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Coronary Artery Disease: HELP
Articles from National Institute for Health and Welfare Finland
Based on 34 articles published since 2010
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These are the 34 published articles about Coronary Artery Disease that originated from National Institute for Health and Welfare Finland during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Editorial Is the association between alcohol use and coronary artery disease causal? Evidence from a long-term twin study. 2015

Kaprio, Jaakko. ·Department of Public Health and the Institute for Molecular Medicine, University of Helsinki, and Department of Health, National Institute for Health and Welfare, Helsinki, Finland jaakko.kaprio@helsinki.fi. ·Am J Clin Nutr · Pubmed #26063692.

ABSTRACT: -- No abstract --

2 Article Outcomes of lipid control in secondary prevention of coronary artery disease in Finland: A 24-month follow-up after acute coronary syndrome. 2020

Leskelä, Riikka-Leena / Torvinen, Anna / Rissanen, Tuomas T / Virtanen, Vesa / Herse, Fredrik / Nuutinen, Mikko / Mustonen, Juha / Laatikainen, Tiina. ·Nordic Healthcare Group, Vattuniemenranta 2, 00210, Helsinki, Finland. Electronic address: riikka-leena.leskela@nhg.fi. · Nordic Healthcare Group, Vattuniemenranta 2, 00210, Helsinki, Finland. · Heart Center, North Karelia Central Hospital, Tikkamäentie 16, 80210, Joensuu, Finland. · Tampere University Hospital, Biokatu 6 PO Box 2000, 33521, Tampere, Finland. · University of Eastern Finland, Joensuu, Finland; National Institute for Health and Welfare, Mannerheimintie 166, 00300, Helsinki, Finland; Joint Municipal Authority for North Karelia Social and Health Care Services (Siun Sote), Joensuu, Finland. ·Atherosclerosis · Pubmed #31999985.

ABSTRACT: BACKGROUND AND AIMS: Ischemic heart diseases are the main cause of death worldwide, therefore secondary prevention and treatment of coronary artery disease (CAD) are highly significant for public health and mortality. The objective of this study is to evaluate LDL cholesterol (LDL-C) levels as outcomes of secondary prevention of CAD in Finland up to 24 months after being diagnosed with acute coronary syndrome (ACS). This retrospective analysis of patients with ACS was conducted in two areas of Finland that have a combined population of 400,000. METHODS: The data used in the study covered all outpatient visits, inpatient episodes, prescriptions and LDL-C results for ACS patients during 2011-2015. To evaluate the outcome of the prevention, three separate measurements of patients' LDL-C levels were considered: baseline, first follow-up and final follow-up. The factors associated with reaching treatment goal were identified using logistic regression analysis. RESULTS: 32% of ACS patients achieved the treatment goal (LDL-C <1.8 mmol/l) at the end of the 24-month follow-up period, but 21% of patients fluctuated between being on and above target. CONCLUSION: Two thirds of CAD patients with ACS and on statin therapy do not achieve LDL-C treatment target recommended by the guidelines. Since LDL-C levels fluctuate in the follow-up, a low level during the first 12 months after the acute event does not guarantee the maintenance of the results in the long term. Hence, LDL-C levels should be monitored at least on an yearly basis on follow-ups, and treatment adapted accordingly.

3 Article Coronary Artery Disease Risk and Lipidomic Profiles Are Similar in Hyperlipidemias With Family History and Population-Ascertained Hyperlipidemias. 2019

Rämö, Joel T / Ripatti, Pietari / Tabassum, Rubina / Söderlund, Sanni / Matikainen, Niina / Gerl, Mathias J / Klose, Christian / Surma, Michal A / Stitziel, Nathan O / Havulinna, Aki S / Pirinen, Matti / Salomaa, Veikko / Freimer, Nelson B / Jauhiainen, Matti / Palotie, Aarno / Taskinen, Marja-Riitta / Simons, Kai / Ripatti, Samuli. ·1 Institute for Molecular Medicine Finland HiLIFE University of Helsinki Finland. · 2 Research Programs Unit Clinical and Molecular Metabolism University of Helsinki Finland. · 3 Endocrinology Abdominal Center Helsinki University Hospital Helsinki Finland. · 4 Lipotype GmbH Dresden Germany. · 5 Łukasiewicz Research Network-PORT Polish Center for Technology Development Wroclaw Poland. · 6 Cardiovascular Division Department of Medicine Washington University School of Medicine St. Louis MO. · 7 Department of Genetics Washington University School of Medicine St. Louis MO. · 8 McDonnell Genome Institute Washington University School of Medicine St. Louis MO. · 9 National Institute for Health and Welfare Helsinki Finland. · 10 Department of Mathematics and Statistics Faculty of Science University of Helsinki Finland. · 16 Department of Public Health Clinicum Faculty of Medicine University of Helsinki Finland. · 11 Center for Neurobehavioral Genetics Semel Institute for Neuroscience and Human Behavior University of California Los Angeles CA. · 12 Minerva Foundation Institute for Medical Research Biomedicum Helsinki Finland. · 13 Program in Medical and Population Genetics and The Stanley Center for Psychiatric Research The Broad Institute of MIT and Harvard Cambridge MA. · 14 Psychiatric and Neurodevelopmental Genetics Unit Department of Psychiatry, Analytic and Translational Genetics Unit Department of Medicine, and the Department of Neurology Massachusetts General Hospital Boston MA. · 15 Max Planck Institute of Cell Biology and Genetics Dresden Germany. ·J Am Heart Assoc · Pubmed #31256696.

ABSTRACT: Background We asked whether, after excluding familial hypercholesterolemia, individuals with high low-density lipoprotein cholesterol ( LDL -C) or triacylglyceride levels and a family history of the same hyperlipidemia have greater coronary artery disease risk or different lipidomic profiles compared with population-based hyperlipidemias. Methods and Results We determined incident coronary artery disease risk for 755 members of 66 hyperlipidemic families (≥2 first-degree relatives with similar hyperlipidemia) and 19 644 Finnish FINRISK population study participants. We quantified 151 circulating lipid species from 550 members of 73 hyperlipidemic families and 897 FINRISK participants using mass spectrometric shotgun lipidomics. Familial hypercholesterolemia was excluded using functional LDL receptor testing and genotyping. Hyperlipidemias ( LDL -C or triacylglycerides >90th population percentile) associated with increased coronary artery disease risk in meta-analysis of the hyperlipidemic families and the population cohort (high LDL -C: hazard ratio, 1.74 [95% CI, 1.48-2.04]; high triacylglycerides: hazard ratio, 1.38 [95% CI, 1.09-1.74]). Risk estimates were similar in the family and population cohorts also after adjusting for lipid-lowering medication. In lipidomic profiling, high LDL -C associated with 108 lipid species, and high triacylglycerides associated with 131 lipid species in either cohort (at 5% false discovery rate; P-value range 0.038-2.3×10

4 Article Genetic Determinants of Circulating Glycine Levels and Risk of Coronary Artery Disease. 2019

Jia, Qiong / Han, Yi / Huang, Pin / Woodward, Nicholas C / Gukasyan, Janet / Kettunen, Johannes / Ala-Korpela, Mika / Anufrieva, Olga / Wang, Qin / Perola, Markus / Raitakari, Olli / Lehtimäki, Terho / Viikari, Jorma / Järvelin, Marjo-Riitta / Boehnke, Michael / Laakso, Markku / Mohlke, Karen L / Fiehn, Oliver / Wang, Zeneng / Tang, W H Wilson / Hazen, Stanley L / Hartiala, Jaana A / Allayee, Hooman. ·1 Department of Preventive Medicine Keck School of Medicine, University of Southern California Los Angeles CA. · 2 Department of Biochemistry & Molecular Medicine Keck School of Medicine, University of Southern California Los Angeles CA. · 3 Xiangya School of Medicine Central South University Hunan China. · 4 Computational Medicine Faculty of Medicine University of Oulu and Biocenter Oulu Oulu Finland. · 5 National Institute for Health and Welfare Helsinki Finland. · 6 Systems Epidemiology Baker Heart and Diabetes Institute Melbourne Victoria Australia. · 7 NMR Metabolomics Laboratory School of Pharmacy University of Eastern Finland Kuopio Finland. · 9 Population Health Science Bristol Medical School University of Bristol United Kingdom. · 10 Medical Research Council Integrative Epidemiology Unit at the University of Bristol United Kingdom. · 11 Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Faculty of Medicine Nursing and Health Sciences The Alfred Hospital Monash University Melbourne Victoria Australia. · 12 Estonian Genome Center University of Tartu Estonia. · 13 Institute for Molecular Medicine (FIMM) University of Helsinki Finland. · 14 Research Centre of Applied and Preventive Cardiovascular Medicine University of Turku Finland. · 17 Department of Clinical Physiology Turku University Hospital Turku Finland. · 18 Department of Clinical Chemistry Fimlab Laboratories and Faculty of Medicine and Health Technology Finnish Cardiovascular Research Center-Tampere Tampere University Tampere Finland. · 15 Department of Medicine University of Turku Finland. · 16 Division of Medicine Turku University Hospital Turku Finland. · 19 Department of Epidemiology and Biostatistics School of Public Health MRC-PHE Centre for Environment and Health Imperial College London London United Kingdom. · 20 Center for Life Course and Systems Epidemiology University of Oulu Finland. · 21 Unit of Primary Care Oulu University Hospital Oulu Finland. · 22 Department of Biostatistics and Center for Statistical Genetics University of Michigan Ann Arbor MI. · 8 School of Medicine University of Eastern Finland Kuopio Finland. · 23 Department of Genetics University of North Carolina Chapel Hill NC. · 24 Genome Center University of California Davis CA. · 25 Department of Cardiovascular Medicine Cleveland Clinic Cleveland OH. · 26 Department of Cellular & Molecular Medicine Cleveland Clinic Cleveland OH. ·J Am Heart Assoc · Pubmed #31070104.

ABSTRACT: Background Recent studies have revealed sexually dimorphic associations between the carbamoyl-phosphate synthase 1 locus, intermediates of the metabolic pathway leading from choline to urea, and risk of coronary artery disease ( CAD ) in women. Based on evidence from the literature, the atheroprotective association with carbamoyl-phosphate synthase 1 could be mediated by the strong genetic effect of this locus on increased circulating glycine levels. Methods and Results We sought to identify additional genetic determinants of circulating glycine levels by carrying out a meta-analysis of genome-wide association study data in up to 30 118 subjects of European ancestry. Mendelian randomization and other analytical approaches were used to determine whether glycine-associated variants were associated with CAD and traditional risk factors. Twelve loci were significantly associated with circulating glycine levels, 7 of which were not previously known to be involved in glycine metabolism ( ACADM , PHGDH , COX 18- ADAMTS 3, PSPH , TRIB 1, PTPRD , and ABO ). Glycine-raising alleles at several loci individually exhibited directionally consistent associations with decreased risk of CAD . However, these effects could not be attributed directly to glycine because of associations with other CAD -related traits. By comparison, genetic models that only included the 2 variants directly involved in glycine degradation and for which there were no other pleiotropic associations were not associated with risk of CAD or blood pressure, lipid levels, and obesity-related traits. Conclusions These results provide additional insight into the genetic architecture of glycine metabolism, but do not yield conclusive evidence for a causal relationship between circulating levels of this amino acid and risk of CAD in humans.

5 Article Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders. 2018

Ligthart, Symen / Vaez, Ahmad / Võsa, Urmo / Stathopoulou, Maria G / de Vries, Paul S / Prins, Bram P / Van der Most, Peter J / Tanaka, Toshiko / Naderi, Elnaz / Rose, Lynda M / Wu, Ying / Karlsson, Robert / Barbalic, Maja / Lin, Honghuang / Pool, René / Zhu, Gu / Macé, Aurélien / Sidore, Carlo / Trompet, Stella / Mangino, Massimo / Sabater-Lleal, Maria / Kemp, John P / Abbasi, Ali / Kacprowski, Tim / Verweij, Niek / Smith, Albert V / Huang, Tao / Marzi, Carola / Feitosa, Mary F / Lohman, Kurt K / Kleber, Marcus E / Milaneschi, Yuri / Mueller, Christian / Huq, Mahmudul / Vlachopoulou, Efthymia / Lyytikäinen, Leo-Pekka / Oldmeadow, Christopher / Deelen, Joris / Perola, Markus / Zhao, Jing Hua / Feenstra, Bjarke / Anonymous6100967 / Amini, Marzyeh / Anonymous6110967 / Lahti, Jari / Schraut, Katharina E / Fornage, Myriam / Suktitipat, Bhoom / Chen, Wei-Min / Li, Xiaohui / Nutile, Teresa / Malerba, Giovanni / Luan, Jian'an / Bak, Tom / Schork, Nicholas / Del Greco M, Fabiola / Thiering, Elisabeth / Mahajan, Anubha / Marioni, Riccardo E / Mihailov, Evelin / Eriksson, Joel / Ozel, Ayse Bilge / Zhang, Weihua / Nethander, Maria / Cheng, Yu-Ching / Aslibekyan, Stella / Ang, Wei / Gandin, Ilaria / Yengo, Loïc / Portas, Laura / Kooperberg, Charles / Hofer, Edith / Rajan, Kumar B / Schurmann, Claudia / den Hollander, Wouter / Ahluwalia, Tarunveer S / Zhao, Jing / Draisma, Harmen H M / Ford, Ian / Timpson, Nicholas / Teumer, Alexander / Huang, Hongyan / Wahl, Simone / Liu, YongMei / Huang, Jie / Uh, Hae-Won / Geller, Frank / Joshi, Peter K / Yanek, Lisa R / Trabetti, Elisabetta / Lehne, Benjamin / Vozzi, Diego / Verbanck, Marie / Biino, Ginevra / Saba, Yasaman / Meulenbelt, Ingrid / O'Connell, Jeff R / Laakso, Markku / Giulianini, Franco / Magnusson, Patrik K E / Ballantyne, Christie M / Hottenga, Jouke Jan / Montgomery, Grant W / Rivadineira, Fernando / Rueedi, Rico / Steri, Maristella / Herzig, Karl-Heinz / Stott, David J / Menni, Cristina / Frånberg, Mattias / St Pourcain, Beate / Felix, Stephan B / Pers, Tune H / Bakker, Stephan J L / Kraft, Peter / Peters, Annette / Vaidya, Dhananjay / Delgado, Graciela / Smit, Johannes H / Großmann, Vera / Sinisalo, Juha / Seppälä, Ilkka / Williams, Stephen R / Holliday, Elizabeth G / Moed, Matthijs / Langenberg, Claudia / Räikkönen, Katri / Ding, Jingzhong / Campbell, Harry / Sale, Michele M / Chen, Yii-Der I / James, Alan L / Ruggiero, Daniela / Soranzo, Nicole / Hartman, Catharina A / Smith, Erin N / Berenson, Gerald S / Fuchsberger, Christian / Hernandez, Dena / Tiesler, Carla M T / Giedraitis, Vilmantas / Liewald, David / Fischer, Krista / Mellström, Dan / Larsson, Anders / Wang, Yunmei / Scott, William R / Lorentzon, Matthias / Beilby, John / Ryan, Kathleen A / Pennell, Craig E / Vuckovic, Dragana / Balkau, Beverly / Concas, Maria Pina / Schmidt, Reinhold / Mendes de Leon, Carlos F / Bottinger, Erwin P / Kloppenburg, Margreet / Paternoster, Lavinia / Boehnke, Michael / Musk, A W / Willemsen, Gonneke / Evans, David M / Madden, Pamela A F / Kähönen, Mika / Kutalik, Zoltán / Zoledziewska, Magdalena / Karhunen, Ville / Kritchevsky, Stephen B / Sattar, Naveed / Lachance, Genevieve / Clarke, Robert / Harris, Tamara B / Raitakari, Olli T / Attia, John R / van Heemst, Diana / Kajantie, Eero / Sorice, Rossella / Gambaro, Giovanni / Scott, Robert A / Hicks, Andrew A / Ferrucci, Luigi / Standl, Marie / Lindgren, Cecilia M / Starr, John M / Karlsson, Magnus / Lind, Lars / Li, Jun Z / Chambers, John C / Mori, Trevor A / de Geus, Eco J C N / Heath, Andrew C / Martin, Nicholas G / Auvinen, Juha / Buckley, Brendan M / de Craen, Anton J M / Waldenberger, Melanie / Strauch, Konstantin / Meitinger, Thomas / Scott, Rodney J / McEvoy, Mark / Beekman, Marian / Bombieri, Cristina / Ridker, Paul M / Mohlke, Karen L / Pedersen, Nancy L / Morrison, Alanna C / Boomsma, Dorret I / Whitfield, John B / Strachan, David P / Hofman, Albert / Vollenweider, Peter / Cucca, Francesco / Jarvelin, Marjo-Riitta / Jukema, J Wouter / Spector, Tim D / Hamsten, Anders / Zeller, Tanja / Uitterlinden, André G / Nauck, Matthias / Gudnason, Vilmundur / Qi, Lu / Grallert, Harald / Borecki, Ingrid B / Rotter, Jerome I / März, Winfried / Wild, Philipp S / Lokki, Marja-Liisa / Boyle, Michael / Salomaa, Veikko / Melbye, Mads / Eriksson, Johan G / Wilson, James F / Penninx, Brenda W J H / Becker, Diane M / Worrall, Bradford B / Gibson, Greg / Krauss, Ronald M / Ciullo, Marina / Zaza, Gianluigi / Wareham, Nicholas J / Oldehinkel, Albertine J / Palmer, Lyle J / Murray, Sarah S / Pramstaller, Peter P / Bandinelli, Stefania / Heinrich, Joachim / Ingelsson, Erik / Deary, Ian J / Mägi, Reedik / Vandenput, Liesbeth / van der Harst, Pim / Desch, Karl C / Kooner, Jaspal S / Ohlsson, Claes / Hayward, Caroline / Lehtimäki, Terho / Shuldiner, Alan R / Arnett, Donna K / Beilin, Lawrence J / Robino, Antonietta / Froguel, Philippe / Pirastu, Mario / Jess, Tine / Koenig, Wolfgang / Loos, Ruth J F / Evans, Denis A / Schmidt, Helena / Smith, George Davey / Slagboom, P Eline / Eiriksdottir, Gudny / Morris, Andrew P / Psaty, Bruce M / Tracy, Russell P / Nolte, Ilja M / Boerwinkle, Eric / Visvikis-Siest, Sophie / Reiner, Alex P / Gross, Myron / Bis, Joshua C / Franke, Lude / Franco, Oscar H / Benjamin, Emelia J / Chasman, Daniel I / Dupuis, Josée / Snieder, Harold / Dehghan, Abbas / Alizadeh, Behrooz Z / and others. ·Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3000 CA, the Netherlands. · Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, the Netherlands; Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran. · Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, the Netherlands; Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu 51010, Estonia. · Université de Lorraine, INSERM, IGE-PCV, 54000 Nancy, France. · Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3000 CA, the Netherlands; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. · Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK. · Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, the Netherlands. · Translational Gerontology Branch, National Institute on Aging, Baltimore, MD 21224, USA. · Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, the Netherlands; Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, the Netherlands. · Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA. · Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden. · University of Split School of Medicine, Split 21000, Croatia. · Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. · Department of Biological Psychology, Netherlands Twin Register, Vrije Universiteit, Amsterdam 1081 BT, the Netherlands; Amsterdam Public Health research institute, VU University Medical Center, Amsterdam 1081 BT, the Netherlands. · QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia. · Department of Computational Biology, University of Lausanne, Lausanne 1010, Switzerland; Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland; Institute of Social and Preventive Medicine, University Hospital of Lausanne, Lausanne 1010, Switzerland. · Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Sardinia 08045, Italy. · Department of Cardiology, Leiden University Medical Center, Leiden 2300 RC, the Netherlands; Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands. · Department of Twin Research & Genetic Epidemiology, King's College London, London SE1 7EH, UK; NIHR Biomedical Research Centre at Guy's and St. Thomas' Foundation Trust, London SE1 9RT, UK. · Unit of Genomics of Complex Diseases, Institut d'Investigació Biomèdica Sant Pau, Barcelona 08025, Spain; Cardiovascular Medicine Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm 17176, Sweden. · University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD 4102, Australia; MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK. · Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, the Netherlands; Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, the Netherlands; MRC Epidemiology Unit, University of Cambridge School of Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. · Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt University Greifswald, Greifswald 17475, Germany; German Centre for Cardiovascular Research, Partner Site Greifswald, Greifswald 17475, Germany. · University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen 9713 AV, the Netherlands. · Icelandic Heart Association, Kopavogur 201, Iceland; Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland. · Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. · Institute of Epidemiology II, Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany; German Center for Diabetes Research, Partner Site Munich, Munich 85764, Germany. · Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63108-2212, USA. · Department of Epidemiology and Prevention, Public Health Sciences, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA. · Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany. · Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, Amsterdam University Medical Center/GGZ inGeest Research & Innovation, Amsterdam 1081 HJ, the Netherlands. · Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg 20246, Germany; Institute of Medical Biometry and Statistics, University Medical Center Schleswig-Holstein, Campus Luebeck, Lübeck 23562, Germany; German Center for Cardiovascular Research, Partner Site RhineMain, 55131 Mainz, Germany. · Transplantation Laboratory, Medicum, University of Helsinki, Helsinki 00014, Finland. · Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33014, Finland; Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere 33520, Finland. · Hunter Medical Research Institute, New Lambon Heights, NSW 2305, Australia; Centre for Clinical Epidemiology & Biostatistics, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia. · Molecular Epidemiology, Leiden University Medical Center, Leiden 2333 ZC, the Netherlands; Max Planck Institute for Biology of Ageing, Cologne 50931, Germany. · National Institute for Health and Welfare, Helsinki 00271, Finland. · MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge CB2 0QQ, UK. · Department of Epidemiology Research, Statens Serum Institut, Copenhagen 2300, Denmark. · Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki 00014, Finland; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki 00014, Finland; Folkhälsan Research Centre, Helsinki 00250, Finland. · Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh EH16 4UX, UK. · Human Genetics Center, School of Public Health and Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. · Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. · Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA. · Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA. · Institute of Genetics and Biophysics "A. Buzzati-Traverso," Consiglio Nazionale delle Ricerche, Napoli 80131, Italy. · Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona 37134, Italy. · Interdisciplinary Center Psychopathology and Emotion regulation, University Medical Center Groningen, University of Groningen, Groningen 9700 RB, the Netherlands. · Human Biology, J. Craig Venter Institute, La Jolla, CA 92037, USA; Quantitative Medicine, Translational Genomics Research Institute, Phoenix, AZ 85004, USA. · Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lübeck, Bolzano 39100, Italy. · Institute of Epidemiology, Helmholtz Zentrum München - German Research Centre for Environmental Health, Neuherberg 85764, Germany; Ludwig Maximilian University of Munich, Dr. von Hauner Children's Hospital, Munich 80337, Germany. · Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. · Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK. · Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu 51010, Estonia. · Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Gothenburg 41345, Sweden. · Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-5618, USA. · Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK; Department of Cardiology, Ealing Hospital, Middlesex UB1 3HW, UK. · Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg 413 90, Sweden. · Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. · Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA. · Medical School, University of Western Australia, Perth, WA 6009, Australia. · AREA Science Park, Trieste 34149, Italy. · Centre National de la Recherche Scientifique UMR 8199, University of Lille, Institut Pasteur de Lille, European Genomic Institute for Diabetes, FR 3508, 59000 Lille, France; Program in Complex Trait Genomics, Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia. · Support OU, Institute of Genetic and Biomedic Research, Consiglio Nazionale delle Ricerche, Sassari 7100, Italy. · Fred Hutchinson Cancer Research Center, Public Health Sciences Division, Mail Stop M3-A410, 1100 Fairview Ave. N., Seattle, WA, USA. · Clinical Division of Neurogeriatrics, Department of Neurology, Medical University Graz, Graz 8036, Austria; Institute of Medical Informatics, Statistics and Documentation, Medical University Graz, Graz 8036, Austria. · Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, USA. · Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. · Department of Medical Statistics and Bio-informatics, Section Molecular Epidemiology, Leiden University Medical Center, Leiden 2333 ZC, the Netherlands. · Steno Diabetes Center Copenhagen, Gentofte 2820, Denmark; Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2100, Denmark. · Center for Integrative Genomics, School of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USA. · Department of Biological Psychology, Netherlands Twin Register, Vrije Universiteit, Amsterdam 1081 BT, the Netherlands; Amsterdam Public Health research institute, VU University Medical Center, Amsterdam 1081 BT, the Netherlands; Neuroscience Campus Amsterdam, Amsterdam 1081 HV, the Netherlands. · Robertson Centre for Biostatistics, University of Glasgow, Glasgow G12 8QQ, UK. · MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK. · Department SHIP-KEF, Institute for Community Medicine, University Medicine Greifswald, Greifswald 17475, Germany. · Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. · Boston VA Research Institute, Inc., Boston, MA 02130, USA. · Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden 2333 ZC, the Netherlands. · GeneSTAR Research Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. · Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK. · Institute for Maternal and Child Health, IRCCS "Burlo Garofolo," Trieste 34140, Italy. · Centre National de la Recherche Scientifique UMR 8199, University of Lille, Institut Pasteur de Lille, European Genomic Institute for Diabetes, FR 3508, 59000 Lille, France. · Institute of Molecular Genetics, Consiglio Nazionale delle Ricerche, Pavia 27100, Italy. · Gottfried Schatz Research Center, Institute for Molecular Biology and Biochemistry, 8010 Graz, Austria. · Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio 70210, Finland. · Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Methodist DeBakey Heart and Vascular Center, Houston, TX 77030, USA. · Department of Biological Psychology, Netherlands Twin Register, Vrije Universiteit, Amsterdam 1081 BT, the Netherlands. · Department of Internal Medicine, Erasmus University Medical Center, Rotterdam 3015 CN, the Netherlands. · Department of Computational Biology, University of Lausanne, Lausanne 1010, Switzerland; Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland. · Department of Physiology, Institute of Biomedicine, University of Oulu, Medical Research Center Oulu and Oulu University Hospital, Oulu 90014, Finland; Biocenter Oulu, University of Oulu, Oulu 90220, Finland; Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan 60-512, Poland. · Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Glasgow G12 8QQ, UK. · Department of Twin Research & Genetic Epidemiology, King's College London, London SE1 7EH, UK. · Cardiovascular Medicine Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm 17176, Sweden; Department of Numerical Analysis and Computer Science, Stockholm University, Stockholm 100 44, Sweden. · MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK; Donders Institute, Radboud University, Nijmegen 6525 XD, the Netherlands. · German Centre for Cardiovascular Research, Partner Site Greifswald, Greifswald 17475, Germany; Department for Internal Medicine B, University Medicine Greifswald, Greifswald 17475, Germany. · Department of Epidemiology Research, Statens Serum Institut, Copenhagen 2300, Denmark; Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2100, Denmark. · Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, the Netherlands. · Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherber 85764, Germany. · Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University Mainz, Mainz 55131, Germany. · Heart and Lung Center, Helsinki University Hospital and Helsinki University, Helsinki 00029, Finland. · Department of Neurology, University of Virginia, Charlottesville, VA 22908, USA. · Molecular Epidemiology, Leiden University Medical Center, Leiden 2333 ZC, the Netherlands. · Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki 00014, Finland. · Department of Internal Medicine/Geriatrics, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA. · Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia; Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia. · Institute of Genetics and Biophysics "A. Buzzati-Traverso," Consiglio Nazionale delle Ricerche, Napoli 80131, Italy; IRCCS Neuromed, Pozzilli (IS) 86077, Italy. · Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK. · Department of Pediatrics and Rady Children's Hospital, School of Medicine, University of California, San Diego, La Jolla, CA 92037, USA. · Center for Cardiovascular Health, Tulane University, New Orleans, LA 70112, USA. · Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA. · Department of Public Health and Caring Sciences, Molecular Geriatrics, Uppsala University, Uppsala 752 37, Sweden. · Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK. · Department of Medical Sciences, Uppsala University, Uppsala 751 41, Sweden. · Department of Medicine, Case Cardiovascular Research Institute, Case Western Reserve University, Harrington Heart & Vascular Institute, University Hospitals, Cleveland, OH 44106, USA. · Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Gothenburg 41345, Sweden; Geriatric Medicine, Sahlgrenska University Hospital, Mölndal 431 80, Sweden. · PathWest Laboratory Medicine WA, Nedlands, WA 6009, Australia; School of Biomedical Sciences, University of Western Australia, Crawley, Perth, WA 6009, Australia. · Medical Sciences, Surgical and Health Department, University of Trieste, Trieste 34137, Italy. · INSERM U1018, Centre de Recherche en Epidémiologie et Santé des Populations, Team 5 (EpReC, Renal, and Cardiovascular Epidemiology), Université de Versailles Saint-Quentin-en-Yvelines, Université Paris-Saclay, Villejuif 94807, France. · Clinical Division of Neurogeriatrics, Department of Neurology, Medical University Graz, Graz 8036, Austria. · Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA. · Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. · Department of Rheumatology, Leiden University Medical Center, Leiden 2300 RC, the Netherlands; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden 2333 ZC, the Netherlands. · Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA. · Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia; Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia. · Department of Psychiatry, Washington University School of Medicine, 4560 Clayton Ave., Suite 1000, St. Louis, MO 63110, USA. · Department of Clinical Physiology, Tampere University Hospital, Tampere 33520, Finland; Department of Clinical Physiology, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere 33520, Finland. · Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland; Institute of Social and Preventive Medicine, University Hospital of Lausanne, Lausanne 1010, Switzerland. · Center for Life Course Health Research, Faculty of Medicine, University of Oulu, 90014 Oulun yliopisto, Finland. · Gerontology and Geriatric Medicine, Sticht Center on Aging and Rehabilitation, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA. · BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, Glasgow G12 8TA, UK. · Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK. · Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, USA. · Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku 20520, Finland; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20520, Finland. · Hunter Medical Research Institute, New Lambon Heights, NSW 2305, Australia; Centre for Clinical Epidemiology & Biostatistics, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia; John Hunter Hospital, New Lambton Heights, NWS 2305, Australia. · Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands. · Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki 00014, Finland; Hospital for Children and Adolescents, Helsinki University Central Hospital and University of Helsinki, Helsinki 00290, Finland; Department of Obstetrics and Gynaecology, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu 90014, Finland. · Division of Nephrology and Dialysis, Columbus-Gemelli University Hospital, Università Cattolica del Sacro Cuore, Roma 168, Italy. · Institute of Epidemiology, Helmholtz Zentrum München - German Research Centre for Environmental Health, Neuherberg 85764, Germany. · Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7FZ, UK; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA. · Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK; Alzheimer's Scotland Dementia Research Centre, University of Edinburgh, Edinburgh EH8 9JZ, UK. · Department of Clinical Sciences and Orthopaedic Surgery, Lund University, Malmo 20502, Sweden. · Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK; Department of Cardiology, Ealing Hospital, Middlesex UB1 3HW, UK; Imperial College Healthcare NHS Trust, London W12 0HS, UK; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore; MRC-PHE Centre for Environment and Health, Imperial College London, London W2 1PG, UK. · Center for Life Course Health Research, Faculty of Medicine, University of Oulu, 90014 Oulun yliopisto, Finland; Unit of Primary Health Care, Oulu University Hospital, Oulu 90220, Finland. · Department of Epidemiology and Public Health, University College Cork, Cork T12 K8AF, Ireland. · Institute of Epidemiology II, Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany; German Center for Cardiovascular Research, Partner Site Munich Heart Alliance, 80636 Munich, Germany. · Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany; Genetic Epidemiology, Institute of Medical Informatics, Biometry, and Epidemiology, Faculty of Medicine, Ludwig Maximilian University of Munich, Neuherberg 85764, Germany. · Institute of Human Genetics, Technische Universität München, Munich 85764, Germany; Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg 85764, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich 81377, Germany. · Hunter Medical Research Institute, New Lambon Heights, NSW 2305, Australia; Information-Based Medicine Stream, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia. · Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA. · Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. · Population Health Research Institute, St. George's, University of London, London SW17 0RE, UK. · Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland. · Biocenter Oulu, University of Oulu, Oulu 90220, Finland; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, 90014 Oulun yliopisto, Finland; Unit of Primary Health Care, Oulu University Hospital, Oulu 90220, Finland; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London W2 1PG, UK; Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Kingston Lane, Uxbridge, Middlesex UB8 3PH, UK. · Department of Cardiology, Leiden University Medical Center, Leiden 2300 RC, the Netherlands; Durrer Center for Cardiogenetic Research, Amsterdam 3501 DG, the Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht 3511 EP, the Netherlands. · Cardiovascular Medicine Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm 17176, Sweden. · Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg 20246, Germany; German Center for Cardiovascular Research, Partner Site RhineMain, 55131 Mainz, Germany. · Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3000 CA, the Netherlands; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam 3015 CN, the Netherlands. · German Centre for Cardiovascular Research, Partner Site Greifswald, Greifswald 17475, Germany; Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald 17475, Germany. · Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA. (and more) ·Am J Hum Genet · Pubmed #30388399.

ABSTRACT: C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10

6 Article A comprehensive evaluation of the genetic architecture of sudden cardiac arrest. 2018

Ashar, Foram N / Mitchell, Rebecca N / Albert, Christine M / Newton-Cheh, Christopher / Brody, Jennifer A / Müller-Nurasyid, Martina / Moes, Anna / Meitinger, Thomas / Mak, Angel / Huikuri, Heikki / Junttila, M Juhani / Goyette, Philippe / Pulit, Sara L / Pazoki, Raha / Tanck, Michael W / Blom, Marieke T / Zhao, XiaoQing / Havulinna, Aki S / Jabbari, Reza / Glinge, Charlotte / Tragante, Vinicius / Escher, Stefan A / Chakravarti, Aravinda / Ehret, Georg / Coresh, Josef / Li, Man / Prineas, Ronald J / Franco, Oscar H / Kwok, Pui-Yan / Lumley, Thomas / Dumas, Florence / McKnight, Barbara / Rotter, Jerome I / Lemaitre, Rozenn N / Heckbert, Susan R / O'Donnell, Christopher J / Hwang, Shih-Jen / Tardif, Jean-Claude / VanDenburgh, Martin / Uitterlinden, André G / Hofman, Albert / Stricker, Bruno H C / de Bakker, Paul I W / Franks, Paul W / Jansson, Jan-Hakan / Asselbergs, Folkert W / Halushka, Marc K / Maleszewski, Joseph J / Tfelt-Hansen, Jacob / Engstrøm, Thomas / Salomaa, Veikko / Virmani, Renu / Kolodgie, Frank / Wilde, Arthur A M / Tan, Hanno L / Bezzina, Connie R / Eijgelsheim, Mark / Rioux, John D / Jouven, Xavier / Kääb, Stefan / Psaty, Bruce M / Siscovick, David S / Arking, Dan E / Sotoodehnia, Nona. ·McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins, 733 N Broadway, Baltimore, MD, USA. · Divisions of Preventive Medicine and Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave East, 3rd Floor, Boston, MA, USA. · Center for Human Genetic Research & Cardiovascular Research Center, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, USA. · Cardiovascular Health Research Unit, Department of Medicine, University of Washington, 1730 Minor Ave, Seattle, WA, USA. · Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstädter Landstraße 1, Neuherberg, Germany. · Chair of Genetic Epidemiology, Institute for Medical Informatics, Biometry and Epidemiology, Faculty of Medicine, Ludwig-Maximilians University, Marchioninistr. 15, Munich, Germany. · Department of Internal Medicine I (Cardiology), Hospital of the Ludwig-Maximilians-University, Marchioninistr. 15, Munich, Germany. · DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Biedersteiner Strasse 29, Munich, Germany. · Institute of Human Genetics, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, Neuherberg, Germany. · Institute of Human Genetics, Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse 22, Munich, Germany. · Cardiovascular Research Institute and Institute for Human Genetics, University of California, San Francisco, 1550 4th Street, San Francisco, CA, USA. · Research Unit of Internal Medicine, University Hospital and University of Oulu, Kajaaninkatu 50, Oulu, Finland. · Montreal Heart Institute, Université de Montréal, 5000 rue Bélanger, Montréal, Quebec, Canada. · Department of Genetics, Center for Molecular Medicine, University Medical Centre Utrecht, Heidelberglaan 100, Utrecht, The Netherlands. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Hospital, Praed St, Paddington, London, UK. · Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Meibergdreef 9, AZ Amsterdam, The Netherlands. · Department of Clinical and Experimental Cardiology, Heart Center, Academic Medical Center, Meibergdreef 9, AZ Amsterdam, The Netherlands. · CVPath Institute, 19 Firstfield Road, Gaithersburg, MD, USA. · National Institute for Health and Welfare, Mannerheimintie 166, Helsinki, Finland. · Department of Cardiology, Rigshospitalet, Inge Lehmanns Vej 7, Copenhagen, Denmark. · Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, University of Utrecht, Heidelberglaan 100, Utrecht, The Netherlands. · Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Barngatan 4, Skånes universitetssjukhus, Malmo, Sweden. · Department of Epidemiology, Johns Hopkins University, 615 N Wolfe Street, Baltimore, MD, USA. · Public Health Sciences, Wake Forest University, Medical Center Boulevard, Winston-Salem, NC, USA. · Institute of Social and Preventative Medicine, University of Bern, Mittelstrasse 43, Bern, Switzerland. · Department of Epidemiology, Erasmus MC, Dr. Molewaterplein 50, GE Rotterdam, The Netherlands. · Department of Statistics, University of Auckland, Private Bag 92014, Auckland, New Zealand. · Paris Sudden Death Expertise Center, University Paris Descartes, Sorbonne Paris Cité, INSERM U970, 56 rue Leblanc, Paris, France. · Department of Biostatistics, University of Washington, F-600, Health Sciences Building 1705 NE Pacific Street, Seattle, WA, USA. · The Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 W. Carson Street, Torrance, CA, USA. · Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, 1959 NE Pacific St, Seattle, WA, USA. · NHLBI Framingham Heart Study, 73 Mount Wayte Avenue, Suite #2, Framingham, MA, USA. · Cardiology Section, Department of Medicine, Boston VA Healthcare System, 1400 VFW Parkway, Boston, MA, USA. · Erasmus MC University Medical Center, Department of Internal Medicine, Dr. Molewaterplein 40, CD Rotterdam, The Netherlands. · Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, The Netherlands. · Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, The Netherlands. · Department of Public Health and Clinical Medicine, Research Unit Skelleftea, Umea University, University Hospital, Building 1A, 4st, Umea, Sweden. · Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, 69-75 Chenies Mews, London, UK. · Institute of Health Informatics, University College London, 222 Euston Road London, UK. · Department of Pathology, Division of Cardiovascular Pathology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Rm 632B, Baltimore, MD, USA. · Department of Laboratory Medicine & Pathology, Mayo Clinic, 3050 Superior Drive, Rochester, MN, USA. · Department of Forensic Medicine, Faculty of Medical Sciences, University of Copenhagen, Inge Lehmanns Vej 7, Copenhagen, Denmark. · Department of Cardiology, University of Lund, Getingevägen 4, Lund, Sweden. · Amsterdam UMC, University of Amsterdam, Heart Center; Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Meibergdreef 9, AZ, Amsterdam, The Netherlands. · Department of Nephrology, University Medical Center Groningen, Hanzeplein 1, GZ, Groningen, The Netherlands. · Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, 1730 Minor Ave, suite #1360, Seattle, WA, USA. · The New York Academy of Medicine, 1216 5th Ave, New York, New York, USA. · Cardiovascular Health Research Unit, Division of Cardiology, Departments of Medicine and Epidemiology, University of Washington, 1730 Minor Ave, Seattle, WA, USA. ·Eur Heart J · Pubmed #30169657.

ABSTRACT: Aims: Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA. Methods and results: We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk. Conclusions: Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.

7 Article Susceptibility of low-density lipoprotein particles to aggregate depends on particle lipidome, is modifiable, and associates with future cardiovascular deaths. 2018

Ruuth, Maija / Nguyen, Su Duy / Vihervaara, Terhi / Hilvo, Mika / Laajala, Teemu D / Kondadi, Pradeep Kumar / Gisterå, Anton / Lähteenmäki, Hanna / Kittilä, Tiia / Huusko, Jenni / Uusitupa, Matti / Schwab, Ursula / Savolainen, Markku J / Sinisalo, Juha / Lokki, Marja-Liisa / Nieminen, Markku S / Jula, Antti / Perola, Markus / Ylä-Herttula, Seppo / Rudel, Lawrence / Öörni, Anssi / Baumann, Marc / Baruch, Amos / Laaksonen, Reijo / Ketelhuth, Daniel F J / Aittokallio, Tero / Jauhiainen, Matti / Käkelä, Reijo / Borén, Jan / Williams, Kevin Jon / Kovanen, Petri T / Öörni, Katariina. ·Atherosclerosis Research Laboratory, Wihuri Research Institute, Haartmaninkatu 8, 00290 Helsinki, Finland. · Research Programs Unit, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014 University of Helsinki, Finland. · Zora Biosciences, Biologinkuja 1, 02150 Espoo, Finland. · Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Tukholmankatu 8, P.O. Box 20, 00014 University of Helsinki, Finland. · Department of Mathematics and Statistics, University of Turku, Vesilinnantie 5, 20014 University of Turku, Finland. · Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, SU Sahlgrenska, 41345 Gothenburg, Sweden. · Department of Medicine, Karolinska University Hospital, Karolinska Institute, Solna 171 76 Stockholm, Sweden. · Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Yliopistonranta 1, P.O. Box 1627, 70211 Kuopio, Finland. · Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Yliopistonranta 1, P.O. Box 1627, 70211 Kuopio, Finland. · Institute of Clinical Medicine, Internal Medicine, Kuopio University Hospital, Puijonlaaksontie 2, P.O. Box 100, 70029 Kuopio, Finland. · Research Unit of Internal Medicine, University of Oulu, Pentti Kaiteran katu 1, P.O. Box 8000, 90014, Oulu, Finland. · Medical Research Center, Oulu University Hospital, Pentti Kaiteran katu 1, P.O. Box 8000, 90014 Oulu, Finland. · Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Haartmaninkatu 4, P.O. Box 340, 00029 Helsinki, Finland. · Transplantation Laboratory, Medicum, University of Helsinki, Haartmaninkatu 3, P.O. Box 21, 00014 Helsinki, Finland. · Genomics and Biomarkers Unit, Department of Health, National Institute for Health and Welfare, Genomics and Biomarkers Unit, Mannerheimintie 166, P.O. Box 30, 00271 Helsinki, Finland. · Institute for Molecular Medicine Finland and Diabetes and Obesity Research Program, University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014 University of Helsinki, Finland. · Heart Center and Gene Therapy Unit, Kuopio University Hospital, Puijonlaaksontie 2, P.O. Box 100, 70029 Kuopio, Finland. · Department of Biochemistry Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. · Information Systems, Åbo Akademi University, Fänriksgatan 3A, 20500 Turku, Finland. · Meilahti Clinical Proteomics Core Facility, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014 University of Helsinki, Finland. · Genentech Research and Early Development, 1 DNA Way Mailstop 258A, South San Francisco, CA 94080, USA. · Finnish Cardiovascular Research Center, University of Tampere, Kalevantie 4, 33100 Tampere, Finland. · Finnish Clinical Biobank Tampere, University Hospital of Tampere, Arvo Ylpön katu 6, 33520 Tampere, Finland. · Minerva Foundation Institute for Medical Research, Tukholmankatu 8, 00290 Helsinki, Finland. · Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 1, P.O. Box 65, 00014 University of Helsinki, Finland. · Helsinki University Lipidomics Unit, Helsinki Institute for Life Science (HiLIFE), Viikinkaari 1, P.O. Box 65, 00014 University of Helsinki, Finland. ·Eur Heart J · Pubmed #29982602.

ABSTRACT: Aims: Low-density lipoprotein (LDL) particles cause atherosclerotic cardiovascular disease (ASCVD) through their retention, modification, and accumulation within the arterial intima. High plasma concentrations of LDL drive this disease, but LDL quality may also contribute. Here, we focused on the intrinsic propensity of LDL to aggregate upon modification. We examined whether inter-individual differences in this quality are linked with LDL lipid composition and coronary artery disease (CAD) death, and basic mechanisms for plaque growth and destabilization. Methods and results: We developed a novel, reproducible method to assess the susceptibility of LDL particles to aggregate during lipolysis induced ex vivo by human recombinant secretory sphingomyelinase. Among patients with an established CAD, we found that the presence of aggregation-prone LDL was predictive of future cardiovascular deaths, independently of conventional risk factors. Aggregation-prone LDL contained more sphingolipids and less phosphatidylcholines than did aggregation-resistant LDL. Three interventions in animal models to rationally alter LDL composition lowered its susceptibility to aggregate and slowed atherosclerosis. Similar compositional changes induced in humans by PCSK9 inhibition or healthy diet also lowered LDL aggregation susceptibility. Aggregated LDL in vitro activated macrophages and T cells, two key cell types involved in plaque progression and rupture. Conclusion: Our results identify the susceptibility of LDL to aggregate as a novel measurable and modifiable factor in the progression of human ASCVD.

8 Article Risk of coronary artery disease and stroke according to sex and presence of diabetic nephropathy in type 1 diabetes. 2018

Harjutsalo, Valma / Thomas, Merlin C / Forsblom, Carol / Groop, Per-Henrik / Anonymous4500953. ·Folkhälsan Institute of Genetics, Folkhälsan Research Centre, Helsinki, Finland. · Abdominal Centre Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. · Research Program Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland. · National Institute for Health and Welfare, Chronic Disease Prevention Unit, Helsinki, Finland. · Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia. ·Diabetes Obes Metab · Pubmed #29962015.

ABSTRACT: AIMS: To determine the effect of different stages of diabetic nephropathy (DN) and sex on the excess and absolute morbidity of coronary artery disease (CAD) and stroke in people with type 1 diabetes (T1D) in order to distinguish different cardiovascular disease (CVD) risk profiles in people with T1D. MATERIALS AND METHODS: The study included 4410 people with T1D from the Finnish Diabetic Nephropathy Study (FinnDiane), divided by DN status, and a control population of 12 434 people without diabetes. CVD events were identified from the Finnish nationwide health registries. Cumulative incidences for CAD and stroke were calculated and standardized incidence ratios (SIRs) were estimated between participants with T1D and the control group, stratified by DN status and sex. RESULTS: There were 487 incident CADs and 290 strokes at the end of 2014 (median follow-up 12.9 years). The cumulative incidence rates of CAD and stroke were similar in men and women within different nephropathy groups. The SIR for CAD was 7.5 (95% confidence interval [CI] 6.9-8.2), 17.2 (95% CI 14.9-19.5) in women and 5.3 (95% CI 4.7-5.9) in men. The women-to-men ratio of SIR increased by nephropathy group: 3.3, 3.7, 5.3 and 6.8 in the normo-, micro- and macroalbuminuria and end-stage renal disease (ESRD) groups, respectively. The SIR for stroke was 5.0 (95% CI 4.3-5.5), similar in men and women. The women-to-men ratio of SIR for stroke was 0.8, 1.3, 1.6 and 1.7, in the normo-, micro- and macroalbuminuria and ESRD groups, respectively. The SIR in participants with normoalbuminuria and an estimated glomerular filtration rate ≥90 mL/min/1.73 m CONCLUSIONS: Although the excess CVD risk is several-fold greater in women compared to men, the absolute CVD risk in men and women was equal when nephropathy was taken into account. Even participants with normoalbuminuria and normal kidney function were found to have an excess CVD risk compared with the control group without diabetes.

9 Article Exome-wide association study of plasma lipids in >300,000 individuals. 2017

Liu, Dajiang J / Peloso, Gina M / Yu, Haojie / Butterworth, Adam S / Wang, Xiao / Mahajan, Anubha / Saleheen, Danish / Emdin, Connor / Alam, Dewan / Alves, Alexessander Couto / Amouyel, Philippe / Di Angelantonio, Emanuele / Arveiler, Dominique / Assimes, Themistocles L / Auer, Paul L / Baber, Usman / Ballantyne, Christie M / Bang, Lia E / Benn, Marianne / Bis, Joshua C / Boehnke, Michael / Boerwinkle, Eric / Bork-Jensen, Jette / Bottinger, Erwin P / Brandslund, Ivan / Brown, Morris / Busonero, Fabio / Caulfield, Mark J / Chambers, John C / Chasman, Daniel I / Chen, Y Eugene / Chen, Yii-Der Ida / Chowdhury, Rajiv / Christensen, Cramer / Chu, Audrey Y / Connell, John M / Cucca, Francesco / Cupples, L Adrienne / Damrauer, Scott M / Davies, Gail / Deary, Ian J / Dedoussis, George / Denny, Joshua C / Dominiczak, Anna / Dubé, Marie-Pierre / Ebeling, Tapani / Eiriksdottir, Gudny / Esko, Tõnu / Farmaki, Aliki-Eleni / Feitosa, Mary F / Ferrario, Marco / Ferrieres, Jean / Ford, Ian / Fornage, Myriam / Franks, Paul W / Frayling, Timothy M / Frikke-Schmidt, Ruth / Fritsche, Lars G / Frossard, Philippe / Fuster, Valentin / Ganesh, Santhi K / Gao, Wei / Garcia, Melissa E / Gieger, Christian / Giulianini, Franco / Goodarzi, Mark O / Grallert, Harald / Grarup, Niels / Groop, Leif / Grove, Megan L / Gudnason, Vilmundur / Hansen, Torben / Harris, Tamara B / Hayward, Caroline / Hirschhorn, Joel N / Holmen, Oddgeir L / Huffman, Jennifer / Huo, Yong / Hveem, Kristian / Jabeen, Sehrish / Jackson, Anne U / Jakobsdottir, Johanna / Jarvelin, Marjo-Riitta / Jensen, Gorm B / Jørgensen, Marit E / Jukema, J Wouter / Justesen, Johanne M / Kamstrup, Pia R / Kanoni, Stavroula / Karpe, Fredrik / Kee, Frank / Khera, Amit V / Klarin, Derek / Koistinen, Heikki A / Kooner, Jaspal S / Kooperberg, Charles / Kuulasmaa, Kari / Kuusisto, Johanna / Laakso, Markku / Lakka, Timo / Langenberg, Claudia / Langsted, Anne / Launer, Lenore J / Lauritzen, Torsten / Liewald, David C M / Lin, Li An / Linneberg, Allan / Loos, Ruth J F / Lu, Yingchang / Lu, Xiangfeng / Mägi, Reedik / Malarstig, Anders / Manichaikul, Ani / Manning, Alisa K / Mäntyselkä, Pekka / Marouli, Eirini / Masca, Nicholas G D / Maschio, Andrea / Meigs, James B / Melander, Olle / Metspalu, Andres / Morris, Andrew P / Morrison, Alanna C / Mulas, Antonella / Müller-Nurasyid, Martina / Munroe, Patricia B / Neville, Matt J / Nielsen, Jonas B / Nielsen, Sune F / Nordestgaard, Børge G / Ordovas, Jose M / Mehran, Roxana / O'Donnell, Christoper J / Orho-Melander, Marju / Molony, Cliona M / Muntendam, Pieter / Padmanabhan, Sandosh / Palmer, Colin N A / Pasko, Dorota / Patel, Aniruddh P / Pedersen, Oluf / Perola, Markus / Peters, Annette / Pisinger, Charlotta / Pistis, Giorgio / Polasek, Ozren / Poulter, Neil / Psaty, Bruce M / Rader, Daniel J / Rasheed, Asif / Rauramaa, Rainer / Reilly, Dermot F / Reiner, Alex P / Renström, Frida / Rich, Stephen S / Ridker, Paul M / Rioux, John D / Robertson, Neil R / Roden, Dan M / Rotter, Jerome I / Rudan, Igor / Salomaa, Veikko / Samani, Nilesh J / Sanna, Serena / Sattar, Naveed / Schmidt, Ellen M / Scott, Robert A / Sever, Peter / Sevilla, Raquel S / Shaffer, Christian M / Sim, Xueling / Sivapalaratnam, Suthesh / Small, Kerrin S / Smith, Albert V / Smith, Blair H / Somayajula, Sangeetha / Southam, Lorraine / Spector, Timothy D / Speliotes, Elizabeth K / Starr, John M / Stirrups, Kathleen E / Stitziel, Nathan / Strauch, Konstantin / Stringham, Heather M / Surendran, Praveen / Tada, Hayato / Tall, Alan R / Tang, Hua / Tardif, Jean-Claude / Taylor, Kent D / Trompet, Stella / Tsao, Philip S / Tuomilehto, Jaakko / Tybjaerg-Hansen, Anne / van Zuydam, Natalie R / Varbo, Anette / Varga, Tibor V / Virtamo, Jarmo / Waldenberger, Melanie / Wang, Nan / Wareham, Nick J / Warren, Helen R / Weeke, Peter E / Weinstock, Joshua / Wessel, Jennifer / Wilson, James G / Wilson, Peter W F / Xu, Ming / Yaghootkar, Hanieh / Young, Robin / Zeggini, Eleftheria / Zhang, He / Zheng, Neil S / Zhang, Weihua / Zhang, Yan / Zhou, Wei / Zhou, Yanhua / Zoledziewska, Magdalena / Anonymous820925 / Anonymous830925 / Anonymous840925 / Anonymous850925 / Anonymous860925 / Howson, Joanna M M / Danesh, John / McCarthy, Mark I / Cowan, Chad A / Abecasis, Goncalo / Deloukas, Panos / Musunuru, Kiran / Willer, Cristen J / Kathiresan, Sekar. ·Department of Public Health Sciences, Institute of Personalized Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA. · Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA. · Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA. · Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA. · MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. · The National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Donor Health and Genomics at the University of Cambridge, Cambridge, UK. · Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. · Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Center for Non-Communicable Diseases, Karachi, Pakistan. · Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. · ICDDR, B, Dhaka, Bangladesh. · Imperial College London, London, UK. · Université Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Risk Factors and Molecular Determinants of Aging-related Diseases, Lille, France. · Department of Epidemiology and Public Health, EA 3430, University of Strasbourg, Strasbourg, France. · VA Palo Alto Health Care System, Palo Alto, California, USA. · Department of Medicine, Stanford University School of Medicine, Stanford, California, USA. · Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA. · Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA. · Department of Medicine, Baylor College of Medicine, Houston, Texas, USA. · Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. · Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark. · Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA. · Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA. · Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA. · Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA. · The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · The Charles Bronfman Institute for Personalized Medicine, Ichan School of Medicine at Mount Sinai, New York, New York, USA. · Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark. · Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark. · Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. · Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy. · The Barts Heart Centre, William Harvey Research Institute, Queen Mary University of London, London, UK. · NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. · Department of Cardiology, Ealing Hospital NHS Trust, Southall, UK. · Imperial College Healthcare NHS Trust, London, UK. · Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA. · Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA. · The Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Departments of Pediatrics and Medicine, Los Angeles, California, USA. · Medical Department, Lillebaelt Hospital, Vejle, Denmark. · NHLBI Framingham Heart Study, Framingham, Massachusetts, USA. · Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK. · Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, Sassari, Italy. · Corporal Michael Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA. · Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. · Department of Psychology, University of Edinburgh, Edinburgh, UK. · Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece. · Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA. · Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA. · British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. · Montreal Heart Institute, Montreal, Quebec, Canada. · Université de Montréal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada. · Université de Montréal, Montreal, Quebec, Canada. · Department of Medicine, Oulu University Hospital and University of Oulu, Oulu, Finland. · The Icelandic Heart Association, Kopavogur, Iceland. · Estonian Genome Center, University of Tartu, Tartu, Estonia. · Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA. · Research Centre in Epidemiology and Preventive Medicine-EPIMED, Department of Medicine and Surgery, University of Insubria, Varese, Italy. · Department of Epidemiology, UMR 1027-INSERM, Toulouse University-CHU Toulouse, Toulouse, France. · Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK. · Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA. · Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden. · Department of Public Health & Clinical Medicine, Umeå University, Umeå, Sweden. · Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA. · Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK. · Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. · Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA. · Department of Cardiology, Peking University Third Hospital, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing, China. · National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA. · German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany. · Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. · Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. · Departments of Medicine and of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA. · Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, California, USA. · Department of Clinical Sciences, Diabetes and Endocrinology, Clinical Research Centre, Lund University, Malmö, Sweden. · Faculty of Medicine, University of Iceland, Reykjavik, Iceland. · Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. · Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, Maryland, USA. · Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. · Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, USA. · Department of Public Health and General Practice, HUNT Research Centre, Norwegian University of Science and Technology, Levanger, Norway. · St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. · Department of Cardiology, Peking University First Hospital, Beijing, China. · K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. · Department of Health Sciences, University of Iceland, Reykjavik, Iceland. · The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark. · Steno Diabetes Center, Gentofte, Denmark. · National Institute of Public Health, Southern Denmark University, Copenhagen, Denmark. · Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands. · The Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands. · Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark. · William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. · Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. · Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, UK. · UKCRC Centre of Excellence for Public Health, Queens University, Belfast, UK. · Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, Massachusetts, USA. · Department of Health, National Institute for Health and Welfare, Helsinki, Finland. · Department of Medicine and Abdominal Center: Endocrinology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. · Minerva Foundation Institute for Medical Research, Helsinki, Finland. · National Heart and Lung Institute, Imperial College London, Hammersmith Hospital, London, UK. · Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. · Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland. · Department of Physiology, Institute of Biomedicine, University of Eastern Finland, Kuopio Campus, Kuopio, Finland. · Kuopio Research Institute of Exercise Medicine, Kuopio, Finland. · Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland. · MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK. · Faculty of Health and Medical Sciences, University of Denmark, Copenhagen, Denmark. · Department of Public Health, Section of General Practice, University of Aarhus, Aarhus, Denmark. · Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark. · Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Research Center for Prevention and Health, Copenhagen, Denmark. · The Mindich Child Health and Development Institute, Ichan School of Medicine at Mount Sinai, New York, New York, USA. · State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. · Cardiovascular Genetics and Genomics Group, Cardiovascular Medicine Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden. · Pharmatherapeutics Clinical Research, Pfizer Worldwide R&D, Sollentuna, Sweden. · Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA. · Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. · Unit of Primary Health Care, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland. · Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. · NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK. · Division of General Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. · Department of Clinical Sciences, University Hospital Malmo Clinical Research Center, Lund University, Malmo, Sweden. · Department of Biostatistics, University of Liverpool, Liverpool, UK. · Department of Medicine I, Ludwig-Maximilians-University, Munich, Germany. · DZHK German Centre for Cardiovascular Research, Munich Heart Alliance, Munich, Germany. · Department of Cardiovascular Epidemiology and Population Genetics, National Center for Cardiovascular Investigation, Madrid, Spain. · IMDEA-Alimentacion, Madrid, Spain. · Nutrition and Genomics Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA. · Genetics, Merck Sharp & Dohme Corporation, Kenilworth, New Jersey, USA. · G3 Pharmaceuticals, Lexington, Massachusetts, USA. · Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA. · Institute of Molecular Medicine FIMM, University of Helsinki, Finland. · Faculty of Medicine, University of Split, Split, Croatia. · Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK. · International Centre for Circulatory Health, Imperial College London, London, UK. · Kaiser Permanente Washington Health Research Institute, Seattle, Washington, USA. · Departments of Epidemiology and Health Services, University of Washington, Seattle, Washington, USA. · Departments of Genetics, Medicine, and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Department of Epidemiology, University of Washington, Seattle, Washington, USA. · Department of Biobank Research, Umeå University, Umeå, Sweden. · Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA. · Imaging, Merck Sharp & Dohme Corporation, Kenilworth, New Jersey, USA. · Saw Swee Hock School of Public Health, National University of Singapore, Singapore. · Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. · Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. · Division of Population Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK. · Generation Scotland, Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, UK. · Scientific Informatics, Merck Sharp & Dohme Corporation, Kenilworth, New Jersey, USA. · Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK. · Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA. · Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK. · Department of Haematology, University of Cambridge, Cambridge, UK. · Cardiovascular Division, Departments of Medicine and Genetics, Washington University School of Medicine, St. Louis, Missouri, USA. · The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, Missouri, USA. · IBE, Faculty of Medicine, Ludwig-Maximilians-Universität Munich, Germany. · Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. · Division of Cardiovascular Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan. · Department of Medicine, Division of Molecular Medicine, Columbia University, New York, New York, USA. · Department of Genetics, Stanford University School of Medicine, Stanford, California, USA. · Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands. · Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland. · Dasman Diabetes Institute, Dasman, Kuwait. · Centre for Vascular Prevention, Danube-University Krems, Krems, Austria. · Saudi Diabetes Research Group, King Abdulaziz University, Fahd Medical Research Center, Jeddah, Saudi Arabia. · The Heart Centre, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. · Department of Epidemiology, Indiana University Fairbanks School of Public Health, Indianapolis, Indiana, USA. · Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA. · Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA. · Atlanta VA Medical Center, Decatur, Georgia, USA. · Emory Clinical Cardiovascular Research Institute, Atlanta, Georgia, USA. · Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China. · Yale College, Yale University, New Haven, Connecticut, USA. · Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. · Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia. ·Nat Genet · Pubmed #29083408.

ABSTRACT: We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.

10 Article Soluble HLA-DR serum levels are associated with smoking but not with acute coronary syndrome. 2017

Tolva, Johanna / Paakkanen, Riitta / Jarva, Hanna / Pussinen, Pirkko / Havulinna, Aki S / Salomaa, Veikko / Sinisalo, Juha / Lokki, Marja-Liisa. ·Transplantation Laboratory, University of Helsinki, Helsinki, Finland. Electronic address: johanna.m.tolva@gmail.com. · Transplantation Laboratory, University of Helsinki, Helsinki, Finland; HUH Heart and Lung Center, Division of Cardiology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. · Department of Bacteriology and Immunology and Research Programs Unit, University of Helsinki, and HUSLAB, Helsinki, Finland. · Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. · National Institute for Health and Welfare, Helsinki, Finland. · HUH Heart and Lung Center, Division of Cardiology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. · Transplantation Laboratory, University of Helsinki, Helsinki, Finland. ·Atherosclerosis · Pubmed #28982023.

ABSTRACT: BACKGROUND & AIMS: Elevated soluble HLA-DR (sHLA-DR) serum levels have been reported in HLA class II-associated inflammatory disorders. We have previously shown that the HLA class II allele HLA-DRB1*01 may predispose to acute coronary syndromes (ACS). To our knowledge, sHLA-DR serum levels have not been studied in ACS. METHODS: sHLA-DR serum levels were measured in 477 ACS patients as cases and 475 area- and sex-matched controls by sandwich enzyme-linked immunosorbent assay. Binary logistic regression and ordinal logistic regression analyses adjusted for clinical parameters were conducted to evaluate the associations of sHLA-DR levels. RESULTS: ACS patients had lower sHLA-DR serum levels compared to controls (OR = 0.837; 95% CI = 0.704-0.994; p = 0.043). After adjustment for smoking status, this association was no longer significant. This was explained by the notion that current smoking was inversely associated with sHLA-DR levels both in cases (OR = 0.592; 95% CI = 0.553-0.908; p = 0.016) and in controls (OR = 0.356; 95% CI = 0.226-0.563; p = 0.000010). A similar effect was not seen with other cardiovascular risk factors. CONCLUSIONS: The results indicate, for the first time, that lower sHLA-DR levels are associated with smoking, but not with ACS. This is an important finding because previous studies of sHLA-DR have not accounted for the possible associations between smoking and sHLA-DR levels. Further studies are required to confirm these novel results and explore the mechanisms behind the observed associations.

11 Article The Prognostic Value of Fasting Plasma Glucose, Two-Hour Postload Glucose, and HbA 2017

Shahim, Bahira / De Bacquer, Dirk / De Backer, Guy / Gyberg, Viveca / Kotseva, Kornelia / Mellbin, Linda / Schnell, Oliver / Tuomilehto, Jaakko / Wood, David / Rydén, Lars. ·Cardiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden bahirashahim@gmail.com. · Department of Public Health, Ghent University, Ghent, Belgium. · Cardiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. · Department of Cardiovascular Medicine, National Heart and Lung Institute, Imperial College London, London, U.K. · Forschergruppe Diabetes e.V., Munich, Germany. · Disease Risk Unit, National Institute for Health and Welfare, Helsinki, Finland. · Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia. ·Diabetes Care · Pubmed #28637653.

ABSTRACT: OBJECTIVE: Three tests are recommended for identifying dysglycemia: fasting glucose (FPG), 2-h postload glucose (2h-PG) from an oral glucose tolerance test (OGTT), and glycated hemoglobin A RESEARCH DESIGN AND METHODS: FPG, 2h-PG, and HbA RESULTS: Complete information including all three glycemic parameters was available in 3,775 patients (94.3%), of whom 246 (6.5%) experienced the primary end point. Neither FPG nor HbA CONCLUSIONS: The 2h-PG, in contrast to FPG and HbA

12 Article Loss of Cardioprotective Effects at the 2017

Saleheen, Danish / Zhao, Wei / Young, Robin / Nelson, Christopher P / Ho, WeangKee / Ferguson, Jane F / Rasheed, Asif / Ou, Kristy / Nurnberg, Sylvia T / Bauer, Robert C / Goel, Anuj / Do, Ron / Stewart, Alexandre F R / Hartiala, Jaana / Zhang, Weihua / Thorleifsson, Gudmar / Strawbridge, Rona J / Sinisalo, Juha / Kanoni, Stavroula / Sedaghat, Sanaz / Marouli, Eirini / Kristiansson, Kati / Hua Zhao, Jing / Scott, Robert / Gauguier, Dominique / Shah, Svati H / Smith, Albert Vernon / van Zuydam, Natalie / Cox, Amanda J / Willenborg, Christina / Kessler, Thorsten / Zeng, Lingyao / Province, Michael A / Ganna, Andrea / Lind, Lars / Pedersen, Nancy L / White, Charles C / Joensuu, Anni / Edi Kleber, Marcus / Hall, Alistair S / März, Winfried / Salomaa, Veikko / O'Donnell, Christopher / Ingelsson, Erik / Feitosa, Mary F / Erdmann, Jeanette / Bowden, Donald W / Palmer, Colin N A / Gudnason, Vilmundur / Faire, Ulf De / Zalloua, Pierre / Wareham, Nicholas / Thompson, John R / Kuulasmaa, Kari / Dedoussis, George / Perola, Markus / Dehghan, Abbas / Chambers, John C / Kooner, Jaspal / Allayee, Hooman / Deloukas, Panos / McPherson, Ruth / Stefansson, Kari / Schunkert, Heribert / Kathiresan, Sekar / Farrall, Martin / Marcel Frossard, Philippe / Rader, Daniel J / Samani, Nilesh J / Reilly, Muredach P. ·From Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia (D.S., W.Z.) · Center for Non-Communicable Diseases, Karachi, Pakistan (D.S., A.R., P.M.F., PROMIS) · Department of Public Health and Primary Care, University of Cambridge, United Kingdom (R.Y., W.K.H., EPIC-CVD) · Department of Cardiovascular Sciences, University of Leicester, United Kingdom (C.P.N., N.J.S.) · Cardiology Division, Department of Medicine, Vanderbilt University, Nashville, TN (J.F.F., K.O.) · Division of Cardiovascular Medicine, Radcliffe Department of Medicine & Wellcome Trust Centre for Human Genetics, University of Oxford, United Kingdom (A.G., M.F.) · The Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY (R.D.) · Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.D.) · Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Canada (A.F.R.S., R.M.) · Institute for Genetic Medicine and Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles (J.H., H.A.) · Department of Epidemiology and Biostatistics, Imperial College London, United Kingdom (W.Z., J.C.C., J.K.) · Department of Cardiology, Ealing Hospital NHS Trust, Middlesex, United Kingdom (W.Z., J.C.C.) · Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden (R.J.S.) · Helsinki University Central Hospital HUCH Heart and Lung Center, Helsinki, Uusimaa, Finland (J.S.) · Cardiology Division, Department of Medicine and the Irving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, NY (R.C.B., M.P.R.) · William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom (S.K., E.M., P.D.) · Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands (S.S., A.D.) · Department of Dietetics-Nutrition, Harokopio University, Athens, Greece (E.M., G.D.) · National Institute for Health and Welfare, Helsinki, Finland (K.K., A.J., V.S., K.K., M.P.) · MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, United Kingdom (J.H.Z., R.S.) · INSERM, UMRS1138, Centre de Recherche des Cordeliers, Paris, France (D.G., N.W.) · Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC (S.H.S.) · Icelandic Heart Association, Kopavogur, Iceland (A.V.S., V.G.) · Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, United Kingdom (N.v.Z., C.N.A.P.) · Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC (A.J.C., D.W.B.) · Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Germany (C.W., J.E.) · DZHK (German Research Center for Cardiovascular Research) partner site Hamburg-Lübeck-Kiel, Germany (C.W., J.E.) · Deutsches Herzzentrum München, Technische Universität München, Germany (T.K., L.Z., H.S.) · Klinikum rechts der Isar, München, Germany (T.K.) · DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Germany (L.Z., H.S.) · Department of Genetics, Washington University School of Medicine, St. Louis, MO (M.A.P., M.F.F.) · Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston (A.G.) · Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (A.G.) · Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Sweden (L.L.) · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (N.L.P.) · Department of Biostatistics Boston University School of Public Health Framingham Heart Study, MA (C.C.W.) · Faculty of Medicine, University of Iceland, Reykjavik (A.V.S., V.G.) · University of Helsinki, Institute for Molecular Medicine, Finland (FIMM) (A.J., M.P.) · Department of Medicine, Mannheim Medical Faculty, Heidelberg University, Germany (M.E.K.) · Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, United Kingdom (A.S.H.) · Synlab Academy, Synlab Services GmbH, Mannheim, Germany and Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria (W.M.) · National Heart, Lung, and Blood Institute and the Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.O'D.) · Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Sweden (E.I.) · Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (E.I.) · Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (U.D.F.) · Lebanese American University, School of Medicine, Beirut (P.Z.) · Department of Health Sciences, University of Leicester, United Kingdom (J.R.T.) · Imperial College Healthcare NHS Trust, London, United Kingdom (J.C.C., J.K.) · Cardiovascular Science, National Heart and Lung Institute, Imperial College London, United Kingdom (J.K.) · Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia (P.D.) · deCODE Genetics, Sturlugata 8, IS-101 Reykjavik, Iceland (G.T., K.S.) · University of Iceland, School of Medicine, Reykjavik, Iceland (G.T., K.S.) · Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge (S.K.) · Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.K.) · Center for Human Genetic Research, Massachusetts General Hospital, Boston (S.K.) · Department of Medicine, Harvard Medical School, Boston, MA (S.K.) · Department of Genetics, University of Pennsylvania, Philadelphia (D.J.R.) · and Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia (S.T.N., D.J.R.). ·Circulation · Pubmed #28461624.

ABSTRACT: BACKGROUND: Common diseases such as coronary heart disease (CHD) are complex in etiology. The interaction of genetic susceptibility with lifestyle factors may play a prominent role. However, gene-lifestyle interactions for CHD have been difficult to identify. Here, we investigate interaction of smoking behavior, a potent lifestyle factor, with genotypes that have been shown to associate with CHD risk. METHODS: We analyzed data on 60 919 CHD cases and 80 243 controls from 29 studies for gene-smoking interactions for genetic variants at 45 loci previously reported to be associated with CHD risk. We also studied 5 loci associated with smoking behavior. Study-specific gene-smoking interaction effects were calculated and pooled using fixed-effects meta-analyses. Interaction analyses were declared to be significant at a RESULTS: We identified novel gene-smoking interaction for a variant upstream of the

13 Article Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease. 2017

Webb, Thomas R / Erdmann, Jeanette / Stirrups, Kathleen E / Stitziel, Nathan O / Masca, Nicholas G D / Jansen, Henning / Kanoni, Stavroula / Nelson, Christopher P / Ferrario, Paola G / König, Inke R / Eicher, John D / Johnson, Andrew D / Hamby, Stephen E / Betsholtz, Christer / Ruusalepp, Arno / Franzén, Oscar / Schadt, Eric E / Björkegren, Johan L M / Weeke, Peter E / Auer, Paul L / Schick, Ursula M / Lu, Yingchang / Zhang, He / Dube, Marie-Pierre / Goel, Anuj / Farrall, Martin / Peloso, Gina M / Won, Hong-Hee / Do, Ron / van Iperen, Erik / Kruppa, Jochen / Mahajan, Anubha / Scott, Robert A / Willenborg, Christina / Braund, Peter S / van Capelleveen, Julian C / Doney, Alex S F / Donnelly, Louise A / Asselta, Rosanna / Merlini, Pier A / Duga, Stefano / Marziliano, Nicola / Denny, Josh C / Shaffer, Christian / El-Mokhtari, Nour Eddine / Franke, Andre / Heilmann, Stefanie / Hengstenberg, Christian / Hoffmann, Per / Holmen, Oddgeir L / Hveem, Kristian / Jansson, Jan-Håkan / Jöckel, Karl-Heinz / Kessler, Thorsten / Kriebel, Jennifer / Laugwitz, Karl L / Marouli, Eirini / Martinelli, Nicola / McCarthy, Mark I / Van Zuydam, Natalie R / Meisinger, Christa / Esko, Tõnu / Mihailov, Evelin / Escher, Stefan A / Alver, Maris / Moebus, Susanne / Morris, Andrew D / Virtamo, Jarma / Nikpay, Majid / Olivieri, Oliviero / Provost, Sylvie / AlQarawi, Alaa / Robertson, Neil R / Akinsansya, Karen O / Reilly, Dermot F / Vogt, Thomas F / Yin, Wu / Asselbergs, Folkert W / Kooperberg, Charles / Jackson, Rebecca D / Stahl, Eli / Müller-Nurasyid, Martina / Strauch, Konstantin / Varga, Tibor V / Waldenberger, Melanie / Anonymous8620896 / Zeng, Lingyao / Chowdhury, Rajiv / Salomaa, Veikko / Ford, Ian / Jukema, J Wouter / Amouyel, Philippe / Kontto, Jukka / Anonymous8630896 / Nordestgaard, Børge G / Ferrières, Jean / Saleheen, Danish / Sattar, Naveed / Surendran, Praveen / Wagner, Aline / Young, Robin / Howson, Joanna M M / Butterworth, Adam S / Danesh, John / Ardissino, Diego / Bottinger, Erwin P / Erbel, Raimund / Franks, Paul W / Girelli, Domenico / Hall, Alistair S / Hovingh, G Kees / Kastrati, Adnan / Lieb, Wolfgang / Meitinger, Thomas / Kraus, William E / Shah, Svati H / McPherson, Ruth / Orho-Melander, Marju / Melander, Olle / Metspalu, Andres / Palmer, Colin N A / Peters, Annette / Rader, Daniel J / Reilly, Muredach P / Loos, Ruth J F / Reiner, Alex P / Roden, Dan M / Tardif, Jean-Claude / Thompson, John R / Wareham, Nicholas J / Watkins, Hugh / Willer, Cristen J / Samani, Nilesh J / Schunkert, Heribert / Deloukas, Panos / Kathiresan, Sekar / Anonymous8640896. ·Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom. · Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany; DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, Lübeck, Germany; University Heart Center Luebeck, Lübeck, Germany. · William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; Department of Haematology, University of Cambridge, Cambridge, United Kingdom. · Cardiovascular Division, Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri; Department of Genetics, Washington University School of Medicine, Saint Louis, Missouri; McDonnell Genome Institute, Washington University School of Medicine, Saint Louis, Missouri. · Deutsches Herzzentrum München, Technische Universität München, München, Germany; DZHK, Partner Site Munich Heart Alliance, Munich, Germany. · William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom. · DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, Lübeck, Germany; Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Lübeck, Germany. · Center for Population Studies, National Heart, Lung, and Blood Institute, The Framingham Heart Study, Framingham, Massachusetts. · Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Sweden; Department of Medical Biochemistry and Biophysics, Vascular Biology Unit, Karolinska Institutet, Stockholm, Sweden. · Department of Physiology, Institute of Biomedicine and Translation Medicine, University of Tartu, Tartu, Estonia; Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia; Clinical Gene Networks AB, Stockholm, Sweden. · Clinical Gene Networks AB, Stockholm, Sweden; Department of Genetics & Genomic Sciences, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York. · Department of Genetics & Genomic Sciences, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York. · Department of Medical Biochemistry and Biophysics, Vascular Biology Unit, Karolinska Institutet, Stockholm, Sweden; Department of Physiology, Institute of Biomedicine and Translation Medicine, University of Tartu, Tartu, Estonia; Clinical Gene Networks AB, Stockholm, Sweden; Department of Genetics & Genomic Sciences, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York. · Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Laboratory for Molecular Cardiology, Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. · School of Public Heath, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin. · Fred Hutchinson Cancer Research Center, Seattle, Washington; The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York. · The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York; The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York. · Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan. · Université de Montréal, Faculté de médecine, Département de médecine, Montreal, Quebec, Canada; Montreal Heart Institute, Montreal, Quebec, Canada. · Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. · Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts; Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts. · Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts; Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts; Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea. · The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York; The Center for Statistical Genetics, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; The Icahn Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; The Zena and Michael A. Weiner Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York. · Department of Biostatistics, Academic Medical Center, Amsterdam, the Netherlands. · Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Hannover, Germany. · Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. · MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom. · Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany. · Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands. · Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Scotland, United Kingdom. · Department of Biomedical Sciences, Humanitas University, Milan, Italy; Humanitas Clinical and Research Center, Milan, Italy. · Niguarda Hospital, Milan, Italy. · Azienda Sanitaria Locale 3 San Francesco, Nuoro, Italy 3, Nuoro, Italy. · Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Biomedical informatics, Vanderbilt University Medical Center, Nashville, Tennessee. · Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. · Klinik für Kardiologie, Pneumologie und Innere Medizin, Imland Klinik Rendsburg, Rendsburg, Germany. · Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany. · Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany. · McDonnell Genome Institute, Washington University School of Medicine, Saint Louis, Missouri; Deutsches Herzzentrum München, Technische Universität München, München, Germany. · Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany; Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland. · HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway; St. Olav Hospital, Trondheim University Hospital, Trondheim, Norway. · HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway; Department of Medicine, Levanger Hospital, Nord-Trøndelag Health Trust, Levanger, Norway. · Department of Public Health and Clinical Medicine, Research Unit Skellefteå, Umeå University, Sweden. · Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany. · Research unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research, Neuherberg, Germany. · DZHK, Partner Site Munich Heart Alliance, Munich, Germany; Institute Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany. · Department of Medicine, Section of Internal Medicine, University of Verona, Verona, Italy. · Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom; Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Old Road Headington, Oxford, Oxford, United Kingdom. · Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom. · Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. · Estonian Genome Center, University of Tartu, Tartu, Estonia; Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts; Department of Genetics, Harvard Medical School, Boston, Massachusetts; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts. · Estonian Genome Center, University of Tartu, Tartu, Estonia. · Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmö, Sweden. · Estonian Genome Center, University of Tartu, Tartu, Estonia; Institute of Molecular and Cell Biology, Tartu, Estonia. · School of Molecular, Genetic and Population Health Sciences, University of Edinburgh, Medical School, Teviot Place, Edinburgh, Scotland, United Kingdom. · National Institute for Health and Welfare (THL), Helsinki, Finland. · Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. · Montreal Heart Institute, Montreal, Quebec, Canada. · Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia. · Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom. · Merck Sharp & Dohme, Rahway, New Jersey. · Department of Cardiology, Division Heart & Lungs, UMC 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, United Kingdom. · Fred Hutchinson Cancer Research Center, Seattle, Washington. · Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Ohio State University, Columbus, Ohio. · Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York. · DZHK, Partner Site Munich Heart Alliance, Munich, Germany; Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany. · Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany. · Research unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. · MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. · Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom. · Department of Cardiology, Leiden University Medical Center, Leiden and Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands. · Université de Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE, Lille, France. · Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Toulouse University School of Medicine, Toulouse, France. · Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Noncommunicable Diseases, Karachi, Pakistan. · British Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom. · Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany. · Department of Epîdemiology and Public Health, University of Strasbourg, Strasbourg, France. · MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; National Institute of Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, United Kingdom. · MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; National Institute of Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom. · Parma University Hospital, Parma, Italy. · The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York. · Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts; Department of Public Health & Clinical Medicine, Umeå University Hospital, Umeå, Sweden. · Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, United Kingdom. · Deutsches Herzzentrum München, Technische Universität München, München, Germany. · Institute of Epidemiology and Biobank popgen, Christian-Albrechts-University Kiel, Kiel, Germany. · DZHK, Partner Site Munich Heart Alliance, Munich, Germany; Institute of Human Genetics, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany. · Duke Molecular Physiology Institute, Duke University, Durham, North Carolina; Division of Cardiology, Department of Medicine, Duke University, Durham, North Carolina. · Department of Clinical Sciences in Malmo, Lund University, Clinical Research Center, Malmo, Sweden. · Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmo, Malmo, Sweden. · DZHK, Partner Site Munich Heart Alliance, Munich, Germany; Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. · Department of Genetics, Cardiovascular Institute and Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. · Division of Cardiology, Department of Medicine and the Irving Institute for Clinical and Translational Research, Columbia University, New York, New York. · The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York; The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York; The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York, New York. · Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Epidemiology, University of Washington, Seattle, Washington. · Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee. · NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom; Department of Health Sciences, University of Leicester, Leicester, United Kingdom. · Université de Montréal, Faculté de médecine, Département de médecine, Montreal, Quebec, Canada; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan; Department of Human Genetics, University of Michigan, Ann Arbor, Michigan. · Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom. Electronic address: njs@le.ac.uk. · William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: p.deloukas@qmul.ac.uk. · Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts; Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts; Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts. ·J Am Coll Cardiol · Pubmed #28209224.

ABSTRACT: BACKGROUND: Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits. OBJECTIVES: This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci. METHODS: In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs. RESULTS: We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 × 10 CONCLUSIONS: We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.

14 Article Impaired HDL2-mediated cholesterol efflux is associated with metabolic syndrome in families with early onset coronary heart disease and low HDL-cholesterol level. 2017

Paavola, Timo / Kuusisto, Sanna / Jauhiainen, Matti / Kakko, Sakari / Kangas-Kontio, Tiia / Metso, Jari / Soininen, Pasi / Ala-Korpela, Mika / Bloigu, Risto / Hannuksela, Minna L / Savolainen, Markku J / Salonurmi, Tuire. ·Department of Internal Medicine, Institute of Clinical Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland and Medical Research Center, Oulu University Hospital, Oulu, Finland. · Genomics and Biomarkers Unit, National Institute for Health and Welfare, Biomedicum, Helsinki, Finland. · Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland. · NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland. · Oulu University Hospital, Oulu, Finland. · Computational Medicine, School of Social and Community Medicine & Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom. · Medical Informatics and Statistics Research Group, University of Oulu, Oulu, Finland. · Department of Clinical Chemistry, Institute of Diagnostics, University of Oulu, Oulu, Finland. ·PLoS One · Pubmed #28207870.

ABSTRACT: OBJECTIVE: The potential of high-density lipoproteins (HDL) to facilitate cholesterol removal from arterial foam cells is a key function of HDL. We studied whether cholesterol efflux to serum and HDL subfractions is impaired in subjects with early coronary heart disease (CHD) or metabolic syndrome (MetS) in families where a low HDL-cholesterol level (HDL-C) predisposes to early CHD. METHODS: HDL subfractions were isolated from plasma by sequential ultracentrifugation. THP-1 macrophages loaded with acetyl-LDL were used in the assay of cholesterol efflux to total HDL, HDL2, HDL3 or serum. RESULTS: While cholesterol efflux to serum, total HDL and HDL3 was unchanged, the efflux to HDL2 was 14% lower in subjects with MetS than in subjects without MetS (p<0.001). The efflux to HDL2 was associated with components of MetS such as plasma HDL-C (r = 0.76 in men and r = 0.56 in women, p<0.001 for both). The efflux to HDL2 was reduced in men with early CHD (p<0.01) only in conjunction with their low HDL-C. The phospholipid content of HDL2 particles was a major correlate with the efflux to HDL2 (r = 0.70, p<0.001). A low ratio of HDL2 to total HDL was associated with MetS (p<0.001). CONCLUSION: Our results indicate that impaired efflux to HDL2 is a functional feature of the low HDL-C state and MetS in families where these risk factors predispose to early CHD. The efflux to HDL2 related to the phospholipid content of HDL2 particles but the phospholipid content did not account for the impaired efflux in cardiometabolic disease, where a combination of low level and poor quality of HDL2 was observed.

15 Article Trends in long-term prognosis after acute coronary syndrome. 2017

Piironen, Marjo / Ukkola, Olavi / Huikuri, Heikki / Havulinna, Aki S / Koukkunen, Heli / Mustonen, Juha / Ketonen, Matti / Lehto, Seppo / Airaksinen, Juhani / Antero Kesäniemi, Y / Salomaa, Veikko. ·1 Research Unit of Internal Medicine, Medical Research Centre Oulu, Finland. · 2 Oulu University Hospital, and University of Oulu, Finland. · 3 Department of Health, National Institute for Health and Welfare, Helsinki, Finland. · 4 University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland. · 5 North Karelia Central Hospital, Joensuu, Finland. · 6 University of Eastern Finland, Kuopio, Finland. · 7 Heart Centre, Turku University Hospital, Finland. ·Eur J Prev Cardiol · Pubmed #27856805.

ABSTRACT: Background Coronary heart disease incidence, mortality and short-term case-fatality have improved substantially during the past decades. Recent changes in the long-term prognosis among survivors of acute coronary syndrome are less well known. Our aim was to investigate the long-term prognosis of acute coronary syndrome. Design An observational myocardial infarction register study. Methods Data was derived from the population based Finnish Myocardial Infarction register. Patients aged 35 or higher, who had their first acute coronary syndrome during 1993-2011 and survived the first 28 days, were included in the analysis ( n = 13,336). Endpoints were fatal and non-fatal cardiovascular disease events and all-cause mortality at one year and three years after the index event. We also compared the prognosis of acute coronary syndrome survivors with the prognosis of an apparently healthy population with the same age, sex and area of residence, derived from the FINRISK study. Results Significant declines over time were observed in the risk of a new cardiovascular disease event. At three year follow-up the age- and study area-adjusted hazard ratio per calendar year was 0.969 (95% confidence interval 0.960-0.977, p = 4.63 × 10

16 Article Time-saving screening for diabetes in patients with coronary artery disease: a report from EUROASPIRE IV. 2016

Gyberg, Viveca / De Bacquer, Dirk / Kotseva, Kornelia / De Backer, Guy / Schnell, Oliver / Tuomilehto, Jaakko / Wood, David / Rydén, Lars. ·Cardiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. · Department of Neurobiology, Care Sciences and Society, Centre for Family Medicine, Karolinska Institutet, Huddinge, Sweden. · Department of Public Health, Ghent University, Ghent, Belgium. · Department of Cardiovascular Medicine, National Heart and Lung Institute, Imperial College London, London, UK. · Forschergruppe Diabetes e.V. at the Helmholtz Center, Munich, Germany. · Danube-University Krems, Krems, Austria. · Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland. · Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia. · Dasman Diabetes Institute, Kuwait City, Kuwait. ·BMJ Open · Pubmed #27932342.

ABSTRACT: BACKGROUND: WHO advocates 2-hour oral glucose tolerance test (OGTT) for detecting diabetes mellitus (DM). OGTT is the most sensitive method to detect DM in patients with coronary artery disease (CAD). Considered time consuming, the use of OGTT is unsatisfactory. A 1-hour plasma glucose (1hPG) test has not been evaluated as an alternative in patients with CAD. OBJECTIVES: To create an algorithm based on glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and 1hPG limiting the need of a 2-hour plasma glucose (2hPG) in patients with CAD. METHODS: 951 patients with CAD without DM underwent OGTT. A 2hPG≥11.1 mmol/L was the reference for undiagnosed DM. The yield of HbA1c, FPG and 1hPG was compared with that of 2hPG. RESULTS: Mean FPG was 6.2±0.9 mmol/L, and mean HbA1c 5.8±0.4%. Based on 2hPG≥11.1 mmol/L 122 patients (13%) had DM. There was no value for the combination of HbA1c and FPG to rule out or in DM (HbA1c≥6.5%; FPG≥7.0 mmol/L). In receiver operating characteristic analysis a 1hPG≥12 mmol/L balanced sensitivity and specificity for detecting DM (both=82%; positive and negative predictive values 40% and 97%). A combination of FPG<6.5 mmol/L and 1hPG<11 mmol/L excluded 99% of DM. A combination of FPG>8.0 mmol/L and 1hPG>15 mmol/L identified 100% of patients with DM. CONCLUSIONS: Based on its satisfactory accuracy to detect DM an algorithm is proposed for screening for DM in patients with CAD decreasing the need for a 2-hour OGTT by 71%.

17 Article No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis. 2016

Loley, Christina / Alver, Maris / Assimes, Themistocles L / Bjonnes, Andrew / Goel, Anuj / Gustafsson, Stefan / Hernesniemi, Jussi / Hopewell, Jemma C / Kanoni, Stavroula / Kleber, Marcus E / Lau, King Wai / Lu, Yingchang / Lyytikäinen, Leo-Pekka / Nelson, Christopher P / Nikpay, Majid / Qu, Liming / Salfati, Elias / Scholz, Markus / Tukiainen, Taru / Willenborg, Christina / Won, Hong-Hee / Zeng, Lingyao / Zhang, Weihua / Anand, Sonia S / Beutner, Frank / Bottinger, Erwin P / Clarke, Robert / Dedoussis, George / Do, Ron / Esko, Tõnu / Eskola, Markku / Farrall, Martin / Gauguier, Dominique / Giedraitis, Vilmantas / Granger, Christopher B / Hall, Alistair S / Hamsten, Anders / Hazen, Stanley L / Huang, Jie / Kähönen, Mika / Kyriakou, Theodosios / Laaksonen, Reijo / Lind, Lars / Lindgren, Cecilia / Magnusson, Patrik K E / Marouli, Eirini / Mihailov, Evelin / Morris, Andrew P / Nikus, Kjell / Pedersen, Nancy / Rallidis, Loukianos / Salomaa, Veikko / Shah, Svati H / Stewart, Alexandre F R / Thompson, John R / Zalloua, Pierre A / Chambers, John C / Collins, Rory / Ingelsson, Erik / Iribarren, Carlos / Karhunen, Pekka J / Kooner, Jaspal S / Lehtimäki, Terho / Loos, Ruth J F / März, Winfried / McPherson, Ruth / Metspalu, Andres / Reilly, Muredach P / Ripatti, Samuli / Sanghera, Dharambir K / Thiery, Joachim / Watkins, Hugh / Deloukas, Panos / Kathiresan, Sekar / Samani, Nilesh J / Schunkert, Heribert / Erdmann, Jeanette / König, Inke R. ·Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany. · DZHK (German Centre for Cardiovascular Research), partner site Hamburg-Lübeck-Kiel, Lübeck, Germany. · Estonian Genome Center, University of Tartu, Tartu, Estonia. · Institute of Molecular and Cell Biology, Tartu, Estonia. · Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine Stanford, Standford, California, USA. · Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA. · Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. · Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. · Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden. · Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland. · Department of Cardiology, Heart Hospital and University of Tampere School of Medicine, Tampere, Finland. · CTSU, Nuffield Department of Population Health, University of Oxford, Oxford, UK. · William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. · Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. · The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, USA. · Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, Finland. · Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. · NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK. · Ruddy Canadian Cardiovascular Genetics Centre University of Ottawa Heart Institute, Ottawa, Canada. · Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Institute for Medical Informatics, Statistics and Epidemiology/Medical Faculty/University of Leipzig, Leipzig, Germany. · LIFE Research Center of Civilization Diseases, Leipzig, Germany. · Analytic and Translation Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA. · Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA. · Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany and University Heart Center Luebeck, Campus Lübeck, Lübeck, Germany. · Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, Korea. · Deutsches Herzzentrum München, Technische Universität München, Munich, Germany. · DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, München, Germany. · Department of Epidemiology and Biostatistics, Imperial College London, London, UK. · Department of Cardiology, Ealing Hospital National Health Service (NHS) Trust, Middlesex, UK. · Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada. · Heart Center Leipzig, Cardiology, University of Leipzig, Leipzig, Germany. · Harokopio University Athens, Athens, Greece. · The Center for Statistical Genetics, Icahn School of Medicine at Mount Sinai, New York, USA. · The Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, USA. · The Zena and Michael A. Weiner Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, USA. · Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA. · INSERM, UMRS1138, Centre de Recherche des Cordeliers, Paris, France. · Department of Public Health and Caring Sciences, Geriatrics, Uppsala Universit, Uppsala, Sweden. · Duke University School of Medicine, Durham, North Carolina, USA. · Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, UK. · Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. · Cleveland Clinic, Cleveland, Ohio, USA. · Boston VA Research Institute, Inc., Boston, Massachusetts, USA. · Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland. · Department of Clinical Physiology, University of Tampere School of Medicine, Tampere, Finland. · Zora Biosciences, Espoo, Finland. · Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden. · Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, USA. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. · Department of Biostatistics, University of Liverpool, Liverpool, UK. · Second Department of Cardiology, University General Hospital Attikon, Athens, Greece. · Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland. · Department of Health Sciences, University of Leicester, Leicester, UK. · Lebanese American University, School of Medicine, Beirut, Lebanon. · Harvard School of Public Health, Boston, Massachusetts, USA. · Imperial College Healthcare NHS Trust, London, UK. · Kaiser Permanente, Division of Research, Oakland, California, USA. · Department of Forensic Medicine, University of Tampere School of Medicine, Tampere, Finland. · Cardiovascular Science, National Heart and Lung Institute, Imperial College London, London, UK. · The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, USA. · Synlab Academy, Synlab Services GmbH, Mannheim, Germany. · Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria. · Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Hjelt Institute, University of Helsinki, Helsinki, Finland. · Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland. · Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. · Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. · Oklahoma Center for Neuroscience, Oklahoma City, Oklahoma, USA. · Institute for Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Medical Faculty, Leipzig, Germany. · Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK. · Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia. · Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA. ·Sci Rep · Pubmed #27731410.

ABSTRACT: In recent years, genome-wide association studies have identified 58 independent risk loci for coronary artery disease (CAD) on the autosome. However, due to the sex-specific data structure of the X chromosome, it has been excluded from most of these analyses. While females have 2 copies of chromosome X, males have only one. Also, one of the female X chromosomes may be inactivated. Therefore, special test statistics and quality control procedures are required. Thus, little is known about the role of X-chromosomal variants in CAD. To fill this gap, we conducted a comprehensive X-chromosome-wide meta-analysis including more than 43,000 CAD cases and 58,000 controls from 35 international study cohorts. For quality control, sex-specific filters were used to adequately take the special structure of X-chromosomal data into account. For single study analyses, several logistic regression models were calculated allowing for inactivation of one female X-chromosome, adjusting for sex and investigating interactions between sex and genetic variants. Then, meta-analyses including all 35 studies were conducted using random effects models. None of the investigated models revealed genome-wide significant associations for any variant. Although we analyzed the largest-to-date sample, currently available methods were not able to detect any associations of X-chromosomal variants with CAD.

18 Article Genome-wide associations for birth weight and correlations with adult disease. 2016

Horikoshi, Momoko / Beaumont, Robin N / Day, Felix R / Warrington, Nicole M / Kooijman, Marjolein N / Fernandez-Tajes, Juan / Feenstra, Bjarke / van Zuydam, Natalie R / Gaulton, Kyle J / Grarup, Niels / Bradfield, Jonathan P / Strachan, David P / Li-Gao, Ruifang / Ahluwalia, Tarunveer S / Kreiner, Eskil / Rueedi, Rico / Lyytikäinen, Leo-Pekka / Cousminer, Diana L / Wu, Ying / Thiering, Elisabeth / Wang, Carol A / Have, Christian T / Hottenga, Jouke-Jan / Vilor-Tejedor, Natalia / Joshi, Peter K / Boh, Eileen Tai Hui / Ntalla, Ioanna / Pitkänen, Niina / Mahajan, Anubha / van Leeuwen, Elisabeth M / Joro, Raimo / Lagou, Vasiliki / Nodzenski, Michael / Diver, Louise A / Zondervan, Krina T / Bustamante, Mariona / Marques-Vidal, Pedro / Mercader, Josep M / Bennett, Amanda J / Rahmioglu, Nilufer / Nyholt, Dale R / Ma, Ronald Ching Wan / Tam, Claudia Ha Ting / Tam, Wing Hung / Anonymous20770882 / Ganesh, Santhi K / van Rooij, Frank Ja / Jones, Samuel E / Loh, Po-Ru / Ruth, Katherine S / Tuke, Marcus A / Tyrrell, Jessica / Wood, Andrew R / Yaghootkar, Hanieh / Scholtens, Denise M / Paternoster, Lavinia / Prokopenko, Inga / Kovacs, Peter / Atalay, Mustafa / Willems, Sara M / Panoutsopoulou, Kalliope / Wang, Xu / Carstensen, Lisbeth / Geller, Frank / Schraut, Katharina E / Murcia, Mario / van Beijsterveldt, Catharina Em / Willemsen, Gonneke / Appel, Emil V R / Fonvig, Cilius E / Trier, Caecilie / Tiesler, Carla Mt / Standl, Marie / Kutalik, Zoltán / Bonas-Guarch, Sílvia / Hougaard, David M / Sánchez, Friman / Torrents, David / Waage, Johannes / Hollegaard, Mads V / de Haan, Hugoline G / Rosendaal, Frits R / Medina-Gomez, Carolina / Ring, Susan M / Hemani, Gibran / McMahon, George / Robertson, Neil R / Groves, Christopher J / Langenberg, Claudia / Luan, Jian'an / Scott, Robert A / Zhao, Jing Hua / Mentch, Frank D / MacKenzie, Scott M / Reynolds, Rebecca M / Anonymous20780882 / Lowe, William L / Tönjes, Anke / Stumvoll, Michael / Lindi, Virpi / Lakka, Timo A / van Duijn, Cornelia M / Kiess, Wieland / Körner, Antje / Sørensen, Thorkild Ia / Niinikoski, Harri / Pahkala, Katja / Raitakari, Olli T / Zeggini, Eleftheria / Dedoussis, George V / Teo, Yik-Ying / Saw, Seang-Mei / Melbye, Mads / Campbell, Harry / Wilson, James F / Vrijheid, Martine / de Geus, Eco Jcn / Boomsma, Dorret I / Kadarmideen, Haja N / Holm, Jens-Christian / Hansen, Torben / Sebert, Sylvain / Hattersley, Andrew T / Beilin, Lawrence J / Newnham, John P / Pennell, Craig E / Heinrich, Joachim / Adair, Linda S / Borja, Judith B / Mohlke, Karen L / Eriksson, Johan G / Widén, Elisabeth E / Kähönen, Mika / Viikari, Jorma S / Lehtimäki, Terho / Vollenweider, Peter / Bønnelykke, Klaus / Bisgaard, Hans / Mook-Kanamori, Dennis O / Hofman, Albert / Rivadeneira, Fernando / Uitterlinden, André G / Pisinger, Charlotta / Pedersen, Oluf / Power, Christine / Hyppönen, Elina / Wareham, Nicholas J / Hakonarson, Hakon / Davies, Eleanor / Walker, Brian R / Jaddoe, Vincent Wv / Jarvelin, Marjo-Riitta / Grant, Struan Fa / Vaag, Allan A / Lawlor, Debbie A / Frayling, Timothy M / Davey Smith, George / Morris, Andrew P / Ong, Ken K / Felix, Janine F / Timpson, Nicholas J / Perry, John Rb / Evans, David M / McCarthy, Mark I / Freathy, Rachel M. ·Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. · Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK. · Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital, Exeter, UK. · MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK. · The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia. · School of Women's and Infants' Health, The University of Western Australia, Perth, Australia. · The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, the Netherlands. · Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands. · Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, the Netherlands. · Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark. · Department of Pediatrics, University of California San Diego, La Jolla, California, USA. · The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. · Population Health Research Institute, St George's University of London, London, Cranmer Terrace, UK. · Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. · COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. · Steno Diabetes Center, Gentofte, Denmark. · Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland. · Swiss Institute of Bioinformatics, Lausanne, Switzerland. · Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland. · Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, Finland. · Institute for Molecular Medicine, Finland (FIMM), University of Helsinki, Helsinki, Finland. · Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. · Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Department of Genetics, University of North Carolina, Chapel Hill, NC, USA. · Institute of Epidemiology I, Helmholtz Zentrum München- German Research Center for Environmental Health, Neuherberg, Germany. · Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, University of Munich Medical Center, Munich, Germany. · Netherlands Twin Register, Department of Biological Psychology, VU University, Amsterdam, the Netherlands. · ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain. · Universitat Pompeu Fabra (UPF), Barcelona, Spain. · CIBER de Epidemiología y Salud Pública (CIBERESP), Spain. · Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, UK. · Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore, Singapore. · William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK. · Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece. · Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland. · Institute of Biomedicine, Physiology, University of Eastern Finland, Kuopio, Finland. · KUL - University of Leuven, Department of Neurosciences, Leuven, Belgium. · Translational Immunology Laboratory, VIB, Leuven, Belgium. · Department of Preventive Medicine, Division of Biostatistics, Feinberg School of Medicine, Northwestern University, Chicago, USA. · Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. · Endometriosis CaRe Centre, Nuffield Department of Obstetrics & Gynaecology, University of Oxford, Oxford, UK. · Center for Genomic Regulation (CRG), Barcelona, Spain. · Department of Internal Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland. · Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain. · Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, Australia. · Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong, China. · Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong, China. · Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China. · Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, Hong Kong, China. · Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. · Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. · Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. · European Centre for Environment and Human Health, University of Exeter, Truro, UK. · Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK. · School of Social and Community Medicine, University of Bristol, Bristol, UK. · Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, UK. · IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany. · Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK. · FISABIO-Universitat Jaume I-Universitat de València, Joint Research Unit of Epidemiology and Environmental Health, Valencia, Spain. · The Children's Obesity Clinic, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark. · Institute of Social and Preventive Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland. · Danish Center for Neonatal Screening, Statens Serum Institute, Copenhagen, Denmark. · Department for Congenital Disorders, Statens Serum Institute, Copenhagen, Denmark. · Computer Sciences Department, Barcelona Supercomputing Center, Barcelona, Spain. · Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. · Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, the Netherlands. · BHF Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, Scotland, UK. · Department of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, USA. · Medical Department, University of Leipzig, Leipzig, Germany. · Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland. · Kuopio Research Institute of Exercise Medicine, Kuopio, Finland. · Pediatric Research Center, Department of Women´s & Child Health, University of Leipzig, Leipzig, Germany. · Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark. · Department of Pediatrics, Turku University Hospital, Turku, Finland. · Department of Physiology, University of Turku, Turku, Finland. · Paavo Nurmi Centre, Sports and Exercise Medicine Unit, Department of Physical Activity and Health, Turku, Finland. · Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland. · Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore. · Life Sciences Institute, National University of Singapore, Singapore, Singapore. · Singapore Eye Research Institute, Singapore, Singapore. · Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark. · Department of Medicine, Stanford School of Medicine, Stanford, California, USA. · MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland, UK. · EMGO Institute for Health and Care Research, VU University and VU University Medical Center, Amsterdam, the Netherlands. · Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland. · Biocenter Oulu, University of Oulu, Finland. · School of Medicine and Pharmacology, Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia. · Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Inner City Clinic, University Hospital Munich, Ludwig Maximilian University of Munich, Munich, Germany. · Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA. · USC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City, Philippines. · Department of Nutrition and Dietetics, University of San Carlos, Cebu City, Philippines. · National Institute for Health and Welfare, Helsinki, Finland. · Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. · Folkhälsan Research Center, Helsinki, Finland. · Department of Clinical Physiology, Tampere University Hopital, Tampere, Finland. · Department of Clinical Physiology, University of Tampere School of Medicine, Tampere, Finland. · Division of Medicine, Turku University Hospital, Turku, Finland. · Department of Medicine, University of Turku, Turku, Finland. · Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands. · Epidemiology Section, BESC Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. · Research Center for Prevention and Health Capital Region, Center for Sundhed, Rigshospitalet - Glostrup, Copenhagen University, Glostrup, Denmark. · Population, Policy and Practice, UCL Institute of Child Health, University College London, London, UK. · Centre for Population Health Research, School of Health Sciences, and Sansom Institute, University of South Australia, Adelaide, Australia. · South Australian Health and Medical Research Institute, Adelaide, Australia. · Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London, UK. · Unit of Primary Care, Oulu University Hospital, Oulu, Finland. · Division of Endocrinology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. · Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark. · Department of Biostatistics, University of Liverpool, Liverpool, UK. · Estonian Genome Center, University of Tartu, Tartu, Estonia. · Department of Paediatrics, University of Cambridge, Cambridge, UK. · Oxford National Institute for Health Research (NIHR) Biomedical Research Centre, Churchill Hospital, Oxford, UK. ·Nature · Pubmed #27680694.

ABSTRACT: Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10

19 Article The Contribution of GWAS Loci in Familial Dyslipidemias. 2016

Ripatti, Pietari / Rämö, Joel T / Söderlund, Sanni / Surakka, Ida / Matikainen, Niina / Pirinen, Matti / Pajukanta, Päivi / Sarin, Antti-Pekka / Service, Susan K / Laurila, Pirkka-Pekka / Ehnholm, Christian / Salomaa, Veikko / Wilson, Richard K / Palotie, Aarno / Freimer, Nelson B / Taskinen, Marja-Riitta / Ripatti, Samuli. ·Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland. · Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America. · Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, United States of America. · Research Programs Unit, Diabetes & Obesity, University of Helsinki, and Heart and Lung Centre, Helsinki University Hospital, Helsinki, Finland. · Endocrinology, Abdominal Center, Helsinki University Hospital, Helsinki, Finland. · Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California Los Angeles (UCLA), Los Angeles, California, United States of America. · National Institute for Health and Welfare, Helsinki, Finland. · Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California, United States of America. · Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland. · Department of Medical Genetics, University of Helsinki, Helsinki, Finland. · McDonnell Genome Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America. · Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America. · The Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America. · Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, United States of America. · Department of Public Health, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland. · Wellcome Trust Sanger Institute, Cambridge, United Kingdom. ·PLoS Genet · Pubmed #27227539.

ABSTRACT: Familial combined hyperlipidemia (FCH) is a complex and common familial dyslipidemia characterized by elevated total cholesterol and/or triglyceride levels with over five-fold risk of coronary heart disease. The genetic architecture and contribution of rare Mendelian and common variants to FCH susceptibility is unknown. In 53 Finnish FCH families, we genotyped and imputed nine million variants in 715 family members with DNA available. We studied the enrichment of variants previously implicated with monogenic dyslipidemias and/or lipid levels in the general population by comparing allele frequencies between the FCH families and population samples. We also constructed weighted polygenic scores using 212 lipid-associated SNPs and estimated the relative contributions of Mendelian variants and polygenic scores to the risk of FCH in the families. We identified, across the whole allele frequency spectrum, an enrichment of variants known to elevate, and a deficiency of variants known to lower LDL-C and/or TG levels among both probands and affected FCH individuals. The score based on TG associated SNPs was particularly high among affected individuals compared to non-affected family members. Out of 234 affected FCH individuals across the families, seven (3%) carried Mendelian variants and 83 (35%) showed high accumulation of either known LDL-C or TG elevating variants by having either polygenic score over the 90th percentile in the population. The positive predictive value of high score was much higher for affected FCH individuals than for similar sporadic cases in the population. FCH is highly polygenic, supporting the hypothesis that variants across the whole allele frequency spectrum contribute to this complex familial trait. Polygenic SNP panels improve identification of individuals affected with FCH, but their clinical utility remains to be defined.

20 Article Genetic Risk Scores Predict Recurrence of Acute Coronary Syndrome. 2016

Vaara, Satu / Tikkanen, Emmi / Parkkonen, Olavi / Lokki, Marja-Liisa / Ripatti, Samuli / Perola, Markus / Nieminen, Markku S / Sinisalo, Juha. ·From the Division of Cardiology, Heart and Lung Center, Helsinki University Central Hospital, Helsinki, Finland (S.V., O.P., M.S.N., J.S.) · Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (E.T., S.P., M.P.) · and Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland (E.T., S.P., M.P.) and Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland (M.-L.L.). ·Circ Cardiovasc Genet · Pubmed #26980882.

ABSTRACT: BACKGROUND: Several clinical risk estimation tools have established their role in the prediction of recurrence of acute coronary syndrome (ACS), but the value of genetic risk scores (GRSs) remains unclear. We examined how well 2 different GRSs estimate recurrent ACS and whether clinical factors are associated with GRSs. METHODS AND RESULTS: A cohort of 2090 consecutive patients with ACS who underwent coronary angiography between July 2006 and March 2008 in a single tertiary center was genotyped and prospectively followed up for a median of 5.5 years. We formed 2 partially overlapping GRSs: GRS47 of 47 single-nucleotide polymorphisms with previously reported significant association with coronary artery disease and GRS153 of 153 single-nucleotide polymorphisms with significant or suggestive association with coronary artery disease. GRS47 showed association with recurrent ACS independent of clinical factors (P=0.037; hazard ratio, 1.17; 95% confidence interval, 1.01-1.36). GRS153 had no association with either recurrent ACS or composite of recurrent ACS or death. Also, GRS47 was associated inversely with smoking and ST-segment-elevation myocardial infarction (P=0.004; odds ratio, 0.22; 95% confidence interval, 0.08-0.62 and P=0.041; odds ratio, 0.36; 95% confidence interval, 0.13-0.96, respectively). CONCLUSIONS: GRSs combined of 47 known coronary artery disease risk single-nucleotide polymorphisms were associated with recurrent ACS after multivariable adjustments in a heterogenic ACS population for the first time. Smoking and ST-segment-elevation myocardial infarction had an inverse association with the GRSs. The significance of smoking in relation to genetic coronary artery disease predisposition may merit further evaluation in patients with ACS.

21 Article Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium. 2016

Dehghan, Abbas / Bis, Joshua C / White, Charles C / Smith, Albert Vernon / Morrison, Alanna C / Cupples, L Adrienne / Trompet, Stella / Chasman, Daniel I / Lumley, Thomas / Völker, Uwe / Buckley, Brendan M / Ding, Jingzhong / Jensen, Majken K / Folsom, Aaron R / Kritchevsky, Stephen B / Girman, Cynthia J / Ford, Ian / Dörr, Marcus / Salomaa, Veikko / Uitterlinden, André G / Eiriksdottir, Gudny / Vasan, Ramachandran S / Franceschini, Nora / Carty, Cara L / Virtamo, Jarmo / Demissie, Serkalem / Amouyel, Philippe / Arveiler, Dominique / Heckbert, Susan R / Ferrières, Jean / Ducimetière, Pierre / Smith, Nicholas L / Wang, Ying A / Siscovick, David S / Rice, Kenneth M / Wiklund, Per-Gunnar / Taylor, Kent D / Evans, Alun / Kee, Frank / Rotter, Jerome I / Karvanen, Juha / Kuulasmaa, Kari / Heiss, Gerardo / Kraft, Peter / Launer, Lenore J / Hofman, Albert / Markus, Marcello R P / Rose, Lynda M / Silander, Kaisa / Wagner, Peter / Benjamin, Emelia J / Lohman, Kurt / Stott, David J / Rivadeneira, Fernando / Harris, Tamara B / Levy, Daniel / Liu, Yongmei / Rimm, Eric B / Jukema, J Wouter / Völzke, Henry / Ridker, Paul M / Blankenberg, Stefan / Franco, Oscar H / Gudnason, Vilmundur / Psaty, Bruce M / Boerwinkle, Eric / O'Donnell, Christopher J. ·Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands. · Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, United States of America. · Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States of America. · Icelandic Heart Association, Kopavogur, Iceland. · University of Iceland, Reykjavik, Iceland. · Human Genetics Center, and Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, TX, United States of America. · Boston University's and National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, United States of America. · Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands. · Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands. · Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America. · Department of Biostatistics, University of Washington, Seattle, WA, United States of America. · Department of Statistics, University of Auckland, Auckland, New Zealand. · Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany. · DZHK (German Center for Cardiovascular Research), partner site, Greifswald, Germany. · Department of Pharmacology and Therapeutics, University College, Cork, Ireland. · Department of Internal Medicine, Division of Geriatrics, Wake Forest University, Winston-Salem, North Carolina, United States of America. · Department of Nutrition, Harvard School of Public Health, Boston, MA, United States of America. · Channing Division of Network Medicine, Harvard Medical School, Boston, MA, United States of America. · Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, United States of America. · Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC, United States of America. · Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, United States of America. · Department of Epidemiology, Merck Research Laboratories, Merck Sharp & Dohme Corp., Whitehouse Station, NJ, United States of America. · Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom. · Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany. · National Institute for Health and Welfare, Helsinki, Finland. · Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. · Department of Epidemiology, Boston University School of Public Health, Boston, MA, United States of America. · Department of Medicine, Boston University School of Medicine, Boston, MA, United States of America. · Department of Preventive Medicine, Boston University School of Medicine, Boston, MA, United States of America. · Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, United States of America. · Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America. · Department of Epidemiology and Public Health, Pasteur Institute of Lille, Lille, France. · Department of Epidemiology and Public Health, EA 3430, University of Strasbourg, Strasbourg, France. · Department of Epidemiology, University of Washington, Seattle, WA, United States of America. · Group Health Research Institute, Group Health Cooperative, Seattle, United States of America. · Departments of Cardiology and Epidemiology, Toulouse University Hospital, Toulouse, France. · National Institute of Health and Medical Research (U258), Paris, France. · Seattle Epidemiologic Research and Information Center of the Department of Veterans Affairs Office of Research and Development, Seattle, WA, United States of America. · Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, MA, United States of America. · The New York Academy of Medicine, New York, NY, United States of America. · Department of Medicine, Umeå University Hospital, Umeå, Sweden. · Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Torrance, CA, United States of America. · Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, United States of America. · UKCRC Centre of Excellence for Public Health Research (Northern Ireland), Queen's University of Belfast, Belfast, United Kingdom. · Department of Mathematics and Statistics, University of Jyväskylä, Jyväskylä, Finland. · Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States of America. · Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States of America. · Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. · Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland. · Department of Epidemiology & Prevention, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27157, United States of America. · Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom. · Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands. · Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands. · Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands. · Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf, Hamburg, Germany. · Department of Health Services, University of Washington, Seattle, WA, United States of America. · Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America. · Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, MD, United States of America. · Cardiology Section, Department of Medicine, Boston Veteran's Administration Healthcare, Boston, MA, United States of America. ·PLoS One · Pubmed #26950853.

ABSTRACT: BACKGROUND: Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. METHODS: We performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10-6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up. RESULTS: In Stage I 15 loci passed the threshold of 5×10-6; 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8×10-3) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2×10-9). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2×10-3). CONCLUSIONS: QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders.

22 Article Primary prevention and risk factor reduction in coronary heart disease mortality among working aged men and women in eastern Finland over 40 years: population based observational study. 2016

Jousilahti, Pekka / Laatikainen, Tiina / Peltonen, Markku / Borodulin, Katja / Männistö, Satu / Jula, Antti / Salomaa, Veikko / Harald, Kennet / Puska, Pekka / Vartiainen, Erkki. ·National Institute for Health and Welfare, Department of Health, PO Box 30, 00271 Helsinki, Finland pekka.jousilahti@thl.fi. · University of Eastern Finland, Institute of Public Health and Clinical Nutrition, Kuopio, Finland. · National Institute for Health and Welfare, Department of Health, PO Box 30, 00271 Helsinki, Finland. ·BMJ · Pubmed #26932978.

ABSTRACT: OBJECTIVE: To estimate how much changes in the main risk factors of cardiovascular disease (smoking prevalence, serum cholesterol, and systolic blood pressure) can explain the reduction in coronary heart disease mortality observed among working aged men and women in eastern Finland. DESIGN: Population based observational study. SETTING: Eastern Finland. PARTICIPANTS: 34,525 men and women aged 30-59 years who participated in the national FINRISK studies between 1972 and 2012. INTERVENTIONS: Change in main cardiovascular risk factors through population based primary prevention. MAIN OUTCOME MEASURES: Predicted and observed age standardised mortality due to coronary heart disease. Predicted change was estimated with a logistic regression model using risk factor data collected in nine consecutive, population based, risk factor surveys conducted every five years since 1972. Data on observed mortality were obtained from the National Causes of Death Register. RESULTS: During the 40 year study period, levels of the three major cardiovascular risk factors decreased except for a small increase in serum cholesterol levels between 2007 and 2012. From years 1969-1972 to 2012, coronary heart disease mortality decreased by 82% (from 643 to 118 deaths per 100,000 people) and 84% (114 to 17) among men and women aged 35-64 years, respectively. During the first 10 years of the study, changes in these three target risk factors contributed to nearly all of the observed mortality reduction. Since the mid-1980s, the observed reduction in mortality has been larger than predicted. In the last 10 years of the study, about two thirds (69% in men and 66% in women) of the reduction could be explained by changes in the three main risk factors, and the remaining third by other factors. CONCLUSION: Reductions in disease burden and mortality due to coronary heart disease can be achieved through the use of population based primary prevention programmes. Secondary prevention among high risk individuals and treatment of acute events of coronary heart disease could confer additional benefit.

23 Article Body Mass Index as a Predictor of Sudden Cardiac Death and Usefulness of the Electrocardiogram for Risk Stratification. 2016

Eranti, Antti / Aro, Aapo L / Kerola, Tuomas / Tikkanen, Jani T / Rissanen, Harri A / Anttonen, Olli / Junttila, M Juhani / Knekt, Paul / Huikuri, Heikki V. ·Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland. Electronic address: antti.eranti@helsinki.fi. · Division of Cardiology, Heart and Lung Center, Helsinki University Central Hospital, Helsinki, Finland. · Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland. · Medical Research Center Oulu, Department of Internal Medicine, University Hospital and University of Oulu, Oulu, Finland. · Department of Health, Functional Capacity, and Welfare, National Institute for Health and Welfare, Helsinki, Finland. ·Am J Cardiol · Pubmed #26723105.

ABSTRACT: Evidence of the role of body mass index (BMI) as a risk factor for sudden cardiac death (SCD) is conflicting, and how electrocardiographic (ECG) SCD risk markers perform in subjects with different BMIs is not known. In this study, a general population cohort consisting of 10,543 middle-aged subjects (mean age 44 years, 52.7% men) was divided into groups of lean (BMI <20, n = 374), normal weight (BMI 20.0 to 24.9, n = 4,334), overweight (BMI 25.0 to 29.9, n = 4,390), and obese (BMI >30, n = 1,445) subjects. Cox proportional hazards models adjusted for confounders were used to assess the risk for SCD associated with BMI and the risk for SCD associated with ECG abnormalities in subjects with different BMIs. The overweight and obese subjects were at increased risk for SCD (hazard ratios [95% CIs] were 1.33 [1.13 to 1.56], p = 0.001 and 1.79 [1.44 to 2.23], p <0.001 for overweight and obese subjects, respectively). The risk of non-SCD had a similar relation with BMI as SCD. Hazard ratios associated with ECG abnormalities were 3.03, 1.75, 1.74, and 1.34 in groups of lean, normal weight, overweight, and obese subjects, respectively, but no statistical significance was reached in the obese. ECG abnormalities improved integrated discrimination indexes and continuous net reclassification indexes statistically significantly only in the normal weight group. In conclusion, the overweight and obese are at increased risk for SCD but also for non-SCD, and ECG abnormalities are associated with increased risk of SCD also in normal weight subjects presenting with less traditional cardiovascular risk factors.

24 Article Prenatal and maternal characteristics and later risk for coronary heart disease among women. 2016

Eriksson, Johan G / Kajantie, Eero / Thornburg, Kent / Osmond, Clive. ·National Institute for Health and Welfare, Department of Chronic Disease Prevention, Finland Department of General Practice and Primary Health Care, University of Helsinki, Finland Vasa Central Hospital, Finland Folkhälsan Research Centre, Helsingfors Universitet, Finland Unit of General Practice, Helsinki University Central Hospital, Finland johan.eriksson@helsinki.fi. · National Institute for Health and Welfare, Department of Chronic Disease Prevention, Finland Hospital for Children and Adolescents, Helsinki University Central Hospital, Finland Department of Obstetrics and Gynaecology, Oulu University Hospital, Finland. · Heart Research Center, Oregon Health and Science University, USA. · MRC Lifecourse Epidemiology Unit, Southampton General Hospital, UK. ·Eur J Prev Cardiol · Pubmed #26152774.

ABSTRACT: OBJECTIVE: The pace and pathways of early growth have major influences on later health. Coronary heart disease (CHD) is a major killer and kills more women than men, but usually manifests about 10 years later in women. Therefore there are fewer studies of early growth and CHD amongst women than men. METHODS: The Helsinki Birth Cohort Study includes 9817 women born during 1924-1944. We used national registers to identify hospital admissions and deaths from CHD during 1971-2010. We used a Cox model to obtain hazard ratios (HRs) for CHD. RESULTS: Altogether 967 women (9.9%) developed CHD. Socioeconomic factors were strongly and inversely associated with CHD. Neither maternal age nor body mass index (BMI) was associated with CHD in the daughters. There were inverse associations of birth weight (p = 0.07) and length (p = 0.02) with CHD in adult life. We divided the mothers according to parity. Daughters of primiparous women had lower birth weight and shorter birth length than the offspring of multiparous women (both p-values < 0.001). Birth weight (p = 0.008), birth length (p = 0.05) and birth BMI (p = 0.02) were all inversely associated with CHD. Among first-born women, a 1 kg increase in birth weight was associated with a 25% lower risk for CHD (HR 0.75, 95% confidence interval (CI) 0.60-0.93). The findings changed little after adjustment for socioeconomic factors. Among later-born women none of the birth characteristics was associated with CHD. CONCLUSIONS: Small birth size is associated with CHD among women. First-born women with high birth weight appear to be at lower risk for CHD compared with later born women.

25 Article Patients with coronary artery disease and diabetes need improved management: a report from the EUROASPIRE IV survey: a registry from the EuroObservational Research Programme of the European Society of Cardiology. 2015

Gyberg, Viveca / De Bacquer, Dirk / De Backer, Guy / Jennings, Catriona / Kotseva, Kornelia / Mellbin, Linda / Schnell, Oliver / Tuomilehto, Jaakko / Wood, David / Rydén, Lars / Amouyel, Philippe / Bruthans, Jan / Conde, Almudena Castro / Cifkova, Renata / Deckers, Jaap W / De Sutter, Johan / Dilic, Mirza / Dolzhenko, Maryna / Erglis, Andrejs / Fras, Zlatko / Gaita, Dan / Gotcheva, Nina / Goudevenos, John / Heuschmann, Peter / Laucevicius, Aleksandras / Lehto, Seppo / Lovic, Dragan / Miličić, Davor / Moore, David / Nicolaides, Evagoras / Oganov, Raphael / Pająk, Andrzej / Pogosova, Nana / Reiner, Zeljko / Stagmo, Martin / Störk, Stefan / Tokgözoğlu, Lale / Vulic, Dusko / Anonymous4140844. ·Cardiology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, 171 76, Stockholm, Sweden. vivecagyberg@gmail.com. · Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden. vivecagyberg@gmail.com. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. Dirk.DeBacquer@UGent.be. · Department of Public Health, Ghent University, Ghent, Belgium. Dirk.DeBacquer@UGent.be. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. guy.debacker@ugent.be. · Department of Public Health, Ghent University, Ghent, Belgium. guy.debacker@ugent.be. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. c.jennings@imperial.ac.uk. · Department of Cardiovascular Medicine, National Heart and Lung Institute, Imperial College London, London, UK. c.jennings@imperial.ac.uk. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. k.kotseva@imperial.ac.uk. · Department of Cardiovascular Medicine, National Heart and Lung Institute, Imperial College London, London, UK. k.kotseva@imperial.ac.uk. · Cardiology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, 171 76, Stockholm, Sweden. linda.mellbin@ki.se. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. linda.mellbin@ki.se. · Forschergruppe Diabetes e.V. at the Helmholtz Center, Munich, Germany. Oliver.Schnell@lrz.uni-muenchen.de. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. jaakko.tuomilehto@thl.fi. · Centre for Vascular Prevention, Danube-University Krems, Krems, Austria. jaakko.tuomilehto@thl.fi. · Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland. jaakko.tuomilehto@thl.fi. · Instituto de Investigacion Sanitaria del Hospital Universario LaPaz (IdiPAZ), Madrid, Spain. jaakko.tuomilehto@thl.fi. · Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia. jaakko.tuomilehto@thl.fi. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. d.wood@imperial.ac.uk. · Department of Cardiovascular Medicine, National Heart and Lung Institute, Imperial College London, London, UK. d.wood@imperial.ac.uk. · Cardiology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, 171 76, Stockholm, Sweden. Lars.Ryden@ki.se. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. Lars.Ryden@ki.se. · Institut Pasteur de Lille, Inserm U744, Université Lille Nord de France, 1 rue du Professeur Calmette B.P. 245, 59019, Lille, France. Philippe.amouyel@pasteur-lille.Fr. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. jan.bruthans@seznam.cz. · Center for Cardiovascular Prevention, 1st School of Medicine, Charles University and Thomayer Hospital, Vídeňská 800, 140 59, Prague, Czech Republic. jan.bruthans@seznam.cz. · Cardiac Rehabilitation Unit, Cardiology Department, Hospital Universitario La Paz, Madrid, Spain. almudenacastroconde@yahoo.es. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. renata.cifkova@ftn.cz. · Center for Cardiovascular Prevention, 1st School of Medicine, Charles University and Thomayer Hospital, Vídeňská 800, 140 59, Prague, Czech Republic. renata.cifkova@ftn.cz. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. j.deckers@erasmusmc.nl. · Thoraxcenter's Department of Cardiology, Dr Molewaterplein 50, 3000 DR, Rotterdam, The Netherlands. j.deckers@erasmusmc.nl. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. johan.desutter@ugent.be. · Department of Internal Medicine, University of Ghent, De Pintelaan 185, 9000, Ghent, Belgium. johan.desutter@ugent.be. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. mdilic@bih.net.ba. · Clinical Center University of Sarajevo, Bolnička 25, 71000, Sarajevo, Bosnia and Herzegovina. mdilic@bih.net.ba. · Department of Cardiology of Shupyk's Medical Academy of Postgraduate Education, 9 Dorohozhyts'ka str, Kiev, 04112, Ukraine. marinadolzhenko@mail.ru. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. a.a.erglis@stradini.lv. · University of Latvia, Pauls Stradins Clinical University Hospital, Pilsonu Street 13, Riga, 1002, Latvia. a.a.erglis@stradini.lv. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. zlatko.fras@telemach.net. · Preventive Cardiology Unit, Division of Internal Medicine, University Medical Centre Ljubljana, Zaloška 7, 1525, Ljubljana, Slovenia. zlatko.fras@telemach.net. · Medical Faculty, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia. zlatko.fras@telemach.net. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. dgaita@cardiologie.ro. · Institutul de Boli Cardiovasculare, Universitatea de Medicina si Farmacie "Victor Babes", Timisoara, Romania. dgaita@cardiologie.ro. · Department of Cardiology, National Heart Hospital, 65, Konyovitsa, 1309, Sofia, Bulgaria. ngotcheva@abv.bg. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. igoudev@cc.uoi.gr. · Cardiology Department of Medical School, University of Ioannina, Ioannina, Greece. igoudev@cc.uoi.gr. · Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany. E_Heuschma_P@klinik.uni-wuerzburg.de. · Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany. E_Heuschma_P@klinik.uni-wuerzburg.de. · Clinical Trial Center Würzburg, University Hospital Würzburg, Josef-Schneider-Str. 2, 97080, Würzburg, Germany. E_Heuschma_P@klinik.uni-wuerzburg.de. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. alius@cardio.it. · Clinic of Cardiovascular Diseases of Vilnius University, Santariskiu 2, 08661, Vilnius, Lithuania. alius@cardio.it. · Heart and Vascular Medicine of Vilnius University Hospital Santariskiu Clinics, Santariskiu 2, 08661, Vilnius, Lithuania. alius@cardio.it. · Kuopio University Hospital, Rakennus 5/6. Kerros, Puijonlaaksontie 2, 70210, Kuopio, Finland. seppo.lehto@varkaus.fi. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. draganl1@sbb.rs. · Clinic for Internal Medicine Intermedica, Jovana Ristica 20/2, 18000, Nis, Serbia. draganl1@sbb.rs. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. d.milicic@mail.inet.hr. · University of Zagreb School of Medicine and University Hospital Centre Zagreb, Kispaticeva 12, HR-10000, Zagreb, Croatia. d.milicic@mail.inet.hr. · The Adelaide and Meath Hospital, Tallaght, Dublin 24, Ireland. David.Moore@amnch.ie. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. evnicor@cytanet.com.cy. · University of Nicosia Medical School, Nicosia General Hospital, 2029 Strovolos, Nicosia, Cyprus. evnicor@cytanet.com.cy. · National Research Center for Preventive Medicine of the Ministry of Healthcare of the Russian Federation, 10 Petroverigsky per, 101990, Moscow, Russia. oganov@gnicpm.ru. · Department of Epidemiology and Population Studies, Faculty of Health Sciences, Jafiellonian University Medical College, Grzegórzecka 20, 31-531, Cracow, Poland. andrzej.pajak@uj.edu.pl. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. NPogosova@gnicpm.ru. · Federal Health Centre and Department of Chronic Noncommunicable Diseases Prevention, National Research Centre for Preventive Medicine, 10 Petroverigsky per, 101953, Moscow, Russia. NPogosova@gnicpm.ru. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. zreiner@kbc-zagreb.hr. · University Hospital Centre Zagreb, School of Medicine, University of Zagreb, Kišpatićeva 12, 10000, Zagreb, Croatia. zreiner@kbc-zagreb.hr. · Department of Heart failure and Valve Disease, Skåne University Hospital, Lund, Sweden. Martin.Stagmo@skane.se. · Comprehensive Heart Failure Centre and Department of Medicine I, University of Würzburg, Straubmühlweg 2a, 97078, Würzburg, Germany. Stoerk_S@medizin.uni-wuerzburg.de. · European Society of Cardiology, Les Templiers, 2035 route des Colles, CS 80179 BIOT, 06903, Sophia Antipolis Cedex, France. lalet@hacettepe.edu.tr. · Hacettepe University, 06690, Ankara, Turkey. lalet@hacettepe.edu.tr. · Centre for Medical Research, School of Medicine, University of Banja Luka, Vuka Karadzica 6, 78000, Banja Luka, Republic of Srpska, Bosnia and Herzegovina. dule@blic.net. ·Cardiovasc Diabetol · Pubmed #26427624.

ABSTRACT: BACKGROUND: In order to influence every day clinical practice professional organisations issue management guidelines. Cross-sectional surveys are used to evaluate the implementation of such guidelines. The present survey investigated screening for glucose perturbations in people with coronary artery disease and compared patients with known and newly detected type 2 diabetes with those without diabetes in terms of their life-style and pharmacological risk factor management in relation to contemporary European guidelines. METHODS: A total of 6187 patients (18-80 years) with coronary artery disease and known glycaemic status based on a self reported history of diabetes (previously known diabetes) or the results of an oral glucose tolerance test and HbA1c (no diabetes or newly diagnosed diabetes) were investigated in EUROASPIRE IV including patients in 24 European countries 2012-2013. The patients were interviewed and investigated in order to enable a comparison between their actual risk factor control with that recommended in current European management guidelines and the outcome in previously conducted surveys. RESULTS: A total of 2846 (46%) patients had no diabetes, 1158 (19%) newly diagnosed diabetes and 2183 (35%) previously known diabetes. The combined use of all four cardioprotective drugs in these groups was 53, 55 and 60%, respectively. A blood pressure target of <140/90 mmHg was achieved in 68, 61, 54% and a LDL-cholesterol target of <1.8 mmol/L in 16, 18 and 28%. Patients with newly diagnosed and previously known diabetes reached an HbA1c <7.0% (53 mmol/mol) in 95 and 53% and 11% of those with previously known diabetes had an HbA1c >9.0% (>75 mmol/mol). Of the patients with diabetes 69% reported on low physical activity. The proportion of patients participating in cardiac rehabilitation programmes was low (≈40 %) and only 27% of those with diabetes had attended diabetes schools. Compared with data from previous surveys the use of cardioprotective drugs had increased and more patients were achieving the risk factor treatment targets. CONCLUSIONS: Despite advances in patient management there is further potential to improve both the detection and management of patients with diabetes and coronary artery disease.

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