328:Adult; D000368:Aged; D001315:Australia; D002309:Cardiology / Q000458:organization & administration*; D008078:Cholesterol, LDL / Q000097:blood; D005192:Family Health; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012307:Risk Factors
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: Cascade screening; Effectiveness; Familial hypercholesterolaemia; Genes; Yield