Asymmetric and Symmetric Dimethylarginine Predict Outcomes in Patients With Atrial Fibrillation An ARISTOTLE Substudy

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F18%3A10377569" target="_blank" >RIV/00064203:_____/18:10377569 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1016/j.jacc.2018.05.058" target="_blank" >https://doi.org/10.1016/j.jacc.2018.05.058</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jacc.2018.05.058" target="_blank" >10.1016/j.jacc.2018.05.058</a>

Result language

angličtina

Original language name

Asymmetric and Symmetric Dimethylarginine Predict Outcomes in Patients With Atrial Fibrillation An ARISTOTLE Substudy

Original language description

BACKGROUND There is little mechanistic information on factors predisposing atrial fibrillation (AF) patients to thromboembolism or bleeding, but generation of nitric oxide (NO) might theoretically contribute to both. OBJECTIVES The authors tested the hypothesis that plasma levels of the methylated arginine derivatives asymmetric and symmetric dimethylarginine (ADMA/SDMA), which inhibit NO generation, might be associated with outcomes in AF. METHODS Plasma samples were obtained from 5,004 patients with AF at randomization to warfarin or apixaban in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. ADMA and SDMA concentrations were measured by high-performance liquid chromatography. Relationships to clinical characteristics were evaluated by multivariable analyses. Associations with major outcomes, during a median of 1.9 years follow-up, were evaluated by adjusted Cox proportional hazards models. RESULTS Both ADMA and SDMA plasma concentrations at study entry increased significantly with patients&apos; age, female sex, renal impairment, permanent AF, or congestive heart failure. ADMA and SDMA increased (p &lt; 0.001) with both increased CHA2DS2-VASc and HAS-BLED scores, but decreased in the presence of diabetes. On multivariable analysis adjusting for established risk factors and treatment, tertile groups of ADMA concentrations were significantly associated with stroke/systemic embolism (p = 0.034), and death (p &lt; 0.0001), whereas tertile groups of SDMA were associated with major bleeding and death (p &lt; 0.001 for both). Incorporating ADMA and SDMA into CHA2DS2-VASc or HAS-BLED predictive models improved C-indices for those outcomes. Neither ADMA nor SDMA predicted differential responses to warfarin or apixaban. CONCLUSIONS In anticoagulated patients with AF, elevated ADMA levels are weakly associated with thromboembolic events, elevated SDMA levels with bleeding events and both are strongly associated with increased mortality. These findings suggest that disturbances of NO function modulate both thrombotic and hemorrhagic risk in anticoagulated patients with AF. (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]; NCT00412984) (c) 2018 Published by Elsevier on behalf of the American College of Cardiology Foundation.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30201 - Cardiac and Cardiovascular systems

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of the American College of Cardiology

ISSN

0735-1097

e-ISSN

—

Volume of the periodical

72

Issue of the periodical within the volume

7

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

721-733

UT code for WoS article

000440783900003

EID of the result in the Scopus database

2-s2.0-85050654810