{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T15:13:32Z","timestamp":1786634012887,"version":"build-2736575974"},"reference-count":66,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,12,19]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Establishing the sex\u2010specific efficacy of cardiovascular medications is pivotal to evidence\u2010based clinical practice, potentially closing the gender gap in longevity. Trials large enough to establish sex differences are unavailable. This study evaluated sex\u2010specific effects of commonly prescribed cardiovascular medications on lifespan.<\/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              In a two\u2010sample Mendelian randomization study, established genetic variants mimicking effects of lipid\u2010lowering drugs, antihypertensives, and diabetes drugs were applied to genetic associations with lifespan proxied by UK Biobank maternal (n=412\u2009937) and paternal (n=415\u2009311) attained age. Estimates were obtained using inverse variance weighting, with sensitivity analyses where possible. For lipid\u2010lowering drugs, genetically mimicked PCSK9 (proprotein convertase subtilisin\/kexin type 9) inhibitors were associated with longer lifespan, particularly in men (2.39\u2009years per SD low\u2010density lipoprotein cholesterol reduction [95% CI, 0.42\u20134.36],\u2009\n              <jats:italic>P<\/jats:italic>\n              for interaction=0.14). Genetically mimicked treatments targeting\n              <jats:italic>APOC3<\/jats:italic>\n              ,\n              <jats:italic>LPL<\/jats:italic>\n              , or possibly\n              <jats:italic>LDLR<\/jats:italic>\n              were associated with longer lifespan in both sexes. For antihypertensives, genetically mimicked \u03b2\u2010blockers and calcium channel blockers were associated with longer lifespan, particularly in men (\n              <jats:italic>P<\/jats:italic>\n              for interaction=0.17 for \u03b2\u2010blockers and 0.31 for calcium channel blockers). For diabetes drugs, genetically mimicked metformin was associated with longer lifespan in both sexes. No associations were found for genetically mimicked statins, ezetimibe, or angiotensin\u2010converting enzyme inhibitors.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              PCSK9 inhibitors, \u03b2\u2010blockers, and calcium channel blockers may prolong lifespan in the general population, particularly men. Treatments targeting\n              <jats:italic>APOC3<\/jats:italic>\n              ,\n              <jats:italic>LPL<\/jats:italic>\n              , or\n              <jats:italic>LDLR<\/jats:italic>\n              and metformin may be relevant to both sexes. Whether other null findings are attributable to lack of efficacy requires investigation. Further investigation of repurposing should be conducted.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.030943","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T10:40:30Z","timestamp":1702896030000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Unraveling Potential Sex\u2010Specific Effects of Cardiovascular Medications on Longevity Using Mendelian Randomization"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3777-4766","authenticated-orcid":false,"given":"Man Ki","family":"Kwok","sequence":"first","affiliation":[{"name":"School of Nursing and Health Studies, Hong Kong Metropolitan University Hong Kong China"},{"name":"School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9933-5887","authenticated-orcid":false,"given":"C. 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