Higher systemic thromboxane A2 generation, measured by urinary TXB2-MGFR, was associated with an increased risk of developing heart failure (HR 1.81; 95% CI 1.38-2.64; P<0.0001).
Cohort (n=2,611)
Does high systemic thromboxane A2 generation increase the risk of developing heart failure in individuals without prior HF and normal LVEF?
Systemic thromboxane A2 generation is independently associated with an increased risk of developing heart failure in individuals with normal LVEF, suggesting its potential as a novel biomarker for primary prevention.
Effect estimate: HR 1.81 (95% CI 1.38-2.64)
p-value: p=< 0.0001
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.
Rade et al. (Wed,) conducted a cohort in Individuals without prior history of heart failure and with normal left ventricular function (n=2,611). Urinary TXB2-MGFR levels above threshold vs. Urinary TXB2-MGFR levels below threshold was evaluated on risk of developing heart failure (HR 1.81, 95% CI 1.38-2.64, p=< 0.0001). Higher systemic thromboxane A2 generation, measured by urinary TXB2-MGFR, was associated with an increased risk of developing heart failure (HR 1.81; 95% CI 1.38-2.64; P<0.0001).