目的:活化血小板释放的血栓烷(TX)A2,在动脉粥样硬化血栓形成中起重要作用。尿11-dehyro-TXB2(U-TXM),反映全身TXA2生物合成的稳定代谢物,每日低剂量阿司匹林减少了70%。U-TXM代表体内血小板活化的非侵入性生物标志物,并在糖尿病患者中得到增强。这项研究评估了U-TXM是否与未来严重血管事件或血运重建(SVE-R)的风险相关。大出血,或糖尿病患者的癌症。
方法:在5948名1型或2型糖尿病且无心血管疾病的患者中,将U-TXM随机分为阿司匹林或安慰剂,在ASCEND试验中。日志U-TXM和SVE-R之间的关联(n=618),主要出血(n=206),和癌症(n=700)在6.6年的随访期间通过Cox回归进行了调查;比较了这些关联与随机服用阿司匹林的影响.
结果:较高的U-TXM与年龄较大有关,女性性别,目前吸烟,2型糖尿病,更高的身体尺寸,尿白蛋白/肌酐比值≥3mg/mmol,和更高的估计肾小球滤过率。在调整这些之后,U-TXM在统计学上与SVE-R和主要出血相关,但与癌症无关[每1SD的风险比更高的logU-TXM(95%置信区间):1.09(1.00-1.18),1.16(1.01-1.34),和1.06(0.98-1.14)]。风险比与随机分配给阿司匹林治疗SVE-R的临床效果所暗示的风险比相似,但与严重出血无关。
结论:在糖尿病患者中,U-TXM与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。
OBJECTIVE: 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.