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

Publication ,  Journal Article
Song, C; Burgess, S; Eicher, JD; O'Donnell, CJ; Johnson, AD
Published in: J Am Heart Assoc
May 26, 2017

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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Published In

J Am Heart Assoc

DOI

EISSN

2047-9980

Publication Date

May 26, 2017

Volume

6

Issue

6

Location

England

Related Subject Headings

  • Risk Factors
  • Risk Assessment
  • Polymorphism, Single Nucleotide
  • Plasminogen Activator Inhibitor 1
  • Odds Ratio
  • Observational Studies as Topic
  • Multivariate Analysis
  • Mendelian Randomization Analysis
  • Lipoproteins, HDL
  • Incidence
 

Citation

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Song, C., Burgess, S., Eicher, J. D., O’Donnell, C. J., & Johnson, A. D. (2017). Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease. J Am Heart Assoc, 6(6). https://doi.org/10.1161/JAHA.116.004918
Song, Ci, Stephen Burgess, John D. Eicher, Christopher J. O’Donnell, and Andrew D. Johnson. “Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease.J Am Heart Assoc 6, no. 6 (May 26, 2017). https://doi.org/10.1161/JAHA.116.004918.
Song C, Burgess S, Eicher JD, O’Donnell CJ, Johnson AD. Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease. J Am Heart Assoc. 2017 May 26;6(6).
Song, Ci, et al. “Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease.J Am Heart Assoc, vol. 6, no. 6, May 2017. Pubmed, doi:10.1161/JAHA.116.004918.
Song C, Burgess S, Eicher JD, O’Donnell CJ, Johnson AD. Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease. J Am Heart Assoc. 2017 May 26;6(6).
Journal cover image

Published In

J Am Heart Assoc

DOI

EISSN

2047-9980

Publication Date

May 26, 2017

Volume

6

Issue

6

Location

England

Related Subject Headings

  • Risk Factors
  • Risk Assessment
  • Polymorphism, Single Nucleotide
  • Plasminogen Activator Inhibitor 1
  • Odds Ratio
  • Observational Studies as Topic
  • Multivariate Analysis
  • Mendelian Randomization Analysis
  • Lipoproteins, HDL
  • Incidence