Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease.
AuthorSong, C; Burgess, S; Eicher, JD; O'Donnell, CJ; Johnson, AD
Source TitleJournal of the American Heart Association
PublisherOvid Technologies (Wolters Kluwer Health)
University of Melbourne Author/sIslam, Rafiqul
AffiliationRural Clinical School
Document TypeJournal Article
CitationsSong, 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.
Access StatusOpen Access
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669150
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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