BACKGROUND AND OBJECTIVES: Circulating fibroblast growth factor-23 is associated with adverse cardiovascular outcomes in CKD and non-CKD individuals, but the underlying mechanism remains unclear. This study tested whether this association is independent of mineral metabolism and indices of subclinical cardiovascular pathology. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The prospective association between fibroblast growth factor-23 and major cardiovascular events (a composite of hospital-treated myocardial infarction, hospital-treated stroke, or all-cause mortality) was investigated in the community-based Prospective Investigation of the Vasculature in Uppsala Seniors (n=973; mean age=70 years, 50% women) using multivariate logistic regression. Subjects were recruited between January of 2001 and June of 2004. RESULTS: During follow-up (median=5.1 years), 112 participants suffered a major cardiovascular event. In logistic regression models adjusted for age, sex, and estimated GFR, higher fibroblast growth factor-23 was associated with increased risk for major cardiovascular events (odds ratio for tertiles 2 and 3 versus tertile 1=1.92, 95% confidence interval=1.19-3.09, P<0.01). After additional adjustments in the model, adding established cardiovascular risk factors, confounders of mineral metabolism (calcium, phosphate, parathyroid hormone, and 25(OH)-vitamin D), and indices of subclinical pathology (flow-mediated vasodilation, endothelial-dependent and -independent vasodilation, arterial stiffness, and atherosclerosis and left ventricular mass) attenuated this relationship, but it remained significant (odds ratio for tertiles 2 and 3 versus tertile 1=1.69, 95% confidence interval=1.01-2.82, P<0.05). CONCLUSIONS: Fibroblast growth factor-23 is an independent predictor of cardiovascular events in the community, even after accounting for mineral metabolism abnormalities and subclinical cardiovascular damage. Circulating fibroblast growth factor-23 may reflect novel and important aspects of cardiovascular risk yet to be unraveled.
BACKGROUND AND OBJECTIVES: Circulating fibroblast growth factor-23 is associated with adverse cardiovascular outcomes in CKD and non-CKD individuals, but the underlying mechanism remains unclear. This study tested whether this association is independent of mineral metabolism and indices of subclinical cardiovascular pathology. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The prospective association between fibroblast growth factor-23 and major cardiovascular events (a composite of hospital-treated myocardial infarction, hospital-treated stroke, or all-cause mortality) was investigated in the community-based Prospective Investigation of the Vasculature in Uppsala Seniors (n=973; mean age=70 years, 50% women) using multivariate logistic regression. Subjects were recruited between January of 2001 and June of 2004. RESULTS: During follow-up (median=5.1 years), 112 participants suffered a major cardiovascular event. In logistic regression models adjusted for age, sex, and estimated GFR, higher fibroblast growth factor-23 was associated with increased risk for major cardiovascular events (odds ratio for tertiles 2 and 3 versus tertile 1=1.92, 95% confidence interval=1.19-3.09, P<0.01). After additional adjustments in the model, adding established cardiovascular risk factors, confounders of mineral metabolism (calcium, phosphate, parathyroid hormone, and 25(OH)-vitamin D), and indices of subclinical pathology (flow-mediated vasodilation, endothelial-dependent and -independent vasodilation, arterial stiffness, and atherosclerosis and left ventricular mass) attenuated this relationship, but it remained significant (odds ratio for tertiles 2 and 3 versus tertile 1=1.69, 95% confidence interval=1.01-2.82, P<0.05). CONCLUSIONS: Fibroblast growth factor-23 is an independent predictor of cardiovascular events in the community, even after accounting for mineral metabolism abnormalities and subclinical cardiovascular damage. Circulating fibroblast growth factor-23 may reflect novel and important aspects of cardiovascular risk yet to be unraveled.
Authors: Richard D Semba; Jeffrey C Fink; Kai Sun; Anne R Cappola; Mansi Dalal; Candace Crasto; Luigi Ferrucci; Linda P Fried Journal: Clin J Am Soc Nephrol Date: 2011-11-10 Impact factor: 8.237
Authors: Christian Faul; Ansel P Amaral; Behzad Oskouei; Ming-Chang Hu; Alexis Sloan; Tamara Isakova; Orlando M Gutiérrez; Robier Aguillon-Prada; Joy Lincoln; Joshua M Hare; Peter Mundel; Azorides Morales; Julia Scialla; Michael Fischer; Elsayed Z Soliman; Jing Chen; Alan S Go; Sylvia E Rosas; Lisa Nessel; Raymond R Townsend; Harold I Feldman; Martin St John Sutton; Akinlolu Ojo; Crystal Gadegbeku; Giovana Seno Di Marco; Stefan Reuter; Dominik Kentrup; Klaus Tiemann; Marcus Brand; Joseph A Hill; Orson W Moe; Makoto Kuro-O; John W Kusek; Martin G Keane; Myles Wolf Journal: J Clin Invest Date: 2011-10-10 Impact factor: 14.808
Authors: Tamara Isakova; Huiliang Xie; Wei Yang; Dawei Xie; Amanda Hyre Anderson; Julia Scialla; Patricia Wahl; Orlando M Gutiérrez; Susan Steigerwalt; Jiang He; Stanley Schwartz; Joan Lo; Akinlolu Ojo; James Sondheimer; Chi-yuan Hsu; James Lash; Mary Leonard; John W Kusek; Harold I Feldman; Myles Wolf Journal: JAMA Date: 2011-06-15 Impact factor: 56.272
Authors: Sigrid Lundberg; Abdul Rashid Qureshi; Sara Olivecrona; Iva Gunnarsson; Stefan H Jacobson; Tobias E Larsson Journal: Clin J Am Soc Nephrol Date: 2012-03-01 Impact factor: 8.237
Authors: Joachim H Ix; Ronit Katz; Bryan R Kestenbaum; Ian H de Boer; Michel Chonchol; Kenneth J Mukamal; Dena Rifkin; David S Siscovick; Mark J Sarnak; Michael G Shlipak Journal: J Am Coll Cardiol Date: 2012-06-13 Impact factor: 24.094
Authors: R Nagai; Y Saito; Y Ohyama; H Aizawa; T Suga; T Nakamura; M Kurabayashi; M Kuroo Journal: Cell Mol Life Sci Date: 2000-05 Impact factor: 9.261
Authors: Myles Wolf; Miklos Z Molnar; Ansel P Amaral; Maria E Czira; Anna Rudas; Akos Ujszaszi; Istvan Kiss; Laszlo Rosivall; Janos Kosa; Peter Lakatos; Csaba P Kovesdy; Istvan Mucsi Journal: J Am Soc Nephrol Date: 2011-03-24 Impact factor: 10.121
Authors: Emilio Gonzalez-Parra; Maria Luisa Gonzalez-Casaus; Antonio Galán; Alberto Martinez-Calero; Victor Navas; Mariano Rodriguez; Alberto Ortiz Journal: Nephrol Dial Transplant Date: 2011-03-24 Impact factor: 5.992
Authors: María E Rodriguez-Ortiz; Ignacio Lopez; Juan R Muñoz-Castañeda; Julio M Martinez-Moreno; Alan Peralta Ramírez; Carmen Pineda; Antonio Canalejo; Philippe Jaeger; Escolastico Aguilera-Tejero; Mariano Rodriguez; Arnold Felsenfeld; Yolanda Almaden Journal: J Am Soc Nephrol Date: 2012-05-10 Impact factor: 10.121
Authors: Farah N Ali; Bonita Falkner; Samuel S Gidding; Heather E Price; Scott W Keith; Craig B Langman Journal: J Pediatr Date: 2014-07-22 Impact factor: 4.406
Authors: Amber L Fyfe-Johnson; Alvaro Alonso; Elizabeth Selvin; Julie K Bower; James S Pankow; Sunil K Agarwal; Pamela L Lutsey Journal: J Hypertens Date: 2016-07 Impact factor: 4.844
Authors: Amarnath Marthi; Killian Donovan; Richard Haynes; David C Wheeler; Colin Baigent; Christopher M Rooney; Martin J Landray; Sharon M Moe; Jun Yang; Lisa Holland; Romina di Giuseppe; Annet Bouma-de Krijger; Borislava Mihaylova; William G Herrington Journal: J Am Soc Nephrol Date: 2018-05-15 Impact factor: 10.121