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北京大学学报（医学版） ›› 2024, Vol. 56 ›› Issue (4): 715-721. doi: 10.19723/j.issn.1671-167X.2024.04.027

• 论著 • 上一篇    下一篇

心房颤动患者血清生长分化因子-15的表达差异和临床意义

韦莹,崔鸣,刘书旺,于海奕,高炜,李蕾*()   

  1. 北京大学第三医院心血管内科、血管医学研究所, 血管稳态与重构全国重点实验室，国家卫生健康委心血管分子生物学与调节肽重点实验室，心血管受体研究北京市重点实验室，北京 100191
  • 收稿日期:2021-01-28 出版日期:2024-08-18 发布日期:2024-07-23
  • 通讯作者: 李蕾 E-mail:dr_lilei@bjmu.edu.cn
  • 基金资助:
    国家自然科学基金(31700674);北京市自然科学基金(7212125)

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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摘要：

目的: 检测心房颤动(简称房颤)患者血清生长分化因子-15(growth differentiation factor-15，GDF-15)水平，分析其表达水平与临床因素、生化指标和心房结构的相关性，进一步分析GDF-15与房颤类型和结构重构的关系。方法: 纳入2017年10月至2019年10月于北京大学第三医院心内科住院的房颤患者，选择同期住院无房颤病史的窦性心律者为对照组。收集患者的临床资料，采用酶联免疫吸附反应法检测血清GDF-15水平。采用SPSS 23.0软件进行统计学分析。结果: 入组156例房颤患者，其中持续性房颤组64例，阵发性房颤组92例；对照组38例。房颤组血清GDF-15水平明显高于对照组[1 112 (723, 1 525) ng/L vs. 697 (499, 825) ng/L，P < 0.001]，持续性房颤组血清GDF-15水平明显高于阵发性房颤组[1 140 (858, 1 708) ng/L vs. 1 090 (662, 1 374) ng/L，P=0.047]，差异具有统计学意义。血清GDF-15预测房颤的受试者工作特征曲线下面积为0.736(95%CI：0.651~0.822，P < 0.001)，最佳临界值843.2 ng/L，其敏感性为68.2%，特异性为78.9%。血清GDF-15预测持续性房颤的受试者工作特征曲线下面积为0.594(95%CI：0.504~0.684，P=0.047)，最佳临界值771.5 ng/L，其敏感性为82.8%，特异性为35.9%。相关分析显示房颤患者血清GDF-15水平与年龄(r=0.480, P < 0.001)、左心房压力(left atrial pressure，LAP，r=0.300，P < 0.001)正相关，与左心耳血流速度(left atrial appendage flow velocity，LAAV，r=-0.252，P=0.002)负相关。多重线性回归显示年龄和LAP对血清GDF-15的影响差异具有统计学意义(P < 0.05)。Logistic回归分析表明GDF-15(OR=1.002，95%CI：1.001~1.003，P=0.004)和左心房前后径(left atrial diameter，LAD，OR=1.400，95%CI：1.214~1.616，P < 0.001)是房颤发生的独立危险因素。结论: 房颤患者血清GDF-15水平显著升高，且持续性房颤患者血清GDF-15水平高于阵发性房颤患者，血清GDF-15表达水平与房颤及心房结构重构具有一定相关性。

关键词: 生长分化因子-15, 心房颤动, 结构重构

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

中图分类号: 

  • R541.7

表1

对照组、阵发性房颤和持续性房颤患者的基线临床资料"

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*

表2

对照组、阵发性房颤和持续性房颤患者的生化指标"

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*

图1

房颤组与对照组的血清GDF-15水平比较"

图2

阵发性房颤组与持续性房颤组的血清GDF-15水平比较"

表3

对照组、阵发性房颤和持续性房颤患者的超声心动图指标"

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*

图3

血清GDF-15水平与临床因素相关性分析"

表4

房颤患者血清GDF-15影响因素的多重线性回归分析"

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*

图4

血清GDF-15水平预测房颤的ROC曲线"

图5

血清GDF-15水平预测持续性房颤的ROC曲线"

表5

房颤的多因素Logistic回归分析"

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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ISSN 1671-167X
CN 11-4691/R
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