Dataset Information

FGF-23 is a biomarker of RV dysfunction and congestion in patients with HFrEF.

ABSTRACT: There is no biomarker reflecting right ventricular dysfunction in HFrEF patients used in clinical practice. We have aimed to look for a circulating marker of RV dysfunction employing a quantitative proteomic strategy. The Olink Proteomics Multiplex panels (Cardiovascular Disease II, III, Cardiometabolic, and Inflammation Target Panels) identified FGF-23 to be the most differentially abundant (more than 2.5-fold) in blood plasma of HF patients with severe RV dysfunction (n = 30) compared to those with preserved RV function (n = 31). A subsequent ELISA-based confirmatory analysis of circulating FGF-23 in a large cohort of patients (n = 344, 72.7% NYHA III/IV, LVEF 22.5%, 54.1% with moderate/severe RV dysfunction), followed by multivariable regression analysis, revealed that the plasma FGF-23 level was most significantly associated with RV dysfunction grade (p = 0.0004) and congestion in the systemic circulation (p = 0.03), but not with LV-ejection fraction (p = 0.69) or estimated glomerular filtration rate (eGFR, p = 0.08). FGF-23 was associated with the degree of RV dysfunction in both sub-cohorts (i.e. in patients with and without congestion, p < 0.0001). The association between FGF-23 and RV-dysfunction remained significant after the adjustment for BNP (p = 0.01). In contrast, when adjusted for BNP, FGF-23 was no longer associated with LV dysfunction (p = 0.59). The Cox proportional hazard model revealed that circulating FGF-23 was significantly associated with adverse outcomes even after adjusting for BNP, LVEF, RV dysfunction grade and eGFR. Circulating FGF-23 is thus a biomarker of right ventricular dysfunction in HFrEF patients regardless of congestion status.

SUBMITTER: Benes J

PROVIDER: S-EPMC10520041 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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FGF-23 is a biomarker of RV dysfunction and congestion in patients with HFrEF.

Benes Jan J Kroupova Katerina K Kotrc Martin M Petrak Jiri J Jarolim Petr P Novosadova Vendula V Kautzner Josef J Melenovsky Vojtech V

Scientific reports 20230925 1

There is no biomarker reflecting right ventricular dysfunction in HFrEF patients used in clinical practice. We have aimed to look for a circulating marker of RV dysfunction employing a quantitative proteomic strategy. The Olink Proteomics Multiplex panels (Cardiovascular Disease II, III, Cardiometabolic, and Inflammation Target Panels) identified FGF-23 to be the most differentially abundant (more than 2.5-fold) in blood plasma of HF patients with severe RV dysfunction (n = 30) compared to those ...[more]

PMID: 37749114

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Project description:Although cognitive impairment is common in hemodialysis patients, the etiology of and risk factors for its development remain unclear. Fibroblast growth factor 23 (FGF-23) levels are elevated in hemodialysis patients and are associated with increased mortality and left ventricular hypertrophy. Despite FGF-23 being found within the brain, there are no prior studies assessing whether FGF-23 levels are associated with cognitive performance. We measured FGF-23 in 263 prevalent hemodialysis patients in whom comprehensive neurocognitive testing was also performed. The cross-sectional association between patient characteristics and FGF-23 levels was assessed. Principal factor analysis was used to derive two factors from cognitive test scores, representing memory and executive function, which carried a mean of 0 and a standard deviation of 1. Multivariable linear regression adjusting for age, sex, education status, and other relevant covariates was used to explore the relationship between FGF-23 and each factor. Mean age was 63 years, 46% were women and 22% were African American. The median FGF-23 level was 3098 RU/mL. Younger age, lower prevalence of diabetes, longer dialysis vintage, and higher calcium and phosphorus were independently associated with higher FGF-23 levels. Higher FGF-23 was independently associated with a lower memory score (per doubling of FGF-23, β = -0.08 SD [95% confidence interval, CI: -0.16, -0.01]) and highest quartile vs. lowest quartile (β = -0.42 SD [-0.82, -0.02]). There was no definite association of FGF 23 with executive function when examined as a continuous variable (β = -0.03 SD [-0.10, 0.04]); however, there was a trend in the quartile analysis (β = -0.28 SD [-0.63, 0.07], P = 0.13, for 4th quartile vs. 1st quartile). FGF-23 was associated with worse performance on a composite memory score, including after adjustment for measures of mineral metabolism. High FGF-23 levels in hemodialysis patients may contribute to cognitive impairment.

Project description:AimsTo investigate the right ventricular (RV) strain in pectus excavatum (PE) patients using cardiac magnetic resonance tissue tracking (CMR TT).Materials and methodsFifty consecutive pectus excavatum patients, 10 to 32 years of age (mean age 15 ± 4 years), underwent routine cardiac magnetic resonance imaging (CMR) including standard measures of chest geometry and cardiac size and function. The control group consisted of 20 healthy patients with a mean age of 17 ± 5 years. RV longitudinal and circumferential strain magnitude was assessed by a dedicated RV tissue tracking software.ResultsFifty patients with images of sufficient quality were included in the analysis. The mean right and left ventricular ejection fractions were 55 ± 5% and 59 ± 4%. The RV global longitudinal strain was -21.88 ± 4.63%. The RV circumferential strain at base, mid-cavity and apex were -13.66 ± 3.09%, -11.31 ± 2.79%, -20.73 ± 3.45%, respectively. There was no statistically significant decrease in right ventricular or left ventricular ejection fraction between patients and controls (p > 0.05 for each). There was no significant difference in RV global longitudinal strain between two groups (-21.88 ± 4.63 versus -21.99 ± 3.58; p = 0.93). However, there was significant decrease in mid-cavity circumferential strain magnitude in pectus patients compared with controls (-11.31 ± 2.79 versus -16.19 ± 2.86; p < 0.001). PE patients had a significantly higher basal circumferential strain (-13.66 ± 3.09% versus -9.76 ± 1.79; p < 0.001) as well as apical circumferential strain (-20.73 ± 3.45% versus -12.07 ± 3.38) than control group.ConclusionMid-cavity circumferential strain but not longitudinal strain is reduced in pectus excavatum patients. Basal circumferential strain as well as apical circumferential strain were increased as compensatory mechanism for reduced mid-cavity circumferential strain. Further studies are needed to establish clinical significance of this finding.

Project description:Background and objectivesPlasma phosphate levels display considerable intraindividual variability. The phosphatonin fibroblast growth factor 23 is a central regulator of plasma phosphate levels, and it has been postulated to be a more stable marker than conventional CKD-mineral and bone disorder parameters. Thus, fibroblast growth factor 23 has been hypothesized to reflect time-averaged plasma phosphate levels in CKD patients.Design, setting, participants, & measurementsAmong 40 patients from the outpatient dialysis center, serial measurements of plasma calcium and phosphate (before every dialysis session) as well as C-terminal fibroblast growth factor 23, parathyroid hormone, and alkaline phosphatase (one time weekly) were performed over a study period of 4 weeks in November and December of 2011. Intraindividual variability of repeated plasma fibroblast growth factor 23 measurements compared with other CKD-mineral and bone disorder markers was tested, and the association of a single plasma fibroblast growth factor 23 measurement with time-averaged plasma phosphate levels was analyzed.ResultsAgainst expectations, intraindividual variability of fibroblast growth factor 23 (median coefficient of variation=27%; interquartile range=20-35) was not lower than variability of plasma phosphate (median coefficient of variation=15%; interquartile range=10-20), parathyroid hormone (median coefficient of variation=24%; interquartile range=15-39), plasma calcium (median coefficient of variation=3%; interquartile range=2-4), or alkaline phosphatase (median coefficient of variation=5%; interquartile range=3-10). Moreover, the correlation between the last fibroblast growth factor 23 measurement after 4 weeks and time-averaged plasma phosphate did not surpass the correlation between the last fibroblast growth factor 23 measurement and a single plasma phosphate value (r=0.67, P<0.001; r=0.76, P<0.001, respectively).ConclusionsSurprisingly, fibroblast growth factor 23 was not more closely associated to time-averaged plasma phosphate levels than a single plasma phosphate value, and it did not show a lower intraindividual variability than other tested markers of CKD-mineral and bone disorder. Thus, fibroblast growth factor 23 should not be used in clinical practice as a reflector of time-averaged plasma phosphate levels.

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FGF-23 is a biomarker of RV dysfunction and congestion in patients with HFrEF.

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FGF-23 is a biomarker of RV dysfunction and congestion in patients with HFrEF.

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