{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T21:56:41Z","timestamp":1789768601716,"version":"4.0.1"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,8,15]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Premature and early menopause are independently associated with greater risk of cardiovascular disease (CVD). However, mechanisms linking age of menopause with CVD remain poorly characterized.<\/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                      We measured 71 circulating CVD protein biomarkers in 1565 postmenopausal women enrolled in the FHS (Framingham Heart Study). We examined the association of early menopause with biomarkers and tested whether early menopause modified the association of biomarkers with incident cardiovascular outcomes (heart failure, major CVD, and all\u2010cause death) using multivariable\u2010adjusted linear regression and Cox models, respectively. Among 1565 postmenopausal women included (mean age 62\u2009years), 395 (25%) had a history of early menopause. Of 71 biomarkers examined, we identified 7 biomarkers that were significantly associated with early menopause, of which 5 were higher in women with early menopause\u00a0including adrenomedullin and resistin, and 2 were higher in women without early menopause\u00a0including insulin growth factor\u20101 and CNTN1 (contactin\u20101) (Benjamini\u2010Hochberg adjusted\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.1 for all). Early menopause also modified the association of specific biomarkers with incident cardiovascular outcomes including adrenomedullin (\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>int<\/jats:sub>\n                      &lt;0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Early menopause is associated with circulating levels of CVD protein biomarkers and appears to modify the association between select biomarkers with incident cardiovascular outcomes. Identified biomarkers reflect several distinct biological pathways, including inflammation, adiposity, and neurohormonal regulation. Further investigation of these pathways may provide mechanistic insights into the pathogenesis, prevention, and treatment of early menopause\u2010associated CVD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.122.028849","type":"journal-article","created":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T05:37:46Z","timestamp":1691386666000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Protein Biomarkers of Early Menopause and Incident Cardiovascular Disease"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1643-7894","authenticated-orcid":false,"given":"Mariana F.","family":"Ramirez","sequence":"first","affiliation":[{"name":"CardioVascular Institute and Division of Cardiology, Department of Medicine Beth Israel Deaconess Medical Center Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8630-5021","authenticated-orcid":false,"given":"Michael","family":"Honigberg","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center and Division of Cardiology, Department of Medicine Massachusetts General Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1317-2739","authenticated-orcid":false,"given":"Dongyu","family":"Wang","sequence":"additional","affiliation":[{"name":"CardioVascular Institute and Division of Cardiology, Department of Medicine Beth Israel Deaconess Medical Center Boston MA USA"},{"name":"Department of Biostatistics Boston University School of Public Health Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6510-0073","authenticated-orcid":false,"given":"Juhi K.","family":"Parekh","sequence":"additional","affiliation":[{"name":"CardioVascular Institute and Division of Cardiology, Department of Medicine Beth Israel Deaconess Medical Center Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6523-106X","authenticated-orcid":false,"given":"Kamila","family":"Bielawski","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center and Division of Cardiology, Department of Medicine Massachusetts General Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5691-6913","authenticated-orcid":false,"given":"Paul","family":"Courchesne","sequence":"additional","affiliation":[{"name":"Framingham Heart Study Framingham MA USA"},{"name":"Population Sciences Branch, Division of Intramural Research National Heart, Lung, and Blood Institute Framingham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9631-1254","authenticated-orcid":false,"given":"Martin D.","family":"Larson","sequence":"additional","affiliation":[{"name":"Framingham Heart Study Framingham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1843-8724","authenticated-orcid":false,"given":"Daniel","family":"Levy","sequence":"additional","affiliation":[{"name":"Framingham Heart Study Framingham MA USA"},{"name":"Population Sciences Branch, Division of Intramural Research National Heart, Lung, and Blood Institute Framingham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0192-7516","authenticated-orcid":false,"given":"Joanne M.","family":"Murabito","sequence":"additional","affiliation":[{"name":"Framingham Heart Study Framingham MA USA"},{"name":"Department of Medicine, Section of General Internal Medicine Boston 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