scholarly journals Quantification of fibroblast growth factor 23 and N-terminal pro-B-type natriuretic peptide to identify patients with atrial fibrillation using a high-throughput platform: A validation study

PLoS Medicine ◽  
2021 ◽  
Vol 18 (2) ◽  
pp. e1003405
Author(s):  
Winnie Chua ◽  
Jonathan P. Law ◽  
Victor R. Cardoso ◽  
Yanish Purmah ◽  
Georgiana Neculau ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Natriuretic Peptide ◽  
High Throughput ◽  
Fibroblast Growth Factor 23 ◽  
High Sensitivity ◽  
Fibroblast Growth ◽  
C Statistic

Background Large-scale screening for atrial fibrillation (AF) requires reliable methods to identify at-risk populations. Using an experimental semi-quantitative biomarker assay, B-type natriuretic peptide (BNP) and fibroblast growth factor 23 (FGF23) were recently identified as the most suitable biomarkers for detecting AF in combination with simple morphometric parameters (age, sex, and body mass index [BMI]). In this study, we validated the AF model using standardised, high-throughput, high-sensitivity biomarker assays. Methods and findings For this study, 1,625 consecutive patients with either (1) diagnosed AF or (2) sinus rhythm with CHA2DS2-VASc score of 2 or more were recruited from a large teaching hospital in Birmingham, West Midlands, UK, between September 2014 and February 2018. Seven-day ambulatory ECG monitoring excluded silent AF. Patients with tachyarrhythmias apart from AF and incomplete cases were excluded. AF was diagnosed according to current clinical guidelines and confirmed by ECG. We developed a high-throughput, high-sensitivity assay for FGF23, quantified plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and FGF23, and compared results to the previously used multibiomarker research assay. Data were fitted to the previously derived model, adjusting for differences in measurement platforms and known confounders (heart failure and chronic kidney disease). In 1,084 patients (46% with AF; median [Q1, Q3] age 70 [60, 78] years, median [Q1, Q3] BMI 28.8 [25.1, 32.8] kg/m2, 59% males), patients with AF had higher concentrations of NT-proBNP (median [Q1, Q3] per 100 pg/ml: with AF 12.00 [4.19, 30.15], without AF 4.25 [1.17, 15.70]; p < 0.001) and FGF23 (median [Q1, Q3] per 100 pg/ml: with AF 1.93 [1.30, 4.16], without AF 1.55 [1.04, 2.62]; p < 0.001). Univariate associations remained after adjusting for heart failure and estimated glomerular filtration rate, known confounders of NT-proBNP and FGF23. The fitted model yielded a C-statistic of 0.688 (95% CI 0.656, 0.719), almost identical to that of the derived model (C-statistic 0.691; 95% CI 0.638, 0.744). The key limitation is that this validation was performed in a cohort that is very similar demographically to the one used in model development, calling for further external validation. Conclusions Age, sex, and BMI combined with elevated NT-proBNP and elevated FGF23, quantified on a high-throughput platform, reliably identify patients with AF. Trial registration Registry IRAS ID 97753 Health Research Authority (HRA), United Kingdom

High parathormone levels are associated with adverse cardiovascular events in coronary patients with high fibroblast growth factor-23

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Gutierrez ◽  
A Acena ◽  
A Pello ◽  
J Martinez-Milla ◽  
O Gonzalez-Lorenzo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Plasma Levels ◽  
Cardiovascular Events ◽  
Fibroblast Growth Factor 23 ◽  
High Sensitivity ◽  
Funding Source ◽  
Fibroblast Growth ◽  
Ischemic Events

Abstract Background Disturbances of the components of the mineral metabolism (MM) (vitamin D, phosphate, parathormone [PTH], fibroblast growth factor-23 [FGF23] and klotho) have been linked to cardiovascular disease. However, the available data are controversial, probably because most studies deal with individual rather than with the whole MM components. Purpose To the study the relationship between MM components and cardiovascular events, after controlling for other well-known markers (N-Terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity troponin I [hs-TnI], and high-sensitivity c-reactive protein [hs-CRP]), and relevant clinical variables in stable coronary artery disease (CAD) patients. Methods We analyzed the aforementioned markers in 964 CAD patients and followed them subsequently. The primary outcome (PO) was the composite of ischemic events (acute coronary syndrome, stroke or transient ischemic attack), heart failure and death. Secondary outcomes were any ischemic event and the composite of heart failure and death. Results Median follow-up was 5.39 years (2.81 - 6.92). Age was 60 (52–72) years and 76.2% patients were male. Median glomerular filtration rate was 80.4 (65.3–93.1) ml/min/1.73 m2. 185 patients developed the PO. At the univariate analysis PTH, FGF23, NT-proBNP and hs-TnI were directly associated with the PO, while calcidiol and Klotho were inversely related, and phosphate did not reach statistical significance. However, only PTH (HR 1.058 [CI 1.021–1.097]; p=0.002) and NT-proBNP (HR 1.020 [CI 1.012–1.028]; p&lt;0.001) were independent predictors of the PO at multivariate Cox regression analysis. Both PTH and NT-proBNP were also independent predictors of HF or death (HR 1.066 [1.016 - 1.119]; p=0.009 and HR 1.024 [1.014 - 1.034]; p&lt;0.001 respectively), while only PTH predicted ischemic events (HR 1.052 [1.010–1.096]; p=0.016). After dividing patients in two subgroups according to whether they had FGF23 plasma levels above the median (85.5 RU/ml) or not, PTH remained as a predictor of the PO only in the subgroup with FGF23 &gt;85.5 RU/ml (p&lt;0.001), but not in patients with FGF23 ≤85.5 RU/ml (p=0.551). There was a significant interaction between FGF23 and PTH plasma levels (p=0.002). Conclusion PTH predicts cardiovascular events in CAD patients with elevated FGF23 levels even after taking into account all the other components of MM and controlling for NT-ProBNP, hs-CPR and TnI. There is an interaction between PTH and FGF23 levels, and they should be assessed together when exploring their potential predictive power. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Fondo de Investigaciones Sanitarias

scholarly journals Nutraceutical, Dietary, and Lifestyle Options for Prevention and Treatment of Ventricular Hypertrophy and Heart Failure

2021 ◽  
Vol 22 (7) ◽  
pp. 3321
Author(s):  
Mark F. McCarty
Keyword(s):  
Heart Failure ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Ventricular Hypertrophy ◽  
Salt Intake ◽  
Fibroblast Growth Factor 23 ◽  
Research Strategy ◽  
Fibroblast Growth Factor 21 ◽  
High Dose ◽  
Fibroblast Growth

Although well documented drug therapies are available for the management of ventricular hypertrophy (VH) and heart failure (HF), most patients nonetheless experience a downhill course, and further therapeutic measures are needed. Nutraceutical, dietary, and lifestyle measures may have particular merit in this regard, as they are currently available, relatively safe and inexpensive, and can lend themselves to primary prevention as well. A consideration of the pathogenic mechanisms underlying the VH/HF syndrome suggests that measures which control oxidative and endoplasmic reticulum (ER) stress, that support effective nitric oxide and hydrogen sulfide bioactivity, that prevent a reduction in cardiomyocyte pH, and that boost the production of protective hormones, such as fibroblast growth factor 21 (FGF21), while suppressing fibroblast growth factor 23 (FGF23) and marinobufagenin, may have utility for preventing and controlling this syndrome. Agents considered in this essay include phycocyanobilin, N-acetylcysteine, lipoic acid, ferulic acid, zinc, selenium, ubiquinol, astaxanthin, melatonin, tauroursodeoxycholic acid, berberine, citrulline, high-dose folate, cocoa flavanols, hawthorn extract, dietary nitrate, high-dose biotin, soy isoflavones, taurine, carnitine, magnesium orotate, EPA-rich fish oil, glycine, and copper. The potential advantages of whole-food plant-based diets, moderation in salt intake, avoidance of phosphate additives, and regular exercise training and sauna sessions are also discussed. There should be considerable scope for the development of functional foods and supplements which make it more convenient and affordable for patients to consume complementary combinations of the agents discussed here. Research Strategy: Key word searching of PubMed was employed to locate the research papers whose findings are cited in this essay.

scholarly journals Increased Fibroblast Growth Factor 23 in Heart Failure: Biomarker, Mechanism, or Both?

2018 ◽  
Vol 32 (1) ◽  
pp. 15-17 ◽  
Author(s):  
Nuria Garcia-Fernandez ◽  
Javier Lavilla ◽  
Paloma L Martín ◽  
Gregorio Romero-González ◽  
Arantxa González ◽  
...  
Keyword(s):  
Heart Failure ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth

scholarly journals Fibroblast Growth Factor 23 and Incident Cardiovascular Disease and Mortality in Middle‐Aged Adults

2021 ◽  
Author(s):  
Shejuti Paul ◽  
Mandy Wong ◽  
Ehimare Akhabue ◽  
Rupal C. Mehta ◽  
Holly Kramer ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Hazard Ratio ◽  
Fibroblast Growth ◽  
Heart Failure Hospitalization ◽  
Middle Aged ◽  
Middle Aged Adults

Background Higher circulating fibroblast growth factor 23 (FGF23) associates with greater risk of cardiovascular disease (CVD) and mortality in older adults. The association of FGF23 with cardiovascular outcomes in younger populations has been incompletely explored. Methods and Results We measured C‐terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) in 3151 middle‐aged adults (mean age, 45±4) who participated in the year 20 examination of the CARDIA (Coronary Artery Risk Development in Young Adults) study. We used separate Cox proportional hazards models to examine the associations of cFGF23 and iFGF23 with incident CVD and mortality, adjusting models sequentially for sociodemographic, clinical, and laboratory factors. A total of 157 incident CVD events and 135 deaths occurred over a median 7.6 years of follow‐up (interquartile range, 4.1–9.9). In fully adjusted models, there were no statistically significant associations of FGF23 with incident CVD events (hazard ratio per doubling of cFGF23: 1.14, 95%CI 0.97,1.34; iFGF23: 0.76, 95%CI 0.57,1.02) or all‐cause mortality (hazard ratio per doubling of cFGF23, 1.17; 95% CI, 1.00–1.38; iFGF23, 0.86; 95% CI, 0.64–1.17). In analyses stratified by CVD subtypes, higher cFGF23 was associated with greater risk of heart failure hospitalization (hazard ratio per doubling of cFGF23, 1.52; 95% CI, 1.18–1.96) but not coronary heart disease or stroke, whereas iFGF23 was not associated with CVD subtypes in any model. Conclusions In middle‐aged adults with few comorbidities, higher cFGF23 and iFGF23 were not independently associated with greater risk of CVD events or death. Higher cFGF23 was independently associated with greater risk of heart failure hospitalization.

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