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Journal of Peking University (Health Sciences) ›› 2024, Vol. 56 ›› Issue (4): 715-721. doi: 10.19723/j.issn.1671-167X.2024.04.027

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Different levels and clinical significance of growth differentiation factor-15 in patients with atrial fibrillation

Ying WEI,Ming CUI,Shuwang LIU,Haiyi YU,Wei GAO,Lei LI*()   

  1. Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University; NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Peking University; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China
  • Received:2021-01-28 Online:2024-08-18 Published:2024-07-23
  • Contact: Lei LI E-mail:dr_lilei@bjmu.edu.cn
  • Supported by:
    the National Natural Science Foundation of China(31700674);the Beijing Natural Science Foundation(7212125)

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Abstract:

Objective: To measure the concentration of growth differentiation factor-15 (GDF-15) in the serum of patients with atrial fibrillation (AF), to study the correlations between the levels of GDF-15 and different factors including basic clinical information, biochemical examinations, and atrial structure, and further to explore the association between GDF-15 and AF types and structural remodeling. Methods: AF patients who were admitted to the ward of the Department of Cardiology at Peking University Third Hospital between October 2017 and October 2019 were prospectively enrolled. Patients admitted to the ward at the same time with sinus rhythm and no prior AF history were enrolled in the control group. Clinical information and blood samples of the patients were collected. Enzyme-linked immunosorbent assay was used to measure the concentration of GDF-15. SPSS 23.0 was used for statistical analysis. Results: In the study, 156 AF patients (64 persistent AF and 92 paroxysmal AF) and 38 patients of the control group were included. Serum GDF-15 levels in the AF group were significantly higher than in the control group [1 112 (723, 1 525) ng/L vs. 697 (499, 825) ng/L, P < 0.001]. Serum GDF-15 levels in the persistent AF group were significantly higher than in the paroxysmal AF group [1 140 (858, 1 708) ng/L vs. 1 090 (662, 1 374) ng/L, P=0.047]. The area under the curve (AUC) of serum GDF-15 levels for prediction of AF was 0.736 (95%CI: 0.651-0.822, P < 0.001). The cut-off value was 843.2 ng/L with a sensitivity of 68.2% and a specificity of 78.9%. The AUC of serum GDF-15 levels for prediction of persistent AF was 0.594 (95%CI: 0.504-0.684, P=0.047). The cut-off va-lue was 771.5 ng/L with a sensitivity of 82.8% and a specificity of 35.9%. Spearman rank correlation analysis showed that the serum GDF-15 levels were positively correlated with age (r=0.480, P < 0.001), left atrial pressure (LAP, r=0.300, P < 0.001), and also negatively correlated with left atrial appendage flow velocity (LAAV, r=-0.252, P=0.002). Multiple linear regression analysis showed that age and LAP affected the GDF-15 levels significantly (P < 0.05). Logistic regression analysis suggested GDF-15 (OR=1.002, 95%CI: 1.001-1.003, P=0.004) and left atrial diameter (LAD, OR=1.400, 95%CI: 1.214-1.616, P < 0.001) were independent predictors of AF. Conclusions: Serum GDF-15 levels are higher in AF patients. Meanwhile, serum GDF-15 levels are higher in persistent AF patients than paroxysmal AF patients. GDF-15 is associated with AF and atrial structural remodeling.

Key words: Growth differentiation factor-15, Atrial fibrillation, Structural remodeling

CLC Number: 

  • R541.7

Table 1

Baseline characteristics of the control group, paroxysmal AF and persistent AF patients"

Characteristics Control (n=38) Paroxysmal AF (n=92) Persistent AF (n=64) F/χ2 P value
Age/years, $\bar x \pm s$ 59±8 64±11 65±10 5.198 0.006*
Male, n (%) 22 (57.9) 44 (47.8) 43 (67.2) 5.804 0.055
BMI/ (kg/m2)，$\bar x \pm s$ 26±4 26±4 26±3 0.118 0.899
Smoker, n (%) 7 (18.4) 21 (22.8) 25 (39.1) 6.896 0.032*
Hypertension, n (%) 7 (18.4) 52 (56.5) 47 (73.4) 29.368 < 0.001*
Diabetes mellitus, n (%) 1 (2.6) 21 (22.8) 17 (26.6) 9.309 0.010*
CHD, n (%) 1 (2.6) 10 (10.9) 9 (14.1) 3.485 0.163
Heart failure, n (%) 0 (0) 2 (2.2) 9 (14.1) 10.684 0.003*
Stroke, n (%) 0 (0) 13 (14.1) 7 (10.9) 6.872 0.030*

Table 2

Laboratory results of the control group, paroxysmal AF and persistent AF patients"

Characteristics Control (n=38) Paroxysmal AF (n=92) Persistent AF (n=64) F/χ2 P value
WBC/(×109/L)，$\bar x \pm s$ 6.6±2.2 6.0±1.5 6.1±1.8 1.191 0.306
ALT/(U/L), M(P25, P75) 20 (13, 29) 20 (14, 30) 20 (15, 29) 0.915 0.633
AST/(U/L)，M(P25, P75) 21 (18, 26) 20 (17, 25) 20 (17, 25) 0.794 0.672
FBG/(mmol/L)，M(P25, P75) 5.3 (5.0, 5.6) 5.3 (4.7, 6.1) 5.4 (5.1, 6.1) 1.804 0.406
Cr/(μmol/L)，$\bar x \pm s$ 74±13 79±15 81±15 2.372 0.096
BUN/(mmol/L)，$\bar x \pm s$ 5.6±1.3 5.8±1.5 5.7±1.7 0.232 0.793
UA/(μmol/L)，M(P25, P75) 321 (273, 385) 322 (257, 396) 379 (313, 446) 8.862 0.012*
eGFR/(mL/min)，$\bar x \pm s$ 91±20 80±16 82±18 5.884 0.003*
GDF-15/ (ng/L)，M(P25, P75) 697(499, 825) 1 090 (662, 1 374) 1 140 (858, 1 708) 25.144 <0.001*

Figure 1

GDF-15 levels in control and AF groups AF, atrial fibrillation; GDF-15, growth differentiation factor-15."

Figure 2

GDF-15 levels in paroxysmal and persistent AF groups AF, atrial fibrillation; GDF-15, growth differentiation factor-15."

Table 3

Echocardiographic data of the control group, paroxysmal AF and persistent AF patients"

Characteristics Control (n=38) Paroxysmal AF (n=92) Persistent AF (n=64) F/χ2 P value
LAD/mm, $\bar x \pm s$ 33.2±2.8 37±4 41±4 41.970 < 0.001*
LAA/cm2, $\bar x \pm s$ 17.6±2.8 21±4 25±6 33.904 < 0.001*
LVEDD/mm, $\bar x \pm s$ 47±4 47±4 48±4 0.909 0.405
LAP/mmHg, M(P25, P75) 9 (8, 11) 10 (8, 13) 10 (9, 13) 4.085 0.130
LVEF/%, M(P25, P75) 70 (67, 74) 70 (68, 73) 68 (62, 71) 16.514 < 0.001*
RAA/cm2, M(P25, P75) 14 (13, 16) 16 (14, 17) 20 (17, 22) 61.295 < 0.001*
RVD/mm, M(P25, P75) 20.0 (18.0, 21.5) 21.0 (19.1, 22.5) 21.0 (19.4, 22.2) 4.931 0.085
LAAV/(m/s), M(P25, P75) 0.53 (0.39, 0.67) 0.33 (0.25, 0.45) -5.427 < 0.001*

Figure 3

Correlation analysis of serum GDF-15 levels and clinical factors A, correlation between GDF-15 and age; B, correlation between GDF-15 and eGFR; C, correlation between GDF-15 and LAP; D, correlation between GDF-15 and LAAV. GDF-15, growth differentiation factor-15; eGFR, estimated glomerular filtration rate; LAP, left atrial pressure; LAAV, left atrial appendage flow velocity."

Table 4

Multivariate linear regression analysis for serum GDF-15 in AF patients"

Variable Non-standardized partial regression coefficient Standard error Standardized partial regression coefficient t value P value
Age 20.968 5.144 0.377 4.077 < 0.001*
LAP 26.714 13.027 0.168 2.051 0.042*

Figure 4

ROC curve of serum GDF-15 level' s prediction for AF ROC, receiver operating characteristic; GDF-15, growth differentiation factor-15; AF, atrial fibrillation."

Figure 5

ROC curve of serum GDF-15 level' s prediction for persistent AF ROC, receiver operating characteristic; GDF-15, growth differentiation factor-15; AF, atrial fibrillation."

Table 5

Logistic regression analysis of AF"

Variable Regression coefficient Standard error Wald value OR 95%CI P value
GDF-15 0.002 0.001 8.29 1.002 1.001-1.003 0.004*
LAD 0.337 0.073 21.24 1.400 1.214-1.616 < 0.001*
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