Background and Aims Thromboxane (TX) A2, released by activated platelets, plays an important role in atherothrombosis. Urinary 11-dehydro-TXB2 (U-TXM), a stable metabolite reflecting the whole-body TXA2 biosynthesis, is reduced by ∼70% by daily low-dose aspirin. The U-TXM represents a non-invasive biomarker of in vivo platelet activation and is enhanced in patients with diabetes. 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. Methods The U-TXM was measured pre-randomization to aspirin or placebo in 5948 people with type 1 or 2 diabetes and no cardiovascular disease, in the ASCEND trial. Associations between log U-TXM and SVE-R (n = 618), major bleed (n = 206), and cancer (n = 700) during 6.6 years of follow-up were investigated by Cox regression; comparisons of these associations with the effects of randomization to aspirin were made. Results 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, and higher estimated glomerular filtration rate. After adjustment for these, U-TXM was marginally 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. Conclusions The U-TXM was log-linearly independently associated with SVE-R in diabetes. This is consistent with the involvement of platelet TXA2 in diabetic atherothrombosis.

中文翻译：

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糖尿病中的血栓素生物合成和未来事件：ASCEND 试验

背景和目的 活化血小板释放的血栓素 (TX) A2 在动脉粥样硬化血栓形成中发挥重要作用。尿液中的 11-脱氢-TXB2 (U-TXM) 是一种反映全身 TXA2 生物合成的稳定代谢物，每天服用小剂量阿司匹林可减少约 70%。U-TXM 代表体内血小板活化的非侵入性生物标志物，并且在糖尿病患者中增强。本研究评估了 U-TXM 是否与糖尿病患者未来发生严重血管事件或血运重建 (SVE-R)、大出血或癌症的风险相关。方法 在 ASCEND 试验中，对 5948 名患有 1 型或 2 型糖尿病且无心血管疾病的患者进行随机分组前测量阿司匹林或安慰剂的 U-TXM。在 6.6 年的随访期间，通过 Cox 回归研究了 log U-TXM 与 SVE-R (n = 618)、大出血 (n = 206) 和癌症 (n = 700) 之间的关联；对这些关联与阿司匹林随机化的影响进行了比较。结果 U-TXM 较高与年龄较大、女性、当前吸烟、2 型糖尿病、体型较大、尿白蛋白/肌酐比率≥3 mg/mmol 以及较高的估计肾小球滤过率相关。对这些进行调整后，U-TXM 与 SVE-R 和大出血有轻微的统计显着相关性，但与癌症无关[每 1 SD 高 log U-TXM 的风险比（95% 置信区间）：1.09 (1.00–1.18)、1.16 ( 1.01–1.34）和1.06（0.98–1.14）]。风险比与随机分配阿司匹林治疗 SVE-R 的临床效果相似，但对于大出血则不然。结论 U-TXM 与糖尿病中的 SVE-R 呈对数线性独立相关。这与血小板 TXA2 参与糖尿病动脉粥样硬化血栓形成是一致的。