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dc.contributor.authorBarton, Bruce A
dc.contributor.authorKronsberg, Shari S
dc.contributor.authorHariri, Essa
dc.contributor.authorVasan, Ramachandran S
dc.contributor.authorRade, Grace A
dc.contributor.authorXanthakis, Vanessa
dc.contributor.authorKickler, Thomas S
dc.contributor.authorRade, Jeffrey J
dc.date.accessioned2024-03-26T13:30:36Z
dc.date.available2024-03-26T13:30:36Z
dc.date.issued2024-02-28
dc.identifier.citationBarton BA, Kronsberg SS, Hariri E, Vasan RS, Rade GA, Xanthakis V, Kickler TS, Rade JJ. Adjustment for Renal Function Improves the Prognostic Performance of Urinary Thromboxane Metabolites. Clin Chem. 2024 Feb 28:hvae015. doi: 10.1093/clinchem/hvae015. Epub ahead of print. PMID: 38416712.en_US
dc.identifier.eissn1530-8561
dc.identifier.doi10.1093/clinchem/hvae015en_US
dc.identifier.pmid38416712
dc.identifier.urihttp://hdl.handle.net/20.500.14038/53217
dc.description.abstractBackground: Systemic thromboxane A2 generation, assessed by quantifying the concentration of stable thromboxane B2 metabolites (TXB2-M) in the urine adjusted for urinary creatinine, is strongly associated with mortality risk. We sought to define optimal TXB2-M cutpoints for aspirin users and nonusers and determine if adjusting TXB2-M for estimated glomerular filtration rate (eGFR) in addition to urinary creatinine improved mortality risk assessment. Methods: Urinary TXB2-M were measured by competitive ELISA in 1363 aspirin users and 1681 nonusers participating in the Framingham Heart Study. Cutpoints were determined for TXB2-M and TXB2-M/eGFR using log-rank statistics and used to assess mortality risk by Cox proportional hazard modeling and restricted mean survival time. Multivariable models were compared using the Akaike Information Criterion (AIC). A cohort of 105 aspirin users with heart failure was used for external validation. Results: Optimized cutpoints of TXB2-M were 1291 and 5609 pg/mg creatinine and of TXB2-M/eGFR were 16.6 and 62.1 filtered prostanoid units (defined as pg·min/creatinine·mL·1.73 m2), for aspirin users and nonusers, respectively. TXB2-M/eGFR cutpoints provided more robust all-cause mortality risk discrimination than TXB2-M cutpoints, with a larger unadjusted hazard ratio (2.88 vs 2.16, AIC P < 0.0001) and greater differences in restricted mean survival time between exposure groups (1.46 vs 1.10 years), findings that were confirmed in the external validation cohort of aspirin users. TXB2-M/eGFR cutpoints also provided better cardiovascular/stroke mortality risk discrimination than TXB2-M cutpoints (unadjusted hazard ratio 3.31 vs 2.13, AIC P < 0.0001). Conclusion: Adjustment for eGFR strengthens the association of urinary TXB2-M with long-term mortality risk irrespective of aspirin use.en_US
dc.language.isoenen_US
dc.relation.ispartofClinical Chemistryen_US
dc.relation.urlhttps://doi.org/10.1093/clinchem/hvae015en_US
dc.rights© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.en_US
dc.titleAdjustment for Renal Function Improves the Prognostic Performance of Urinary Thromboxane Metabolitesen_US
dc.typeJournal Articleen_US
dc.source.journaltitleClinical chemistry
dc.source.countryEngland
dc.identifier.journalClinical chemistry
dc.contributor.departmentBiostatistics and Health Services Researchen_US
dc.contributor.departmentPopulation and Quantitative Health Sciencesen_US


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