Michael A Rosenberg1, Marlena Maziarz2, Alex Y Tan3, Nicole L Glazer4, Susan J Zieman5, Jorge R Kizer6, Joachim H Ix7, Luc Djousse8, David S Siscovick9, Susan R Heckbert10, Kenneth J Mukamal11. 1. 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. 2. Department of Biostatistics, University of Washington, Seattle, WA. 3. Division of Electrophysiology, Virginia Commonwealth University, Richmond, VA. 4. Translational and Health Informatics, Merck Pharmaceuticals, Boston, MA. 5. Department of Medicine, Cardiology Division, National Institute on Aging, Johns Hopkins Medical Institutions, Baltimore, MD. 6. Department of Medicine, Weill Cornell Medical College, New York, NY. 7. Nephrology Section, Veterans Affairs San Diego Healthcare System, and Division of Nephrology, Department of Medicine, University of California San Diego, San Diego, CA. 8. Division of Aging, Department of Medicine, Brigham and Women's Hospital and Boston Veterans Affairs Healthcare System, Harvard Medical School, Boston, MA. 9. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA; Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, WA. 10. Cardiovascular Health Research Unit and Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA. 11. 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.
Abstract
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. CONCLUSION: 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.
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. CONCLUSION: 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.
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