Search Our Scientific Publications & Authors

Pediatr Dermatol 2020 Jun 15. Epub 2020 Jun 15.

Department of Dermatology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.

Cutaneous xanthomas develop as a result of lipid deposition in the dermis and may be a manifestation of various systemic diseases. The morphology and anatomic location of xanthomas are often a clue to the underlying cause. Xanthoma striatum palmare (XSP) is classically associated with dysbetalipoproteinemia and rarely observed in hepatic disorders. Read More

Crit Rev Clin Lab Sci 2020 Apr 7:1-12. Epub 2020 Apr 7.

Department of Blood Sciences, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

Familial dysbetalipoproteinemia (type III hyperlipoproteinemia) is a potentially underdiagnosed inherited dyslipidemia associated with greatly increased risk of coronary and peripheral vascular disease. The mixed hyperlipidemia observed in this disorder usually responds well to appropriate medical therapy and lifestyle modification. Although there are characteristic clinical features such as palmar and tuberous xanthomata, associated with dysbetalipoproteinemia, they are not always present, and their absence cannot be used to exclude the disorder. Read More

Curr Opin Cardiol 2020 May;35(3):226-233

Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital.

Purpose Of Review: With the exception of familial hypercholesterolaemia, the value of genetic testing for managing dyslipidaemias is not established. We review the genetics of major dyslipidaemias in context of clinical practice.

Recent Findings: Genetic testing for familial hypercholesterolaemia is valuable to enhance diagnostic precision, cascade testing, risk prediction and the use of new medications. Read More

J Clin Lipidol 2020 Jan - Feb;14(1):46-52. Epub 2019 Dec 24.

Lipids, Nutrition and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute, Québec, Canada; Divisions of Experimental Medicine and Medical Biochemistry, Department of Medicine, McGill University, Québec, Canada. Electronic address:

Background: Dysbetalipoproteinemia (DBL) is an autosomal recessive lipid disorder associated with a reduced clearance of remnant lipoproteins and is associated with an increased cardiovascular disease (CVD) risk. The genetic cause of DBL is apoE2 homozygosity in 90% of cases. However, a second metabolic hit must be present to precipitate the disease. Read More

N Engl J Med 2019 12;381(26):2584

Akcea Therapeutics, Cambridge, MA.

Atheroscler Suppl 2019 Dec 17;40:79-87. Epub 2019 Aug 17.

Lipidology and Lipoprotein Apheresis Center, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.

Familial hypercholesterolemia (FH) is associated with a very high risk of cardiovascular complications and the need for an early aggressive lipid-lowering therapy. The achievement of lipid target levels is often an extremely difficult task in these patients.

Aims: to analyze sex and age structure of ischemic heart disease (IHD) in patients with a definite, possible and probable FH. Read More

Atheroscler Suppl 2019 Dec;40:38-43

Lipidology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.

Purpose: We analyzed efficacy and safety of PCSK9i in patients undergoing lipoprotein apheresis (LA) and in patients treated at our outpatient department for metabolic disorders.

Methods: The medical records of 40 LA patients, taking PCSK9i were reviewed with respect to LDL-cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) lowering as well as occurrence of adverse events. Furthermore, we analyzed the data of 152 patients of our outpatient department, undergoing PCSK9i therapy. Read More

JAMA Cardiol 2019 12;4(12):1287-1295

Centre for Naturally Randomized Trials, University of Cambridge, Cambridge, United Kingdom.

Importance: The conventional model of atherosclerosis presumes that the mass of cholesterol within very low-density lipoprotein particles, low-density lipoprotein particles, chylomicron, and lipoprotein (a) particles in plasma is the principal determinant of the mass of cholesterol that will be deposited within the arterial wall and will drive atherogenesis. However, each of these particles contains one molecule of apolipoprotein B (apoB) and there is now substantial evidence that apoB more accurately measures the atherogenic risk owing to the apoB lipoproteins than does low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol.

Observations: Cholesterol can only enter the arterial wall within apoB particles. Read More

J Investig Med High Impact Case Rep 2019 Jan-Dec;7:2324709619877050

Western University, London, Ontario, Canada.

Familial dysbetalipoproteinemia (also known as type 3 hyperlipoproteinemia) is typically associated with homozygosity for the apolipoprotein E2 isoform, but also sometimes with dominant rare missense variants in the gene. Patients present with roughly equimolar elevations of cholesterol and triglyceride (TG) due to pathologic accumulation of remnant lipoprotein particles. Clinical features include tuberoeruptive xanthomas, palmar xanthomas, and premature vascular disease. Read More

Cardiovasc J Afr 2019 Sep/Oct 23;30(5):279-284. Epub 2019 Sep 11.

Carbohydrate and Lipid Metabolism Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.

Background: Alirocumab reduces low-density lipoprotein cholesterol (LDL-C) levels by up to 61%. The ODYSSEY Open-Label Extension study investigated the effect of alirocumab in patients with heterozygous familial hypercholesterolaemia (HeFH) over 144 weeks.

Methods: Eligible patients with HeFH had completed an earlier double-blind, randomised, placebo-controlled parent study. Read More

N Engl J Med 2019 08;381(6):531-542

From the Department of Medicine, University of California San Diego, La Jolla (J.L.W., S.T.), and Ionis Pharmaceuticals, Carlsbad (V.J.A., Q.Y., S.G.H., R.S.G., S.T.) - both in California; the Department of Medicine, Université de Montréal and ECOGENE 21, Chicoutimi, QC (D.G.), and the Department of Medicine and Laboratory Medicine, Centre Hospitalier Universitaire de Québec-University Laval, Quebec, QC (J.B.) - both in Canada; the Department of Medicine, Beth Israel Deaconess Medical Center (S.D.F.), and the Department of Medicine, Massachusetts General Hospital (L.H.), Boston, and Akcea Therapeutics, Cambridge (A.D., K.R.W., L.O.) - all in Massachusetts; Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome (M.A.); Academic Medical Center, Department of Vascular Medicine, Amsterdam (E.S.G.S.); the Department of Medicine, Manchester University Hospital NHS Foundation Trust, Manchester, United Kingdom (H.S.); the Department of Internal Medicine, Hospital Universitario Miguel Servet, IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain (F.C.); the Division of Lipidology and Hatter Institute for Cardiovascular Research in Africa, University of Cape Town, Cape Town, South Africa (D.J.B.); and the Department of Endocrinology and Cardiovascular Disease Prevention, Assistance Publique-Hôpitaux de Paris, La Pitié-Salpêtrière Hospital, Institut de Création et d'Animation Numériques, Paris (E.B.).

Background: Familial chylomicronemia syndrome is a rare genetic disorder that is caused by loss of lipoprotein lipase activity and characterized by chylomicronemia and recurrent episodes of pancreatitis. There are no effective therapies. In an open-label study of three patients with this syndrome, antisense-mediated inhibition of hepatic mRNA with volanesorsen led to decreased plasma apolipoprotein C-III and triglyceride levels. Read More

Drug Metab Dispos 2019 10 26;47(10):1164-1173. Epub 2019 Jul 26.

PK and Clinical Pharmacology (N.P., R.Y., S.G., J.M., Y.W.) and Medicinal Chemistry (H.G.), Ionis Pharmaceuticals, Inc., Carlsbad, California; and PK and Clinical Pharmacology, Akcea Therapeutics, Boston, Massachusetts (E.H.).

Volanesorsen (previously known as ISIS 304801) is a 20-nucleotide partially 2'--(2-methoxyethyl) (2'-MOE)-modified antisense oligonucleotide (ASO) gapmer, which was recently approved in the European Union as a novel, first-in-class treatment in the reduction of triglyceride levels in patients with familial chylomicronemia syndrome. We characterized the absorption, distribution, metabolism, and excretion characteristics of volanesorsen in mice, rats, monkeys, and humans, in either radiolabeled or nonradiolabeled studies. This also included the characterization of all of the observed ASO metabolite species excreted in urine. Read More

Drugs 2019 Aug;79(12):1349-1354

Springer Nature, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand.

Volanesorsen (Waylivra), an antisense oligonucleotide inhibitor of apolipoprotein CIII (apoCIII) mRNA, is being developed by Ionis Pharmaceuticals through its subsidiary company, Akcea Therapeutics, to treat familial chylomicronemia syndrome (FCS), hypertriglyceridemia and familial partial lipodystrophy (FPL). In May 2019, volanesorsen was approved in the EU for the treatment of adult patients with FCS based on positive results from the multinational, phase III APPROACH and COMPASS studies. Other clinical trials are ongoing to assess its utility in hypertriglyceridemia, FPL and partial lipodystrophy. Read More

Clin Investig Arterioscler 2019 May - Jun;31(3):128-139. Epub 2019 May 24.

Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, España.

A group of experts convened by the Spanish Society of Arteriosclerosis (SEA) has been in charge of updating the SEA document on the indications of PCSK9 inhibitors (PCSK9i) in clinical practice that was published in 2016. This update is justified by the fact that the data from clinical trials carried out on a large scale with PCSK9i have shown that in addition to their high potency to lower atherogenic cholesterol, they reduce the risk of atherosclerotic cardiovascular disease, both in patients with stable disease, and with recent disease, and with a high degree of security. This update provides the recommendations and level of evidence for the prescription of iPCSK9 in patients with homozygous and heterozygous familial hypercholesterolemia, with atherosclerotic cardiovascular disease, and in primary prevention in patients with very high cardiovascular risk. Read More

Hum Mutat 2019 08 18;40(8):1181-1190. Epub 2019 Jun 18.

Department of Genetics of Metabolics Diseases, Institute of Medical & Molecular Genetics (INGEMM), Hospital Universitario La Paz, Madrid, Spain.

Familial hypercholesterolemia is an autosomal dominant disease of lipid metabolism caused by defects in the genes LDLR, APOB, and PCSK9. The prevalence of heterozygous familial hypercholesterolemia (HeFH) is estimated between 1/200 and 1/250. Early detection of patients with FH allows initiation of treatment, thus reducing the risk of coronary heart disease. Read More

Aging (Albany NY) 2019 05;11(9):2549-2550

Cardiovascular Center, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan.

J Clin Lipidol 2019 May - Jun;13(3):443-454. Epub 2019 Apr 10.

Harvard Clinical Research Institute, Preventive Cardiology Section, Boston, MA, USA.

Background: Patients with prior cardiovascular events are at very high risk of recurrent events and may benefit from low-density lipoprotein cholesterol (LDL-C) lowering beyond that achieved with maximally tolerated statins.

Objective: To assess potential differences between the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor, alirocumab, in patients with vs without prior myocardial infarction (MI)/ischemic stroke.

Methods: Data (n = 4880) were pooled from nine ODYSSEY phase 3 trials of alirocumab 75/150 mg or 150 mg every 2 weeks, mostly on background statins ± other lipid-lowering therapies. Read More

Arterioscler Thromb Vasc Biol 2019 06;39(6):1172-1181

From the Cardiovascular-Program ICCC, Research Institute Hospital Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain (R.S., T.P., J.C., L.B.).

Objective- Circulating microvesicles (cMVs) exert regulatory roles in atherothrombosis. Patients with familial hypercholesterolemia (FH) that are at high risk for premature cardiovascular events (CVEs) have previously shown high levels of cMVs related to disease severity. However, much remains unknown about their value as markers of CVE. Read More

Atherosclerosis 2019 06 31;285:17-22. Epub 2019 Mar 31.

Fundación Hipercolesterolemia Familiar, Madrid, Spain. Electronic address:

Background And Aims: Heterozygous familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C). The magnitude of atherosclerotic cardiovascular disease (ASCVD) risk in FH patients is highly variable, and this can result from genetic factors. The aim of our study was to characterize whether polymorphisms in VEGFR2 and OPG genes could influence the expression of ASCVD in FH patients. Read More

BMJ Case Rep 2019 Apr 3;12(4). Epub 2019 Apr 3.

Universitair Medisch Centrum Utrecht, Utrecht, The Netherlands.

A 44-year-old woman was admitted with pancreatitis caused by hypertriglyceridaemia (fasting triglycerides 28 mmol/L). She used oral contraceptives and ezetimibe 10 mg. She was overweight (body mass index 29. Read More

J Clin Lipidol 2019 May - Jun;13(3):411-414. Epub 2019 Mar 6.

Department of Medicine and Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.

We present a 37-year-old man diagnosed with familial dysbetalipoproteinemia who presented with the severe hyperlipidemic phenotype. None of the usual metabolic triggers were found to explain his severe lipid abnormalities. Genetic analysis revealed the expected APOE E2/E2 genotype, but no other mutations were found to explain any monogenic dyslipidemia or syndrome. Read More

Klin Lab Diagn 2019 ;64(1):4-13

FGBNU "Research Institute of General Pathology and Pathophysiology", Academy of Sciences of the Russian Federation, 125315, Moscow.

The abuse of food of carnivores (meat) by phylogeneticallyI herbivorous Homo sapiens (a patient) initiates atherosclerosis. Addressing biogenetic law of E. Haeckel that ontogeny recapitulates phylogeny (a universal anamnesis), we suggest a diagnostic technique that allows evaluation of the meat diet abuse by a herbivorous Homo sapiens. Read More

Arterioscler Thromb Vasc Biol 2019 05;39(5):945-955

From the Cardiovascular Science Institute - ICCC; IIB-Sant Pau, Hospital de Sant Pau, Barcelona, Spain (G.C.-B., T.P., J.C., L.B.).

Objective- Heterozygous familial hypercholesterolemia (FH) is the most common genetic disorder associated with premature atherosclerotic cardiovascular disease. Circulating microvesicles (cMV) are released when cells are activated. We investigated whether cMV could provide information on coronary calcification and atherosclerosis in FH patients. Read More

J Am Coll Cardiol 2019 03;73(9):1029-1039

Fundación Hipercolesterolemia Familiar, Madrid, Spain. Electronic address:

Background: Familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] are inherited disorders associated with premature atherosclerotic cardiovascular disease (ASCVD). Cascade testing is recommended for FH, but there are no similar recommendations for elevated Lp(a).

Objectives: This study investigated whether testing for Lp(a) was effective in detecting and risk stratifying individuals participating in an FH cascade screening program. Read More

Cardiovasc Drugs Ther 2019 02;33(1):69-76

Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Purpose: This post-hoc analysis examined whether age modified the efficacy and safety of alirocumab, a PCSK9 inhibitor, in patients with heterozygous familial hypercholesterolemia (HeFH), using pooled data from four 78-week placebo-controlled phase 3 trials (ODYSSEY FH I, FH II, LONG TERM, and HIGH FH).

Methods: Data from 1257 patients with HeFH on maximally tolerated statin ± other lipid-lowering therapies were analyzed by an alirocumab dose regimen and by age subgroups (18 to < 45, 45 to < 55, 55 to < 65, and ≥ 65 years). In the FH I and II trials, patients received 75 mg subcutaneously every 2 weeks (Q2W), with dose increase to 150 mg Q2W at week 12 if week 8 low-density lipoprotein cholesterol (LDL-C) was ≥ 70 mg/dl. Read More

Klin Lab Diagn 2018;63(6):324-332

FGBNU "Research Institute of General Pathology and Pathophysiology", Academy of Sciences of the Russian Federation, 125315, Moscow.

The abuse of food of carnivores (meat) by phylogeneticallyI herbivorous Homo sapiens (a patient) initiates atherosclerosis. Addressing biogenetic law of E. Haeckel that ontogeny recapitulates phylogeny (a universal anamnesis), we suggest a diagnostic technique that allows evaluation of the meat diet abuse by a herbivorous Homo sapiens. Read More

Atherosclerosis 2019 03 20;282:45-51. Epub 2019 Jan 20.

Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden. Electronic address:

Background And Aims: Type I hyperlipoproteinemia is an autosomal recessive disorder of lipoprotein metabolism caused by mutations in the LPL gene, with an estimated prevalence in the general population of 1 in a million. In this work, we studied the molecular mechanism of two known mutations in the LPL gene in ex vivo and in vitro experiments and also the effect of two splice site mutations in ex vivo experiments.

Methods: Two patients with hypertriglyceridemia were selected from the Lipid Clinic in Vienna. Read More

J Clin Lipidol 2019 Mar - Apr;13(2):251-253. Epub 2018 Dec 19.

Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong. Electronic address:

Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant renal disease with incomplete penetrance, associated with specific protein-modifying mutations in the APOE gene. LPG is associated with poor renal prognosis, in which lipoprotein thrombi are seen in the glomerular capillaries. Dyslipidemia in LPG generally resembles type III hyperlipoproteinemia with elevated serum apolipoprotein E level. Read More

Pathology 2019 Feb 28;51(2):165-176. Epub 2018 Dec 28.

Chemical Pathology Division, Pathology Department, University of Cape Town Health Science Faculty and National Health Laboratory Service, Cape Town, South Africa. Electronic address:

Apolipoprotein E (apoE), a 34 kDa circulating glycoprotein of 299 amino acids, predominantly synthesised in the liver, associates with triglyceride-rich lipoproteins to mediate the clearance of their remnants after enzymatic lipolysis in the circulation. Its synthesis in macrophages initiates the formation of high density-like lipoproteins to effect reverse cholesterol transport to the liver. In the nervous system apoE forms similar lipoproteins which perform the function of distributing lipids amongst cells. Read More

Drugs Today (Barc) 2018 Dec;54(12):721-735

Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon, USA.

Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder typically caused by mutations in genes for lipoprotein lipase (LPL), apolipoprotein C-II (Apo-CII), apolipoprotein A-V (Apo-AV), lipase maturation factor 1 (LMF1) and glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPI-HBP1). FCS is associated with severe morbidity that includes recurrent pancreatitis and other problems. Effective treatment to reliably prevent complications has been unavailable, so there is a quest to identify novel interventions to achieve sustained triglyceride lowering and prevention of pancreatitis. Read More

Klin Lab Diagn 2018;63(1):4-15

The Federal state budget scientifc institution "The research institute of general pathology and pathophysiology" of the Russian academy of sciences, 125315, Moscow, Russia.

According to phylogenetic theory of general pathology, when living in ocean all were carnivorous (piscivorous) fatty acids transferring to cells in form of non-polar triglycerides nitially began apoB-48 chylomicrons, continued lipoproteins of very low and low density and fnalized its apoB-100 endocytosis. The fatty acids are transferred by chylomicrons + lipoproteins of very low density + lipoproteins of low density and non-polar triglycerides are hydrolyzed by hepatic glycerolhydrogenase and co-enzyme apoC-III; according WHO classifcation, hyperlipoproteinemia corresponds to type V. On land, in herbivorous who are not yet synthesized insulin, apoB-48 and chylomicrons left process of non-polar triglycerides transferring. Read More

Clin Nephrol Case Stud 2018 30;6:45-51. Epub 2018 Nov 30.

Division of Nephrology, Kansai Electric Power Hospital.

A 79-year-old man was admitted to our hospital for proteinuria due to nephrotic syndrome. Renal biopsy revealed focal sclerosis and foam cell infiltration in the glomerulus. In addition, electron microscopic findings (EM) revealed peculiar electron-dense deposits (EDDs) in both sides of the glomerular basement membrane. Read More

Clin Chem 2019 02 11;65(2):313-320. Epub 2018 Dec 11.

Department of Blood Sciences, Directorate of Integrated Laboratory Medicine, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

Background: Familial dysbetalipoproteinemia is associated with the accumulation of remnant lipoproteins and premature cardiovascular disease. Identification of dysbetalipoproteinemia is important because family members may be affected. Diagnostic testing involves demonstration of β-lipoprotein in the VLDL fraction or characterization of apo E. Read More

Clin Chem 2019 02 11;65(2):225-227. Epub 2018 Dec 11.

McGill University Health Centre, McGill University, Montreal, Quebec.

Atherosclerosis 2019 03 10;282:169-175. Epub 2018 Nov 10.

Departments of Epidemiology and Internal Medicine, Division of Cardiology, University of Iowa, 145 N Riverside Dr S455 CPHB, Iowa City, IA, 52242, United States.

Whether apoB adds significantly to the assessment of the risk and therapy of the atherogenic dyslipoproteinemias has been vigorously contested over many years. That trapping of apoB lipoprotein particles within the arterial wall is fundamental to the initiation and maturation of atherosclerotic lesions within the arterial wall is now widely accepted. At the same time, the concept that primary prevention should be based on the risk of a cardiovascular event, a measure that integrates the effects of age, sex, blood pressure, lipids and other factors, has also become widely accepted. Read More

J Bras Nefrol 2019 Jul-Sep;41(3):393-399. Epub 2018 Nov 8.

Santa Casa de Misericórdia de Porto Alegre, Departamento de Patologia, Porto Alegre, RS, Brasil.

Lipoprotein glomerulopathy (LPG) is an uncommon cause of nephrotic syndrome and/or kidney failure. At microscopy, LPG is characterized by the presence of lipoprotein thrombi in dilated glomerular capillaries due to different ApoE mutations. ApoE gene is located on chromosome 19q13. Read More

J Clin Lipidol 2018 Nov - Dec;12(6):1383-1389. Epub 2018 Sep 14.

Centre Hospitalier de l'Universite Laval, Quebec, Quebec, Canada.

Background: Type III hyperlipoproteinemia is a highly atherogenic dyslipoproteinemia characterized by hypercholesterolemia and hypertriglyceridemia due to markedly increased numbers of cholesterol-enriched chylomicron and very-low-density lipoprotein (VLDL) remnant lipoprotein particles. Type III can be distinguished from mixed hyperlipidemia based on a simple diagnostic algorithm, which involves total cholesterol, triglycerides, and apolipoprotein B (apoB). However, apoB is not measured routinely. Read More

J Clin Lipidol 2018 Sep - Oct;12(5):1234-1243.e5. Epub 2018 May 31.

Department of Medicine, University California San Diego, La Jolla, CA, USA.

Background: Familial chylomicronemia syndrome (FCS) is a rare metabolic disorder caused by mutations in lipoprotein lipase (LPL) or genes required for LPL functionality and is characterized by hyperchylomicronemia that results in recurrent episodes of acute pancreatitis. Owing to the rarity of FCS, there are few case series describing the phenotypic variability in FCS patients in detail.

Objective: To provide baseline characteristics in the largest study population to date of patients with FCS. Read More

Atherosclerosis 2018 11 1;278:307-314. Epub 2018 Sep 1.

Duke University Medical Center, Durham, NC, USA.

Background And Aims: ODYSSEY OLE (open-label extension; NCT01954394) included patients diagnosed with heterozygous familial hypercholesterolemia (HeFH), receiving maximally tolerated statins, who had completed one of four Phase 3 double-blind parent studies (all 18 months' duration), with the aim to assess longer-term safety and efficacy of alirocumab.

Methods: Patients received starting dose alirocumab 75 mg every 2 weeks (Q2W; patients from FH I, FH II, and LONG TERM) or alirocumab 150 mg Q2W (patients from HIGH FH). Low-density lipoprotein cholesterol (LDL-C) levels were blinded to the patient and physician until Week 8; from Week 8, LDL-C levels were communicated to physicians. Read More

Biochim Biophys Acta Mol Basis Dis 2018 12 5;1864(12):3697-3713. Epub 2018 Oct 5.

Centro Andaluz de Biología del Desarrollo (CABD-CSIC-Universidad Pablo de Olavide), Centro de Investigación Biomédica en Red: Enfermedades Raras, Instituto de Salud Carlos III, Sevilla 41013, Spain. Electronic address:

Familial Hypercholesterolemia (FH) is an autosomal co-dominant genetic disorder characterized by elevated low-density lipoprotein (LDL) cholesterol levels and increased risk for premature cardiovascular disease. Here, we examined FH pathophysiology in skin fibroblasts derived from FH patients harboring heterozygous mutations in the LDL-receptor. Fibroblasts from FH patients showed a reduced LDL-uptake associated with increased intracellular cholesterol levels and coenzyme Q (CoQ) deficiency, suggesting dysregulation of the mevalonate pathway. Read More

J Clin Lipidol 2018 Nov - Dec;12(6):1463-1470. Epub 2018 Aug 30.

Lipid Clinic, Point Médical and Department of Cardiology, CHU Dijon-Bourgogne, Dijon, France.

Background: ODYSSEY OLE (NCT01954394) was an open-label extension (OLE) study for patients with heterozygous familial hypercholesterolemia (HeFH) who had completed previous phase 3 clinical trials with alirocumab. Alirocumab dose could be increased or decreased as per physician judgment.

Objective: To assess how the alirocumab dosing strategy was used by physicians during OLE. Read More

Atherosclerosis 2018 10;277:314-322

D A CH Society for the Prevention of Heart and Circulatory Diseases (registered society), Hamburg, Germany; Department of Internal Medicine V Medical Faculty Mannheim, Heidelberg University, Germany; Klinisches Institut für Medizinische und Chemische Labordiagnostik, Medizinische Universität Graz, Graz, Austria; Synlab Akademie, Synlab Holding Deutschland GmbH, Mannheim und Augsburg, Germany.

Background And Aims: Familial hypercholesterolemia (FH) is amongst the most common genetic disorders encountered in primary care. Yet, only a minority of affected patients is diagnosed and treated. This interim analysis of the CaRe High Registry aims at examining the state of treatment and attainment of lipid goals in German FH patients. Read More

J Atheroscler Thromb 2019 Apr 26;26(4):368-377. Epub 2018 Sep 26.

Aegerion Pharmaceuticals, Inc.

Aim: Lomitapide is an approved lipid-lowering agent indicated as adjunct to low-fat diet and standard lipid-lowering therapies (LLTs) including lipoprotein apheresis for the treatment of homozygous familial hypercholesterolemia (HoFH). Clinical data from Phase 3 studies have demonstrated the prolonged lipid-lowering capacity of lomitapide in patients with HoFH. We assessed the long-term lipid-lowering capacity of daily oral lomitapide in a cohort of Japanese patients with HoFH enrolled in a Phase 3 extension study. Read More

Endocr Pract 2018 08;24(8):756-763

Objective: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder caused by mutations in lipoprotein lipase, resulting in accumulation of chylomicrons in plasma and hypertriglyceridemia. Elevated triglycerides cause several complications in patients, the most serious being episodes of acute pancreatitis. This review focuses on expert guidance and opinion from an experienced lipidologist and endocrinologist as well as a current review of the literature, as there are no specific guidelines on FCS. Read More

J Atheroscler Thromb 2019 Mar 1;26(3):282-293. Epub 2018 Aug 1.

PCSK9 Development and Launch Unit, Sanofi.

Aim: To examine the efficacy and safety of alirocumab in Japanese patients with dyslipidemia with or without diabetes mellitus (DM).

Methods: Patients (n=216) with heterozygous familial hypercholesterolemia (heFH), non-FH at high cardiovascular risk with coronary artery disease (CAD), or category III (primary prevention) were enrolled; 148 (68.5%) patients had a diagnosis of DM at baseline. Read More

JACC Basic Transl Sci 2017 Oct 30;2(5):591-600. Epub 2017 Oct 30.

Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

Deficiency of apolipoprotein E (APOE) causes familial dysbetalipoproteinemia in humans resulting in a higher risk of atherosclerotic disease. In mice, APOE deficiency results in a severe atherosclerosis phenotype, but it is unknown to what extent this is unique to mice. In this study, was targeted in Yucatan minipigs. Read More

Arterioscler Thromb Vasc Biol 2018 08;38(8):1940-1947

Division of Cardiology (W.S.), Nippon Medical School, Tokyo, Japan.

Objective- Although postprandial hypertriglyceridemia can be a risk factor for coronary artery disease, the extent of its significance remains unknown. This study aimed to investigate the correlation between the postprandial lipid profiles rigorously estimated with the meal tolerance test and the presence of lipid-rich plaque, such as thin-cap fibroatheroma (TCFA), in the nonculprit lesion. Approach and Results- A total of 30 patients with stable coronary artery disease who underwent a multivessel examination using optical coherence tomography during catheter intervention for the culprit lesion were enrolled. Read More

Clin Biochem 2018 Sep 18;59:31-36. Epub 2018 Jun 18.

Departments of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, RB 9700, The Netherlands.

Objective: Familial dysbetalipoproteinemia (FD) or Type III hyperlipoproteinemia is closely associated with the ε2ε2 genotype of the common APOE polymorphism although not all ε2 homozygotes develop FD indicating that additional factors play a role including insulin resistance (IR). The current study was undertaken to explore relationships and influences among factors, especially IR, that might elucidate FD progression pathways.

Methods: Bayesian network (BN) modeling, a probabilistic graphical exploratory data analysis tool that portrays relationships and influences among variables as simple diagrams, was applied to 52 e2e2 subjects. Read More

Orphanet J Rare Dis 2018 06 20;13(1):96. Epub 2018 Jun 20.

Aegerion Pharmaceuticals Ltd, Uxbridge, UK.

Background: Homozygous familial hypercholesterolaemia (HoFH) is characterized by a markedly increased risk of premature cardiovascular (CV) events and cardiac death. Lomitapide reduces low-density lipoprotein cholesterol (LDL-C) levels; however, the probable impact on LDL-C goals and CV events is unknown.

Methods: We used data collected in the first 26 weeks of the lomitapide pivotal phase 3 study (NCT00730236) to evaluate achievement of European Atherosclerosis Society (EAS) LDL-C targets. Read More