Dataset Information

Association of Fibroblast Growth Factor 23 With Risk of Incident Coronary Heart Disease in Community-Living Adults.

ABSTRACT:

Importance

Higher circulating fibroblast growth factor 23 (FGF23) concentrations are associated with cardiovascular disease events linked to heart failure, but associations of FGF23 with coronary heart disease (CHD) have been less consistent.

Objective

To determine the association of plasma FGF23 concentrations with incident CHD and whether this association differs by race, sex, or chronic kidney disease status.

Design, setting, and participants

We examined the association of FGF23 concentrations with incident CHD risk within the Reasons for Geographic and Racial Differences in Stroke study, a prospective cohort of black and white adults 45 years and older enrolled between January 2003 and October 2007 with follow-up through December 31, 2011. Using a case-cohort design, we measured FGF23 concentrations in 829 participants who developed incident CHD and in 812 participants randomly selected from the Reasons for Geographic and Racial Differences in Stroke study cohort (cohort random sample). To account for the stratified sampling design, the cohort random sample was weighted back to the original cohort overall (n?=?22?127). Cox proportional hazards models were used to examine the association of FGF23 concentration with incident CHD, adjusting for CHD risk factors and kidney function. In prespecified analyses, we examined whether race, sex, or chronic kidney disease modified the association of FGF23 concentration with incident CHD.

Exposures

Plasma C-terminal FGF23 concentrations.

Main outcomes and measures

Investigator-adjudicated incident CHD events.

Results

Of the 22?127 participants in the weighted cohort random sample, 13?059 (58.9%) were female and 9435 (42.6%) were black, and the mean age was 64.3 (95% CI, 63.7-64.9) years. Greater age, lower estimated glomerular filtration rate, higher urine albumin to creatinine ratio, and female sex were associated with higher FGF23 concentration at baseline. In multivariable models adjusted for established CHD risk factors and kidney function, higher FGF23 concentrations were associated with greater risk of CHD (hazard ratio [HR] comparing fourth with first quartile, 2.15; 95% CI, 1.35-3.42). The magnitude and strength of these associations differed by sex. However, these differences were no longer observed when adjusting for hormone therapy in women (men: HR comparing fourth with first quartile, 2.40; 95% CI, 1.30-4.42; women: HR comparing fourth with first quartile, 2.34; 95% CI, 1.04-5.27) or when using sex-specific FGF23 quartiles (men: HR comparing fourth with first quartile, 2.65; 95% CI, 1.43-4.90; women: HR comparing fourth with first quartile, 2.26; 95% CI, 1.02-5.03).

Conclusions and relevance

Higher FGF23 concentrations were associated with greater risk of CHD. Heterogeneity in the association by sex may be caused by differences in the distribution of plasma FGF23 concentrations or the use of hormone therapy in men vs women.

SUBMITTER: Panwar B

PROVIDER: S-EPMC5875372 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Fibroblast Growth Factor 23 With Risk of Incident Coronary Heart Disease in Community-Living Adults.

Panwar Bhupesh B Judd Suzanne E SE Wadley Virginia G VG Jenny Nancy S NS Howard Virginia J VJ Safford Monika M MM Gutiérrez Orlando M OM

JAMA cardiology 20180401 4

<h4>Importance</h4>Higher circulating fibroblast growth factor 23 (FGF23) concentrations are associated with cardiovascular disease events linked to heart failure, but associations of FGF23 with coronary heart disease (CHD) have been less consistent.<h4>Objective</h4>To determine the association of plasma FGF23 concentrations with incident CHD and whether this association differs by race, sex, or chronic kidney disease status.<h4>Design, setting, and participants</h4>We examined the association ...[more]

PMID: 29516098

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Project description:OBJECTIVES:This study sought to determine the association of fibroblast growth factor (FGF)-23 with death, heart failure (HF), and cardiovascular disease (CVD) in the general population, as well as the influence of chronic kidney disease (CKD) in this setting. BACKGROUND:FGF-23 increases renal phosphorus excretion and inhibits vitamin D activation. In end-stage renal disease, high FGF-23 levels are associated with mortality. The association of FGF-23 with death, HF, and CVD in the general population, and the influence of CKD in this setting, are unknown. METHODS:Plasma FGF-23 was measured in 3,107 community-living persons ? 65 years of age in 1996 and 1997, and participants were followed through 2008. HF and CVD events were adjudicated by a panel of experts. Associations of FGF-23 with each outcome were evaluated using Cox proportional hazards models, and we tested whether associations differed by CKD status. RESULTS:Both lower estimated glomerular filtration rate and higher urine albumin to creatinine ratios were associated with high FGF-23 at baseline. During 10.5 years (median) follow-up, there were 1,730 deaths, 697 incident HF events, and 797 incident CVD events. Although high FGF-23 concentrations were associated with each outcome in combined analyses, the associations were consistently stronger for those with CKD (p interactions all <0.006). In the CKD group (n = 1,128), the highest FGF-23 quartile had adjusted hazards ratios (HR) of 1.87 (95% confidence interval [CI]: 1.47 to 2.38) for all-cause death, 1.94 (95% CI: 1.32 to 2.83) for incident HF, and 1.49 (95% CI: 1.02 to 2.18) for incident CVD events compared with the lowest quartile. Corresponding HRs in those without CKD (n = 1,979) were 1.29 (95% CI: 1.05 to 1.59), 1.37 (95% CI: 0.99 to 1.89), and 1.07 (95% CI: 0.79 to 1.45). CONCLUSIONS:FGF-23, a hormone involved in phosphorous and vitamin D homeostasis, is independently associated with all-cause death and incident HF in community-living older persons. These associations appear stronger in persons with CKD.

Project description:BackgroundElevated Fibroblast Growth Factor-23 (FGF23) levels have been associated with greater left ventricular mass (LVM) and heart failure. Whether higher FGF23 is associated with higher LVH prevalence and longitudinal changes in LVM and myocardial strain in middle-aged adults without cardiovascular disease (CVD) or chronic kidney disease (CKD) is unknown.MethodsWe studied 3,113 adults without CVD at baseline participating in the Year 25 (2010-2011) follow-up exam of the Coronary Artery Risk Development in Young Adults (CARDIA) study. We studied the association of Year 25 c-terminal FGF23 concentrations with indexed LVM (LVMI=LVM/height2.7), LVH and myocardial strain as assessed by speckle tracking strain echocardiography. Among the 2,758 (88.6%) participants who returned for the Year 30 examination, we also investigated the association of Year 25 FGF23 with 5 Year change in LVMI, strain parameters and incident LVH.ResultsThe mean age was 50.0 (±3.6) years, 56.8% were female, 45.7% were Black and 6.4% had CKD. There was 6.0% LVH prevalence at Year 25. Mean 5 Year change in LVMI was 5.3 (±7.7) grams/meter. In multivariable models, FGF23 in the highest quartile was associated with greater odds of LVH at Year 25 compared to lower quartiles. [Odds Ratio 95% CI: 1.81 (1.28, 2.58)] with similar findings after exclusion of participants with CKD. There was no interaction between FGF23 and race (P = .18) or sex (P = .80). There was no association between FGF23 and global longitudinal strain. There was no association between FGF23 and 5 Year change in LVMI. There was no association between higher FGF23 and 5 year incident LVH.ConclusionsIn a middle-aged adult population without known CVD or CKD, higher FGF23 was associated with greater odds of LVH, but not with greater increases in LVM over time. Further study is needed to elucidate whether FGF23 is a risk marker for underlying LVH or a mechanism for increased LVM over time in younger and middle-aged adult populations without CKD.

Dataset Information

Association of Fibroblast Growth Factor 23 With Risk of Incident Coronary Heart Disease in Community-Living Adults.

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Conclusions and relevance

Publications

Association of Fibroblast Growth Factor 23 With Risk of Incident Coronary Heart Disease in Community-Living Adults.

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