Jasleen Ghuman1, Xuan Cai2, Ravi B Patel3, Sadiya S Khan3, Jonathan Hecktman2, Margaret M Redfield4, Gregory Lewis5, Sanjiv J Shah3, Myles Wolf6, Tamara Isakova7, Rupal Mehta8. 1. McGaw Medical Center of Northwestern University Feinberg School of Medicine, Department of Medicine, Chicago, Illinois. 2. Center for Translational Metabolism and Health, Institute of Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 3. Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 4. Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota. 5. Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. 6. Division of Nephrology, Department of Medicine, Duke University, Durham, North Carolina. 7. Center for Translational Metabolism and Health, Institute of Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Division of Nephrology and Hypertension, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 8. Center for Translational Metabolism and Health, Institute of Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Division of Nephrology and Hypertension, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Division of Nephrology, Department of Medicine, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois. Electronic address: rupal.mehta@northwestern.edu.
Abstract
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is characterized by left ventricular hypertrophy and decreased exercise capacity. Fibroblast growth factor 23 (FGF23), a hormone involved in phosphate, vitamin D, and iron homeostasis, is linked to left ventricular hypertrophy and HF. We measured c-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels and examined their associations with exercise capacity in patients with HFpEF. METHODS AND RESULTS: Using multivariable linear regression and linear mixed models, we studied the associations of cFGF23 and iFGF23 with baseline and mean weekly change over 24 weeks in peak oxygen consumption and 6-minute walk distance in individuals enrolled in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF trial. Our study population included 172 individuals with available plasma for cFGF23 and iFGF23 measurements. Median (25th-75th percentile) baseline cFGF23 and iFGF23 levels were 208.7 RU/mL (132.1-379.5 RU/mL) and 90.3 pg/mL (68.6-128.5 pg/mL), respectively. After adjustment for cardiovascular disease and hematologic and kidney parameters, higher cFGF23 was independently associated with a lower peak oxygen consumption at baseline. Higher iFGF23 was independently associated with shorter 6-minute walk distance at baseline. No significant associations were appreciated with the longitudinal outcomes. CONCLUSIONS: In patients with HFpEF, higher FGF23 levels are independently associated with decreased exercise capacity at baseline. Published by Elsevier Inc.
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is characterized by left ventricular hypertrophy and decreased exercise capacity. Fibroblast growth factor 23 (FGF23), a hormone involved in phosphate, vitamin D, and iron homeostasis, is linked to left ventricular hypertrophy and HF. We measured c-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels and examined their associations with exercise capacity in patients with HFpEF. METHODS AND RESULTS: Using multivariable linear regression and linear mixed models, we studied the associations of cFGF23 and iFGF23 with baseline and mean weekly change over 24 weeks in peak oxygen consumption and 6-minute walk distance in individuals enrolled in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF trial. Our study population included 172 individuals with available plasma for cFGF23 and iFGF23 measurements. Median (25th-75th percentile) baseline cFGF23 and iFGF23 levels were 208.7 RU/mL (132.1-379.5 RU/mL) and 90.3 pg/mL (68.6-128.5 pg/mL), respectively. After adjustment for cardiovascular disease and hematologic and kidney parameters, higher cFGF23 was independently associated with a lower peak oxygen consumption at baseline. Higher iFGF23 was independently associated with shorter 6-minute walk distance at baseline. No significant associations were appreciated with the longitudinal outcomes. CONCLUSIONS: In patients with HFpEF, higher FGF23 levels are independently associated with decreased exercise capacity at baseline. Published by Elsevier Inc.
Authors: Thomas A Pearson; George A Mensah; R Wayne Alexander; Jeffrey L Anderson; Richard O Cannon; Michael Criqui; Yazid Y Fadl; Stephen P Fortmann; Yuling Hong; Gary L Myers; Nader Rifai; Sidney C Smith; Kathryn Taubert; Russell P Tracy; Frank Vinicor Journal: Circulation Date: 2003-01-28 Impact factor: 29.690
Authors: Omar F AbouEzzeddine; Bradley J Kemp; Barry A Borlaug; Brian P Mullan; Atta Behfar; Sorin V Pislaru; Marat Fudim; Margaret M Redfield; Panithaya Chareonthaitawee Journal: Circ Heart Fail Date: 2019-10-15 Impact factor: 8.790
Authors: Andreas B Gevaert; Hadis Shakeri; Arthur J Leloup; Cor E Van Hove; Guido R Y De Meyer; Christiaan J Vrints; Katrien Lemmens; Emeline M Van Craenenbroeck Journal: Circ Heart Fail Date: 2017-06 Impact factor: 8.790
Authors: Margaret M Redfield; Barry A Borlaug; Greg D Lewis; Selma F Mohammed; Marc J Semigran; Martin M Lewinter; Anita Deswal; Adrian F Hernandez; Kerry L Lee; Eugene Braunwald Journal: Circ Heart Fail Date: 2012-09-01 Impact factor: 8.790
Authors: Julia J Scialla; Huiliang Xie; Mahboob Rahman; Amanda Hyre Anderson; Tamara Isakova; Akinlolu Ojo; Xiaoming Zhang; Lisa Nessel; Takayuki Hamano; Juan E Grunwald; Dominic S Raj; Wei Yang; Jiang He; James P Lash; Alan S Go; John W Kusek; Harold Feldman; Myles Wolf Journal: J Am Soc Nephrol Date: 2013-10-24 Impact factor: 10.121
Authors: Jerzy Chudek; Piotr Kocełak; Aleksander Owczarek; Maria Bożentowicz-Wikarek; Małgorzata Mossakowska; Magdalena Olszanecka-Glinianowicz; Andrzej Wiecek Journal: Nephrol Dial Transplant Date: 2014-04-11 Impact factor: 5.992
Authors: Giovana Seno Di Marco; Stefan Reuter; Dominik Kentrup; Alexander Grabner; Ansel Philip Amaral; Manfred Fobker; Jörg Stypmann; Hermann Pavenstädt; Myles Wolf; Christian Faul; Marcus Brand Journal: Nephrol Dial Transplant Date: 2014-05-29 Impact factor: 5.992
Authors: Arvin Halim; Heather N Burney; Xiaochun Li; Yang Li; Claudia Tomkins; Andrew M Siedlecki; Tzong-Shi Lu; Sahir Kalim; Ravi Thadhani; Sharon Moe; Stephen M S Ting; Daniel Zehnder; Thomas F Hiemstra; Kenneth Lim Journal: Kidney360 Date: 2022-07-05