Association of Systemic Thromboxane Generation With Risk of Developing Heart Failure

Jeffrey J. Rade, Shari S. Kronsberg, Thomas S. Kickler, Ramachandran S. Vasan, Vanessa Xanthakis, Matthew G. Nayor, Bruce A. Barton

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Systemic thromboxane A2 generation, which is readily assessed by quantifying thromboxane B2 metabolites (TXB2-M) in the urine, is associated with impaired cardiac performance and mortality in aspirin (ASA) users with heart failure (HF). Objectives: This study sought to determine the association of urinary TXB2-M with the risk of developing HF in individuals without prior history of HF and with normal left ventricular function irrespective of ASA use. Methods: Urine TXB2-M were measured by immunoassay and adjusted to urine concentration and renal function (TXB2-MGFR) in 2,611 Framingham Heart Study participants (54.9% women, mean age 65 ± 9 years, 43.8% ASA users) without prior history of HF and with left ventricular ejection fraction (LVEF) ≥55%. The association of TXB2-MGFR with HF risk over a median observation period of 14.8 years (Q1-Q3: 12.6-15.7 years) was modeled using Cox regression. Results: HF occurred in 189 participants (7.2%), with 104 of the first events (55.0%) classified as HF with preserved LVEF, 56 (29.6%) as HF with reduced LVEF, and 29 (15.3%) were unclassifiable. TXB2-MGFR levels, above compared to below, of 16.6 and 62.1 filtered prostanoid units for ASA users and nonusers, respectively, were associated with increased risk of developing HF (HR: 1.81; 95% CI: 1.38-2.64; P < 0.0001, adjusted for age, sex, ASA use, and HF risk factors), including both HF subtypes (HF with preserved LVEF: HR: 1.81; 95% CI: 1.17-2.80; P = 0.0081, and HF with reduced LVEF: HR: 2.63; 95% CI: 1.48-4.68; P = 0.0010, adjusted for age, sex, ASA use, and cardiovascular disease). Neither ASA use nor evidence of platelet activation, as measured by plasma P-selectin, were independently associated with HF risk. Conclusions: Systemic thromboxane A2 generation as measured by urinary TXB2-MGFR was significantly associated with HF risk and remained so after accounting for traditional risk factors. Urinary TXB2-MGFR is therefore a potentially useful novel biomarker to identify at-risk individuals who might benefit from aggressive primary prevention.

Original languageEnglish (US)
Pages (from-to)58-70
Number of pages13
JournalJournal of the American College of Cardiology
Volume85
Issue number1
DOIs
StatePublished - Jan 7 2025

Keywords

  • aspirin
  • heart failure
  • platelets
  • thromboxane

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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