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AuthorPetrucci, Giovanna
AuthorBuck, Georgina A.
AuthorRocca, Bianca
AuthorParish, Sarah
AuthorBaigent, Colin
AuthorHatem, Duaa
AuthorMafham, Marion
AuthorHabib, Aida
AuthorBowman, Louise
AuthorArmitage, Jane
AuthorPatrono, Carlo
Available date2024-04-29T07:27:53Z
Publication Date2024-02-22
Publication NameEuropean Heart Journal
Identifierhttp://dx.doi.org/10.1093/eurheartj/ehad868
CitationPetrucci, G., Buck, G. A., Rocca, B., Parish, S., Baigent, C., Hatem, D., ... & Patrono, C. (2024). Thromboxane biosynthesis and future events in diabetes: the ASCEND trial. European Heart Journal, ehad868.
ISSN0195-668X
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85190549103&origin=inward
URIhttp://hdl.handle.net/10576/54423
AbstractBackground and Thromboxane (TX) A2, released by activated platelets, plays an important role in atherothrombosis. Urinary 11-dehydro-Aims 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.
Languageen
PublisherOxford University Press
SubjectDaily low-dose aspirin
Diabetes
Platelet activation
Randomized placebo-controlled trial
Urinary 11-dehydro-thromboxane B 2
TitleThromboxane biosynthesis and future events in diabetes: the ASCEND trial
TypeArticle
Issue Number15
Volume Number45
ESSN1522-9645
dc.accessType Open Access


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