{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T19:31:19Z","timestamp":1785526279353,"version":"3.56.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>\n                      Systemic thromboxane A\n                      <jats:sub>2<\/jats:sub>\n                      generation, assessed via measurement of its urinary metabolites, is associated with cardiovascular disease (CVD) risk. Modifiable correlates with thromboxane A\n                      <jats:sub>2<\/jats:sub>\n                      generation, including potential nonplatelet sources not readily affected by aspirin, are poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      We investigated 2655 FHS (Framingham Heart Study) participants with measurements of urinary thromboxane B\n                      <jats:sub>2<\/jats:sub>\n                      metabolites normalized for renal function (TXB\n                      <jats:sub>2<\/jats:sub>\n                      -M\n                      <jats:sub>GFR<\/jats:sub>\n                      ). Life\u2019s Essential 8 (LE8) score was constructed from 8 modifiable factors. We additionally examined erythrocyte omega-3 fatty acids and omega-6 fatty acid levels, namely, eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid. In a subset of participants, objective measurements of vascular stiffness and adiposity were obtained. We related these factors to TXB\n                      <jats:sub>2<\/jats:sub>\n                      -M\n                      <jats:sub>GFR<\/jats:sub>\n                      using linear models, adjusting for age, sex, and aspirin use. We also explored the association of LE8 or omega-3 fatty acids with total CVD or heart failure stratified by TXB\n                      <jats:sub>2<\/jats:sub>\n                      -M\n                      <jats:sub>GFR<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Both total LE8 score (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001) and individual LE8 components (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.05 for each), including favorable diet, physical activity, blood glucose, blood pressure, and nonsmoking, were associated with lower TXB\n                      <jats:sub>2<\/jats:sub>\n                      -M\n                      <jats:sub>GFR<\/jats:sub>\n                      . Higher omega-3 fatty acids (eicosapentaenoic acid+docosahexaenoic acid) and lower arachidonic acid were associated with lower TXB\n                      <jats:sub>2<\/jats:sub>\n                      -M\n                      <jats:sub>GFR<\/jats:sub>\n                      (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.005 for each). Higher TXB\n                      <jats:sub>2<\/jats:sub>\n                      -M\n                      <jats:sub>GFR<\/jats:sub>\n                      was related to greater waist circumference, computed tomography\u2013measured visceral adipose tissue, and hepatic steatosis (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.01 for each), and higher large artery vascular stiffness (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001). Findings were generally consistent across aspirin use status. After median follow-up of 12.9 years (371 CVD and 214 heart failure events), individuals with both high TXB\n                      <jats:sub>2<\/jats:sub>\n                      -M\n                      <jats:sub>GFR<\/jats:sub>\n                      and low LE8 displayed an over 5-fold higher risk of heart failure (hazard ratio, 5.07 [95% CI, 3.26\u20137.89]) and 2.5-fold higher risk of CVD (hazard ratio, 2.74 [95% CI, 2.04\u20133.68]) compared with participants with low TXB\n                      <jats:sub>2<\/jats:sub>\n                      -M\n                      <jats:sub>GFR<\/jats:sub>\n                      and high LE8.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>\n                      Our findings suggest several modifiable factors that may impact systemic thromboxane A\n                      <jats:sub>2<\/jats:sub>\n                      generation. Higher systemic thromboxane A\n                      <jats:sub>2<\/jats:sub>\n                      generation also appears to modulate the association of lifestyle measures (as assessed by LE8 score) with CVD and heart failure.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.126.324561","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T09:00:25Z","timestamp":1776934825000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Modifiable Correlates With Systemic Thromboxane Generation and Association With Cardiovascular Outcomes: Results From the Framingham Heart Study"],"prefix":"10.1161","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5579-3410","authenticated-orcid":true,"given":"Frank","family":"Qian","sequence":"first","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Medicine, Boston Medical Center and Boston University Chobanian &amp; Avedisian School of Medicine, MA (F.Q., P.G., M.N.)."},{"name":"Section of Preventive Medicine and Epidemiology, Department of Medicine (F.Q., B.P., V.X., M.N.), Boston University Chobanian &amp; Avedisian School of Medicine, Framingham, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2693-1578","authenticated-orcid":true,"given":"Priya","family":"Gajjar","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Medicine, Boston Medical Center and Boston University Chobanian &amp; Avedisian School of Medicine, MA (F.Q., P.G., M.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3805-9070","authenticated-orcid":true,"given":"Brenton","family":"Prescott","sequence":"additional","affiliation":[{"name":"Section of Preventive Medicine and Epidemiology, Department of Medicine (F.Q., B.P., V.X., M.N.), Boston University Chobanian &amp; Avedisian School of Medicine, Framingham, MA."},{"name":"Framingham Center for Population &amp; Prevention Science and Framingham Heart Study (B.P., V.X., M.N.), Boston University Chobanian &amp; Avedisian School of Medicine, Framingham, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5643-3145","authenticated-orcid":true,"given":"Gary F.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Cardiovascular Engineering, Inc, Needham, MA (G.F.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7352-621X","authenticated-orcid":true,"given":"Vanessa","family":"Xanthakis","sequence":"additional","affiliation":[{"name":"Section of Preventive Medicine and Epidemiology, Department of Medicine (F.Q., B.P., V.X., M.N.), Boston University Chobanian &amp; Avedisian School of Medicine, Framingham, MA."},{"name":"Framingham Center for Population &amp; Prevention Science and Framingham Heart Study (B.P., V.X., M.N.), Boston University Chobanian &amp; Avedisian School of Medicine, Framingham, MA."},{"name":"Department of Biostatistics, Boston University School of Public Health, MA (V.X.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8607-4569","authenticated-orcid":true,"given":"Jeffrey J.","family":"Rade","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, University of Massachusetts Chan Medical School, Worcester (J.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6993-9396","authenticated-orcid":true,"given":"Matthew","family":"Nayor","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Medicine, Boston Medical Center and Boston University Chobanian &amp; Avedisian School of Medicine, MA (F.Q., P.G., M.N.)."},{"name":"Section of Preventive Medicine and 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