Thromboxane (TX) A2, released by activated platelets, plays an important role in atherothrombosis, and its urinary metabolite in humans, the 11-dehydro-TXB2 (U-TXM), reflects the whole-body TXA2 biosynthesis, and it is reduced by ∼70% by daily low-dose aspirin. The U-TXM represents a non-invasive biomarker of in vivo platelet activation, is enhanced in conditions at high cardiovascular risk, including patients with diabetes, and it can predict fatal and non-fatal cardiovascular complications in large, prospective cohorts.
This study assessed whether U-TXM is associated with the risk of future serious vascular events or revascularizations (SVE-R), major bleeding, or cancer in patients with diabetes participating to the ASCEND trial. U-TXM was measured pre-randomization to aspirin or placebo in 5,948 people with type 1 or 2 diabetes and no cardiovascular disease followed for 6.6 years. Higher U-TXM was associated with older age, female sex, current smoking, type 2 diabetes, higher body size, urinary albumin/creatinine ratio of ≥3 mg/mmol. After adjustment for these, U-TXM was statistically significantly associated with SVE-R and major bleed but not cancer [hazard ratios per 1 SD higher log U-TXM (95% confidence interval): 1.09 (1.00-1.18), 1.16 (1.01-1.34), and 1.06 (0.98-1.14)]. The hazard ratio was similar to that implied by the clinical effects of randomization to aspirin for SVE-R but not for major bleed. The U-TXM was log-linearly independently associated with SVE-R in diabetes. This is consistent with the role of platelet-derived TXA2 in the first clinical overt presentation of major cardiovascular complications.
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