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Exploration of pathophysiological pathways for incident atrial fibrillation using a multiplex proteomic chip

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

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  • John Molvin
  • Amra Jujic
  • Olle Melander
  • Manan Pareek
  • Lennart Råstam
  • Ulf Lindblad
  • Bledar Daka
  • Margret Leosdottir
  • Peter Nilsson
  • Michael Olsen
  • Martin Magnusson
Vis graf over relationer

Objective: Atrial fibrillation (AF) is the most common arrhythmia and associated with increased morbidity and mortality. Its increasing prevalence calls for novel biomarkers to identify underlying pathophysiological mechanisms as well as patients at risk.

Methods: Plasma samples from 1694 individuals from the Swedish population-based Malmö Preventive Project (mean age 69.5 years; 29.3% female; mean follow-up time 9.7±3.1 years) were analysed with the Olink proximity extension assay CVD III panel consisting of 92 proteins to identify proteins associated with incident AF or atrial flutter, referred to as incident AF. Incident cases of AF (n=278) were retrieved by linkage to the registers. Participants were followed until the first episode of AF or until censoring by death or emigration. Bonferroni-corrected multivariable Cox regression models adjusted for known risk factors were used to explore possible associations of the 92 proteins and incidence of AF.

Results: Multivariable Cox regression analyses of 11 proteins associated with incident AF (mean follow-up time 9.7±3.1 years) after Bonferroni correction confirmed N-terminal pro-B-type natriuretic peptide (HR per 1 SD increment (95% CI) 1.80 (1.58 to 2.04); p=1.2×10-19) as risk marker of incident AF. Further, matrix metalloproteinase-2 (1.22 (1.07 to 1.39); p=0.002) and osteopontin (1.27 (1.12 to 1.44); p=2.7×10-4) were associated with incident AF at follow-up independently of traditional risk markers and NT-proBNP.

Conclusion: In a general Swedish population, we confirmed the well-known association of NT-proBNP with incident AF and also identified matrix metalloproteinase-2 and osteopontin as novel risk markers for incident AF, independently of traditional risk factors and NT-proBNP.

OriginalsprogEngelsk
Artikelnummere001190
TidsskriftOpen Heart
Vol/bind7
Udgave nummer1
Sider (fra-til)e001190
ISSN2053-3624
DOI
StatusUdgivet - feb. 2020

Bibliografisk note

Funding Information:
Funding MM was supported by grants from the Wallenberg Centre for Molecular Medicine, Lund University (ALFSKANE-675271), Medical Faculty of Lund University (ALFSKANE-432021; ALFSKANE-436111), Skåne University Hospital, the Crafoord Foundation, the Ernhold Lundstroms Research Foundation, Region Skåne, the Hulda and Conrad Mossfelt Foundation, the Southwest Skåne's Diabetes Foundation, the Kockska Foundation, the Research Funds of Region Skåne and the Swedish Heart and Lung Foundation (2018-0260).

ID: 59580201