血清non-HDL-C/HDL-C、血浆致动脉粥样硬化指数与慢性肾病发病风险的前瞻性队列研究

游金龙; 王雪; 唐靖; 李秀茜; 王瑞; 姜敏; 张文君; 白亚娜; 王敏珍; 郑山

doi:10.16462/j.cnki.zhjbkz.2025.09.013

血清non-HDL-C/HDL-C、血浆致动脉粥样硬化指数与慢性肾病发病风险的前瞻性队列研究

doi: 10.16462/j.cnki.zhjbkz.2025.09.013

游金龙¹,
王雪¹,
唐靖¹,
李秀茜¹,
王瑞¹,
姜敏²,
张文君³,
白亚娜¹,
王敏珍¹,
郑山^1, ,

1.
兰州大学公共卫生学院流行病与卫生统计学系, 兰州 730000
2.
甘肃省武威市人民医院肾内科, 武威 733000
3.
兰州大学第二医院(第二临床医学院)肾内科, 兰州 730030

基金项目:

甘肃省联合基金项目 24JRRA819

兰州大学第二医院(第二临床医学院)“萃英科技创新”计划 CY2023-MS-A08

详细信息

通讯作者:
郑山, E-mail: zhengsh@lzu.edu.cn

中图分类号: R181.3;R692.6
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- 文章访问数: 1
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出版历程
- 收稿日期: 2025-01-03
- 修回日期: 2025-04-14
- 网络出版日期: 2025-10-10
- 刊出日期: 2025-09-10

Association between serum NHHR, AIP and the risk of chronic kidney disease: a prospective cohort study

1.
Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, China
2.
Department of Nephrology, the People's Hospital of Wuwei, Wuwei 733000, China
3.
Department of Nephrology, the Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China

Funds:

Gansu Provincial Joint Research Fund Program 24JRRA819

"Cuiying Science and Technology Innovation" Program of the Second Hospital & Clinical Medical School, Lanzhou University CY2023-MS-A08

More Information

Corresponding author: ZHENG Shan, E-mail: zhengsh@lzu.edu.cn

摘要

摘要: 目的评估血清非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值(non-high density lipoprotein cholesterol/high density lipoprotein cholesterol, NHHR)、血浆致动脉粥样硬化指数(atherogenic index of plasma, AIP)与慢性肾病(chronic kidney disease, CKD)发病风险的关系, 为CKD的防治提供依据。方法以金昌队列中25 377名未患CKD的参与者作为研究对象, 采用Cox比例风险回归模型、限制性立方样条分别评估NHHR和AIP对CKD的发病风险及剂量-反应关系, 并进行亚组分析。采用受试者工作特征曲线评估NHHR和AIP对CKD发病风险的预测能力。结果经过平均4.77年的随访调查后, 新发CKD患者有1 213例, 发病密度为10.03/1 000人年。调整混杂因素后, 相较于Q1组, Q4组人群中NHHR和AIP的CKD发病风险比分别为1.270(95% CI: 1.066~1.512)和1.294(95% CI: 1.081~1.548), 且均存在一定的剂量-反应关系(均P＜0.05)。NHHR和AIP预测CKD的AUC值分别为0.750(95% CI: 0.736~0.764)和0.735(95% CI: 0.721~0.749)。亚组分析发现, 吸烟和糖尿病与NHHR、糖尿病和AIP间存在交互作用(均P＜0.05)。结论 NHHR和AIP是CKD发病的独立危险因素, 并对CKD发病风险有一定的预测能力。
- 非高密度脂蛋白胆固醇 /
- 高密度脂蛋白胆固醇 /
- 血浆致动脉粥样硬化指数 /
- 血脂代谢 /
- 慢性肾病 /
- 前瞻性队列研究
Abstract: Objective To analyse serum non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR), plasma atherogenic index (AIP) and the risk of chronic kidney disease (CKD). Methods A total of 25 377 participants without CKD from the Jinchang Cohort matched at baseline and follow-up were enrolled for the study. Cox proportional risk regression model and restricted cubic spline method were used to estimate the relationship between NHHR and AIP on the risk and dose response of CKD, and subgroup analyses were performed. Receiver operating characteristic curve and area under the curve (AUC) were conducted to evaluate the predictive ability on the risk of CKD. Results After an average follow-up period of 4.77 years, 1 213 new cases of CKD were identified, and the incidence density is 10.03/1 000 person-years. After adjusting for confounders, the HRs of NHHR and AIP in the Q4 population were 1.270 (95% CI: 1.066-1.512) and 1.294 (95% CI: 1.081-1.548), respectively, compared with the Q1 group, and all had dose-response relationship (all P < 0.05). The AUCs of NHHR and AIP for the prediction of CKD were 0.750 (95% CI: 0.736-0.764) and 0.735 (95% CI: 0.721-0.749), respectively. Subgroup analysis revealed interactions between smoking and diabetes with NHHR, and diabetes with AIP (all P < 0.05). Conclusions NHHR and AIP are independent risk factors for the development of CKD and have some predictive power with regard to the risk of CKD.
- Non-high density lipoprotein cholesterol /
- High density lipoprotein cholesterol /
- Atherogenic index of plasma /
- Lipid metabolism /
- Chronic kidney disease /
- Prospective cohort study

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图 1 NHHR、AIP与CKD发病风险的剂量-反应关系

NHHR: 非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值; AIP: 血浆致动脉粥样硬化指数; CKD: 慢性肾病; 模型调整了性别、年龄、职业、文化程度、个人月收入、吸烟、饮酒、体育锻炼、高盐饮食、高脂饮食、高糖饮食、体质量指数、高血压、糖尿病、高尿酸血症、基线估算的肾小球滤过率、谷丙转氨酶、谷草转氨酶和血红蛋白。

Figure 1. Dose-response relationship between NHHR, AIP and risk of CKD

NHHR: non-high density lipoprotein cholesterol/high density lipoprotein cholesterol; AIP: atherogenic index of plasma; CKD: chronic kidney disease; Models adjusted for gender, age, occupation, education, individual monthly incomes, smoking, drinking, physical exercise, high salt diet, high fat diet, high sugar diet, body mass index, hypertension, diabetes, hyperuricemia, baseline estimated-glomerular filtration rate, alanine aminotransferase, aspartate aminotransferase, and hemoglobin on the basis of model 2.

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图 2 NHHR和AIP预测CKD发病风险的ROC曲线

NHHR: 非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值; AIP: 血浆致动脉粥样硬化指数; CKD: 慢性肾病; AUC: 曲线下面积。

Figure 2. ROC curves of NHHR and AIP for predicting the risk of CKD

NHHR: non-high density lipoprotein cholesterol/high density lipoprotein cholesterol; AIP: atherogenic index of plasma; CKD: chronic kidney disease; AUC: area under the curve.

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图 3 NHHR、AIP与CKD发病风险关联的亚组分析

NHHR: 非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值; AIP: 血浆致动脉粥样硬化指数; CKD: 慢性肾病。

Figure 3. Subgroup analysis of the association between NHHR, AIP, and risk of CKD

NHHR: non-high density lipoprotein cholesterol/high density lipoprotein cholesterol; AIP: atherogenic index of plasma; CKD: chronic kidney disease.

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表 1 研究对象的基线特征

Table 1. Baseline characteristics of the participants

变量Variable	非CKD组 Non-CKD group (n=24 164)^①	CKD组 CKD group (n=1 213)^①	Z/χ² 值value	P值 value
性别Gender			101.82	0.001
男Male	14 462(59.85)	902(74.36)
女Female	9 702(40.15)	311(25.64)
年龄/岁Age/years	44.00(39.00, 55.00)	48.00(41.00, 65.00)	-11.33	0.001
职业Occupation			11.05	0.011
工人Worker	19 468(80.57)	1 011(83.35)
干部Managerial staff	2 752(11.39)	106(8.74)
技术人员Technical staff	999(4.13)	41(3.38)
内勤人员Logistics staff	945(3.91)	55(4.53)
文化程度Education			80.98	< 0.001
初中及以下Junior middle school or below	9 546(39.50)	621(51.19)
高中或中专Senior middle school or equivalent	6 758(27.97)	327(26.96)
大专及以上College or above	7 860(32.53)	265(21.85)
个人月收入/元Individual monthly incomes/yuan			8.14	0.005
≥2 000	12 613(52.20)	684(56.39)
< 2 000	11 551(47.80)	529(43.61)
体质量指数Body mass index/(kg·m^-2)	23.34(21.21, 25.61)	24.68(22.45, 26.97)	-12.04	< 0.001
吸烟Smoking			103.45	< 0.001
从不Never	13 340(55.21)	521(42.95)
仍然Still	8 879(36.74)	513(42.29)
戒烟Quit	1 945(8.05)	179(14.76)
饮酒Drinking			87.09	< 0.001
从不Never	18 173(75.21)	789(65.04)
偶尔Occasionally	4 974(20.58)	318(26.22)
经常Regular	1 017(4.21)	106(8.74)
体育锻炼Physical exercise			8.93	0.012
从不Never	2 161(8.94)	139(11.46)
偶尔Occasionally	10 285(42.56)	498(41.05)
经常Regular	11 718(48.50)	576(47.49)
高盐饮食High salt diet	5 496(22.74)	281(23.17)	0.12	0.759
高脂饮食High fat diet	4 680(19.37)	246(20.28)	0.61	0.455
高糖饮食High sugar diet	4 877(20.18)	232(19.13)	0.80	0.390
高血压Hypertension	6 363(26.33)	612(50.45)	337.17	< 0.001
糖尿病Diabetes	1 567(6.48)	258(21.27)	378.27	< 0.001
高尿酸血症Hyperuricemia	2 738(11.33)	234(19.29)	70.78	< 0.001
血清尿酸Serum uric acid/(μmol·L^-1)	316.00(263.00, 373.00)	345.00(294.00, 402.00)	-11.66	< 0.001
血清肌酐Serum creatinine/(μmol·L^-1)	68.50(59.00, 77.00)	72.00(62.00, 83.00)	-9.48	< 0.001
谷丙转氨酶Alanine aminotransferase/(U·L^-1)	27.00(19.00, 40.00)	30.00(21.00, 45.00)	-6.61	< 0.001
谷草转氨酶Aspartate aminotransferase/(U·L^-1)	31.00(26.00, 38.00)	33.00(27.00, 41.00)	-5.94	< 0.001
收缩压Systolic blood pressure/mmHg	121.00(109.00, 134.00)	131.00(119.00, 146.00)	-17.14	< 0.001
舒张压Diastolic blood pressure/mmHg	77.00(70.00, 86.00)	83.00(75.00, 93.00)	-15.32	< 0.001
空腹血糖Fasting plasma glucose/(mmol·L^-1)	5.10(4.70, 5.50)	5.40(4.90, 6.20)	-15.22	< 0.001
碱性磷酸酶Alkaline phosphatase/(U·L^-1)	65.00(54.00, 79.00)	68.00(56.00, 81.00)	-4.55	< 0.001
血红蛋白Hemoglobin/(g·L^-1)	151.00(139.00, 161.00)	158.00(151.00, 165.00)	-18.16	< 0.001
基线e-GFR Baseline e-GFR/(mL·min^-1·1.73m^-2)	105.00(94.95, 112.55)	101.28(85.77, 111.34)	-9.36	< 0.001
总胆固醇Total cholesterol/(mmol·L^-1)	4.60(4.10, 5.20)	4.70(4.20, 5.40)	-4.46	< 0.001
三酰甘油Triglyceride/(mmol·L^-1)	1.50(1.10, 2.30)	1.80(1.30, 2.70)	-9.49	< 0.001
HDL-C/(mmol·L^-1)	1.33(1.13, 1.57)	1.27(1.07, 1.51)	-6.45	< 0.001
LDL-C/(mmol·L^-1)	3.02(2.56, 3.51)	3.12(2.62, 3.62)	-3.68	< 0.001
NHHR	2.46(1.88, 3.14)	2.71(2.12, 3.49)	-9.12	< 0.001
AIP	0.06(-0.14, 0.28)	0.15(-0.05, 0.37)	-9.63	< 0.001
注: CKD, 慢性肾病; e-GFR, 估算的肾小球滤过率; HDL-C, 高密度脂蛋白胆固醇; LDL-C, 低密度脂蛋白胆固醇; NHHR, 非HDL-C与HDL-C比值; AIP, 血浆致动脉粥样硬化指数。 ①以人数(占比/%)或M(P₂₅, P₇₅)表示。 Note: CKD, chronic kidney disease; e-GFR, estimated-glomerular filtration rate; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; NHHR, non-HDL-C/HDL-C; AIP, atherogenic index of plasma. ① Number of people (proportion/%) or M(P₂₅, P₇₅).

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表 2 NHHR、AIP对CKD发病风险的影响

Table 2. Influence of NHHR and AIP on the risk of CKD

变量 Variable	模型1 Model 1		模型2 Model 2		模型3 Model 3
变量 Variable	HR值value(95% CI)	P值value	HR值value(95% CI)	P值value	HR值value(95% CI)	P值value
NHHR^①	1.170(1.116~1.227)	< 0.001	1.123(1.065~1.183)	< 0.001	1.083(1.026~1.144)	0.004
Q1	1.000		1.000		1.000
Q2	1.260(1.053~1.507)	0.012	1.103(0.921~1.321)	0.289	1.072(0.895~1.285)	0.450
Q3	1.506(1.267~1.790)	< 0.001	1.215(1.019~1.449)	0.030	1.182(0.991~1.410)	0.064
Q4	1.922(1.629~2.267)	< 0.001	1.456(1.227~1.727)	< 0.001	1.270(1.066~1.512)	0.007
AIP^①	1.215(1.149~1.285)	< 0.001	1.149(1.082~1.219)	< 0.001	1.087(1.022~1.157)	0.008
Q1	1.000		1.000		1.000
Q2	1.210(1.008~1.453)	0.041	1.199(0.998~1.439)	0.052	1.140(0.949~1.369)	0.163
Q3	1.319(1.103~1.577)	0.002	1.308(1.093~1.564)	0.003	1.155(0.964~1.385)	0.119
Q4	1.610(1.354~1.914)	< 0.001	1.576(1.324~1.876)	< 0.001	1.294(1.081~1.548)	0.005
注: NHHR, 非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值; AIP, 血浆致动脉粥样硬化指数; CKD, 慢性肾病; 模型1调整了性别和年龄; 模型2在模型1的基础上进一步调整了职业、文化程度、个人月收入、吸烟、饮酒、体育锻炼、高盐饮食、高脂饮食、高糖饮食和体质量指数; 模型3在模型2的基础上进一步调整了高血压、糖尿病、高尿酸血症、基线估算的肾小球滤过率、谷丙转氨酶、谷草转氨酶和血红蛋白。 ①代表指标作为连续型变量, 每增加1个标准差时CKD的HR(95% CI)值。 Note: NHHR, non-high density lipoprotein cholesterol/high density lipoprotein cholesterol; AIP, atherogenic index of plasma; CKD, chronic kidney disease; Model 1 adjusted for gender and age; Model 2 further adjusted for occupation, education, individual monthly incomes, smoking, drinking, physical exercise, high salt diet, high fat diet, high sugar diet, and body mass index on the basis of model 1; and model 3 further adjusted for hypertension, diabetes, hyperuricemia, baseline estimated-glomerular filtration rate, alanine aminotransferase, aspartate aminotransferase, and hemoglobin on the basis of model 2. ① Represents the HR (95% CI) values for CKD for each 1 standard deviation increase in the representative indicator as a continuous variable.

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