Association of Thromboxane Generation With Survival in Aspirin Users and Nonusers

Jeffrey J. Rade, Bruce A. Barton, Ramachandran S. Vasan, Shari S. Kronsberg, Vanessa Xanthakis, John F. Keaney, Naomi M. Hamburg, Nikolaos Kakouros, Thomas A. Kickler

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Background: 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.

Original languageEnglish (US)
Pages (from-to)233-250
Number of pages18
JournalJournal of the American College of Cardiology
Issue number3
StatePublished - Jul 19 2022
Externally publishedYes


  • aspirin
  • isoprostane
  • mortality
  • platelets
  • thromboxane

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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