Rade, Jeffrey JBarton, Bruce AVasan, Ramachandran SKronsberg, Shari SXanthakis, VanessaKeaney, John FHamburg, Naomi MKakouros, NikolaosKickler, Thomas A2022-11-232022-11-232022-06-01Rade JJ, Barton BA, Vasan RS, Kronsberg SS, Xanthakis V, Keaney JF Jr, Hamburg NM, Kakouros N, Kickler TA. Association of Thromboxane Generation With Survival in Aspirin Users and Nonusers. J Am Coll Cardiol. 2022 Jul 19;80(3):233-250. doi: 10.1016/j.jacc.2022.04.034. Epub 2022 Jun 1. PMID: 35660296.1558-359710.1016/j.jacc.2022.04.03435660296https://hdl.handle.net/20.500.14038/51314Background: Persistent systemic thromboxane generation, predominantly from nonplatelet sources, in aspirin (ASA) users with cardiovascular disease (CVD) is a mortality risk factor. Objectives: This study sought to determine the mortality risk associated with systemic thromboxane generation in an unselected population irrespective of ASA use. Methods: Stable thromboxane B2 metabolites (TXB2-M) were measured by enzyme-linked immunosorbent assay in banked urine from 3,044 participants (mean age 66 ± 9 years, 53.8% women) in the Framingham Heart Study. The association of TXB2-M to survival over a median observation period of 11.9 years (IQR: 10.6-12.7 years) was determined by multivariable modeling. Results: In 1,363 (44.8%) participants taking ASA at the index examination, median TXB2-M were lower than in ASA nonusers (1,147 pg/mg creatinine vs 4,179 pg/mg creatinine; P < 0.0001). TXB2-M were significantly associated with all-cause and cardiovascular mortality irrespective of ASA use (HR: 1.96 and 2.41, respectively; P < 0.0001 for both) for TXB2-M in the highest quartile based on ASA use compared with lower quartiles, and remained significant after adjustment for mortality risk factors for similarly aged individuals (HR: 1.49 and 1.82, respectively; P ≤ 0.005 for both). In 2,353 participants without CVD, TXB2-M were associated with cardiovascular mortality in ASA nonusers (adjusted HR: 3.04; 95% CI: 1.29-7.16) but not in ASA users, while ASA use was associated with all-cause mortality in those with low (adjusted HR: 1.46; 95% CI: 1.14-1.87) but not elevated TXB2-M. Conclusions: Systemic thromboxane generation is an independent risk factor for all-cause and cardiovascular mortality irrespective of ASA use, and its measurement may be useful for therapy modification, particularly in those without CVD.enCopyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.aspirinisoprostanemortalityplateletsthromboxaneJournal ArticleJournal of the American College of Cardiology