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Nutrients 2022 May 18;14(10). Epub 2022 May 18.

Hypertension and Cardiovascular Risk Research Center, Medical and Surgical Sciences Department, Sant'Orsola-Malpighi University Hospital, 40138 Bologna, Italy.

We aimed to evaluate if dietary supplementation with a nutraceutical compound (Eufortyn Colesterolo Plus) containing standardized bergamot polyphenolic fraction phytosome (Vazguard), artichoke extract (Pycrinil), artichoke dry extract. ( L.), Q10 phytosome(Ubiqosome) and zinc, could positively affect serum lipids concentration, systemic inflammation and indexes of non-alcoholic fatty liver disease (NAFLD) in 60 healthy subjects with polygenic hypercholesterolemia. Read More

Int J Mol Sci 2022 May 21;23(10). Epub 2022 May 21.

Laboratory for Vascular Translational Science (LVTS), Paris Cité University and Sorbonne Paris Nord University, INSERM, F-75018 Paris, France.

Primary hypercholesterolemia is characterized by elevated LDL-cholesterol (LDL-C) levels isolated in autosomal dominant hypercholesterolemia (ADH) or associated with elevated triglyceride levels in familial combined hyperlipidemia (FCHL). Rare variants are known in ADH and FCHL. We explored the molecular spectrum in a French ADH/FCHL cohort of 5743 unrelated probands. Read More

Cell Rep Methods 2022 Feb 8;2(2):100166. Epub 2022 Feb 8.

Department of Anatomy, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland.

Systematic insight into cellular dysfunction can improve understanding of disease etiology, risk assessment, and patient stratification. We present a multiparametric high-content imaging platform enabling quantification of low-density lipoprotein (LDL) uptake and lipid storage in cytoplasmic droplets of primary leukocyte subpopulations. We validate this platform with samples from 65 individuals with variable blood LDL-cholesterol (LDL-c) levels, including familial hypercholesterolemia (FH) and non-FH subjects. Read More

Front Genet 2022 31;13:845498. Epub 2022 Mar 31.

Institute of Cardiovascular Science, Faculty of Population Health, University College London, London, United Kingdom.

: Monogenic familial hypercholesterolaemia (FH) is an autosomal dominant disorder characterised by elevated low-density lipoprotein cholesterol (LDL-C) concentrations due to monogenic mutations in , , , and . Some mutation-negative patients have a polygenic cause for elevated LDL-C due to a burden of common LDL-C-raising alleles, as demonstrated in people of White British (WB) ancestry using a 12-single nucleotide polymorphism (SNP) score. This score has yet to be evaluated in people of South Asian (SA), and Black and Caribbean (BC) ethnicities. Read More

Nutrients 2022 Mar 23;14(7). Epub 2022 Mar 23.

Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy.

Background: Diet is considered the cornerstone of lipid management in hyperlipidemic children but evidence to demonstrate the effects of nutrient benefits on the lipid profile is limited.

Aim: The aim of this study is to evaluate the impact of the Mediterranean diet on low-density lipoprotein (LDL-C) and non-high density lipoprotein (HDL-C) decrease in primary hyperlipidemia affected children and in the achievement of therapeutical target levels.

Methods: A retrospective cohort study was used, recruiting = 223 children (10. Read More

Curr Atheroscler Rep 2022 Jun 7;24(6):419-426. Epub 2022 Apr 7.

Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street, London, ON, N6A 5B7, Canada.

Purpose Of Review: Common DNA variants with small effects work together to create susceptibility to polygenic hypercholesterolemia. Some clinicians wonder whether patients with polygenic hypercholesterolemia have less severe clinical features compared to patients with monogenic familial hypercholesterolemia (FH) caused by rare deleterious variants.

Recent Findings: Studies performed in cohorts of patients with both monogenic and polygenic hypercholesterolemia have assessed lipid levels, non-invasive markers of atherosclerosis, and clinical end points, including major adverse cardiovascular events. Read More

Metabolites 2022 Mar 18;12(3). Epub 2022 Mar 18.

INSERM, Laboratory for Vascular Translational Science (LVTS), F-75018 Paris, France.

Autosomal Dominant Hypercholesterolemia (ADH) is a genetic disorder caused by pathogenic variants in , , and genes. We sought to identify new candidate genes responsible for the ADH phenotype in patients without pathogenic variants in the known ADH-causing genes by focusing on a French family with affected and non-affected members who presented a high ADH polygenic risk score (wPRS). Linkage analysis, whole exome and whole genome sequencing resulted in the identification of variants p. Read More

J Am Heart Assoc 2022 04 24;11(7):e023668. Epub 2022 Mar 24.

Epidemiology and Preventive Pharmacology Service (SEFAP) Department of Pharmacological and Biomolecular Sciences University of Milan Italy.

Background A significant proportion of individuals clinically diagnosed with familial hypercholesterolemia (FH), but without any disease-causing mutation, are likely to have polygenic hypercholesterolemia. We evaluated the distribution of a polygenic risk score, consisting of 12 low-density lipoprotein cholesterol (LDL-C)-raising variants (polygenic LDL-C risk score), in subjects with a clinical diagnosis of FH. Methods and Results Within the Lipid Transport Disorders Italian Genetic Network (LIPIGEN) study, 875 patients who were FH-mutation positive (women, 54. Read More

Eur Heart J Suppl 2021 Oct 8;23(Suppl E):E33-E35. Epub 2021 Oct 8.

CEO Allelica Ink, Rome, Italy.

Although coronary heart disease is a highly preventable disease, it is still the leading cause of morbidity and mortality in developed countries. This is also due to the fact that the risk models used in clinical practice have proved ineffective in identifying people at risk: up to 30% of cases of myocardial infarction do not have traditional risk factors used in risk estimation models. Although the genetic component of myocardial infarction has been known for many years, with an inheritance rate of between 40% and 60%, it is not yet used as a risk factor in primary prevention models such as the Heart Card or the European SCORE. Read More

J Am Coll Cardiol 2022 03;79(8):819-836

University of Texas Southwestern Medical Center, Dallas, Texas, USA.

There is a need to identify high-risk features that predict early-onset atherosclerotic cardiovascular disease (ASCVD). The authors provide insights to help clinicians identify and address high-risk conditions in the 20- to 39-year age range (young adults). These include tobacco use, elevated blood pressure/hypertension, family history of premature ASCVD, primary severe hypercholesterolemia such as familial hypercholesterolemia, diabetes with diabetes-specific risk-enhancing factors, or the presence of multiple other risk-enhancing factors, including in females, a history of pre-eclampsia or menopause under age 40. Read More

Eur J Public Health 2022 Jun;32(3):422-428

Department of Cardiology, Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.

Background: Heterozygous familial hypercholesterolemia (FH) represents the most frequent monogenic disorder with an estimated prevalence of 1:250 in the general population. Diagnosis during childhood enables early initiation of preventive measures, reducing the risk of severe consecutive atherosclerotic manifestations. Nevertheless, population-based screening programs for FH are scarce. Read More

Clin Chim Acta 2022 Feb 6;527:47-55. Epub 2022 Jan 6.

Department of Cardiology, Government Medical College, Trivandrum, Kerala, India. Electronic address:

Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder with elevated LDL-C levels which can ultimately lead to premature Coronary Artery Disease (CAD).

Objectives: In presence of limited genetic data on FH in India, the present study was aimed to determine the mutation spectrum in Indian FH patients using a targeted exome sequencing.

Methods: 54 FH cases (31 index cases + 23 extended family members) were categorized according to Dutch Lipid Clinic Network Criteria (DLCNC). Read More

Atherosclerosis 2022 01 6;340:35-43. Epub 2021 Dec 6.

Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada; Experimental Medicine Program, University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Background And Aims: Familial combined hyperlipidemia (FCHL) is one of the most common inherited lipid phenotypes, characterized by elevated plasma concentrations of apolipoprotein B-100 and triglycerides. The genetic inheritance of FCHL remains poorly understood. The goals of this study were to investigate the polygenetic architecture and cardiovascular risk associated with FCHL. Read More

Atherosclerosis 2022 01 5;340:46-47. Epub 2021 Dec 5.

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

J Clin Endocrinol Metab 2022 04;107(5):1216-1224

Pharmacology Department, School of Medicine, FASTA University, Mar del Plata, Buenos Aires, Argentina.

Primary hyperlipidemias include a heterogeneous set of monogenic and polygenic conditions characterized by a strong family aggregation, severe forms of hypercholesterolemia and/or hypertriglyceridemia, appearance early on life, and a high risk of cardiovascular events and/or recurrent pancreatitis. In real life, a small proportion of the primary hyperlipidemia cases is recognized and treated properly. Our goal is to present an update of current and upcoming therapies for patients with primary hyperlipidemia. Read More

Eur J Prev Cardiol 2022 05;29(6):925-937

Nuffield Department of Population Health, University of Oxford Big Data Institute, Old Road Campus, Headington, Oxford, OX3 7LF, UK.

Aims: Many studies have investigated associations between polygenic risk scores (PRS) and the incidence of cardiovascular disease (CVD); few have examined whether risk factor-related PRS predict CVD outcomes among adults treated with risk-modifying therapies. We assessed whether PRS for systolic blood pressure (PRSSBP) and for low-density lipoprotein cholesterol (PRSLDL-C) were associated with achieving SBP and LDL-C-related targets, and with major adverse cardiovascular events (MACE: non-fatal stroke or myocardial infarction, CVD death, and revascularization procedures).

Methods And Results: Using observational data from the UK Biobank (UKB), we calculated PRSSBP and PRSLDL-C and constructed two sub-cohorts of unrelated adults of White British ancestry aged 40-69 years and with no history of CVD, who reported taking medications used in the treatment of hypertension or hypercholesterolaemia. Read More

Biomedicines 2021 Nov 19;9(11). Epub 2021 Nov 19.

Stroke Pharmacogenomics and Genetics Group, Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau (IR-HSCSP)-Biomedical Research Institute Sant Pau (IIB-Sant Pau), C/Sant Quintí 77-79, 08041 Barcelona, Spain.

Changes in plasma low-density lipoprotein cholesterol (LDL-c) levels relate to a high risk of developing some common and complex diseases. LDL-c, as a quantitative trait, is multifactorial and depends on both genetic and environmental factors. In the pregenomic age, targeted genes were used to detect genetic factors in both hyper- and hypolipidemias, but this approach only explained extreme cases in the population distribution. Read More

Genes (Basel) 2021 11 17;12(11). Epub 2021 Nov 17.

Department of Psychiatry, McGill University, Montreal, QC H3A 0G4, Canada.

Midlife hypercholesterolemia is a well-known risk factor for sporadic Alzheimer's disease (AD), and like AD, it is highly influenced by genetics with heritability estimates of 32-63%. We thus hypothesized that genetics underlying peripheral blood total cholesterol (TC) levels could influence the risk of developing AD. We created a weighted polygenic score (TC-PGS) using summary data from a meta-analysis of TC genome-wide association studies for evaluation in three independent AD-related cohorts spanning pre-clinical, clinical, and pathophysiologically proved AD. Read More

Methodist Debakey Cardiovasc J 2021 24;17(4):28-35. Epub 2021 Sep 24.

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

Familial hypercholesterolemia (FH) is a monogenic form of severe hypercholesterolemia that, if left untreated, is associated with early onset of atherosclerosis. FH derives from genetic variants that lead to inefficient hepatic clearance of low-density lipoprotein (LDL) particles from the circulation. The FH phenotype is encountered in approximately 1 of every 300 people. Read More

Atherosclerosis 2022 01 2;340:61-67. Epub 2021 Nov 2.

Department of Clinical Genetics, Amsterdam UMC Location AMC, Meibergdreef 9, 1105, AZ, Amsterdam, the Netherlands. Electronic address:

Background And Aims: Low-density lipoprotein cholesterol (LDL-C) levels vary in patients with familial hypercholesterolemia (FH) and can be explained by a single deleterious genetic variant or by the aggregate effect of multiple, common small-effect variants that can be captured in a polygenic score (PS). We set out to investigate the contribution of a previously published PS to the inter-individual LDL-C variation and coronary artery disease (CAD) risk in patients with a clinical FH phenotype.

Methods: First, in a cohort of 628 patients referred for genetic FH testing, we evaluated the distribution of a PS for LDL-C comprising 12 genetic variants. Read More

Curr Opin Lipidol 2021 12;32(6):392-395

Unidade de I&D, Grupo de Investigação Cardiovascular, Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge.

Purpose Of Review: The present review summarizes different polygenic risk scores associated with hypercholesterolemia applied to cohorts with a genetic diagnosis of familial hypercholesterolemia (FH).

Recent Findings: Several single-nucleotide polymorphisms associated with increased levels of LDL-C or Lp(a) have been genotyped in population cohorts with FH phenotype, to identify the cause of hypercholesterolemia in mutation negative individuals. In different studies, a large proportion of individuals without a monogenic causative variant (in low density lipoprotein receptor gene (LDLR), apolipoprotein B gene (APOB) or proprotein convertase subtilisin/kexin type 9 gene (PCSK9 genes) was considered to have a hypercholesterolemia with a polygenic basis. Read More

Curr Opin Lipidol 2022 04;33(2):126-132

Robarts Research Institute.

Purpose Of Review: : Familial combined hyperlipidemia (FCH), defined by concurrently elevated plasma triglyceride (TG) and low-density lipoprotein (LDL) cholesterol, has long been investigated to characterize its genetic basis. Despite almost half a century of searching, a single gene cause for the phenotype has not yet been identified.

Recent Findings: : Recent studies using next-generation genetic analytic methods confirm that FCH has a polygenic basis, with a clear large contribution from the accumulation of small-to-moderate effect common single nucleotide polymorphisms (SNPs) throughout the genome that is associated with raising TG, and probably also those raising LDL cholesterol. Read More

Endocr Rev 2021 Oct 22. Epub 2021 Oct 22.

Department of Medicine; Schulich School of Medicine and Dentistry, Western University, 1151 Richmond St, London, ON, Canada.

Lipid disorders involving derangements in serum cholesterol, triglycerides or both are commonly encountered in clinical practice and often have implications for cardiovascular risk and overall health. Recent advances in knowledge, recommendations and treatment options have necessitated an updated approach to these disorders. Older classification schemes have outlived their usefulness yielding to an approach based on the primary lipid disturbance identified on a routine lipid panel as a practical starting point. Read More

J Lipid Res 2021 16;62:100139. Epub 2021 Oct 16.

Institute of Cardiovascular Science, University College London, London, United Kingdom. Electronic address:

In the early 1980s, the Nobel Prize winning cellular and molecular work of Mike Brown and Joe Goldstein led to the identification of the LDL receptor gene as the first gene where mutations cause the familial hypercholesterolemia (FH) phenotype. We now know that autosomal dominant monogenic FH can be caused by pathogenic variants of three additional genes (APOB/PCSK9/APOE) and that the plasma LDL-C concentration and risk of premature coronary heart disease differs according to the specific locus and associated molecular cause. It is now possible to use next-generation sequencing to sequence all exons of all four genes, processing 96 patient samples in one sequencing run, increasing the speed of test results, and reducing costs. Read More

Heart 2021 12 14;107(24):1956-1961. Epub 2021 Sep 14.

Centre for Academic Primary Care, School of Medicine, University of Nottingham, Nottingham, UK.

Objective: Familial hypercholesterolaemia (FH) is a common inherited disorder that remains mostly undetected in the general population. Through FH case-finding and direct access to genetic testing in primary care, this intervention study described the genetic and lipid profile of patients found at increased risk of FH and the outcomes in those with positive genetic test results.

Methods: In 14 Central England general practices, a novel case-finding tool (Familial Hypercholetserolaemia Case Ascertainment Tool, FAMCAT1) was applied to the electronic health records of 86 219 patients with cholesterol readings (44. Read More

Atherosclerosis 2022 05 23;349:211-218. Epub 2021 Aug 23.

Hospital Universitario Miguel Servet, IIS Aragón, CIBERCV, Zaragoza, Spain; Department of Medicine, Psychiatry and Dermatology, Universidad de Zaragoza, Zaragoza, Spain. Electronic address:

Background And Aims: Lipoprotein(a) [Lp(a)] concentration in heterozygous familial hypercholesterolemia (heFH) is not well established. Whether the genetic defect responsible for heFH plays a role in Lp(a) concentration is unknown. We aimed to compare Lp(a) in controls from a healthy population, in genetically diagnosed heFH and mutation-negative hypercholesterolemia subjects, and to assess the influence on Lp(a) of the genetic defect responsible for heFH. Read More

Genes (Basel) 2021 07 29;12(8). Epub 2021 Jul 29.

Department of Paediatrics, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands.

The genetic screening program for familial hypercholesterolemia (FH) in the Netherlands, which was embraced by the Dutch Ministry of Health from 1994 to 2014, has led to twenty years of identification of at least 1500 FH cases per year. Although funding by the government was terminated in 2014, the approach had proven its effectiveness and had built the foundation for the development of more sophisticated diagnostic tools, clinical collaborations, and new molecular-based treatments for FH patients. As such, the community was driven to continue the program, insurance companies were convinced to collaborate, and multiple approaches were launched to find new index cases with FH. Read More

Arterioscler Thromb Vasc Biol 2021 10 19;41(10):2616-2628. Epub 2021 Aug 19.

deCODE genetics/Amgen, Inc, Reykjavík, Iceland (E.B., G. Thorgeirsson, A.H., G. Thorleifsson, G.S., S.K., H.J., Aðalbjörg Jónasdóttir, Áslaug Jónasdóttir, A.S., S.G., V.S., B.V.H., D.O.A., I.J., D.F.G., H.H., U.T., P.S., K.S.).

Objective: Familial hypercholesterolemia (FH) is traditionally defined as a monogenic disease characterized by severely elevated LDL-C (low-density lipoprotein cholesterol) levels. In practice, FH is commonly a clinical diagnosis without confirmation of a causative mutation. In this study, we sought to characterize and compare monogenic and clinically defined FH in a large sample of Icelanders. Read More

Vasc Health Risk Manag 2021 21;17:415-419. Epub 2021 Jul 21.

Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.

The "Lebanese allele" { c.2043 C>A (p.cys681X)} is a nonsense mutation in the low-density lipoprotein receptor () gene that results in a truncated non-functioning LDLR protein. Read More

Expert Rev Mol Diagn 2021 09 21;21(9):887-895. Epub 2021 Jul 21.

Department of Vascular Medicine, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands.

: Familial hypercholesterolemia (FH) is a highly prevalent condition, predisposing individuals to premature cardiovascular disease and with a genetic basis more complex than initially thought. Advances in molecular technologies have provided novel insights into the role of next-generation-sequencing, the assessment and classification of newly found variants, the complex genotype-phenotype correlation, and the position of FH in the context of other dyslipidaemias.: Understanding the scope of genetic determinants of FH has expanded substantially. Read More