血清DKK-1检测对类风湿关节炎患者颈动脉内中膜增厚的临床价值

doi:10.3969/j.issn.1004-583X.2025.02.007

摘要/Abstract

摘要：

目的探讨血清Dickkopf相关蛋白1(Dickkopf-related protein 1,DKK-1)对类风湿关节炎(rheumatoid arthritis,RA)患者颈动脉内中膜厚度(carotid intima-media thickness,cIMT)增厚的临床价值。方法纳入2022年12月-2024年1月在梅州市人民医院风湿免疫科诊断为RA的患者82例。根据cIMT,将患者分为cIMT增厚组(n=29)和cIMT正常组(n=53)。比较两组临床资料,分析RA患者cIMT增厚的危险因素。最后比较不同疾病活动度下,cIMT增厚和cIMT正常患者临床资料的差异。结果两组年龄、性别、脑血管疾病史、总胆固醇及血清DKK-1水平差异均有统计学意义(P<0.05)。多因素logistic回归分析提示,血清DKK-1水平、男性和高龄是RA合患者cIMT增厚的独立危险因素(P<0.05)。亚组分析提示,低疾病活动度RA患者中,cIMT增厚和cIMT正常患者性别、年龄、C反应蛋白、血沉、病程、类风湿因子、抗环瓜氨酸肽抗体、白介素6和血清DKK-1水平差异均无统计学意义(P>0.05);在中疾病活动度RA患者中,cIMT增厚患者抗环瓜氨酸肽抗体水平较高(P<0.05);在高疾病活动度RA患者中,cIMT增厚和cIMT正常患者年龄、病程和血清DKK-1水平差异均有统计学意义(P<0.05)。结论血清DKK-1水平是RA患者cIMT增厚的独立危险因素,可能对RA的早期动脉粥样硬化起到临床预测作用。

关键词: 关节炎, 类风湿, Dickkopf相关蛋白1, 颈动脉内膜中膜厚度, 动脉粥样硬化

Abstract:

Objective To investigate the clinical value of serum Dickkopf-related protein 1 (DKK-1) in the carotid intima-media thickness (cIMT) in patients with rheumatoid arthritis (RA). Methods A total of 82 patients diagnosed with RA in the Department of Rheumatology and Immunology, Meizhou People's Hospital from December 2022 to January 2024 were included. According to cIMT, patients were divided into cIMT thickening group (n=29) and cIMT normal group (n=53). The clinical data of the two groups were compared, and the risk factors of cIMT thickening in RA patients were explored by multivariate logistic regression analysis. Finally, the clinical data of RA patients with cIMT thickening and normal cIMT were compared under different disease activity. Results There were significant differences in age, sex, history of cerebrovascular disease, total cholesterol and serum DKK-1 levels between groups (P<0.05). Multivariate logistic regression analysis showed that serum DKK-1 level, male and advanced age were independent risk factors for cIMT thickening in RA patients (P<0.05). The results of subgroup analysis prompted that there was no significant difference in gender, age, C-reactive protein, erythrocyte sedimentation rate, course of disease, rheumatoid factor, anti-cyclic citrullinated peptide antibody, interleukin-6, and serum DKK-1 levels between cIMT thickening and cIMT normal patients in RA patients with low disease activity (P>0.05). In RA patients with moderate disease activity, the level of anti-cyclic citrullinated peptide antibody was significantly higher in the cIMT thickening group than the cIMT normal group (P<0.05). In RA patients with high disease activity, there were significant differences in age, course of disease and serum DKK-1 level between cIMT thickening and cIMT normal groups (P<0.05). Conclusion Serum DKK-1 level is an independent risk factor for cIMT thickening in RA patients, which may play a clinical predictive role in early atherosclerosis of RA.

Key words: arthritis, rheumatoid, Dickkopf-related protein 1, carotid intima-media thickness, atherosclerosis

中图分类号:

R593.22

詹雅萍, 张科, 李文根, 何春媚, 杨大山. 血清DKK-1检测对类风湿关节炎患者颈动脉内中膜增厚的临床价值[J]. 临床荟萃, 2025, 40(2): 138-142.

Zhan Yaping, Zhang Ke, Li Wengen, He Chunmei, Yang Dashan. Clinical value of serum DKK-1 detection in carotid intima-media thickening in patients with rheumatoid arthritis[J]. Clinical Focus, 2025, 40(2): 138-142.

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https://lchc.magtechjournal.com/CN/Y2025/V40/I2/138

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参考文献 28

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组别	例数		男性 [例( % ) ]			年龄 (岁)		病程 (年)	吸烟史超过10年 [例(%) ]				高血压史 [例( % ) ]	糖尿病史 [例(%) ]			脑血管疾病 [例(%) ]			脂肪肝 [例(%) ]
cIMT增厚组	29		12(41.3)			67.34±8.893		7.44±9.346	3(10.3)				14(48.3)	5(17.2)			4(13.8)			5(17.2)
cIMT正常组	53		13(24.5)			61.40±9.626		7.32±7.54	5(9.4)				15(28.3)	10(18.8)			1(1.9)			8(15.1)
t/χ²值			2.511			-2.812		0.625	0.417				0.710	0.550			0.033			0.787
P值			0.040			0.037		0.946	0.894				0.059	0.855			0.031			0.799
组别		BMI (kg/m²)			C反应蛋白 (mg/L)		血沉 (mm/h)			DAS28-ESR 评分(分)		类风湿因子 (IU/ml)			抗CCP抗体 (U/ml)				白介素6 (ng/L)
cIMT增厚组		20.99±4.959			54.51±51.88		47.84±22.33			5.27±1.525		287.54±436.215			101.82±86.964				84.17±161.396
cIMT正常组		21.93±4.552			47.16±59.06		43.97±59.064			4.90±1.273		502.77±118.813			108.21±90.726				38.46±44.620
t值		-0.09			-1.449		0.353			0.735		-0.195			-1.484				-1.534
P值		0.379			0.551		0.418			0.255		0.239			0.748				0.108
组别	免疫球蛋白G (g/L)			补体C3 (g/L)			补体C4 (g/L)				血尿酸 (μmol/L)		甘油三酯 (mmol/L)			总胆固醇 (mmol/L)		DKK-1 (ng/L)
cIMT增厚组	16.82±6.24			0.94±0.239			0.21±0.0100				276.57±155.724		1.16±0.520			4.58±1.561		2063.80±1074.922
cIMT正常组	15.57±6.011			0.94±0.319			0.20±0.0100				317.02±136.081		1.37±0.532			3.84±1.189		1497.54±1056.55
t值	2.989			1.179			0.604				-1.041		-0.165			0.436		-0.206
P值	0.383			0.929			0.721				0.219		0.066			0.048		0.019

组别	例数		男性 [例( % ) ]			年龄 (岁)		病程 (年)	吸烟史超过10年 [例(%) ]				高血压史 [例( % ) ]	糖尿病史 [例(%) ]			脑血管疾病 [例(%) ]			脂肪肝 [例(%) ]
cIMT增厚组	29		12(41.3)			67.34±8.893		7.44±9.346	3(10.3)				14(48.3)	5(17.2)			4(13.8)			5(17.2)
cIMT正常组	53		13(24.5)			61.40±9.626		7.32±7.54	5(9.4)				15(28.3)	10(18.8)			1(1.9)			8(15.1)
t/χ²值			2.511			-2.812		0.625	0.417				0.710	0.550			0.033			0.787
P值			0.040			0.037		0.946	0.894				0.059	0.855			0.031			0.799
组别		BMI (kg/m²)			C反应蛋白 (mg/L)		血沉 (mm/h)			DAS28-ESR 评分(分)		类风湿因子 (IU/ml)			抗CCP抗体 (U/ml)				白介素6 (ng/L)
cIMT增厚组		20.99±4.959			54.51±51.88		47.84±22.33			5.27±1.525		287.54±436.215			101.82±86.964				84.17±161.396
cIMT正常组		21.93±4.552			47.16±59.06		43.97±59.064			4.90±1.273		502.77±118.813			108.21±90.726				38.46±44.620
t值		-0.09			-1.449		0.353			0.735		-0.195			-1.484				-1.534
P值		0.379			0.551		0.418			0.255		0.239			0.748				0.108
组别	免疫球蛋白G (g/L)			补体C3 (g/L)			补体C4 (g/L)				血尿酸 (μmol/L)		甘油三酯 (mmol/L)			总胆固醇 (mmol/L)		DKK-1 (ng/L)
cIMT增厚组	16.82±6.24			0.94±0.239			0.21±0.0100				276.57±155.724		1.16±0.520			4.58±1.561		2063.80±1074.922
cIMT正常组	15.57±6.011			0.94±0.319			0.20±0.0100				317.02±136.081		1.37±0.532			3.84±1.189		1497.54±1056.55
t值	2.989			1.179			0.604				-1.041		-0.165			0.436		-0.206
P值	0.383			0.929			0.721				0.219		0.066			0.048		0.019

因素	回归系数	标准误	Waldχ²值	P值	OR值	95%CI
因素	回归系数	标准误	Waldχ²值	P值	OR值	下限	上限
性别	3.309	1.005	9.144	0.023	1.155	1.096	1.223
年龄	0.163	0.069	5.521	0.009	1.086	1.022	1.154
DKK-1	0.001	0.001	5.260	0.013	1.067	1.013	1.129

因素	回归系数	标准误	Waldχ²值	P值	OR值	95%CI
因素	回归系数	标准误	Waldχ²值	P值	OR值	下限	上限
性别	3.309	1.005	9.144	0.023	1.155	1.096	1.223
年龄	0.163	0.069	5.521	0.009	1.086	1.022	1.154
DKK-1	0.001	0.001	5.260	0.013	1.067	1.013	1.129

组别	例数	男性 [例(%) ]	年龄 (岁)	C反应蛋白 (mg/L)	血沉 (mm/h)	病程 (年)	类风湿因子 (IU/ml)	抗CCP抗体 (U/ml)	白介素6 (ng/L)	DKK-1 (ng/L)
cIMT增厚组	5	4(80.0)	72.6±7.369	37.05±35.645	19±17.306	7.60±6.280	506.97±710.807	107.9±89.539	68.18±106.332	2354.84±1100.648
cIMT正常组	8	3(37.5)	63.25±8.844	32.314±33.703	36±22.878	4.506±8.186	116.86±74.609	90.84±89.427	28.8±30.006	1746.36±953.76
t/χ²值		1.412	-1.967	-0.241	1.450	-0.329	-1.581	-0.335	-1.009	-2.125
P值		0.600	0.055	0.814	0.175	0.749	0.142	0.744	0.335	0.111