Serum Fibroblast Growth Factor-21 Levels Are Associated With Carotid Atherosclerosis Independent of Established Cardiovascular Risk Factors

Background and Aims: Fibroblast growth factor 21 (FGF21), an emerging metabolic hepatokine, is associated with atherosclerosis. An interaction with sex has been described in various populations. We aimed to study whether sex modulates the relationship between FGF21 and subclinical carotid atherosclerosis in a diabetes-enriched multiethnic population of Singapore. We explore differences in intermediary mechanisms, in terms of hypertension, lipids, and inflammation, between FGF21 and atherosclerosis.Methods: We recruited 425 individuals from a single diabetes center in Singapore, and demographics, anthropometry, metabolic profile, FGF21, and carotid ultrasonography were performed. Multivariable logistic regression models were used to study the association between subclinical atherosclerosis and FGF21 adjusting for age, ethnicity, body mass index (BMI), hemoglobin A1c (HbA1c), systolic and diastolic blood pressures, and low-density lipoprotein (LDL)-cholesterol separately for males and females as two groups after an interaction test.Results: An interaction test assessing interaction by sex on the relationship between subclinical atherosclerosis and FGF21 showed a significant interaction with sex (Pinteraction = 0.033). In the female subgroup, significant independent associations of standardized lnFGF21 with subclinical atherosclerosis were seen, with 1 SD increment in lnFGF21 being associated with 1.48-fold (95% CI: 1.03, 2.12; p = 0.036) increase in risk. In the male subgroup, the association of subclinical atherosclerosis with standardized lnFGF21 was not significant [odds ratio (OR) (95% CI): 0.90 (0.63, 1.28); p = 0.553]. We found sex interactions with pulse pressure being significantly associated in females only and triglycerides and C-reactive protein being associated with males only.Conclusion: FGF21 is positively associated with subclinical carotid atherosclerosis in women, but not in men. The sex–racial patterns in the mechanisms by which FGF21 causes subclinical atherosclerosis needs to be explored in larger population-based studies and mechanistically studied in greater detail.

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Gender differences in the association between fibroblast growth factor 21 and subclinical carotid atherosclerosis

Atherosclerosis ◽

10.1016/j.atherosclerosis.2020.10.397 ◽

2020 ◽

Vol 315 ◽

pp. e129

Author(s):

Y.J. Chee ◽

C.J. Lim ◽

L.L. Goh ◽

L.X.G. Toh ◽

R. Dalan

Keyword(s):

Gender Differences ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Carotid Atherosclerosis ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth

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Circulating level of fibroblast growth factor 21 is independently associated with the risks of unstable angina pectoris

Bioscience Reports ◽

10.1042/bsr20181099 ◽

2018 ◽

Vol 38 (5) ◽

Cited By ~ 3

Author(s):

Jing Cheng ◽

Xing Su ◽

Lei Qiao ◽

Chungang Zhai ◽

Wenqiang Chen

Keyword(s):

Risk Factors ◽

Growth Factor ◽

Angina Pectoris ◽

Unstable Angina ◽

Fibroblast Growth Factor ◽

Unstable Angina Pectoris ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Fgf21 Level ◽

And Control

There is increasing evidence that serum adipokine levels are associated with higher risks of cardiovascular diseases. As an important adipokine, fibroblast growth factor 21 (FGF21) has been demonstrated to be associated with atherosclerosis and coronary artery disease (CAD). However, circulating level of FGF21 in patients with angina pectoris has not yet been investigated. Circulating FGF21 level was examined in 197 patients with stable angina pectoris (SAP, n=66), unstable angina pectoris (UAP, n=76), and control subjects (n=55) along with clinical variables of cardiovascular risk factors. Serum FGF21 concentrations on admission were significantly increased more in patients with UAP than those with SAP (Ln-FGF21: 5.26 ± 0.87 compared with 4.85 ± 0.77, P<0.05) and control subjects (natural logarithm (Ln)-FGF21: 5.26 ± 0.87 compared with 4.54 ± 0.72, P<0.01). The correlation analysis revealed that serum FGF21 concentration was positively correlated with the levels of cardiac troponin I (cTnI) (r2 = 0.026, P=0.027) and creatine kinase-MB (CK-MB) (r2 = 0.023, P= 0.04). Furthermore, FGF21 level was identified as an independent factor associated with the risks of UAP (odds ratio (OR): 2.781; 95% CI: 1.476–5.239; P=0.002), after adjusting for gender, age, and body mass index (BMI). However, there were no correlations between serum FGF21 levels and the presence of SAP (OR: 1.248; 95% CI: 0.703–2.215; P=0.448). The present study indicates that FGF21 has a strong correlation and precise predictability for increased risks of UAP, that is independent of traditional risk factors of angina pectoris.

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