@article {8487, title = {Intact and C-Terminal FGF23 Assays-Do Kidney Function, Inflammation, and Low Iron Influence Relationships With Outcomes?}, journal = {J Clin Endocrinol Metab}, volume = {105}, year = {2020}, month = {2020 Dec 01}, abstract = {

CONTEXT: Higher fibroblast growth factor-23 (FGF23) concentrations are associated with heart failure and mortality in diverse populations, but the strengths of associations differ markedly depending up on which assay is used.

OBJECTIVE: We sought to evaluate whether iron deficiency, inflammation, or kidney function account for differences in the strengths of associations between these 2 FGF23 assays with clinical outcomes.

DESIGN: Case cohort study from the Cardiovascular Health Study.

SETTING: A total of 844 community-dwelling individuals aged 65 years or older with and without chronic kidney disease were followed for 10 years.

OUTCOMES: Outcomes included death, incident heart failure (HF), and incident myocardial infarction (MI). Exposure was baseline intact and C-terminal FGF23. Using modified Cox models, adjusting sequentially we tested whether observed associations of each assay with outcomes were attenuated by iron status, inflammation, kidney function, or their combinations.

RESULTS: FGF23 measured by either assay was associated with mortality in unadjusted analysis (intact FGF23 hazard ratio [HR] per 2-fold higher 1.45; 95\% CI, 1.25-1.68; C-terminal FGF23 HR 1.38; 95\% CI, 1.26-1.50). Adjustment for kidney function completely attenuated associations of intact FGF23 with mortality (HR 1.00; 95\% CI, 0.85-1.17), but had much less influence on the association of C-terminal FGF23, for which results remained significant after adjustment (HR 1.15; 95\% CI, 1.04-1.28). Attenuation was much less with adjustment for iron status or inflammation. Results were similar for the HF end point. Neither C-terminal or intact FGF23 was associated with MI risk.

CONCLUSIONS: The relationship of FGF23 with clinical end points is markedly different depending on the type of FGF23 assay used. The associations of biologically active FGF23 with clinical end points may be confounded by kidney disease, and thus much weaker than previously thought.

}, issn = {1945-7197}, doi = {10.1210/clinem/dgaa665}, author = {Sharma, Shilpa and Katz, Ronit and Bullen, Alexander L and Chaves, Paulo H M and de Leeuw, Peter W and Kroon, Abraham A and Houben, Alfons J H M and Shlipak, Michael G and Ix, Joachim H} } @article {9853, title = {Association of Fibroblast Growth Factor 23 and Cardiac Mechanics in the Cardiovascular Health Study.}, journal = {Kidney360}, year = {2024}, month = {2024 Nov 19}, abstract = {

BACKGROUND: Elevated levels of fibroblast growth factor 23 (FGF23) are associated with left ventricular hypertrophy and heart failure (HF) in individuals with and without kidney disease. Prior studies investigated the association of FGF23 and structural cardiac changes using conventional echocardiography, which is limited in its ability to detect early cardiac dysfunction. We investigated the relationship between FGF23 levels and cardiac dynamics using two-dimensional speckle tracking echocardiography (2D-STE), a novel imaging modality.

METHODS: This was a cross-sectional analysis of data from the Cardiovascular Health Study, an ongoing prospective, population-based cohort study. The study population included 506 participants from CHS with available c-terminal (cFGF23) and intact FGF23 (iFGF23) measurements from 1996-1997 and 2D-STE images from 1994-1995. Forty two percent of the study population had CKD, defined as an eGFR < 60 ml/min/1.73m2, and the mean eGFR was 63 ml/min/1.73m2. The primary exposures were cFGF23 and iFGF23. The primary outcomes were six 2D-STE parameters performed at the 1994-1995 study visit. Linear regression models were used to examine the independent associations of FGF23 with six cardiac 2D-STE indices adjusting for demographics, cardiovascular risk factors, markers of kidney disease severity, and inflammation.

RESULTS: cFGF23 levels were moderately correlated with iFGF23 levels in the CHS population. In fully adjusted models, cFGF23 was associated with left atrial dysfunction, but no other cardiac imaging parameter (β estimate -2.47; 95\% Confidence Interval -4.68, -0.25; Table 2 ). iFGF23 was not associated with any of the six 2D-STE indices. Limitations include small sample size and noncurrent FGF23 measurements and 2D-STE imaging.

CONCLUSIONS: In a limited sample of individuals enrolled in the CHS with c- and i-FGF23 measurements, we did not find consistent associations between FGF23 levels and 2D-STE parameters. Further investigations in a larger population with concurrent 2D-STE are needed to better understand the associations of FGF23 with early changes in cardiac mechanics.

}, issn = {2641-7650}, doi = {10.34067/KID.0000000643}, author = {Jain, Keertana and Katz, Ronit and Isakova, Tamara and Kizer, Jorge R and Sharma, Shilpa and Psaty, Bruce M and Shah, Sanjiv and Ix, Joachim and Mehta, Rupal} } @article {9615, title = {Iron Deficiency and Incident Heart Failure in Older Community-Dwelling Individuals.}, journal = {ESC Heart Fail}, year = {2024}, month = {2024 Feb 26}, abstract = {

AIMS: Among persons with prevalent heart failure (HF), iron deficiency has been linked to HF admissions, and intravenous iron replacement improves HF outcomes. Recent studies in persons with chronic kidney disease (CKD) demonstrate that iron deficiency is associated with incident HF. This study aimed to determine the relationship of iron status with incident HF in community-dwelling older adults irrespective of their kidney function.

METHODS: In this case-cohort study, 1,006 Cardiovascular Health Study participants (785 from the random sub-cohort [including 193 HF cases] and 221 additional HF cases [N~=~414 total HF cases]) aged >= 65~years without HF (41\% with CKD), we used weighted Cox models to evaluate associations of iron status with incident HF. Participants were categorized based on quartiles of transferrin saturation and ferritin as "iron replete" (27.3\%), "functional iron deficiency" (7.7\%), "iron deficiency" (11.8\%), "mixed iron deficiency" (5.6\%), "high iron" (9.3\%) and "non-classified" (38.1\%), consistent with prior studies.

RESULTS: Compared to older persons who were iron replete, those with iron deficiency were at higher risk of incident HF (HR 1.47; 1.02-2.11) in models adjusting for demographics, HF risk factors, and estimated glomerular filtration rate. Other iron categories did not associate with incident HF. The relationship of iron deficiency with incident HF did not differ by CKD status (interaction P value 0.2).

CONCLUSIONS: Among community-dwelling elders, iron deficiency is independently associated with incident HF, an association that was similar irrespective of CKD status. Our findings support conduct of clinical trials of iron replacement for prevention of HF in older adults with iron deficiency.

}, issn = {2055-5822}, doi = {10.1002/ehf2.14724}, author = {Sharma, Shilpa and Katz, Ronit and Chaves, Paulo H M and Hoofnagle, Andrew N and Kizer, Jorge R and Bansal, Nisha and Ganz, Tomas and Ix, Joachim H} }