title: Long-term outcome in 53 patients with homozygous familial hypercholesterolaemia in a single centre in France.
abstract: Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited condition characterized by elevated plasma low-density lipoprotein-cholesterol (LDL-C) levels, severe, accelerated atherosclerosis and premature coronary heart disease. We evaluated cardiovascular complications in HoFH patients over extended follow-up and investigated their association with changes in cholesterol over time, as well as total cholesterol burden.
  
  
  
  In this retrospective single-centre study, 53 patients (baseline mean ± standard deviation [SD], total cholesterol 15.5 ± 3.7 mmol/L and LDL-C 13.2 ± 2.6 mmol/L) were followed for up to 38 years (21.2 ± 10 years). The primary outcome was an adverse clinical event, defined as cardiovascular death, nonfatal myocardial infarction, or angina.
  
  
  
  Twenty-eight patients experienced an event, of whom 8 died due to complications of major surgery (4), myocardial infarction (3) or stroke (1). While total cholesterol levels were comparable in patients with and without an event at baseline (20 mmol/L), those who subsequently experienced an event showed a slower decline in total cholesterol. Cumulative total cholesterol (i.e. total-cholesterol year score) was highly associated with the incidence of an adverse clinical event in a linear dose-response relation. A 100 mmol/L increase in cumulative total cholesterol (i.e. an average exposure of 10 mmol/L per 10 years or 20 mmol/L per 5 years) was associated with a doubling of the risk of a cardiovascular event (age-adjusted incidence rate ratio: 1.99, 95% CI, 1.16-3.41).
  
  
  
  Our findings reinforce the importance of early diagnosis and initiation of maximal treatment, including lipoprotein apheresis, to ensure long-term reduction in the cholesterol burden, expressed as the total-cholesterol year score, and risk of cardiovascular complications in HoFH.
authors.affiliation: Endocrinology Department and Apheresis Center, Hôpital Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, 83 Bd de l'Hôpital, 75013 Paris, France. Electronic address: eric.bruckert@aphp.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Bruckert
authors.affiliation: Endocrinology Department and Apheresis Center, Hôpital Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, 83 Bd de l'Hôpital, 75013 Paris, France.
authors.forename: Olga
authors.initials: O
authors.lastname: Kalmykova
authors.affiliation: Metabolic Biochemistry Department, Hôpital Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, 83 Bd de l'Hôpital, 75013 Paris, France.
authors.forename: Randa
authors.initials: R
authors.lastname: Bittar
authors.affiliation: Endocrinology Department and Apheresis Center, Hôpital Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, 83 Bd de l'Hôpital, 75013 Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Carreau
authors.affiliation: Hôpital de la Conception, Assistance Publique-Hôpitaux de Marseille, 147 boulevard Baille, 13285 Marseille cedex 05, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Béliard
authors.affiliation: Endocrinology Department and Apheresis Center, Hôpital Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, 83 Bd de l'Hôpital, 75013 Paris, France.
authors.forename: Samir
authors.initials: S
authors.lastname: Saheb
authors.affiliation: Endocrinology Department and Apheresis Center, Hôpital Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, 83 Bd de l'Hôpital, 75013 Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Rosenbaum
authors.affiliation: Metabolic Biochemistry Department, Hôpital Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, 83 Bd de l'Hôpital, 75013 Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnefont-Rousselot
authors.affiliation: Cardiology Department, Hôpital Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, 83 Bd de l'Hôpital 75013 Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Thomas
authors.affiliation: CEMKA-EVAL, 43 Bd du Marechal Joffre, F92340 Bourg La Reine, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Emery
authors.affiliation: Obstetric, Perinatal & Pediatric Epidemiology Research Team, Center for Biostatistics & Epidemiology, INSERM U1153, Maternité de Port-Royal, 53 av. de l'Observatoire, 75014 Paris, France.
authors.forename: Babak
authors.initials: B
authors.lastname: Khoshnood
authors.affiliation: Hôpital Pitié-Salpêtrière, Service de Biochimie Endocrinienne et Oncologique, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France, Institute of Cardiometabolism and Nutrition, Paris, France Université Pierre et Marie Curie 06, Unité Mixte de Recherche, S 1166 Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Carrié
mesh_terms: D000293:Adolescent; D000787:Angina Pectoris / Q000235:genetics / Q000517:prevention & control; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001781:Blood Component Removal; D002318:Cardiovascular Diseases / Q000235:genetics / Q000401:mortality / Q000517:prevention & control*; D002648:Child; D002675:Child, Preschool; D008078:Cholesterol, LDL / Q000097:blood*; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D042241:Early Diagnosis; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D009154:Mutation; D009203:Myocardial Infarction / Q000235:genetics / Q000517:prevention & control; D010375:Pedigree; D010641:Phenotype; D011237:Predictive Value of Tests; D011973:Receptors, LDL / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D015415:Biomarkers; D008078:Cholesterol, LDL; C573412:LDLR protein, human; D011973:Receptors, LDL
keywords: Cardiovascular; Cholesterol; Cholesterol burden; Cholesterol-year score; Homozygous familial hypercholesterolaemia; Lipoprotein apheresis; Statin