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

Molvin, John LU ; Jujic, Amra LU ; Melander, Olle LU orcid ; Pareek, Manan ; Råstam, Lennart LU ; Lindblad, Ulf LU ; Daka, Bledar ; Leosdottir, Margret LU ; Nilsson, Peter LU and Olsen, Michael , et al. (2020) In Open Heart 7(1).
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
atrial fibrillation, matrix metalloproteinase-2, NT-proBNP, osteopontin
in
Open Heart
volume
7
issue
1
article number
e001190
publisher
BMJ Publishing Group
external identifiers
  • scopus:85082126520
  • pmid:32201587
ISSN
2398-595X
DOI
10.1136/openhrt-2019-001190
language
English
LU publication?
yes
id
68742fff-4f08-41e0-85a7-cae582b5137f
date added to LUP
2020-03-31 13:03:34
date last changed
2024-06-26 12:55:01
@article{68742fff-4f08-41e0-85a7-cae582b5137f,
  abstract     = {{<p>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.</p>}},
  author       = {{Molvin, John and Jujic, Amra and Melander, Olle and Pareek, Manan and Råstam, Lennart and Lindblad, Ulf and Daka, Bledar and Leosdottir, Margret and Nilsson, Peter and Olsen, Michael and Magnusson, Martin}},
  issn         = {{2398-595X}},
  keywords     = {{atrial fibrillation; matrix metalloproteinase-2; NT-proBNP; osteopontin}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{1}},
  publisher    = {{BMJ Publishing Group}},
  series       = {{Open Heart}},
  title        = {{Exploration of pathophysiological pathways for incident atrial fibrillation using a multiplex proteomic chip}},
  url          = {{http://dx.doi.org/10.1136/openhrt-2019-001190}},
  doi          = {{10.1136/openhrt-2019-001190}},
  volume       = {{7}},
  year         = {{2020}},
}