高尿酸血症与脂肪肝关联的前瞻性队列研究

段琼; 张紫行; 徐娟; 洪文清; 周程; 许夕海; 方心宇

doi:10.16462/j.cnki.zhjbkz.2022.12.010

高尿酸血症与脂肪肝关联的前瞻性队列研究

doi: 10.16462/j.cnki.zhjbkz.2022.12.010

段琼¹,
张紫行^{2, 3},
徐娟¹,
洪文清¹,
周程^{2, 3},
许夕海^1, ,,
方心宇^{2, 3, ,}

1.
230032 合肥，安徽医科大学第一附属医院健康管理中心
2.
230032 合肥，安徽医科大学公共卫生学院流行病与卫生统计学系
3.
230032 合肥，炎症免疫性疾病安徽省实验室

段琼和张紫行为共同第一作者

基金项目:

炎症免疫性疾病安徽省实验室开放课题 IMMDL202110

详细信息

通讯作者:
许夕海，E-mail: 2xihai@163.com

方心宇，E-mail: xinyufang@ahmu.edu.cn

中图分类号: R181
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- 被引次数: 0
出版历程
- 收稿日期: 2022-10-31
- 修回日期: 2022-11-14
- 网络出版日期: 2022-12-30
- 刊出日期: 2022-12-10

A prospective cohort study on the relationship between hyperuricemia and fatty liver

DUAN Qiong¹,
ZHANG Zi-xing^{2, 3},
XU Juan¹,
HONG Wen-qing¹,
ZHOU Cheng^{2, 3},
XU Xi-hai^{1
, ,},
FANG Xin-yu^{2, 3
, ,}

1.
Health Management Center, the First Affiliated Hospital of Anhui Medical University, Hefei 230032, China
2.
Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei 230032, China
3.
Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei 230032, China

DUAN Qiong and ZHANG Zi-xing contribution equally to this work

Funds:

Inflammation and Immune Mediated Diseases Laboratory of Anhui Province Open Project IMMDL202110

More Information

Corresponding author: XU Xi-hai, E-mail: 2xihai@163.com; FANG Xin-yu, E-mail: xinyufang@ahmu.edu.cn

摘要

摘要: 目的通过前瞻性队列研究分析高尿酸血症(hyperuricemia, HUA)与脂肪性肝病(简称脂肪肝)发病风险的关系，为脂肪肝的防治提供依据。方法基于炎症免疫性疾病队列，纳入2017年―2021年至少完成了两次随访、与研究相关的关键指标无缺失且基线调查时未患脂肪肝的16 322名受试者作为本次研究对象。采用Cox比例风险回归模型分析HUA与脂肪肝发病风险之间的关联关系。模型1为单因素Cox分析；模型2调整年龄、性别和BMI；模型3在模型2的基础上调整高血糖、高血压、尿素氮、肌酐、总胆红素、AST、ALT和血脂异常。结果研究对象共随访42 472.75人年，平均随访时间2.60年，队列中新发脂肪肝病例3 150例，总人群发病密度为74.17/1 000人年。Cox比例风险回归模型分析结果显示，HUA组脂肪肝发病风险较高。3个模型风险比(hazard ration, HR)分别为2.049(95% CI: 1.861~2.256)、1.360(95% CI: 1.233~1.501)和2.049(95% CI: 1.861~2.256)。在对高血糖、高血压、血脂异常等因素分层后，HUA与脂肪肝发病风险仍呈正相关(均有P < 0.05)。交互作用研究显示：BMI(P=0.003)、高血压(P=0.012)与HUA存在相乘交互作用。结论 HUA是脂肪肝发生的独立危险因素，及时干预HUA可以降低脂肪肝的发生或延缓脂肪肝的进展，为临床预防和治疗脂肪肝提供了参考依据。
- 高尿酸血症 /
- 脂肪肝 /
- 队列研究 /
- Cox比例风险回归模型
Abstract: Objective The study aims to probe the relationship between hyperuricemia (HUA) and the risk of the fatty liver through a prospective cohort study, so as to provide the basis for the prevention and treatment of fatty liver. Methods Based on the Inflammatory and Immune Mediated Diseases Cohort, a total of 16 322 subjects who had completed at least two follow-ups from 2017 to 2021, had no missing key indicators related to the study and fatty liver at baseline were investigated. Cox proportional hazard model was used to analyze the relationship between HUA and the risk of fatty liver. Model 1 was a univariate Cox analysis, model 2 adjusted age, sex and BMI, and model 3 further adjusted hyperglycemia, hypertension, urea nitrogen, creatinine, total bilirubin, AST, ALT and dyslipidemia. Results The subjects were followed up for 42 472.75 person-years, with an average follow-up time of 2.60 years. There were 3 150 incidence cases of fatty liver, with an incidence density of 74.17/1 000 person-years. Cox proportional hazard model analysis showed that the risk of fatty liver was higher in HUA group. The hazard ration(HR) of the three models were 2.049(95% CI: 1.861-2.256), 1.360(95% CI: 1.233-1.501) and 2.049(95% CI: 1.861-2.256) respectively. After stratification of hyperglycemia, hypertension, dyslipidemia and other factors, HUA was still positively associated with the risk of fatty liver (all P < 0.05). In the multiplication model, significant multiplier interactions were found between BMI (P=0.003), hypertension (P=0.012) and HUA. Conclusions HUA is an independent risk factor for fatty liver. The timely intervention of HUA can reduce the occurrence of fatty liver or delay the progress of fatty liver. Our study provides reference for the clinical prevention and treatment of fatty liver.
- Hyperuricemia /
- Fatty liver /
- Cohort study /
- Cox proportional hazard model

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图 1 样本筛选流程图

Figure 1. The flowchart of sample screening

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表 1 研究对象的基线特征[M(P₂₅, P₇₅)]

Table 1. Baseline characteristics of the study participants [M(P₂₅, P₇₅)]

变量	合计(N=16 322)	有无脂肪肝		Z/χ²值	P值
变量	合计(N=16 322)	无(n=13 172)	有(n=3 150)	Z/χ²值	P值
年龄(岁)	44(33, 55)	43(33, 54)	48(37, 57)	-12.851	< 0.001
性别				733.980	< 0.001
女	8 083(49.52)	7 206(54.71)	877(27.84)
男	8 239(50.48)	5 966(45.29)	2 273(72.16)
BMI(kg/m²)				1 036.440	< 0.001
＜18.5	1 108(6.79)	1 080(8.20)	28(0.89)
18.5~＜24.0	11 204(68.64)	9 496(72.09)	1 708(54.22)
24.0~＜28.0	3 674(22.51)	2 433(18.47)	1 241(39.40)
≥28.0	336(2.06)	163(1.24)	173(5.49)
SBP(mm Hg)	122(112, 135)	121(111, 134)	128(117, 139)	-18.630	< 0.001
DBP(mm Hg)	74(67, 82)	73(67, 81)	78(71, 86)	-19.481	< 0.001
FPG(mmol/L)	5.03(4.75, 5.38)	5.01(4.73, 5.35)	5.14(4.84, 5.54)	-13.574	< 0.001
SUA(μmol/L)	296(247, 351)	287(240, 340)	334(286, 386)	-29.188	< 0.001
HDL-C(mmol/L)	1.44(1.21, 1.72)	1.49(1.26, 1.76)	1.27(1.08, 1.49)	-30.339	< 0.001
LDL-C(mmol/L)	2.58(2.12, 3.11)	2.54(2.09, 3.06)	2.76(2.29, 3.29)	-14.800	< 0.001
TC(mmol/L)	4.52(4.00, 5.13)	4.49(3.97, 5.09)	4.67(4.13, 5.29)	-10.483	< 0.001
TG(mmol/L)	1.07(0.79, 1.48)	1.00(0.76, 1.37)	1.41(1.03, 1.93)	-34.369	< 0.001
Scr(μmol/L)	69(58, 81)	67(57, 80)	75(64, 84)	-19.945	< 0.001
UN(mmol/L)	4.78(4.03, 5.67)	4.73(3.99, 5.60)	4.99(4.20, 5.93)	-10.701	< 0.001
TBIL(μmol/L)	12.90(10.30, 16.20)	12.80(10.30, 16.20)	12.90(10.20, 16.30)	-0.204	0.838
ALT(U/L)	17.00(14.00, 23.00)	17.00(13.00, 22.00)	21.00(16.00, 28.00)	-26.913	< 0.001
AST(U/L)	18.00(16.00, 22.00)	18.00(16.00, 22.00)	19.00(17.00, 23.00)	-13.614	< 0.001
高血糖				103.804	< 0.001
否	15 198(93.11)	12 395(94.10)	2 803(88.98)
是	1 124(6.89)	777(5.90)	347(11.02)
高血压				149.453	< 0.001
否	12 906(79.07)	10 666(80.97)	2 240(71.11)
是	3 416(20.93)	2 506(19.03)	910(28.89)
血脂异常				511.308	< 0.001
否	10 292(63.06)	8 856(67.23)	1 436(45.59)
是	6 030(36.94)	4 316(32.77)	1 714(54.41)
高尿酸血症				206.796	< 0.001
否	14 853(91.00)	12 194(92.58)	2 659(84.41)
是	1 469(9.00)	978(7.42)	491(15.59)

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表 2 HUA与脂肪肝发病风险的关联[HR(95% CI)]

Table 2. Association between HUA and fatty liver disease [HR(95% CI)]

变量	模型1	模型2	模型3	变量	模型1	模型2	模型3
SUA分组				UN(mmol/L)			1.027(0.997~1.058)
非HUA组	1.000	1.000	1.000	TBIL(μmol/L)			0.989(0.982~0.996) ^b
HUA组	2.049(1.861~2.256) ^a	1.360(1.233~1.501) ^a	1.353(1.222~1.497) ^a	ALT(U/L)			1.012(1.009~1.015) ^a
年龄(岁)		1.005(1.003~1.008) ^a	1.004(1.002~1.007) ^b	AST(U/L)			0.985(0.980~0.990) ^a
性别				高血糖
女		1.000	1.000	否			1.000
男		2.195(2.025~2.378) ^a	2.499(2.252~2.773) ^a	是			1.194(1.060~1.345) ^b
BMI(kg/m²)				高血压
18.5~＜24.0		1.000	1.000	否			1.000
＜18.5		0.182(0.125~0.265) ^a	0.202(0.139~0.294) ^a	是			1.059(0.973~1.153)
24.0~＜28.0		2.020(1.874~2.178) ^a	1.834(1.699~1.979) ^a	血脂异常
≥28.0		3.421(2.922~4.005) ^a	2.893(2.467~3.394) ^a	否			1.000
Scr(μmol/L)			0.991(0.988~0.995) ^a	是			1.719(1.599~1.847) ^a
注：^a表示P < 0.001; ^b表示P < 0.05。

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表 3 HUA与脂肪肝发病风险的亚组分析和相乘交互作用分析

Table 3. Subgroup analysis and multiplicative interaction effect of HUA and risk of fatty liver disease

变量	例数/总例数	多因素Cox分析		P_{相乘交互作用}值
变量	例数/总例数	HR (95% CI) 值	P值	P_{相乘交互作用}值
BMI(kg/m²)				0.003
＜18.5	1 108/16 322	1.386(0.302~6.364)	0.675
18.5~＜24.0	11 204/16 322	1.582(1.367~1.832)	< 0.001
24.0~＜28.0	3 674/16 322	1.180(1.014~1.373)	0.032
≥28.0	336/16 322	1.047(0.711~1.541)	0.815
高血糖				0.495
否	15 198/16 322	1.344(1.207~1.498)	< 0.001
是	1 124/16 322	1.392(1.033~1.875)	0.030
高血压				0.012
否	12 906/16 322	1.446(1.277~1.638)	< 0.001
是	3 416/16 322	1.231(1.034~1.466)	0.019
血脂异常				0.668
否	10 292/16 322	1.325(1.115~1.575)	0.001
是	6 030/16 322	1.375(1.212~1.559)	< 0.001
注：各模型均调整其余变量(年龄、性别、BMI、Scr、UN、TBIL、ALT、AST、高血糖、高血压和血脂异常)。

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表 4 HUA与脂肪肝发病风险的关联^a

Table 4. Association between HUA and risk of fatty liver disease ^a

变量	模型1	模型2	模型3
SUA分组
非HUA组	1.000	1.000	1.000
HUA组	2.171(1.959~2.405) ^b	1.275(1.147~1.417) ^b	1.260(1.130~1.405) ^b
年龄(岁)		1.005(1.003~1.008) ^b	1.004(1.002~1.007) ^c
性别
女		1.000	1.000
男		2.183(2.012~2.368) ^b	2.456(2.214~2.725) ^b
BMI(kg/m²)
18.5~ < 24.0		1.000	1.000
< 18.5		0.181(0.125~0.263) ^b	0.201(0.139~0.293) ^b
24.0~ < 28.0		2.033(1.886~2.191) ^b	1.843(1.708~1.988) ^b
≥28.0		3.464(2.959~4.055) ^b	2.920(2.490~3.426) ^b
Scr(μmol/L)			0.992(0.989~0.995) ^b
UN(mmol/L)			1.027(0.997~1.058)
TBIL(μmol/L)			0.989(0.983~0.996) ^c
ALT(U/L)			1.012(1.009~1.014) ^b
AST(U/L)			0.985(0.980~0.991) ^b
高血糖
否			1.000
是			1.194(1.060~1.345) ^c
高血压
否			1.000
是			1.064(0.978~1.159)
血脂异常
否			1.000
是			1.728(1.607~1.857) ^b
注：^a表示根据SUA>420 μmol/L即为HUA的标准对SUA分组进行的Cox分析。模型1为单因素Cox分析，模型2调整了年龄、性别和BMI，模型3调整了年龄、性别、BMI、Scr、UN、TBIL、ALT、AST、高血糖、高血压和血脂异常; ^b表示P < 0.001; ^c表示P < 0.05。

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高尿酸血症与脂肪肝关联的前瞻性队列研究

doi: 10.16462/j.cnki.zhjbkz.2022.12.010

通讯作者:
许夕海，E-mail: 2xihai@163.com

方心宇，E-mail: xinyufang@ahmu.edu.cn

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A prospective cohort study on the relationship between hyperuricemia and fatty liver

Corresponding author: XU Xi-hai, E-mail: 2xihai@163.com; FANG Xin-yu, E-mail: xinyufang@ahmu.edu.cn

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高尿酸血症与脂肪肝关联的前瞻性队列研究

doi: 10.16462/j.cnki.zhjbkz.2022.12.010

通讯作者: 许夕海，E-mail: 2xihai@163.com 方心宇，E-mail: xinyufang@ahmu.edu.cn

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A prospective cohort study on the relationship between hyperuricemia and fatty liver

Corresponding author: XU Xi-hai, E-mail: 2xihai@163.com; FANG Xin-yu, E-mail: xinyufang@ahmu.edu.cn

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出版历程

目录

通讯作者:
许夕海，E-mail: 2xihai@163.com

方心宇，E-mail: xinyufang@ahmu.edu.cn