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Coronary Artery Disease: HELP
Articles by Jonathon M. White
Based on 7 articles published since 2010
(Why 7 articles?)
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Between 2010 and 2020, Jon White wrote the following 7 articles about Coronary Artery Disease.
 
+ Citations + Abstracts
1 Review Three, six, or twelve months of dual antiplatelet therapy after DES implantation in patients with or without acute coronary syndromes: an individual patient data pairwise and network meta-analysis of six randomized trials and 11 473 patients. 2017

Palmerini, Tullio / Della Riva, Diego / Benedetto, Umberto / Bacchi Reggiani, Letizia / Feres, Fausto / Abizaid, Alexandre / Gilard, Martine / Morice, Marie-Claude / Valgimigli, Marco / Hong, Myeong-Ki / Kim, Byeong-Keuk / Jang, Yangsoo / Kim, Hyo-Soo / Park, Kyung Woo / Colombo, Antonio / Chieffo, Alaide / Sangiorgi, Diego / Biondi-Zoccai, Giuseppe / Généreux, Philippe / Angelini, Gianni D / Pufulete, Maria / White, Jonathon / Bhatt, Deepak L / Stone, Gregg W. ·Dipartimento Cardio-Toraco-Vascolare, University of Bologna, Italy. · Bristol Heart Institute, University of Bristol School of Clinical Sciences, Bristol, Bristol, UK. · Istituto Dante Pazzanese de Cardiologia, Sao Paulo, Brazil. · Department of Cardiology, Brest University, Brest, France. · Générale de Santé, Institut Cardiovasculaire Paris Sud, Massy, France. · Swiss Cardiovascular Center, Bern, Switzerland. · Severance Cardiovascular Hospital and Science Institute, Yonsei University College of Medicine, Seoul, Korea. · Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. · San Raffaele Scientific Institute, Milan, Italy. · Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, and Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy. · Columbia University Medical Center/New York-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, NY. · Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA. ·Eur Heart J · Pubmed #28110296.

ABSTRACT: Aim: We sought to determine whether the optimal dual antiplatelet therapy (DAPT) duration after drug-eluting stent (DES) placement varies according to clinical presentation. Methods and Results: We performed an individual patient data pairwise and network meta-analysis comparing short-term (≤6-months) versus long-term (1-year) DAPT as well as 3-month vs. 6-month vs 1-year DAPT. The primary study outcome was the 1-year composite risk of myocardial infarction (MI) or definite/probable stent thrombosis (ST). Six trials were included in which DAPT after DES consisted of aspirin and clopidogrel. Among 11 473 randomized patients 6714 (58.5%) had stable CAD and 4758 (41.5%) presented with acute coronary syndrome (ACS), the majority of whom (67.0%) had unstable angina. In ACS patients, ≤6-month DAPT was associated with non-significantly higher 1-year rates of MI or ST compared with 1-year DAPT (Hazard Ratio (HR) 1.48, 95% Confidence interval (CI) 0.98-2.22; P = 0.059), whereas in stable patients rates of MI and ST were similar between the two DAPT strategies (HR 0.93, 95%CI 0.65-1.35; P = 0.71; Pinteraction = 0.09). By network meta-analysis, 3-month DAPT, but not 6-month DAPT, was associated with higher rates of MI or ST in ACS, whereas no significant differences were apparent in stable patients. Short DAPT was associated with lower rates of major bleeding compared with 1-year DAPT, irrespective of clinical presentation. All-cause mortality was not significantly different with short vs. long DAPT in both patients with stable CAD and ACS. Conclusions: Optimal DAPT duration after DES differs according to clinical presentation. In the present meta-analysis, despite the fact that most enrolled ACS patients were relatively low risk, 3-month DAPT was associated with increased ischaemic risk, whereas 3-month DAPT appeared safe in stable CAD. Prolonged DAPT increases bleeding regardless of clinical presentation. Further study is required to identify the optimal duration of DAPT after DES in individual patients based on their relative ischaemic and bleeding risks.

2 Article Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis. 2017

Dale, Caroline E / Fatemifar, Ghazaleh / Palmer, Tom M / White, Jon / Prieto-Merino, David / Zabaneh, Delilah / Engmann, Jorgen E L / Shah, Tina / Wong, Andrew / Warren, Helen R / McLachlan, Stela / Trompet, Stella / Moldovan, Max / Morris, Richard W / Sofat, Reecha / Kumari, Meena / Hyppönen, Elina / Jefferis, Barbara J / Gaunt, Tom R / Ben-Shlomo, Yoav / Zhou, Ang / Gentry-Maharaj, Aleksandra / Ryan, Andy / Anonymous10541124 / Mutsert, Renée de / Noordam, Raymond / Caulfield, Mark J / Jukema, J Wouter / Worrall, Bradford B / Munroe, Patricia B / Menon, Usha / Power, Chris / Kuh, Diana / Lawlor, Debbie A / Humphries, Steve E / Mook-Kanamori, Dennis O / Sattar, Naveed / Kivimaki, Mika / Price, Jacqueline F / Davey Smith, George / Dudbridge, Frank / Hingorani, Aroon D / Holmes, Michael V / Casas, Juan P. ·From Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, United Kingdom (C.E.D., G.F., D.P.-M., A.D.H., J.P.C.) · Department of Mathematics and Statistics, Lancaster University, United Kingdom (T.M.P.) · UCLGenetics Institute, University College London, United Kingdom (J.W.) · Applied Statistical Methods in Medical Research Group, Universidad Catolica de San Antonio de Murcia, Spain (D.P.-M.) · Social Genetic & Developmental Psychiatry, King's College London, United Kingdom (D.Z.) · Institute of Cardiovascular Science, University College London, United Kingdom (J.E.L.E., T.S., A.D.H., S.E.H.) · MRC Unit for Lifelong Health & Ageing at UCL, London, United Kingdom (A.W., D.K.) · Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom (H.R.W., M.J.C., P.B.M.) · NIHR Barts Cardiovascular Biomedical Research Unit, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom (H.R.W., M.J.C., P.B.M.) · Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, United Kingdom (S.M., J.F.P.) · Department of Cardiology, Leiden University Medical Center, The Netherlands (S.T., W.J.) · South Australian Health and Medical Research Institute, Adelaide (M.M., E.H.) · EMBL Australia, Adelaide (M.M.) · School of Social and Community Medicine, University of Bristol, United Kingdom (R.W.M., T.R.G., Y.B.-S., D.A.L., G.D.S.) · Centre for Clinical Pharmacology, University College London, United Kingdom (R.S.) · Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M.K.) · Centre for Population Health Research, School of Health Sciences and Sansom Institute, University of South Australia, Adelaide (E.H., A.Z.) · Population, Policy & Practice, UCL Great Ormond Street Institute of Child Health, London, United Kingdom (E.H., C.P.) · Department of Primary Care & Population Health, University College London, Royal Free Campus, United Kingdom (B.J.J.) · MRC Integrative Epidemiology Unit, University of Bristol, United Kingdom (T.R.G., D.A.L., G.D.S.) · Department of Women's Cancer, Institute for Women's Health, UCL, London, United Kingdom (A.G.-M., A.R., U.M.) · Department of Clinical Epidemiology, Leiden University Medical Center, The Netherlands (R.d.M., D.O.M.-K.) · Department of Internal Medicine, Section Gerontology and Geriatrics, Leiden University Medical Center, The Netherlands (R.N., S.T.) · Interuniversity Cardiology Institute Netherlands, Utrecht (W.J.) · Departments of Neurology and Public Health Sciences, University of Virginia, Charlottesville (B.B.W.) · Department of Public Health and Primary Care, Leiden University Medical Center, The Netherlands (D.O.M.-K.) · BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, United Kingdom (N.S.) · Department of Epidemiology and Public Health, University College London, United Kingdom (M.K.) · Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, United Kingdom (F.D.) · Department of Health Sciences, University of Leicester, United Kingdom (F.D.) · Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population Health, Big Data Institute Building, University of Oxford, United Kingdom (M.V.H.) · Medical Research Council Population Health Research Unit at the University of Oxford, United Kingdom (M.V.H.) · and National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospitals, United Kingdom (M.V.H.). ·Circulation · Pubmed #28500271.

ABSTRACT: BACKGROUND: The implications of different adiposity measures on cardiovascular disease etiology remain unclear. In this article, we quantify and contrast causal associations of central adiposity (waist-to-hip ratio adjusted for body mass index [WHRadjBMI]) and general adiposity (body mass index [BMI]) with cardiometabolic disease. METHODS: Ninety-seven independent single-nucleotide polymorphisms for BMI and 49 single-nucleotide polymorphisms for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with coronary heart disease (CHD) data from CARDIoGRAMplusC4D (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics; combined total 66 842 cases), stroke from METASTROKE (12 389 ischemic stroke cases), type 2 diabetes mellitus from DIAGRAM (Diabetes Genetics Replication and Meta-analysis; 34 840 cases), and lipids from GLGC (Global Lipids Genetic Consortium; 213 500 participants) consortia. Primary outcomes were CHD, type 2 diabetes mellitus, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits. RESULTS: Each one standard deviation (SD) higher WHRadjBMI (1 SD≈0.08 U) associated with a 48% excess risk of CHD (odds ratio [OR] for CHD, 1.48; 95% confidence interval [CI], 1.28-1.71), similar to findings for BMI (1 SD≈4.6 kg/m CONCLUSIONS: Both general and central adiposity have causal effects on CHD and type 2 diabetes mellitus. Central adiposity may have a stronger effect on stroke risk. Future estimates of the burden of adiposity on health should include measures of central and general adiposity.

3 Article Impact of Coronary Artery Disease Severity Assessed With the SYNTAX Score on Outcomes Following Transcatheter Aortic Valve Replacement. 2017

Paradis, Jean-Michel / White, Jonathon M / Généreux, Philippe / Urena, Marina / Doshi, Darshan / Nazif, Tamim / Hahn, Rebecca / George, Isaac / Khalique, Omar / Harjai, Kishore / Lasalle, Laura / Labbé, Benoit M / DeLarochellière, Robert / Doyle, Daniel / Dumont, Éric / Mohammadi, Siamak / Leon, Martin B / Rodés-Cabau, Josep / Kodali, Susheel. ·Quebec Heart and Lung Institute, Quebec, Canada. · Cardiovascular Research Foundation, New-York, NY. · Columbia University Medical Center, New-York, NY. · Hopital du Sacre-Coeur de Montreal, Montreal, Quebec Canada. · Gagnon Cardiovascular Institute Morristown Medical Center, Morristown, New Jersey. · Cardiovascular Research Foundation, New-York, NY sk2427@cumc.columbia.edu. ·J Am Heart Assoc · Pubmed #28219920.

ABSTRACT: BACKGROUND: The influence of coronary artery disease (CAD) on clinical and echocardiographic outcomes after transcatheter aortic valve replacement (TAVR) is still controversial. We sought to evaluate the impact of CAD severity as measured by the SYNTAX score (SS) on patients undergoing TAVR. METHODS AND RESULTS: A total of 377 patients who underwent TAVR in 2 high-volume centers in North America were included in our retrospective analysis. A blinded angiographic core laboratory calculated the SS on all available coronary angiograms with the use of quantitative coronary analysis. Patients were stratified into 4 groups: (1) no CAD (SS=0); (2) low SS (SS between 1 and 22); (3) intermediate SS (SS between 23 and 32); and (4) high SS (SS ≥33). Patients who had undergone percutaneous coronary intervention within 6 months prior to TAVR were separated into 2 categories based on their residual SS (<8 and ≥8). Patients with previous coronary artery bypass grafting (CABG) were divided into 2 groups: (1) low CABG SS and (2) high CABG SS. The primary end point was a composite of all-cause mortality, myocardial infarction, and stroke. At 30 days and 1 year, both the presence and the severity of CAD had no impact on the rate of the combined primary end point and on all-cause mortality, cardiovascular mortality, and myocardial infarction. Patients with less complete revascularization (residual SS ≥8 versus residual SS <8 and low CABG SS versus high CABG SS, had similar rates of the combined primary end point, all-cause mortality, cardiovascular mortality, MI, and stroke, at both 30 days and 1 year. CONCLUSIONS: In our core laboratory-validated study, neither the severity of CAD nor completeness of revascularization after percutaneous coronary intervention or CABG were associated with clinical outcomes after TAVR, at both 30 days and 1 year.

4 Article Identification of the Functional Variant(s) that Explain the Low-Density Lipoprotein Receptor (LDLR) GWAS SNP rs6511720 Association with Lower LDL-C and Risk of CHD. 2016

Fairoozy, Roaa Hani / White, Jon / Palmen, Jutta / Kalea, Anastasia Z / Humphries, Steve E. ·Centre for Cardiovascular Genetics, BHF Laboratories, Institute of Cardiovascular Science, University College London, London, United Kingdom. · University College London Genetics Institute, Department of Genetics, Environment and Evolution, London, United Kingdom. ·PLoS One · Pubmed #27973560.

ABSTRACT: BACKGROUND: The Low-Density Lipoprotein Receptor (LDLR) SNP rs6511720 (G>T), located in intron-1 of the gene, has been identified in genome-wide association studies (GWAS) as being associated with lower plasma levels of LDL-C and a lower risk of coronary heart disease (CHD). Whether or not rs6511720 is itself functional or a marker for a functional variant elsewhere in the gene is not known. METHODS: The association of LDLR SNP rs6511720 with incidence of CHD and levels of LDL-C was determined by reference to CARDIoGRAM, C4D and Global lipids genetics consortium (GLGC) data. SNP annotation databases were used to identify possible SNP function and prioritization. Luciferase reporter assays in the liver cell line Huh7 were used to measure the effect of variant genotype on gene expression. Electrophoretic Mobility Shift Assays (EMSAs) were used to identify the Transcription Factors (TFs) involved in gene expression regulation. RESULTS: The phenotype-genotype analysis showed that the rs6511720 minor allele is associated with lower level of LDL-C [beta = -0.2209, p = 3.85 x10-262], and lower risk of CHD [log (OR) = 0.1155, p = 1.04 x10-7]. Rs6511720 is in complete linkage. Rs6511720 is in complete linkage disequilibrium (LD) with three intron-1 SNPs (rs141787760, rs60173709, rs57217136). Luciferase reporter assays in Huh7 cells showed that the rare alleles of both rs6511720 and rs57217136 caused a significant increase in LDLR expression compared to the common alleles (+29% and +24%, respectively). Multiplex Competitor-EMSAs (MC-EMSA) identified that the transcription factor serum response element (SRE) binds to rs6511720, while retinoic acid receptor (RAR) and signal transducer and activator of transcription 1 (STAT1) bind to rs57217136. CONCLUSION: Both LDLR rs6511720 and rs57217136 are functional variants. Both these minor alleles create enhancer-binding protein sites for TFs and may contribute to increased LDLR expression, which is consequently associated with reduced LDL-C levels and 12% lower CHD risk.

5 Article Association of Lipid Fractions With Risks for Coronary Artery Disease and Diabetes. 2016

White, Jon / Swerdlow, Daniel I / Preiss, David / Fairhurst-Hunter, Zammy / Keating, Brendan J / Asselbergs, Folkert W / Sattar, Naveed / Humphries, Steve E / Hingorani, Aroon D / Holmes, Michael V. ·University College London Genetics Institute, University College London, London, England. · Farr Institute at University College London, London, England3Department of Medicine, Imperial College London, London, England. · Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, England. · The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, England. · Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 7Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania. · Division of Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands9Durrer Center for Cardiovascular Research, Netherlands Heart Institute, Utrecht, Netherlands10Institute of Cardiovascular Science, University College London, London, England. · Institute of Cardiovascular and Medical Science, University of Glasgow, Glasgow, Scotland. · Cardiovascular Genetics, British Heart Foundation Laboratories, Institute Cardiovascular Science, University College London, London, United Kingdom. · Farr Institute at University College London, London, England10Institute of Cardiovascular Science, University College London, London, England. ·JAMA Cardiol · Pubmed #27487401.

ABSTRACT: IMPORTANCE: Low-density lipoprotein cholesterol (LDL-C) is causally related to coronary artery disease (CAD), but the relevance of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) is uncertain. Lowering of LDL-C levels by statin therapy modestly increases the risk of type 2 diabetes, but it is unknown whether this effect is specific to statins. OBJECTIVE: To investigate the associations of 3 routinely measured lipid fractions with CAD and diabetes through mendelian randomization (MR) using conventional MR and making use of newer approaches, such as multivariate MR and MR-Egger, that address the pleiotropy of genetic instruments where relevant. DESIGN, SETTING, AND PARTICIPANTS: Published data from genome-wide association studies were used to construct genetic instruments and then applied to investigate associations between lipid fractions and the risk of CAD and diabetes using MR approaches that took into account pleiotropy of genetic instruments. The study was conducted from March 12 to December 31, 2015. MAIN OUTCOMES AND MEASURES: Coronary artery disease and diabetes. RESULTS: Genetic instruments composed of 130 single-nucleotide polymorphisms (SNPs) were used for LDL-C (explaining 7.9% of its variance), 140 SNPs for HDL-C (6.6% of variance), and 140 SNPs for TGs (5.9% of variance). A 1-SD genetically instrumented elevation in LDL-C levels (equivalent to 38 mg/dL) and TG levels (equivalent to 89 mg/dL) was associated with higher CAD risk; odds ratios (ORs) were 1.68 (95% CI, 1.51-1.87) for LDL-C and 1.28 (95% CI, 1.13-1.45) for TGs. The corresponding OR for HDL-C (equivalent to a 16-mg/dL increase) was 0.95 (95% CI, 0.85-1.06). All 3 lipid traits were associated with a lower risk of type 2 diabetes. The ORs were 0.79 (95% CI, 0.71-0.88) for LDL-C and 0.83 (95% CI, 0.76-0.90) for HDL-C per 1-SD elevation. For TG, the MR estimates for diabetes were inconsistent, with MR-Egger giving an OR of 0.83 (95%CI, 0.72-0.95) per 1-SD elevation. CONCLUSIONS AND RELEVANCE: Routinely measured lipid fractions exhibit contrasting associations with the risk of CAD and diabetes. Increased LDL-C, HDL-C, and possibly TG levels are associated with a lower risk of diabetes. This information will be relevant to the design of clinical trials of lipid-modifying agents, which should carefully monitor participants for dysglycemia and the incidence of diabetes.

6 Article Role of Adiponectin in Coronary Heart Disease Risk: A Mendelian Randomization Study. 2016

Borges, Maria Carolina / Lawlor, Debbie A / de Oliveira, Cesar / White, Jon / Horta, Bernardo Lessa / Barros, Aluísio J D. ·From the Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil (M.C.B., B.L.H., A.J.D.B.) · MRC Integrative Epidemiology Unit (D.A.L.) · School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (D.A.L.) · and Epidemiology and Public Health, Institute of Epidemiology and Health Care (C.d.O.) and UCL Genetics Institute, Division of Biosciences, Faculty of Life Sciences (J.W.), University College London, London, United Kingdom. ·Circ Res · Pubmed #27252388.

ABSTRACT: RATIONALE: Hypoadiponectinemia correlates with several coronary heart disease (CHD) risk factors. However, it is unknown whether adiponectin is causally implicated in CHD pathogenesis. OBJECTIVE: We aimed to investigate the causal effect of adiponectin on CHD risk. METHODS AND RESULTS: We undertook a Mendelian randomization study using data from genome-wide association studies consortia. We used the ADIPOGen consortium to identify genetic variants that could be used as instrumental variables for the effect of adiponectin. Data on the association of these genetic variants with CHD risk were obtained from CARDIoGRAM (22 233 CHD cases and 64 762 controls of European ancestry) and from CARDIoGRAMplusC4D Metabochip (63 746 cases and 130 681 controls; ≈ 91% of European ancestry) consortia. Data on the association of genetic variants with adiponectin levels and with CHD were combined to estimate the influence of blood adiponectin on CHD risk. In the conservative approach (restricted to using variants within the adiponectin gene as instrumental variables), each 1 U increase in log blood adiponectin concentration was associated with an odds ratio for CHD of 0.83 (95% confidence interval, 0.68-1.01) in CARDIoGRAM and 0.97 (95% confidence interval, 0.84-1.12) in CARDIoGRAMplusC4D Metabochip. Findings from the liberal approach (including variants in any locus across the genome) indicated a protective effect of adiponectin that was attenuated to the null after adjustment for known CHD predictors. CONCLUSIONS: Overall, our findings do not support a causal role of adiponectin levels in CHD pathogenesis.

7 Article Mendelian randomization of blood lipids for coronary heart disease. 2015

Holmes, Michael V / Asselbergs, Folkert W / Palmer, Tom M / Drenos, Fotios / Lanktree, Matthew B / Nelson, Christopher P / Dale, Caroline E / Padmanabhan, Sandosh / Finan, Chris / Swerdlow, Daniel I / Tragante, Vinicius / van Iperen, Erik P A / Sivapalaratnam, Suthesh / Shah, Sonia / Elbers, Clara C / Shah, Tina / Engmann, Jorgen / Giambartolomei, Claudia / White, Jon / Zabaneh, Delilah / Sofat, Reecha / McLachlan, Stela / Anonymous1640783 / Doevendans, Pieter A / Balmforth, Anthony J / Hall, Alistair S / North, Kari E / Almoguera, Berta / Hoogeveen, Ron C / Cushman, Mary / Fornage, Myriam / Patel, Sanjay R / Redline, Susan / Siscovick, David S / Tsai, Michael Y / Karczewski, Konrad J / Hofker, Marten H / Verschuren, W Monique / Bots, Michiel L / van der Schouw, Yvonne T / Melander, Olle / Dominiczak, Anna F / Morris, Richard / Ben-Shlomo, Yoav / Price, Jackie / Kumari, Meena / Baumert, Jens / Peters, Annette / Thorand, Barbara / Koenig, Wolfgang / Gaunt, Tom R / Humphries, Steve E / Clarke, Robert / Watkins, Hugh / Farrall, Martin / Wilson, James G / Rich, Stephen S / de Bakker, Paul I W / Lange, Leslie A / Davey Smith, George / Reiner, Alex P / Talmud, Philippa J / Kivimäki, Mika / Lawlor, Debbie A / Dudbridge, Frank / Samani, Nilesh J / Keating, Brendan J / Hingorani, Aroon D / Casas, Juan P. ·Genetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK Division of Transplant Surgery, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104, USA mvholmes@gmail.com. · Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK. · Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK. · Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, Rayne Building, London WC1E 6JF, UK MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK. · Department of Medicine, McMaster University, Hamilton, ON, Canada L8S 4L8. · Department of Cardiovascular Sciences, University of Leicester, Leicester, UK NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK. · Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. · Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK. · Genetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK. · Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands Department of Medical Genetics, Division of Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands. · Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands. · Department of Vascular Medicine, Academic Medical Center, Amsterdam 1105 AZ, The Netherlands. · Department of Genetics Environment and Evolution, UCL Genetics Institute, 2nd Floor, Darwin Building, Gower Street, London WC1E 6BT, UK. · Department of Medical Genetics, Division of Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. · Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK. · Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands. · Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK. · Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA. · Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. · Baylor College of Medicine, Department of Medicine, Division of Atherosclerosis and Vascular Medicine, Houston, TX 77030, USA. · Department of Medicine, University of Vermont, 208 South Park Dr, Colchester, VT 05446, USA Department of Pathology, University of Vermont, 208 South Park Dr, Colchester, VT 05446, USA. · The University of Texas Health Science Center at Houston, Houston, TX, USA. · Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. · Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA Department of Epidemiology, University of Washington, Seattle, WA, USA. · Department of Laboratory Medicine and Pathology, University of Minnesota. · Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. · Department Pathology and Medical Biology, Medical Biology Division, Molecular Genetics, University Medical Center Groningen and Groningen University, Groningen, The Netherlands. · Centre for Prevention and Health Services Research at National Institute for Public Health and the Environment, Utrecht, The Netherlands. · Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. · Lund University, Malmö, Sweden. · Department of Primary Care and Population Health, UCL, Royal Free Campus, Rowland Hill St, London, UK. · School of Social and Community Medicine, University of Bristol. · Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. · Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany. · MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK. · Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, Rayne Building, London WC1E 6JF, UK. · Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. · Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. · Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA. · Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA. · Department of Medical Genetics, Division of Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Genetics, University of North Carolina School of Medicine at Chapel Hill, Chapel Hill,NC27514, USA. · Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. · Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London WC1E 6BT, UK. · Division of Transplant Surgery, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104, USA Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA Department of Paediatrics, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. · Genetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. ·Eur Heart J · Pubmed #24474739.

ABSTRACT: AIMS: To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization. METHODS AND RESULTS: We developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholesterol (LDL-C). For each trait, we constructed two scores. The first was unrestricted, including all independent SNPs associated with the lipid trait identified from a prior meta-analysis (threshold P < 2 × 10(-6)); and the second a restricted score, filtered to remove any SNPs also associated with either of the other two lipid traits at P ≤ 0.01. Mendelian randomization meta-analyses were conducted in 17 studies including 62,199 participants and 12,099 CHD events. Both the unrestricted and restricted allele scores for LDL-C (42 and 19 SNPs, respectively) associated with CHD. For HDL-C, the unrestricted allele score (48 SNPs) was associated with CHD (OR: 0.53; 95% CI: 0.40, 0.70), per 1 mmol/L higher HDL-C, but neither the restricted allele score (19 SNPs; OR: 0.91; 95% CI: 0.42, 1.98) nor the unrestricted HDL-C allele score adjusted for triglycerides, LDL-C, or statin use (OR: 0.81; 95% CI: 0.44, 1.46) showed a robust association. For triglycerides, the unrestricted allele score (67 SNPs) and the restricted allele score (27 SNPs) were both associated with CHD (OR: 1.62; 95% CI: 1.24, 2.11 and 1.61; 95% CI: 1.00, 2.59, respectively) per 1-log unit increment. However, the unrestricted triglyceride score adjusted for HDL-C, LDL-C, and statin use gave an OR for CHD of 1.01 (95% CI: 0.59, 1.75). CONCLUSION: The genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain.