血清生长刺激表达基因2蛋白和脂蛋白相关磷脂酶A2与维持性血液透析患者心血管事件的关系

doi:10.16138/j.1673-6087.2022.04.005

摘要/Abstract

摘要：

目的： 探究生长刺激表达基因2蛋白（growth stimulation expressed gene 2,ST2）和脂蛋白相关磷脂酶A2（lipoprotein-associated phospholipase A2,LP-PLA2）与维持性血液透析（maintenance hemodialysis,MHD）患者心血管事件的关系。方法： 选取2016年1月至2017年1月于我院行MHD的177例患者为研究对象。检测患者透析当日透析前血清ST2和LP-PLA2水平。随访患者,随访终点为出现心血管事件。利用受试者工作特征曲线明确ST2和LP-PLA2鉴别患者有无心血管事件的能力。通过单因素和多因素Cox回归分析明确影响患者心血管事件的危险因素。结果： 有心血管事件组患者血清ST2和LP-PLA2水平显著高于无心血管事件组（均P<0.05）。ST2和LP-PLA2鉴别MHD患者有无心血管事件的曲线下面积分别为0.77和0.70,两者联合使用后曲线下面积升高至0.83。Kaplan-Meier曲线分析提示ST2≤61 μg/L组患者中位无心血管事件时间明显长于ST2>61 μg/L组患者（53个月比28个月,P<0.001）;LP-PLA2≤266 μg/L组患者中位无心血管事件时间明显长于LP-PLA2>266 μg/L组患者（50个月比37个月,P=0.001）。多因素分析结果显示,患者脑钠肽（brain natriuretic peptide,BNP）[风险比（hazard ratio,HR）=1.01, P<0.001]、ST2>61 μg/L（HR=1.27, P<0.001）以及LP-PLA2>266 μg/L（HR=1.92, P<0.001）是影响MHD患者心血管事件的独立危险因素。结论： 血清ST2>61 μg/L和LP-PLA2>266 μg/L是MHD患者心血管事件风险的独立危险因素。检测ST2和LP-PLA2可能有助于患者危险分层。

关键词: 生长刺激表达基因2蛋白, 脂蛋白相关磷脂酶A2, 维持性血液透析, 心血管事件

Abstract:

Objactive To explore the association between suppression of growth stimulation expressed gene 2 (ST2), lipoprotein-associated phospholipase A2(LP-PLA2) and cardiovascular events in the patients with maintenance hemodialysis (MHD). Methods A total of 117 MHD patients at our hospital from January 2016 to January 2017 were selected. The serum ST2 and LP-PLA2 levels were measured before hemodialysis. The patients were followed up, and the primary endpoint was occurrence of cardiovascular events. The receiver-operating characteristic curve was analyzed to determine if ST2 and LP-PLA2 were associated with cardiovascular events in MHD patients. The univariate and multivariate Cox regression analysis was used to determine the risk factors of cardiovascular events in the MHD patients. Results The ST2 and LP-PLA2 levels were significantly higher in the patients with cardiovascular events than those without events (all P<0.05). The areas under the curve of ST2 and LP-PLA2 distinguishing the MHD patients with or without cardiovascular events were 0.77 and 0.70, respectively; and it increased to 0.83 when the 2 biomarkers were used in combination. The Kaplan-Meier curve analysis showed that the MHD patients with ST2≤61 μg/L had a significantly longer time free from cardiovascular events than those with ST2>61 μg/L(53 months vs 28 months, P<0.001). Similarly, the MHD patients with LP-PLA2≤266 μg/L had a significantly longer time free from cardiovascular events than those with LP-PLA2>266 μg/L (50 months vs 37 months, P=0.001). The multivariate Cox regression analysis presented the brain natriuretic peptide (BNP) [ hazard ratio(HR)=1.01, P<0.001], ST2>61 μg/L (HR=1.27, P<0.001) and LP-PLA2>266 μg/L (HR=1.92, P<0.001) was independent risk factor for cardiovascular events in the MHD patients. Conclusions The serum ST2 and LP-PLA2 are independent risk factors for cardiovascular events in the MHD patients, and measurement of ST2 and LP-PLA2 may help to evaluate risk stratification.

Key words: Growth stimulation expressed gene 2, Lipoprotein-associated phospholipase A2, Maintenance hemodialysis, Cardiovascular events

中图分类号:

R459.5
R54

高健, 王德琴, 周永华, 缪娴静, 陈宇, 景鑫, 王艳. 血清生长刺激表达基因2蛋白和脂蛋白相关磷脂酶A2与维持性血液透析患者心血管事件的关系[J]. 内科理论与实践, 2022, 17(04): 295-300.

GAO Jian, WANG Deqin, ZHOU Yonghua, MIAO Xianjing, CHEN Yu, JING Xin, WANG Yan. Study on relationship between serum growth stimulation expressed gene 2 and lipoprotein-associated phospholipase 2 and cardiovascular events in maintenance hemodialysis patients[J]. Journal of Internal Medicine Concepts & Practice, 2022, 17(04): 295-300.

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参考文献 19

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项目	有心血管事件组（n=66）	无心血管事件组（n=111）	t/χ²	P
年龄（岁）	69.55±7.32	61.24±5.84	8.30	<0.001
性别（男）[n（%）]	38（57.58）	62（55.86）	0.05	0.82
原发病[n（%）]			0.27	0.97
肾小球肾炎	6（9.1）	9（8.1）
糖尿病肾病	21（31.8）	39（35.1）
其他	11（16.7）	19（17.1）
不明	28（42.4）	44（39.6）
透析龄（月）	50.74±7.68	39.43±8.91	8.58	<0.001
MAP（mmHg）	101.85±13.45	103.16±16.02	-0.59	0.56
TC（mmol/L）	5.12±0.75	4.63±0.71	4.35	<0.001
LDL（mmol/L）	2.79±0.71	2.51±0.48	2.87	0.005
HDL（mmol/L）	0.94±0.25	1.10±0.30	-3.73	<0.001
TG（mmol/L）	1.99±0.25	1.89±0.29	2.28	0.03
Ca（mmol/L）	2.33±0.22	2.20±0.22	3.70	<0.001
P（mmol/L）	1.88±0.40	1.77±0.31	1.90	0.06
UA（mmol/L）	442.95±19.92	406.04±25.65	10.69	<0.001
Alb（g/L）	34.60±2.12	37.93±2.51	-9.03	<0.001
BNP（ng/L）	745.71±35.21	355.63±61.23	47.28	<0.001
Hb（g/L）	103.26±10.76	119.12±7.53	-10.54	<0.001
LVEF（%）	48.56±7.28	54.73±6.69	-5.74	<0.001
LVDD（mm）	47.24±5.83	48.05±6.24	-0.85	0.40
ST2（μg/L）	68.47±19.32	50.53±16.37	6.59	<0.001
LP-PLA2（μg/L）	269.27±46.30	234.38±39.19	5.35	<0.001

指标	截断值	AUC（95% CI）	灵敏度（%）（95%CI）	特异度（%）（95%CI）	P
ST2（μg/L）	61	0.77（0.71~0.83）	74.2（60.2~84.2）	77.5（68.6~84.9）	<0.001
LP-PLA2（μg/L）	266	0.70（0.63~0.77）	48.5（36.0~61.1）	82.0（73.6~88.6）	<0.001
ST2+LP-PLA2	/	0.83（0.77~0.89）	74.2（60.2~84.2）	82.0（73.6~88.6）	<0.001

变量	单因素分析		多因素分析
变量	HR（95% CI）	P	HR（95% CI）	P
年龄（≥60岁）	6.67（2.42~18.36）	<0.001	1.22（0.37~3.99）	0.75
性别（男性）	1.20（0.73~1.95）	0.48
原发病
肾小球肾炎		1
糖尿病肾病	1.25（0.51~3.03）	0.62
其他	1.07（0.61~1.89）	0.82
不明	1.05（0.52~2.12）	0.89
透析龄	1.07（1.05~1.09）	<0.001	1.00（0.97~1.04）	0.98
MAP	1.00（0.98~1.02）	0.97
TC	1.93（1.40~2.66）	<0.001	1.12（0.77~1.63）	0.55
LDL	1.58（1.09~2.28）	0.02	1.18（0.78~1.78）	0.44
HDL	0.14（0.06~0.34）	<0.001	0.29（0.08~1.04）	0.06
TG	1.93（0.78~4.79）	0.16
Ca	3.88（1.36~11.07）	0.01	1.21（0.05~1.82）	0.48
P	2.48（1.17~5.29）	0.02	1.45（0.21~1.98）	0.05
UA	1.04（1.03~1.05）	<0.001	1.00（0.99~1.02）	0.89
Alb	0.74（0.67~0.81）	<0.001	0.99（0.86~1.13）	0.86
BNP	1.01（1.00~1.02）	<0.001	1.01（1.00~1.02）	<0.001
Hb	0.93（0.91~0.94）	<0.001	1.01（0.98~1.04）	0.55
LVEF	0.93（0.90~0.96）	<0.001	1.02（0.99~1.07）	0.20
LVDD	0.99（0.95~1.03）	0.55
ST2（>61 μg/L）	11.28（6.38~19.95）	<0.001	1.27（1.13~1.57）	<0.001
LP-PLA2（>266 μg/L）	2.18（1.34~3.55）	0.002	1.92（1.49~2.73）	<0.001