Assessment of Inflammatory Biomarkers and Incident Atrial Fibrillation in Older Adults

Background Available evidence supports the importance of inflammation in atrial fibrillation (AF) pathogenesis, yet general anti‐inflammatory therapies have failed to show benefit for prevention of the arrhythmia. Better understanding of the specific inflammatory pathways involved is necessary to ad...

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Main Authors: Sanyog G. Shitole, Susan R. Heckbert, Gregory M. Marcus, Sanjiv J. Shah, Nona Sotoodehnia, Jeremy D. Walston, Alexander P. Reiner, Russell P. Tracy, Bruce M. Psaty, Jorge R. Kizer
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.035710
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author Sanyog G. Shitole
Susan R. Heckbert
Gregory M. Marcus
Sanjiv J. Shah
Nona Sotoodehnia
Jeremy D. Walston
Alexander P. Reiner
Russell P. Tracy
Bruce M. Psaty
Jorge R. Kizer
author_facet Sanyog G. Shitole
Susan R. Heckbert
Gregory M. Marcus
Sanjiv J. Shah
Nona Sotoodehnia
Jeremy D. Walston
Alexander P. Reiner
Russell P. Tracy
Bruce M. Psaty
Jorge R. Kizer
author_sort Sanyog G. Shitole
collection DOAJ
description Background Available evidence supports the importance of inflammation in atrial fibrillation (AF) pathogenesis, yet general anti‐inflammatory therapies have failed to show benefit for prevention of the arrhythmia. Better understanding of the specific inflammatory pathways involved is necessary to advance therapeutics. Methods and Results We evaluated 9 circulating markers of inflammation measured by immunoassays and incidence of AF in a population‐based older cohort. Biomarkers included measures of general inflammation and the NLR (nucleotide‐binding oligomerization domain‐like receptor) family pyrin domain containing 3 inflammasome, TNF‐α (tumor necrosis factor α), monocyte activation markers, and sIL‐2 (soluble interleukin‐2). Among 5726 participants (median age 72 years), 1836 developed AF over median follow‐up of 11.5 years. After adjustment for conventional risk factors, 5 biomarkers were positively associated with incident AF: IL‐6 (interleukin‐6), hazard ratio (HR), 1.14 (95% CI, 1.07–1.21); hs‐CRP (high‐sensitivity C‐reactive protein), HR, 1.05 (95% CI, 1.01–1.09); white blood cell count, HR, 1.18 (95% CI, 1.04–1.35); sTNFR1 (soluble TNF receptor 1), HR, 1.21 (95% CI, 1.05–1.39); and sIL‐2Rα (sIL‐2 receptor α), HR, 1.16 (95% CI, 1.05–1.29) (all per doubling of biomarker). sCD14, sCD163, IL‐18, and IL‐1 receptor antagonist showed no association with AF. Upon concurrent adjustment for all biomarkers, only IL‐6 remained significantly associated with the arrhythmia, HR, 1.17 (95% CI, 1.07–1.26). Conclusions Among older adults, IL‐6, hs‐CRP, white blood cell count, sTNFR1, and sIL‐2Rα were positively associated with incident AF, but only IL‐6 retained significance on concurrent adjustment. These findings newly document associations for sTNFR1 and sIL‐2Rα and lend support to a preeminent role for IL‐6 in development of this arrhythmia. The efficacy of IL‐6 blockade for AF prevention awaits completion of appropriate clinical trials.
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spelling doaj-art-c6a3cf13714b4a809e65e36751beabf32024-12-17T12:51:22ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-12-01132410.1161/JAHA.124.035710Assessment of Inflammatory Biomarkers and Incident Atrial Fibrillation in Older AdultsSanyog G. Shitole0Susan R. Heckbert1Gregory M. Marcus2Sanjiv J. Shah3Nona Sotoodehnia4Jeremy D. Walston5Alexander P. Reiner6Russell P. Tracy7Bruce M. Psaty8Jorge R. Kizer9Cardiology Section San Francisco Veterans Affairs Health Care System San Francisco CA USADepartment of Epidemiology University of Washington Seattle WA USADepartment of Medicine University of California San Francisco San Francisco CA USADepartment of Medicine Northwestern University Chicago IL USADepartment of Epidemiology University of Washington Seattle WA USADepartment of Medicine Johns Hopkins University Baltimore MD USADepartment of Epidemiology University of Washington Seattle WA USADepartment of Pathology and Laboratory Medicine The University of Vermont Burlington VT USADepartment of Epidemiology University of Washington Seattle WA USACardiology Section San Francisco Veterans Affairs Health Care System San Francisco CA USABackground Available evidence supports the importance of inflammation in atrial fibrillation (AF) pathogenesis, yet general anti‐inflammatory therapies have failed to show benefit for prevention of the arrhythmia. Better understanding of the specific inflammatory pathways involved is necessary to advance therapeutics. Methods and Results We evaluated 9 circulating markers of inflammation measured by immunoassays and incidence of AF in a population‐based older cohort. Biomarkers included measures of general inflammation and the NLR (nucleotide‐binding oligomerization domain‐like receptor) family pyrin domain containing 3 inflammasome, TNF‐α (tumor necrosis factor α), monocyte activation markers, and sIL‐2 (soluble interleukin‐2). Among 5726 participants (median age 72 years), 1836 developed AF over median follow‐up of 11.5 years. After adjustment for conventional risk factors, 5 biomarkers were positively associated with incident AF: IL‐6 (interleukin‐6), hazard ratio (HR), 1.14 (95% CI, 1.07–1.21); hs‐CRP (high‐sensitivity C‐reactive protein), HR, 1.05 (95% CI, 1.01–1.09); white blood cell count, HR, 1.18 (95% CI, 1.04–1.35); sTNFR1 (soluble TNF receptor 1), HR, 1.21 (95% CI, 1.05–1.39); and sIL‐2Rα (sIL‐2 receptor α), HR, 1.16 (95% CI, 1.05–1.29) (all per doubling of biomarker). sCD14, sCD163, IL‐18, and IL‐1 receptor antagonist showed no association with AF. Upon concurrent adjustment for all biomarkers, only IL‐6 remained significantly associated with the arrhythmia, HR, 1.17 (95% CI, 1.07–1.26). Conclusions Among older adults, IL‐6, hs‐CRP, white blood cell count, sTNFR1, and sIL‐2Rα were positively associated with incident AF, but only IL‐6 retained significance on concurrent adjustment. These findings newly document associations for sTNFR1 and sIL‐2Rα and lend support to a preeminent role for IL‐6 in development of this arrhythmia. The efficacy of IL‐6 blockade for AF prevention awaits completion of appropriate clinical trials.https://www.ahajournals.org/doi/10.1161/JAHA.124.035710atrial fibrillationinflammationolder adults
spellingShingle Sanyog G. Shitole
Susan R. Heckbert
Gregory M. Marcus
Sanjiv J. Shah
Nona Sotoodehnia
Jeremy D. Walston
Alexander P. Reiner
Russell P. Tracy
Bruce M. Psaty
Jorge R. Kizer
Assessment of Inflammatory Biomarkers and Incident Atrial Fibrillation in Older Adults
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
atrial fibrillation
inflammation
older adults
title Assessment of Inflammatory Biomarkers and Incident Atrial Fibrillation in Older Adults
title_full Assessment of Inflammatory Biomarkers and Incident Atrial Fibrillation in Older Adults
title_fullStr Assessment of Inflammatory Biomarkers and Incident Atrial Fibrillation in Older Adults
title_full_unstemmed Assessment of Inflammatory Biomarkers and Incident Atrial Fibrillation in Older Adults
title_short Assessment of Inflammatory Biomarkers and Incident Atrial Fibrillation in Older Adults
title_sort assessment of inflammatory biomarkers and incident atrial fibrillation in older adults
topic atrial fibrillation
inflammation
older adults
url https://www.ahajournals.org/doi/10.1161/JAHA.124.035710
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