The relationship between plasma IGFBP2, SMOC2 levels and cardiac function and prognosis in patients with chronic heart failure

doi:10.11958/20250289

Abstract

Abstract:

Objective To explore the relationship between plasma insulin-like growth factor-binding protein 2 (IGFBP2), secreted modular calcium-binding protein 2 (SMOC2) levels and cardiac function and prognosis in patients with chronic heart failure (CHF). Methods A total of 120 CHF patients (the CHF group) and 60 healthy volunteers undergoing physical examination during the same period (the control group) were enrolled. CHF patients were classified according to the New York Heart Association (NYHA) functional classification into the class Ⅱ (46 cases) group, the class Ⅲ group (42 cases) and the class Ⅳ group (32 cases). Based on the 6-month prognosis, patients were further divided into the poor prognosis group (42 cases) and the good prognosis group (78 cases). Plasma IGFBP2 and SMOC2 levels were measured using enzyme-linked immunosorbent assay. The correlation between plasma IGFBP2 and SMOC2 levels with NYHA functional classification was analyzed using Spearman rank correlation. Multivariate unconditional Logistic regression was used to analyze the relationship between plasma IGFBP2 and SMOC2 levels and poor prognosis in CHF patients. The predictive efficacy of plasma IGFBP2 and SMOC2 levels for CHF prognosis was evaluated using receiver operating characteristic (ROC) curve analysis. Results Compared with the control group, plasma IGFBP2 and SMOC2 levels were significantly higher in the CHF group (P<0.05). Plasma IGFBP2 and SMOC2 levels increased progressively in the class Ⅱ group, the class Ⅲ group and the class Ⅳ group (P<0.05). Plasma IGFBP2 and SMOC2 levels were positively correlated with NYHA classification of CHF patients (P<0.05). The 6-month poor prognosis rate for the 120 CHF patients was 35.00% (42/120). Compared with the good prognosis group, the plasma IGFBP2 and SMOC2 levels were significantly higher in the poor prognosis group (P<0.05). After adjusting for confounding factors, high levels of IGFBP2 and SMOC2 were independent risk factors for poor prognosis in CHF patients (P<0.05). The area under the curve (AUC) for the combined prediction of poor prognosis in CHF patients by plasma IGFBP2 and SMOC2 levels was 0.899, which was higher than that of plasma IGFBP2 (0.800) and SMOC2 (0.782) alone (P<0.05). Conclusion The plasma levels of IGFBP2 and SMOC2 in CHF patients are increased, which is related to the decrease of cardiac function and poor prognosis. The combination of plasma IGFBP2 and SMOC2 levels has a high predictive efficiency for the prognosis of CHF patients.

Key words: heart failure, prognosis, insulin-like growth factor-binding protein 2, secreted modular calcium-binding protein 2

CLC Number:

R541.62

Figures/Tables 6

References 24

[1]	国家心血管病中心, 中国心血管健康与疾病报告编写组. 中国心血管健康与疾病报告编写组. 中国心血管健康与疾病报告2023概要[J]. 中国循环杂志, 2024, 39(7):625-660.
	National Cardiovascular Center, China Cardiovascular Health and Disease Reporting Group. Chinese Cardiovascular Health and Disease Report 2023 Summary[J]. Chinese Journal of Circulation, 2024, 39(7):625-660. doi:10.3969/j.issn.1000-3614.2024.07.001.
[2]	中华医学会心血管病学分会, 中国医师协会心血管内科医师分会, 中国医师协会心力衰竭专业委员会, 等. 中国心力衰竭诊断和治疗指南2024[J]. 中华心血管病杂志, 2024, 52(3):235-275.
	Cardiovascular Branch of Chinese Medical Association,Cardiovascular Physicians Branch of Chinese Medical Doctor Association, Heart Failure Professional Committee of Chinese Medical Doctor Association, et al. Chinese heart failure diagnosis and treatment guidelines 2024[J]. Chinese Journal of Cardiovascular Diseases, 2024, 52(3):235-275. doi:10.3760/cma.j.cn112148-20231101-00405.
[3]	蒋美燕, 黄恒贵, 袁仕国. QRS波群时限联合血清angptl2、angptl7、sST2对急性心力衰竭患者短期预后的评估价值[J]. 天津医药, 2023, 51(10):1136-1140.
	JIANG M Y, HUANG H G, YUAN S G. The value of QRS wave duration combined with serum angptl2,angptl7 and sST2 in evaluating the short-term prognosis of patients with acute heart failure[J]. Tianjin Med J, 2023, 51(10):1136-1140. doi:10.11958/20230053.
[4]	中国医师协会心力衰竭专业委员会, 国家心血管病专家委员会心力衰竭专业委员会, 中华心力衰竭和心肌病杂志编辑委员会. 心力衰竭生物标志物临床应用中国专家共识[J]. 中华心力衰竭和心肌病杂志, 2022, 6(3):175-192.
	Chinese Medical Association Heart Failure Committee, National Cardiovascular Expert Committee Heart Failure Committee, Editorial Board of Chinese Journal of Heart Failure and Cardiomyopathy. Chinese expert consensus on clinical application of heart failure biomarkers[J]. Chinese Journal of Heart Failure and Cardiomyopathy, 2022, 6(3):175-192. doi:10.3760/cma.j.cn101460-20220810-00071.
[5]	SONG F, ZHOU X X, HU Y, et al. The roles of insulin-like growth factor binding protein family in development and diseases[J]. Adv Ther, 2021, 38(2):885-903. doi:10.1007/s12325-020-01581-x.
[6]	BERRY M, GALINIER M, DELMAS C, et al. Proteomics analysis reveals IGFBP2 as a candidate diagnostic biomarker for heart failure[J]. IJC Metabolic & Endocrine, 2015, 3(6):5-12. doi:10.1016/j.ijcme.2014.11.003.
[7]	AWWAD K, HU J, SHI L, et al. Role of secreted modular calcium-binding protein 1(SMOC1)in transforming growth factor β signalling and angiogenesis[J]. Cardiovasc Res, 2015, 106(2):284-294. doi:10.1093/cvr/cvv098.
[8]	TU D, XU Q, ZUO X, et al. Uncovering hub genes and immunological characteristics for heart failure utilizing RRA,WGCNA and machine learning[J]. Int J Cardiol Heart Vasc, 2024,51:101335. doi:10.1016/j.ijcha.2024.101335.
[9]	MCDONAGH T A, METRA M, ADAMO M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure[J]. Eur Heart J,2021, 42(48):4901. doi:10.1093/eurheartj/ehab670.
[10]	吴凡, 张文杰. 慢性心力衰竭患者出院后6个月内发生不良结局风险预测模型构建及验证[J]. 实用心脑肺血管病杂志, 2023, 31(1):27-32.
	WU F, ZHANG W J. Construction and verification of a risk prediction model for adverse outcomes in patients with chronic heart failure within 6 months after discharge[J]. Practical Journal of Cardiopulmonary Vascular Disease, 2023, 31(1):27-32. doi:10.12114/j.issn.1008-5971.2023.00.007.
[11]	中国老年医学学会心电及心功能分会, 中国医师协会心血管内科分会, 中国心衰中心联盟专家委员会. 慢性心力衰竭加重患者的综合管理中国专家共识2022[J]. 中国循环杂志, 2022, 37(3):215-225.
	China Geriatrics Society ECG and Cardiac Function Branch, Chinese Medical Association Cardiovascular Branch, China Heart Failure Center Alliance Expert Committee. Chinese expert consensus on comprehensive management of patients with exacerbation of chronic heart failure 2022[J]. Chinese Circulation Journal, 2022, 37(3):215-225. doi:10.3969/j.issn.1000-3614.2022.03.003.
[12]	中国医师协会心血管内科医师分会, 中国心衰中心联盟,《慢性心力衰竭"新四联"药物治疗临床决策路径专家共识》工作组. 慢性心力衰竭"新四联"药物治疗临床决策路径专家共识[J]. 中国循环杂志, 2022, 37(8):769-781.
	Chinese College of Cardiovascular Physicians, Chinese Heart Failure Center Alliance, The Task Force for Expert Consensus,Decision Pathway for Quadruple Pharmacotherapy Management of Chronic Heart Failure. Expert consensus on decision-making pathway for quadruple pharmacotherapy management of chronic heart failure[J]. Chinese Journal of Circulation, 2022, 37(8):769-781. doi:10.3969/j.issn.1000-3614.2022.08.003.
[13]	胡盛寿. 心室辅助装置治疗心力衰竭现状和未来思考[J]. 中华心力衰竭和心肌病杂志, 2022, 6(2):77-79.
	HU S S. Current status and future thinking of ventricular assist device in the treatment of heart failure[J]. Chinese Journal of Heart Failure and Cardiomyopathy, 2022, 6(2):77-79. doi:10.3760/cma.j.cn101460-20220829-00078.
[14]	ADASHEVA D A, SEREBRYANAYA D V. IGF signaling in the heart in health and disease[J]. Biochemistry (Mosc), 2024, 89(8):1402-1428. doi:10.1134/S0006297924080042.
[15]	TAKAHASHI S I, PERKS C M. Editorial:The role of the IGF/insulin-IGFBP axis in normal physiology and disease[J]. Front Endocrinol (Lausanne), 2022, 4(13):892140. doi:10.3389/fendo.2022.892140.
[16]	LEE W S, ABEL E D, KIM J. New insights into IGF-1 signaling in the heart[J]. Physiology(Bethesda), 2024, 39(5):10. doi:10.1152/physiol.00003.2024.
[17]	DE GIORGI A, MARRA A M, IACOVIELLO M, et al. Investigators. Insulin-like growth factor-1(IGF-1) as predictor of cardiovascular mortality in heart failure patients: data from the T.O.S.CA. registry[J]. Intern Emerg Med, 2022, 17(6):1651-1660. doi:10.1007/s11739-022-02980-4.
[18]	赵松, 张毅. 心外膜脂肪组织:从解剖生理、临床评估到心血管疾病的干预靶点[J]. 中华心血管病杂志(网络版), 2022, 5(1):1-8.
	ZHAO S, ZHANG Y. Epicardial adipose tissue:from anatomical physiology, clinical evaluation to cardiovascular disease intervention targets[J]. Chinese Journal of Cardiovascular Disease(online version), 2022, 5(1):1-8. doi:10.3760/cma.j.cn116031.2022.1000111.
[19]	CHOY M, HUANG Y, PENG Y, et al. Association between epicardial adipose tissue and incident heart failure mediating by alteration of natriuretic peptide and myocardial strain[J]. BMC Med, 2023, 21(1):117. doi:10.1186/s12916-023-02836-4.
[20]	王晓萍, 周婵娟, 谭玲玲, 等. 慢性心力衰竭合并肌少症的研究进展[J]. 中华老年多器官疾病杂志, 2022, 21(7):552-556.
	WANG X P, ZHOU C J, TAN L L, et al. Research progress on chronic heart failure with sarcopenia[J]. Chinese Journal of Geriatric Multiple Organ Diseases, 2022, 21(7):552-556. doi:10.11915/j.issn.1671-5403.2022.07.119.
[21]	WANG Y, YANG H, SU X, et al. TGF-β1/SMOC2/AKT and ERK axis regulates proliferation, migration, and fibroblast to myofibroblast transformation in lung fibroblast,contributing with the asthma progression[J]. Hereditas, 2021, 158(1):47. doi:10.1186/s41065-021-00213-w.
[22]	XIN C, LEI J, WANG Q, et al. Therapeutic silencing of SMOC2 prevents kidney function loss in mouse model of chronic kidney disease[J]. iScience, 2021, 24(10):103193. doi:10.1016/j.isci.2021.103193.
[23]	RUI H, ZHAO F, YUHUA L, et al. Suppression of SMOC2 alleviates myocardial fibrosis via the ILK/p38 pathway[J]. Front Cardiovasc Med, 2023,9:951704. doi:10.3389/fcvm.2022.951704.
[24]	REN Y, WU Y, HE W, et al. SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy[J]. Open Med(Wars), 2023, 18(1):20230752. doi:10.1515/med-2023-0752.

组别	n	性别（男/女）	年龄/岁	IGFBP2/（μg/L）	SMOC2/（ng/L）
对照组	60	38/22	57.85±8.30	533.43±206.61	676.70±305.20
CHF组	120	70/50	59.93±10.13	893.84±189.93	1 264.86±334.44
χ²或t		0.519	0.171	11.653^＊＊	11.444^＊＊

组别	n	性别（男/女）	年龄/岁	IGFBP2/（μg/L）	SMOC2/（ng/L）
对照组	60	38/22	57.85±8.30	533.43±206.61	676.70±305.20
CHF组	120	70/50	59.93±10.13	893.84±189.93	1 264.86±334.44
χ²或t		0.519	0.171	11.653^＊＊	11.444^＊＊

组别	n	IGFBP2/（μg/L）	SMOC2/（ng/L）
Ⅱ级组	46	767.24±132.98	1 010.02±263.71
Ⅲ级组	42	873.86±95.31^a	1 258.23±202.78^a
Ⅳ级组	32	1 102.03±178.11^ab	1 639.89±180.01^ab
F		115.021^＊＊	150.522^＊＊

组别	n	IGFBP2/（μg/L）	SMOC2/（ng/L）
Ⅱ级组	46	767.24±132.98	1 010.02±263.71
Ⅲ级组	42	873.86±95.31^a	1 258.23±202.78^a
Ⅳ级组	32	1 102.03±178.11^ab	1 639.89±180.01^ab
F		115.021^＊＊	150.522^＊＊

组别			n	性别（男/女）			年龄/岁		NYHA心功能分级（Ⅱ级/Ⅲ级/Ⅳ级）			吸烟史			饮酒史			糖尿病	高血压			冠心病
良好预后组			78	44/34			58.35±11.11		43/26/9			23（29.5）			13（16.7）			20（25.6）	58（74.4）			36（46.2）
不良预后组			42	26/16			62.86±7.23		3/16/23			18（42.9）			11（26.2）			16（38.1）	32（76.2）			20（47.6）
χ²、t或Z				0.339			2.683^＊		5.935^＊＊			2.170			1.548			2.016	0.049			0.024
组别		心房颤动			高脂血症			收缩压/mmHg			舒张压/mmHg			LVEF		NT-proBNP/（ng/L）					白蛋白/（g/L）
良好预后组		22（28.2）			19（24.4）			138.68±16.62			82.65±13.84			0.52±0.07		2 380.6±936.0					37.04±6.03
不良预后组		20（47.6）			14（33.3）			142.95±18.43			86.31±16.43			0.48±0.04		3 293.1±1 235.1					35.07±5.38
χ²或t		4.523^＊			1.103			1.293			1.291			3.696^＊＊		4.542^＊＊					1.777
组别	血尿酸/（μmol/L）					总胆红素/（μmol/L）				血肌酐/（μmol/L）			血尿素氮/（mmol/L）				IGFBP2/（μg/L）			SMOC2/（ng/L）
良好预后组	474.03±146.67					15.22±3.94				82.17±33.66			10.88±3.86				827.15±157.31			1 148.92±310.39
不良预后组	509.79±171.21					14.00±4.04				90.24±29.97			12.22±4.01				1 017.67±184.54			1 480.17±265.78
t	1.200					1.597				1.301			1.797				5.591^＊＊			5.854^＊＊