{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:26:31Z","timestamp":1790871991592,"version":"4.1.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,8,6]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Observational studies have reported associations between primary aldosteronism (PA) and cardiovascular outcomes, including coronary artery diseases (CAD), congestive heart failure (CHF), and stroke. However, establishing causality remains a challenge due to the lack of randomized controlled trial data on this topic. We thus aimed to investigate the causal relationship between PA and the risk of developing CAD, CHF, and stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Cross\u2010ancestry meta\u2010analysis of genome\u2010wide association studies combining East Asian and European ancestry (1560 PA cases and 742\u2009139 controls) was conducted to identify single\u2010nucleotide variants that are associated with PA. Then, using the identified genetic variants as instrumental variables, we conducted the 2\u2010sample Mendelian randomization analysis to investigate the causal relationship between PA and incident CAD, CHF, and stroke among both East Asian and European ancestry. Summary association results were extracted from large genome\u2010wide association studies consortia. Our cross\u2010ancestry meta\u2010analysis of East Asian and European populations identified 7 genetic loci significantly associated with the risk of PA, for which the genes nearest to the lead variants were\n                      <jats:italic>CASZ1<\/jats:italic>\n                      ,\n                      <jats:italic>WNT2B<\/jats:italic>\n                      ,\n                      <jats:italic>HOTTIP<\/jats:italic>\n                      ,\n                      <jats:italic>LSP1<\/jats:italic>\n                      ,\n                      <jats:italic>TBX3<\/jats:italic>\n                      ,\n                      <jats:italic>RXFP2<\/jats:italic>\n                      , and\n                      <jats:italic>NDP<\/jats:italic>\n                      . Among the East Asian population, the pooled odds ratio estimates using these 7 genetic instruments of PA were 1.07 (95% CI, 1.03\u20131.11) for CAD, 1.10 (95% CI, 1.01\u20131.20) for CHF, and 1.13 (95% CI, 1.09\u20131.18) for stroke. The results were consistent among the European population.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Our 2\u2010sample Mendelian randomization study revealed that PA had increased risks of CAD, CHF, and stroke. These findings highlight that early and active screening of PA is critical to prevent future cardiovascular events.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.123.034180","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T07:16:51Z","timestamp":1722842211000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Primary Aldosteronism and Risk of Cardiovascular Outcomes: Genome\u2010Wide Association and Mendelian Randomization Study"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9614-8103","authenticated-orcid":false,"given":"Kosuke","family":"Inoue","sequence":"first","affiliation":[{"name":"Kyoto University","place":["Kyoto, Japan"]},{"name":"Kyoto University","place":["Kyoto, 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