{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:17:34Z","timestamp":1790288254124,"version":"4.1.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2016,3,9]]},"abstract":"\n Background<\/jats:title>\n \n Persistent thromboxane (\n TX<\/jats:styled-content>\n ) generation while receiving aspirin therapy is associated with an increased risk of cardiovascular events. The Reduction in Graft Occlusion Rates (\n RIGOR<\/jats:styled-content>\n ) study found that aspirin\u2010insensitive\n TXA<\/jats:styled-content>\n 2<\/jats:sub>\n generation, indicated by elevated urine 11\u2010dehydro\u2010\n TXB<\/jats:styled-content>\n 2<\/jats:sub>\n (\n UTXB<\/jats:styled-content>\n 2<\/jats:sub>\n ) 6\u00a0months after coronary artery bypass graft surgery, was a potent risk factor for vein graft thrombosis and originated predominantly from nonplatelet sources. Our goal was to identify risks factors for nonplatelet\n TXA<\/jats:styled-content>\n 2<\/jats:sub>\n generation.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Multivariable modeling was performed by using clinical and laboratory variables obtained from 260\n RIGOR<\/jats:styled-content>\n subjects with verified aspirin\u2010mediated inhibition of platelet\n TXA<\/jats:styled-content>\n 2<\/jats:sub>\n generation. The strongest variable associated with\n UTXB<\/jats:styled-content>\n 2<\/jats:sub>\n 6\u00a0months after surgery, accounting for 47.2% of the modeled effect, was urine 8\u2010iso\u2010prostaglandin (\n PG)F<\/jats:styled-content>\n 2\u03b1<\/jats:sub>\n , an arachidonic acid metabolite generated nonenzymatically by oxidative stress (standardized coefficient 0.442,\n P<\/jats:italic>\n <0.001). Age, sex, race, lipid therapy, creatinine, left ventricular ejection fraction, and aspirin dose were also significantly associated with\n UTXB<\/jats:styled-content>\n 2<\/jats:sub>\n (\n P<\/jats:italic>\n <0.03), although they accounted for only 4.8% to 10.2% of the modeled effect. Urine 8\u2010iso\u2010\n PGF<\/jats:styled-content>\n 2\u03b1<\/jats:sub>\n correlated with risk of vein graft occlusion (odds ratio 1.67,\n P<\/jats:italic>\n =0.001) but was not independent of\n UTXB<\/jats:styled-content>\n 2<\/jats:sub>\n . In vitro studies revealed that endothelial cells generate\n TXA<\/jats:styled-content>\n 2<\/jats:sub>\n in response to oxidative stress and direct exposure to 8\u2010iso\u2010\n PGF<\/jats:styled-content>\n 2\u03b1<\/jats:sub>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Oxidative stress\u2013induced formation of 8\u2010iso\u2010\n PGF<\/jats:styled-content>\n 2\u03b1<\/jats:sub>\n is strongly associated with nonplatelet thromboxane formation and early vein graft thrombosis after coronary artery bypass graft surgery. The endothelium is potentially an important source of oxidative stress\u2013induced thromboxane generation. These findings suggest therapies that reduce oxidative stress could be useful in reducing cardiovascular risks associated with aspirin\u2010insensitive thromboxane generation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.115.002615","type":"journal-article","created":{"date-parts":[[2016,3,16]],"date-time":"2016-03-16T02:53:41Z","timestamp":1458096821000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Risk Factors for Nonplatelet Thromboxane Generation After Coronary Artery Bypass Graft Surgery"],"prefix":"10.1161","volume":"5","author":[{"given":"Nikolaos","family":"Kakouros","sequence":"first","affiliation":[{"name":"University of Massachusetts Medical School, Worcester, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna M.","family":"Nazarian","sequence":"additional","affiliation":[{"name":"Johns Hopkins School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia B.","family":"Stadler","sequence":"additional","affiliation":[{"name":"University of Massachusetts Medical School, Worcester, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Kickler","sequence":"additional","affiliation":[{"name":"Johns Hopkins School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey J.","family":"Rade","sequence":"additional","affiliation":[{"name":"University of Massachusetts Medical School, Worcester, MA"},{"name":"Johns Hopkins School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12472"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000013777.21160.07"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.768283"},{"key":"e_1_3_3_5_2","first-page":"168","article-title":"Collaborative overview of randomised trials of antiplatelet therapy\u2010II: maintenance of vascular graft or arterial patency by antiplatelet therapy","volume":"308","author":"Antiplatelet Trialists\u2019 Collaboration","year":"1994","unstructured":"Antiplatelet Trialists\u2019 Collaboration . 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