Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease

  title={Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease},
  author={Ci Song and Stephen Burgess and John D. Eicher and Christopher J. O'Donnell and Junchao Huang and Maria Sabater‐Lleal and Folkert W. Asselbergs and David Tregouet and So‐Youn Shin and Jingzhong Ding and Tiphaine Oudot‐Mellakh and Lasse Folkersen and Scott M. Williams and M. Arfan Ikram and Marcus E. Kleber and Diane M. Becker and Vinh Truong and Josyf C Mychaleckyj and Weihong Tang and Qiong Yang and Bengt Sennblad and Jason H. Moore and F. M. Williams and Guenther Silbernagel and Elisabeth M. C. Schrijvers and S. Smith and M. {\"U}mit Karakas and Geoffrey H. Tofler and Angela Silveira and Gerjan J. Navis and Kurt Lohman and Annette Peters and Per E Lundmark and Rona J. Strawbridge and B O Boehm and Angela M. Carter and Barbara Mcknight and John {\"O}hrvik and Maria Grazia Franzosi and Udo Seedorf and Rory Collins and Anders Franco‐Cereceda and Ann‐Christine Syv{\"a}nen and Alison H. Goodall and Lisa R Yanek and Mary Cushman and Martina M{\"u}ller‐Nurasyid and Aaron R Folsom and Saonli Basu and Nena Matijevic and James B. Meigs and Bernhard Rudolf Winkelmann and Peter J. Grant and Hans L. Hillege and Tim D. Spector and Lewis C. Becker and Russell P Tracy and Winfried Maerz and Per Eriksson and François Cambien and Pierre‐Emmanuel Morange and Georg B. Ehret and Patricia B. Munroe and Kenneth M Rice and Murielle Bochud and Daniel Chasman and Martin D Tobin and Germaine C. Verwoert and Vasyl Pihur and Peter Vollenweider and Paul F. O'Reilly and Najaf Amin and Jennifer L. Bragg‐Gresham and Alexander Teumer and Lenore J. Launer and Jing Hua Zhao and Yurii S. Aulchenko and Simon Heath and Siim S{\~o}ber and Jian'an Luan and Pankaj Arora and Feng Zhang and Gavin Lucas and Andrew A Hicks and Anne U. Jackson and John F. Peden and Toshiko Tanaka and Sarah H Wild and Igor Rudan and Wilmar Igl and Yuri Milaneschi and Alex N. Parker and Cristiano Fava and John Campbell Chambers and Ervin R. Fox and Meena Kumari and Min Jin Go and Pim van der Harst and W. H. Linda Kao and Marketa Sj{\"o}gren and D. G. Vinay and Myriam Alexander and Yasuharu Tabara and Sue Shaw‐Hawkins and Peter Whincup and Gang Shi and Johanna Kuusisto and Bamidele O. Tayo and Mark Seielstad and Xueling Sim and Khanh‐Dung Hoang Nguyen and Giuseppe Matullo and Ying Wu and Tom R. Gaunt and N. Charlotte Onland‐Moret and Matthew N Cooper and Carl G. P. Platou and Elin Org and Rebecca Hardy and Santosh Dahgam and Jutta A Palmen and Veronique Vitart and Peter S. Braund and Tatiana Kuznetsova and Cuno S. P. M. Uiterwaal and Adebowale Adeyemo and Walter Palmas and Harry Campbell and B. Ludwig and Maciej Tomaszewski and Ioanna Tzoulaki and Nicholette D. Palmer and M Garc{\'i}a and Y C Chang and Nanette I. Steinle and Diederick E. Grobbee and Dan E Arking and Sharon L. R. Kardia and Alanna C. Morrison and Dena Hernandez and Samer Najjar and Wendy L. Mcardle and David Hadley and Morris Jonathan Brown and John M. Connell and Aroon D. Hingorani and Ian N. M. Day and Debbie A Lawlor and John P Beilby and Robert Wm Lawrence and Robert Clarke and Jemma C. Hopewell and Halit Ongen and Albert W Dreisbach and Yali Li and Jeffery Young and Linda S. Adair and Nanette R. Lee and Ming‐Huei Chen and Matthias Olden and Judith A. Hoffman Bolton and Anna K{\"o}ttgen and Sven Bergmann and Vincent Mooser and Nishi Chaturvedi and Timothy M. Frayling and Muhammad Islam and Tazeen Hasan Jafar and Jeanette Erdmann and Smita R. Kulkarni and Stefan R. Bornstein and Juergen Graessler and Leif Groop and Johannes Kettunen and P. Howard and Andrew Taylor and Simonetta Guarrera and Fulvio Ricceri and Valur Emilsson and Andrew Plump and In{\^e}s Barroso and Kay‐Tee Khaw and Alan B. Weder and Steven C. Hunt and Richard N Bergman and Francis S. Collins and Lori L. Bonnycastle and Laura J. Scott and Heather M Stringham and Markus Perola and Erkki Vartiainen and Samson Brand and Jan A Staessen and Thomas J. Wang and Paul R. Burton and Mar{\'i}a Soler Artigas and Yanbin Dong and Harold Snieder and X Wang and Haidong Zhu and Kurt K. Lohman and Megan E. Rudock and Nicholas L. Smith and Kerri L Wiggins and Ayo Doumatey and Daniel Shriner and Gudrun Veldre and Margus Viigimaa and Sanjay Kinra and Dorairaj Prabhakaran and V. Mushrif Tripathy and Carl D. Langefeld and Annika Rosengren and Dag Steinar Thelle and Anna Maria Corsi and Andrew Singleton and Terrence Forrester and Gina M Hilton and Colin A Mckenzie and Tunde Salako and Naoharu Iwai and Yoshikuni Kita and Toshio Ogihara and Takayoshi Ohkubo and Tomonori Okamura and Hirotsugu Ueshima and Satoshi Umemura and Susana Eyheramendy and Thomas Meitinger and H. Erich Wichmann and Yoon Shin Cho and Hyung‐Lae Kim and Jong‐Young Lee and James Scott and Joban S. Sehmi and Weihua Zhang and Bo Hedblad and Peter Nilsson and George Davey Smith and Andrew Wong and Narisu Narisu and Alena Stan{\vc}{\'a}kov{\'a} and Leslie J. Raffel and Jie Yao and Will T. Longstreth and Thomas H. Mosley and Sudha Seshadri and Nick Shrine and Louise V Wain and Mario A. Morken and Amy J. Swift and Jaana H. Laitinen and Inga Prokopenko and Paavo Zitting and J W Astley Cooper and Steve E Humphries and John Danesh and Asif Rasheed and Anuj Goel and Anders Hamsten and Hugh Watkins and Stephan J. L. Bakker and Wiek H van Gilst and Charles Spurgeon Janipalli and Kulathu Radha Mani and Chittaranjan Yajnik and Francesco U. S. Mattace‐Raso and Ben A. Oostra and Ayşe Demirkan and Mika Ala‐Korpela and Antti J. Kangas and Leo‐Pekka Lyytik{\"a}inen and Pasi Soininen and Taru Tukiainen and Peter W{\"u}rtz and Rick Twee‐Hee Ong and Heyo Klaus Kroemer and Uwe V{\"o}lker and Pilar Galan and Serge Hercberg and Mark Lathrop and Diana Z{\'e}l{\'e}nika and Panos Deloukas and Massimo Mangino and Guangju Zhai and James F Meschia and Michael A. Nalls and Pankaj Sharma and Jano{\vs} Terzi{\'c} and M. V. Kranthi Kumar and Matthew Denniff and Ewa Zukowska‐Szczechowska and Lynne E. Wagenknecht and Francis Gerry R. Fowkes and Fadi Charchar and Peter E. H. Schwarz and Xiuqing Guo and Charles Rotimi and Michiel L. Bots and E. Vlugt-van den Brand and Nilesh J. Samani and Ozren Pola{\vs}ek and Philippa J. Talmud and Fredrik Nyberg and Diana Kuh and M. ter Laan and Kristian Hveem and Lyle John Palmer and Yvonne T van der Schouw and Juan P. Casas and Karen L. Mohlke and Paolo Vineis and Santhi K. Ganesh and Tien Yin Wong and E. Shyong Tai and Richard S. Cooper and Markku Laakso and D. Chandrasekhra Rao and Richard W Morris and Anna F. Dominiczak and Mika Kivimaki and Michael Marmot and Tetsuro Miki and Danish Saleheen and Giriraj Ratan Chandak and Josef Coresh and Gerjan Navis and Bok‐Ghee Han and Xiaofeng Zhu and Jaspal Singh Kooner and Olle Melander and Paul M. Ridker and Stefania Bandinelli and Ulf Gyllensten and Alan F. Wright and Luigi Ferrucci and Martin Farrall and Jaakko Tuomilehto and Peter P. Pramstaller and Nicole Soranzo and Eric J G Sijbrands and Ruth J F Loos and Christian Gieger and Pierre Meneton and Nicholas J Wareham and Rainer Rettig and David P. Strachan and Jacqueline C. M. Witteman and Anna‐Liisa Hartikainen and Jacques S. Beckmann and Ramachandran S. Vasan and Michael Boehnke and Martin G. Larson and Marjo‐Riitta J{\"a}rvelin and Aravinda Chakravarti and Paul Elliott and Cornelia M van Duijn and Christopher Newton‐Cheh and Daniel L{\'e}vy and Mark J. Caulfield and Toby Johnson and Aad van der Lugt and Aaron Isaacs and Abbas Dehghan and Afshin Parsa and Alan R. Shuldiner and Albert Hofman and Albert Vernon Smith and Aldi Kraja and Andr{\'e} G. Uitterlinden and A Ziegler and A D Johnson and Angelo Scuteri and Anne B. Newman and Arne Schillert and Benjamin F. Voight and Bolli Th{\'o}rsson and Braxton D. Mitchell and Bruce M. Psaty and Caroline Hayward and Caroline Fox and Charles Cody White and Christa Meisinger and Christie Ballantyne and David Altshuler and David M. Herrington and Daniel H. O'Leary and David S Siscovick and David Couper and Edward G. Lakatta and Eran Halperin and Eric Boerwinkle and Eva‐Maria Stoegerer and Fernando Rivadeneira and Frances Ernst and Gabriel P. Krestin and Georg Homuth and Gerardo Heiss and Gianluca Usala and Gonçalo R. Abecasis and Gudny Eir{\'i}ksdott{\'i}r and Haiqing Shen and Helena Schmidt and Henry V{\"o}lzke and Ingrid B. Borecki and Hugh S. Markus and James F Wilson and Jan Luedemann and Jeffrey R. O'Connell and Jennifer E Huffman and J. Baumert and Jerome I. Rotter and Joanne M. Murabito and Joachim Thiery and J{\"u}rgen Seissler and Jorma Viikari and Joseph M. Massaro and Joseph F. Polak and J. Cunningham and Joshua C Bis and Kari North and Katja Petrovic and Kenneth Rice and L. Adrienne Cupples and Lawrence F. Bielak and Leena Peltonen and Mariza de Andrade and Manuela Uda and Marco Orr{\'u} and Marcus D{\"o}rr and Mary F Feitosa and Maryam Kavousi and Matthias Sitzer and Matthijs Oudkerk and Michael A. Province and Mika K{\"a}h{\"o}nen and Muredach P. Reilly and Nicole L. Glazer and Nora Franceschini and Norman Klopp and Olli Raitakari and Patricia A. Peyser and Philip A. Wolf and Qunyuan Zhang and Philipp S Wild and Roberto Elos{\'u}a and Ralph B. D'Agostino and Ravi Kumar Chilukoti and Reinhold Schmidt and Renate B. Schnabel and Sekar Kathiresan and Serena Sanna and S Hwang and Serkalem Demissie and Sigurdur Sigurdsson and Stephen M Schwartz and Stefan Blankenberg and Steve N Bevan and Suzette E. Elias‐Smale and Susan R. Heckbert and T. B. Harris and Tanja Zeller and Terho Lehtim{\"a}ki and Thomas Illig and Thomas F. M{\"u}nzel and Thor Aspelund and Timothy D. Howard and Udo Hoffmann and Ulf Schminke and Veikko V Salomaa and Vijay Nambi and Vilmundur Gudnason and Yongmei Liu and Yan V. Sun and Wendy S. Post and Wolfgang Koenig and Wolfgang Rathmann and X Li and Yu‐Ching Cheng},
  booktitle={Journal of the American Heart Association},
BACKGROUND Plasminogen activator inhibitor type 1 (PAI-1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI-1 levels are associated with increased risk of coronary heart disease (CHD). However, it is unclear whether the association reflects a causal influence of PAI-1 on CHD risk. METHODS AND RESULTS To evaluate the association between PAI-1 and CHD, we applied a 3-step strategy. First, we investigated the observational… CONTINUE READING
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