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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Causal effect of plasminogen activator inhibitor type 1 on coronary heart disease
Journal of the American Heart Association, Volume 6, No. 6, Article e004918, Year 2017
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Description
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. © 2017 The Authors.
Authors & Co-Authors
Song, Ci
United States, Framingham
Framingham Heart Study
United States, Bethesda
National Heart, Lung, and Blood Institute Nhlbi
Burgess, Stephen
United Kingdom, Cambridge
University of Cambridge
Eicher, John D.
United States, Framingham
Framingham Heart Study
United States, Bethesda
National Heart, Lung, and Blood Institute Nhlbi
O'Donnell, Christopher J.
United States, Framingham
Framingham Heart Study
Johnson, Andrew Danner
United States, Framingham
Framingham Heart Study
United States, Bethesda
National Heart, Lung, and Blood Institute Nhlbi
Huang, Jie
Unknown Affiliation
Sabater-Lleal, Maria
Unknown Affiliation
Asselbergs, Folkert W.
Unknown Affiliation
Trégouët, David Alexandre
Unknown Affiliation
Shin, So-youn
Unknown Affiliation
Ding, Jingzhong
Unknown Affiliation
Baumert, Jens J.
Unknown Affiliation
Folkersen, Lasse
Unknown Affiliation
Williams, Scott M.
Unknown Affiliation
Kleber, Marcus Edi
Unknown Affiliation
Becker, Diane M.
Unknown Affiliation
Mychaleckyj, Josyf C.
Unknown Affiliation
Tang, Weihong
Unknown Affiliation
Yang, Qiong
Unknown Affiliation
Sennblad, Bengt
Unknown Affiliation
Moore, Jason H.
Unknown Affiliation
Williams, Frances M.K.
Unknown Affiliation
Dehghan, Abbas
Unknown Affiliation
Silbernagel, Günther
Unknown Affiliation
Karakas, Mahir
Unknown Affiliation
Silveira, Angela Maria Vidigal
Unknown Affiliation
Navis, Gerjan
Unknown Affiliation
Chen, Minghuei
Unknown Affiliation
Peters, Annette Michael
Unknown Affiliation
Goel, Anuj
Unknown Affiliation
Hopewell, Jemma C.
Unknown Affiliation
Chambers, John Campbell
Unknown Affiliation
Saleheen, Danish
Unknown Affiliation
Lundmark, Per E.
Unknown Affiliation
Psaty, Bruce M.
Unknown Affiliation
Strawbridge, Rona J.
Unknown Affiliation
Böehm, Bernhard Otto
Unknown Affiliation
Meisinger, Christa
Unknown Affiliation
Peden, John F.
Unknown Affiliation
Bis, Joshua C.M.
Unknown Affiliation
McKnight, Barbara
Unknown Affiliation
Taylor, Kent D.
Unknown Affiliation
Franzosi, Maria Grazia
Unknown Affiliation
Seedorf, Udo
Unknown Affiliation
Collins, Rory
Unknown Affiliation
Franco-Cereceda, Anders
Unknown Affiliation
Syvänen, Ann Christine
Unknown Affiliation
Goodall, Alison H.
Unknown Affiliation
Yanek, Lisa R.
Unknown Affiliation
Cushman, Mary E.
Unknown Affiliation
Müller-Nurasyid, Martina
Unknown Affiliation
Folsom, Aaron R.
Unknown Affiliation
Basu, Saonli
Unknown Affiliation
Matijević-Aleksić, Nena
Unknown Affiliation
Van Gilst, Wiek H.
Unknown Affiliation
Kooner, Jaspal Singh
Unknown Affiliation
Danesh, John N.
Unknown Affiliation
Clarke, Robert Joseph
Unknown Affiliation
Meigs, James B.
Unknown Affiliation
Kathiresan, Sekar
Unknown Affiliation
Reilly, Muredach P.
Unknown Affiliation
Klopp, Norman
Unknown Affiliation
Harris, Tamara B.
Unknown Affiliation
Winkelmann, Bernhard Rudolf
Unknown Affiliation
Grant, Peter J.
Unknown Affiliation
Watkins, Hugh C.
Unknown Affiliation
Spector, Tim David
Unknown Affiliation
Becker, Lewis C.
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Tracy, Russell P.
Unknown Affiliation
Mar̈z, Winfried
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Uitterlinden, André G.
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Cambien, François A.
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Morange, Pierre Emmanuel
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Koenig, Wolfgang F.
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Soranzo, Nicole
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Van Der Harst, Pim
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Liu, Yongmei
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Hamsten, Anders
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Ehret, Georg B.
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Munroe, Patricia B.
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Rice, Kenneth Martin
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Bochud, Murielle
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Chasman, Daniel I.
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Smith, Albert Vernon
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Tobin, Martin D.
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Hwang, Shihjen
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Vollenweider, Peter K.
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Amin, Najaf A.
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Bragg-Gresham, Jennifer Lynn
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Teumer, Alexander
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Glazer, Nicole L.
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Aulchenko, Yurii S.
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Heath, Simon C.
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Luan, Jian'fan N.An
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Hicks, Andrew Anthony
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Jackson, Anne U.
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Tanaka, Toshiko
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Wild, Sarah Helen
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Rudan, Igor
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Igl, Wilmar
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Milaneschi, Yuri
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Fava, Cristiano
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Fox, Ervin R.
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Kumari, Meena
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Sjögren, Marketa
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Alexander, Myriam
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Tabara, Yasuharu
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Whincup, Peter Hynes
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Kuusisto, Johanna K.
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Tayo, Bamidele O.
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Seielstad, Mark
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Sim, Xueling
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Lehtimäki, Terho J.
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Matullo, Giuseppe
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Wu, Ying
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Gaunt, Tom R.
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Onland-Moret, N. Charlotte
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Hardy, Rebecca J.
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Palmen, Jutta M.
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Vitart, Véronique
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Braund, Peter S.
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Kuznetsova, Tatiana N.
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Uiterwaal, Cuno Spm
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Adeyemo, Adebowale A.
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Palmas, Walter R.
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Campbell, Harry
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Tomaszewski, Maciej
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Tzoulaki, Ioanna
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Palmer, Nicholette (Nichole)
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Aspelund, Thor
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Grobbee, Diederick E Egbertus
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Arking, Dan E.
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Kardia, Sharon L.R.
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Morrison, Alanna C.
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Hernandez, Dena G.
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McArdle, Wendy L.
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Brown, Morris J.
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Connell, John M.C.
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Hingorani, Aroon Dinesh
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Day, Ian N.M.
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Lawlor, Debbie A.
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Ongen, Halit
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Young, Jeffery Hunter
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Kähönen, Mika A.P.
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Viikari, Jorma S.A.
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Mayol, Nanette L.
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Olden, Matthias
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Köttgen, Anna
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Mooser, Vincent E.
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Chaturvedi, Nish R.
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Jafar, Tazeen Hasan
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Gräßler, Jürgen
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Voight, Benjamin F.
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Ricceri, Fulvio
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Plump, Andrew S.
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Barroso, Inês E.
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Khaw, Kay Tee T.
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Hunt, Steven C.
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Sun, Yan V.
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Bonnycastle, Lori L.C.
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Scott, Laura J.
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Stringham, Heather M.
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Peltonen-Palotie, Leena Johanna
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Vartiainen, Erkki A.
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Longstreth, William T.
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Prokopenko, Inga I.
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Bakker, Stephan J.L.
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Yajnik, Chittaranjan Sakerlal
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Demirkan, Ayşe
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Rivadeneira, Fernando F.
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Lakatta, Edward G.
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Scuteri, Angelo
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Ala-Korpela, Mika
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Kangas, Antti J.
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Lyytikäinen, Leo Pekka
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Soininen, Pasi P.
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Tukiainen, Taru
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Twee-Hee Ong, Rick Hee
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Dörr, Marcus
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Völker, Uwe
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Völzke, Henry
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Galán, Pilar Redondo
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Hercberg, Serge
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Lathrop, Mark G.
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Zélénika, Diana
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Deloukas, Panos
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Mangino, Massimo
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Zhai, Guangju
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Meschia, James Frederick
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Nalls, Michael A.
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Sharma, Pankaj Kumar
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Wagenknecht, Lynne E.
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Fowkes, Francis Gerald R.
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Charchar, Fadi J.
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Rotimi, Charles N.
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Samani, Nilesh J.
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Talmud, Philippa J.
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Markus, Hugh Stephen
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Witteman, Jacqueline C.M.
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Huffman, Jennifer E.
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Thiery, Joachim
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Massaro, Joseph M.
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Polak, Joseph F.
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Cunningham, Julie M.
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North, Kari E.
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Petrovic, Katja Elisabeth
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Cupples, Laura Adrienne
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Bielak, Lawrence F.
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Launer, Lenore J.
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de Andrade, Mariza A.
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Feitosa, Mary Furlan
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Kavousi, Maryam
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Province, Michael A.
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Nalls, Mike A.
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Franceschini, Nora
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Peyser, Patricia A.
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Wild, Philipp S.
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Schnabel, Renate B.
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D’Agostino, Ralph B.
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Schmidt, Reinhold T.
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Sanna, Serena
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Demissie, Serkalem
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Bevan, Stephen N.
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Zeller, Tanja
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Illig, Thomas
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Münzel, Tomas F.
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Howard, Timothy D.
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Hoffmann, Udo
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Schminke, Ulf
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Post, Wendy S.
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Statistics
Citations: 85
Authors: 365
Affiliations: 3
Identifiers
Doi:
10.1161/JAHA.116.004918
ISSN:
20479980
Research Areas
Noncommunicable Diseases
Study Design
Randomised Control Trial
Cross Sectional Study
Cohort Study
Case-Control Study
Study Approach
Systematic review