A Longitudinal Cohort Study on the Effect of Serum Bilirubin on the Progression of Carotid Atherosclerosis in Healthy People

doi:10.12114/j.issn.1007-9572.2022.0050

Chinese General Practice ›› 2022, Vol. 25 ›› Issue (13): 1576-1581.DOI: 10.12114/j.issn.1007-9572.2022.0050

Special Issue: 全民健康最新文章合辑

• Original Research·Population Health & Epidemiological Study • Previous Articles Next Articles

A Longitudinal Cohort Study on the Effect of Serum Bilirubin on the Progression of Carotid Atherosclerosis in Healthy People

1. School of Graduate, Hebei Medical University, Shijiazhuang 050000, China
2. Department of Neurology, Hebei General Hospital, Shijiazhuang 050000, China

Received:2022-01-17 Revised:2022-03-04 Published:2022-04-12 Online:2022-04-22
Contact: Hebo WANG
About author:
QIN L, GU Y S, LI L, et al. A longitudinal cohort study on the effect of serum bilirubin on the progression of carotid atherosclerosis in healthy people[J]. Chinese General Practice, 2022, 25 (13) : 1576-1581.

健康体检人群血清胆红素水平对颈动脉粥样硬化进展影响的队列研究

1．050000　河北省石家庄市，河北医科大学研究生学院
2．050000　河北省石家庄市，河北省人民医院神经内科

通讯作者: 王贺波
作者简介:
秦璐，谷永胜，李琳，等.健康体检人群血清胆红素水平对颈动脉粥样硬化进展影响的队列研究[J].中国全科医学，2022，25（13）：1576-1581.[www.chinagp.net] 作者贡献：秦璐负责文章的构思与设计、论文撰写；秦璐、谷永胜、王贺波负责研究的实施与可行性分析、结果的分析与解释；秦璐、谷永胜、李琳、张凯华负责数据收集；秦璐、谷永胜、李琳、张凯华、姚文涛负责数据整理；秦璐、谷永胜负责统计学处理；秦璐、吴宗锴、何伟亮、王贺波负责论文的修订；秦璐、牛小莉、李俐涛负责英文的修订；王贺波负责文章的质量控制及审校，并对文章整体负责，监督管理。
基金资助:
河北省自然科学基金重点项目(H2020307041)

Abstract

Abstract:

Background

Cross-sectional studies have shown that the level of bilirubin in vivo is related to the progression of atherosclerosis, but the data from large-scale studies in China and even in the world are very limited.

Objective

To investigate the effect of serum total bilirubin (TBIL) and indirect bilirubin (IBIL) on the progression of carotid atherosclerosis in healthy people.

Methods

Retrospective cohort study was adopted to select 11 394 healthy people who had continuous physical examination and carotid intima-media thickness (cIMT) ≤1 mm displayed by carotid artery ultrasound examination as the research subjects in Hebei General Hospital from January 2010 to December 2019. Demographic characteristics, past medical history, physical examination, laboratory examination results of previous physical examination, carotid artery ultrasound and other information of subjects were collected. The subjects were divided into the progressive carotid atherosclerosis group and the non-progressive group according to whether cIMT increased during follow-up. The Cox proportional regression model was used to explore the effect of bilirubin on the progression of carotid atherosclerosis, and Cox regression analysis was performed by gender, age, body mass index (BMI) , hypertension, diabetes, smoking and alcohol consumption.

Results

1 586 cases of carotid atherosclerosis progression were detected in 10 years, with a cumulative incidence rate of 13.9%. The results of Cox regression analysis showed that for every 1 standard deviation increase in TBIL and IBIL levels, the risk of carotid atherosclerosis progression decreased by 6.6% and 17.4%, respectively〔HR (95%CI) =0.934 (0.881, 0.990) ; HR (95%CI) =0.826 (0.777, 0.877) 〕 after adjustment for age, sex, BMI, smoking, alcohol consumption, hypertension, diabetes, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglyceride, alanine aminotransferase and estimated glomerular filtration rate. Subgroup analysis showed that there was no statistical difference in the protective effects of TBIL and IBIL on different subgroups.

Conclusion

TBIL and IBIL levels are independent protective factors for the progression of carotid atherosclerosis in healthy subjects. Elevated bilirubin levels reduce the risk of carotid atherosclerosis progression, with IBIL being more potent in preventing carotid atherosclerosis progression.

Key words: Atherosclerosis, Carotid artery disease, Bilirubin, Carotid intima-media thickness, Cohort studies

摘要：

背景

横断面研究表明，体内胆红素水平与动脉粥样硬化的进展有关，但国内乃至世界的大样本纵向研究数据有限。

目的

探讨血清总胆红素（TBIL）和间接胆红素（IBIL）水平对健康体检人群颈动脉粥样硬化进展的影响。

方法

采用回顾性队列研究方法，选取2010年1月至2019年12月于河北省人民医院接受健康体检且基线颈动脉超声检查显示颈动脉内膜-中膜厚度（cIMT）≤1 mm的健康体检者11 394例为研究对象。采集研究对象人口学特征、既往史、体格检查结果，以及历次体检的实验室检查结果、颈动脉超声等信息。将研究对象按随访过程中cIMT是否增加分为颈动脉粥样硬化进展组和非进展组。运用Cox比例风险回归模型探讨胆红素对颈动脉粥样硬化进展的影响，并按性别、年龄、体质指数（BMI）、高血压、糖尿病、吸烟、饮酒特征进行亚组Cox回归分析。

结果

10年间检出颈动脉粥样硬化进展者1 586例，累积发生率为13.9%。Cox回归分析结果显示，在调整年龄、性别、BMI、吸烟、饮酒、高血压、糖尿病、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、总胆固醇、三酰甘油、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、估算的肾小球滤过率后，TBIL和IBIL水平每升高1个标准差，颈动脉粥样硬化进展的风险分别下降6.6%和17.4%〔HR（95%CI）分别为0.934（0.881，0.990）、0.826（0.777，0.877）〕。亚组分析显示，TBIL和IBIL对于不同亚组人群的保护作用无统计学差异（P>0.05）。

结论

TBIL和IBIL水平是健康体检人群颈动脉粥样硬化进展的独立保护因素，胆红素水平升高可降低颈动脉粥样硬化进展的风险，其中，IBIL对于预防颈动脉粥样硬化进展的作用更强。

关键词: 动脉粥样硬化, 颈动脉疾病, 胆红素, 颈动脉内膜-中膜厚度, 队列研究

Lu QIN,Yongsheng GU,Lin LI, et al. A Longitudinal Cohort Study on the Effect of Serum Bilirubin on the Progression of Carotid Atherosclerosis in Healthy People[J]. Chinese General Practice, 2022, 25(13): 1576-1581. DOI: 10.12114/j.issn.1007-9572.2022.0050.
秦璐,谷永胜,李琳等. 健康体检人群血清胆红素水平对颈动脉粥样硬化进展影响的队列研究[J]. 中国全科医学, 2022, 25(13): 1576-1581. DOI: 10.12114/j.issn.1007-9572.2022.0050.

Figures/Tables 5

References 29

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组别	例数	年龄（±s，岁）	性别〔n（%）〕		BMI（±s，kg/m²）	吸烟史〔n（%）〕		饮酒史〔n（%）〕		高血压〔n（%）〕^d		糖尿病〔n（%）〕^d
组别	例数	年龄（±s，岁）	女	男	BMI（±s，kg/m²）	无	有	无	有	有	无	有	无
进展组	1 586	52.5±11.1	477（30.08）	1 109（69.92）	24.99±3.04	1 027（64.75）	559（35.25）	820（51.70）	766（48.30）	509（32.09）	1 077（67.91）	189（11.98）	1 388（88.02）
非进展组	9 808	47.9±12.5	3 485（35.53）	6 323（64.47）	24.66±3.25	7 031（71.69）	2 777（28.31）	5 088（51.88）	4 720（48.12）	2 529（25.80）	7 274（74.20）	619（6.36）	9 113（93.64）
检验统计量值		15.05^a	17.68^b		4.07^a	1.99^b		0.01^b		141.32^b		42.47^b
P值		<0.001	<0.001		<0.001	0.158		0.919		<0.001		<0.001
组别	WBC（±s，×10⁹/L）	NEUT（±s，×10¹²/L）	LDL-C（±s，mmol/L）	HDL-C（±s，mmol/L）	TC（±s，mmol/L）	TG 〔M（QR），mmol/L〕	ALT 〔M（QR），mmol/L〕	AST 〔M（QR），mmol/L〕	Scr（±s，μmol/L）	BUN（±s，mmol/L）	eGFR〔±s，ml·min^-1·（1.73 m²）^-1〕
进展组	6.22±1.56	4.74±0.46	3.00±0.87	1.24±0.32	5.00±0.91	1.32（1.05）	18.00（11.00）	19.00（6.00）	78.96±14.43	5.06±1.30	84.69±12.25
非进展组	6.19±1.57	4.74±0.47	2.73±0.84	1.25±0.32	4.77±0.89	1.22（1.01）	18.00（12.00）	19.00（6.00）	79.14±18.12	4.96±1.31	90.49±13.91
检验统计量值	0.80^a	0.47^a	11.38^a	1.09^a	9.00^a	4.32^c	2.32^c	2.71^c	0.44^a	2.74^a	17.15^a
P值	0.426	0.638	<0.001	0.277	<0.001	<0.001	0.021	0.007	0.660	0.006	<0.001

组别	例数	年龄（±s，岁）	性别〔n（%）〕		BMI（±s，kg/m²）	吸烟史〔n（%）〕		饮酒史〔n（%）〕		高血压〔n（%）〕^d		糖尿病〔n（%）〕^d
组别	例数	年龄（±s，岁）	女	男	BMI（±s，kg/m²）	无	有	无	有	有	无	有	无
进展组	1 586	52.5±11.1	477（30.08）	1 109（69.92）	24.99±3.04	1 027（64.75）	559（35.25）	820（51.70）	766（48.30）	509（32.09）	1 077（67.91）	189（11.98）	1 388（88.02）
非进展组	9 808	47.9±12.5	3 485（35.53）	6 323（64.47）	24.66±3.25	7 031（71.69）	2 777（28.31）	5 088（51.88）	4 720（48.12）	2 529（25.80）	7 274（74.20）	619（6.36）	9 113（93.64）
检验统计量值		15.05^a	17.68^b		4.07^a	1.99^b		0.01^b		141.32^b		42.47^b
P值		<0.001	<0.001		<0.001	0.158		0.919		<0.001		<0.001
组别	WBC（±s，×10⁹/L）	NEUT（±s，×10¹²/L）	LDL-C（±s，mmol/L）	HDL-C（±s，mmol/L）	TC（±s，mmol/L）	TG 〔M（QR），mmol/L〕	ALT 〔M（QR），mmol/L〕	AST 〔M（QR），mmol/L〕	Scr（±s，μmol/L）	BUN（±s，mmol/L）	eGFR〔±s，ml·min^-1·（1.73 m²）^-1〕
进展组	6.22±1.56	4.74±0.46	3.00±0.87	1.24±0.32	5.00±0.91	1.32（1.05）	18.00（11.00）	19.00（6.00）	78.96±14.43	5.06±1.30	84.69±12.25
非进展组	6.19±1.57	4.74±0.47	2.73±0.84	1.25±0.32	4.77±0.89	1.22（1.01）	18.00（12.00）	19.00（6.00）	79.14±18.12	4.96±1.31	90.49±13.91
检验统计量值	0.80^a	0.47^a	11.38^a	1.09^a	9.00^a	4.32^c	2.32^c	2.71^c	0.44^a	2.74^a	17.15^a
P值	0.426	0.638	<0.001	0.277	<0.001	<0.001	0.021	0.007	0.660	0.006	<0.001

性别		例数	TBIL	IBIL
颈动脉粥样硬化进展组
	男	1 109	15.34±4.69	11.38±3.64
	女	477	12.16±3.86	9.79±3.01
	t值		-11.04	-9.00
	P值		<0.001	<0.001
非进展组
	男	6 323	15.38±4.63	11.55±3.69
	女	3 485	11.90±4.01	9.69±3.19
	t值		-29.64	-26.15
	P值		<0.001	<0.001

性别		例数	TBIL	IBIL
颈动脉粥样硬化进展组
	男	1 109	15.34±4.69	11.38±3.64
	女	477	12.16±3.86	9.79±3.01
	t值		-11.04	-9.00
	P值		<0.001	<0.001
非进展组
	男	6 323	15.38±4.63	11.55±3.69
	女	3 485	11.90±4.01	9.69±3.19
	t值		-29.64	-26.15
	P值		<0.001	<0.001

自变量		b	SE	Wald χ²值	P值	HR（95%CI）
模型1
	TBIL	-0.025	0.025	-0.996	0.319	0.975（0.927，1.025）
	IBIL	-0.095	0.026	-3.602	<0.001	0.910（0.864，0.958）
模型2
	TBIL	-0.074	0.027	-2.725	0.006	0.929（0.880，0.979）
	IBIL	-0.147	0.028	-5.311	<0.001	0.863（0.818，0.911）
模型3
	TBIL	-0.060	0.027	-2.218	0.027	0.941（0.892，0.993）
	IBIL	-0.135	0.028	-4.842	<0.001	0.874（0.828，0.923）
模型4
	TBIL	-0.069	0.030	-2.299	0.021	0.934（0.881，0.990）
	IBIL	-0.191	0.031	-6.191	<0.001	0.826（0.777，0.877）
模型5
	TBIL	-0.093	0.046	-2.007	0.044	0.912（0.833，0.998）
	IBIL	-0.174	0.047	-3.699	<0.001	0.841（0.767，0.922）

A Longitudinal Cohort Study on the Effect of Serum Bilirubin on the Progression of Carotid Atherosclerosis in Healthy People

健康体检人群血清胆红素水平对颈动脉粥样硬化进展影响的队列研究

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分层因素		TBIL		IBIL
分层因素		HR（95%CI）	P值	HR（95%CI）	P值
年龄（岁）			0.455		0.236
	<60	0.920（0.861，0.984）		0.807（0.752，0.865）
	≥60	0.970（0.859，1.096）		0.879（0.777，0.995）
性别			0.868		0.659
	女	0.942（0.833，1.064）		0.846（0.745，0.960）
	男	0.931（0.871，0.995）		0.819（0.764，0.877）
BMI（kg/m²）			0.248		0.268
	<24	0.975（0.888，1.070）		0.861（0.782，0.949）
	≥24	0.908（0.842，0.979）		0.803（0.742，0.868）
饮酒史			0.691		0.729
	无	0.980（0.846，1.005）		0.815（0.745，0.891）
	有	0.944（0.872，1.022）		0.833（0.767，0.905）
吸烟史			0.540		0.511
	无	0.922（0.855，0.994）		0.813（0.752，0.879）
	有	0.957（0.872，1.050）		0.848（0.770，0.934）
高血压			0.202		0.217
	无	0.959（0.893，1.029）		0.848（0.788，0.912）
	有	0.883（0.794，0.981）		0.781（0.700，0.871）
糖尿病			0.075		0.105
	无	0.949（0.893，1.010）		0.838（0.786，0.893）
	有	0.792（0.656，0.958）		0.708（0.583，0.859）

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