Eric Bruckert1, Olga Kalmykova2, Randa Bittar3, Valérie Carreau2, Sophie Béliard4, Samir Saheb2, David Rosenbaum2, Dominique Bonnefont-Rousselot3, Daniel Thomas5, Corinne Emery6, Babak Khoshnood7, Alain Carrié8. 1. 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. 2. Endocrinology Department and Apheresis Center, Hôpital Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, 83 Bd de l'Hôpital, 75013 Paris, France. 3. Metabolic Biochemistry Department, Hôpital Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, 83 Bd de l'Hôpital, 75013 Paris, France. 4. Hôpital de la Conception, Assistance Publique-Hôpitaux de Marseille, 147 boulevard Baille, 13285 Marseille cedex 05, France. 5. Cardiology Department, Hôpital Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, 83 Bd de l'Hôpital 75013 Paris, France. 6. CEMKA-EVAL, 43 Bd du Marechal Joffre, F92340 Bourg La Reine, France. 7. Obstetric, Perinatal & Pediatric Epidemiology Research Team, Center for Biostatistics & Epidemiology, INSERM U1153, Maternité de Port-Royal, 53 av. de l'Observatoire, 75014 Paris, France. 8. 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.
Abstract
BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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: Gerald F Watts; Samuel S Gidding; Pedro Mata; Jing Pang; David R Sullivan; Shizuya Yamashita; Frederick J Raal; Raul D Santos; Kausik K Ray Journal: Nat Rev Cardiol Date: 2020-01-23 Impact factor: 32.419