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Association of Thromboxane Generation With Survival in Aspirin Users and Nonusers
Journal of the American College of Cardiology ( IF 24.0 ) Pub Date : 2022-06-01 , DOI: 10.1016/j.jacc.2022.04.034
Jeffrey J Rade 1 , Bruce A Barton 2 , Ramachandran S Vasan 3 , Shari S Kronsberg 2 , Vanessa Xanthakis 3 , John F Keaney 4 , Naomi M Hamburg 3 , Nikolaos Kakouros 2 , Thomas A Kickler 5
Affiliation  

Background

Persistent systemic thromboxane generation, predominantly from nonplatelet sources, in aspirin (ASA) users with cardiovascular disease (CVD) is a mortality risk factor.

Objectives

This study sought to determine the mortality risk associated with systemic thromboxane generation in an unselected population irrespective of ASA use.

Methods

Stable thromboxane B2 metabolites (TXB2-M) were measured by enzyme-linked immunosorbent assay in banked urine from 3,044 participants (mean age 66 ± 9 years, 53.8% women) in the Framingham Heart Study. The association of TXB2-M to survival over a median observation period of 11.9 years (IQR: 10.6-12.7 years) was determined by multivariable modeling.

Results

In 1,363 (44.8%) participants taking ASA at the index examination, median TXB2-M were lower than in ASA nonusers (1,147 pg/mg creatinine vs 4,179 pg/mg creatinine; P < 0.0001). TXB2-M were 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 TXB2-M in the highest quartile based on ASA use compared with 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 2,353 participants without CVD, TXB2-M were associated with cardiovascular mortality in ASA nonusers (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 TXB2-M.

Conclusions

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 therapy modification, particularly in those without CVD.



中文翻译:

阿司匹林使用者和非使用者中血栓素生成与生存的关联

背景

在患有心血管疾病 (CVD) 的阿司匹林 (ASA) 使用者中,主要来自非血小板来源的持续全身血栓素生成是死亡风险因素。

目标

本研究旨在确定与未选择的人群中全身血栓素生成相关的死亡风险,无论是否使用 ASA。

方法

弗雷明汉心脏研究中的 3,044 名参与者(平均年龄 66 ± 9 岁,53.8% 为女性)通过酶联免疫吸附试验测定了稳定的血栓素 B 2代谢物 (TXB 2 -M)。通过多变量模型确定TXB 2 -M 与中位观察期 11.9 年(IQR:10.6-12.7 年)的生存率的关联。

结果

在指数检查中服用 ASA 的 1,363 名 (44.8%) 参与者中,中位 TXB 2 -M 低于未使用 ASA 的参与者(1,147 pg/mg 肌酐对比 4,179 pg/mg 肌酐;P < 0.0001)。TXB 2 -M 与全因死亡率和心血管死亡率显着相关,与 ASA 使用无关(HR:分别为 1.96 和 2.41;两者的P < 0.0001)对于 TXB 2 -M 在 ASA 使用的最高四分位数中与较低四分位数相比,并且在调整了年龄相近的个体的死亡风险因素后仍然显着(HR:分别为 1.49 和 1.82;两者的P  ≤ 0.005)。在 2,353 名没有 CVD 的参与者中,TXB 2-M 与 ASA 非使用者的心血管死亡率相关(调整后的 HR:3.04;95% CI:1.29-7.16),但与 ASA 使用者无关,而 ASA 的使用与低(调整后的 HR:1.46; 95% CI:1.14-1.87)但 TXB 2 -M 没有升高。

结论

全身性血栓素生成是全因死亡率和心血管死亡率的独立危险因素,与使用 ASA 无关,其测量值可能有助于治疗调整,尤其是在没有 CVD 的患者中。

更新日期:2022-06-01
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