{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T23:44:06Z","timestamp":1780530246508,"version":"3.54.1"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:sec>\n            <jats:title>Objective:<\/jats:title>\n            <jats:p>Case-control studies have identified plasma homocysteine as a risk marker for venous thromboembolism (VTE). Prospective data, particularly among women, are sparse. We examined whether plasma homocysteine associates with incident VTE in 2 large prospective cohorts of women.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results:<\/jats:title>\n            <jats:p>\n              In the WHS (Women\u2019s Health Study), a prospective cohort study of 27\u2009555 women \u226545 years old and free of cardiovascular disease and VTE, we assessed baseline homocysteine concentration along with other thrombotic biomarkers for association with future VTE (n=743), pulmonary embolism (n=363), and deep vein thrombosis (n=545). We used a second cohort of 2672 women (n=102 VTE events) in the WAFACS (Women\u2019s Antioxidant and Folic Acid Cardiovascular Study) to corroborate our findings. In age-adjusted analyses, elevated homocysteine, hsCRP (high-sensitivity C-reactive protein), fibrinogen, and sICAM-1 (soluble intercellular adhesion molecule-1) were associated with incident VTE (\n              <jats:italic>P<\/jats:italic>\n              for extreme quartile comparisons and\n              <jats:italic>P<\/jats:italic>\n              -trend &lt;0.05). In multivariable models adjusting for body mass index and other traditional VTE risk factors, only the association for homocysteine persisted (HR\n              <jats:sub>Q4<\/jats:sub>\n              , 1.31 [95% CI, 1.06\u20131.63]). Elevated homocysteine levels were associated with unprovoked pulmonary embolism (HR\n              <jats:sub>Q4<\/jats:sub>\n              , 2.13 [95% CI, 1.30\u20133.51]) and deep vein thrombosis (HR\n              <jats:sub>Q4<\/jats:sub>\n              , 1.59 [95% CI, 1.05\u20132.40]) but not provoked events. In WAFACS, elevated homocysteine levels were also associated with VTE events (\n              <jats:italic>P<\/jats:italic>\n              -trend 0.023).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Higher plasma homocysteine levels associate with VTE events in 2 cohorts of middle-aged and older women. Among VTE subtypes, homocysteine was associated with unprovoked, but not provoked, events. These data suggest a plausible biological role for homocysteine in the development of VTE.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Registration:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT00000479, NCT00000541.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.121.316397","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T09:03:53Z","timestamp":1622106233000},"page":"2215-2224","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Homocysteine Is Associated With Future Venous Thromboembolism in 2 Prospective Cohorts of Women"],"prefix":"10.1161","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct00000479","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00000541","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6243-3432","authenticated-orcid":true,"given":"Aaron W.","family":"Aday","sequence":"first","affiliation":[{"name":"Division of Preventive Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (A.W.A., E.K.D., M.V.D., E.K., W.G.C., J.E.M., P.M.R., A.D.P.)."},{"name":"Now with Vanderbilt Translational and Clinical Cardiovascular Research Center, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (A.W.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward K.","family":"Duran","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (A.W.A., E.K.D., M.V.D., E.K., W.G.C., J.E.M., P.M.R., A.D.P.)."},{"name":"Now with Cardiovascular Division, University of Minnesota, Minneapolis (E.K.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Van Denburgh","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (A.W.A., E.K.D., M.V.D., E.K., W.G.C., J.E.M., P.M.R., A.D.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunjung","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (A.W.A., E.K.D., M.V.D., E.K., W.G.C., J.E.M., P.M.R., A.D.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G.","family":"Christen","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (A.W.A., E.K.D., M.V.D., E.K., W.G.C., J.E.M., P.M.R., A.D.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9426-7595","authenticated-orcid":true,"given":"JoAnn E.","family":"Manson","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (A.W.A., E.K.D., M.V.D., E.K., W.G.C., J.E.M., P.M.R., A.D.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1249-4522","authenticated-orcid":true,"given":"Paul M","family":"Ridker","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (P.M.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aruna D.","family":"Pradhan","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, VA Boston Medical 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