title: Cascade screening based on genetic testing is cost-effective: evidence for the implementation of models of care for familial hypercholesterolemia.
abstract: BACKGROUND
  Familial hypercholesterolemia (FH) imposes significant burden of premature coronary heart disease (CHD).
  
  
  OBJECTIVE
  This study aimed to determine the cost-effectiveness of FH detection based on genetic testing, supplemented with the measurement of plasma low-density lipoprotein cholesterol concentration, and treatment with statins.
  
  
  METHODS
  A Markov model with a 10-year time horizon was constructed to simulate the onset of first-ever CHD and death in close relatives of probands with genetically confirmed FH. The model comprised of 3 health states: "alive without CHD," "alive with CHD," and "dead." Decision-analysis compared the clinical consequences and costs of cascade-screening vs no-screening from an Australian health care perspective. The annual risk of CHD and benefits of treatment was estimated from a cohort study. The underlying prevalence of FH, sensitivity, specificity, cost of screening, treatment, and clinic follow-up visits were derived from a cascade screening service for FH in Western Australia. An annual discount rate of 5% was applied to costs and benefits.
  
  
  RESULTS
  The model estimated that screening for FH would reduce the 10-year incidence of CHD from 50.0% to 25.0% among people with FH. Of every 100 people screened, there was an overall gain of 24.95 life-years and 29.07 quality-adjusted life years (discounted). The incremental cost-effectiveness ratio was in Australian dollars, $4155 per years of life saved and $3565 per quality-adjusted life years gained.
  
  
  CONCLUSIONS
  This analysis within an Australian context, demonstrates that cascade screening for FH, using genetic testing supplemented with the measurement of plasma low-density lipoprotein cholesterol concentrations and treatment with statins, is a cost-effective means of preventing CHD in families at risk of FH.
authors.affiliation: Department of Medicine (RMH), Melbourne EpiCentre, The University of Melbourne and Melbourne Health, Australia; Department of Epidemiology & Preventive Medicine, Monash University, Australia. Electronic address: zademi@unimelb.edu.au.
authors.forename: Zanfina
authors.initials: Z
authors.lastname: Ademi
authors.affiliation: Lipid Disorders Clinic, Metabolic Research Centre and Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, The University of Western Australia, Australia.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
authors.affiliation: Lipid Disorders Clinic, Metabolic Research Centre and Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, The University of Western Australia, Australia.
authors.forename: Jing
authors.initials: J
authors.lastname: Pang
authors.affiliation: Section of Pharmacology, Vascular and Metabolic Diseases of the Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Eric J G
authors.initials: EJ
authors.lastname: Sijbrands
authors.affiliation: Department of Clinical Biochemistry, Royal Perth Hospital, Australia.
authors.forename: Frank M
authors.initials: FM
authors.lastname: van Bockxmeer
authors.affiliation: School of Surgery, The University of Western Australia, Crawley, Australia; Centre for Population Health Research, Faculty of Health Sciences, Curtin University, Perth, Australia; School of Pathology & Laboratory Medicine, The University of Western Australia, Crawley, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: O'Leary
authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Crawley, Australia; School of Population Health, The University of Western Australia, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Geelhoed
authors.affiliation: Department of Medicine (RMH), Melbourne EpiCentre, The University of Melbourne and Melbourne Health, Australia.
authors.forename: Danny
authors.initials: D
authors.lastname: Liew
mesh_terms: D000328:Adult; D001315:Australia; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D003362:Cost-Benefit Analysis; D019317:Evidence-Based Medicine; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis* / Q000191:economics / Q000235:genetics; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D012680:Sensitivity and Specificity
chemical_list: D008078:Cholesterol, LDL
keywords: Cost-effectiveness; Prevention; Screening