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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 Jan 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 2018 Dec 19. 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

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 Feb 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 Feb 11;65(2):225-227. Epub 2018 Dec 11.

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

J Bras Nefrol 2018 Nov 8. Epub 2018 Nov 8.

Departamento de Patologia, Santa Casa de Misericórdia de Porto Alegre, 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

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

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

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

Expert Rev Cardiovasc Ther 2018 Jul 22;16(7):537-546. Epub 2018 Jun 22.

b Akcea Therapeutics , Cambridge , MA , USA.

Background: Volanesorsen, an investigational inhibitor of apoC-III synthesis, significantly reduced triglyceride levels in clinical trials in patients with familial chylomicronemia syndrome (FCS), a rare genetic disorder characterized by marked chylomicronemia leading to a spectrum of symptoms, including recurrent abdominal pain and episodes of potentially fatal acute pancreatitis (AP).

Objective: To determine the effect of volanesorsen on burden of disease on patients with FCS Methods: ReFOCUS was a retrospective global web-based survey open to patients with FCS who received volanesorsen for ≥3 months in an open-label extension study. The survey included questions about patients' experiences before and after volanesorsen treatment. Read More

Expert Rev Clin Pharmacol 2018 Jun 11;11(6):589-598. Epub 2018 Jun 11.

c Department of Metabolic Medicine/Chemical Pathology , Guy's and St Thomas' Hospitals , London , UK.

Introduction: A spectrum of disorders, ranging from rare severe cases of homozygous null lipoprotein lipase deficiency (LPLD)-familial chylomicronemia syndrome (FCS) to heterozygous missense LPLD or polygenic causes, result in hypertriglyceridemia and pancreatitis. The effects of mutations are exacerbated by environmental factors such as diet, pregnancy, and insulin resistance. Areas covered: In this review, authors discuss chronic treatment of FCS by ultra-low fat diets allied with the use of fibrates, omega-3 fatty acids, niacin, statins, and insulin-sensitizing therapies depending on the extent of residual lipoprotein lipase (LPL) activity; novel therapies in development target triglyceride (TG)-rich lipoprotein particle clearance. Read More

N Engl J Med 2018 May;378(19):e26

Klinikum der Universität München, Munich, Germany

Per Med 2018 03 31;15(2):87-92. Epub 2018 Jan 31.

Fundacion Hipercolesterolemia Familial, Madrid, Spain.

Aim: rs599839 polymorphism has been related with low levels of cholesterol and reduced coronary heart disease (CHD).

Methods: We investigated the frequency of this polymorphism in patients with heterozygous familial hypercholesterolemia (HeFH) in the Spanish familial hypercholesterolemia cohort, 230 with and 202 without CHD. Results & discussion: A lower G-allele prevalence was observed in HeFH patients with CHD with respect to controls, 35 versus 45%, respectively (p = 0. Read More

CEN Case Rep 2018 May 22;7(1):127-131. Epub 2018 Jan 22.

Sanko Clinic, Fukuoka, Japan.

Lipoprotein glomerulopathy (LPG) is a rare inherited disease characterized by histopathological features of lipoprotein thrombi in dilated glomerular capillaries and type III like hyperlipoproteinemia with heterozygous mutation of the apolipoprotein (apo) E gene. We herein present the case of a 50-year-old woman with LPG complicated by neurofibromatosis type 1 (NF1). To the best of our knowledge, this is the first report of a case of LPG complicated by NF1. Read More

Clin Biochem 2018 Feb 20;52:67-72. Epub 2017 Nov 20.

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

Objective: Familial dysbetalipoproteinemia (FD) or Type III hyperlipoproteinemia is a mixed hyperlipidemia closely associated with the ε2ε2 genotype of the common APOE polymorphism although not all homozygotes progress to FD. Unlike the polymorphism, few studies explore effects of apolipoprotein E (apoE) blood levels on FD development. Likewise, despite the known apoE2 lipoprotein binding preference for high-density lipoprotein (HDL); little work exists exploring HDL in FD. Read More

World J Gastroenterol 2017 Oct;23(40):7332-7336

Division of Gastroenterology and Liver Disease, Department of Internal Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH 44106, United States.

Hypertriglyceridemic pancreatitis (HTGP) accounts for up to 10% of acute pancreatitis presentations in non-pregnant individuals and is the third most common cause of acute pancreatitis after alcohol and gallstones. There are a number of retrospective studies and case reports that have suggested a role for apheresis and insulin infusion in the acute inpatient setting. We report a case of HTGP in a male with hyperlipoproteinemia type III who was treated successfully with insulin and apheresis on the initial inpatient presentation followed by bi-monthly outpatient maintenance apheresis sessions for the prevention of recurrent HTGP. Read More

Atheroscler Suppl 2017 Nov 1;30:72-76. Epub 2017 Jun 1.

D•A•CH-Gesellschaft Prävention von Herz-Kreislauf-Erkrankungen e.V., Hamburg, Germany; Synlab Academy, Synlab Holding Germany GmbH, Mannheim, Germany; Clinical Institut for Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria; Medical Clinic V (Nephrology, Hypertension, Rheumatology, Endocrinology, Diabetology), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.

Introduction: Familial hypercholesterolemia (FH) is an inherited disorder of the LDL metabolism, leading to cardiovascular disease, even at young age. This risk can be significantly lowered by early diagnosis and treatment. About 270,000 patients affected in Germany are not diagnosed correctly and only a small number is treated properly. Read More

Atheroscler Suppl 2017 Nov 1;30:56-62. Epub 2017 Jun 1.

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.

Aim: to analyze the relationship between lipid disturbance, including lipoprotein(a) (Lp(a)) levels, and development of ischemic heart disease (IHD) in patients with familial hypercholesterolemia (FH).

Materials And Methods: 81 patients (middle age was 39.1 ± 0. Read More

Atheroscler Suppl 2017 Nov 1;30:44-49. Epub 2017 Jun 1.

Department of Medicine II for Nephrology, Hypertension and Vascular Risks, AGAPLESION Markus Hospital, Frankfurt, Germany.

According to current European guidelines, lipid lowering therapy for progressive cardiovascular disease including cardiovascular events has to be focused on a target level for LDL-C. In contrast for Lp(a) a threshold has to be defined with respect to the method of measurement. However, due to new lipid lowering drug developments like PCSK9-inhibitors (PCSK-9-I) a therapeutic algorithm for patients with severe hypercholesterolemia or isolated Lipoprotein(a)-hyperlipoproteinemia with progressive cardiovascular disease may be necessary to manage the use of PCSK9-I, lipoprotein apheresis (LA) or both. Read More

Atheroscler Suppl 2017 Nov 1;30:122-127. Epub 2017 Jun 1.

Medical University of Vienna, Dept. of Internal Medicine III, Nephrology, Vienna, Austria.

Background: Lipoprotein(LP)-apheresis is the treatment of choice in patients suffering from severe familial hypercholesterolemia. A wide range of mechanisms has been claimed to be responsible for the known clinical benefit.

Methods: Patients suffering from heterozygous familial hypercholesterolemia undergoing LP-apheresis either with direct adsorption of lipoproteins (DALI) or dextran sulfate (DS) were examined. Read More

Arterioscler Thromb Vasc Biol 2017 12 26;37(12):2356-2363. Epub 2017 Oct 26.

From the Endocrinology and Nutrition Service, Institut d'Investigacions Biomèdiques August Pi Sunyer, Hospital Clínic, Barcelona, Spain (A.J.A., E.O., M.C., A.S.-V., E.R.); Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain (A.J.A., E.O., M.C., A.S.-V., E.R.); Service of Endocrinology, Hospital Universitari Mútua de Terrassa, Spain (V.P.); and Vascular Unit, Centre de Diagnòstic per l'Imatge, Institut d'Investigacions Biomèdiques August Pi Sunyer, Hospital Clínic, Barcelona, Spain (I.N., R.G.).

Objective: Bilirubin is a potent antioxidant that has been inversely related to cardiovascular disease. There is little information on serum total bilirubin (TB) in relation to atherosclerosis in familial dyslipidemia. We assessed the association between TB and carotid and femoral atherosclerosis in this high-risk group. Read More

J Clin Lipidol 2017 Nov - Dec;11(6):1448-1457. Epub 2017 Sep 22.

Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.

Background: Evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9, is safe and effective when dosed biweekly (Q2W) or monthly (QM) in patients with heterozygous familial hypercholesterolemia (HeFH) as demonstrated in two 12-week trials: Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD; phase 2) and RUTHERFORD-2 (phase 3).

Objective: The objective of the study was to evaluate long-term efficacy, safety, and tolerability of evolocumab during open-label extension trials.

Methods: Patients completing parent trials were re-randomized 2:1 to evolocumab plus standard of care (SOC) or SOC alone for 52 weeks (Open-Label Study of Long-term Evaluation Against LDL-C [OSLER-1]) or 48 weeks (OSLER-2). Read More

J Clin Lipidol 2017 Nov - Dec;11(6):1432-1440.e4. Epub 2017 Oct 4.

Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), CIBERCV, Universidad de Zaragoza, Zaragoza, Spain.

Context: Approximately 20% to 40% of clinically defined familial hypercholesterolemia (FH) cases do not show a causative mutation in candidate genes (mutation-negative FH), and some of them may have a polygenic origin.

Objective: The aim of this work was to study the prevalence of ABCG5/G8 genetic variants in mutation-negative FH, as defects in these genes relate to intestinal hyperabsorption of cholesterol and thus ABCG5/G8 variants could explain in part the mechanism of hypercholesterolemia.

Design, Setting, And Patients: We sequenced the ABCG5/G8 genes in 214 mutation-negative FH and 97 controls. Read More

J Lipid Res 2017 11 19;58(11):2180-2187. Epub 2017 Sep 19.

Department of Vascular Medicine University Medical Center Utrecht, Utrecht, The Netherlands

Familial dysbetalipoproteinemia (FD) is a genetic disorder associated with impaired postprandial lipid clearance. The effect of adding bezafibrate to standard lipid-lowering therapy on postprandial and fasting lipid levels in patients with FD is unknown. In this randomized placebo-controlled double-blind crossover trial, 15 patients with FD received bezafibrate and placebo for 6 weeks in randomized order in addition to standard lipid-lowering therapy (statin, ezetimibe, and/or lifestyle). Read More

Vasc Health Risk Manag 2017 4;13:343-351. Epub 2017 Sep 4.

Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano.

Heterozygous familial hypercholesterolemia (FH) is a genetic disorder characterized by high low-density lipoprotein cholesterol levels from birth, which exposes the arteries to high levels of atherogenic lipoproteins lifelong and results in a significantly increased risk of premature cardiovascular events. The diagnosis of FH, followed by an appropriate and early treatment is critical to reduce the cardiovascular burden in this population. Phase I-III clinical trials showed the benefit of proprotein convertase subtilisin kexin 9 inhibitors, both alirocumab and evolocumab, in these patients with an average low-density lipoprotein cholesterol reduction ranging from -40% to -60%. Read More

Expert Rev Clin Pharmacol 2017 Dec 14;10(12):1375-1381. Epub 2017 Sep 14.

a First Propedeutic Department of Internal Medicine, Medical School , Aristotle University of Thessaloniki, AHEPA Hospital , Thessaloniki , Greece.

Introduction: Even though statins represent the mainstay of treatment of heterozygous familial hypercholesterolemia (FH), their low-density lipoprotein cholesterol (LDL-C) lowering efficacy is finite and most patients with FH will not achieve LDL-C targets with statin monotherapy. Addition of ezetimibe with or without bile acid sequestrants will also not lead to treatment goals in many of these patients, particularly in those with established cardiovascular disease. In this selected subgroup of the FH population, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors provide substantial reductions in LDL-C levels, reduce cardiovascular morbidity and appear to be safe. Read More

Endocrinol Diabetes Nutr 2017 Aug - Sep;64(7):341-344. Epub 2017 Jun 3.

Servicio de Endocrinología y Nutrición, Hospital Clínic de Barcelona, IDIBAPS, Universidad de Barcelona (UB), Barcelona, España; CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, España. Electronic address:

Sci Rep 2017 07 17;7(1):5596. Epub 2017 Jul 17.

Lipid and Vascular Unit, Department of Endocrinology and Nutrition, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain.

Patients with heterozygous familial hypercholesterolemia (HeFH) have been reported to be less vulnerable to type 2 diabetes mellitus (T2DM), although the mechanism is unknown. The aims of the present study were to assess the effects of low density lipoprotein (LDL) cholesterol concentration and the presence of FH-causing mutations on T2DM prevalence in HeFH. Data were collected from the Dyslipidemia Registry of the Spanish Arteriosclerosis Society. Read More

J Coll Physicians Surg Pak 2017 Jun;27(6):378-379

Department of Clinical Pathology, Northampton General Hospital, Cliftonville, Northampton, UK.

Dysbetalipoproteinemia is often associated with apolipoprotein E2E2 homozygosity; however, lipoprotein electrophoresis may also be used to assist in the diagnosis. The aim of this study was to compare apolipoprotein E (apo E) genotyping and lipoprotein electrophoresis in investigating dysbetalipoproteinemia. Data were collected over a three-year period from a lipid clinic in a tertiary referral centre and reviewed for apo E genotyping and lipoprotein electrophoresis. Read More

Comput Struct Biotechnol J 2017 6;15:359-365. Epub 2017 Jun 6.

Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 8 B. P. Hasdeu Street, Sector 5, 050568 Bucharest, Romania.

Apolipoprotein E (apoE), a 34 kDa glycoprotein, mediates hepatic and extrahepatic uptake of plasma lipoproteins and cholesterol efflux from lipid-laden macrophages. In humans, three structural different apoE isoforms occur, with subsequent functional changes and pathological consequences. Here, we review data supporting the involvement of apoE structural domains and isoforms in normal and altered lipid metabolism, cardiovascular and neurodegenerative diseases, as well as stress-related pathological states. Read More

J Clin Lipidol 2017 Jul - Aug;11(4):858-871.e3. Epub 2017 Apr 25.

Division of Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA.

Background: Despite advances in pharmacotherapy of lipid disorders, many dyslipidemic patients do not attain sufficient lipid lowering to mitigate risk of atherosclerotic cardiovascular disease. Several classes of novel lipid-lowering agents are being evaluated to reduce atherosclerotic cardiovascular disease risk. Lipoprotein apheresis (LA) is effective in acutely lowering the plasma concentrations of atherogenic lipoproteins including low-density lipoprotein cholesterol and lipoprotein(a), and novel lipid-lowering drugs may dampen the lipid rebound effect of LA, with the possibility that LA frequency may be decreased, in some cases even be discontinued. Read More

Sci Rep 2017 05 30;7(1):2509. Epub 2017 May 30.

Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília-DF, Brazil.

ApoE3 is the major chylomicron apolipoprotein, binding in a specific liver peripheral cell receptor, allowing transport and normal catabolism of triglyceride-rich lipoprotein constituents. Point mutations in ApoE3 have been associated with Alzheimer's disease, type III hyperlipoproteinemia, atherosclerosis, telomere shortening and impaired cognitive function. Here, we evaluate the impact of missense SNPs in APOE retrieved from dbSNP through 16 computational prediction tools, and further evaluate the structural impact of convergent deleterious changes using 100 ns molecular dynamics simulations. Read More

Herz 2017 Aug;42(5):449-458

Medizinische Klinik V (Nephrologie, Hypertensiologie, Rheumatologie, Endokrinologie, Diabetologie), Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Deutschland.

Congenital disorders of lipid metabolism are caused by a wide range of variants of the genes for receptors, apolipoproteins, enzymes, transfer factors, and cellular cholesterol transporters. Clinically most relevant are autosomal dominant familial hypercholesterolemia (FH) and familial combined hyperlipoproteinemia (FCHL). FH has a prevalence of 1:250. Read More

Cardiovasc Diabetol 2017 05 25;16(1):70. Epub 2017 May 25.

Sanofi, Paris, France.

Background: Type 2 diabetes mellitus (T2DM) is often associated with mixed dyslipidaemia, where non-high-density lipoprotein cholesterol (non-HDL-C) levels may more closely align with cardiovascular risk than low-density lipoprotein cholesterol (LDL-C). We describe the design and rationale of the ODYSSEY DM-DYSLIPIDEMIA study that assesses the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, versus lipid-lowering usual care in individuals with T2DM and mixed dyslipidaemia at high cardiovascular risk with non-HDL-C inadequately controlled despite maximally tolerated statin therapy. For the first time, atherogenic cholesterol-lowering with a PCSK9 inhibitor will be assessed with non-HDL-C as the primary endpoint with usual care as the comparator. Read More

J Clin Lipidol 2017 Jan - Feb;11(1):260-271. Epub 2017 Jan 10.

Fundación Hipercolesterolemia Familiar, Madrid, Spain.

Background: Although familial hypercholesterolemia (FH) confers a high risk of coronary artery disease, most patients are undiagnosed, and little is known about the efficiency of genetic cascade screening programs at national level.

Objective: The aim of the study was to estimate the cost-effectiveness of a national genetic cascade screening program in Spain.

Methods: An economic evaluation was performed using a decision tree analysis. Read More

J Clin Lipidol 2017 Jan - Feb;11(1):12-23.e1. Epub 2016 Oct 13.

Department of Chemical Pathology, University of Cape Town Health Science Faculty, Cape Town, South Africa. Electronic address:

Familial dysbetalipoproteinemia (FD) is a genetic disorder of lipoprotein metabolism associated with an increased risk for premature cardiovascular disease. In about 10% of the cases, FD is caused by autosomal dominant mutations in the apolipoprotein E gene (APOE). This review article provides a pathophysiological framework for autosomal dominant FD (ADFD) and discusses diagnostic challenges and therapeutic options. Read More

Pediatr Blood Cancer 2017 11 1;64(11). Epub 2017 Apr 1.

Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.

Arterioscler Thromb Vasc Biol 2017 05 23;37(5):969-975. Epub 2017 Mar 23.

From the Departments of Vascular Medicine (S.J.B.M., S.L.V., L.C.A.S., M.B., S.B., E.S.G.S., J.K.), Experimental Vascular Medicine (J.G.S.), and Nuclear Medicine (H.J.V.), AMC, Amsterdam, The Netherlands; The Copenhagen General Population Study (A.L., B.G.N.) and Department of Clinical Biochemistry (A.L., B.G.N.), Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark; and Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, The Netherlands (C.K., C.V.).

Objective: Mendelian randomization studies revealed a causal role for remnant cholesterol in cardiovascular disease. Remnant particles accumulate in the arterial wall, potentially propagating local and systemic inflammation. We evaluated the impact of remnant cholesterol on arterial wall inflammation, circulating monocytes, and bone marrow in patients with familial dysbetalipoproteinemia (FD). Read More

Lancet Diabetes Endocrinol 2017 04 16;5(4):280-290. Epub 2017 Feb 16.

Metabolic and Atherosclerosis Research Center, Cincinnati, OH, USA. Electronic address:

Background: Homozygous familial hypercholesterolaemia is a genetic disorder characterised by substantially raised LDL cholesterol, reduced LDL receptor function, xanthomas, and cardiovascular disease before age 20 years. Conventional therapy is with statins, ezetimibe, and apheresis. We aimed to assess the long-term safety and efficacy of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab in a subset of patients with homozygous familial hypercholesterolaemia enrolled in an open-label, non-randomised phase 3 trial. Read More

Rev Esp Cardiol (Engl Ed) 2017 Jul 17;70(7):551-558. Epub 2017 Feb 17.

Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.

Introduction And Objectives: The equations used in the general population to calculate cardiovascular risk are not useful in genetic hypercholesterolemia (GH). Carotid plaque detection has proved useful in cardiovascular prediction and risk reclassification but there have been no studies of its usefulness in GH. The aim of this study was to determine the association between the presence of carotid artery plaque and the occurrence of cardiovascular events in patients with GH. Read More

J Atheroscler Thromb 2017 Apr 2;24(4):402-411. Epub 2017 Feb 2.

National Cerebral and Cardiovascular Research Center.

Aim: There is an unmet need in Japan for more optimal lipid-lowering therapy (LLT) for patients with homozygous familial hypercholesterolemia (HoFH) who respond inadequately to available drug therapies and/or apheresis, to achieve goals of low-density lipoprotein cholesterol (LDL-C) reduction by 50% or to ＜100 mg/dL.

Methods: In this study, Japanese patients with HoFH on stable LLT and diet were treated with lomitapide, initiated at 5 mg/day and escalated to maximum tolerated dose (up to 60 mg/day) over 14 weeks. The primary efficacy endpoint was mean percentage change from baseline to Week 26 in LDL-C. Read More

Arkh Patol 2016;78(6):52-57

Research Institute of Nephrology, I.P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of the Russian Federation, Saint Petersburg, Russia.

Lipoprotein glomerulopathy (LPG) is a rare disease characterized by specific histological, immunomorphological, and ultrastructural changes. The main pathomorphological signs of LPG are lipoprotein thrombi in the lumen of the capillary loops, proteinuria, and dyslipoproteinemia as an increased concentration of apolipoprotein E (phenotypes E2/E3, E2/E4). A patient aged 47 years had nephrotic syndrome with a daily protein loss of 12. Read More

Vnitr Lek Fall 2016;62(11):887-894

Hyperlipoproteinemia (HLP) and dyslipidemia (DLP) are of course mainly perceived as diseases of common incidence and are typically seen as the greatest risk factors (RF) in the context of the pandemic of cardiovascular diseases. This is certainly true and HLP or DLP overall affect tens of percents of adults. However we cannot overlook the fact that disorders (mostly congenital) of lipid metabolism exist which, though not formally defined as such, amply satisfy the conditions for classification as rare diseases. Read More

Curr Opin Endocrinol Diabetes Obes 2017 Apr;24(2):133-139

aVascular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands bDivision of Chemical Pathology, University of Cape Town Health Science Faculty and National Health Laboratory Service, Cape Town, South Africa.

Purpose Of Review: To review pathophysiological, epidemiological and clinical aspects of familial dysbetalipoproteinemia; a model disease for remnant metabolism and remnant-associated cardiovascular risk.

Recent Findings: Familial dysbetalipoproteinemia is characterized by remnant accumulation caused by impaired remnant clearance, and premature cardiovascular disease. Most familial dysbetalipoproteinemia patients are homozygous for apolipoprotein ε2, which is associated with decreased binding of apolipoprotein E to the LDL receptor. Read More

Am J Cardiol 2017 03 2;119(5):742-748. Epub 2016 Dec 2.

Unidad Clínica e Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain.

Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein (LDL) cholesterol with co-dominant transmission and high risk of cardiovascular disease (CVD), although with high variability among subjects. Currently, CVD stratification tools for heterozygous FH (HeFH) are not available. A definition of severe HeFH has been recently proposed by the International Atherosclerosis Society (IAS), but it has not been validated. Read More

J Clin Lipidol 2016 Nov - Dec;10(6):1397-1405.e2. Epub 2016 Sep 22.

Departamento de Anatomía, Embriología y Genetica Animal, Universidad de Zaragoza, Zaragoza, Spain.

Background: A substantial proportion of individuals clinically diagnosed as familial hypercholesterolemia (FH) do not carry pathogenic mutations in candidate genes. Whether in them the high cholesterol trait is transmitted monogenically has not been studied.

Objectives: We assessed the inheritance pattern, penetrance, and expression of high low-density lipoprotein (LDL)-cholesterol (LDLc) in families with genetic hypercholesterolemia (GH) without known causative mutations (non-FH-GH). Read More