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Coronary Artery Disease: HELP
Articles by Daniel Gaudet
Based on 12 articles published since 2010
(Why 12 articles?)
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Between 2010 and 2020, Daniel Gaudet wrote the following 12 articles about Coronary Artery Disease.
 
+ Citations + Abstracts
1 Guideline Canadian Cardiovascular Society Position Statement on Familial Hypercholesterolemia: Update 2018. 2018

Brunham, Liam R / Ruel, Isabelle / Aljenedil, Sumayah / Rivière, Jean-Baptiste / Baass, Alexis / Tu, Jack V / Mancini, G B John / Raggi, Paolo / Gupta, Milan / Couture, Patrick / Pearson, Glen J / Bergeron, Jean / Francis, Gordon A / McCrindle, Brian W / Morrison, Katherine / St-Pierre, Julie / Henderson, Mélanie / Hegele, Robert A / Genest, Jacques / Goguen, Jeannette / Gaudet, Daniel / Paré, Guillaume / Romney, Jacques / Ransom, Thomas / Bernard, Sophie / Katz, Pamela / Joy, Tisha R / Bewick, David / Brophy, James. ·Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Heart Lung Innovation, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: Liam.brunham@ubc.ca. · Research Institute of the McGill University Health Centre, Royal Victoria Hospital, Montréal, Quebec, Canada. · Department of Medicine, McGill University, Montréal, Quebec, Canada; Nutrition, Metabolism and Atherosclerosis Clinic, Institut de recherches cliniques de Montréal, Montréal, Quebec, Canada. · Faculty of Medicine, University of Toronto, Institute for Clinical Evaluative Sciences, Schulich Heart Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. · Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. · Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada. · Department of Medicine, McMaster University, Hamilton, and Canadian Collaborative Research Network, Brampton, Ontario, Canada. · Departments of Medicine and Laboratory Medicine, CHU de Québec-Université Laval, Québec City, Quebec, Canada. · Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Heart Lung Innovation, University of British Columbia, Vancouver, British Columbia, Canada. · Department of Pediatrics, The Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. · Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada. · Department of Pediatrics, McGill University, Clinique 180, Montréal, Quebec, Canada. · Department of Pediatrics, Université de Montréal, CHU Sainte-Justine, Montréal, Quebec, Canada. · Departments of Medicine and Biochemistry, Schulich School of Medicine and Robarts Research Institute, Western University, London, Ontario, Canada. · Research Institute of the McGill University Health Centre, Royal Victoria Hospital, Montréal, Quebec, Canada; Department of Medicine, McGill University, Montréal, Quebec, Canada. · Department of Medicine, University of Toronto and Division of Endocrinology, St Michael's Hospital, Toronto Ontario, Canada. · Lipidology Unit, Community Genomic Medicine Centre and ECOGENE-21, Department of Medicine, Université de Montréal, Saguenay, Quebec, Canada. · Department of Pathology and Molecular Medicine, Department of Clinical Epidemiology and Biostatistics, Population Health Research Institute and Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada. · Division of Endocrinology and Metabolism, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. · Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, Nova Scotia, Canada. · Nutrition, Metabolism and Atherosclerosis Clinic, Institut de recherches cliniques de Montréal, Montréal, Quebec, Canada; Department of Medicine, Division of Endocrinology, Université de Montreal, Montréal, Quebec, Canada. · Department of Medicine, Section of Endocrinology and Metabolism, University of Manitoba, St Boniface Hospital, Winnipeg, Manitoba, Canada. · Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. · Division of Cardiology, Department of Medicine, Dalhousie University, St John, New Brunswick, Canada. ·Can J Cardiol · Pubmed #30527143.

ABSTRACT: Familial hypercholesterolemia (FH) is the most common monogenic disorder causing premature atherosclerotic cardiovascular disease. It affects 1 in 250 individuals worldwide, and of the approximately 145,000 Canadians estimated to have FH, most are undiagnosed. Herein, we provide an update of the 2014 Canadian Cardiovascular Society position statement on FH addressing the need for case identification, prompt recognition, and treatment with statins and ezetimibe, and cascade family screening. We provide a new Canadian definition for FH and tools for clinicians to make a diagnosis. The risk of atherosclerotic cardiovascular disease in patients with "definite" FH is 10- to 20-fold that of a normolipidemic individual and initiating treatment in youth or young adulthood can normalize life expectancy. Target levels for low-density lipoprotein cholesterol are proposed and are aligned with the Canadian Cardiovascular Society guidelines on dyslipidemia. Recommendation for the use of inhibitors of proprotein convertase kexin/subtilisin type 9 are made in patients who cannot achieve therapeutic low-density lipoprotein cholesterol targets on maximally tolerated statins and ezetimibe. The writing committee used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology in the preparation of the present document, which offers guidance for practical evaluation and management of patients with FH. This position statement also aims to raise awareness of FH nationally, and to mobilize patient support, promote knowledge translation, and availability of treatment and health care resources for this under-recognized, but important medical condition.

2 Review HDL and atherosclerotic cardiovascular disease: genetic insights into complex biology. 2018

Rosenson, Robert S / Brewer, H Bryan / Barter, Philip J / Björkegren, Johan L M / Chapman, M John / Gaudet, Daniel / Kim, Daniel Seung / Niesor, Eric / Rye, Kerry-Anne / Sacks, Frank M / Tardif, Jean-Claude / Hegele, Robert A. ·Cardiometabolics Unit, Icahn School of Medicine at Mount Sinai, Hospital Box 1030, One Gustave L. Levy Place, New York, New York 10029, USA. · Medstar Heart and Vascular Institute, Washington Hospital Center, 110 Irving Street NW, Washington, DC 20010, USA. · School of Medical Sciences, Faculty of Medicine, Level 4E, Wallace Wurth Building, University of New South Wales Sydney, 18 High Street, Sydney, Kensington New South Wales 2052, Australia. · Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA. · Integrated Cardio Metabolic Centre, Department of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, 171 77 Huddinge, Sweden. · National Institute for Health and Medical Research (INSERM) and Endocrinology Metabolism Service, Pitie-Salpetriere University Hospital, 83 Boulevard de l'Hôpital, 75651 Paris, France. · Lipidology Unit, Community Genomic Medicine Centre and ECOGENE-21, Department of Medicine, Université de Montréal, 930 Jacques-Cartier, Saguenay, Québec G7H 7K9, Canada. · University of Michigan School of Public Health, M4045 SPH II, 1415 Washington Heights, Ann Arbor, Michigan 48109-2029, USA. · Hartis-Pharma Sàrl, 13c Chemin de Bonmont, 1260 Nyon, Switzerland. · Nutrition Department, Harvard T. H. Chan School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02478, USA. · Montreal Heart Institute, Université de Montréal, 5000 Belanger Street, Montréal, Québec H1T 1C8, Canada. · Department of Medicine and Robarts Research Institute, Western University, 4288A-1151 Richmond Street North, London, Ontario N6A 5B7, Canada. ·Nat Rev Cardiol · Pubmed #28795686.

ABSTRACT: Plasma levels of HDL cholesterol (HDL-C) predict the risk of cardiovascular disease at the epidemiological level, but a direct causal role for HDL in cardiovascular disease remains controversial. Studies in animal models and humans with rare monogenic disorders link only particular HDL-associated mechanisms with causality, including those mechanisms related to particle functionality rather than cholesterol content. Mendelian randomization studies indicate that most genetic variants that affect a range of pathways that increase plasma HDL-C levels are not usually associated with reduced risk of cardiovascular disease, with some exceptions, such as cholesteryl ester transfer protein variants. Furthermore, only a fraction of HDL-C variation has been explained by known loci from genome-wide association studies (GWAS), suggesting the existence of additional pathways and targets. Systems genetics can enhance our understanding of the spectrum of HDL pathways, particularly those pathways that involve new and non-obvious GWAS loci. Bioinformatic approaches can also define new molecular interactions inferred from both large-scale genotypic data and RNA sequencing data to reveal biologically meaningful gene modules and networks governing HDL metabolism with direct relevance to disease end points. Targeting these newly recognized causal networks might inform the development of novel therapeutic strategies to reduce the risk of cardiovascular disease.

3 Clinical Trial The effect of an apolipoprotein A-I-containing high-density lipoprotein-mimetic particle (CER-001) on carotid artery wall thickness in patients with homozygous familial hypercholesterolemia: The Modifying Orphan Disease Evaluation (MODE) study. 2015

Hovingh, G Kees / Smits, Loek P / Stefanutti, Claudia / Soran, Handrean / Kwok, See / de Graaf, Jacqueline / Gaudet, Daniel / Keyserling, Constance H / Klepp, Heather / Frick, Jennifer / Paolini, John F / Dasseux, Jean-Louis / Kastelein, John J P / Stroes, Erik S. ·Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands. Electronic address: g.k.hovingh@amc.uva.nl. · Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands. · Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy. · Cardiovascular Trials Unit, Central Manchester University Hospital NHS Foundation Trust, Manchester, United Kingdom. · Department of Vascular Medicine, Radboud University Medical Center, Nijmegen, the Netherlands. · Lipid Clinic, Department of Medicine, Université de Montreal, Chicoutimi, Quebec, Canada. · Cerenis Therapeutics Holdings, Toulouse, France. ·Am Heart J · Pubmed #25965722.

ABSTRACT: BACKGROUND: Patients with homozygous familial hypercholesterolemia (HoFH) are at extremely elevated risk for early cardiovascular disease because of exposure to elevated low-density lipoprotein cholesterol (LDL-C) plasma levels from birth. Lowering LDL-C by statin therapy is the cornerstone for cardiovascular disease prevention, but the residual risk in HoFH remains high, emphasizing the need for additional therapies. In the present study, we evaluated the effect of serial infusions with CER-001, a recombinant human apolipoprotein A-I (apoA-I)-containing high-density lipoprotein-mimetic particle, on carotid artery wall dimensions in patients with HoFH. METHODS AND RESULTS: Twenty-three patients (mean age 39.4 ± 13.5 years, mean LDL-C 214.2 ± 81.5 mg/dL) with genetically confirmed homozygosity or compound heterozygosity for LDLR, APOB, PCSK9, or LDLRAP1 mutations received 12 biweekly infusions with CER-001 (8 mg/kg). Before and 1 hour after the first infusion, lipid values were measured. Magnetic resonance imaging (3-T magnetic resonance imaging) scans of the carotid arteries were acquired at baseline and after 24 weeks to assess changes in artery wall dimensions. After CER-001 infusion, apoA-I increased from 114.8 ± 20.7 mg/dL to 129.3 ± 23.0 mg/dL. After 24 weeks, mean vessel wall area (primary end point) decreased from 17.23 to 16.75 mm(2) (P = .008). A trend toward reduction of mean vessel wall thickness was observed (0.75 mm at baseline and 0.74 mm at follow-up, P = .0835). CONCLUSIONS: In HoFH, 12 biweekly infusions with an apoA-I-containing high-density lipoprotein-mimetic particle resulted in a significant reduction in carotid mean vessel wall area, implying that CER-001 may reverse atherogenic changes in the arterial wall on top of maximal low-density lipoprotein-lowering therapy. This finding supports further clinical evaluation of apoA-I-containing particles in patients with HoFH.

4 Clinical Trial Apolipoprotein B synthesis inhibition with mipomersen in heterozygous familial hypercholesterolemia: results of a randomized, double-blind, placebo-controlled trial to assess efficacy and safety as add-on therapy in patients with coronary artery disease. 2012

Stein, Evan A / Dufour, Robert / Gagne, Claude / Gaudet, Daniel / East, Cara / Donovan, Joanne M / Chin, Wai / Tribble, Diane L / McGowan, Mary. ·Metabolic and Atherosclerosis Research Center, 5355 Medpace Way, Cincinnati, OH 45227, USA. esteinmrl@aol.com ·Circulation · Pubmed #23060426.

ABSTRACT: BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) is a common genetic disorder leading to premature coronary artery disease. Despite statins and additional lipid-lowering therapies, many HeFH patients fail to achieve low-density lipoprotein cholesterol (LDL-C) goals. We evaluated mipomersen, an apolipoprotein B synthesis inhibitor, to further lower LDL-C in HeFH patients with coronary artery disease. METHODS AND RESULTS: This double-blind, placebo-controlled, phase 3 trial randomized patients with HeFH and coronary artery disease on maximally tolerated statin and LDL-C ≥2.6 mmol/L (≥100 mg/dL) to weekly subcutaneous mipomersen 200 mg or placebo (2:1) for 26 weeks. The primary end point was percent change in LDL-C from baseline at week 28. Safety assessments included adverse events, laboratory tests, and magnetic resonance imaging assessment of hepatic fat. Of 124 randomized patients (41 placebo, 83 mipomersen), 114 (41 placebo, 73 mipomersen) completed treatment. Mean (95% confidence interval) LDL-C decreased significantly with mipomersen (-28.0% [-34.0% to -22.1%] compared with 5.2% [-0.5% to 10.9%] increase with placebo; P<0.001). Mipomersen significantly reduced apolipoprotein B (-26.3%), total cholesterol (-19.4%), and lipoprotein(a) (-21.1%) compared with placebo (all P<0.001). No significant change occurred in high-density lipoprotein cholesterol. Adverse events included injection site reactions and influenza-like symptoms. Five mipomersen patients (6%) had 2 consecutive alanine aminotransferase values ≥3 times the upper limit of normal at least 7 days apart; none were associated with significant bilirubin increases. Hepatic fat content increased a median of 4.9% with mipomersen versus 0.4% with placebo (P<0.001). CONCLUSIONS: Mipomersen is an effective therapy to further reduce apolipoprotein B-containing lipoproteins, including LDL and lipoprotein(a), in HeFH patients with coronary artery disease on statins and other lipid-lowering therapy. The significance of hepatic fat and transaminase increases remains uncertain at this time. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00706849.

5 Article Simplified Canadian Definition for Familial Hypercholesterolemia. 2018

Ruel, Isabelle / Brisson, Diane / Aljenedil, Sumayah / Awan, Zuhier / Baass, Alexis / Bélanger, Alexandre / Bergeron, Jean / Bewick, David / Brophy, James M / Brunham, Liam R / Couture, Patrick / Dufour, Robert / Francis, Gordon A / Frohlich, Jiri / Gagné, Claude / Gaudet, Daniel / Grégoire, Jean C / Gupta, Milan / Hegele, Robert A / Mancini, G B John / McCrindle, Brian W / Pang, Jing / Raggi, Paolo / Tu, Jack V / Watts, Gerald F / Genest, Jacques. ·Research Institute of the McGill University Health Centre, Royal Victoria Hospital, Montreal, Quebec, Canada. Electronic address: isabelle.ruel@mail.mcgill.ca. · Lipidology Unit, Community Genomic Medicine Centre and ECOGENE-21, Department of Medicine, Université de Montréal, Saguenay, Quebec, Canada. · Research Institute of the McGill University Health Centre, Royal Victoria Hospital, Montreal, Quebec, Canada. · Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. · Division of Experimental Medicine and Medical Biochemistry, Department of Medicine, McGill University, Quebec, Canada; Nutrition, Metabolism and Atherosclerosis Clinic, Institut de recherches cliniques de Montréal, Quebec, Canada. · Lipid Research Centre, CHU de Québec-Université Laval, Québec City, Quebec, Canada. · Division of Cardiology, Department of Medicine, Dalhousie University, St John, New Brunswick, Canada. · Research Institute of the McGill University Health Centre, Royal Victoria Hospital, Montreal, Quebec, Canada; Department of Medicine, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada. · Healthy Heart Program Prevention Clinic, St Paul's Hospital, Vancouver, British Columbia, Canada, Department of Medicine, University of British Columbia, Vancouver, British Columbia, and Centre for Heart Lung Innovation, Providence Health Care Research Institute, University of British Columbia, Vancouver, British Columbia, Canada. · Nutrition, Metabolism and Atherosclerosis Clinic, Institut de recherches cliniques de Montréal, Quebec, Canada, Department of Nutrition, Université de Montréal, Quebec, Canada. · Healthy Heart Program Prevention Clinic, St Paul's Hospital, Vancouver, British Columbia, Canada, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada. · Montreal Heart Institute, Montreal, Quebec, Canada. · McMaster University, Hamilton, Ontario, Canada, Canadian Collaborative Research Network, Brampton, Ontario, Canada. · Departments of Medicine and Biochemistry, Schulich School of Medicine and Robarts Research Institute, Western University, London, Ontario, Canada. · Department of Medicine, Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada. · Division of Cardiology, The Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Ontario, Canada. · School of Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia. · Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada. · Faculty of Medicine, University of Toronto, Institute for Clinical Evaluative Sciences, Schulich Heart Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. · School of Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia; Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Perth, Australia. ·Can J Cardiol · Pubmed #30093300.

ABSTRACT: Familial hypercholesterolemia (FH) is an autosomal codominant lipoprotein disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) and high risk of premature atherosclerotic cardiovascular disease. Definitions for FH rely on complex algorithms that are on the basis of levels of total or LDL-C, clinical features, family history, and DNA analysis that are often difficult to obtain. We propose a novel simplified definition for FH. Definite FH includes: (1) elevated LDL-C (≥ 8.50 mmol/L); or (2) LDL-C ≥ 5.0 mmol/L (for age 40 years or older; ≥ 4.0 mmol/L if age younger than 18 years; and ≥ 4.5 mmol/L if age is between 18 and 39 years) when associated with at least 1 of: (1) tendon xanthomas; or (2) causal DNA mutation in the LDLR, APOB, or PCSK9 genes in the proband or first-degree relative. Probable FH is defined as subjects with an elevated LDL-C (≥ 5.0 mmol/L) and the presence of premature atherosclerotic cardiovascular disease in the patient or a first-degree relative or an elevated LDL-C in a first-degree relative. LDL-C cut points were determined from a large database comprising > 3.3 million subjects. To compare the proposed definition with currently used algorithms (ie, the Simon Broome Register and Dutch Lipid Clinic Network), we performed concordance analyses in 5987 individuals from Canada. The new FH definition showed very good agreement compared with the Simon Broome Register and Dutch Lipid Clinic Network criteria (κ = 0.969 and 0.966, respectively). In conclusion, the proposed FH definition has diagnostic performance comparable to existing criteria, but adapted to the Canadian population, and will facilitate the diagnosis of FH patients.

6 Article Association study between a polymorphic poly-T repeat sequence in the promoter of the somatostatin gene and metabolic syndrome. 2018

Tremblay, Monique / Brisson, Diane / Gaudet, Daniel. ·Lipidology Unit, Community Genomic Medicine Center, Department of Medicine, Université de Montréal and ECOGENE-21 Clinical and Translational Research Center, 225 St-Vallier Chicoutimi, Québec, G7H 7P2, Canada. · Lipidology Unit, Community Genomic Medicine Center, Department of Medicine, Université de Montréal and ECOGENE-21 Clinical and Translational Research Center, 225 St-Vallier Chicoutimi, Québec, G7H 7P2, Canada. daniel.gaudet@umontreal.ca. ·BMC Med Genet · Pubmed #30053852.

ABSTRACT: BACKGROUND: Metabolic syndrome is a cluster of factors associated with an increased risk of developing type 2 diabetes mellitus (T2D) and coronary artery disease (CAD). It is a complex disorder resulting from the interaction between various environmental factors and genetic susceptibility. The somatostatin (SST) gene has been shown to regulate a wide range of functions, particularly in energy homeostasis. In addition, low levels of SST have been reported to have effects on the progression of metabolic syndrome components. The aim of this study was therefore to evaluate the association between polymorphic T sequences in the promoter of the SST gene and metabolic syndrome expression. METHODS: We studied 1725 French-Canadian subjects from a founder population selected on the basis of having a positive family history of dyslipidemia, CAD or T2D. The analysis were performed on four groups created according to the poly T polymorphism length in the 5' flanking promoter region of SST. Anova, Ancova and logistic regression models and Chi 2 analyses were used to evaluate the association between the poly T polymorphisms and metabolic syndrome components expression. RESULTS: Analyses showed that means, frequencies and odds ratio of metabolic syndrome components expression increase as the number of poly-T repeats in the promoter region of SST increases. Women exhibit more significant differences than men. However, the trends are the same in both genders and differences for most of the components are significant in the entire sample. CONCLUSION: Those results suggest that the poly T polymorphisms in the SST promoter region may influence several metabolic processes implicated in metabolic syndrome expression. More analyses are needed to document the mechanisms that could underlie genetic regulation effect of SST on metabolic syndrome components and to clarify its specific role.

7 Article Epigenetic and genetic variations at the TNNT1 gene locus are associated with HDL-C levels and coronary artery disease. 2016

Guay, Simon-Pierre / Légaré, Cécilia / Brisson, Diane / Mathieu, Patrick / Bossé, Yohan / Gaudet, Daniel / Bouchard, Luigi. ·Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada. · ECOGENE-21 & Lipid Clinic, Chicoutimi Hospital, Saguenay, QC G7H 5H6, Canada. · Department of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada. · Centre de recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC G1V 0A6, Canada. · Department of Molecular Medicine, Université Laval, Québec, QC G1V 0A6, Canada. ·Epigenomics · Pubmed #26950807.

ABSTRACT: AIM: To assess whether epigenetic and genetic variations at the TNNT1 gene locus are associated with high-density lipoprotein cholesterol (HDL-C) and coronary artery disease (CAD). Patients, materials & methods: TNNT1 DNA methylation and c.-20G>A polymorphism were genotyped in subjects with and without familial hypercholesterolemia (FH). RESULTS: Lower TNNT1 DNA methylation levels were independently associated with lower HDL-C levels and with the TNNT1 c.-20G>A polymorphism. In FH men, carriers of the TNNT1 c.-20G>A polymorphism had lower HDL-C levels and an increased risk of CAD compared with noncarriers. In non-FH men, a higher TNNT1 DNA methylation level was associated with CAD. CONCLUSION: These results suggest that TNNT1 genetic and epigenetic variations are associated with HDL-C levels and CAD.

8 Article A study in familial hypercholesterolemia suggests reduced methylomic plasticity in men with coronary artery disease. 2015

Guay, Simon-Pierre / Brisson, Diane / Mathieu, Patrick / Bossé, Yohan / Gaudet, Daniel / Bouchard, Luigi. ·Department of Biochemistry, Université de Sherbrooke, University-Affiliated Chicoutimi Hospital, 305 rue St-Vallier, Saguenay, Québec G7H 5H6, Canada. ·Epigenomics · Pubmed #25687463.

ABSTRACT: AIM: To assess whether DNA methylation is associated with coronary artery disease (CAD). MATERIALS & METHODS: An epigenome-wide analysis has been performed on leucocytes from familial hypercholesterolemic (FH) men with (n = 6) or without CAD (n = 6). The results were replicated in an extended sample of FH men (n = 61) and in non-FH men (n = 100) for two of the top differentially methylated loci. RESULTS: FH men with CAD had significantly more hypomethylated and hypermethylated loci and showed less DNA methylation level variability compared with men without CAD (p < 0.001). Moreover, COL14A1 and MMP9 DNA methylation levels were associated with CAD, age of onset of CAD or CAD risk factors. CONCLUSION: These results suggest that epigenome-wide changes are associated with CAD occurrence in men.

9 Article Epipolymorphisms within lipoprotein genes contribute independently to plasma lipid levels in familial hypercholesterolemia. 2014

Guay, Simon-Pierre / Brisson, Diane / Lamarche, Benoit / Gaudet, Daniel / Bouchard, Luigi. ·Department of Biochemistry; Université de Sherbrooke; Sherbrooke, QC Canada; ECOGENE-21 and Lipid Clinic; Chicoutimi Hospital; Saguenay, QC Canada. · ECOGENE-21 and Lipid Clinic; Chicoutimi Hospital; Saguenay, QC Canada; Department of Medicine; Université de Montréal; Montréal, QC Canada. · Institute of Nutrition and Functional Foods; Université Laval; Québec, QC Canada. ·Epigenetics · Pubmed #24504152.

ABSTRACT: Gene polymorphisms associated so far with plasma lipid concentrations explain only a fraction of their heritability, which can reach up to 60%. Recent studies suggest that epigenetic modifications (DNA methylation) could contribute to explain part of this missing heritability. We therefore assessed whether the DNA methylation of key lipoprotein metabolism genes is associated with high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride levels in patients with familial hypercholesterolemia (FH). Untreated FH patients (61 men and 37 women) were recruited for the measurement of blood DNA methylation levels at the ABCG1, LIPC, PLTP and SCARB1 gene loci using bisulfite pyrosequencing. ABCG1, LIPC and PLTP DNA methylation was significantly associated with HDL-C, LDL-C and triglyceride levels in a sex-specific manner (all P<0.05). FH subjects with previous history of coronary artery disease (CAD) had higher LIPC DNA methylation levels compared with FH subjects without CAD (P = 0.02). Sex-specific multivariable linear regression models showed that new and previously reported epipolymorphisms (ABCG1-CpGC3, LIPC-CpGA2, mean PLTP-CpGC, LPL-CpGA3, CETP-CpGA2, and CETP-CpGB2) significantly contribute to variations in plasma lipid levels (all P<0.001 in men and P<0.02 in women), independently of traditional predictors such as age, waist circumference, blood pressure, fasting plasma lipids and glucose levels. These results suggest that epigenetic perturbations of key lipoprotein metabolism genes are associated with plasma lipid levels, contribute to the interindividual variability and might partially explain the missing heritability of plasma lipid levels, at least in FH.

10 Article Angiographically-assessed coronary artery disease associates with HDL particle size in women. 2012

Blackburn, Patricia / Lemieux, Isabelle / Lamarche, Benoît / Bergeron, Jean / Perron, Patrice / Tremblay, Gérald / Gaudet, Daniel / Després, Jean-Pierre. ·Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec (Québec), Canada. ·Atherosclerosis · Pubmed #22695528.

ABSTRACT: OBJECTIVE: To investigate, in women, the relationship between HDL particle size and coronary artery disease (CAD). METHODS: Average HDL particle size was measured in a sample of 239 women on whom CAD was assessed by angiography. RESULTS: Overall, women who had CAD were characterized by a deteriorated fasting metabolic risk profile, which was accompanied by smaller HDL particles compared to women without CAD (80.4 ± 2.2 Å vs. 81.5 ± 2.7 Å, p < 0.01). In addition, a reduced HDL particle size was a significant correlate of several features of the atherogenic metabolic profile of abdominal obesity such as increased triglyceride and apolipoprotein B concentrations, decreased HDL cholesterol levels, an elevated cholesterol/HDL cholesterol ratio and hyperinsulinemia and was also associated with an increased waist circumference (0.13≤|r|≤0.21, p < 0.05). Odds ratio of being affected by CAD was increased by 2.5-fold (95% CI: 1.4-4.5; p < 0.01) among women with smaller HDL particles compared to women with larger HDL particles. Finally, women characterized by the presence of the NCEP-ATP III clinical criteria or by hypertriglyceridemic waist were characterized by smaller HDL particles compared to women without these clinical phenotypes (p < 0.05). CONCLUSION: HDL particle size appears to be another relevant feature of a dysmetabolic state which is related to CAD risk in women.

11 Article ABCA1 gene promoter DNA methylation is associated with HDL particle profile and coronary artery disease in familial hypercholesterolemia. 2012

Guay, Simon-Pierre / Brisson, Diane / Munger, Johannie / Lamarche, Benoit / Gaudet, Daniel / Bouchard, Luigi. ·Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada. ·Epigenetics · Pubmed #22419126.

ABSTRACT: High-density lipoproteins cholesterol (HDL-C) level, a strong coronary artery disease (CAD) clinical biomarker, shows significant interindividual variability. However, the molecular mechanisms involved remain mostly unknown. ATP-binding cassette A1 (ABCA1) catalyzes the cholesterol transfer from peripheral cells to nascent HDL particles. Recently, a differentially methylation region was identified in ABCA1 gene promoter locus, near the first exon. Therefore, we hypothesized that DNA methylation changes at ABCA1 gene locus is one of the molecular mechanisms involved in HDL-C interindividual variability. The study was conducted in familial hypercholesterolemia (FH), a monogenic disorder associated with a high risk of CAD . Ninety-seven FH patients (all p.W66G for the LDLR gene mutation and not under lipid-lowering treatment) were recruited and finely phenotyped for DNA methylation analyses at ABCA1 gene locus. ABCA1 DNA methylation levels were found negatively correlated with circulating HDL-C (r = -0.20; p = 0.05), HDL2-phospholipid levels (r = -0.43; p = 0.04), and with a trend for association with HDL peak particle size (r = -0.38; p = 0.08). ABCA1 DNA methylation levels were also found associated with prior history of CAD (CAD = 40.2% vs. without CAD = 34.3%; p = 0.003). These results suggest that epigenetic changes within the ABCA1 gene promoter contribute to the interindividual variability in plasma HDL-C concentrations and are associated with CAD expression. These findings could change our understanding of the molecular mechanisms involved in the pathophysiological processes leading to CAD.

12 Article Hypertriglyceridemic waist: a simple clinical phenotype associated with coronary artery disease in women. 2012

Blackburn, Patricia / Lemieux, Isabelle / Lamarche, Benoît / Bergeron, Jean / Perron, Patrice / Tremblay, Gérald / Gaudet, Daniel / Després, Jean-Pierre. ·Division of Kinesiology, Department of Health Sciences, Université du Québec à Chicoutimi, Saguenay (Québec), Canada. ·Metabolism · Pubmed #21733531.

ABSTRACT: The aim of the present study was to compare the ability of the hypertriglyceridemic waist phenotype and the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) clinical criteria to predict coronary artery disease (CAD) risk in a sample of women. We studied 254 women among whom the presence/absence of CAD was assessed by angiography. The hypertriglyceridemic waist phenotype was defined as having both a high waist circumference (≥85 cm) and increased fasting triglyceride levels (≥1.5 mmol/L), whereas the presence of at least 3 of the 5 NCEP-ATP III criteria was used as the "reference" screening approach to identify women with the features of the metabolic syndrome. Women with hypertriglyceridemic waist were characterized by higher adiposity indices as well as by a more disturbed fasting metabolic risk profile compared with women without this phenotype. Similar differences were observed when comparing the metabolic profile of women with vs without at least 3 of the NCEP-ATP III clinical criteria. Moreover, differences in the Framingham risk score were essentially similar when women were considered at low or high risk by either hypertriglyceridemic waist or by NCEP-ATP III clinical criteria (P < .0001). Finally, both clinical phenotypes were predictive of CAD (hypertriglyceridemic waist: relative odds ratio, 2.1; 95% confidence interval, 1.1-3.8; P = .02; NCEP-ATP III clinical criteria: relative odds ratio, 2.5; 95% confidence interval, 1.4-4.6; P < .003). These results suggest that hypertriglyceridemic waist is a simple screening tool to identify women with clustering metabolic abnormalities and at increased CAD risk.