Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease. Issue 6 (June 2017)

• Record Type: Journal Article
• Authors: Song, Ci; Burgess, Stephen; Eicher, John D.; O'Donnell, Christopher J.; Johnson, Andrew D.
• Other Names: Huang Jie investigator.; Sabater‐Lleal Maria investigator.; Asselbergs Folkert W. investigator.; Tregouet David investigator.; Shin So‐Youn investigator.; Ding Jingzhong investigator.; Baumert Jens investigator.; Oudot‐Mellakh Tiphaine investigator.; Folkersen Lasse investigator.; Smith Nicholas L. investigator.; Williams Scott M. investigator.; Ikram Mohammad A. investigator.; Kleber Marcus E. investigator.; Becker Diane M. investigator.; Truong Vinh investigator.; Mychaleckyj Josyf C. investigator.; Tang Weihong investigator.; Yang Qiong investigator.; Sennblad Bengt investigator.; Moore Jason H. investigator.; Williams Frances M. K. investigator.; Dehghan Abbas investigator.; Silbernagel Günther investigator.; Schrijvers Elisabeth M. C. investigator.; Smith Shelly investigator.; Karakas Mahir investigator.; Tofler Geoffrey H. investigator.; Silveira Angela investigator.; Navis Gerjan J. investigator.; Lohman Kurt investigator.; Chen Ming‐Huei investigator.; Peters Annette investigator.; Goel Anuj investigator.; Hopewell Jemma C. investigator.; Chambers John C. investigator.; Saleheen Danish investigator.; Lundmark Per investigator.; Psaty Bruce M. investigator.; Strawbridge Rona J. investigator.; Boehm Bernhard O. investigator.; Carter Angela M. investigator.; Meisinger Christa investigator.; Peden John F. investigator.; Bis Joshua C. investigator.; McKnight Barbara investigator.; Öhrvik John investigator.; Taylor Kent investigator.; Franzosi Maria Grazia investigator.; Seedorf Udo investigator.; Collins Rory investigator.; Franco‐Cereceda Anders investigator.; Syvänen Ann‐Christine investigator.; Goodall Alison H. investigator.; Yanek Lisa R. investigator.; Cushman Mary investigator.; Müller‐Nurasyid Martina investigator.; Folsom Aaron R. investigator.; Basu Saonli investigator.; Matijevic Nena investigator.; van Gilst Wiek H. investigator.; Kooner Jaspal S. investigator.; Hofman Albert investigator.; Danesh John investigator.; Clarke Robert investigator.; Meigs James B. investigator.; Kathiresan Sekar investigator.; Reilly Muredach P. investigator.; Klopp Norman investigator.; Harris Tamara B. investigator.; Winkelmann Bernhard R. investigator.; Grant Peter J. investigator.; Hillege Hans L. investigator.; Watkins Hugh investigator.; Spector Timothy D. investigator.; Becker Lewis C. investigator.; Tracy Russell P. investigator.; März Winfried investigator.; Uitterlinden Andre G. investigator.; Eriksson Per investigator.; Cambien Francois investigator.; Morange Pierre‐Emmanuel investigator.; Koenig Wolfgang investigator.; Soranzo Nicole investigator.; van der Harst Pim investigator.; Liu Yongmei investigator.; Hamsten Anders investigator.; Ehret Georg B. investigator.; Munroe Patricia B. investigator.; Rice Kenneth M. investigator.; Bochud Murielle investigator.; Johnson Andrew D. investigator.; Chasman Daniel I. investigator.; Smith Albert V. investigator.; Tobin Martin D. investigator.; Verwoert Germaine C. investigator.; Hwang Shih‐Jen investigator.; Pihur Vasyl investigator.; Vollenweider Peter investigator.; O'Reilly Paul F. investigator.; Amin Najaf investigator.; Bragg‐Gresham Jennifer L. investigator.; Teumer Alexander investigator.; Glazer Nicole L. investigator.; Launer Lenore investigator.; Zhao Jing Hua investigator.; Aulchenko Yurii investigator.; Heath Simon investigator.; Sõber Siim investigator.; Parsa Afshin investigator.; Luan Jian'an investigator.; Arora Pankaj investigator.; Dehghan Abbas investigator.; Zhang Feng investigator.; Lucas Gavin investigator.; Hicks Andrew A. investigator.; Jackson Anne U. investigator.; Peden John F. investigator.; Tanaka Toshiko investigator.; Wild Sarah H. investigator.; Rudan Igor investigator.; Igl Wilmar investigator.; Milaneschi Yuri investigator.; Parker Alex N. investigator.; Fava Cristiano investigator.; Chambers John C. investigator.; Fox Ervin R. investigator.; Kumari Meena investigator.; Go Min Jin investigator.; van der Harst Pim investigator.; Kao Wen Hong Linda investigator.; Sjögren Marketa investigator.; Vinay D. G. investigator.; Alexander Myriam investigator.; Tabara Yasuharu investigator.; Shaw‐Hawkins Sue investigator.; Whincup Peter H. investigator.; Liu Yongmei investigator.; Shi Gang investigator.; Kuusisto Johanna investigator.; Tayo Bamidele investigator.; Seielstad Mark investigator.; Sim Xueling investigator.; Nguyen Khanh‐Dung Hoang investigator.; Lehtimäki Terho investigator.; Matullo Giuseppe investigator.; Wu Ying investigator.; Gaunt Tom R. investigator.; Onland‐Moret N. Charlotte investigator.; Cooper Matthew N. investigator.; Platou Carl G. P. investigator.; Org Elin investigator.; Hardy Rebecca investigator.; Dahgam Santosh investigator.; Palmen Jutta investigator.; Vitart Veronique investigator.; Braund Peter S. investigator.; Kuznetsova Tatiana investigator.; Uiterwaal Cuno S. P. M. investigator.; Adeyemo Adebowale investigator.; Palmas Walter investigator.; Campbell Harry investigator.; Ludwig Barbara investigator.; Tomaszewski Maciej investigator.; Tzoulaki Ioanna investigator.; Palmer Nicholette D. investigator.; Aspelund Thor investigator.; Garcia Melissa investigator.; Chang Yen‐Pei C. investigator.; O'Connell Jeffrey R. investigator.; Steinle Nanette I. investigator.; Grobbee Diederick E. investigator.; Arking Dan E. investigator.; Kardia Sharon L. investigator.; Morrison Alanna C. investigator.; Hernandez Dena investigator.; Najjar Samer investigator.; McArdle Wendy L. investigator.; Hadley David investigator.; Brown Morris J. investigator.; Connell John M. investigator.; Hingorani Aroon D. investigator.; Day Ian N. M. investigator.; Lawlor Debbie A. investigator.; Beilby John P. investigator.; Lawrence Robert W. investigator.; Clarke Robert investigator.; Hopewell Jemma C. investigator.; Ongen Halit investigator.; Dreisbach Albert W. investigator.; Li Yali investigator.; Young J. Hunter investigator.; Bis Joshua C. investigator.; Kähönen Mika investigator.; Viikari Jorma investigator.; Adair Linda S. investigator.; Lee Nanette R. investigator.; Chen Ming‐Huei investigator.; Olden Matthias investigator.; Pattaro Cristian investigator.; Hoffman Bolton Judith A. investigator.; Köttgen Anna investigator.; Bergmann Sven investigator.; Mooser Vincent investigator.; Chaturvedi Nish investigator.; Frayling Timothy M. investigator.; Islam Muhammad investigator.; Jafar Tazeen H. investigator.; Erdmann Jeanette investigator.; Kulkarni Smita R. investigator.; Bornstein Stefan R. investigator.; Grässler Jürgen investigator.; Groop Leif investigator.; Voight Benjamin F. investigator.; Kettunen Johannes investigator.; Howard Philip investigator.; Taylor Andrew investigator.; Guarrera Simonetta investigator.; Ricceri Fulvio investigator.; Emilsson Valur investigator.; Plump Andrew investigator.; Barroso Inês investigator.; Khaw Kay‐Tee investigator.; Weder Alan B. investigator.; Hunt Steven C. investigator.; Sun Yan V. investigator.; Bergman Richard N. investigator.; Collins Francis S. investigator.; Bonnycastle Lori L. investigator.; Scott Laura J. investigator.; Stringham Heather M. investigator.; Peltonen Leena investigator.; Perola Markus investigator.; Vartiainen Erkki investigator.; Brand Stefan‐Martin investigator.; Staessen Jan A. investigator.; Wang Thomas J. investigator.; Burton Paul R. investigator.; Artigas Maria Soler investigator.; Dong Yanbin investigator.; Snieder Harold investigator.; Wang Xiaoling investigator.; Zhu Haidong investigator.; Lohman Kurt K. investigator.; Rudock Megan E. investigator.; Heckbert Susan R. investigator.; Smith Nicholas L. investigator.; Wiggins Kerri L. investigator.; Doumatey Ayo investigator.; Shriner Daniel investigator.; Veldre Gudrun investigator.; Viigimaa Margus investigator.; Kinra Sanjay investigator.; Prabhakaran Dorairaj investigator.; Tripathy Vikal investigator.; Langefeld Carl D. investigator.; Rosengren Annika investigator.; Thelle Dag S. investigator.; Corsi Anna Maria investigator.; Singleton Andrew investigator.; Forrester Terrence investigator.; Hilton Gina investigator.; McKenzie Colin A. investigator.; Salako Tunde investigator.; Iwai Naoharu investigator.; Kita Yoshikuni investigator.; Ogihara Toshio investigator.; Ohkubo Takayoshi investigator.; Okamura Tomonori investigator.; Ueshima Hirotsugu investigator.; Umemura Satoshi investigator.; Eyheramendy Susana investigator.; Meitinger Thomas investigator.; Wichmann H.‐Erich investigator.; Cho Yoon Shin investigator.; Kim Hyung‐Lae investigator.; Lee Jong‐Young investigator.; Scott James investigator.; Sehmi Joban S. investigator.; Zhang Weihua investigator.; Hedblad Bo investigator.; Nilsson Peter investigator.; Smith George Davey investigator.; Wong Andrew investigator.; Narisu Narisu investigator.; Stančáková Alena investigator.; Raffel Leslie J. investigator.; Yao Jie investigator.; Kathiresan Sekar investigator.; Schwartz Stephen M. investigator.; Arfan Ikram M. investigator.; Longstreth W. T. investigator.; Mosley Thomas H. investigator.; Seshadri Sudha investigator.; Shrine Nick R. G. investigator.; Wain Louise V. investigator.; Morken Mario A. investigator.; Swift Amy J. investigator.; Laitinen Jaana investigator.; Prokopenko Inga investigator.; Zitting Paavo investigator.; Cooper Jackie A. investigator.; Humphries Steve E. investigator.; Danesh John investigator.; Rasheed Asif investigator.; Goel Anuj investigator.; Hamsten Anders investigator.; Watkins Hugh investigator.; Bakker Stephan J. L. investigator.; van Gilst Wiek H. investigator.; Janipalli Charles S. investigator.; Mani K. Radha investigator.; Yajnik Chittaranjan S. investigator.; Hofman Albert investigator.; Mattace‐Raso Francesco U. S. investigator.; Oostra Ben A. investigator.; Demirkan Ayse investigator.; Isaacs Aaron investigator.; Rivadeneira Fernando investigator.; Lakatta Edward G. investigator.; Orru Marco investigator.; Scuteri Angelo investigator.; Ala‐Korpela Mika investigator.; Kangas Antti J. investigator.; Lyytikäinen Leo‐Pekka investigator.; Soininen Pasi investigator.; Tukiainen Taru investigator.; Würtz Peter investigator.; Ong Rick Twee‐Hee investigator.; Dörr Marcus investigator.; Kroemer Heyo K. investigator.; Völker Uwe investigator.; Völzke Henry investigator.; Galan Pilar investigator.; Hercberg Serge investigator.; Lathrop Mark investigator.; Zelenika Diana investigator.; Deloukas Panos investigator.; Mangino Massimo investigator.; Spector Tim D. investigator.; Zhai Guangju investigator.; Meschia James F. investigator.; Nalls Michael A. investigator.; Sharma Pankaj investigator.; Terzic Janos investigator.; Kranthi Kumar M. V. investigator.; Denniff Matthew investigator.; Zukowska‐Szczechowska Ewa investigator.; Wagenknecht Lynne E. investigator.; Fowkes F. Gerald R. investigator.; Charchar Fadi J. investigator.; Schwarz Peter E. H. investigator.; Hayward Caroline investigator.; Guo Xiuqing investigator.; Rotimi Charles investigator.; Bots Michiel L. investigator.; Brand Eva investigator.; Samani Nilesh J. investigator.; Polasek Ozren investigator.; Talmud Philippa J. investigator.; Nyberg Fredrik investigator.; Kuh Diana investigator.; Laan Maris investigator.; Hveem Kristian investigator.; Palmer Lyle J. investigator.; van der Schouw Yvonne T. investigator.; Casas Juan P. investigator.; Mohlke Karen L. investigator.; Vineis Paolo investigator.; Raitakari Olli investigator.; Ganesh Santhi K. investigator.; Wong Tien Y. investigator.; Tai E. Shyong investigator.; Cooper Richard S. investigator.; Laakso Markku investigator.; Rao Dabeeru C. investigator.; Harris Tamara B. investigator.; Morris Richard W. investigator.; Dominiczak Anna F. investigator.; Kivimaki Mika investigator.; Marmot Michael G. investigator.; Miki Tetsuro investigator.; Saleheen Danish investigator.; Chandak Giriraj R. investigator.; Coresh Josef investigator.; Navis Gerjan investigator.; Salomaa Veikko investigator.; Han Bok‐Ghee investigator.; Zhu Xiaofeng investigator.; Kooner Jaspal S. investigator.; Melander Olle investigator.; Ridker Paul M. investigator.; Bandinelli Stefania investigator.; Gyllensten Ulf B. investigator.; Wright Alan F. investigator.; Wilson James F. investigator.; Ferrucci Luigi investigator.; Farrall Martin investigator.; Tuomilehto Jaakko investigator.; Pramstaller Peter P. investigator.; Elosua Roberto investigator.; Soranzo Nicole investigator.; Sijbrands Eric J. G. investigator.; Altshuler David investigator.; Loos Ruth J. F. investigator.; Shuldiner Alan R. investigator.; Gieger Christian investigator.; Meneton Pierre investigator.; Uitterlinden Andre G. investigator.; Wareham Nicholas J. investigator.; Gudnason Vilmundur investigator.; Rotter Jerome I. investigator.; Rettig Rainer investigator.; Uda Manuela investigator.; Strachan David P. investigator.; Witteman Jacqueline C. M. investigator.; Hartikainen Anna‐Liisa investigator.; Beckmann Jacques S. investigator.; Boerwinkle Eric investigator.; Vasan Ramachandran S. investigator.; Boehnke Michael investigator.; Larson Martin G. investigator.; Järvelin Marjo‐Riitta investigator.; Psaty Bruce M. investigator.; Abecasis Gonçalo R. investigator.; Chakravarti Aravinda investigator.; Elliott Paul investigator.; van Duijn Cornelia M. investigator.; Newton‐Cheh Christopher investigator.; Levy Daniel investigator.; Caulfield Mark J. investigator.; Johnson Toby investigator.; van der Lugt Aad investigator.; Isaacs Aaron investigator.; Dehghan Abbas investigator.; Parsa Afshin investigator.; Shuldiner Alan R. investigator.; Hofman Albert investigator.; Smith Albert V. investigator.; Kraja Aldi T. investigator.; Uitterlinden Andre G. investigator.; Uitterlinden Andre investigator.; Ziegler Andreas investigator.; Johnson Andrew D. investigator.; Scuteri Angelo investigator.; Newman Anne B. investigator.; Schillert Arne investigator.; Voight Benjamin F. investigator.; Oostra Ben investigator.; Thorsson Bolli investigator.; Mitchell Braxton D. investigator.; Psaty Bruce M. investigator.; Hayward Caroline investigator.; Fox Caroline S. investigator.; White Charles C. investigator.; Meisinger Christa investigator.; Ballantyne Christie investigator.; van Duijn Cornelia investigator.; Altshuler David investigator.; Herrington David M. investigator.; O'Leary Daniel H. investigator.; Siscovick David S. investigator.; Couper David J. investigator.; Lakatta Edward G. investigator.; Halperin Eran investigator.; Boerwinkle Eric investigator.; Stoegerer Eva‐Maria investigator.; Rivadeneira Fernando investigator.; Ernst Florian investigator.; Krestin Gabriel P. investigator.; Homuth Georg investigator.; Heiss Gerardo investigator.; Usala Gianluca investigator.; Abecasis Gonçalo R. investigator.; Eiriksdottir Gudny investigator.; Shen Haiqing investigator.; Wichmann H. Erich investigator.; Schmidt Helena investigator.; Völzke Henry investigator.; Borecki Ingrid B. investigator.; Markus Hugh S. investigator.; Witteman Jacqueline investigator.; Wilson James F. investigator.; Lüdemann Jan investigator.; O'Connell Jeffrey R. investigator.; Huffman Jennifer E. investigator.; Baumert Jens investigator.; Rotter Jerome I. investigator.; Murabito Joanne M. investigator.; Thiery Joachim investigator.; Seissler Jochen investigator.; Viikari Jorma investigator.; Massaro Joseph M. investigator.; Polak Joseph F. investigator.; Cunningham Julie investigator.; Bis Joshua C. investigator.; North Kari investigator.; Petrovic Katja E. investigator.; Rice Kenneth investigator.; Taylor Kent investigator.; Cupples L. Adrienne investigator.; Bielak Lawrence F. investigator.; Peltonen Leena investigator.; Launer Lenore J. investigator.; de Andrade Mariza investigator.; Uda Manuela investigator.; Orru Marco investigator.; Dörr Marcus investigator.; Feitosa Mary F. investigator.; Kavousi Maryam investigator.; Sitzer Matthias investigator.; Oudkerk Matthijs investigator.; Province Michael A. investigator.; Nalls Michael investigator.; Kähönen Mika investigator.; Reilly Muredach P. investigator.; Glazer Nicole L. investigator.; Franceschini Nora investigator.; Klopp Norman investigator.; Raitakari Olli investigator.; Peyser Patricia A. investigator.; Wolf Philip A. investigator.; Zhang Qunyuan investigator.; Wild Philipp S. investigator.; Schnabel Renate B. investigator.; Elosua Roberto investigator.; D'Agostino Ralph B. investigator.; Chilukoti Ravi Kumar investigator.; Schmidt Reinhold investigator.; Schnabel Renate B. investigator.; Kathiresan Sekar investigator.; Sanna Serena investigator.; Kardia Sharon L. R. investigator.; Hwang Shih‐Jen investigator.; Demissie Serkalem investigator.; Sigurdsson Sigurdur investigator.; Schwartz Stephen M. investigator.; Blankenberg Stefan investigator.; Bevan Steve investigator.; Elias‐Smale Suzette E. investigator.; Heckbert Susan R. investigator.; Harris Tamara B. investigator.; Zeller Tanja investigator.; Lehtimäki Terho investigator.; Illig Thomas investigator.; Münzel Thomas investigator.; Aspelund Thor investigator.; Howard Timothy D. investigator.; Hoffmann Udo investigator.; Schminke Ulf investigator.; Salomaa Veikko investigator.; Nambi Vijay investigator.; Gudnason Vilmundur investigator.; Liu Yongmei investigator.; Sun Yan V. investigator.; Post Wendy S. investigator.; Koenig Wolfgang investigator.; Rathmann Wolfgang investigator.; Li Xia investigator.; Cheng Yu‐Ching investigator.;
• Is Part Of: Journal of the American Heart Association. Volume 6:Issue 6(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-06
• Subjects: coronary heart disease -- genome‐wide association study -- Mendelian randomization -- plasminogen activator inhibitor type 1 -- single nucleotide polymorphism; Heart -- Diseases -- Periodicals; Cardiovascular system -- Diseases -- Periodicals; Cerebrovascular disease -- Periodicals; Cardiology -- Periodicals; 616.1
• DOI: 10.1161/JAHA.116.004918
• Languages: English
• ISSNs: 2047-9980

Abstract

Abstract : 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 association between PAI‐1 and CHD incidence using a systematic review based on a literature search for PAI‐1 and CHD studies. Second, we explored the causal association between PAI‐1 and CHD using a Mendelian randomization approach using summary statistics from large genome‐wide association studies. Finally, we explored the causal effect of PAI‐1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta‐analysis, the highest quantile of blood PAI‐1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age‐ and sex‐adjusted model. The effect size was reduced in studies using a multivariable‐adjusted model (odds ratio=1.46; 95% CI: 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI‐1 level on CHD risk (odds ratio=1.22 per unit increase of log‐transformed PAI‐1; 95% CI: 1.01, 1.47). In addition, we also detected a causal effect of PAI‐1 on elevating blood glucose and high‐density lipoprotein cholesterol. Conclusions: Our study indicates a causal effect of elevated PAI‐1 level on CHD risk, which may be mediated by glucose dysfunction.