老年急性脑梗死患者血清高残余胆固醇水平与Lp-PLA2表达的相关性研究

林永娟; 蒋澄; 黄明敏; 李玲玲

doi:10.16766/j.cnki.issn.1674-4152.002576

老年急性脑梗死患者血清高残余胆固醇水平与Lp-PLA2表达的相关性研究

doi: 10.16766/j.cnki.issn.1674-4152.002576

南京大学医学院附属鼓楼医院老年科，江苏南京 210008

基金项目:

国家自然科学基金项目 81400965

江苏省干部保健科研课题 BJ18006

详细信息

通讯作者:
李玲玲, E-mail: seulilingling@126.com

中图分类号: R743.33
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- 被引次数: 0
出版历程
- 收稿日期: 2021-12-20
- 网络出版日期: 2022-09-26

Association of high residual cholesterol levels and Lp-PLA2 expression in elderly patients with acute ischemic stroke

Department of Geriatric, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China

摘要

摘要: 目的探讨老年急性脑梗死(AIS)患者残余胆固醇(RC)和脂蛋白相关磷脂酶A2(Lp-PLA2)的相关性，评估两者对AIS病情的预测价值。方法选取2019年1月—2021年3月南京大学医学院附属鼓楼医院收治的老年高RC-AIS患者162例(观察组)，另外选取同期正常RC-AIS患者165例(对照组)，比较2组间血脂指标和Lp-PLA2的差异，采用Pearson法分析相关性，采用ROC曲线评价两者对AIS病情的预测价值。结果观察组Lp-PLA2水平、治疗后美国国立卫生院卒中量表(NIHSS)评分高于对照组(Z=4.361、2.182，均P＜0.05)。Logistic回归分析示Lp-PLA2(95% CI：1.000~1.007，P=0.045)、治疗后NIHSS评分(95% CI：1.026~1.369，P=0.021)是AIS患者RC水平的独立影响因素。AIS患者RC、Lp-PLA2水平及治疗后NIHSS评分互呈正相关(r=0.683、0.635、0.640，均P＜0.001)。RC＞0.845 mmol/L、Lp-PLA2＞242 ng/mL预测AIS病情严重程度的ROC曲线下面积分别为0.835、0.854，2项指标联合评估的AUC为0.897。结论高RC-AIS患者血清Lp-PLA2水平显著升高，两者呈正相关，在预测AIS治疗后神经功能缺损程度和预后中具有良好价值。
- 急性脑梗死 /
- 残余胆固醇 /
- 脂蛋白相关磷脂酶A2 /
- 相关性研究
Abstract: Objective To investigate the correlation between residual cholesterol (RC) and lipoprotein-related phospholipase A2 (Lp-PLA2) and evaluated their predictive value in elderly patients with acute ischemic stroke (AIS) and high RC. Methods A total of 162 elderly AIS patients with high RC (observation group) admitted in Nanjing Drum Tower Hospital from Jan. 2019 to Mar. 2021 were included in the study, and 165 normal RC-AIS patients during the same period were selected as the control group. The levels of blood lipid parameters and Lp-PLA2 in the two groups were compared, and the correlation between RC and Lp-PLA2 were analysed by the Pearson method. ROC analysis was used to evaluate the predictive value of RC and Lp-PLA2 in neurological impairment. Results The levels of Lp-PLA2 and National Institute of Health stroke scale (NIHSS) score after treatment in the observation group were significantly higher than those in the control group (Z=4.361, 2.182, all P < 0.05). Logistic regression analysis showed that Lp-PLA2 (95% CI: 1.000-1.007, P=0.045) and NIHSS score after treatment (95% CI: 1.026-1.369, P=0.021) were independent factors of RC levels in patients with AIS. RC, Lp-PLA2 and NIHSS score after treatment in patients with AIS were positively correlated with each other (r=0.683, 0.635, 0.640, all P < 0.001). The area under the ROC curve for serum RC>0.845 mmol/L and Lp-PLA2>242 ng/mL in predicting the severity of AIS were 0.835 and 0.854, respectively. When combined with two indicators, the AUC was 0.897. Conclusion Lp-PLA2 levels were significantly increased in patients with high RC-AIS. A positive correlation was found between the levels of RC and Lp-PLA2. High levels of RC or Lp-PLA2 have a good value in predicting the degree of neurological impairment and the prognosis after treatment of patients with AIS.
- Acute ischemic stroke /
- Remnant cholesterol /
- Lipoprotein-associated phospholipase A2 /
- Correlation study

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图 1 不同浓度RC脑梗死患者血清Lp-PLA2、治疗后NIHSS评分比较

注：^aP＜0.05。

Figure 1. Comparison of serum Lp-PLA2 and NIHSS score in patients with RC cerebral infarction at different concentrations

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图 2 Lp-PLA2、RC对AIS病情严重程度诊断ROC曲线

Figure 2. ROC curve of Lp-PLA2 and RC in the diagnosis of severity of AIS

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表 1 2组脑梗死患者基线资料比较

Table 1. Comparison of baseline data of cerebral infarction patients between two groups

组别	例数	年龄(x±s，岁)	性别(例)		BMI(x±s)	吸烟史[例(%)]	高血压病史[例(%)]	糖尿病病史[例(%)]	冠心病病史[例(%)]	入院NIHSS评分[M(P₂₅, P₇₅), 分]	治疗后NIHSS评分[M(P₂₅, P₇₅), 分]
组别	例数	年龄(x±s，岁)	男性	女性	BMI(x±s)	吸烟史[例(%)]	高血压病史[例(%)]	糖尿病病史[例(%)]	冠心病病史[例(%)]	入院NIHSS评分[M(P₂₅, P₇₅), 分]	治疗后NIHSS评分[M(P₂₅, P₇₅), 分]
观察组	162	67.59±12.13	97	65	23.25±2.56	43(26.5)	123(75.9)	52(29.6)	22(13.6)	5.00(2.00, 11.00)	2.50(1.00, 8.00)
对照组	165	68.27±11.53	109	56	22.56±2.66	42(25.5)	113(68.5)	57(34.5)	21(12.7)	4.00(2.00, 8.00)	2.00(1.00, 4.00)
统计量		-0.521^a	-1.342^b		1.401^a	0.051^b	2.252^b	-0.911^b	0.050^b	1.404^c	2.182^c
P值		0.632	0.247		0.750	0.822	0.133	0.341	0.819	0.160	0.029
注：^a为t值，^b为χ²值，^c为Z值。

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表 2 2组脑梗死患者实验室指标比较

Table 2. Comparison of laboratory indexes between two groups of cerebral infarction patients

组别	例数	糖化血红蛋白[M(P₂₅, P₇₅), %]	FPG [M(P₂₅, P₇₅), mmol/L]	TC [M(P₂₅, P₇₅), mmol/L]	TG [M(P₂₅, P₇₅), mmol/L]	HDL-C (x±s, mmol/L)
观察组	162	5.80(5.40, 6.50)	5.46(4.83, 6.87)	4.05(3.42, 4.90)	1.56(0.99, 2.29)	2.40±0.92
对照组	165	5.80(5.40, 6.85)	5.40(4.76, 6.49)	3.64(3.09, 4.32)	1.10(0.88, 1.40)	2.17±0.79
统计量		-0.111^a	1.651^a	4.271^a	7.190^a	2.460^b
P值		0.707	0.193	0.001	0.001	0.270

组别	例数	LDL-C[M(P₂₅, P₇₅), mmol/L]	Hcy[M(P₂₅, P₇₅), μmol/L]		CRP[M(P₂₅, P₇₅), g/L]	Lp-PLA2[M(P₂₅, P₇₅), ng/mL]
观察组	162	0.67(0.27, 0.87)	4.29(2.58, 8.43)		3.70(2.30, 8.20)	283.50(170.00, 393.00)
对照组	165	1.07(0.87, 1.25)	3.40(2.70, 7.70)		2.90(2.10, 6.20)	169.00(115.00, 356.00)
统计量		-10.497^a	3.850^a		2.590^a	4.361^a
P值		＜0.001	0.029		0.016	＜0.001
注：^a为Z值，^b为t值。

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表 3 AIS患者RC水平的多因素logistic回归分析

Table 3. Multivariate logistic regression analysis of RC level in AIS patients

变量	B	SE	Wald χ²	P值	OR值	95% CI
TC	1.548	0.270	32.771	＜0.001	4.701	2.767~7.986
TG	1.864	0.384	23.551	＜0.001	6.451	3.038~13.696
LDL-C	-7.880	1.058	55.472	＜0.001	0.000	0.000~0.003
Lp-PLA2	0.004	0.002	4.011	0.045	1.004	1.000~1.007
Hcy	0.026	0.036	0.553	0.457	1.027	0.958~1.101
CRP	0.006	0.009	0.491	0.483	1.006	0.989~1.023
入院基线NIHSS	-0.059	0.054	1.179	0.278	0.943	0.848~1.048
治疗后NIHSS	0.170	0.074	5.321	0.021	1.185	1.026~1.369

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表 4 Lp-PLA2、RC对AIS病情严重程度的预测价值

Table 4. Predictive value of Lp-PLA2 and RC in AIS

项目	最佳临界值	灵敏度(%)	特异度(%)	AUC	95% CI
Lp-PLA2(ng/mL)	242	92.2	68.0	0.854	0.814~0.894
RC(mmol/L)	0.845	81.4	73.8	0.835	0.790~0.880
两者联合		86.3	82.7	0.897	0.864~0.930

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参考文献(21)

[1]	SMITH J W, BARLAS R S, MAMAS M A, et al. Association between serum secretory phospholipase A2 and risk of ischaemic stroke[J]. Eur J Neurol, 2021, 28(11): 3650-3655. doi: 10.1111/ene.15004
[2]	IZUMIDA T, NAKAMURA Y, HINO Y, et al. Combined effect of small dense low-density lipoprotein cholesterol (sdLDL-C) and remnant-like particle cholesterol (RLP-C) on low-grade inflammation[J]. J Atheroscler Thromb, 2020, 27(4): 319-330. doi: 10.5551/jat.49528
[3]	郝泽林, 吴建跃, 滕振飞, 等. 急性脑梗死患者血清学指标与神经功能缺损和脑梗死体积及颈动脉斑块性质的相关性研究[J]. 中华全科医学, 2020, 18(11): 1803-1806. doi: 10.16766/j.cnki.issn.1674-4152.001623 HAO Z L, WU J Y, TENG Z F, et al. Correlation of hs-CRP, MMP-9 and Lp-PLA2 with neurological deficit, cerebral infarction volume and carotid plaque properties in patients with acute cerebral infarction[J]. Chinese Journal of General Practice, 2020, 18(11): 1803-1806. doi: 10.16766/j.cnki.issn.1674-4152.001623
[4]	高腾龙, 钱文茹, 赵春生, 等. 残余胆固醇与急性冠脉综合征发病相关性的研究[J]. 河北医学, 2021, 27(2): 276-278. doi: 10.3969/j.issn.1006-6233.2021.02.021 GAO T L, QIAN W R, ZHAO C S, et al. A Research on the Relevance of Residual Cholesterol to Acute Coronary Syndrome[J]. Hebei Medicine, 2021, 27(2): 276-278. doi: 10.3969/j.issn.1006-6233.2021.02.021
[5]	杜晓辉. 血清脂蛋白a和游离脂肪酸水平与冠心病患者颈动脉粥样硬化的相关性[J]. 医药论坛杂志, 2021, 42(19): 120-122. https://www.cnki.com.cn/Article/CJFDTOTAL-HYYX202119029.htm DU X H. Correlation between serum lipoprotein A and free fatty acid levels and carotid atherosclerosis in patients with coronary heart disease[J]. Journal of Medical Forum, 2021, 42(19): 120-122. https://www.cnki.com.cn/Article/CJFDTOTAL-HYYX202119029.htm
[6]	SUCATO V, COPPOLA G, TESTA G, et al. Evaluation of remnant cholesterol levels and Monocyte-to-HDL-cholesterol ratio in South Asian patients with acute coronary syndrome[J]. Nutr Metab Cardiovasc Dis, 2021, 31(7): 2144-2150. doi: 10.1016/j.numecd.2021.04.007
[7]	VARBO A, NORDESTGAARD B G. Remnant cholesterol and risk of ischemic stroke in 112, 512 individuals from the general population[J]. Ann Neurol, 2019, 85(4): 550-559. doi: 10.1002/ana.25432
[8]	WANG Y, HU S Y, REN L T, et al. Lp-PLA2 as a risk factor of early neurological deterioration in acute ischemic stroke with TOAST type of large arterial atherosclerosis[J]. Neurol Res, 2019, 41(1): 1-8. doi: 10.1080/01616412.2018.1493850
[9]	LIANG T, WANG S C, ZHANG D T, et al. Evaluation of lipoprotein-associated phospholipase A2, serum amyloid A, and fibrinogen as diagnostic biomarkers for patients with acute cerebral infarction[J]. J Clin Lab Anal, 2020, 34(3): e23084. DOI: 10.1002/jcla.23084.
[10]	CASTANER O, PINTO X, SUBIRANA I, et al. Remnant cholesterol, not LDL cholesterol, is associated with incident cardiovascular disease[J]. J Am Coll Cardiol, 2020, 76(23): 2712-2724. doi: 10.1016/j.jacc.2020.10.008
[11]	HERPICH F, RINCON F. Management of acute ischemic stroke[J]. Crit Care Med, 2020, 48(11): 1654-1663. doi: 10.1097/CCM.0000000000004597
[12]	FUJIHARA Y, NAKAMURA T, HORIKOSHI T, et al. Remnant lipoproteins are residual risk factor for future cardiovascular events in patients with stable coronary artery disease and on-statin low-density lipoprotein cholesterol levels < 70 mg/dL[J]. Circ J, 2019, 83(6): 1302-1308. doi: 10.1253/circj.CJ-19-0047
[13]	BIAN L, MAO L G, SUN Y, et al. Serum lipoprotein-associated phospholipase A2 as a promising prognostic biomarker in association with 90-day outcome of acute intracerebral hemorrhage[J]. Clin Chim Acta, 2019, 495: 429-435. doi: 10.1016/j.cca.2019.05.017
[14]	BERNELOT MOENS S J, VERWEIJ S L, SCHNITZLER J G, et al. Remnant cholesterol elicits arterial wall inflammation and a multilevel cellular immune response in humans[J]. Arterioscler Thromb Vasc Biol, 2017, 37(5): 969-975. doi: 10.1161/ATVBAHA.116.308834
[15]	来佳成, 韩永生. 脂蛋白相关磷脂酶A2与颈动脉粥样硬化病变程度的相关性研究[J]. 中华全科医学, 2021, 19(10): 1626-1628, 1705. doi: 10.16766/j.cnki.issn.1674-4152.002127 LAI J C, HAN Y S. Relationship between lipoprotein-associated phospholipase A2 with degree of carotid atherosclerosis[J]. Chinese Journal of General Practice, 2021, 19(10): 1626-1628, 1705. doi: 10.16766/j.cnki.issn.1674-4152.002127
[16]	刘莉, 吴钢, 吴庆, 等. 外周血脂蛋白相关磷脂酶水平与糖尿病患者冠状动脉硬化斑块的相关性研究[J]. 中华全科医学, 2020, 18(1): 68-70, 118. doi: 10.16766/j.cnki.issn.1674-4152.001170 LIU L WU G WU Q, et al. Study on the relationship between the level of Lp-PLA2 in peripheral blood and coronary atherosclerotic plaque in diabetic patients[J]. Chinese Journal of General Practice, 2020, 18(1): 68-70, 118. doi: 10.16766/j.cnki.issn.1674-4152.001170
[17]	ELSHAZLY M B, MANI P, NISSEN S, et al. Remnant cholesterol, coronary atheroma progression and clinical events in statin-treated patients with coronary artery disease[J]. Eur J Prev Cardiol, 2020, 27(10): 1091-1100. doi: 10.1177/2047487319887578
[18]	TUREK-JAKUBOWSKA A, DEBSKI J, JAKUBOWSKI M, et al. New candidates for biomarkers and drug targets of ischemic stroke-a first dynamic LC-MS human serum proteomic study[J]. J Clin Med, 2022, 11(2): 339. doi: 10.3390/jcm11020339
[19]	MELITA H, MANOLIS A A, MANOLIS T A, et al. Lipoprotein(a) and cardiovascular disease: A missing link for premature atherosclerotic heart disease and/or residual risk[J]. J Cardiovasc Pharmacol, 2022, 79(1): e18-e35.
[20]	AMBROSY A P, YANG J, SUNG S H, et al. Triglyceride levels and residual risk of atherosclerotic cardiovascular disease events and death in adults receiving statin therapy for primary or secondary prevention: Insights from the KP REACH study[J]. J Am Heart Assoc, 2021, 10(20): e020377. DOI: 10.1161/JAHA.120.020377.
[21]	WOO J S, HONG S J, CHA D H, et al. Comparison of the efficacy and safety of atorvastatin 40 mg/omega-3 fatty acids 4 g fixed-dose combination and atorvastatin 40 mg monotherapy in hypertriglyceridemic patients who poorly respond to atorvastatin 40 mg monotherapy: An 8-week, multicenter, randomized, double-blind phase Ⅲ study[J]. Clin Ther, 2021, 43(8): 1419-1430.