Association of fibroblast growth factor 23 With atrial fibrillation in chronic kidney disease, from the Chronic Renal Insufficiency Cohort Study

Chronic Renal Insufficiency Cohort (CRIC) Study Investigators

Research output: Contribution to journalArticle

Abstract

Importance: Levels of fibroblast growth factor 23 (FGF23) are elevated in chronic kidney disease (CKD) and strongly associated with left ventricular hypertrophy, heart failure, and death. Whether FGF23 is an independent risk factor for atrial fibrillation in CKD is unknown. Objective: To investigate the association of FGF23 with atrial fibrillation in CKD. Design, Setting, and Participants: Prospective cohort study of 3876 individuals with mild to severe CKD who enrolled in the Chronic Renal Insufficiency Cohort Study between June 19, 2003, and September 3, 2008, and were followed up through March 31, 2013. Exposures: Baseline plasma FGF23 levels. Main Outcomes and Measures: Prevalent and incident atrial fibrillation. Results: The study cohort comprised 3876 participants. Their mean (SD) age was 57.7 (11.0) years, and 44.8%(1736 of 3876) were female. Elevated FGF23 levels were independently associated with increased odds of prevalent atrial fibrillation (n = 660) after adjustment for cardiovascular and CKD-specific factors (odds ratio of highest vs lowest FGF23 quartile, 2.30; 95%CI, 1.69-3.13; P < .001 for linear trend across quartiles). During a median follow-up of 7.6 years (interquartile range, 6.3-8.6 years), 247 of the 3216 participants who were at risk developed incident atrial fibrillation (11.9 events per 1000 person-years). In fully adjusted models, elevated FGF23 was independently associated with increased risk of incident atrial fibrillation after adjustment for demographic, cardiovascular, and CKD-specific factors, and other markers of mineral metabolism (hazard ratio of highest vs lowest FGF23 quartile, 1.59; 95%CI, 1.00-2.53; P = .02 for linear trend across quartiles). The results were unchanged when further adjusted for ejection fraction, but individual adjustments for left ventricular mass index, left atrial area, and interim heart failure events partially attenuated the association of elevated FGF23 with incident atrial fibrillation. Conclusions and Relevance: Elevated FGF23 is independently associated with prevalent and incident atrial fibrillation in patients with mild to severe CKD. The effectmay be partially mediated through a diastolic dysfunction pathway that includes left ventricular hypertrophy, atrial enlargement, and heart failure events.

Original languageEnglish (US)
Pages (from-to)548-556
Number of pages9
JournalJAMA Cardiology
Volume1
Issue number5
DOIs
StatePublished - Aug 1 2016

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Chronic Renal Insufficiency
Atrial Fibrillation
Cohort Studies
Heart Failure
Left Ventricular Hypertrophy
fibroblast growth factor 23
Minerals
Odds Ratio
Demography
Outcome Assessment (Health Care)
Prospective Studies

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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Association of fibroblast growth factor 23 With atrial fibrillation in chronic kidney disease, from the Chronic Renal Insufficiency Cohort Study. / Chronic Renal Insufficiency Cohort (CRIC) Study Investigators.

In: JAMA Cardiology, Vol. 1, No. 5, 01.08.2016, p. 548-556.

Research output: Contribution to journalArticle

Chronic Renal Insufficiency Cohort (CRIC) Study Investigators. / Association of fibroblast growth factor 23 With atrial fibrillation in chronic kidney disease, from the Chronic Renal Insufficiency Cohort Study. In: JAMA Cardiology. 2016 ; Vol. 1, No. 5. pp. 548-556.
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title = "Association of fibroblast growth factor 23 With atrial fibrillation in chronic kidney disease, from the Chronic Renal Insufficiency Cohort Study",
abstract = "Importance: Levels of fibroblast growth factor 23 (FGF23) are elevated in chronic kidney disease (CKD) and strongly associated with left ventricular hypertrophy, heart failure, and death. Whether FGF23 is an independent risk factor for atrial fibrillation in CKD is unknown. Objective: To investigate the association of FGF23 with atrial fibrillation in CKD. Design, Setting, and Participants: Prospective cohort study of 3876 individuals with mild to severe CKD who enrolled in the Chronic Renal Insufficiency Cohort Study between June 19, 2003, and September 3, 2008, and were followed up through March 31, 2013. Exposures: Baseline plasma FGF23 levels. Main Outcomes and Measures: Prevalent and incident atrial fibrillation. Results: The study cohort comprised 3876 participants. Their mean (SD) age was 57.7 (11.0) years, and 44.8{\%}(1736 of 3876) were female. Elevated FGF23 levels were independently associated with increased odds of prevalent atrial fibrillation (n = 660) after adjustment for cardiovascular and CKD-specific factors (odds ratio of highest vs lowest FGF23 quartile, 2.30; 95{\%}CI, 1.69-3.13; P < .001 for linear trend across quartiles). During a median follow-up of 7.6 years (interquartile range, 6.3-8.6 years), 247 of the 3216 participants who were at risk developed incident atrial fibrillation (11.9 events per 1000 person-years). In fully adjusted models, elevated FGF23 was independently associated with increased risk of incident atrial fibrillation after adjustment for demographic, cardiovascular, and CKD-specific factors, and other markers of mineral metabolism (hazard ratio of highest vs lowest FGF23 quartile, 1.59; 95{\%}CI, 1.00-2.53; P = .02 for linear trend across quartiles). The results were unchanged when further adjusted for ejection fraction, but individual adjustments for left ventricular mass index, left atrial area, and interim heart failure events partially attenuated the association of elevated FGF23 with incident atrial fibrillation. Conclusions and Relevance: Elevated FGF23 is independently associated with prevalent and incident atrial fibrillation in patients with mild to severe CKD. The effectmay be partially mediated through a diastolic dysfunction pathway that includes left ventricular hypertrophy, atrial enlargement, and heart failure events.",
author = "{Chronic Renal Insufficiency Cohort (CRIC) Study Investigators} and Rupal Mehta and Xuan Cai and Jungwha Lee and Scialla, {Julia J.} and Nisha Bansal and Sondheimer, {James H.} and Jing Chen and Hamm, {L. Lee} and Ricardo, {Ana C.} and Navaneethan, {Sankar D.} and Rajat Deo and Mahboob Rahman and Feldman, {Harold I.} and Go, {Alan S.} and Tamara Isakova and Myles Wolf and Lawrence Appel and Jiang He and Kusek, {John W.} and Lash, {James P.} and Akinlolu Ojo and Townsend, {Raymond R.}",
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T1 - Association of fibroblast growth factor 23 With atrial fibrillation in chronic kidney disease, from the Chronic Renal Insufficiency Cohort Study

AU - Chronic Renal Insufficiency Cohort (CRIC) Study Investigators

AU - Mehta, Rupal

AU - Cai, Xuan

AU - Lee, Jungwha

AU - Scialla, Julia J.

AU - Bansal, Nisha

AU - Sondheimer, James H.

AU - Chen, Jing

AU - Hamm, L. Lee

AU - Ricardo, Ana C.

AU - Navaneethan, Sankar D.

AU - Deo, Rajat

AU - Rahman, Mahboob

AU - Feldman, Harold I.

AU - Go, Alan S.

AU - Isakova, Tamara

AU - Wolf, Myles

AU - Appel, Lawrence

AU - He, Jiang

AU - Kusek, John W.

AU - Lash, James P.

AU - Ojo, Akinlolu

AU - Townsend, Raymond R.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Importance: Levels of fibroblast growth factor 23 (FGF23) are elevated in chronic kidney disease (CKD) and strongly associated with left ventricular hypertrophy, heart failure, and death. Whether FGF23 is an independent risk factor for atrial fibrillation in CKD is unknown. Objective: To investigate the association of FGF23 with atrial fibrillation in CKD. Design, Setting, and Participants: Prospective cohort study of 3876 individuals with mild to severe CKD who enrolled in the Chronic Renal Insufficiency Cohort Study between June 19, 2003, and September 3, 2008, and were followed up through March 31, 2013. Exposures: Baseline plasma FGF23 levels. Main Outcomes and Measures: Prevalent and incident atrial fibrillation. Results: The study cohort comprised 3876 participants. Their mean (SD) age was 57.7 (11.0) years, and 44.8%(1736 of 3876) were female. Elevated FGF23 levels were independently associated with increased odds of prevalent atrial fibrillation (n = 660) after adjustment for cardiovascular and CKD-specific factors (odds ratio of highest vs lowest FGF23 quartile, 2.30; 95%CI, 1.69-3.13; P < .001 for linear trend across quartiles). During a median follow-up of 7.6 years (interquartile range, 6.3-8.6 years), 247 of the 3216 participants who were at risk developed incident atrial fibrillation (11.9 events per 1000 person-years). In fully adjusted models, elevated FGF23 was independently associated with increased risk of incident atrial fibrillation after adjustment for demographic, cardiovascular, and CKD-specific factors, and other markers of mineral metabolism (hazard ratio of highest vs lowest FGF23 quartile, 1.59; 95%CI, 1.00-2.53; P = .02 for linear trend across quartiles). The results were unchanged when further adjusted for ejection fraction, but individual adjustments for left ventricular mass index, left atrial area, and interim heart failure events partially attenuated the association of elevated FGF23 with incident atrial fibrillation. Conclusions and Relevance: Elevated FGF23 is independently associated with prevalent and incident atrial fibrillation in patients with mild to severe CKD. The effectmay be partially mediated through a diastolic dysfunction pathway that includes left ventricular hypertrophy, atrial enlargement, and heart failure events.

AB - Importance: Levels of fibroblast growth factor 23 (FGF23) are elevated in chronic kidney disease (CKD) and strongly associated with left ventricular hypertrophy, heart failure, and death. Whether FGF23 is an independent risk factor for atrial fibrillation in CKD is unknown. Objective: To investigate the association of FGF23 with atrial fibrillation in CKD. Design, Setting, and Participants: Prospective cohort study of 3876 individuals with mild to severe CKD who enrolled in the Chronic Renal Insufficiency Cohort Study between June 19, 2003, and September 3, 2008, and were followed up through March 31, 2013. Exposures: Baseline plasma FGF23 levels. Main Outcomes and Measures: Prevalent and incident atrial fibrillation. Results: The study cohort comprised 3876 participants. Their mean (SD) age was 57.7 (11.0) years, and 44.8%(1736 of 3876) were female. Elevated FGF23 levels were independently associated with increased odds of prevalent atrial fibrillation (n = 660) after adjustment for cardiovascular and CKD-specific factors (odds ratio of highest vs lowest FGF23 quartile, 2.30; 95%CI, 1.69-3.13; P < .001 for linear trend across quartiles). During a median follow-up of 7.6 years (interquartile range, 6.3-8.6 years), 247 of the 3216 participants who were at risk developed incident atrial fibrillation (11.9 events per 1000 person-years). In fully adjusted models, elevated FGF23 was independently associated with increased risk of incident atrial fibrillation after adjustment for demographic, cardiovascular, and CKD-specific factors, and other markers of mineral metabolism (hazard ratio of highest vs lowest FGF23 quartile, 1.59; 95%CI, 1.00-2.53; P = .02 for linear trend across quartiles). The results were unchanged when further adjusted for ejection fraction, but individual adjustments for left ventricular mass index, left atrial area, and interim heart failure events partially attenuated the association of elevated FGF23 with incident atrial fibrillation. Conclusions and Relevance: Elevated FGF23 is independently associated with prevalent and incident atrial fibrillation in patients with mild to severe CKD. The effectmay be partially mediated through a diastolic dysfunction pathway that includes left ventricular hypertrophy, atrial enlargement, and heart failure events.

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