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Front Cardiovasc Med 2019 29;6. Epub 2019 Jan 29.

Division of Cardiovascular Medicine and Cardiovascular Institute, Stanford University, Stanford, CA, United States.

Familial Hypercholesterolemia (FH) is an inherited lipid disorder affecting 1 in 220 individuals resulting in highly elevated low-density lipoprotein levels and risk of premature coronary disease. Pathogenic variants causing FH typically involve the LDL receptor (), apolipoprotein B-100 (), and proprotein convertase subtulisin/kexin type 9 genes () and if identified convey a risk of early onset coronary artery disease (ASCVD) of 3- to 10-fold vs. the general population depending on the severity of the mutation. Read More

Curr Opin Lipidol 2019 Jan 14. Epub 2019 Jan 14.

Heart Institute (InCor) University of Sao Paulo Medical School Hospital.

Purpose Of Review: To discuss the heterogeneity of atherosclerotic cardiovascular disease (ASCVD) risk in heterozygous familial hypercholesterolemia and evidence and limitations of clinical risk scores and subclinical coronary atherosclerosis (SCA) imaging to evaluate risk.

Recent Findings: Risk evaluation in contemporary familial hypercholesterolemia cohorts needs to consider the cause of the familial hypercholesterolemia phenotype, for example the presence of autosomal molecular defects that impart a greater ASCVD risk than in polygenic hypercholesterolemia, prospective follow-up and the impact of statin treatment. As atherosclerosis is multifactorial, clinical scores like the Montreal familial hypercholesterolemia score and SAFEHEART risk equation have been proposed to stratify ASCVD in statin-treated, molecularly defined familial hypercholesterolemia individuals. Read More

Circulation 2018 Nov 11. Epub 2018 Nov 11.

Massachusetts General Hospital, Boston, MA.

Background: The relative prevalence and clinical importance of monogenic mutations related to familial hypercholesterolemia and of high polygenic score (cumulative impact of many common variants) pathways for early-onset myocardial infarction remain uncertain. Whole genome sequencing enables simultaneous ascertainment of both monogenic mutations and polygenic score for each individual.

Methods: We performed deep-coverage whole genome sequencing of 2,081 patients from four racial subgroups hospitalized in the U. Read More

Pathology 2019 Feb 14;51(2):184-192. Epub 2018 Dec 14.

Departments of Medicine and Biochemistry, and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. Electronic address:

Dyslipidaemias encompass about two dozen relatively rare monogenic disorders and syndromes for which the genetic basis has largely been defined. In addition, the complex polygenic basis of disturbed lipids and lipoproteins has been characterised in many patients, and has been shown to result from accumulation of many common polymorphisms with small effects on lipids. Genetic technologies, including dedicated genotyping and sequencing methods can detect both rare and common DNA variants underlying dyslipidaemias. Read More

Am J Cardiol 2019 Feb 23;123(4):588-591. Epub 2018 Nov 23.

Department of Medical and Surgical Sciences, Alma Mater Studiorum - Università di Bologna, Bologna, Italy.

Hypercholesterolemia represents one of the main reversible cardiovascular risk factors. In this pilot clinical trial, we have tested the short-term efficacy and safety of a new combined cholesterol-lowering nutraceutical containing artichoke dry extract and berberine at enhanced bioavailability in subjects with moderate polygenic hypercholesterolemia in primary prevention for cardiovascular disease. After 2 months of treatment, the tested nutraceutical induced a significant reduction in plasma total cholesterol (-19%), low-density lipoprotein cholesterol (-16%), non-high-density lipoprotein cholesterol (-19%) and triglyceride levels (-15%), in association with a standardized control diet. Read More

Praxis (Bern 1994) 2018 Nov;107(24):1345-1353

1 Klinik für Endokrinologie, Diabetologie, Osteologie und Stoffwechselkrankheiten, Kantonsspital St. Gallen.

Diagnosis and Treatment of Familial Hypercholesterolemia Abstract. Familial hypercholesterolemia secondary to heterozygous mutations in the LDL receptor, Apolipoprotein B or PCSK9 gene is characterized by 2- to 3-fold elevated LDL cholesterol levels, premature atherosclerosis and extravascular cholesterol deposits (tendon xanthomata, corneal arcus). The same phenotype may occur if a person carries several LDL cholesterol rising polymorphisms (polygenic FH). Read More

Transl Psychiatry 2018 10 12;8(1):218. Epub 2018 Oct 12.

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Bipolar disorder (BD) is a mental disorder characterized by alternating periods of depression and mania. Individuals with BD have higher levels of early mortality than the general population, and a substantial proportion of this is due to increased risk for comorbid diseases. To identify the molecular events that underlie BD and related medical comorbidities, we generated imputed whole-genome sequence data using a population-specific reference panel for an extended multigenerational Old Order Amish pedigree (n = 394), segregating BD and related disorders. Read More

J Clin Lipidol 2018 Nov - Dec;12(6):1452-1462. Epub 2018 Sep 7.

Institut de Recerca - Hospital de la Santa Creu i Sant Pau, Serveis de Bioquímica, i d'Endocrinologia i Nutrició, IIB Sant Pau, CIBERDEM, Universitat Autònoma de Barcelona, Departaments de Bioquímica i Biologia Molecular, i Medicina, Barcelona, Spain. Electronic address:

Background: Autosomal dominant hypercholesterolemia (ADH) is associated with mutations in the low-density lipoprotein (LDL) receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9) genes, and it is estimated to be greatly underdiagnosed. The most cost-effective strategy for increasing ADH diagnosis is a cascade screening from mutation-positive probands.

Objective: The objective of this study was to evaluate the results from 2008 to 2016 of ADH genetic analysis performed in our clinical laboratory, serving most lipid units of Catalonia, a Spanish region with approximately 7. Read More

Atherosclerosis 2018 Oct;277:457-463

Institute of Cardiovascular Science, University College London, 5 University St, London, WC1E 6JF, United Kingdom. Electronic address:

Mutations in any of three genes (LDLR, APOB and PCSK9) are known to cause autosomal dominant FH, but a mutation can be found in only ∼40% of patients with a clinical diagnosis of FH. In the remainder, a polygenic aetiology may be the cause of the phenotype, due to the co-inheritance of common LDL-C raising variants. In 2013, we reported the development of a 12-SNP LDL-C "SNP-Score" based on common variants identified as LDL-C raising from genome wide association consortium studies, and have confirmed the validity of this score in samples of no-mutation FH adults and children from more than six countries with European-Caucasian populations. Read More

Atherosclerosis 2018 Oct;277:256-261

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Bioquímica Clínica, Laboratorio de Lípidos y Aterosclerosis, INFIBIOC-UBA, Buenos Aires, Argentina. Electronic address:

Background And Aims: Marked hypercholesterolemia, defined as low density lipoprotein cholesterol (LDL-C) levels ≥ 190 mg/dL, may be due to LDLR, APOB, and PCSK9 variants. In a recent analysis, only 1.7% of cases had such variants. Read More

J Clin Lipidol 2018 Nov - Dec;12(6):1436-1444. Epub 2018 Aug 23.

Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.

Background: The genetic background of severe familial hypercholesterolemia (FH) has yet to be determined.

Objective: We tested if genetic variants associated with low-density lipoprotein (LDL)-altering autosomal recessive diseases influenced LDL cholesterol levels and the odds for coronary artery disease in patients with high LDL cholesterol.

Methods: We recruited 500 individuals with elevated LDL cholesterol levels (≥180 mg/dL or ≥140 mg/dL for subjects <15 years). Read More

J Pers Med 2018 Aug 23;8(3). Epub 2018 Aug 23.

Department of Health Sciences Research (KRB), Mayo Clinic, Rochester, MN 55902, USA.

To inform guidelines for screening family members of patients with familial hypercholesterolemia (FH), we designed a clinical trial to compare the yield of cascade screening in FH patients with and without an identifiable pathogenic variant. Participants with hypercholesterolemia (Low-density lipoprotein cholesterol (LDL-C) > 155 mg/dL) underwent sequencing of , , and and genotyping of six single nucleotide polymorphisms associated with LDL-C followed by calculation of a polygenic score for LDL-C. We identified 24 patients with definite FH (pathogenic variant in one of the three FH genes), 76 patients with probable FH (Dutch lipid clinic network (DLCN) score ≥ 6, no pathogenic variant), and 262 patients with possible FH (DLCN score 3⁻5, no pathogenic variant). Read More

Nat Commun 2018 08 23;9(1):3391. Epub 2018 Aug 23.

Center for Genomic Medicine and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, 02114, USA.

Large-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth >29X and analyze genotypes with four quantitative traits-plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Common variant association yields known loci except for few variants previously poorly imputed. Read More

Nat Rev Cardiol 2019 Jan;16(1):9-20

Departments of Medicine and Biochemistry, and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.

Familial hypercholesterolaemia is the most commonly encountered genetic condition that predisposes individuals to premature cardiovascular disease. Nevertheless, most patients are undiagnosed, and treatment is often suboptimal even when the diagnosis seems certain. Advances in molecular technologies are reshaping our understanding of this condition, including revision upwards of the population prevalence. Read More

Circ Genom Precis Med 2018 01 8;11(1):e001849. Epub 2018 Jan 8.

From the Department of Pathology and Molecular Medicine (S.T., G.P.), Department of Biochemistry and Biomedical Sciences (R.L.), and Division of Cardiology, Department of Medicine (J.L.V., M.K.N.), Hamilton Health Sciences, McMaster University, Ontario; Population Health Research Institute, Hamilton, Ontario (S.T., M.C., G.P.); and Quebec Heart and Lung Institute Research Center, Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University, Canada (S.T.).

Background: Despite evidence of high heritability, monogenic disorders are identified in a minor fraction of individuals with early-onset coronary artery disease (EOCAD). We hypothesized that some individuals with EOCAD carry a high number of common genetic risk variants, with a combined effect similar to Mendelian forms of coronary artery disease, such as familial hypercholesterolemia.

Methods And Results: To confirm the polygenic contribution to EOCAD (age of ≤40 years for men and ≤45 years for women), we calculated in 111 418 British participants from the UK Biobank cohort a genetic risk score (GRS) based on the presence of 182 independent variants associated with coronary artery disease (GRS182). Read More

Curr Atheroscler Rep 2018 May 19;20(6):31. Epub 2018 May 19.

School of Medicine, Royal Perth Hospital, University of Western Australia, GPO Box X2213, Perth, WA, 6847, Australia.

Purpose Of Review: We summarize recent advances in the understanding of genetic testing in familial hypercholesterolemia (FH), the use of expanded FH next-generation sequencing panels, and directions for future research.

Recent Findings: The uptake of massively parallel sequencing in research and diagnostic laboratories has enabled expanded testing for FH and its phenocopies, with the added advantage that copy number variants can be detected. However, increasing the number of genes tested increases the number of variants detected, which may or may not be pathogenic. Read More

Lipids Health Dis 2018 May 2;17(1):100. Epub 2018 May 2.

Human Genetics Unit, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo, 00800, Sri Lanka.

Background: Hypercholesterolemia is a major determinant of cardiovascular disease-associated morbidity and mortality. Mutations in the LDL-receptor (LDLR) gene are implicated in the majority of the cases with familial hypercholesterolemia (FH). However, the spectrum of mutations in the LDLR gene in Sri Lankan patients has not been investigated. Read More

Clin Investig Arterioscler 2018 Jul - Aug;30(4):170-178. Epub 2018 Mar 27.

Unitat de Medicina Vascular i Metabolisme, Hospital Universitari Sant Joan, Unitat d'Investigació en Lípids i Arteriosclerosi, Universitat Rovira i Virgili, Institut d'Investigació Sanitària Pere Virgili (IISPV), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas (CIBERDEM), Reus, Tarragona, España.

Background: Familial hypercholesterolaemia (FH) in children is under-detected and is difficult to diagnose in clinical practice. The aim of this study was to evaluate clinical, biochemical and vascular imaging variables in order to detect children and adolescents with FH.

Methods: A total of 222 children aged 4-18 years old were recruited to participate in a project for the early detection of FH (The DECOPIN Project). Read More

Vnitr Lek 2018 ;64(1):25-29

Familial combined hyperlipidemia (FCH) is the most frequent genetic dyslipidemia (DLP) with high risk of early atherosclerosis manifestation. It is characterized by elevated both triglycerides 1.5 mmol/l and apolipoprotein B 1. Read More

Circulation 2018 Feb;137(8):820-831

Department of Pediatrics, Section Molecular Genetics, University Medical Center Groningen, University of Groningen, the Netherlands (J.-W.B., A.R., P.L., J.A.K.)

Background: Atherosclerosis starts in childhood but low-density lipoprotein cholesterol (LDL-C), a causal risk factor, is mostly studied and dealt with when clinical events have occurred. Women are usually affected later in life than men and are underdiagnosed, undertreated, and understudied in cardiovascular trials and research. This study aims at a better understanding of lifestyle and genetic factors that affect LDL-C in young women. Read More

Atherosclerosis 2018 03 31;270:117-122. Epub 2018 Jan 31.

Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Universitat Rovira i Virgili, IISPV, Reus, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.

Background And Aims: Familial hypercholesterolaemia (FH) is underdiagnosed in children. In addition to lipid concentrations, lipoprotein particle quantity and quality could influence cardiovascular risk. We aimed to perform a comprehensive plasma lipid study, including lipoprotein particle number and size assessment by two-dimensional nuclear magnetic resonance (2D-1H-NMR), in children with FH compared to non-affected children and to evaluate the clinical value of these factors as subclinical atherosclerosis biomarkers. Read More

Curr Opin Lipidol 2018 Apr;29(2):65-71

Purpose Of Review: We provide an overview of molecular diagnosis for familial hypercholesterolemia in France including descriptions of the mutational spectrum, polygenic susceptibility and perspectives for improvement in familial hypercholesterolemia diagnosis.

Recent Findings: Molecular testing for familial hypercholesterolemia is recommended for patients with a LDL-cholesterol level above 190 mg/dl (adults) associated with criteria related to personal and family history of hypercholesterolemia and premature cardiovascular disease. Among the 3381 index cases included with these characteristics in the French registry for familial hypercholesterolemia, 2054 underwent molecular diagnosis and 1150 (56%) were found to have mutations (93. Read More

Eur J Hum Genet 2018 04 26;26(4):570-578. Epub 2018 Jan 26.

LVTS, INSERM U1148, Paris, France.

Familial hypercholesterolemia (FH) is caused by mutations in LDLR (low-density lipoprotein receptor), APOB (apolipoprotein B), PCSK9 (proprotein convertase subtilisin/kexin type 9), or APOE (apolipoprotein E) genes in approximately 80% of the cases. Polygenic forms of hypercholesterolemia may be present among patients clinically diagnosed with FH but with no identified mutation (FH mutation-negative (FH/M-)). To address whether polygenic forms may explain phenocopies in FH families, we calculated a 6-single-nucleotide polymorphism (SNP) genetic risk score (GRS) in all members from five French FH families where a mutation was identified (FH/M+) as well as some phenocopies (FH/M-). Read More

J Nutr Biochem 2018 Mar 27;53:48-57. Epub 2017 Nov 27.

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

Primary hypercholesterolemia of genetic origin, negative for mutations in LDLR, APOB, PCSK9 and APOE genes (non-FH GH), and familial combined hyperlipidemia (FCHL) are polygenic genetic diseases that occur with hypercholesterolemia, and both share a very high cardiovascular risk. In order to better characterize the metabolic abnormalities associated with these primary hypercholesterolemias, we used noncholesterol sterols, as markers of cholesterol metabolism, to determine their potential differences. Hepatic cholesterol synthesis markers (desmosterol and lanosterol) and intestinal cholesterol absorption markers (sitosterol and campesterol) were determined in non-FH GH (n=200), FCHL (n=100) and genetically defined heterozygous familial hypercholesterolemia subjects (FH) (n=100) and in normolipidemic controls (n=100). Read More

Proteomics Clin Appl 2018 01 11;12(1). Epub 2017 Dec 11.

Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center at the Heinrich-Heine-University Duesseldorf, Leibniz Center for Diabetes Research, Duesseldorf, Germany.

Purpose: Metabolic syndrome (MetS) consists of five risk factors: elevated blood pressure and fasting glucose, visceral obesity, dyslipidemia, and hypercholesterinemia. The physiological impact of lipid metabolism indicated as visceral obesity and hepatic lipid accumulation on MetS is still under debate. One major cause of disturbed lipid metabolism might be dysfunction of cellular organelles controlling energy homeostasis, i. 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 Am Coll Cardiol 2017 Oct;70(14):1732-1740

Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain; CIBER in Cardiovascular Diseases (CIBERCV), Madrid, Spain; Faculty of Health Sciences, University Francisco de Vitoria (UFV), Pozuelo de Alarcon, Madrid, Spain. Electronic address:

Background: Genetic screening programs in unselected individuals with increased levels of low-density lipoprotein cholesterol (LDL-C) have shown modest results in identifying individuals with familial hypercholesterolemia (FH).

Objectives: This study assessed the prevalence of genetically confirmed FH in patients with acute coronary syndrome (ACS) and compared the diagnostic performance of FH clinical criteria versus FH genetic testing.

Methods: Genetic study of 7 genes (LDLR, APOB, PCSK9, APOE, STAP1, LDLRAP1, and LIPA) associated with FH and 12 common alleles associated with polygenic hypercholesterolemia was performed in 103 patients with ACS, age ≤65 years, and LDL-C levels ≥160 mg/dl. Read More

Rev Esp Cardiol (Engl Ed) 2018 May 14;71(5):351-356. Epub 2017 Sep 14.

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.

Introduction And Objectives: Approximately 20% to 40% of clinically defined familial hypercholesterolemia cases do not show a causative mutation in candidate genes, and some of them may have a polygenic origin. A cholesterol gene risk score for the diagnosis of polygenic hypercholesterolemia has been demonstrated to be valuable to differentiate polygenic and monogenic hypercholesterolemia. The aim of this study was to determine the contribution to low-density lipoprotein cholesterol (LDL-C) of the single nucleotide variants associated with polygenic hypercholesterolemia in probands with genetic hypercholesterolemia without mutations in candidate genes (nonfamilial hypercholesterolemia genetic hypercholesterolemia) and the genetic score in cascade screening in their family members. Read More

Adv Ther 2017 08 7;34(8):1966-1975. Epub 2017 Jul 7.

Department of Medicine and Surgery Sciences, University of Bologna, Bologna, Italy.

Introduction: There is a growing interest in nutraceuticals improving cardiovascular risk factor levels and related organ damage.

Methods: This double-blind, placebo-controlled randomized clinical trial aims to compare the effect of a combined nutraceutical containing red yeast rice (10 mg), phytosterols (800 mg), and L-tyrosol (5 mg) on lipid profile, blood pressure, endothelial function, and arterial stiffness in a group of 60 patients with polygenic hypercholesterolemia resistant to Mediterranean diet.

Results: After 8 weeks of treatment, when compared to the placebo group, the active treated patients experienced a more favorable percentage change in total cholesterol (-16. Read More

J Physiol Anthropol 2017 Jun 14;36(1):25. Epub 2017 Jun 14.

Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman (UTAR) Kampar Campus, Jalan Universiti, Bandar Barat, 31900, Kampar, Perak, Malaysia.

Background: Despite the fact that insertions/deletions (INDELs) are the second most common type of genetic variations and variable number tandem repeats (VNTRs) represent a large portion of the human genome, they have received far less attention than single nucleotide polymorphisms (SNPs) and larger forms of structural variation like copy number variations (CNVs), especially in genome-wide association studies (GWAS) of complex diseases like polygenic obesity. This is exemplified by the vast amount of review papers on the role of SNPs and CNVs in obesity, its related traits (like anthropometric measurements, biochemical variables, and eating behavior), and its related complications (like hypertension, hypertriglyceridemia, hypercholesterolemia, and insulin resistance-collectively known as metabolic syndrome). Hence, this paper reviews the types of INDELs and VNTRs that have been studied for association with obesity and its related traits and complications. Read More

Lipids Health Dis 2017 Jun 2;16(1):103. Epub 2017 Jun 2.

Human Genetics Unit, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo, 00800, Sri Lanka.

Hypercholesterolemia is a strong determinant of mortality and morbidity associated with cardiovascular diseases and a major contributor to the global disease burden. Mutations in four genes (LDLR, APOB, PCSK9 and LDLRAP1) account for the majority of cases with familial hypercholesterolemia. However, a substantial proportion of adults with hypercholesterolemia do not have a mutation in any of these four genes. Read More

Ann Cardiol Angeiol (Paris) 2018 Feb 31;67(1):1-8. Epub 2017 May 31.

Hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France. Electronic address:

Background: Familial hypercholesterolemia is a monogenic autosomal dominant dyslipidemia characterized by a permanent and isolated increase of cholesterol carried by low-density lipoproteins. The prevalence of its heterozygous form is estimated between 1/500 and 1/250, and in the absence of specific treatment, this form is responsible for an increase by a factor of 13 of the risk of premature coronary artery disease compared to patients non-affected by the disease.

Objectives: To perform an inventory of the knowledge of heterozygous familial hypercholesterolemia in France for physicians involved in the management of the disease. Read More

Atherosclerosis 2017 08 13;263:405-411. Epub 2017 May 13.

Centre for Cardiovascular Genetics, University College London, The Rayne Institute, University Street, London, WC1E 6JF, UK. Electronic address:

Background And Aims: Familial hypercholesterolemia (FH) is a common inherited disorder of low density lipoprotein-cholesterol (LDL-C) metabolism. It is associated with higher risk of premature coronary heart disease. Around 60% of patients with a clinical diagnosis of FH do not have a detectable mutation in the genes causing FH and are most likely to have a polygenic cause for their raised LDL-C. Read More

Herz 2017 Aug;42(5):440-448

Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität München, Lazarettstr. 36, 80636, München, Deutschland.

Genetic testing plays an increasing role in cardiovascular medicine. Advances in technology and the development of novel and more affordable (high throughput) methods have led to the identification of genetic risk factors in research and clinical practice. Also, this progress has simplified the screening of patients and individuals at risk. Read More

J Clin Lipidol 2017 Jul - Aug;11(4):880-890. Epub 2017 May 19.

NYU School of Medicine & NYU Center for Prevention of Cardiovascular Disease, New York, NY, USA.

An Expert Panel convened by the National Lipid Association was charged with updating the recommendations on the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody therapy that were provided by the 2015 National Lipid Association Recommendations for the Patient-Centered Management of Dyslipidemia: Part 2. Recent studies have demonstrated the efficacy of these agents in reducing low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol and have confirmed their excellent safety profile. A cardiovascular outcomes study has shown that these agents reduce incident atherosclerotic cardiovascular disease (ASCVD) events in patents with stable ASCVD and concomitant risk factors. Read More

Expert Rev Mol Diagn 2017 07 29;17(7):641-651. Epub 2017 May 29.

a Departments of Medicine and Biochemistry, Schulich School of Medicine and Dentistry , Western University , London , Canada.

Introduction: Familial hypercholesterolemia (FH) is a common genetic cause of premature coronary heart disease that is widely underdiagnosed and undertreated. To improve the identification of FH and initiate timely and appropriate treatment strategies, genetic testing is becoming increasingly offered worldwide as a central part of diagnosis. Areas covered: Recent advances have been propelled by an improved understanding of the genetic determinants of FH together with substantially reduced costs of appropriate screening strategies. Read More

Curr Opin Lipidol 2017 Aug;28(4):313-320

aMolecular Diagnostics, Randox Laboratories Ltd., Crumlin bRegional Genetics Centre, Belfast City Hospital, Belfast Health and Social Care Trust, Belfast, UK.

Purpose Of Review: Familial hypercholesterolaemia is a hereditary disorder of lipoprotein metabolism which causes a lifelong increase in LDL-C levels resulting in premature coronary heart disease. The present review looks at some of the recent literature on how molecular methods can be used to assist in the definitive diagnosis of familial hypercholesterolaemia in a range of patient groups.

Recent Findings: Several recent studies have shown that the prevalence of clinical familial hypercholesterolaemia is higher than previously thought at 1/200 to 1/300, and that 2-5% of patients presenting with early myocardial infarction can be found to have a familial hypercholesterolaemia mutation. Read More

J Clin Lipidol 2017 May - Jun;11(3):725-732.e5. Epub 2017 Apr 6.

Nutrition, Metabolism and Atherosclerosis Clinic, Institut de recherches cliniques de Montréal, Québec, Canada; Division of Experimental Medicine, Department of Medicine, McGill University, Québec, Canada; Division of Medical Biochemistry, Department of Medicine, McGill University, Québec, Canada. Electronic address:

Background: Although familial hypercholesterolemia (FH) is a severe monogenic disease, it has been shown that clinical risk factors and common genetic variants can modify cardiovascular disease (CVD) risk.

Objective: The aim of the study was to evaluate the polygenic contribution to lipid traits and CVD in FH using genetic risk scores (GRSs).

Methods: Among the 20,434 subjects attending the lipid clinic, we identified and included 725 individuals who carried an FH causing mutation in this retrospective cohort study. Read More

Curr Cardiol Rep 2017 05;19(5):44

Institute of Cardiovascular Science, University College London, 5 University St, London, WC1E 6JF, UK.

Purpose Of Review: Familial hypercholesterolaemia (FH) is an inherited disorder of low-density lipoprotein cholesterol (LDL-C) which is characterised by a raised cholesterol level from birth and a high risk of premature coronary heart disease. In this paper, we review the genetic basis of FH and its impact on the clinical presentation.

Recent Findings: Mutations in any of three genes (LDLR, APOB and PCSK9) are known to cause autosomal dominant FH, but a mutation can be found in only ∼40% of patients with a clinical diagnosis of FH. Read More

Physiol Res 2017 Apr;66(Supplementum 1):S101-S111

Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Since 2007, the year of their first widespread use, genome-wide association studies (GWAS) have become the "gold standard" for the detection of causal genes and polymorphisms in all fields of human medicine. Cardiovascular disease (CVD), one of the major causes of morbidity and mortality, is no exception. The first GWAS focused on hypercholesterolemia and dyslipidemia as the major CVD determinants. 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

Cardiovasc Pathol 2017 Mar - Apr;27:71-75. Epub 2017 Jan 29.

Department of Cardiovascular Sciences and the NIHR Leicester Cardiovascular Biomedical Research Unit, University of Leicester, Leicester, UK.

Atherosclerosis and abdominal aortic aneurysms (AAAs) are multifactorial and polygenic diseases with known environmental and genetic risk factors that contribute toward disease development. Atherosclerosis represents an important independent risk factor for AAA, as people with AAA often have atherosclerosis. Studies have shown that comorbidity is usually between ~25% and 55%, but it is still not fully known whether this association is causal or a result of common shared risk profiles. Read More

J Pediatr 2017 04 1;183:100-107.e3. Epub 2017 Feb 1.

Department of Internal Medicine and Allied Sciences, Sapienza University of Rome, Rome, Italy. Electronic address:

Objective: To evaluate the effectiveness of criteria based on child-parent assessment in predicting familial hypercholesterolemia (FH)-causative mutations in unselected children with hypercholesterolemia.

Study Design: LDLR, APOB, and PCSK9 genes were sequenced in 78 children and adolescents (mean age 8.4 ± 3. Read More

Vnitr Lek Fall 2016;62(11):882-886

Hyperlipoproteinemia (HLP) is one of the most common metabolic disorder in childhood. We assume that 20 % of children have a disorder of the lipid metabolism. Some HLP are very common in the population, and moderate, and some are very rare, but are very severe. Read More

Atherosclerosis 2017 02 18;257:55-63. Epub 2016 Dec 18.

Center for Research Prevention and Treatment of Atherosclerosis, Department of Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel.

Background And Aims: Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the genes for LDL receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type9 (PCSK9). The purpose of the current investigation was to define the current spectrum of mutations causing FH in Israel.

Methods: New families were collected through the MEDPED (Make Early Diagnosis Prevent Early Death) FH program. Read More

JIMD Rep 2017 9;35:67-70. Epub 2016 Dec 9.

Robarts Research Institute and Department of Medicine, Schulich School of Medicine, Western University, London, ON, Canada, N6A 5B7.

Familial hypercholesterolemia (FH) is an autosomal codominantly inherited disease. The severity of clinical presentation depends on the zygosity of the mutations in the LDLR, APOB, or PCSK9 genes. The homozygous form (HoFH) is associated with high mortality rate by third decade of life, while individuals with HeFH begin to suffer from premature cardiovascular disease in fourth or fifth decade of life. 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

Arterioscler Thromb Vasc Biol 2016 12 20;36(12):2439-2445. Epub 2016 Oct 20.

From the Robarts Research Institute (J.W., J.S.D., M.R.B., J.F.R., A.D.M., A.A.D., H.C., M.W.H., R.A.H.), Department of Biochemistry (J.S.D., M.A., A.A.D., M.W.H., R.A.H.), and Department of Medicine (P.J.Z., M.W.H., R.A.H.), Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada; Faculté de Médicine, Université de Montréal, Québec, Canada (M.-P.D., G.L., J.-C.T.); and Montréal Heart institute, Québec, Canada (D.R., C.L.-K., M.-P.D., G.L., J.-C.T.).

Objective: Next-generation sequencing technology is transforming our understanding of heterozygous familial hypercholesterolemia, including revision of prevalence estimates and attribution of polygenic effects. Here, we examined the contributions of monogenic and polygenic factors in patients with severe hypercholesterolemia referred to a specialty clinic.

Approach And Results: We applied targeted next-generation sequencing with custom annotation, coupled with evaluation of large-scale copy number variation and polygenic scores for raised low-density lipoprotein cholesterol in a cohort of 313 individuals with severe hypercholesterolemia, defined as low-density lipoprotein cholesterol >5. Read More

Crit Rev Clin Lab Sci 2017 01 1;54(1):26-48. Epub 2016 Oct 1.

b Department of Cell Biology , State University of New York Downstate Medical Center , Brooklyn , NY , USA.

Homozygous familial hypercholesterolemia (HoFH) is a polygenic disease arising from defects in the clearance of plasma low-density lipoprotein (LDL), which results in extremely elevated plasma LDL cholesterol (LDL-C) and increased risk of atherosclerosis, coronary heart disease, and premature death. Conventional lipid-lowering therapies, such as statins and ezetimibe, are ineffective at lowering plasma cholesterol to safe levels in these patients. Other therapeutic options, such as LDL apheresis and liver transplantation, are inconvenient, costly, and not readily available. Read More

Med J Aust 2016 Sep;205(5):232-6

University of Western Australia, Perth, WA.

Familial hypercholesterolaemia (FH) is the most common autosomal dominant condition, with a prevalence of between one in 200 and one in 350 people in the general population. Untreated FH is associated with premature atherosclerotic cardiovascular disease (CVD). The prevalence of homozygous or compound heterozygous FH is now considered to be about one in 300 000 people. Read More