Advertisement

Patient acceptance of genetic testing for familial hypercholesterolemia in the CASCADE FH Registry

Published:February 11, 2020DOI:https://doi.org/10.1016/j.jacl.2020.02.001

      Highlights

      • In the USA, there is interest in genetic testing when offered for free and online.
      • In those diagnosed with FH by a lipidologist, about 58% had a positive test.
      • Uptake of cascade screening by a family in those with a positive test was minimal.

      Background

      Barriers to genetic testing and subsequent family cascade screening for familial hypercholesterolemia (FH) include cost, patient and provider awareness, privacy and discrimination concerns, need for a physician order, underutilization of genetic counselors, and family concerns about the implications of genetic testing for care.

      Objectives

      The objective of the study was to determine the uptake of genetic testing with cost and privacy removed.

      Methods

      The FH Foundation offered free genetic testing and counseling to patients in the patient portal of the CASCADE FH Registry, who had not previously undergone genetic testing for 3 genes associated with FH (LDLR, APOB, and PCSK9). The free testing offer was extended to first-degree relatives of participants who had a positive genetic test result for cascade screening.

      Results

      Of 435 eligible patients, 147 opted in to participate, 122 consented, and 110 (68.2% female, median age: 52 years) received genetic testing. Of the participants, 64 had a positive genetic test result for a pathogenic variant in LDLR (59) or APOB (5); 11 had a variant of uncertain significance. Only 3 first-degrees relatives underwent genetic testing.

      Conclusions

      Although there was substantial interest in genetic testing, uptake of family cascade screening was poor. Innovative approaches to increase family cascade screening should be explored.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Clinical Lipidology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Sturm A.
        • Knowles J.W.
        • Gidding S.S.
        • et al.
        Clinical genetic testing for familial hypercholesterolemia: JACC scientific expert panel.
        J Am Coll Cardiol. 2018; 72: 662-680
        • Nordestgaard B.G.
        • Chapman M.J.
        • Humphries S.E.
        • et al.
        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; 34: 3478-3490
        • Kerr M.
        • Pears R.
        • Miedzybrodzka Z.
        • et al.
        Cost effectiveness of cascade testing for familial hypercholesterolaemia services in the UK.
        Eur Heart J. 2017; 38: 1832-1839
        • Ademi Z.
        • Watts G.F.
        • Pang J.
        • et al.
        Cascade screening based on genetic testing is cost- effective: evidence for the implementation of models of care for familial hypercholesterolaemia.
        J Clin Lipidol. 2014; 8: 390-400
        • Wonderling D.
        • Umans-Eckenhausen M.A.W.
        • Marks D.
        • et al.
        A cost-effectiveness analysis of the genetic screening program for Familial Hypercholesterolemia in the Netherlands.
        Semin Vasc Med. 2004; 4: 97-104
        • Ahmad Z.S.
        • Andersen R.L.
        • Andersen L.H.
        • et al.
        US physician practices for diagnosing familial hypercholesterolemia: data from the CASCADE-FH registry.
        J Clin Lipidol. 2016; 10: 1223-1229
        • Hendricks-Sturrup R.M.
        • Mazor K.M.
        • Sturm A.C.
        • Lu C.Y.
        Barriers and facilitators to genetic testing for familial hypercholesterolemia in the United States.
        J Pers Med. 2019; 1: E32
        • Neben C.
        • Zimmer A.D.
        • Stedden W.
        • et al.
        Multi-gene panel testing of 23,179 individuals for hereditary cancer risk identifies pathogenic variant carriers missed by current genetic testing guidelines.
        J Mol Diagn. 2019; 21: 646-657
        • National Center for Biotechnology Information
        ClinVar.
        (Available at:)
        • Wurtmann E.
        • Steinberger J.
        • Veach P.M.
        • et al.
        Risk communication in families of children with familial hypercholesterolemia: identifying motivators and barriers to cascade screening to improve diagnosis at a single medical center.
        J Pers Med. 2019; 9https://doi.org/10.3390/jpm9030032
        • Gidding S.S.
        • Champagne M.A.
        • de Ferranti S.D.
        • et al.
        The agenda for familial hypercholesterolemia a scientific statement from the American heart association.
        Circulation. 2015; 132: 2167-2192
        • Langsted A.
        • Kamstrup P.R.
        • Benn M.
        • Tybjaerg-Hansen A.
        • Nordestgaard B.G.
        High lipoprotein(a) as a possible cause of clinical familial hypercholesterolaemia: a prospective cohort study.
        Lancet Diabetes Endocrinol. 2016; 4: 577-587
        • Sharifi M.
        • Futema M.
        • Nair D.
        • Humphries S.E.
        Polygenic hypercholesterolemia and cardiovascular disease risk.
        Curr Cardiol Rep. 2019; 21: 43
        • Berberich A.J.
        • Hegele R.A.
        The complex genetics of familial hypercholesterolaemia.
        Nat Rev Cardiol. 2019; 16: 9-20
        • Futema M.
        • Whittall R.A.
        • Kiley A.
        • et al.
        Analysis of the frequency and spectrum of mutations recognised to cause familial hypercholesterolaemia in routine clinical practice in a UK specialist hospital lipid clinic.
        Atherosclerosis. 2013; 229: 161-168
        • Haralambos K.
        • Whatley S.D.
        • Edwards R.
        • et al.
        Clinical experience of scoring criteria for Familial Hypercholesterolaemia (FH) genetic testing in Wales.
        Atherosclerosis. 2015; 240: 190-196
        • Wald D.S.
        • Bestwick J.P.
        • Morris J.K.
        • Whyte K.
        • Jenkins L.
        • Wald N.J.
        Child-parent familial hypercholesterolemia screening in primary care.
        N Engl J Med. 2016; 375: 1628-1637
        • Bell D.A.
        • Pang J.
        • Burrows S.
        • et al.
        Effectiveness of genetic cascade screening for familial hypercholesterolaemia using a centrally coordinated clinical service: An Australian experience.
        Atherosclerosis. 2015; 239: 93-100
        • Neuner J.
        • Dimmock D.
        • Kirschner A.L.P.
        • et al.
        Results and lessons of a pilot study of cascade screening for familial hypercholesterolemia in us primary care practices.
        J Gen Intern Med. 2019; 35: 351-353
        • Huiiigen R.
        • Kindt I.
        • Verhoeven S.B.
        • et al.
        Two years after molecular diagnosis of familial hypercholesterolemia: majority on cholesterol-lowering treatment but a minority reaches treatment goal.
        PLoS One. 2010; 5: e9220