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Using multimarker s...
Using multimarker screening to identify biomarkers associated with cardiovascular death in patients with atrial fibrillation.
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- Pol, Tymon (författare)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi
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- Hijazi, Ziad (författare)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi
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- Lindbäck, Johan (författare)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Institutionen för medicinska vetenskaper
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- Oldgren, Jonas, 1964- (författare)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi
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Alexander, John H (författare)
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Connolly, Stuart J (författare)
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Eikelboom, John W (författare)
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Ezekowitz, Michael D (författare)
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Granger, Christopher B (författare)
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Lopes, Renato D (författare)
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Yusuf, Salim (författare)
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- Siegbahn, Agneta, 1947- (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Uppsala kliniska forskningscentrum (UCR),UCR
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- Wallentin, Lars, 1943- (författare)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Institutionen för medicinska vetenskaper
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(creator_code:org_t)
- 2021-08-06
- 2021
- Engelska.
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Ingår i: Cardiovascular Research. - : Oxford University Press. - 0008-6363 .- 1755-3245. ; 118:9, s. 2112-2123
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- AIMS: Atrial fibrillation (AF) is associated with higher mortality. Biomarkers may improve the understanding of key pathophysiologic processes in AF that lead to death. Using a new multiplex analytic technique, we explored the association between 268 biomarkers and cardiovascular (CV) death in anticoagulated patients with AF.METHODS AND RESULTS: A case-cohort design with 1.8 -1.9 years follow-up. The identification cohort included 517 cases and 4057 randomly selected patients from ARISTOTLE. The validation cohort included 277 cases and 1042 randomly selected controls from RE-LY. Plasma collected at randomization was analyzed with conventional immunoassays and the OLINK proximity extension assay-panels; CVDII, CVDIII, and Inflammation. Association between biomarkers and CV-death was evaluated using Random Survival Forest, Boruta and adjusted Cox-regression analyses.The biomarkers most strongly and consistently associated with CV-death were (hazard ratio for inter-quartile comparison [95% CI]): N-terminal pro-B-type natriuretic peptide (NT-proBNP; 1.63 [1.37-1.93]), cardiac troponin T (cTnT-hs; 1.60[1.35-1.88]), interleukin-6 (IL-6; 1.29[1.13-1.47]), growth differentiation factor-15 (GDF-15; 1.30[1.10-1.53]) fibroblast growth factor 23 (FGF-23; 1.21[1.10-1.33]), urokinase receptor (uPAR; 1.38[1.16-1.64]), trefoil factor 3 (TFF3; 1.27[1.10-1.46]), tumor necrosis factor receptor 1 (TNFR1; 1.21[1.01-1.45]), TNF-related apoptosis-inducing ligand receptor 2 (TRAILR2; 1.18[1.04-1.34]) and cathepsin L1 (CTSL1; 1.22[1.07-1.39]).CONCLUSION: In this comprehensive screening of 268 biomarkers in anticoagulated patients with AF the underlying mechanisms most strongly associated with CV-death were cardiorenal dysfunction (NT-proBNP, cTnT-hs, CTSL1, TFF3), oxidative stress (GDF-15), inflammation (IL-6, GDF-15), calcium balance, vascular and renal dysfunction (FGF-23), fibrinolysis (suPAR) and apoptosis (TNFR1, TRAILR2). These findings provide novel insights into pathophysiologic aspects associated with CV-death in AF.TRANSLATIONAL PERSPECTIVE: In patients with AF there is an unmet need for better understanding of the pathophysiological processes involved with CV-death. Using a targeted proteomic approach, 10 biomarkers were identified as having a strong association with CV-death. The identified biomarkers reflect several biological pathways involved with CV-death in AF. The present study provides valuable insights into important processes involved with CV-death in patients with AF and may facilitate the identification of important risk factors for death, thus allowing for earlier intervention and possibly even for targeted therapy to reduce AF-related mortality.CLINICALTRIALS.GOV IDENTIFIER: NCT00412984 and NCT00262600.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
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- Av författaren/redakt...
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Pol, Tymon
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Hijazi, Ziad
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Lindbäck, Johan
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Oldgren, Jonas, ...
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Alexander, John ...
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Connolly, Stuart ...
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visa fler...
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Eikelboom, John ...
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Ezekowitz, Micha ...
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Granger, Christo ...
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Lopes, Renato D
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Yusuf, Salim
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Siegbahn, Agneta ...
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Wallentin, Lars, ...
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kirurgi
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kardiologi
- Artiklar i publikationen
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Cardiovascular R ...
- Av lärosätet
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Uppsala universitet