Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease
نویسندگان
- Ci Song
- Stephen Burgess
- John D. Eicher
- Christopher J. O'Donnell
- Andrew D. Johnson
- Jie Huang
- Maria Sabater‐Lleal
- Folkert W. Asselbergs
- David Tregouet
- So‐Youn Shin
- Jingzhong Ding
- Jens Baumert
- Tiphaine Oudot‐Mellakh
- Lasse Folkersen
- Nicholas L. Smith
- Scott M. Williams
- Mohammad A. Ikram
- Marcus E. Kleber
- Diane M. Becker
- Vinh Truong
- Josyf C. Mychaleckyj
- Weihong Tang
- Qiong Yang
- Bengt Sennblad
- Jason H. Moore
- Frances M. K. Williams
- Abbas Dehghan
- Günther Silbernagel
- Elisabeth M. C. Schrijvers
- Shelly Smith
- Mahir Karakas
- Geoffrey H. Tofler
- Angela Silveira
- Gerjan J. Navis
- Kurt Lohman
- Ming‐Huei Chen
- Annette Peters
- Anuj Goel
- Jemma C. Hopewell
- John C. Chambers
- Danish Saleheen
- Per Lundmark
- Bruce M. Psaty
- Rona J. Strawbridge
- Bernhard O. Boehm
- Angela M. Carter
- Christa Meisinger
- John F. Peden
- Joshua C. Bis
- Barbara McKnight
- John Öhrvik
- Kent Taylor
- Maria Grazia Franzosi
- Udo Seedorf
- Rory Collins
- Anders Franco‐Cereceda
- Ann‐Christine Syvänen
- Alison H. Goodall
- Lisa R. Yanek
- Mary Cushman
- Martina Müller‐Nurasyid
- Aaron R. Folsom
- Saonli Basu
- Nena Matijevic
- Wiek H. van Gilst
- Jaspal S. Kooner
- Albert Hofman
- John Danesh
- Robert Clarke
- James B. Meigs
- Sekar Kathiresan
- Muredach P. Reilly
- Norman Klopp
- Tamara B. Harris
- Bernhard R. Winkelmann
- Peter J. Grant
- Hans L. Hillege
- Hugh Watkins
- Timothy D. Spector
- Lewis C. Becker
- Russell P. Tracy
- Winfried März
- Andre G. Uitterlinden
- Per Eriksson
- Francois Cambien
- Pierre‐Emmanuel Morange
- Wolfgang Koenig
- Nicole Soranzo
- Pim van der Harst
- Yongmei Liu
- Anders Hamsten
- Georg B. Ehret
- Patricia B. Munroe
- Kenneth M. Rice
- Murielle Bochud
- Daniel I. Chasman
- Albert V. Smith
- Martin D. Tobin
- Germaine C. Verwoert
- Shih‐Jen Hwang
- Vasyl Pihur
- Peter Vollenweider
- Paul F. O'Reilly
- Najaf Amin
- Jennifer L. Bragg‐Gresham
- Alexander Teumer
- Nicole L. Glazer
- Lenore Launer
- Jing Hua Zhao
- Yurii Aulchenko
- Simon Heath
- Siim Sõber
- Afshin Parsa
- Jian'an Luan
- Pankaj Arora
- Feng Zhang
- Gavin Lucas
- Andrew A. Hicks
- Anne U. Jackson
- Toshiko Tanaka
- Sarah H. Wild
- Igor Rudan
- Wilmar Igl
- Yuri Milaneschi
- Alex N. Parker
- Cristiano Fava
- Ervin R. Fox
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- Min Jin Go
- Wen Hong Linda Kao
- Marketa Sjögren
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- Sue Shaw‐Hawkins
- Peter H. Whincup
- Gang Shi
- Johanna Kuusisto
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- Mark Seielstad
- Xueling Sim
- Khanh‐Dung Hoang Nguyen
- Terho Lehtimäki
- Giuseppe Matullo
- Ying Wu
- Tom R. Gaunt
- N. Charlotte Onland‐Moret
- Matthew N. Cooper
- Carl G. P. Platou
- Elin Org
- Rebecca Hardy
- Santosh Dahgam
- Jutta Palmen
- Veronique Vitart
- Peter S. Braund
- Tatiana Kuznetsova
- Cuno S. P. M. Uiterwaal
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- Walter Palmas
- Harry Campbell
- Barbara Ludwig
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- Johannes Kettunen
- Philip Howard
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- Simonetta Guarrera
- Fulvio Ricceri
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- Andrew Plump
- Inês Barroso
- Kay‐Tee Khaw
- Alan B. Weder
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- Margus Viigimaa
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- Amy J. Swift
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- Paavo Zitting
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- Antti J. Kangas
- Leo‐Pekka Lyytikäinen
- Pasi Soininen
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- Georg Homuth
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- Gudny Eiriksdottir
- Haiqing Shen
- H. Erich Wichmann
- Helena Schmidt
- Ingrid B. Borecki
- Hugh S. Markus
- Jacqueline Witteman
- Jan Lüdemann
- Jennifer E. Huffman
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- Reinhold Schmidt
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- Serkalem Demissie
- Sigurdur Sigurdsson
- Stefan Blankenberg
- Steve Bevan
- Suzette E. Elias‐Smale
- Tanja Zeller
- Thomas Illig
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- Udo Hoffmann
- Ulf Schminke
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- Yu‐Ching Cheng
چکیده
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.
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ورودعنوان ژورنال:
دوره 6 شماره
صفحات -
تاریخ انتشار 2017