Association of Thromboxane Generation With Survival in Aspirin Users and Nonusers

Persistent systemic thromboxane generation, predominantly from non-platelet sources, in aspirin (ASA) users with cardiovascular disease (CVD) is a mortality risk factor. To determine the mortality risk associated with systemic thromboxane generation in an unselected population irrespective of ASA use. Stable thromboxane metabolites (TXB 2 -M) were measured by ELISA in banked urine from 3044 participants (mean age 66±9 years, 53.8% women) in the Framingham Heart Study. The association of TXB 2 -M to survival over a median observation period of 11.9 years (IQR 10.6, 12.7) was determined by multivariable modeling. In 1363 participants (44.8%) taking ASA at the index examination, median TXB 2 -M was lower than in ASA non-users (1147 vs. 4179 pg/mg creatinine, P<0.0001). TXB 2 -M was 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 TXB 2 -M in the highest quartile based on ASA use compared to 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 2353 participants without CVD, TXB 2 -M was associated with cardiovascular mortality in ASA non-users (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 TXB 2 -M. 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 risk stratification, particularly in those without CVD.