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, Yucong; Yan, Jinhua; Ni, Yang; Qian, Zonghao; Nie, Hao; Yang, Zhen; Yan, Dan; Xiu-xian, Wei; Ruan, Lei; Huang, Yi Hsiang; Zhang, Cuntai; Zhang, Le

doi:10.3389/fcvm.2021.705273

Cited by 14 publications

(12 citation statements)

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“…Several studies have revealed the intrinsic link between FGF21 and CAD. Zhang Y et al analyzed a large population and discovered that high levels of circulating FGF21 were strongly associated with increased risk of CAD (23). A cross-sectional study in a Chinese population unmasked that serum FGF21 levels in CAD patients increased with the severity of metabolic disorders, independent of age, gender and BMI (24).…”

Section: Discussionmentioning

confidence: 99%

Circulating Fibroblast Growth Factor 21 and Total Testosterone in Type 2 Diabetes Mellitus Men With Coronary Heart Disease

et al. 2022

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BackgroundFibroblast growth factor 21 increased in population with type 2 diabetes mellitus (T2DM), while serum total testosterone often decreased in men with T2DM. This study aimed to investigate the relationship between the prevalence of coronary artery disease (CAD) and circulating FGF21 concentrations and serum testosterone in T2DM men.Methods490 men with T2DM from January 2021 to December 2021 were recruited from the Renmin Hospital of Wuhan University, and they were divided into CAD group (n=248) and control group (n=242). FGF21 were determined based on ELISA principle and serum total testosterone was measured in a liquid chromatography mass spectrometer LC/MS-8050 (Shimadzu, Japan). Logistic and restricted cubic spline analyses were performed to examine the association between the prevalence of CAD and circulating FGF21 concentrations and serum testosterone in T2DM men. The receiver operating curve (ROC) analysis was used to explore the predictive performance.ResultsCirculating FGF21 levels were higher in T2DM men with CAD compared with those without CAD [214.63 (121.82, 348.64) pg/ml vs 166.55 (94.81,254.48) pg/ml, p<0.001], while serum total testosterone was lower [3.08 ± 0.07 ng/ml vs 3.76 ± 0.09 ng/ml, p<0.001]. The fully adjusted odds ratio (OR) and 95% confidence intervals (95%CI) was 2.956(1.409,6.201) for those in quartile 4 of FGF21 versus quartile 1 and the fully adjusted OR (95%CI) was 0.346(0.174,0.686) for those in quartile 4 of testosterone versus quartile 1. The receiver operating curve (ROC) analysis showed that the area under the curve (AUC) of combination of FGF21 and testosterone for predicting the occurrence of CAD in men with T2DM was 0.702 (95% CI: 0.667-0.741).ConclusionCirculating FGF21 levels were positively associated with CAD in men with T2DM, whereas serum total testosterone levels showed an inverse correlation with CAD in diabetic men.

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Section: Discussionmentioning

confidence: 99%

Circulating Fibroblast Growth Factor 21 and Total Testosterone in Type 2 Diabetes Mellitus Men With Coronary Heart Disease

et al. 2022

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“…Lakhani et al analysed FGF21 in different cardiometabolic disorders, including metabolic syndrome, diabetes, diabetic nephropathy, CAD, and cardiovascular motality, and reported elevated FGF21 levels were significant predictors of these disorders [105]. Although these findings were subsequently confirmed by Zhang et al [26], both of these reports identified moderate-to-significant heterogeneity between studies which may impact the validity of the results.…”

Section: Circulating Fgf21 Levels and Atherosclerotic Cvds In Humansmentioning

confidence: 98%

“…In humans, circulating FGF21 levels are elevated in metabolic syndrome, obesity, CVDs, diabetes, non-alcoholic fatty liver disease, mitochondrial myopathies, and cold exposure [26,38,[62][63][64][65][66][67][68][69]. Given the beneficial metabolic effects of FGF21 that have been demonstrated in vitro, the paradoxical increase reported in these conditions is thought to be due to an FGF21 resistant state, caused by the impaired FGF21 signalling which results in the need for a higher FGF21 level to exert its beneficial metabolic effects [43,70,71].…”

Section: Metabolic Functions Of Fgf21mentioning

confidence: 99%

“…FGF21 protects against oxidative stress [24], hypertrophy and cardiac inflammation in animal, and in vitro cell culture studies [25]. However, in clinical studies, FGF21 levels are often elevated in cardiovascular diseases, including HF [21,26,27]. This review will discuss the potential role of FGF21 in HF pathophysiology and the basis for its use as a HF biomarker.…”

Section: Introductionmentioning

confidence: 99%

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Fibroblast growth factor 21 in heart failure

Tucker

Rye

2022

Heart Fail Rev

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Fibroblast growth factor 21 (FGF21) is a peptide hormone involved in energy homeostasis that protects against the development of obesity and diabetes in animal models. Its level is elevated in atherosclerotic cardiovascular diseases (CVD) in humans. However, little is known about the role of FGF21 in heart failure (HF). HF is a major global health problem with a prevalence that is predicted to rise, especially in ageing populations. Despite improved therapies, mortality due to HF remains high, and given its insidious onset, prediction of its development is challenging for physicians. The emergence of cardiac biomarkers to improve prediction, diagnosis, and prognosis of HF has received much attention over the past decade. Recent studies have suggested FGF21 is a promising biomarker candidate for HF. Preclinical research has shown that FGF21 is involved in the pathophysiology of HF through the prevention of oxidative stress, cardiac hypertrophy, and inflammation in cardiomyocytes. However, in the available clinical literature, FGF21 levels appear to be paradoxically raised in HF, potentially implying a FGF21 resistant state as occurs in obesity. Several potential confounding variables complicate the verdict on whether FGF21 is of clinical value as a biomarker. Further research is thus needed to evaluate whether FGF21 has a causal role in HF, and whether circulating FGF21 can be used as a biomarker to improve the prediction, diagnosis, and prognosis of HF. This review draws from preclinical and clinical studies to explore the role of FGF21 in HF.

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“…cFGF21 levels have been shown to be elevated in subjects with metabolic syndrome, nonalcoholic fatty liver, hyperlipidemia, and cardiovascular diseases ( 9 , 10 ). Thus, cFGF21 is regarded as a useful biomarker of metabolic disorders.…”

Section: Introductionmentioning

confidence: 99%

Close association between lifestyle and circulating FGF21 levels: A systematic review and meta-analysis

Qian

Zhang

et al. 2022

Front. Endocrinol.

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BackgroundThe impact of lifestyle factors on circulating fibroblast growth factor 21 (cFGF21) remains unclear. We conducted this systematic review and meta-analysis to evaluate the association between lifestyle factors and cFGF21 levels.MethodsWe included studies that evaluated the effects of different lifestyles on cFGF21 concentration in adults, which included smoking, exercise, diets, alcohol consumption and weight loss. Random effects models or fixed effects models were used for meta-analysis to calculate the standardized mean difference (SMD) and 95% confidence interval according to the heterogeneity among studies. Study quality was assessed using the Newcastle–Ottawa Scale for cohort studies, the Joanna Briggs Institution Checklist for cross-sectional studies, and the PEDro scale for experimental studies.ResultsA total of 50 studies with 1438 individuals were included. Overall, smoking, a hypercaloric carbohydrate-rich diet, a hypercaloric fat-rich diet, amino acid or protein restriction, excessive fructose intake and alcohol consumption significantly upregulated cFGF21 levels (p<0.05), whereas fish oil intake and calorie restriction with sufficient protein intake significantly decreased cFGF21 (p<0.05). Compared to the preexercise cFGF21 level, the cFGF21 level significantly increased within 3 hours postexercise (p<0.0001), while it significantly decreased in the blood sampled >6 h postexercise (p=0.01). Moreover, higher exercise intensity resulted in higher upregulation of cFGF21 at 1-hour post exercise (p=0.0006).ConclusionFGF21 could serve as a potential biomarker for the assessment of different lifestyle interventions. When it is used for this purpose, a standard study protocol needs to be established, especially taking into consideration the intervention types and the sampling time post-intervention.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021254758, identifier CRD42021254758.

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

Cited by 14 publications

References 55 publications

Circulating Fibroblast Growth Factor 21 and Total Testosterone in Type 2 Diabetes Mellitus Men With Coronary Heart Disease

Circulating Fibroblast Growth Factor 21 and Total Testosterone in Type 2 Diabetes Mellitus Men With Coronary Heart Disease

Fibroblast growth factor 21 in heart failure

Close association between lifestyle and circulating FGF21 levels: A systematic review and meta-analysis

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