Abstract
Objective: The purpose of this study was to examine the level of serum FGF21 in acute myocardial infarction (AMI) and to explore the association between serum FGF21 and major adverse cardiovascular events in AMI patients. Methods: A total of 238 Chinese patients were recruited for this study between January 2016 and June 2016, including 183 AMI patients and 55 patients without AMI were enrolled in this study. The level of serum FGF21 was measured by ELISA. Patients were followed-up after admission using a standardized protocol that included Outpatient follow-up and telephone contacts to record the Major Adverse Cardiovascular Events (MACEs). Finally, 165 patients were enrolled and followed up during the period of 24 months. Results: Circulating FGF21 level was elevated in the AMI patients compared to control (P < 0.05). Multivariate linear regression analysis showed that cTnI (β = -0.001, 95% CI = 0.021-0.001, P = 0.002), fibrinogen (β = -0.055, 95% CI = 0.098-0.013, P = 0.011) and hyperlipidemia (β = 0.129, 95% CI = 0.014-0.243, P = 0.011) were the independent risk factors for the serum of FGF21 in AMI patients. After follow-up, A Kaplan-Meier analysis showed that the all-cause mortality rate was not significantly different between the two groups (P = 0.4146). Meanwhile the rate of cardiovascular events was significantly higher in the high-FGF21 group than in the low-FGF21 group (P = 0.0399). In the multivariate Cox proportional hazards regression model suggested that the predictive independent risk factors for the occurrence of MACEs were FGF21 ≥ cut-off (HR: 1.637; 95% CI: 1.357-3.647, P = 0.029) and D-Dimer (HR: 1.420; 95% CI: 1.069-3.014, P = 0.046). Conclusion: Circulating FGF21 level is elevated in the AMI patients. In AMI patients, cTnI, fibrinogen and hyperlipidemia are the inde pendent risk factors for the serum of FGF21. Higher circulating FGF21 level is associated with increased MACEs rate. This study suggests that circulating FGF21 level may be a predictive marker of the clinical outcomes in AMI patients.
Keywords: FGF21, acute myocardial infarction, major adverse cardiovascular events
Introduction
In recent years, biomarkers have been widely studied in attempts to understand different cell functions and their role in cardiovascular disease (CVD). A number of biomarkers have been proved to be excellent predictors of outcome in patients with acute myocardial infarction (AMI). The family of fibroblast growth factors (FGFs) is a hormone-like factor that modulates a number of metabolic processes, including cell proliferation, development and hyperplasia in vitro and vivo. FGF21 plays a significant role in those processes including endothelial cell apoptosis, myocardial ischemia protection and so on [5,11]. Under the oxidative stress, myocardial cells can secrete FGF21, which can protect from damage myocardial hypertrophy induced by isoproterenol [16]. Recent studies show that there were a large amount of FGFR1 receptors and β Klotho distributing in cardiac myocytes and FGF21 also plays an important role in the field of cardiovascular disease [3,4].
Moreover, FGF21 was identified as an independent factor of acute myocardial infarction [22]. Although there are data to demonstrate that FGF21 might be a marker of coronary artery Disease, the role of FGF21 in the prognostication of AMI patients is still unclear. The aim of our study is to explore the relationship between FGF21 and clinical major adverse cardiovascular events in Chinese AMI patients.
Materials and methods
Study population
Totally 238 Chinese patients visiting the Department of Cardiology in Fujian Provincial Hospital for examination by coronary arteriography were recruited for this study from January 2016 and June 2016. After the coronary angiography, a total of 183 AMI patients were enrolled in this study (including ST-segment and non-ST-segment elevation). The control group included 55 patients with chest pain, whose coronary angiography and Troponin I (cTn I) were negative.
The included patients were Chinese patients aged over 18 years old in whom AMI was diagnosed according to published criteria. Exclusion criteria was the presence of acute or chronic viral hepatitis, fatty liver, drug or alcoholic-induced liver disease, a history of valvular heart disease, cardiomyopathy, myocarditis, congenital heart disease, peripheral vascular disease, or infective endocarditis, or of a combination of these ailments, acute or chronic kidney diseases (CKD stage 3-5), total parenteral nutrition, alcoholism, hyper-or hypothyroidism, cancer, current treatment with systemic corticosteroid, fenofibrate, metformin or thiazolidane theatment [13,14].
The local Ethics Committee of Fujian Provincial Hospital has approved this study, the Ethics research number (K2016-01-001) (Supplemental Materials) and all enrolled subjects provided informed consent.
Anthropometric and biochemical parameter
The base characteristics including height, weight and Blood pressure (BP) were measured. The body mass index (BMI) and mean arterial pressure (MAP) were calculated respectively. Smoking status was also recorded.
At hospital admission, Blood samples were measured and obtained 12 hours in the Department of Clinical Laboratory. The concentrations of glucose, total cholesterol, triglycerides, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, apolipoprotein (a), apolipoprotein (b), Serum creatinine, alkaline phosphatase (ALT), D-dimer two polymer and fibrinogen were measured using the Cobas 8000 biochemical autoanalyzer (Roche, Tokyo, Japan). Glycated hemoglobin A1c (HbA1c) was measured by high-performance liquid chromatography using HA-8180 automatic glycosylated hemoglobin analyzer (arkray, Tokyo, Japan).
Specific FGF21 ELISA
Plasma was collected with the patient in the fasting state on the next morning after hospitalization. Blood was collected and immediately processed. Peripheral blood was centrifuged at 2000 rpm for 10 minutes. Serum was collected and stored at -70°C until analysis. Serum concentrations of FGF21 were measured with a sandwich ELISA and a biotin-labelles antibody with the RD191108200R human FGF21 ELISA Kit (Biovendor Laboratory Medicine, Inc. Brno, Czech Republic). The intra-assay variation among the duplicates was < 4%. All of the coefficient of variation (CV) of inter-assay for quantitative detection were less than 5%.
Coronary angiography
All participated patients were subjected to coronary angiography. The arteriography analysis was conducted by two experienced interventional cardiologists, who were blinded to the study’s objective and design. A patient was considered to have CAD when a stenotic lesion resulting in a 50% or greater reduction in lumen diameter existed in at least one of the coronary arteries. According to the number of stenosis was detected in ≥ 50% of the lumen diameter of a coronary artery, we also divided it into single-vessel lesion, double vessel lesion and multi-vessel lesion.
Follow-up and endpoints definitions
Patients were followed-up after admission using a standardized protocol that included Out-patient follow-up and telephone contacts to record the Major Adverse Cardiovascular Events (MACEs). Endpoints were all-cause mortality and the occurrence of MACEs, including cardiac death and nonfatal outcomes: recurrent myocardial infarction (re-MI), target vessel revascularization (TVR) or re-admission due to advanced heart failure.
Death was defined as all causes of death. ReMI was defined by the presence of recurrent ischemic symptoms or EKG changes accompanied with t least one cardiac serum biomarker e.g. troponin I rises above the upper limit of 99% normal reference values measured during hospitalization. We defined TVR as the repeat PCI performed in the revascularization vessel during the index admission. Advanced heart failure requiring re-admission was diagnosed on the basis of clinical symptoms, NT-proBNP and echocardiography.
Statistical analysis
The version 19.0 SPSS software suite was used for all statistical analyses. All distributed data was expressed as mean ± standard deviation, and skewed data was expressed as median (inter-quartile range). Inter-group comparisons of clinical values were performed with student’s t test (normally distributed data) or the Mann-Whitney U test. Inter-group comparisons of categorical variables were analyzed using by the chi-square test. Multivariate linear regression analysis was performed to the correlation analysis. The correlation of two factors was assessed by Spearman or Kendall correlation test. The cut-off valve for FGF21 as a predictor for occurrence of MACEs was calculated by receiving operating characteristics (ROC) analysis. We then assessed the impact of the serum FGF21 levels on the cumulative patient and cardiovascular event-free survival rates according to the Kaplan-Meier method. Cox regression models were used to analyze the relationships between MACEs and the serum FGF21 levels. All reported values were two-tailed and considered statistically significant for P < 0.05.
Results
Clinical characteristics
A total of 238 patients were enrolled in this study and represented by 183 patients with AMI and 55 patients as control group. The flow chart of group in this follow-up study is Figure 1. The mean age of participates was 64.4 ± 10.7 years old. For the established cardio-vascular risk factors, the proportions of males (84.7%), smokers (62.8%) and diabetics (30.6%) were much larger in AMI group than in control group. In AMI group, lower proportion of patients were taking medication. The proportions of taking anti-hypertensive drugs, Anti-hyperlipidemic drugs and Anti-diabetic drugs were respectively 25.7%, 3.8% and 5.1%. The clinical characteristics analysis showed the AMI group had significantly higher fasting blood glucose, serum creatinine, Apo B, fibrinogen, NT-proBNP, cTnI, D-dimer (all P < 0.05) and lower HbA1c, HDL-C, albumin compared with control group. Meanwhile, age, BMI, medication, systolic blood pressure and diastolic blood pressure, HbA1c, TC, TG, LDL-C, Apo A, ALP and other clinical parameters were not different between this two groups (Table 1). As seen in Figure 2, serum FGF21 level was elevated in the AMI group compared to control group [143.8 (75.2-254.3) vs 121.0 (57.1-179.6), P < 0.05].
Figure 1.
Flow chart of this study.
Table 1.
Clinical and biochemistry characteristics of participants
| Variables | Control (N = 55) | AMI (N = 183) | P valve |
|---|---|---|---|
| Age (years) | 66.9 ± 9.5 | 63.6 ± 10.9 | 0.053 |
| Gender (male) (%) | 33 (60) | 155 (84.7)** | <0.001 |
| BMI (kg/m2) | 23.5 ± 2.3 | 23.9 ± 2.9 | 0.347 |
| Diabetes [n (%)] | 10 (18.2) | 56 (30.6) | 0.071 |
| Hypertension [n (%)] | 33 (60) | 74 (40.4)* | 0.011 |
| Hyperlipidemia [n (%)] | 21 (38.2) | 34 (18.6)** | 0.002 |
| AMI history [n (%)] | 0 | 25 (13.7)** | 0.004 |
| Smoker [n (%)] | 17 (30.9) | 115 (62.8)** | <0.001 |
| Medication [n (%)] | |||
| Anti-hypertensive drugs | 15 (27.3) | 47 (25.7) | 0.814 |
| Anti-diabetic drugs | 2 (3.6) | 14 (5.1) | 0.297 |
| Anti-hyperlipidemic drugs | 2 (3.6) | 7 (3.8) | 0.949 |
| Systolic blood pressure (mmHg) | 129.0 ± 19.7 | 128.7 ± 19.8 | 0.400 |
| Diastolic blood pressure (mmHg) | 74.4 ± 10.5 | 75.9 ± 11.9 | 0.387 |
| Mean arterial pressure (mmHg) | 95.5 ± 11.9 | 93.5 ± 12.9 | 0.311 |
| Fast plasma glucose (mmol/L) | 5.6 ± 1.5 | 6.2 ± 2.1* | 0.026 |
| HbA1c (%) | 6.2 (5.8, 6.7) | 6.0 (5.4, 6.9) | 0.870 |
| TG (mmol/L) | 1.4 ± 0.6 | 1.5 ± 0.9 | 0.244 |
| TC (mmol/L) | 4.2 ± 1.0 | 4.3 ± 1.0 | 0.768 |
| HDL-C (mmol/L) | 1.2 ± 0.3 | 1.0 ± 0.3** | <0.001 |
| LDL-C (mmol/L) | 2.6 ± 0.8 | 2.5 ± 0.9 | 0.199 |
| Apolipoprotein A (g/L) | 1.3 ± 0.2 | 1.2 ± 0.4 | 0.090 |
| Apolipoprotein B (g/L) | 0.8 ± 0.2 | 0.9 ± 0.3* | 0.014 |
| Albumin (g/L) | 42.9 ± 4.3 | 39.5 ± 4.3** | <0.001 |
| ALP (U/L) | 76.4 ± 25.0 | 79.5 ± 38.5 | 0.572 |
| Creatinine (μmol/L) | 73.3 ± 18.8 | 81.6 ± 26.0* | 0.028 |
| D-Dimer (mg/L) | 0.4 ± 0.2 | 0.7 ± 1.1* | 0.016 |
| Fibrinogen (g/L) | 3.3 ± 0.8 | 4.2 ± 1.2** | <0.001 |
| cTnI (ng/mL) | 0.01 (0, 0.01) | 5.6 (1.1, 28.3)** | <0.001 |
| NT-proBNP (pg/mL) | 124.0 (59.0, 200.9) | 678.0 (278.0, 1862.0)** | <0.001 |
| FGF21 (pg/mL) | 121.0 (57.1, 179.6) | 143.8 (75.2, 254.3)** | <0.001 |
Data were expressed as mean ± SD or median (25th and 75th percentile). P values in bold were statistically significant in the Student t-test or Chi-square test. AMI, acute myocardial infarction; ALP, alkaline phosphatase; BMI, body mass index; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol; NT-proBNP, N-terminal pro-brain natriuretic peptide; cTnI, cardiac Troponin I; FGF21, fibroblast growth factor 21.
AMI group vs control group;
P < 0.05;
P < 0.01.
Figure 2.
Serum FGF21 levels in patients with acute myocardial infarction (n = 183), compared with control patients (n = 55). Values are shown as medians with the interquartile range. Data were log-transformed before analysis, *P < 0.01.
Multivariate linear regression model for FGF21
In the spearman correlation analysis, serum FGF21 levels correlated negatively with Fibrinogen and HDL-C (r = -0.192, P = 0.009; r = -0.149, P = 0.044), positively correlated with HbA1C and triacylglycerol (r = 0.169, P = 0.014; r = 0.181, P = 0.024). The stepwise selection method was used to create a multivariate linear regression model for FGF21 (Table 2). Multivariate linear regression analysis show that cTnI (β = -0.001, 95% CI = 0.021-0.001, P = 0.002), fibrinogen (β = -0.055, 95% CI = 0.098-0.013, P = 0.011) and hyperlipidemia (β = 0.129, 95% CI = 0.014-0.243, P = 0.011) are the independent risk factors for the serum of FGF21 in AMI patients.
Table 2.
Independent factors of FGF21 were analyzed by multivariate linear regression analysis
| β | S.E | 95% CI | P value | |
|---|---|---|---|---|
| cTnI | -0.001 | 0.001 | 1.021-1.058 | 0.002 |
| Fibrinogen | -0.055 | 0.022 | 0.098-0.013 | 0.011 |
| Hyperlipidemia | 0.129 | 0.058 | 0.014-0.243 | 0.028 |
β: standardized regression coefficient; S.E: standard errors; OR: odds ratio; 95% CI, 95% confidence interval.
Predictive value and prognostic value of FGF21
Incidence of follow-up in AMI patients
A total of 183 patients were hospitalized during the study period. Among them, 18 patients refused to participate. Only 165 patients were enrolled and followed up during the period of 24 months. The total incidence of all-cause mortality was 9.1% (15 of 165 patients), including seven patients cardiac death and eight patients non-cardiac death. Additionally, the incidence of Major Adverse Cardiovascular Events (MACEs) was 18.2% (30 of 165 patients). There were 2 patients recurrent myocardial infarction, 13 patients re-admission due to advanced heart failure, 8 patients suffered the TVR and 7 patients had cardiac death.
ROC analysis
The receiver operating characteristic (ROC) curves of FGF21 and traditional cardiovascular risk factors in predicting MACEs were presented in Figure 3, and pairwise comparison between areas under ROC curves (AUCs) were performed. the model consisting of traditional cardiovascular risk factors such as age, BMI smoking status, hypertension, diabetes and hyperlipidemia showed a 0.676 AUC (95% CI, 0.577-0.775, P = 0.04) with a 88.9% sensitivity and 59.2% specificity.
Figure 3.
The ROC curve between FGF21 and traditional cardiovascular risk factors in predicting occurrence of MACEs.
Contribution of Serum FGF21 Levels in discriminating MACEs was assessed by receiver-operating characteristic analysis which showed that the serum FGF21 levels had a 0.672 area under curve (AUC) (95% CI, 0.564-0.780, P = 0.005) with a 80.0% sensitivity and 50.4% specificity for predicting MACEs. After calculation of the Youden index, the cut-off value of a FGF21 for predicting the occurrence of MACEs produced was 123.0 pg/mL.
Overall survival and MACE-free survival analysis
In 183 AMI patients, the serum FGF21 concentrations ranged from 16.24 to 925.11 pg/mL (median: 143.78, [IQR]: 75.2-254.3 pg/mL). The subjects were categorized as follows: low-FGF21 group: (subjects with circulating FGF21 level < cut-off value) and high-FGF21 group: subjects with circulating FGF21 level ≥ cut-off value).
According to the serum FGF21 concentrations, the subjects were categorized as low-FGF21 group (n = 73) and high-FGF21 group (n = 92). After the follow-up, four patients (two congestive heart failure, one re-myocardial infarction, one sudden cardiac death) in the low-FGF21 group and six patients (four heart failure, two sudden cardiac death) in the high-FGF21 died of cardiac events. Meanwhile there were two patients (one pneumonia, one esophageal cancer) in the low-FGF21 group and three patients (one leukemia, one stroke, one pulmonary embolism) in the high-FGF21 group died of non-cardiovascular events. A Kaplan-Meier analysis showed that the all-cause mortality rate was not significantly different between the two groups [9.8% (n = 9) vs 8.3% (n = 6), log-rank, P = 0.4146] (Figure 4A). Furthermore, the cardiac death rate was similar between the two groups [6.5% (n = 6) vs 5.4% (n = 4), log-rank, P = 0.826].
Figure 4.
Kaplan-Meier curve for cumulative probability of different clinical outcomes.
Meanwhile, we also found that nine patients (congestive heart failure, n = 3; re-infarction, n = 1; TVR, n = 1; cardiac death, n = 4) in the low-FGF21 group and twenty-one patients (congestive heart failure, n = 10; re-infarction, n = 2; TVR, n = 3; cardiac death, n = 6) in the high-FGF21 group experienced MACEs. A Kaplan-Meier analysis showed the rate of cardio-vascular events was significantly higher in the high-FGF21 group than in the low-FGF21 group [24.4% (n = 20) vs 12.1% (n = 10), log-rank, P = 0.0399] (Figure 4B).
The Kaplan-Meier analysis showed that the mortality rate was not different between the two groups (Log-rank, P = 0.4146) (Figure 4A). while the MACE-free survival rate was significantly higher in the low-FGF21 group than in the high-FGF21 group (Log-rank, P = 0.0399) (Figure 4B).
A univariate Cox regression analysis showed that age, history of hyperlipideia, high total cholesterol, low LDL-cholesterol, higher D-Dimer and FGF21 were predictive for the Cardiovascular events cardiovascular events. In the multivariate Cox proportional hazards regression model including age, gender, BMI, diabetes history, hypertension history, history of hyperlipideia, LDL-c, HDL-c D-Dimer, TG, TC, Fibrinogen, FGF21 ≥ 123 (pg/mL)) suggested that the predictive independent risk factors for the occurrence of MACEs were FGF21 ≥ 123 (pg/mL) (HR: 1.637; 95% CI: 1.357-3.647, P = 0.029) and D-Dimer (HR: 1.420; 95% CI: 1.069-3.014, P = 0.046). Higher circulating FGF21 level and D-Dimer level were associated with a higher MACEs rate (Tables 3, 4).
Table 3.
Univariate Cox regression of cardiovascular events
| Variable | Major Adverse Cardiovascular events | |
|---|---|---|
|
| ||
| HR (95% CI) | P value | |
| Age (years) | 1.042 (1.005-1.080) | 0.025 |
| Gender (male) | 0.488 (0.217-1.0970 | 0.082 |
| BMI (kg/m2) | 0.985 (0.871-1.114) | 0.811 |
| Diabetes history | 1.734 (0.825-3.643) | 1.734 |
| Hypertension history | 1.925 (0.901-4.113) | 0.091 |
| History of Hyperlipideia | 0.379 (0.131-1.095) | 0.044 |
| Smoking | 0.677 (0.329-1.394) | 0.29 |
| HDL-c (mmol/L) | 0.237 (0.053-1.064) | 0.06 |
| LDL-c (mmol/L) | 0.547 (0.35-0.856) | 0.008 |
| TG (mmol/L) | 0.569 (0.294-1.102) | 0.094 |
| TC (mmol/L) | 1.528 (0.356-0.782) | 0.001 |
| D-Dimer (mg/L) | 1.526 (1.174-1.983) | 0.002 |
| Fibrinogen (g/L) | 0.981 (0.737-1.305) | 0.893 |
| FGF21 ≥ 123 (pg/mL) | 1.914 (1.142-3.207) | 0.014 |
HR, hazard ratio; 95% CI, 95% confidence interval.
Table 4.
Multivariate Cox regression of cardiovascular events
| Variable | Major Adverse Cardiovascular events | |
|---|---|---|
|
| ||
| HR (95% CI) | P value | |
| Age (years) | 1.013 (0.976-1.051) | 0.500 |
| Gender (male) | 0.520 (0.213-1.267) | 0.150 |
| LDL-c (mmol/L) | 0.756 (0.449-1.274) | 0.294 |
| D-Dimer (mg/L) | 1.420 (1.069-3.014) | 0.046 |
| FGF21 ≥ 123 (pg/mL) | 1.637 (1.357-3.647) | 0.028 |
HR, hazard ratio; 95% CI, 95% confidence interval.
Discussion
FGF21 is a novel polypeptide ligand that has been shown to play a pivotal role in the regulation of glucose homeostasis and lipid metabolism [15,17]. After binding to the FGF receptor and β-Klotho, FGF21 activates the Mitogen-Activated Protein Kinase (MAPK) signaling pathway and enhances glucose uptake and ketogenesis. The heart was traditionally not regarded as a target or source of FGF21 because of modest expression of FGF21 and β-Klotho. However, emerging evidence suggests that the cardiomyocyte secreted FGF21 as an autocrine factor to protect the heart from adverse cardiac remodeling. Additionally, FGF21 was found to enhance cholesterol efflux mediated by LXRα-dependent ATP binding cassette (ABC) A1 and G1, which may have a protective effect against atherosclerosis [10]. Therefore, the anti-atherosclerosis function of FGF21 may provide both direct and indirect effects through the direct inhibition of apoptosis of the endotheliocyte and the indirect improvement of metabolism of glucose and serum lipid.
Many studies had shown that FGF21, as a potential biomarker, played an important role in cardiovascular diseases. FGF21 was elevated in heart failure with preserved LV ejection fraction (HFpEF) and associated with left ventricular diastolic dysfunction [1]. Researchers found circulating FGF21 was significantly elevated in atrial fibrillation patients which may be associated with atrial remodeling [19]. Several studies had demonstrated that FGF21 may play a physiological role in improving endothelial cell apoptosis and in regulating atherosclerosis [7]. Chow found that there was a positive correlation between FGF21 and carotid atherosclerosis and FGF21 was an independent risk factors for carotid atherosclerosis [2]. Lin et al found that serum FGF21 was significantly elevated in the coronary artery disease (CAD) patient. Multivariate linear regression analysis found that FGF21 correlated independently with CAD occurrence [12]. Shen [18] found that elevated serum FGF21 was an independent risk factor for CAD in 233 patients. However, only a few study analyzed the correlation between FGF21 and AMI. In our study, FGF21 level was elevated in the AMI group compared with control group [143.8 (75.2-254.3) vs 121.0 (57.1-179.6) (P < 0.05)]. In the spearman correlation analysis, serum FGF21 levels correlated negatively with Fibrinogen and HDL-C (r = -0.192, P = 0.009; r = -0.149, P = 0.044), positively correlated with HbA1C and triacylglycerol (r = 0.169, P = 0.014; r = 0.181, P = 0.024). Multivariate linear regression analysis showed that cTnI (β = -0.001, 95% CI = 0.021-0.001, P = 0.002), fibrinogen (β = -0.055, 95% CI = 0.098-0.013, P = 0.011) and hyperlipidemia (β = 0.129, 95% CI = 0.014-0.243, P = 0.011) were the independent risk factors for the serum of FGF21 in AMI patients. More and more research results found FGF21 showed a close relationship with cardiovascular diseases.
Several studies also indicated that FGF21 might function as a critical metabolic hormone in metabolic related diseases [6,8,9,21]. FGF-21 was a hormone-like factors which was identified as a potent metabolic regulator in the recent years. The researchers found that circulating FGF21 was significantly elevated in metabolic related diseases [20]. Although it had been reported that FGF21 can improve insulin-sensitivity and exert beneficial effects on lipid metabolism, its role as a prognostic factor in cardiovascular disease had not been analyzed so far. Recent clinical studies had reported that the correlation between serum FGF21 and cardiovascular disease, but very few reports had investigated FGF21 as a predictive marker of the clinical outcomes. Our study showed that the rate of 24-months cardiovascular events was significantly higher in the high-FGF21 group than in the low-FGF21 group (P = 0.0399). In the multivariate Cox proportional hazards regression model, including age, gender, History of Hyperlipideia, LDL-c, D-Dimer, TC and FGF21 ≥ 123 pg/mL, the predictive independent risk factors for the occurrence of MACEs were FGF21 ≥ 123 pg/mL (HR: 1.637; 95% CI: 1.357-3.647, P = 0.028) and D-Dimer (HR: 1.420; 95% CI: 1.069-3.014, P = 0.046). Higher circulating FGF21 level is associated with increased MACEs rate. Although our results did not support FGF21 to replace the role of cTnI, the strong association between FGF21 and acute myocardial infarction supported the findings of previous animal studies and provided us novel insight of how metabolic regulators affect the progression of cardiovascular disease and its clinical outcomes.
There were some limitations in our study. Firstly, our study population was composed of Chinese middle-and elderly patients presenting at a single hospital. The sample size was relatively inadequate and came from a single center. As a novel member of the endocrine FGF subfamily, the mechanisms of FGF21 in the cardiovascular system are still unclear, more multi-centers studies should be considered to resolve the controversy problem. In addition, correlation analysis is likely to be affected by a variety of uncorrected confounding factors present in daily life. Furthermore, our finding of the association between serum FGF21 and AMI patients’ prognosis remains to be confirmed in other population-based studies involving even larger sample sizes and a wider multi-centers study.
Conclusions
We conclude circulating FGF21 level was elevated in the AMI patients compared to control. In AMI patients, cTnI, fibrinogen and hyperlipidemia were the independent risk factors for the serum of FGF21. Higher circulating FGF21 level is associated with increased MACEs rate. This study suggests that circulating FGF21 levels may be a predictive marker of the clinical outcomes.
Acknowledgements
This work was supported by National Natural Science Foundation of China (81470021). It was also supported by the Key Project of Cultivating Young Talent in Fujian provincial health and family planning commission (2016-ZQN-8).
Disclosure of conflict of interest
None.
Supporting Information
References
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