uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
N-Terminal Pro-B-Type Natriuretic Peptide for Risk Assessment in Patients With Atrial Fibrillation: Insights from the ARISTOTLE trial
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
Show others and affiliations
2013 (English)In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 61, no 22, 2274-2284 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE:

This study sought to assess the prognostic value of N-terminal pro–B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF) enrolled in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial, and the treatment effect of apixaban according to NT-proBNP levels.

BACKGROUND:

Natriuretic peptides are associated with mortality and cardiovascular events in several cardiac diseases.

METHODS:

In the ARISTOTLE trial, 18,201 patients with AF were randomized to apixaban or warfarin. Plasma samples at randomization were available from 14,892 patients. The association between NT-proBNP concentrations and clinical outcomes was evaluated using Cox proportional hazard models, after adjusting for established cardiovascular risk factors.

RESULTS:

Quartiles of NT-proBNP were Q1:≤363, Q2:364-713, Q3:714-1250 and Q4:>1250 ng/L. During 1.8 years the annual rates of stroke or systemic embolism ranged from 0.74% in the bottom NT-proBNP quartile to 2.21% in the top quartile, adjusted hazard ratio (HR) 2.35 (95% CI 1.62-3.40, p<0.0001. Annual rates of cardiac death ranged from 0.86% in Q1 to 4.14% in Q4, adjusted HR 2.50 (1.81-3.45), p<0.0001. Adding NT-proBNP levels to the CHA2DS2VASc score improved C-statistics from 0.62 to 0.65 (p=0.0009) for stroke or systemic embolism and from 0.59 to 0.69 for cardiac death (p<0.0001). Apixaban reduced stroke, mortality, and bleeding regardless of the NT-proBNP level.

CONCLUSIONS:

NT-proBNP levels are often elevated in AF and independently associated with an increased risk of stroke and mortality. NT-proBNP improves risk stratification beyond the CHA2DS2VASc score and might be a novel tool for improved stroke prediction in AF. The efficacy of apixaban compared with warfarin is independent of the NT-proBNP level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE].

Place, publisher, year, edition, pages
2013. Vol. 61, no 22, 2274-2284 p.
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-198153DOI: 10.1016/j.jacc.2012.11.082ISI: 000320600700008PubMedID: 23563134OAI: oai:DiVA.org:uu-198153DiVA: diva2:615323
Available from: 2013-04-09 Created: 2013-04-09 Last updated: 2017-12-06Bibliographically approved
In thesis
1. New Risk Markers in Atrial Fibrillation
Open this publication in new window or tab >>New Risk Markers in Atrial Fibrillation
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Atrial fibrillation (AF) confers an independent increased risk of stroke and death. The stroke risk is very heterogeneous and current risk stratification models based on clinical variables, such as the CHADS2 and CHA2DS2VASc score, only offer a modest discriminating value.

The aims of this thesis were to study cardiac biomarkers, cardiac troponin and natriuretic peptides e.g. N-terminal prohormone-B-type natriuretic peptide (NT-proBNP), and describe levels in AF patients, investigate the association with stroke or systemic embolism, cardiovascular event, major bleeding and mortality, and to assess how levels of cardiac biomarkers change over time. Cardiac troponin was analyzed with contemporary assays and high sensitivity assays. The study populations consisted of patients with atrial fibrillation and one risk factor for stroke included in the RE-LY (n=6189) and the ARISTOTLE (n=14892) biomarker substudies. Median follow-up time was 2.2 years and 1.9 years, respectively. In a subset of participants (n=2514) data from repeated measurements was available at three months.

Cardiac troponin was detectable in 57.0% with the contemporary assay and 99.4% with the high sensitivity assay. NT-proBNP was elevated in approximately three quarters of the participants. In Cox models adjusted for established risk factors the cardiac biomarkers levels was independently associated with stroke or systemic embolism, cardiovascular events, and mortality. Only cardiac troponin was associated with major bleeding. In ROC analyses the prediction of stroke or systemic embolism, cardiovascular events, and mortality increased significantly by addition of cardiac troponin or NT-proBNP to the models. Persistent detectable cardiac troponin (contemporary assay) and elevated NT-proBNP levels were found in a large number of participants. Persistent detectable or elevated levels conferred significantly higher risk for stroke or systemic embolism, cardiovascular events, and mortality. By using both cardiac biomarkers simultaneously the risk stratification improved even further for all outcomes.

In conclusion the analyses for the first time display that elevation of troponin I and NT-proBNP are common in patients with AF and independently related to increased risks of stroke, cardiovascular events and mortality. Persistent elevation of troponin and NT-proBNP indicate a worse prognosis than transient elevations or no elevations of either marker. The cardiac biomarkers added substantial improvements to existing risk stratification models.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 76 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 906
Keyword
atrial fibrillation, stroke risk, cardiac biomarkers, troponin, natriuretic peptides, NT-proBNP, risk stratification
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:uu:diva-198833 (URN)978-91-554-8680-8 (ISBN)
Public defence
2013-06-13, Ebba Enghoffsalen, Ingång 50, bv. Akademiska Sjukhuset, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2013-05-21 Created: 2013-04-25 Last updated: 2013-08-30Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Hijazi, ZiadWallentin, LarsSiegbahn, AgnetaAndersson, UlrikaChristersson, Christina

Search in DiVA

By author/editor
Hijazi, ZiadWallentin, LarsSiegbahn, AgnetaAndersson, UlrikaChristersson, Christina
By organisation
UCR-Uppsala Clinical Research CenterCardiologyClinical ChemistryDepartment of Medical Sciences
In the same journal
Journal of the American College of Cardiology
Cardiac and Cardiovascular Systems

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 383 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf