血清艾帕素-12水平与冠状动脉钙化的相关性研究

doi:10.16138/j.1673-6087.2024.02.04

摘要/Abstract

摘要：

目的：探究血清血管活性多肽艾帕素-12（apelin-12）与冠状动脉钙化（coronary artery calcification，CAC）之间的相关性。方法：选取于2015年1月至2018年12月在上海交通大学医学院附属瑞金医院心血管内科住院并行冠状动脉CT成像的197例患者，根据Agatston评分法将患者分为CAC评分（CAC score，CACS）≤100分（n=72）与CACS>100分（n=125）2组，收集2组患者相关临床指标，采用酶联免疫吸附法（enzyme-linked immunosorbent assay，ELISA）检测患者血清艾帕素-12水平，探究其与CAC及其相关心血管事件之间的关系。结果：2组患者基线特征显示，与CACS≤100分组相比，CACS>100分组患者的血清艾帕素-12水平[79.50 （68.35，97.49） ng/L比91.94（80.13，110.19） ng/L]明显降低，差异有统计学意义（P=0.002）。二元Logistic回归分析显示，在未经调整的模型中，艾帕素-12水平与CAC的发生相关（OR=0.988, 95% CI: 0.978~0.997, P=0.013），调整了基线有差异的指标后，血清艾帕素-12水平与CAC的发生仍独立相关。Kaplan-Meier生存分析发现，较低的艾帕素-12水平与较高的心血管事件发生风险相关（Log rank检验，P=0.019）。在CACS>100分的亚组中，艾帕素-12水平与结局事件发生风险有关（Log rank检验，P=0.035）。采用Cox回归分析来确定艾帕素-12水平在不同亚组中的预测作用，发现艾帕素-12水平对结局事件的预测作用在年龄>65岁、肾功能不全、糖尿病患者中更强。结===论：血清艾帕素-12与CAC及相关心血管事件之间存在相关性，艾帕素-12可能是预测CAC及其预后的生物标志物。

关键词: 冠状动脉钙化, 冠状动脉钙化评分, 心血管事件, 艾帕素-12

Abstract:

Objective To investigate the correlation between serum vasoactive polypeptide-12 (apelin-12) and coronary artery calcification （CAC）. Methods Totally 197 cases of patients, who were treated with coronary artery CT angiography (CTA) in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2015 to December 2018 were selected. According to Agatson score, the patients were divided into two groups, which were CAC scores≤100（n=72）and CAC scores>100 （n=125）. The relevant clinical indexes of patients were collected, and the serum apelin-12 level was detected by enzyme-linked immunosorbent assay to explore its relationship with CAC and its related cardiovascular events. Results The baseline characteristics in two groups showed that serum apelin-12 level in CAC scores >100 group was lower than that in CAC scores ≤100 group [79.50 （68.35，97.49） ng/L vs 91.94 （80.13，110.19） ng/L]， which showed significant difference（P=0.02）. Binary Logistic regression analysis showed that apelin-12 levels were associated with the occurrence of CAC in the unadjusted model （P=0.013）. After adjusting for the indicators with baselines difference， apelin-12 levels were still associated with the occurrence of CAC. Kaplan-Meier survival analysis found that compared to higher apelin-12 levels, lower apelin-12 levels were associated with an increased risk of cardiovascular events（Log rank test， P=0.019）. In subgroups with CAC scores >100， apelin-12 levels were associated with an increased risk of outcome events （Log rank test， P=0.035）. Cox regression analysis was used to determine the predictive effect of apelin-12 levels in different subgroups and found that the predictive effect of apelin-12 levels on outcome events was found to be stronger in patients aged > 65 years, with renal insufficiency and diabetes mellitus. Conclusions Serum apelin-12 is correlated with CAC and related cardiovascular events, suggesting that apelin-12 may be a biomarker for predicting CAC and its prognosis.

Key words: Coronary artery calcification, Coronary artery calcification scores, Cardiovascular event, Apelin-12

中图分类号:

R543.3

赵安琪, 杨玲, 查晴, 杨克, 刘艳. 血清艾帕素-12水平与冠状动脉钙化的相关性研究[J]. 内科理论与实践, 2024, 19(02): 107-114.

ZHAO Anqi, YANG Ling, ZHA Qing, YANG Ke, LIU Yan. Study on correlation between serum apelin-12 level and coronary artery calcification[J]. Journal of Internal Medicine Concepts & Practice, 2024, 19(02): 107-114.

图/表 8

图1

表1

表2

图2

图3

图4

图5

图6

参考文献 29

[1]	Wang L, Jerosch-Herold M, Jacobs DR Jr, et al. Coronary artery calcification and myocardial perfusion in asymptomatic adults[J]. J Am Coll Cardiol, 2006, 48(5):1018-1026. pmid: 16949496
[2]	Greenland P, Blaha MJ, Budoff MJ, et al. Coronary calcium score and cardiovascular risk[J]. J Am Coll Cardiol, 2018, 72(4):434-447. doi: S0735-1097(18)34936-2 pmid: 30025580
[3]	LaMonte MJ, FitzGerald SJ, Church TS, et al. Coronary artery calcium score and coronary heart disease events in a large cohort of asymptomatic men and women[J]. Am J Epidemiol, 2005, 162(5):421-429. doi: 10.1093/aje/kwi228 pmid: 16076829
[4]	Dellegrottaglie S, Sanz J, Rajagopalan S. Molecular determinants of vascular calcification: a bench to bedside view[J]. Curr Mol Med, 2006, 6(5):515-524. doi: 10.2174/156652406778018653 pmid: 16918372
[5]	Xie H, Tang SY, Cui RR, et al. Apelin and its receptor are expressed in human osteoblasts[J]. Regul Pept, 2006, 134(2-3):118-125.
[6]	Kronmal RA, McClelland RL, Detrano R, et al. Risk factors for the progression of coronary artery calcification in asymptomatic subjects: results from the Multi-Ethnic Study of Atherosclerosis (MESA)[J]. Circulation, 2007, 115(21):2722-2730. doi: 10.1161/CIRCULATIONAHA.106.674143 pmid: 17502571
[7]	Antushevich H, Wójcik M. Review: apelin in disease[J]. Clin Chim Acta, 2018,483:241-248.
[8]	Askin L, Askin HS, Tanrıverdi O, et al. Serum apelin levels and cardiovascular diseases[J]. North Clin Istanb, 2022, 9(3):290-294. doi: 10.14744/nci.2021.33427 pmid: 36199867
[9]	Song J, Tang J, Zhang Z, et al. Targeting the elabela/apelin-apelin receptor axis as a novel therapeutic approach for hypertension[J]. Chin Med J (Engl), 2022, 135(9):1019-1026.
[10]	Busch R, Strohbach A, Pennewitz M, et al. Regulation of the endothelial apelin/APJ system by hemodynamic fluid flow[J]. Cell Signal, 2015, 27(7):1286-1296. doi: 10.1016/j.cellsig.2015.03.011 pmid: 25817266
[11]	Zhou Y, Wang Y, Qiao S. Apelin: a potential marker of coronary artery stenosis and atherosclerotic plaque stability in ACS patients[J]. Int Heart J, 2014, 55(3):204-212. doi: 10.1536/ihj.13-234 pmid: 24806385
[12]	Ceylan-Isik AF, Kandadi MR, Xu X, et al. Apelin administration ameliorates high fat diet-induced cardiac hypertrophy and contractile dysfunction[J]. J Mol Cell Cardiol, 2013,63:4-13.
[13]	Azizi Y, Faghihi M, Imani A, et al. Post-infarct treatment with [Pyr1]-apelin-13 reduces myocardial damage through reduction of oxidative injury and nitric oxide enhancement in the rat model of myocardial infarction[J]. Peptides, 2013,46:76-82.
[14]	Tatemoto K, Hosoya M, Habata Y, et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor[J]. Biochem Biophys Res Commun, 1998, 251(2):471-476.
[15]	Cirillo P, Ziviello F, Pellegrino G, et al. The adipokine apelin-13 induces expression of prothrombotic tissue factor[J]. Thromb Haemost, 2015, 113(2):363-372.
[16]	Tatemoto K, Takayama K, Zou MX, et al. The novel peptide apelin lowers blood pressure via a nitric oxide-dependent mechanism[J]. Regul Pept, 2001, 99(2-3):87-92.
[17]	Pisarenko OI, Serebryakova LI, Pelogeykina YA, et al. In vivo reduction of reperfusion injury to the heart with apelin-12 peptide in rats[J]. Bull Exp Biol Med, 2011, 152(1):79-82.
[18]	Ashley EA, Powers J, Chen M, et al. The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo[J]. Cardiovasc Res, 2005, 65(1):73-82. pmid: 15621035
[19]	Agatston AS, Janowitz WR, Hildner FJ, et al. Quantification of coronary artery calcium using ultrafast computed tomography[J]. J Am Coll Cardiol, 1990, 15(4):827-832. doi: 10.1016/0735-1097(90)90282-t pmid: 2407762
[20]	Budoff MJ, Kinninger A, Gransar H, et al. When does a calcium score equate to secondary prevention?[J]. JACC Cardiovasc Imaging, 2023, 16(9):1181-1189.
[21]	Harrington RA, Stone GW, McNulty S, et al. Platelet inhibition with cangrelor in patients undergoing PCI[J]. N Engl J Med, 2009, 361(24):2318-2329.
[22]	Yin C, Zhang H, Zhang M, et al. Adropin and apelin-12 efficiently predict metabolic syndrome in obese children[J]. Pediatr Diabetes, 2020, 21(7):1132-1139.
[23]	Chen K, Zhao XL, Li LB, et al. miR-503/apelin-12 mediates high glucose-induced microvascular endothelial cells injury via JNK and p38MAPK signaling pathway[J]. Regen Ther, 2020,14:111-118.
[24]	Liaquat A, Khan A, Ullah Shah S, et al. Evaluating the use of coronary artery calcium scoring as a tool for coronary artery disease (CAD) risk stratification and its association with coronary stenosis and CAD risk factors[J]. BMJ Open, 2022, 12(7):e057703.
[25]	Liu Y, Xia H, Li M, et al. Prognostic value of combining apelin-12 and estimated glomerular filtration rate in patients with ST-segment elevation myocardial infarction[J]. J Interv Cardiol, 2022,2022:2272928.
[26]	Pisarenko OI, Bespalova ZhD, Lankin VZ, et al. Antioxidant properties of apelin-12 and its structural analogue in experimental ischemia and reperfusion[J]. Kardiologiia, 2013, 53(5):61-67. pmid: 23952997
[27]	Pisarenko OI, Pelogeĭkina IuA, Shul'zhenko VS, et al. The influence of inhibiting no formation on metabolic recovery of ischemic rat heart by apelin-12[J]. Biomed Khim, 2012, 58(6):702-711. pmid: 23350202
[28]	Pisarenko OI, Serebryakova LI, Studneva IM, et al. Effects of structural analogues of apelin-12 in acute myocardial infarction in rats[J]. J Pharmacol Pharmacother, 2013, 4(3):198-203. doi: 10.4103/0976-500X.114600 pmid: 23960425
[29]	Pisarenko OI, Lankin VZ, Konovalova GG, et al. Apelin-12 and its structural analog enhance antioxidant defense in experimental myocardial ischemia and reperfusion[J]. Mol Cell Biochem, 2014, 391(1-2):241-250. doi: 10.1007/s11010-014-2008-4 pmid: 24599747

指标	CACS≤100分（n=72）	CACS>100分（n=125）	χ²/U/Z	P
年龄（岁）	59（53，68）	67（61，76）	-4.816	0.000
男性[n（%）]	42（58.3）	96（76.8）	7.426	0.006
吸烟史[n（%）]	16（29.1）	26（34.2）	0.384	0.535
BMI（kg/㎡）	25.28（23.04，27.48）	24.86（23.57，27.70）	-0.435	0.664
心率（次/min）	78（68，88）	76（70，84）	-0.278	0.781
收缩压（mmHg）	129.350±17.927	136.250±19.119	-2.482	0.014
舒张压（mmHg）	73.460±9.985	74.960±10.950	-0.948	0.334
血钙（mmol/L）	2.820±4.920	2.236±0.119	1.327	0.186
血磷（mmol/L）	1.14（1.01，1.27）	1.12（1.01，1.22）	-0.805	0.421
eGFR [mL/（min·1.73 m²）]	90.80（73.50，99.90）	84.60（69.65，95.35）	-2.160	0.031
肌酐（μmol/L）	73（63，89）	80（70，91）	-2.163	0.031
尿酸（mmol/L）	363.08±11.00	353.55±7.37	0.743	0.458
TG（mmol/L）	1.485（1.108，1.870）	1.330（0.965，1.930）	-0.828	0.408
TC（mmol/L）	4.265（3.590，4.900）	3.60（3.03，4.56）	-3.180	0.001
HDL-C（mmol/L）	1.070（0.920，1.210）	1.090（0.930，1.315）	-0.577	0.564
LDL-C（mmol/L）	2.635（2.108，3.068）	2.050（1.560，2.810）	-3.493	0.000
艾帕素-12（ng/L）	91.94（80.13，110.19）	79.50（68.35，97.49）	-3.128	0.002
高血压[n（%）]	40（55.6）	91（72.8）	6.098	0.014
冠心病[n（%）]	46（63.9）	119（95.2）	32.912	0.000
糖尿病[n（%）]	14（19.4）	41（32.8）	4.049	0.044
抗血小板药[n（%）]	47（65.3）	117（93.6）	28.191	0.000
他汀类药物[n（%）]	46（63.9）	117（93.6）	28.241	0.000
降糖药[n（%）]	12（16.7）	38（30.4）	4.550	0.033
降压药[n（%）]	64（88.9）	112（89.6）	0.024	0.876

模型	OR（95%CI）	β	P
未调整模型	0.988（0.978~0.997）	-0.012	0.013
模型1	0.983（0.973~0.994）	-0.017	0.002
模型2	0.982（0.970~0.993）	-0.019	0.002