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Aroon Hingorani

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https://www.readbyqxmd.com/read/29183961/oral-anticoagulants-for-prevention-of-stroke-in-atrial-fibrillation-systematic-review-network-meta-analysis-and-cost-effectiveness-analysis
#1
REVIEW
José A López-López, Jonathan A C Sterne, Howard H Z Thom, Julian P T Higgins, Aroon D Hingorani, George N Okoli, Philippa A Davies, Pritesh N Bodalia, Peter A Bryden, Nicky J Welton, William Hollingworth, Deborah M Caldwell, Jelena Savović, Sofia Dias, Chris Salisbury, Diane Eaton, Annya Stephens-Boal, Reecha Sofat
Objective To compare the efficacy, safety, and cost effectiveness of direct acting oral anticoagulants (DOACs) for patients with atrial fibrillation.Design Systematic review, network meta-analysis, and cost effectiveness analysis. Data sources Medline, PreMedline, Embase, and The Cochrane Library.Eligibility criteria for selecting studies Published randomised trials evaluating the use of a DOAC, vitamin K antagonist, or antiplatelet drug for prevention of stroke in patients with atrial fibrillation.Results 23 randomised trials involving 94 656 patients were analysed: 13 compared a DOAC with warfarin dosed to achieve a target INR of 2...
November 28, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/29030599/genome-wide-meta-analysis-associates-hla-dqa1-drb1-and-lpa-and-lifestyle-factors-with-human-longevity
#2
Peter K Joshi, Nicola Pirastu, Katherine A Kentistou, Krista Fischer, Edith Hofer, Katharina E Schraut, David W Clark, Teresa Nutile, Catriona L K Barnes, Paul R H J Timmers, Xia Shen, Ilaria Gandin, Aaron F McDaid, Thomas Folkmann Hansen, Scott D Gordon, Franco Giulianini, Thibaud S Boutin, Abdel Abdellaoui, Wei Zhao, Carolina Medina-Gomez, Traci M Bartz, Stella Trompet, Leslie A Lange, Laura Raffield, Ashley van der Spek, Tessel E Galesloot, Petroula Proitsi, Lisa R Yanek, Lawrence F Bielak, Antony Payton, Federico Murgia, Maria Pina Concas, Ginevra Biino, Salman M Tajuddin, Ilkka Seppälä, Najaf Amin, Eric Boerwinkle, Anders D Børglum, Archie Campbell, Ellen W Demerath, Ilja Demuth, Jessica D Faul, Ian Ford, Alessandro Gialluisi, Martin Gögele, MariaElisa Graff, Aroon Hingorani, Jouke-Jan Hottenga, David M Hougaard, Mikko A Hurme, M Arfan Ikram, Marja Jylhä, Diana Kuh, Lannie Ligthart, Christina M Lill, Ulman Lindenberger, Thomas Lumley, Reedik Mägi, Pedro Marques-Vidal, Sarah E Medland, Lili Milani, Reka Nagy, William E R Ollier, Patricia A Peyser, Peter P Pramstaller, Paul M Ridker, Fernando Rivadeneira, Daniela Ruggiero, Yasaman Saba, Reinhold Schmidt, Helena Schmidt, P Eline Slagboom, Blair H Smith, Jennifer A Smith, Nona Sotoodehnia, Elisabeth Steinhagen-Thiessen, Frank J A van Rooij, André L Verbeek, Sita H Vermeulen, Peter Vollenweider, Yunpeng Wang, Thomas Werge, John B Whitfield, Alan B Zonderman, Terho Lehtimäki, Michele K Evans, Mario Pirastu, Christian Fuchsberger, Lars Bertram, Neil Pendleton, Sharon L R Kardia, Marina Ciullo, Diane M Becker, Andrew Wong, Bruce M Psaty, Cornelia M van Duijn, James G Wilson, J Wouter Jukema, Lambertus Kiemeney, André G Uitterlinden, Nora Franceschini, Kari E North, David R Weir, Andres Metspalu, Dorret I Boomsma, Caroline Hayward, Daniel Chasman, Nicholas G Martin, Naveed Sattar, Harry Campbell, Tōnu Esko, Zoltán Kutalik, James F Wilson
Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated...
October 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28986451/impact-of-selection-bias-on-estimation-of-subsequent-event-risk
#3
Yi-Juan Hu, Amand F Schmidt, Frank Dudbridge, Michael V Holmes, James M Brophy, Vinicius Tragante, Ziyi Li, Peizhou Liao, Arshed A Quyyumi, Raymond O McCubrey, Benjamin D Horne, Aroon D Hingorani, Folkert W Asselbergs, Riyaz S Patel, Qi Long
BACKGROUND: Studies of recurrent or subsequent disease events may be susceptible to bias caused by selection of subjects who both experience and survive the primary indexing event. Currently, the magnitude of any selection bias, particularly for subsequent time-to-event analysis in genetic association studies, is unknown. METHODS AND RESULTS: We used empirically inspired simulation studies to explore the impact of selection bias on the marginal hazard ratio for risk of subsequent events among those with established coronary heart disease...
October 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28898252/impact-of-common-genetic-determinants-of-hemoglobin-a1c-on-type-2-diabetes-risk-and-diagnosis-in-ancestrally-diverse-populations-a-transethnic-genome-wide-meta-analysis
#4
Eleanor Wheeler, Aaron Leong, Ching-Ti Liu, Marie-France Hivert, Rona J Strawbridge, Clara Podmore, Man Li, Jie Yao, Xueling Sim, Jaeyoung Hong, Audrey Y Chu, Weihua Zhang, Xu Wang, Peng Chen, Nisa M Maruthur, Bianca C Porneala, Stephen J Sharp, Yucheng Jia, Edmond K Kabagambe, Li-Ching Chang, Wei-Min Chen, Cathy E Elks, Daniel S Evans, Qiao Fan, Franco Giulianini, Min Jin Go, Jouke-Jan Hottenga, Yao Hu, Anne U Jackson, Stavroula Kanoni, Young Jin Kim, Marcus E Kleber, Claes Ladenvall, Cecile Lecoeur, Sing-Hui Lim, Yingchang Lu, Anubha Mahajan, Carola Marzi, Mike A Nalls, Pau Navarro, Ilja M Nolte, Lynda M Rose, Denis V Rybin, Serena Sanna, Yuan Shi, Daniel O Stram, Fumihiko Takeuchi, Shu Pei Tan, Peter J van der Most, Jana V Van Vliet-Ostaptchouk, Andrew Wong, Loic Yengo, Wanting Zhao, Anuj Goel, Maria Teresa Martinez Larrad, Dörte Radke, Perttu Salo, Toshiko Tanaka, Erik P A van Iperen, Goncalo Abecasis, Saima Afaq, Behrooz Z Alizadeh, Alain G Bertoni, Amelie Bonnefond, Yvonne Böttcher, Erwin P Bottinger, Harry Campbell, Olga D Carlson, Chien-Hsiun Chen, Yoon Shin Cho, W Timothy Garvey, Christian Gieger, Mark O Goodarzi, Harald Grallert, Anders Hamsten, Catharina A Hartman, Christian Herder, Chao Agnes Hsiung, Jie Huang, Michiya Igase, Masato Isono, Tomohiro Katsuya, Chiea-Chuen Khor, Wieland Kiess, Katsuhiko Kohara, Peter Kovacs, Juyoung Lee, Wen-Jane Lee, Benjamin Lehne, Huaixing Li, Jianjun Liu, Stephane Lobbens, Jian'an Luan, Valeriya Lyssenko, Thomas Meitinger, Tetsuro Miki, Iva Miljkovic, Sanghoon Moon, Antonella Mulas, Gabriele Müller, Martina Müller-Nurasyid, Ramaiah Nagaraja, Matthias Nauck, James S Pankow, Ozren Polasek, Inga Prokopenko, Paula S Ramos, Laura Rasmussen-Torvik, Wolfgang Rathmann, Stephen S Rich, Neil R Robertson, Michael Roden, Ronan Roussel, Igor Rudan, Robert A Scott, William R Scott, Bengt Sennblad, David S Siscovick, Konstantin Strauch, Liang Sun, Morris Swertz, Salman M Tajuddin, Kent D Taylor, Yik-Ying Teo, Yih Chung Tham, Anke Tönjes, Nicholas J Wareham, Gonneke Willemsen, Tom Wilsgaard, Aroon D Hingorani, Josephine Egan, Luigi Ferrucci, G Kees Hovingh, Antti Jula, Mika Kivimaki, Meena Kumari, Inger Njølstad, Colin N A Palmer, Manuel Serrano Ríos, Michael Stumvoll, Hugh Watkins, Tin Aung, Matthias Blüher, Michael Boehnke, Dorret I Boomsma, Stefan R Bornstein, John C Chambers, Daniel I Chasman, Yii-Der Ida Chen, Yduan-Tsong Chen, Ching-Yu Cheng, Francesco Cucca, Eco J C de Geus, Panos Deloukas, Michele K Evans, Myriam Fornage, Yechiel Friedlander, Philippe Froguel, Leif Groop, Myron D Gross, Tamara B Harris, Caroline Hayward, Chew-Kiat Heng, Erik Ingelsson, Norihiro Kato, Bong-Jo Kim, Woon-Puay Koh, Jaspal S Kooner, Antje Körner, Diana Kuh, Johanna Kuusisto, Markku Laakso, Xu Lin, Yongmei Liu, Ruth J F Loos, Patrik K E Magnusson, Winfried März, Mark I McCarthy, Albertine J Oldehinkel, Ken K Ong, Nancy L Pedersen, Mark A Pereira, Annette Peters, Paul M Ridker, Charumathi Sabanayagam, Michele Sale, Danish Saleheen, Juha Saltevo, Peter Eh Schwarz, Wayne H H Sheu, Harold Snieder, Timothy D Spector, Yasuharu Tabara, Jaakko Tuomilehto, Rob M van Dam, James G Wilson, James F Wilson, Bruce H R Wolffenbuttel, Tien Yin Wong, Jer-Yuarn Wu, Jian-Min Yuan, Alan B Zonderman, Nicole Soranzo, Xiuqing Guo, David J Roberts, Jose C Florez, Robert Sladek, Josée Dupuis, Andrew P Morris, E-Shyong Tai, Elizabeth Selvin, Jerome I Rotter, Claudia Langenberg, Inês Barroso, James B Meigs
BACKGROUND: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c...
September 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28770004/discovery-and-replication-of-snp-snp-interactions-for-quantitative-lipid-traits-in-over-60-000-individuals
#5
Emily R Holzinger, Shefali S Verma, Carrie B Moore, Molly Hall, Rishika De, Diane Gilbert-Diamond, Matthew B Lanktree, Nathan Pankratz, Antoinette Amuzu, Amber Burt, Caroline Dale, Scott Dudek, Clement E Furlong, Tom R Gaunt, Daniel Seung Kim, Helene Riess, Suthesh Sivapalaratnam, Vinicius Tragante, Erik P A van Iperen, Ariel Brautbar, David S Carrell, David R Crosslin, Gail P Jarvik, Helena Kuivaniemi, Iftikhar J Kullo, Eric B Larson, Laura J Rasmussen-Torvik, Gerard Tromp, Jens Baumert, Karen J Cruickshanks, Martin Farrall, Aroon D Hingorani, G K Hovingh, Marcus E Kleber, Barbara E Klein, Ronald Klein, Wolfgang Koenig, Leslie A Lange, Winfried Mӓrz, Kari E North, N Charlotte Onland-Moret, Alex P Reiner, Philippa J Talmud, Yvonne T van der Schouw, James G Wilson, Mika Kivimaki, Meena Kumari, Jason H Moore, Fotios Drenos, Folkert W Asselbergs, Brendan J Keating, Marylyn D Ritchie
BACKGROUND: The genetic etiology of human lipid quantitative traits is not fully elucidated, and interactions between variants may play a role. We performed a gene-centric interaction study for four different lipid traits: low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG). RESULTS: Our analysis consisted of a discovery phase using a merged dataset of five different cohorts (n = 12,853 to n = 16,849 depending on lipid phenotype) and a replication phase with ten independent cohorts totaling up to 36,938 additional samples...
2017: BioData Mining
https://www.readbyqxmd.com/read/28714975/association-analyses-based-on-false-discovery-rate-implicate-new-loci-for-coronary-artery-disease
#6
Christopher P Nelson, Anuj Goel, Adam S Butterworth, Stavroula Kanoni, Tom R Webb, Eirini Marouli, Lingyao Zeng, Ioanna Ntalla, Florence Y Lai, Jemma C Hopewell, Olga Giannakopoulou, Tao Jiang, Stephen E Hamby, Emanuele Di Angelantonio, Themistocles L Assimes, Erwin P Bottinger, John C Chambers, Robert Clarke, Colin N A Palmer, Richard M Cubbon, Patrick Ellinor, Raili Ermel, Evangelos Evangelou, Paul W Franks, Christopher Grace, Dongfeng Gu, Aroon D Hingorani, Joanna M M Howson, Erik Ingelsson, Adnan Kastrati, Thorsten Kessler, Theodosios Kyriakou, Terho Lehtimäki, Xiangfeng Lu, Yingchang Lu, Winfried März, Ruth McPherson, Andres Metspalu, Mar Pujades-Rodriguez, Arno Ruusalepp, Eric E Schadt, Amand F Schmidt, Michael J Sweeting, Pierre A Zalloua, Kamal AlGhalayini, Bernard D Keavney, Jaspal S Kooner, Ruth J F Loos, Riyaz S Patel, Martin K Rutter, Maciej Tomaszewski, Ioanna Tzoulaki, Eleftheria Zeggini, Jeanette Erdmann, George Dedoussis, Johan L M Björkegren, Heribert Schunkert, Martin Farrall, John Danesh, Nilesh J Samani, Hugh Watkins, Panos Deloukas
Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 × 10-8) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs. 1,2,3,4). Here we leverage an interim release of UK Biobank (UKBB) data to evaluate the validity of the FDR approach. We tested a CAD phenotype inclusive of angina (SOFT; ncases = 10,801) as well as a stricter definition without angina (HARD; ncases = 6,482) and selected cases with the former phenotype to conduct a meta-analysis using the two most recent CAD GWAS...
September 2017: Nature Genetics
https://www.readbyqxmd.com/read/28629510/screening-strategies-for-atrial-fibrillation-a-systematic-review-and-cost-effectiveness-analysis
#7
Nicky J Welton, Alexandra McAleenan, Howard Hz Thom, Philippa Davies, Will Hollingworth, Julian Pt Higgins, George Okoli, Jonathan Ac Sterne, Gene Feder, Diane Eaton, Aroon Hingorani, Christopher Fawsitt, Trudie Lobban, Peter Bryden, Alison Richards, Reecha Sofat
BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia that increases the risk of thromboembolic events. Anticoagulation therapy to prevent AF-related stroke has been shown to be cost-effective. A national screening programme for AF may prevent AF-related events, but would involve a substantial investment of NHS resources. OBJECTIVES: To conduct a systematic review of the diagnostic test accuracy (DTA) of screening tests for AF, update a systematic review of comparative studies evaluating screening strategies for AF, develop an economic model to compare the cost-effectiveness of different screening strategies and review observational studies of AF screening to provide inputs to the model...
May 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28566218/relations-between-lipoprotein-a-concentrations-lpa-genetic-variants-and-the-risk-of-mortality-in-patients-with-established-coronary-heart-disease-a-molecular-and-genetic-association-study
#8
Stephen Zewinger, Marcus E Kleber, Vinicius Tragante, Raymond O McCubrey, Amand F Schmidt, Kenan Direk, Ulrich Laufs, Christian Werner, Wolfgang Koenig, Dietrich Rothenbacher, Ute Mons, Lutz P Breitling, Herrmann Brenner, Richard T Jennings, Ioannis Petrakis, Sarah Triem, Mira Klug, Alexandra Filips, Stefan Blankenberg, Christoph Waldeyer, Christoph Sinning, Renate B Schnabel, Karl J Lackner, Efthymia Vlachopoulou, Ottar Nygård, Gard Frodahl Tveitevåg Svingen, Eva Ringdal Pedersen, Grethe S Tell, Juha Sinisalo, Markku S Nieminen, Reijo Laaksonen, Stella Trompet, Roelof A J Smit, Naveed Sattar, J Wouter Jukema, Heinrich V Groesdonk, Graciela Delgado, Tatjana Stojakovic, Anna P Pilbrow, Vicky A Cameron, A Mark Richards, Robert N Doughty, Yan Gong, Rhonda Cooper-DeHoff, Julie Johnson, Markus Scholz, Frank Beutner, Joachim Thiery, J Gustav Smith, Ragnar O Vilmundarson, Ruth McPherson, Alexandre F R Stewart, Sharon Cresci, Petra A Lenzini, John A Spertus, Oliviero Olivieri, Domenico Girelli, Nicola I Martinelli, Andreas Leiherer, Christoph H Saely, Heinz Drexel, Axel Mündlein, Peter S Braund, Christopher P Nelson, Nilesh J Samani, Daniel Kofink, Imo E Hoefer, Gerard Pasterkamp, Arshed A Quyyumi, Yi-An Ko, Jaana A Hartiala, Hooman Allayee, W H Wilson Tang, Stanley L Hazen, Niclas Eriksson, Claes Held, Emil Hagström, Lars Wallentin, Axel Åkerblom, Agneta Siegbahn, Igor Karp, Christopher Labos, Louise Pilote, James C Engert, James M Brophy, George Thanassoulis, Peter Bogaty, Wojciech Szczeklik, Marcin Kaczor, Marek Sanak, Salim S Virani, Christie M Ballantyne, Vei-Vei Lee, Eric Boerwinkle, Michael V Holmes, Benjamin D Horne, Aroon Hingorani, Folkert W Asselbergs, Riyaz S Patel, Bernhard K Krämer, Hubert Scharnagl, Danilo Fliser, Winfried März, Thimoteus Speer
BACKGROUND: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. METHODS: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy...
July 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28500271/causal-associations-of-adiposity-and-body-fat-distribution-with-coronary-heart-disease-stroke-subtypes-and-type-2-diabetes-mellitus-a-mendelian-randomization-analysis
#9
Caroline E Dale, Ghazaleh Fatemifar, Tom M Palmer, Jon White, David Prieto-Merino, Delilah Zabaneh, Jorgen E L Engmann, Tina Shah, Andrew Wong, Helen R Warren, Stela McLachlan, Stella Trompet, Max Moldovan, Richard W Morris, Reecha Sofat, Meena Kumari, Elina Hyppönen, Barbara J Jefferis, Tom R Gaunt, Yoav Ben-Shlomo, Ang Zhou, Aleksandra Gentry-Maharaj, Andy Ryan, Renée de Mutsert, Raymond Noordam, Mark J Caulfield, J Wouter Jukema, Bradford B Worrall, Patricia B Munroe, Usha Menon, Chris Power, Diana Kuh, Debbie A Lawlor, Steve E Humphries, Dennis O Mook-Kanamori, Naveed Sattar, Mika Kivimaki, Jacqueline F Price, George Davey Smith, Frank Dudbridge, Aroon D Hingorani, Michael V Holmes, Juan P Casas
BACKGROUND: The implications of different adiposity measures on cardiovascular disease etiology remain unclear. In this article, we quantify and contrast causal associations of central adiposity (waist-to-hip ratio adjusted for body mass index [WHRadjBMI]) and general adiposity (body mass index [BMI]) with cardiometabolic disease. METHODS: Ninety-seven independent single-nucleotide polymorphisms for BMI and 49 single-nucleotide polymorphisms for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with coronary heart disease (CHD) data from CARDIoGRAMplusC4D (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics; combined total 66 842 cases), stroke from METASTROKE (12 389 ischemic stroke cases), type 2 diabetes mellitus from DIAGRAM (Diabetes Genetics Replication and Meta-analysis; 34 840 cases), and lipids from GLGC (Global Lipids Genetic Consortium; 213 500 participants) consortia...
June 13, 2017: Circulation
https://www.readbyqxmd.com/read/28456096/identifying-low-density-lipoprotein-cholesterol-associated-variants-in-the-annexin-a2-anxa2-gene
#10
Roaa Hani Fairoozy, Jackie Cooper, Jon White, Claudia Giambartolomei, Lasse Folkersen, S Goya Wannamethee, Barbara J Jefferis, Peter Whincup, Yoav Ben-Shlomo, Meena Kumari, Mika Kivimaki, Andrew Wong, Rebecca Hardy, Diana Kuh, Tom R Gaunt, J P Casas, Stela McLachlan, Jackie F Price, Aroon Hingorani, Anders Franco-Cereceda, Thomas Grewal, Anastasia Z Kalea, Steve E Humphries
BACKGROUND AND AIMS: Annexin-A2 (AnxA2) is an endogenous inhibitor of proprotein convertase subtilisin/kexin type-9 (PCSK9). The repeat-one (R1) domain of AnxA2 binds to PCSK9, blocking its ability to promote degradation of low-density lipoprotein cholesterol-receptors (LDL-R) and thereby regulate low-density lipoprotein cholesterol (LDL-C) levels. Here we identify variants in ANXA2 influencing LDL-C levels and we determine the molecular mechanisms of their effects. RESULTS: The ANXA2 single nucleotide polymorphism (SNP) genotype-phenotype association was examined using the Second-Northwick-Park Heart Study (NPHSII) (n∼2700) and the UCL-LSHTM-Edinburgh-Bristol (UCLEB) consortium (n∼14,600)...
June 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28453187/pcsk9-monoclonal-antibodies-for-the-primary-and-secondary-prevention-of-cardiovascular-disease
#11
REVIEW
Amand F Schmidt, Lucy S Pearce, John T Wilkins, John P Overington, Aroon D Hingorani, Juan P Casas
BACKGROUND: Despite the availability of effective drug therapies that reduce low-density lipoprotein (LDL)-cholesterol (LDL-C), cardiovascular disease (CVD) remains an important cause of mortality and morbidity. Therefore, additional LDL-C reduction may be warranted, especially for patients who are unresponsive to, or unable to take, existing LDL-C-reducing therapies. By inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, monoclonal antibodies (PCSK9 inhibitors) may further reduce LDL-C, potentially reducing CVD risk as well...
April 28, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28423765/evaluation-of-machine-learning-methods-to-predict-coronary-artery-disease-using-metabolomic-data
#12
Henrietta Forssen, Riyaz Patel, Natalie Fitzpatrick, Aroon Hingorani, Adam Timmis, Harry Hemingway, Spiros Denaxas
Metabolomic data can potentially enable accurate, non-invasive and low-cost prediction of coronary artery disease. Regression-based analytical approaches however might fail to fully account for interactions between metabolites, rely on a priori selected input features and thus might suffer from poorer accuracy. Supervised machine learning methods can potentially be used in order to fully exploit the dimensionality and richness of the data. In this paper, we systematically implement and evaluate a set of supervised learning methods (L1 regression, random forest classifier) and compare them to traditional regression-based approaches for disease prediction using metabolomic data...
2017: Studies in Health Technology and Informatics
https://www.readbyqxmd.com/read/28356508/the-druggable-genome-and-support-for-target-identification-and-validation-in-drug-development
#13
Chris Finan, Anna Gaulton, Felix A Kruger, R Thomas Lumbers, Tina Shah, Jorgen Engmann, Luana Galver, Ryan Kelley, Anneli Karlsson, Rita Santos, John P Overington, Aroon D Hingorani, Juan P Casas
Target identification (determining the correct drug targets for a disease) and target validation (demonstrating an effect of target perturbation on disease biomarkers and disease end points) are important steps in drug development. Clinically relevant associations of variants in genes encoding drug targets model the effect of modifying the same targets pharmacologically. To delineate drug development (including repurposing) opportunities arising from this paradigm, we connected complex disease- and biomarker-associated loci from genome-wide association studies to an updated set of genes encoding druggable human proteins, to agents with bioactivity against these targets, and, where there were licensed drugs, to clinical indications...
March 29, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28349888/screening-for-familial-hypercholesterolaemia-in-childhood-avon-longitudinal-study-of-parents-and-children-alspac
#14
Marta Futema, Jackie A Cooper, Marietta Charakida, Christopher Boustred, Naveed Sattar, John Deanfield, Debbie A Lawlor, Nicholas J Timpson, Steve E Humphries, Aroon D Hingorani
BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is an autosomal-dominant disease with frequency of 1/500 to 1/250 that leads to premature coronary heart disease. New approaches to identify FH mutation-carriers early are needed to prevent premature cardiac deaths. In a cross-sectional study of the Avon Longitudinal Study of Parents and Children (ALSPAC), we evaluated the biochemical thresholds for FH screening in childhood, and modelled a two-stage biochemical and sequencing screening strategy for FH detection...
May 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28279251/oral-anticoagulants-for-primary-prevention-treatment-and-secondary-prevention-of-venous-thromboembolic-disease-and-for-prevention-of-stroke-in-atrial-fibrillation-systematic-review-network-meta-analysis-and-cost-effectiveness-analysis
#15
Jonathan Ac Sterne, Pritesh N Bodalia, Peter A Bryden, Philippa A Davies, Jose A López-López, George N Okoli, Howard Hz Thom, Deborah M Caldwell, Sofia Dias, Diane Eaton, Julian Pt Higgins, Will Hollingworth, Chris Salisbury, Jelena Savović, Reecha Sofat, Annya Stephens-Boal, Nicky J Welton, Aroon D Hingorani
BACKGROUND: Warfarin is effective for stroke prevention in atrial fibrillation (AF), but anticoagulation is underused in clinical care. The risk of venous thromboembolic disease during hospitalisation can be reduced by low-molecular-weight heparin (LMWH): warfarin is the most frequently prescribed anticoagulant for treatment and secondary prevention of venous thromboembolism (VTE). Warfarin-related bleeding is a major reason for hospitalisation for adverse drug effects. Warfarin is cheap but therapeutic monitoring increases treatment costs...
March 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28254179/neutrophil-counts-and-initial-presentation-of-12-cardiovascular-diseases-a-caliber-cohort%C3%A2-study
#16
Anoop Dinesh Shah, Spiros Denaxas, Owen Nicholas, Aroon D Hingorani, Harry Hemingway
BACKGROUND: Neutrophil counts are a ubiquitous measure of inflammation, but previous studies on their association with cardiovascular disease (CVD) were limited by small numbers of patients or a narrow range of endpoints. OBJECTIVES: This study investigated associations of clinically recorded neutrophil counts with initial presentation for a range of CVDs. METHODS: We used linked primary care, hospitalization, disease registry, and mortality data in England...
March 7, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28146662/child-parent-familial-hypercholesterolemia-screening-in-primary-care
#17
LETTER
Aroon D Hingorani, Marta Futema, Steve Humphries
No abstract text is available yet for this article.
February 2, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/27908689/pcsk9-genetic-variants-and-risk-of-type-2-diabetes-a-mendelian-randomisation-study
#18
Amand F Schmidt, Daniel I Swerdlow, Michael V Holmes, Riyaz S Patel, Zammy Fairhurst-Hunter, Donald M Lyall, Fernando Pires Hartwig, Bernardo Lessa Horta, Elina Hyppönen, Christine Power, Max Moldovan, Erik van Iperen, G Kees Hovingh, Ilja Demuth, Kristina Norman, Elisabeth Steinhagen-Thiessen, Juri Demuth, Lars Bertram, Tian Liu, Stefan Coassin, Johann Willeit, Stefan Kiechl, Karin Willeit, Dan Mason, John Wright, Richard Morris, Goya Wanamethee, Peter Whincup, Yoav Ben-Shlomo, Stela McLachlan, Jackie F Price, Mika Kivimaki, Catherine Welch, Adelaida Sanchez-Galvez, Pedro Marques-Vidal, Andrew Nicolaides, Andrie G Panayiotou, N Charlotte Onland-Moret, Yvonne T van der Schouw, Giuseppe Matullo, Giovanni Fiorito, Simonetta Guarrera, Carlotta Sacerdote, Nicholas J Wareham, Claudia Langenberg, Robert Scott, Jian'an Luan, Martin Bobak, Sofia Malyutina, Andrzej Pająk, Ruzena Kubinova, Abdonas Tamosiunas, Hynek Pikhart, Lise Lotte Nystrup Husemoen, Niels Grarup, Oluf Pedersen, Torben Hansen, Allan Linneberg, Kenneth Starup Simonsen, Jackie Cooper, Steve E Humphries, Murray Brilliant, Terrie Kitchner, Hakon Hakonarson, David S Carrell, Catherine A McCarty, H Lester Kirchner, Eric B Larson, David R Crosslin, Mariza de Andrade, Dan M Roden, Joshua C Denny, Cara Carty, Stephen Hancock, John Attia, Elizabeth Holliday, Martin O'Donnell, Salim Yusuf, Michael Chong, Guillaume Pare, Pim van der Harst, M Abdullah Said, Ruben N Eppinga, Niek Verweij, Harold Snieder, Tim Christen, Dennis O Mook-Kanamori, Stefan Gustafsson, Lars Lind, Erik Ingelsson, Raha Pazoki, Oscar Franco, Albert Hofman, Andre Uitterlinden, Abbas Dehghan, Alexander Teumer, Sebastian Baumeister, Marcus Dörr, Markus M Lerch, Uwe Völker, Henry Völzke, Joey Ward, Jill P Pell, Daniel J Smith, Tom Meade, Anke H Maitland-van der Zee, Ekaterina V Baranova, Robin Young, Ian Ford, Archie Campbell, Sandosh Padmanabhan, Michiel L Bots, Diederick E Grobbee, Philippe Froguel, Dorothée Thuillier, Beverley Balkau, Amélie Bonnefond, Bertrand Cariou, Melissa Smart, Yanchun Bao, Meena Kumari, Anubha Mahajan, Paul M Ridker, Daniel I Chasman, Alex P Reiner, Leslie A Lange, Marylyn D Ritchie, Folkert W Asselbergs, Juan-Pablo Casas, Brendan J Keating, David Preiss, Aroon D Hingorani, Naveed Sattar
BACKGROUND: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk...
February 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/27898682/genetic-predisposition-to-an-impaired-metabolism-of-the-branched-chain-amino-acids-and-risk-of-type-2-diabetes-a-mendelian-randomisation-analysis
#19
Luca A Lotta, Robert A Scott, Stephen J Sharp, Stephen Burgess, Jian'an Luan, Therese Tillin, Amand F Schmidt, Fumiaki Imamura, Isobel D Stewart, John R B Perry, Luke Marney, Albert Koulman, Edward D Karoly, Nita G Forouhi, Rasmus J O Sjögren, Erik Näslund, Juleen R Zierath, Anna Krook, David B Savage, Julian L Griffin, Nishi Chaturvedi, Aroon D Hingorani, Kay-Tee Khaw, Inês Barroso, Mark I McCarthy, Stephen O'Rahilly, Nicholas J Wareham, Claudia Langenberg
BACKGROUND: Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine) are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question. METHODS AND FINDINGS: Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p < 5 × 10-8)...
November 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27755538/circulating-apolipoprotein-e-concentration-and-cardiovascular-disease-risk-meta-analysis-of-results-from-three-studies
#20
Reecha Sofat, Jackie A Cooper, Meena Kumari, Juan P Casas, Jacqueline P Mitchell, Jayshree Acharya, Simon Thom, Alun D Hughes, Steve E Humphries, Aroon D Hingorani
BACKGROUND: The association of APOE genotype with circulating apolipoprotein E (ApoE) concentration and cardiovascular disease (CVD) risk is well established. However, the relationship of circulating ApoE concentration and CVD has received little attention. METHODS AND FINDINGS: To address this, we measured circulating ApoE concentration in 9,587 individuals (with 1,413 CVD events) from three studies with incident CVD events: two population-based studies, the English Longitudinal Study of Ageing (ELSA) and the men-only Northwick Park Heart Study II (NPHSII), and a nested sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)...
October 2016: PLoS Medicine
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