Aspirin (ASA) users with cardiovascular disease (CVD) have persistent systemic thromboxane production that comes mostly from nonplatelet sources, which is a mortality risk factor. Therefore, for a study, regardless of ASA usage, researchers sought to determine what mortality risk was connected to systemic thromboxane production in an unselected sample.

Enzyme-linked immunosorbent assays were used to quantify stable thromboxane B2 metabolites (TXB2-M) in banked urine from 3,044 patients in the Framingham Heart Study (mean age 66 ±9 years; 53.8% women). Multivariable modeling was used to establish the relationship between TXB2-M and survival over a median observation time of 11.9 years (IQR: 10.6-12.7 years).

At the index examination, 1,363 (44.8%) patients who were using ASA had median TXB2-M values that were lower than those of ASA nonusers (1,147 pg/mg creatinine vs. 4,179 pg/mg creatinine; P<0.0001). For TXB2-M in the highest quartile based on ASA use compared with lower quartiles, there was a significant association between TXB2-M and all-cause and cardiovascular mortality (HR: 1.96 and 2.41, respectively; P<0.0001 for both), and this association persisted after adjusting for mortality risk factors for similarly aged individuals (HR: 1.49 and 1.82, respectively; P ≤0.005 for both). In addition, TXB2-M was linked with cardiovascular mortality in 2,353 people without CVD (adjusted HR: 3.04; 95% CI: 1.29-7.16) but not in ASA users, whereas ASA usage was associated with all-cause mortality in those with low but not increased TXB2-M (adjusted HR: 1.46; 95% CI: 1.14-1.87).

Regardless of ASA usage, systemic thromboxane production is an independent risk factor for all-cause and cardiovascular death, and its assessment may help modify medication, even in patients without CVD.