Advertisement

A Belgian consensus strategy to identify familial hypercholesterolaemia in the coronary care unit and its subsequent cascade screening and treatment: BEL-FaHST (The BELgium Familial Hypercholesterolaemia STrategy)

      Highlights

      • A strategy to facilitate the detection and management of FH among patients hospitalized for CVD.

      Abstract

      Background and aims

      Familial hypercholesterolaemia (FH) is an autosomal dominant lipoprotein disorder characterized by significant elevation of low-density lipoprotein cholesterol (LDL-C) and markedly increased risk of premature cardiovascular disease (CVD). Because of the very high coronary artery disease risk associated with this condition, the prevalence of FH among patients admitted for CVD outmatches many times the prevalence in the general population. Awareness of this disease is crucial for recognizing FH in the aftermath of a hospitalization of a patient with CVD, and also represents a unique opportunity to identify relatives of the index patient, who are unaware they have FH. This article aims to describe a feasible strategy to facilitate the detection and management of FH among patients hospitalized for CVD.

      Methods

      A multidisciplinary national panel of lipidologists, cardiologists, endocrinologists and cardio-geneticists developed a three-step diagnostic algorithm, each step including three key aspects of diagnosis, treatment and family care.

      Results

      A sequence of tasks was generated, starting with the process of suspecting FH amongst affected patients admitted for CVD, treating them to LDL-C target, finally culminating in extensive cascade-screening for FH in their family. Conceptually, the pathway is broken down into 3 phases to provide the treating physicians with a time-efficient chain of priorities.

      Conclusions

      We emphasize the need for optimal collaboration between the various actors, starting with a "vigilant doctor" who actively develops the capability or framework to recognize potential FH patients, continuing with an "FH specialist", and finally involving the patient himself as ”FH ambassador” to approach his/her family and facilitate cascade screening and subsequent treatment of relatives.

      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 Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Nordestgaard B.G.
        • Chapman M.J.
        • Humphries S.E.
        • Ginsberg H.N.
        • Masana L.
        • Descamps O.S.
        • et al.
        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; 34: 3478-3490a
        • Descamps O.
        • Hondekijn J.C.
        • Van Acker P.
        • Deslypere J.P.
        • Heller F.R.
        High prevalence of a novel mutation in exon 4 in the LDL receptor gene in Belgium.
        Clin. Genet. 1997; 51: 301-308
        • Descamps O.S.
        • Gilbeau J.P.
        • Hondekijn J.C.
        • Leysen X.
        • Van Leuven F.
        • Heller F.
        Impact of genetic defects on atheroclerosis in patients suspected of familial hypercholesterolemia.
        Eur. J. Clin. Invest. 2001; 31: 958-965
        • Descamps O.S.
        • Gilbeau J.B.
        • Luwaert R.
        • Heller F.
        Impact of Genetic Defects on coronary atherosclerosis in patients suspected of familial hypercholesterolemia.
        Eur. J. Clin. Invest. 2003; 33: 1-9
        • Descamps O.S.
        • de Meester A.
        • Cheron P.
        • Kastelein J.J.
        • Heller F.R.
        Clinical and preclinical myocardial ischaemia in familial hypercholesterolemia.
        Atherosclerosis. 2003; : 7-8
        • Descamps O.S.
        • Tenoutasse S.
        • Stephenne X.
        • Gies I.
        • Beauloye V.
        • et al.
        Management of familial hypercholesterolemia in children and young adults: consensus paper developed by a panel of lipidologists, cardiologists, paediatricians, nutritionists, gastroenterologists, general practitioners and a patient organization.
        Atherosclerosis. 2011; 218: 272-280
        • Van Gaal L.F.
        • Peeters A.V.
        • De Block C.E.M.
        • Thiart R.
        • De Leeuw I.H.
        • Kotze M.J.
        Low-density lipoprotein receptor gene mutation analysis and clinical correlation in Belgian hypercholesterolaemics.
        Mol. Cell. Probes. 2001; 15: 329-336
        • Sanna C.
        • Stéphenne X.
        • Revencu N.
        • Smets F.
        • Sassolas A.
        • Di Filippo M.
        • Descamps O.S.
        • Sokal E.M.
        Homozygous familial hypercholesterolemia in childhood: genotype-phenotype description, established therapies and perspectives.
        Atherosclerosis. 2016; 247: 97-104
        • Vallejo-Vaz A.J.
        • Kondapally Seshasai S.R.
        • Cole D.
        • Hovingh G.K.
        • Kastelein J.J.
        • et al.
        Familial hypercholesterolaemia: a global call to arms.
        Atherosclerosis. 2015; 243: 257-259
        • De Backer G.
        • Besseling J.
        • Chapman J.
        • Hovingh G.K.
        • Kastelein J.J.
        • et al.
        EUROASPIRE Investigators. Prevalence and management of familial hypercholesterolaemia in coronary patients: an analysis of EUROASPIRE IV, a study of the European Society of Cardiology.
        Atherosclerosis. 2015; 241: 169-175
        • Robinson J.G.
        Management of familial hypercholesterolemia: a review of the recommendations from the national lipid association expert panel on familial hypercholesterolemia.
        J. Manag. Care Pharm. 2013; 19: 139-149
        • Catapano A.L.
        • Graham I.
        • De Backer G.
        • Wiklund O.
        • Chapman M.J.
        • et al.
        2016 ESC/EAS guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the european society of cardiology (ESC) and european atherosclerosis society (EAS) developed with the special contribution of the european assocciation for cardiovascular prevention & rehabilitation (EACPR).
        Atherosclerosis. 2016; 253: 281-344
        • Nordestgaard B.G.
        • Langsted A.
        • Mora S.
        • Kolovou G.
        • Baum H.
        • et al.
        European atherosclerosis society (EAS) and the european federation of clinical chemistry and laboratory medicine (EFLM) joint consensus initiative. Fasting is not routinely required for determination of a lipid profile: clinical and laboratory implications including flagging at desirable concentration cutpoints-a joint consensus statement from the european atherosclerosis society and european federation of clinical chemistry and laboratory medicine.
        Eur. Heart J. 2016; 37: 1944-1958
        • Jackson R.
        • Scragg R.
        • Marshall R.
        • et al.
        Changes in serum lipid concentrations during first 24 hours after myocardial infarction.
        BMJ. 1987; 294: 1588-1589
        • Wattanasuwan N.
        • Khan I.A.
        • Gowda R.M.
        • Vasavada B.C.
        • Sacchi T.J.
        Effect of acute myocardial infarction on cholesterol ratios.
        Chest. 2001; 120: 1196-1199
        • Haralambos K.
        • Whatley S.D.
        • Edwards R.
        • Gingell R.
        • Townsend D.
        • et al.
        Clinical experience of scoring criteria for Familial Hypercholesterolaemia (FH) genetic testing in Wales.
        Atherosclerosis. 2015; 240: 190-196
        • Descamps O.S.
        • Hondekijn J.C.
        • Van Leuven F.
        • Heller F.R.
        The use of Achilles tendon ultrasonography for the diagnosis of familial hypercholesterolemia.
        Atherosclerosis. 2001; 157: 514-518
        • Harada-Shiba M.
        • Arai H.
        • Okamura T.
        • Yokote K.
        • Oikawa S.
        • Nohara A.
        • Okada T.
        • Ohta T.
        • Bujo H.
        • Watanabe M.
        • Wakatsuki A.
        • Yamashita S.
        Multicenter study to determine the diagnosis criteria of heterozygous familial hypercholesterolemia in Japan.
        J. Atherosclerosis Thromb. 2012; 19: 1019-1026
        • Kassner U.
        • Marion Wühle-Demuth M.
        • Missala I.
        • Humphries S.E.
        • et al.
        Clinical utility gene card for: hyperlipoproteinemia, TYPE II.
        Eur. J. Hum. Genet. November 2013; 2014 (published online 20): 22https://doi.org/10.1038/ejhg.2013.271
        • Kastelein J.J.
        • Ginsberg H.N.
        • Langslet G.
        • Hovingh G.K.
        • Ceska R.
        • et al.
        ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia.
        Eur. Heart J. 2015; 36: 2996-3003
        • Ginsberg H.N.
        • Rader D.J.
        • Raal F.J.
        • Guyton J.R.
        • Baccara-Dinet M.T.
        • et al.
        Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia and LDL-C of 160 mg/dl or higher.
        Cardiovasc. Drugs Ther. 2016; 30: 473-483
        • Raal F.J.
        • Stein E.A.
        • Dufour R.
        • Turner T.
        • Civeira F.
        • et al.
        RUTHERFORD-2 Investigators. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial.
        Lancet. 2015; 385: 331-340
        • Gouni-Berthold I.
        • Descamps O.S.
        • Fraass U.
        • Hartfield E.
        • Allcott K.
        • et al.
        Systematic review of published Phase 3 data on anti-PCSK9 monoclonal antibodies in patients with hypercholesterolaemia.
        Br. J. Clin. Pharmacol. 2016; 82: 1412-1443
        • Starr B.
        • Hadfield S.G.
        • Hutten B.A.
        • Lansberg P.J.
        • Leren T.P.
        • et al.
        Development of sensitive and specific age- and gender-specific low-density lipoprotein cholesterol cutoffs for diagnosis of first-degree relatives with familial hypercholesterolaemia in cascade testing.
        Clin. Chem. Lab. Med. 2008; 46: 791-803
        • Williams R.R.
        • Hunt S.C.
        • Schumacher M.C.
        • Hegele R.A.
        • Leppert M.F.
        • Ludwig E.H.
        • Hopkins P.N.
        Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics.
        Am. J. Cardiol. 1993; 72: 171-176
        • Wiegman A.
        • Gidding S.S.
        • Watts G.F.
        • Chapman M.J.
        • Ginsberg H.N.
        • et al.
        For the European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment.
        Eur. Heart J. 2015; 36: 2425-2437
        • Rietzschel E.R.
        • De Buyzere M.L.
        • Bekaert S.
        • Segers P.
        • De Bacquer D.
        • Cooman L.
        • Van Damme P.
        • Cassiman P.
        • Langlois M.
        • van Oostveldt P.
        • Verdonck P.
        • De Backer G.
        • Gillebert T.C.
        Asklepios Investigators. Rationale, design, methods and baseline characteristics of the Asklepios Study.
        Eur. J. Cardiovasc. Prev. Rehabil. 2007; 14: 179-191
        • Khera A.V.
        • Won H.H.
        • Peloso G.M.
        • Lawson K.S.
        • Bartz T.M.
        • et al.
        Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia.
        J. Am. Coll. Cardiol. 2016; 67: 2578-2589