Bryan Kestenbaum1, Michael C Sachs2, Andy N Hoofnagle2, David S Siscovick2, Joachim H Ix2, Cassianne Robinson-Cohen2, Joao A C Lima2, Joseph F Polak2, Marc Blondon2, John Ruzinski2, Denise Rock2, Ian H de Boer2. 1. From the Kidney Research Institute, Department of Medicine, Division of Nephrology (B.K., M.C.S., C.R.-C., J.R., D.R., I.H.d.B.), Department of Laboratory Medicine (A.N.H.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (D.S.S.), and Department of Epidemiology (M.B.), University of Washington, Seattle; Division of Nephrology, Department of Medicine, University of California at San Diego (J.H.I.); Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.); and Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California at San Diego (J.H.I.); Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.A.C.L.); and Department of Radiology, Tufts-New England Medical Center, Boston, MA (J.F.P.). brk@u.wasington.edu. 2. From the Kidney Research Institute, Department of Medicine, Division of Nephrology (B.K., M.C.S., C.R.-C., J.R., D.R., I.H.d.B.), Department of Laboratory Medicine (A.N.H.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (D.S.S.), and Department of Epidemiology (M.B.), University of Washington, Seattle; Division of Nephrology, Department of Medicine, University of California at San Diego (J.H.I.); Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.); and Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California at San Diego (J.H.I.); Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.A.C.L.); and Department of Radiology, Tufts-New England Medical Center, Boston, MA (J.F.P.).
Abstract
BACKGROUND: Fibroblast growth factor-23 (FGF-23) is a phosphate regulatory hormone that directly stimulates left ventricular hypertrophy in experimental models. The role of FGF-23 in cardiovascular disease development in the general population is unclear. We tested associations of FGF-23 with major subclinical and clinical cardiovascular disease outcomes in a large prospective cohort. METHODS AND RESULTS: We evaluated 6547 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who were initially free of cardiovascular disease. We measured serum FGF-23 using the Kainos immunoassay. The MESA measured left ventricular mass by MRI, coronary calcium by computed tomography, and carotid intima-media thickness by ultrasound. The MESA adjudicated incident heart failure, coronary heart disease, and stroke by medical record review. After adjustment, the highest FGF-23 quartile was associated with an estimated 2.4-g greater left ventricular mass (95% confidence interval, 0.4-4.5 greater) and a 26% greater odds of higher coronary calcium scores (95% confidence interval, 9%-46% greater) compared with the lowest quartile. During 7.5-year follow-up, each 20-pg/mL higher FGF-23 concentration was associated with a 19% greater risk of heart failure (95% confidence interval, 3%-37% greater) and a 14% greater risk of coronary heart disease (95% confidence interval, 1%-28% greater). FGF-23 was not associated with carotid intima-media thickness or stroke. CONCLUSIONS: Higher serum FGF-23 concentrations are associated with subclinical cardiac disease and with new heart failure and coronary disease events, but not with carotid intima-media thickness or stroke. FGF-23 may be a novel cardiovascular risk factor in the general population.
BACKGROUND:Fibroblast growth factor-23 (FGF-23) is a phosphate regulatory hormone that directly stimulates left ventricular hypertrophy in experimental models. The role of FGF-23 in cardiovascular disease development in the general population is unclear. We tested associations of FGF-23 with major subclinical and clinical cardiovascular disease outcomes in a large prospective cohort. METHODS AND RESULTS: We evaluated 6547 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who were initially free of cardiovascular disease. We measured serum FGF-23 using the Kainos immunoassay. The MESA measured left ventricular mass by MRI, coronary calcium by computed tomography, and carotid intima-media thickness by ultrasound. The MESA adjudicated incident heart failure, coronary heart disease, and stroke by medical record review. After adjustment, the highest FGF-23 quartile was associated with an estimated 2.4-g greater left ventricular mass (95% confidence interval, 0.4-4.5 greater) and a 26% greater odds of higher coronary calcium scores (95% confidence interval, 9%-46% greater) compared with the lowest quartile. During 7.5-year follow-up, each 20-pg/mL higher FGF-23 concentration was associated with a 19% greater risk of heart failure (95% confidence interval, 3%-37% greater) and a 14% greater risk of coronary heart disease (95% confidence interval, 1%-28% greater). FGF-23 was not associated with carotid intima-media thickness or stroke. CONCLUSIONS: Higher serum FGF-23 concentrations are associated with subclinical cardiac disease and with new heart failure and coronary disease events, but not with carotid intima-media thickness or stroke. FGF-23 may be a novel cardiovascular risk factor in the general population.
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