{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:59:46Z","timestamp":1787885986380,"version":"build-2784847793"},"reference-count":58,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,11,6]]},"abstract":"\n Background<\/jats:title>\n \n Plasminogen activator inhibitor type 1 (\n PAI<\/jats:styled-content>\n \u20101) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood\n PAI<\/jats:styled-content>\n \u20101 levels are associated with increased risk of coronary heart disease (\n CHD<\/jats:styled-content>\n ). However, it is unclear whether the association reflects a causal influence of\n PAI<\/jats:styled-content>\n \u20101 on\n CHD<\/jats:styled-content>\n risk.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n To evaluate the association between\n PAI<\/jats:styled-content>\n \u20101 and\n CHD<\/jats:styled-content>\n , we applied a 3\u2010step strategy. First, we investigated the observational association between\n PAI<\/jats:styled-content>\n \u20101 and\n CHD<\/jats:styled-content>\n incidence using a systematic review based on a literature search for\n PAI<\/jats:styled-content>\n \u20101 and\n CHD<\/jats:styled-content>\n studies. Second, we explored the causal association between\n PAI<\/jats:styled-content>\n \u20101 and\n CHD<\/jats:styled-content>\n using a Mendelian randomization approach using summary statistics from large genome\u2010wide association studies. Finally, we explored the causal effect of\n PAI<\/jats:styled-content>\n \u20101 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta\u2010analysis, the highest quantile of blood\n PAI<\/jats:styled-content>\n \u20101 level was associated with higher\n CHD<\/jats:styled-content>\n risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age\u2010 and sex\u2010adjusted model. The effect size was reduced in studies using a multivariable\u2010adjusted model (odds ratio=1.46; 95%\n CI<\/jats:styled-content>\n : 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased\n PAI<\/jats:styled-content>\n \u20101 level on\n CHD<\/jats:styled-content>\n risk (odds ratio=1.22 per unit increase of log\u2010transformed\n PAI<\/jats:styled-content>\n \u20101; 95%\n CI<\/jats:styled-content>\n : 1.01, 1.47). In addition, we also detected a causal effect of\n PAI<\/jats:styled-content>\n \u20101 on elevating blood glucose and high\u2010density lipoprotein cholesterol.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our study indicates a causal effect of elevated\n PAI<\/jats:styled-content>\n \u20101 level on\n CHD<\/jats:styled-content>\n risk, which may be mediated by glucose dysfunction.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.116.004918","type":"journal-article","created":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T20:35:22Z","timestamp":1495830922000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":108,"title":["Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease"],"prefix":"10.1161","volume":"6","author":[{"given":"Ci","family":"Song","sequence":"first","affiliation":[{"name":"Framingham Heart Study, Framingham, MA"},{"name":"The Population Sciences Branch, 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