Circulating fibrosis biomarkers and risk of atrial fibrillation: The Cardiovascular Health Study (CHS).
BACKGROUND
Cardiac fibrosis is thought to play a central role in the pathogenesis of atrial fibrillation (AF). Retrospective studies have suggested that circulating fibrosis biomarkers are associated with AF, but prospective studies are limited.


METHODS
We measured circulating levels of 2 fibrosis biomarkers, procollagen type III, N-terminal propeptide (PIIINP) and transforming growth factor β1 among participants of the CHS, a population-based study of older Americans. We used Cox proportional hazards and competing risks models to examine adjusted risk of incident AF over a median follow-up of 8.8 years.


RESULTS
Levels of PIIINP were assessed in 2,935 participants, of whom 767 developed AF. Compared with the median PIIINP level (4.45 μg/L), adjusted hazard ratios (95% CIs) were 0.85 (0.72-1.00) at the 10th percentile, 0.93 (0.88-0.99) at the 25th percentile, 1.04 (0.95-1.04) at the 75th percentile, and 1.07 (0.90-1.26) at the 90th. Transforming growth factor β1 levels, assessed in 1,538 participants with 408 cases of incident AF, were not associated with AF risk.


CONCLUSIONS
In older adults, PIIINP levels were associated with risk of incident AF in a complex manner, with an association that appeared to be positive up to median levels but with little relationship beyond that. Further studies are required to confirm and possibly delineate the mechanism for this relationship.
Division of Cardiac Electrophysiology, VA Boston Healthcare System, Harvard Medical School, Boston, MA; Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA. Electronic address: Michael.rosenberg@va.gov.
Michael A
MA
Rosenberg
Department of Biostatistics, University of Washington, Seattle, WA.
Marlena
M
Maziarz
Division of Electrophysiology, Virginia Commonwealth University, Richmond, VA.
Alex Y
AY
Tan
Translational and Health Informatics, Merck Pharmaceuticals, Boston, MA.
Nicole L
NL
Glazer
Department of Medicine, Cardiology Division, National Institute on Aging, Johns Hopkins Medical Institutions, Baltimore, MD.
Susan J
SJ
Zieman
Department of Medicine, Weill Cornell Medical College, New York, NY.
Jorge R
JR
Kizer
Nephrology Section, Veterans Affairs San Diego Healthcare System, and Division of Nephrology, Department of Medicine, University of California San Diego, San Diego, CA.
Joachim H
JH
Ix
Division of Aging, Department of Medicine, Brigham and Women's Hospital and Boston Veterans Affairs Healthcare System, Harvard Medical School, Boston, MA.
Luc
L
Djousse
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA; Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, WA.
David S
DS
Siscovick
Cardiovascular Health Research Unit and Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA.
Susan R
SR
Heckbert
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Department of Epidemiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Kenneth J
KJ
Mukamal
D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood* / Q000453:epidemiology / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D009202:Cardiomyopathies / Q000097:blood* / Q000150:complications / Q000453:epidemiology; D004562:Electrocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005355:Fibrosis / Q000097:blood / Q000150:complications / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D010446:Peptide Fragments / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000097:blood*; D014481:United States / Q000453:epidemiology
D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; D053773:Transforming Growth Factor beta1; C041876:procollagen Type III-N-terminal peptide