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Fibroblast Growth Factor-23 and Incident Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS)
Open accessAbstract
Background—: Fibroblast growth factor-23 (FGF-23) is a hormone that promotes urinary phosphate excretion and regulates vitamin D metabolism. Circulating FGF-23 concentrations increase markedly in chronic kidney disease and are associated with increased risk of clinical cardiovascular events. FGF-23 may promote atrial fibrillation (AF) by inducing left ventricular hypertrophy and diastolic and left atrial dysfunction. Methods and Results—: We tested the associations of circulating FGF-23 concentration with incident AF among 6398 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 1350 participants in the Cardiovascular Health Study (CHS), all free of clinical cardiovascular disease at baseline. Over a median of 7.7 and 8.0 years of follow-up, we observed 291 and 229 incident AF events in MESA and CHS, respectively. In multivariable Cox proportional hazards models, each 2-fold-higher FGF-23 concentration was associated with a 41% higher risk of incident AF in MESA (hazard ratio, 1.41; 95% confidence interval, 1.13–1.76; P =0.003) and a 30% higher risk of incident AF in CHS (hazard ratio, 1.30; 95% confidence interval, 1.05–1.61; P =0.016) after adjustment for potential confounding characteristics, including kidney disease. Serum phosphate concentration was significantly associated with incident AF in MESA (hazard ratio, 1.15 per 0.5 mg/dL; 95% confidence interval, 1.02–1.31; P =0.023) but not CHS. In MESA, an association of low estimated glomerular filtration rate with incident AF was partially attenuated by adjustment for FGF-23. Conclusion—: Higher circulating FGF-23 concentration is associated with incident AF and may, in part, explain the link between chronic kidney disease and AF.
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Metadata
- Authors
- Mathew, J. S., Sachs, M. C., Katz, R., Patton, K. K., Heckbert, S. R., Hoofnagle, A. N., Alonso, A., Chonchol, M., Deo, R., Ix, J. H., Siscovick, D. S., Kestenbaum, B., & de Boer, I. H.
- Affiliations
- University of Minnesota (US)
- From the Division of Cardiology (J.S.M., K.K.P.), Division of Nephrology and Kidney Research Institute (J.S.M., M.C.S., R.K., B.K., I.H.d.B.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (S.R.H., D.S.S.), Department of Epidemiology (S.R.H., B.K., I.H.d.B.), and Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.); Division of...
- ORCID
- Venue
- Circulation
- Published
- 2014-07-22
- Volume
- 130
- Issue
- 4
- Pages
- 298-307
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC4108550
- OpenAlex
- W2114238925
- Cited by
- 153
- References
- 54
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 8 · 2023: 11 · 2022: 16 · 2021: 18 · 2020: 11 · 2019: 7 · 2018: 18 · 2017: 12 · 2016: 19 · 2015: 12 · 2014: 5
- FWCI
- 12.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01hc085082-026, n01hc085081-021, n01hc085079-024, n01hc085083-027, n01hc085080-026, n01hc095169-003, n01hc085086-022, n01hc55222-0-0-0, n01hc95159-40-0-1)
- National Institute on Aging (R56AG023629, AG023629, R01AG023629)
- National Heart, Lung, and Blood Institute (N01 HC085086, R01HL096875, N01-HC095169, N01 HC085079, N01 HC085083, N01 HC085080, N01-HC-095159, R01HL102214, N01HC085082, N01 HC055222, N01 HC085081, R01HL080295)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK035816)
- National Center for Research Resources (UL1RR024156, UL1RR025005)
- Topics
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- fibroblast growth factor 23, atrial fibrillation, chronic kidney disease, serum phosphorus, vitamin D metabolism, left atrial dysfunction, left ventricular hypertrophy, estimated glomerular filtration rate, cardiovascular risk factors
- MeSH terms
- Fibroblast Growth Factor-23, Aged, Aged, 80 and over, Atrial Fibrillation, Ethnicity, Female, Follow-Up Studies, Glomerular Filtration Rate, Heart Failure, Humans, Male, Middle Aged, Phosphates, Risk Factors, United States, Vitamin D, Comorbidity, Proportional Hazards Models, Hypertrophy, Left Ventricular, Ventricular Dysfunction, Left, Ventricular Remodeling, Renal Insufficiency, Chronic, Fibroblast Growth Factor 3
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