Exploration of pathophysiological pathways for incident atrial fibrillation using a multiplex proteomic chip
ObjectiveAtrial 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.MethodsPlasma samples from 1694 individuals fro...
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doaj-a8a6f6abd77f401a8df47c7c92ab0bd42020-12-14T14:46:18ZengBMJ Publishing GroupOpen Heart2053-36242020-06-017110.1136/openhrt-2019-001190Exploration of pathophysiological pathways for incident atrial fibrillation using a multiplex proteomic chipManan PareekJohn MolvinAmra JujicMartin MagnussonLennart Råstam0Ulf Lindblad1Bledar Daka2Margret Leosdottir3Peter Nilsson4Michael Olsen5Department of Clinical Sciences, Lund University, Clinical Research Center, Malmö, SwedenDepartment of Public Health and Community Medicine, Sahlgrenska Academy, Goteborg, SwedenDepartment of Public Health and Community Medicine, Sahlgrenska Academy, Goteborg, SwedenDepartment of Clinical Sciences, Lund University, Clinical Research Center, Malmö, SwedenDepartment of Clinical Sciences, Lund University, Clinical Research Center, Malmö, SwedenCentre for Individualized Medicine in Arterial Diseases, University of Southern Denmark, Odense, DenmarkObjectiveAtrial 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.MethodsPlasma 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.ResultsMultivariable 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.ConclusionIn 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.https://openheart.bmj.com/content/7/1/e001190.full |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Manan Pareek John Molvin Amra Jujic Martin Magnusson Lennart Råstam Ulf Lindblad Bledar Daka Margret Leosdottir Peter Nilsson Michael Olsen |
spellingShingle |
Manan Pareek John Molvin Amra Jujic Martin Magnusson Lennart Råstam Ulf Lindblad Bledar Daka Margret Leosdottir Peter Nilsson Michael Olsen Exploration of pathophysiological pathways for incident atrial fibrillation using a multiplex proteomic chip Open Heart |
author_facet |
Manan Pareek John Molvin Amra Jujic Martin Magnusson Lennart Råstam Ulf Lindblad Bledar Daka Margret Leosdottir Peter Nilsson Michael Olsen |
author_sort |
Manan Pareek |
title |
Exploration of pathophysiological pathways for incident atrial fibrillation using a multiplex proteomic chip |
title_short |
Exploration of pathophysiological pathways for incident atrial fibrillation using a multiplex proteomic chip |
title_full |
Exploration of pathophysiological pathways for incident atrial fibrillation using a multiplex proteomic chip |
title_fullStr |
Exploration of pathophysiological pathways for incident atrial fibrillation using a multiplex proteomic chip |
title_full_unstemmed |
Exploration of pathophysiological pathways for incident atrial fibrillation using a multiplex proteomic chip |
title_sort |
exploration of pathophysiological pathways for incident atrial fibrillation using a multiplex proteomic chip |
publisher |
BMJ Publishing Group |
series |
Open Heart |
issn |
2053-3624 |
publishDate |
2020-06-01 |
description |
ObjectiveAtrial 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.MethodsPlasma 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.ResultsMultivariable 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.ConclusionIn 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. |
url |
https://openheart.bmj.com/content/7/1/e001190.full |
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