{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:54:13Z","timestamp":1791863653709,"version":"4.3.4"},"reference-count":47,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Hypertensive disorders in pregnancy (HDPs) are major causes of maternal and fetal morbidity and are observationally associated with future maternal risk of cardiovascular disease. However, observational results may be subject to residual confounding and bias.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To investigate the association of HDPs with multiple cardiovascular diseases.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n A genome-wide genetic association study using mendelian randomization (MR) was performed from February 16 to March 4, 2022. Primary analysis was conducted using inverse-variance-weighted MR. Mediation analyses were performed using a multivariable MR framework. All studies included patients predominantly of European ancestry. Female-specific summary-level data from FinnGen (sixth release).<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n \n Uncorrelated (\n r<\/jats:italic>\n 2<\/jats:sup>\n &amp;lt;0.001) single-nucleotide variants (SNVs) were selected as instrumental variants from the FinnGen consortium summary statistics for exposures of any HDP, gestational hypertension, and preeclampsia or eclampsia.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Genetic association estimates for outcomes were extracted from genome-wide association studies of 122\u202f733 cases for coronary artery disease, 34\u202f217 cases for ischemic stroke, 47\u202f309 cases for heart failure, and 60\u202f620 cases for atrial fibrillation.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Genetically predicted HDPs were associated with a higher risk of coronary artery disease (odds ratio [OR], 1.24; 95% CI, 1.08-1.43;\n P<\/jats:italic>\n \u2009=\u2009.002); this association was evident for both gestational hypertension (OR, 1.08; 95% CI, 1.00-1.17;\n P<\/jats:italic>\n \u2009=\u2009.04) and preeclampsia\/eclampsia (OR, 1.06; 95% CI, 1.01-1.12;\n P<\/jats:italic>\n \u2009=\u2009.03). Genetically predicted HDPs were also associated with a higher risk of ischemic stroke (OR, 1.27; 95% CI, 1.12-1.44;\n P<\/jats:italic>\n \u2009=\u20092.87\u2009\u00d7\u200910\n \u22124<\/jats:sup>\n ). Mediation analysis revealed a partial attenuation of the effect of HDPs on coronary artery disease after adjustment for systolic blood pressure (total effect OR, 1.24; direct effect OR, 1.10; 95% CI, 1.02-1.08;\n P<\/jats:italic>\n \u2009=\u2009.02) and type 2 diabetes (total effect OR, 1.24; direct effect OR, 1.16; 95% CI, 1.04-1.29;\n P<\/jats:italic>\n \u2009=\u2009.008). No associations were noted between genetically predicted HDPs and heart failure (OR, 0.97; 95% CI, 0.76-1.23;\n P<\/jats:italic>\n \u2009=\u2009.79) or atrial fibrillation (OR, 1.11; 95% CI, 0.65-1.88;\n P<\/jats:italic>\n \u2009=\u2009.71).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n The findings of this study provide genetic evidence supporting an association between HDPs and higher risk of coronary artery disease and stroke, which is only partially mediated by cardiometabolic factors. This supports classification of HDPs as risk factors for cardiovascular disease.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.0034","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T11:01:09Z","timestamp":1676631669000},"page":"e230034","source":"Crossref","is-referenced-by-count":96,"title":["Association of Hypertensive Disorders of Pregnancy With Future Cardiovascular Disease"],"prefix":"10.1001","volume":"6","author":[{"given":"Bilal","family":"Rayes","sequence":"first","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Ardissino","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London, United Kingdom"},{"name":"Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A. W.","family":"Slob","sequence":"additional","affiliation":[{"name":"Medical Research Council Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom"},{"name":"Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands"},{"name":"Erasmus University Rotterdam Institute for Behavior and Biology, Erasmus University Rotterdam, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran Haresh Kumar","family":"Patel","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Girling","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Chelsea and Westminster National Health Service Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu 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