Different circulating biomarkers in women and men with paroxysmal atrial fibrillation: results from the AF-RISK and RACE V studies

Ruben R De With; Vicente Artola Arita; Bao-Oanh Nguyen; Dominik Linz; Hugo Ten Cate; Henri Spronk; Ulrich Schotten; Anton Jan van Zonneveld; Ömer Erküner; M Agustina Bayón; Anders S Schmidt; Justin G L M Luermans; Harry J G M Crijns; Isabelle C Van Gelder; Michiel Rienstra

doi:10.1093/europace/euab179

Different circulating biomarkers in women and men with paroxysmal atrial fibrillation: results from the AF-RISK and RACE V studies

Ruben R De With, Vicente Artola Arita, Bao-Oanh Nguyen, Dominik Linz, Hugo Ten Cate, Henri Spronk, Ulrich Schotten, Anton Jan van Zonneveld, Ömer Erküner, M Agustina Bayón, Anders S Schmidt, Justin G L M Luermans, Harry J G M Crijns, Isabelle C Van Gelder, Michiel Rienstra^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

8 Citations (Web of Science)

Abstract

AIMS: The clinical risk profile of atrial fibrillation (AF) patients is different in men and women. Our aim was to identify sex differences in blood biomarkers in patients with paroxysmal AF.

METHODS AND RESULTS: Sex differences in 92 blood biomarkers were measured in 364 patients included in our discovery cohort, the identification of a risk profile to guide atrial fibrillation therapy (AF-RISK) study, assessed by multivariable logistic regression and enrichment pathway analysis. Findings were subsequently confirmed in 213 patients included in our validation cohort, the Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) study. In the discovery cohort, mean age was 59 ± 12 years, 41% were women. CHA2DS2-VASc-score was 1.6 ± 1.4. A total of 46% had hypertension, 10% diabetes, and 50% had heart failure, predominantly with preserved ejection fraction (47%). In women, activated leucocyte cell adhesion molecule (ALCAM) and fatty acid binding protein-4 (FABP-4) were higher. In men, matrix metalloproteinase-3 (MMP-3), C-C motif chemokine-16 (CCL-16), and myoglobin were higher. In the validation cohort, four out of five biomarkers could be confirmed: levels of ALCAM (P = 1.73 × 10-4) and FABP-4 (P = 2.46 × 10-7) and adhesion biological pathways [false discovery rate (FDR) = 1.23 × 10-8] were higher in women. In men, levels of MMP-3 (P = 4.31 × 10-8) and myoglobin (P = 2.10 × 10-4) and markers for extracellular matrix degradation biological pathways (FDR = 3.59 × 10-9) were higher.

CONCLUSION: In women with paroxysmal AF, inflammatory biomarkers were more often higher, while in men with paroxysmal AF, biomarkers for vascular remodelling were higher. Our data support the clinical notion that pathophysiological mechanisms in women and men with AF may differ.

TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01510210 for AF-RISK; Clinicaltrials.gov NCT02726698 for RACE V.

Original language	English
Pages (from-to)	193-201
Number of pages	9
Journal	EP Europace
Volume	24
Issue number	2
Early online date	30 Jul 2021
DOIs	https://doi.org/10.1093/europace/euab179
Publication status	Published - 2 Feb 2022

Keywords

Atrial fibrillation
Blood biomarkers
Sex differences
Inflammation
Vascular disease
ATHEROSCLEROSIS
PROGRESSION

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10.1093/europace/euab179Licence: CC BY-NC

Cite this

De With, R. R., Artola Arita, V., Nguyen, B-O., Linz, D., Ten Cate, H., Spronk, H., Schotten, U., van Zonneveld, A. J., Erküner, Ö., Bayón, M. A., Schmidt, A. S., Luermans, J. G. L. M., Crijns, H. J. G. M., Van Gelder, I. C., & Rienstra, M. (2022). Different circulating biomarkers in women and men with paroxysmal atrial fibrillation: results from the AF-RISK and RACE V studies. EP Europace, 24(2), 193-201. https://doi.org/10.1093/europace/euab179

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title = "Different circulating biomarkers in women and men with paroxysmal atrial fibrillation: results from the AF-RISK and RACE V studies",

abstract = "AIMS: The clinical risk profile of atrial fibrillation (AF) patients is different in men and women. Our aim was to identify sex differences in blood biomarkers in patients with paroxysmal AF.METHODS AND RESULTS: Sex differences in 92 blood biomarkers were measured in 364 patients included in our discovery cohort, the identification of a risk profile to guide atrial fibrillation therapy (AF-RISK) study, assessed by multivariable logistic regression and enrichment pathway analysis. Findings were subsequently confirmed in 213 patients included in our validation cohort, the Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) study. In the discovery cohort, mean age was 59 ± 12 years, 41% were women. CHA2DS2-VASc-score was 1.6 ± 1.4. A total of 46% had hypertension, 10% diabetes, and 50% had heart failure, predominantly with preserved ejection fraction (47%). In women, activated leucocyte cell adhesion molecule (ALCAM) and fatty acid binding protein-4 (FABP-4) were higher. In men, matrix metalloproteinase-3 (MMP-3), C-C motif chemokine-16 (CCL-16), and myoglobin were higher. In the validation cohort, four out of five biomarkers could be confirmed: levels of ALCAM (P = 1.73 × 10-4) and FABP-4 (P = 2.46 × 10-7) and adhesion biological pathways [false discovery rate (FDR) = 1.23 × 10-8] were higher in women. In men, levels of MMP-3 (P = 4.31 × 10-8) and myoglobin (P = 2.10 × 10-4) and markers for extracellular matrix degradation biological pathways (FDR = 3.59 × 10-9) were higher.CONCLUSION: In women with paroxysmal AF, inflammatory biomarkers were more often higher, while in men with paroxysmal AF, biomarkers for vascular remodelling were higher. Our data support the clinical notion that pathophysiological mechanisms in women and men with AF may differ.TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01510210 for AF-RISK; Clinicaltrials.gov NCT02726698 for RACE V.",

keywords = "Atrial fibrillation, Blood biomarkers, Sex differences, Inflammation, Vascular disease, ATHEROSCLEROSIS, PROGRESSION",

author = "{De With}, {Ruben R} and {Artola Arita}, Vicente and Bao-Oanh Nguyen and Dominik Linz and {Ten Cate}, Hugo and Henri Spronk and Ulrich Schotten and {van Zonneveld}, {Anton Jan} and {\"O}mer Erk{\"u}ner and Bay{\'o}n, {M Agustina} and Schmidt, {Anders S} and Luermans, {Justin G L M} and Crijns, {Harry J G M} and {Van Gelder}, {Isabelle C} and Michiel Rienstra",

note = "{\textcopyright} The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.",

year = "2022",

month = feb,

day = "2",

doi = "10.1093/europace/euab179",

language = "English",

volume = "24",

pages = "193--201",

journal = "EP Europace",

issn = "1099-5129",

publisher = "Oxford University Press",

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De With, RR, Artola Arita, V, Nguyen, B-O, Linz, D , Ten Cate, H , Spronk, H , Schotten, U, van Zonneveld, AJ, Erküner, Ö, Bayón, MA, Schmidt, AS, Luermans, JGLM , Crijns, HJGM, Van Gelder, IC & Rienstra, M 2022, 'Different circulating biomarkers in women and men with paroxysmal atrial fibrillation: results from the AF-RISK and RACE V studies', EP Europace, vol. 24, no. 2, pp. 193-201. https://doi.org/10.1093/europace/euab179

TY - JOUR

T1 - Different circulating biomarkers in women and men with paroxysmal atrial fibrillation

T2 - results from the AF-RISK and RACE V studies

AU - De With, Ruben R

AU - Artola Arita, Vicente

AU - Nguyen, Bao-Oanh

AU - Linz, Dominik

AU - Ten Cate, Hugo

AU - Spronk, Henri

AU - Schotten, Ulrich

AU - van Zonneveld, Anton Jan

AU - Erküner, Ömer

AU - Bayón, M Agustina

AU - Schmidt, Anders S

AU - Luermans, Justin G L M

AU - Crijns, Harry J G M

AU - Van Gelder, Isabelle C

AU - Rienstra, Michiel

PY - 2022/2/2

Y1 - 2022/2/2

N2 - AIMS: The clinical risk profile of atrial fibrillation (AF) patients is different in men and women. Our aim was to identify sex differences in blood biomarkers in patients with paroxysmal AF.METHODS AND RESULTS: Sex differences in 92 blood biomarkers were measured in 364 patients included in our discovery cohort, the identification of a risk profile to guide atrial fibrillation therapy (AF-RISK) study, assessed by multivariable logistic regression and enrichment pathway analysis. Findings were subsequently confirmed in 213 patients included in our validation cohort, the Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) study. In the discovery cohort, mean age was 59 ± 12 years, 41% were women. CHA2DS2-VASc-score was 1.6 ± 1.4. A total of 46% had hypertension, 10% diabetes, and 50% had heart failure, predominantly with preserved ejection fraction (47%). In women, activated leucocyte cell adhesion molecule (ALCAM) and fatty acid binding protein-4 (FABP-4) were higher. In men, matrix metalloproteinase-3 (MMP-3), C-C motif chemokine-16 (CCL-16), and myoglobin were higher. In the validation cohort, four out of five biomarkers could be confirmed: levels of ALCAM (P = 1.73 × 10-4) and FABP-4 (P = 2.46 × 10-7) and adhesion biological pathways [false discovery rate (FDR) = 1.23 × 10-8] were higher in women. In men, levels of MMP-3 (P = 4.31 × 10-8) and myoglobin (P = 2.10 × 10-4) and markers for extracellular matrix degradation biological pathways (FDR = 3.59 × 10-9) were higher.CONCLUSION: In women with paroxysmal AF, inflammatory biomarkers were more often higher, while in men with paroxysmal AF, biomarkers for vascular remodelling were higher. Our data support the clinical notion that pathophysiological mechanisms in women and men with AF may differ.TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01510210 for AF-RISK; Clinicaltrials.gov NCT02726698 for RACE V.

AB - AIMS: The clinical risk profile of atrial fibrillation (AF) patients is different in men and women. Our aim was to identify sex differences in blood biomarkers in patients with paroxysmal AF.METHODS AND RESULTS: Sex differences in 92 blood biomarkers were measured in 364 patients included in our discovery cohort, the identification of a risk profile to guide atrial fibrillation therapy (AF-RISK) study, assessed by multivariable logistic regression and enrichment pathway analysis. Findings were subsequently confirmed in 213 patients included in our validation cohort, the Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) study. In the discovery cohort, mean age was 59 ± 12 years, 41% were women. CHA2DS2-VASc-score was 1.6 ± 1.4. A total of 46% had hypertension, 10% diabetes, and 50% had heart failure, predominantly with preserved ejection fraction (47%). In women, activated leucocyte cell adhesion molecule (ALCAM) and fatty acid binding protein-4 (FABP-4) were higher. In men, matrix metalloproteinase-3 (MMP-3), C-C motif chemokine-16 (CCL-16), and myoglobin were higher. In the validation cohort, four out of five biomarkers could be confirmed: levels of ALCAM (P = 1.73 × 10-4) and FABP-4 (P = 2.46 × 10-7) and adhesion biological pathways [false discovery rate (FDR) = 1.23 × 10-8] were higher in women. In men, levels of MMP-3 (P = 4.31 × 10-8) and myoglobin (P = 2.10 × 10-4) and markers for extracellular matrix degradation biological pathways (FDR = 3.59 × 10-9) were higher.CONCLUSION: In women with paroxysmal AF, inflammatory biomarkers were more often higher, while in men with paroxysmal AF, biomarkers for vascular remodelling were higher. Our data support the clinical notion that pathophysiological mechanisms in women and men with AF may differ.TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01510210 for AF-RISK; Clinicaltrials.gov NCT02726698 for RACE V.

KW - Atrial fibrillation

KW - Blood biomarkers

KW - Sex differences

KW - Inflammation

KW - Vascular disease

KW - ATHEROSCLEROSIS

KW - PROGRESSION

U2 - 10.1093/europace/euab179

DO - 10.1093/europace/euab179

M3 - Article

C2 - 34329401

SN - 1099-5129

VL - 24

SP - 193

EP - 201

JO - EP Europace

JF - EP Europace

IS - 2

ER -