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Song, Ci; Burgess, Stephen; Eicher, John D.; O'Donnell, Christopher J.; Johnson, Andrew D.; Huang, Jie; Sabater‐Lleal, Maria; Asselbergs, Folkert W.; Tregouet, David; Shin, So‐Youn; Ding, Jingzhong; Baumert, Jens; Oudot‐Mellakh, Tiphaine; Folkersen, Lasse; Smith, Nicholas L.; Williams, Scott M.; Ikram, Mohammad A.; Kleber, Marcus E.; Becker, Diane M.; Truong, Vinh; Mychaleckyj, Josyf C.; Tang, Weihong; Yang, Qiong; Sennblad, Bengt; [...]

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

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  • Media type: E-Article
  • Title: Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease
  • Contributor: Song, Ci; Burgess, Stephen; Eicher, John D.; O'Donnell, Christopher J.; Johnson, Andrew D.; Huang, Jie; Sabater‐Lleal, Maria; Asselbergs, Folkert W.; Tregouet, David; Shin, So‐Youn; Ding, Jingzhong; Baumert, Jens; Oudot‐Mellakh, Tiphaine; Folkersen, Lasse; Smith, Nicholas L.; Williams, Scott M.; Ikram, Mohammad A.; Kleber, Marcus E.; Becker, Diane M.; Truong, Vinh; Mychaleckyj, Josyf C.; Tang, Weihong; Yang, Qiong; Sennblad, Bengt; [...]
  • imprint: Ovid Technologies (Wolters Kluwer Health), 2017
  • Published in: Journal of the American Heart Association
  • Language: English
  • DOI: 10.1161/jaha.116.004918
  • ISSN: 2047-9980
  • Keywords: Cardiology and Cardiovascular Medicine
  • Origination:
  • Footnote:
  • Description: <jats:sec xml:lang="en"> <jats:title>Background</jats:title> <jats:p xml:lang="en"> Plasminogen activator inhibitor type 1 ( <jats:styled-content style="fixed-case">PAI</jats:styled-content> ‐1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood <jats:styled-content style="fixed-case">PAI</jats:styled-content> ‐1 levels are associated with increased risk of coronary heart disease ( <jats:styled-content style="fixed-case">CHD</jats:styled-content> ). However, it is unclear whether the association reflects a causal influence of <jats:styled-content style="fixed-case">PAI</jats:styled-content> ‐1 on <jats:styled-content style="fixed-case">CHD</jats:styled-content> risk. </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Methods and Results</jats:title> <jats:p xml:lang="en"> To evaluate the association between <jats:styled-content style="fixed-case">PAI</jats:styled-content> ‐1 and <jats:styled-content style="fixed-case">CHD</jats:styled-content> , we applied a 3‐step strategy. First, we investigated the observational association between <jats:styled-content style="fixed-case">PAI</jats:styled-content> ‐1 and <jats:styled-content style="fixed-case">CHD</jats:styled-content> incidence using a systematic review based on a literature search for <jats:styled-content style="fixed-case">PAI</jats:styled-content> ‐1 and <jats:styled-content style="fixed-case">CHD</jats:styled-content> studies. Second, we explored the causal association between <jats:styled-content style="fixed-case">PAI</jats:styled-content> ‐1 and <jats:styled-content style="fixed-case">CHD</jats:styled-content> using a Mendelian randomization approach using summary statistics from large genome‐wide association studies. Finally, we explored the causal effect of <jats:styled-content style="fixed-case">PAI</jats:styled-content> ‐1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta‐analysis, the highest quantile of blood <jats:styled-content style="fixed-case">PAI</jats:styled-content> ‐1 level was associated with higher <jats:styled-content style="fixed-case">CHD</jats:styled-content> 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% <jats:styled-content style="fixed-case">CI</jats:styled-content> : 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased <jats:styled-content style="fixed-case">PAI</jats:styled-content> ‐1 level on <jats:styled-content style="fixed-case">CHD</jats:styled-content> risk (odds ratio=1.22 per unit increase of log‐transformed <jats:styled-content style="fixed-case">PAI</jats:styled-content> ‐1; 95% <jats:styled-content style="fixed-case">CI</jats:styled-content> : 1.01, 1.47). In addition, we also detected a causal effect of <jats:styled-content style="fixed-case">PAI</jats:styled-content> ‐1 on elevating blood glucose and high‐density lipoprotein cholesterol. </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Conclusions</jats:title> <jats:p xml:lang="en"> Our study indicates a causal effect of elevated <jats:styled-content style="fixed-case">PAI</jats:styled-content> ‐1 level on <jats:styled-content style="fixed-case">CHD</jats:styled-content> risk, which may be mediated by glucose dysfunction. </jats:p> </jats:sec>
  • Access State: Open Access