Nonplatelet thromboxane generation is associated with impaired cardiovascular performance and mortality in heart failure.

التفاصيل البيبلوغرافية
العنوان:	Nonplatelet thromboxane generation is associated with impaired cardiovascular performance and mortality in heart failure.
المؤلفون:	Hariri E; Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, Massachusetts.; Department of Medicine, Cleveland Clinic Foundation, Cleveland, Ohio., Kakouros N; Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, Massachusetts., Bunsick DA; Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, Massachusetts., Russell SD; Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland., Mudd JO; Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland., Laws K; Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland., Lake MW; Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland., Rade JJ; Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, Massachusetts.; Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland.
المصدر:	American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2022 Jul 01; Vol. 323 (1), pp. H248-H255. Date of Electronic Publication: 2022 Jun 17.
نوع المنشور:	Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة:	English
بيانات الدورية:	Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901228 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1539 (Electronic) Linking ISSN: 03636135 NLM ISO Abbreviation: Am J Physiol Heart Circ Physiol Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Bethesda, Md. : American Physiological Society,
مواضيع طبية MeSH:	Heart Failure/diagnosis , Ventricular Function, Left, Humans ; Stroke Volume ; Thromboxane B2/urine ; Thromboxanes
مستخلص:	Nonplatelet thromboxane generation, stimulated largely by oxidative stress, is a novel mortality risk factor in individuals with coronary artery disease. Though inversely associated with left ventricular ejection fraction (LVEF), a potential role in the pathobiology of heart failure (HF) remains poorly defined. Nonplatelet thromboxane generation and oxidative stress were assessed by measuring urine thromboxane-B 2 metabolites (TXB 2 -M) and 8-isoPGF 2α by ELISA in 105 subjects taking aspirin and undergoing right heart catheterization for evaluation of HF, valve disease, or after transplantation. Multivariable logistic regression and survival analyses were used to define associations of TXB 2 -M to invasive measures of cardiovascular performance and 4-year clinical outcomes. TXB 2 -M was elevated (>1,500 pg/mg creatinine) in 46% of subjects and correlated with HF severity by New York Heart Association (NYHA) functional class and brain natriuretic peptide level, modestly with LVEF, but not with HF etiology. There was no association of oxidative stress to HF type or etiology but a trend with NYHA functional class. Multiple invasive hemodynamic parameters independently associated with TXB 2 -M after adjustment for oxidative stress, age, sex, and race with pulmonary effective arterial elastance ( E a pulmonary ), reflective of right ventricular afterload, being the most robust on hierarchical analysis. Similar to E a pulmonary , elevated urinary TXB 2 -M is associated with increased risk of death (adjusted HR = 2.15, P = 0.037) and a combination of death, transplant, or mechanical support initiation (adjusted HR = 2.0, P = 0.042). Nonplatelet TXA 2 thromboxane generation is independently associated with HF severity reflected by invasive measures of cardiovascular performance, particularly right ventricular afterload, and independently predicted long-term mortality risk. NEW & NOTEWORTHY Nonplatelet thromboxane generation in heart failure is independently associated with risk of death, transplant, or need for mechanical support. Measurement of urine thromboxane metabolites using a clinically available assay may be a useful surrogate for invasive measurement of cardiovascular hemodynamics and performance that could provide prognostic information and facilitate tailoring of therapy in patients with heart failure. Inhibiting thromboxane generation or its biological effects is a potential strategy for improving cardiovascular performance and outcomes in heart failure.
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معلومات مُعتمدة:	TL1 TR001454 United States TR NCATS NIH HHS
فهرسة مساهمة:	Keywords: heart failure; hemodynamics; outcome; thromboxane
سلسلة جزيئية:	figshare 10.6084/m9.figshare.20052125.v1
المشرفين على المادة:	0 (Thromboxanes) 54397-85-2 (Thromboxane B2)
تواريخ الأحداث:	Date Created: 20220617 Date Completed: 20220711 Latest Revision: 20230703
رمز التحديث:	20240628
مُعرف محوري في PubMed:	PMC9273282
DOI:	10.1152/ajpheart.00212.2022
PMID:	35714178
قاعدة البيانات:	MEDLINE

الوصف
تدمد:	1522-1539
DOI:	10.1152/ajpheart.00212.2022