Serum level of fibroblast growth factor 21 predicts long-term  prognosis in patients with both diabetes mellitus and coronary  artery calcification

Guo, Feng; Huang, Jiafang; Dai, Tianran; Li, Maorong; Liu, Jinghua

doi:10.21037/apm.2020.03.28

Cited by 15 publications

(22 citation statements)

References 30 publications

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“…Supplementary Table 1 summarizes the patient selection criteria of these studies. Among these studies, 14 reported serum FGF21 concentration in patients with or without CVDs ( 10 – 23 ), 14 reported ORs or HRs of serum FGF21 concentration and incidence of CVDs ( 11 , 14 , 17 , 18 , 20 , 24 – 32 ), 8 reported Pearson's r of serum FGF21 concentration and vascular parameters ( 12 , 15 , 16 , 25 , 30 , 33 – 35 ), and 6 reported incidence of CVDs in individuals with different serum FGF21 levels ( 27 , 30 , 36 – 39 ).…”

Section: Resultsmentioning

confidence: 99%

High-Level Serum Fibroblast Growth Factor 21 Concentration Is Closely Associated With an Increased Risk of Cardiovascular Diseases: A Systematic Review and Meta-Analysis

Zhang

Yan

et al. 2021

Front. Cardiovasc. Med.

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Background: The association between fibroblast growth factor 21 (FGF21) and cardiovascular disease (CVD) risk remains unclear. We conducted this systematic review and meta-analysis to evaluate the association between FGF21 and CVDs, and relevant vascular parameters.Methods: PubMed and Web of Science databases were systematically searched to identify relevant studies published before March 2021. The FGF21 concentration was compared between individuals with and without CVDs. The effect of FGF21 on CVD risk was assessed by using hazard ratio (HR) and odds ratio (OR). The association between FGF21 and vascular parameters was assessed by Pearson's r. Study quality was assessed using Newcastle–Ottawa Scale and Joanna Briggs Institution Checklist.Results: A total of 29,156 individuals from 30 studies were included. Overall, the serum FGF21 concentration was significantly higher in CVD patients (p < 0.001), especially for coronary artery disease (CAD) (p < 0.001) and hypertension (p < 0.001). The pooled OR (p = 0.009) and HR (p < 0.001) showed that the risk of CVDs increased with FGF21. The linear association between FGF21 and vascular parameters, including pulse wave velocity (r = 0.32), carotid intima-media thickness (r = 0.21), ankle-brachial index (r = 0.33), systolic blood pressure (r = 0.13), and diastolic blood pressure (r = 0.05), was insignificant. The incidence of overall CVDs (p = 0.03) was significantly higher in individuals with higher FGF21 levels.Conclusion: High-level serum FGF21 concentration is closely associated with an increased risk of CVDs, which may be independent of vascular parameters. A standard FGF21 classification threshold needs to be established before clinical use for CVD risk assessment.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=241968, identifier: CRD42021241968.

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Section: Resultsmentioning

confidence: 99%

High-Level Serum Fibroblast Growth Factor 21 Concentration Is Closely Associated With an Increased Risk of Cardiovascular Diseases: A Systematic Review and Meta-Analysis

Zhang

Yan

et al. 2021

Front. Cardiovasc. Med.

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“…was powered to detect cardiovascular outcomes, and elevated FGF21 levels predicted cardiac death independently of N-terminal pro-BNP levels 24 . More broadly, elevated FGF21 levels have been associated with adverse cardiac events in individuals with coronary disease and/or diabetes, though in subclinical disease such elevations are no longer predictive after adjustment for traditional risk factors 21,22,39,40 . Thus, elevated FGF21 is a potential biomarker for severity in cardiac disease, raising the question of what derangements are causing this elevation, and whether the elevated FGF21 is an intrinsic or hormonal signal for the diseased heart.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, whereas FGF21 appears protective in most animal models of heart disease, elevated levels are poor prognostic indicators in humans. In two studies of diabetic patients with coronary disease, higher levels of FGF21 were predictive of poorer outcomes 21,22 . In cardiomyopathies, FGF21 elevations predicted adverse events in both heart failure with reduced or preserved ejection fraction, though >40% of patients in both these studies had diabetes 23,24 .…”

Section: Introductionmentioning

confidence: 98%

FGF21 defines a potential cardio-hepatic signaling circuit in human heart failure

Sommakia

et al. 2021

Preprint

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BackgroundExtrinsic control of cardiac contractility and ultrastructure via neurohormonal signaling is well established, but how other organs regulate cardiomyocyte metabolism is less well understood. Fibroblast growth factor-21 (FGF21) a hormonal regulator of metabolism mainly produced in the liver and adipose tissue, is a prime candidate for such signaling.MethodsTo investigate this further, we examined blood and tissue obtained from human subjects with heart failure with reduced ejection fraction (HFrEF) at the time of left ventricular assist device (LVAD) implantation, and correlated serum FGF21 levels with cardiac gene expression, immunohistochemistry, and clinical parameters.ResultsCirculating FGF21 levels were substantially elevated in HFrEF, compared to healthy subjects (HFrEF: 834.4 ± 101.8 pg/mL, n = 40; controls: 145.9 ± 28.6 pg/mL, n = 20, p = 5.5 × 10−8). There was clear FGF21 staining in diseased cardiomyocytes, and circulating FGF21 levels negatively correlated with the expression of cardiac genes involved in ketone metabolism, consistent with cardiac FGF21 signaling. FGF21 gene expression was low in failing and non-failing hearts, suggesting at least partial extracardiac production of the circulating hormone. Circulating FGF21 levels were correlated with BNP and total bilirubin, markers of chronic cardiac and hepatic congestion.ConclusionsCirculating FGF21 levels are elevated in HFrEF. The liver is likely the main extracardiac source, and congestive hepatopathy, common in HFrEF, was likely the proximate signal leading to FGF21 elevations. This supports a model of venous congestion from cardiomyopathy driving hepatic FGF21 communication to diseased cardiomyocytes, defining a potential cardio-hepatic signaling circuit in human heart failure.

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“…It is reported that DM may promote VC by enhancing the expression of inflammatory cytokines, activating bone morphogenetic proteins pathway and receptor activator of nuclear factor-kβ (RANK)/RANK ligand pathway ( 73 ). Recently, Gan et al demonstrated that lower baseline level of FGF21 in serum could predict a better long-term prognosis in patients with both DM and coronary artery calcification ( 22 ). But it has been proved that the application of FGF21 could resist to the calcification of VSMCs by the activation of FGFR1/3/β-klotho/P38/MAPK/runt-related transcription factor 2 signaling pathway ( 72 ).…”

Section: Fgf21 and Diabetic Vascular Complicationsmentioning

confidence: 99%

“…The cardiovascular protective effect of exogenous FGF21 is mainly mediated by the anti-oxidative stress ( 11 ), anti-inflammatory ( 19 ), anti-apoptosis ( 20 ) and lipid-lowering effects ( 21 ). However, despite as a biomarker and diagnostic indicator of DM-related cardiovascular diseases in clinic ( 14 , 22 ), the clinical implementation of FGF21 still has some obstacles due to its complex pharmacokinetic and biophysical characteristics ( 23 ).…”

Section: Introductionmentioning

confidence: 99%

The Role of Fibroblast Growth Factor 21 in Diabetic Cardiovascular Complications and Related Epigenetic Mechanisms

et al. 2021

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Fibroblast growth factor 21 (FGF21), is an emerging metabolic regulator mediates multiple beneficial effects in the treatment of metabolic disorders and related complications. Recent studies showed that FGF21 acts as an important inhibitor in the onset and progression of cardiovascular complications of diabetes mellitus (DM). Furthermore, evidences discussed so far demonstrate that epigenetic modifications exert a crucial role in the initiation and development of DM-related cardiovascular complications. Thus, epigenetic modifications may involve in the function of FGF21 on DM-induced cardiovascular complications. Therefore, this review mainly interprets and delineates the recent advances of role of FGF21 in DM cardiovascular complications. Then, the possible changes of epigenetics related to the role of FGF21 on DM-induced cardiovascular complications are discussed. Thus, this article not only implies deeper understanding of the pathological mechanism of DM-related cardiovascular complications, but also provides the possible novel therapeutic strategy for DM-induced cardiovascular complications by targeting FGF21 and related epigenetic mechanism.

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Serum level of fibroblast growth factor 21 predicts long-term prognosis in patients with both diabetes mellitus and coronary artery calcification

Abstract: FGF-21 among the FGF family members has become a research focus. Different from other FGF members, FGF-21 has no positive effect on the growth of fibroblasts and cannot bind with unfractionated heparin specifically (1).Early studies revealed that the main function of FGF-21

Cited by 15 publications

References 30 publications

High-Level Serum Fibroblast Growth Factor 21 Concentration Is Closely Associated With an Increased Risk of Cardiovascular Diseases: A Systematic Review and Meta-Analysis

High-Level Serum Fibroblast Growth Factor 21 Concentration Is Closely Associated With an Increased Risk of Cardiovascular Diseases: A Systematic Review and Meta-Analysis

FGF21 defines a potential cardio-hepatic signaling circuit in human heart failure

The Role of Fibroblast Growth Factor 21 in Diabetic Cardiovascular Complications and Related Epigenetic Mechanisms

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