Association between Serum Fibroblast Growth Factor 21 and Coronary Artery Disease in Patients with Type 2 Diabetes

Kim, Won Jin; Kim, Sang Soo; Lee, Han Cheol; Song, Sang Heon; Bae, Min Jung; Yi, Yang; Jeon, Yun Kyung; Kim, Bo Hyun; Kim, Yong Ki; Kim, In Joo

doi:10.3346/jkms.2015.30.5.586

Cited by 28 publications

(30 citation statements)

References 18 publications

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“…In a study involving 100 Chinese subjects, with 38% of them having T2DM, serum FGF21 levels were independently associated with the presence of acute myocardial infarction and were significantly higher in those who developed reinfarction within 30 days 15. However, conflicting results were also reported from a few studies, which showed a lack of significant association after adjusting for body mass index and glycemic status 16, 17. Given that circulating FGF21 levels were higher in T2DM,6, 9 and most cross‐sectional studies consisted of relatively small sample size and therefore a limited number of subjects with T2DM, the association of serum FGF21 with CHD in T2DM could only be, at most, speculative.…”

Section: Discussionmentioning

confidence: 99%

“…Over the years, the association of circulating FGF21 with CHD in T2DM has not been clearly defined. In cross‐sectional studies, conflicting results were reported regarding circulating FGF21 levels in subjects with CHD, with an association of raised FGF21 levels with CHD reported in some studies,13, 14, 15 but not in others 16, 17. The association of circulating FGF21 with CHD in T2DM, especially among those without known cardiovascular disease (CVD), remains to be defined.…”

Section: Introductionmentioning

confidence: 99%

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Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus

Lee

Woo

Chow

et al. 2017

JAHA

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BackgroundFibroblast growth factor 21 (FGF21) has demonstrated beneficial effects on lipid and carbohydrate metabolism. In cross‐sectional studies, an association of raised circulating FGF21 levels with coronary heart disease (CHD) was found in some but not all studies. Here we investigated prospectively whether baseline serum FGF21 levels could predict incident CHD in subjects with type 2 diabetes mellitus and no known cardiovascular diseases.Methods and ResultsBaseline serum FGF21 levels were measured in 3528 Chinese subjects with type 2 diabetes mellitus recruited from the Hong Kong West Diabetes Registry. The role of baseline serum FGF21 levels in predicting incident CHD over a median follow‐up of 3.8 years was analyzed using Cox regression analysis. Among 3528 recruited subjects without known cardiovascular diseases, 147 (4.2%) developed CHD over a mean follow‐up of 4 years. Baseline serum log‐transformed FGF21 levels were significantly higher in those who had incident CHD than those who did not (222.7 pg/mL [92.8–438.4] versus 151.1 pg/mL [75.6–274.6]; P<0.001). On multivariable Cox regression analysis, baseline serum FGF21 levels, using an optimal cutoff of 206.22 pg/mL derived from our study, independently predicted incident CHD (hazard ratio, 1.55; 95% CI, 1.10–2.19; P=0.013) and significantly improved net reclassification index and integrated discrimination improvement after adjustment for conventional cardiovascular risk factors.ConclusionsWe have demonstrated, for the first time, that serum FGF21 level is an independent predictor of incident CHD and might be usefully utilized as a biomarker for identifying type 2 diabetes mellitus subjects with raised CHD risk, for primary prevention.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus

Lee

Woo

Chow

et al. 2017

JAHA

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“…Kim et al 10 showed that serum FGF21 levels measured in 120 patients are significantly However, the number of patients involved in studies of the correlation between serum FGF21 and coronary artery severity is so far quite small, and further investigations will be required to clarify whether such a correlation exists, and if it does, to determine its precise nature.…”

Section: Discussionmentioning

confidence: 99%

“…2 Moreover, serum FGF21 concentrations are associated with established cardiovascular risk factors, and are higher in patients with CAD than in those without CAD. 5,10 However, the precise nature of the association between serum FGF21 concentrations and CAD has yet to be confirmed. 4,11,12 In this study, we compared serum FGF21 concentrations in individuals with or without coronary artery narrowing, as identified by coronary angiography (CAG), and determined whether circulating FGF21 concentrations are associated with the severity of CAD.…”

Section: Introductionmentioning

confidence: 99%

Relationship between Circulating FGF21 Concentrations and the Severity of Coronary Artery Damage in Subjects with Cardiovascular Disease

Park

Bae

Choi

et al. 2018

J Lipid Atheroscler

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Objective: Fibroblast growth factor (FGF) 21 is a recently established therapeutic target for treating metabolic syndromes, which include potential precursors to cardiovascular disease, suggesting a link between FGF21 and atherosclerosis. However, the association between serum FGF21 concentrations and coronary artery disease remain controversial. The aim of this study is to evaluate the association between circulating FGF21 concentrations and coronary artery lesions and clinical severity. Methods: We enrolled 137 subjects who underwent coronary angiography, due to suspected acute coronary syndrome (ACS), from December 2009 to July 2012. Serum FGF21 levels were measured. Coronary artery lesions and clinical severities of the subjects were evaluated using the SYNergy between percutaneous coronary intervention with (paclitaxel-eluting) TAXus stent and cardiac surgery (SYNTAX) and Global Registry of Acute Coronary Events (GRACE) scoring system, respectively. Results: After adjusting for established cardiovascular disease risk factors, including age, body mass index, total cholesterol, and low-density lipoprotein cholesterol, patients with coronary artery lesions (n=112 men) had significantly higher levels of FGF21 than individuals without such lesions (n=25; men) (377.1±20.1 pg/mL vs. 267.1±43.5 pg/mL; p=0.026). However, no correlations were found between serum levels of FGF21 and either the calculated STNTAX score (r=0.117; p=0.176) or GRACE risk score, which is a risk prediction tool applicable for ACS subjects (r=0.113; p=0.193). Conclusion: Although serum levels of FGF21 were higher in individuals with coronary lesions than in those without such lesions, FGF21 levels were not associated with angiographic severity.

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“…We report here, for the first time, that 280M genetic variants of CX3CR1 are also significantly associated with decreased risk for CAD in patients with T2DM. Diabetes mellitus and vascular inflammation leading to CAD is a multifactorial process involving various chemokines (20), scavenger receptors (20), monocytes, endothelial cells, vascular smooth muscle cells (22,23) and growth factors (24,25), which function in disarray, leading to the diabetic vascular disease phenotype. Polymorphisms in CX3CR1 result in reduced chemokine binding.…”

Section: Discussionmentioning

confidence: 99%

Nonsynonymous T280M gene variant of CX3CR1 in South Indian population is associated with reduced risk for vascular disease in patients with diabetes mellitus

Sumi¹,

Ramachandran²,

Vr³

et al. 2015

Curr Res Cardiol

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BaCKgRouNd: Vascular inflammation leading to coronary artery disease (CAD) is a major complication of type 2 diabetes mellitus (T2DM). The chemokine receptor CX3CR1 is a key regulator in vascular injuryrelated inflammation. oBjeCTIVe: The authors examined the T280M and V249I gene variants of the CX3CR1 gene in patients with T2DM, CAD and CAD associated with T2DM, to understand the effect of these polymorphisms on the disease phenotype. MeThodS: Whole blood samples were collected from 913 South Indian subjects comprising 160 patients with T2DM, 284 with T2DM and CAD, 198 with CAD and 271 healthy subjects. T280M and V249I variants of the CX3CR1 gene were genotyped in these study subjects using polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis and PCR-DNA sequencing. ReSulTS:Multivariate logistic regression analysis revealed that the frequencies of 280M and 249I alleles were higher in controls than in cases in both the CAD and T2DM groups. Adjusted odds of T280M according to logistic regression were significant in all disease groups compared withhealthy subjects. Both MM and II genotypes of T280M and V249I polymorphisms were found to have an atheroprotective role in CAD and T2DM. The association of these polymorphisms were then examined in patients with CAD who were also diagnosed with diabetes. The M allele of T280M polymorphism was associated with attenuated risk for CAD and T2DM. CoNCluSIoNS:The present study demonstrated a protective role of the T280M variant of CX3CR1 gene for vascular complication in patients with T2DM. This polymorphism may reduce the binding strength of the chemokine receptor, thus attenuating inflammation both in vascular wall and adipose tissue.

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Association between Serum Fibroblast Growth Factor 21 and Coronary Artery Disease in Patients with Type 2 Diabetes

Cited by 28 publications

References 18 publications

Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus

Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus

Relationship between Circulating FGF21 Concentrations and the Severity of Coronary Artery Damage in Subjects with Cardiovascular Disease

Nonsynonymous T280M gene variant of CX3CR1 in South Indian population is associated with reduced risk for vascular disease in patients with diabetes mellitus

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