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

Author:

Molvin JohnORCID,Jujic AmraORCID,Melander Olle,Pareek Manan,Råstam Lennart,Lindblad Ulf,Daka Bledar,Leosdottir Margret,Nilsson Peter,Olsen Michael,Magnusson MartinORCID

Abstract

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.

Funder

Hulda and Conrad Mossfelt Foundation

Kockska foundation

Crafoordska Stiftelsen

Research Funds of Region Skåne

Hjärt-Lungfonden

Lund University Medical Faculty Foundation

Ernhold Lundstroms Research Foundation

Wallenberg Centre for Molecular Medicine

Region Skåne

the Southwest Skåne's Diabetes Foundation

Skånes universitetssjukhus

Publisher

BMJ

Subject

Cardiology and Cardiovascular Medicine

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