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炎症因子参与介导了冠心病(CHD)动脉粥样硬化的病理损伤过程[1-2],而中性粒细胞明胶酶相关载脂蛋白(NGAL)及超敏-C反应蛋白(hs-CRP)在炎症方面起重要的调节作用[3-4]。hs-CRP是目前被认为与动脉粥样硬化关系最密切的非特异性炎症标志物,在众多炎症因子中具有代表意义[5-6]。NGAL正常表达于人体中性粒细胞、肝实质细胞、肾小管上皮细胞及血管内皮细胞等。在心血管系统,NGAL可调节炎症反应,影响基质金属蛋白酶活性,调节细胞能量代谢,影响CHD及其他心血管疾病的发生、发展[7]。多项研究[8-9]表明,NGAL是心血管疾病的危险因子,对CHD的发生及预后有一定的诊断价值。本研究拟通过测定CHD病人的血清NGAL水平,探讨其与血清hs-CRP及冠状动脉粥样硬化病变程度间的关系,分析NGAL在CHD诊断中的作用。
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各组年龄、性别、BMI、高血压病史、糖尿病史、吸烟史、TC、TG、HDL-C、LDL-C、SCr差异均无统计学意义(P>0.05)。SAP组、UA组和AMI组血清hs-CRP水平高于CON组(P < 0.05),且SAP组、UA组和AMI组间hs-CRP差异均有统计学意义(P < 0.05)(见表 1)。
指标 SAP(n=40) UA(n=50) AMI(n=45) CON(n=30) F P MS组内 年龄/岁 61.98±9.52 62.11±8.95 63.96±10.03 59.63±9.90 1.24 >0.05 91.480 性别(男/女) 26/14 28/22 22/23 17/13 6.48# >0.05 — BMI/(kg/m2) 25.80±3.47 25.62±3.86 25.95±3.51 25.11±3.70 50.34 >0.05 13.284 吸烟史 21(52.50) 22(44.00) 26(57.80) 13(43.30) 7.32# >0.05 — 糖尿病病史 7(17.50) 10(20.00) 12(26.70) 5(16.70) 9.82# >0.05 — 高血压病史 25(62.50) 29(58.00) 27(60.00) 16(53.30) 6.89# >0.05 — TC/(mmol/L) 3.98±0.83 3.86±1.02 4.05±1.02 3.91±0.89 0.34 >0.05 0.911 TG/(mmol/L) 1.66±0.67 1.68±0.89 1.70±0.87 1.42±0.56 0.93 >0.05 0.613 HDL-C/(mmol/L) 1.20±0.33 1.23±0.35 1.21±0.35 1.37±0.37 1.68 >0.05 0.122 LDL-C/(mmol/L) 2.49±0.53 2.51±0.62 2.54±0.60 2.21±0.46 2.41 >0.05 13.640 SCr/(mol/L) 67.26±10.87 68.55±10.21 68.63±9.84 64.08±9.82 1.49 >0.05 104.180 hs-CRP /(mg/L) 3.24±1.67Δ 5.06±2.11Δ* 8.39±3.45Δ*& 1.89±1.07 56.53 < 0.01 5.490 #示χ2值;q检验:与CON组比较ΔP < 0.05;与SAP组比较*P < 0.05;与UA组比较&P < 0.05 表 1 一般临床资料比较(x±s)
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Gensini评分30分组、30~60分组和>60分组血清NGAL和hs-CRP水平差异均有统计学意义(P < 0.05~P < 0.01)(见表 2)。
分组 n NGAL/(ng/mL) hs-CRP/(mg/L) Gensini评分/分 < 30 41 55.49±18.47 3.03±1.51 30~60 56 83.52±26.61** 5.35±1.93** >60 38 100.64±36.22**# 8.95±2.99**## F — 27.09 73.73 P — < 0.01 < 0.01 MS组内 — 76.661 4.749 q检验:与30分组比较**P < 0.01;与30~60分组比较#P < 0.05,##P < 0.01 表 2 不同冠状动脉Gensini评分病人血清NGAL和hs-CRP水平比较(x±s)
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血清NGAL和Gensini评分、hs-CRP水平均呈正相关关系(r=0.733、0.908,P < 0.05),血清hs-CRP与Gensini评分呈正相关关系(r=0.708,P < 0.05)。
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CHD组血清NGAL的浓度(79.82±32.63)ng/mL,高于CON组(38.38±12.95)ng/mL(t=6.82,P < 0.05)。当截断值为59.02 ng/mL,血清NGAL诊断CHD的ROC曲线下面积为0.875, 95%CI 0.820~0.929, 灵敏度为74.8%,特异度为96.0%。
血清中性粒细胞明胶酶相关载脂蛋白在冠心病疾病评估及诊断中的作用
Role of serum neutrophil gelatinase-associated apolipoprotein in the assessment and diagnosis of coronary heart disease
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摘要:
目的研究血清中性粒细胞明胶酶相关载脂蛋白(NGAL)在评估冠状动脉粥样硬化病变严重程度中的作用及在冠心病诊断中的价值。 方法选取行冠脉造影检查并确诊冠心病的病人135例作为冠心病组(CHD组),以冠脉造影检查排除冠心病30例作为对照组(CON组)。CHD组病人分为稳定性心绞痛组(SAP组)、不稳定性心绞痛组(UA组)和急性心肌梗死组(AMI组),比较各组临床资料、一般生化指标及血清hs-CRP水平。分析NGAL、超敏-C反应蛋白(hs-CRP)及Gensini评分间的相关性。受试者工作曲线(ROC)分析血清NGAL在冠心病诊断中的价值。 结果SAP组、UA组和AMI组血清hs-CRP水平高于CON组(P < 0.05),且SAP组、UA组和AMI组间hs-CRP差异均有统计学意义(P < 0.05)。血清NGAL和hs-CRP水平随Gensini积分增加逐渐升高(P < 0.01);Gensini评分30分组、30~60分组和>60分组血清NGAL和hs-CRP水平差异均有统计学意义(P < 0.05~P < 0.01)。血清NGAL和Gensini评分、hs-CRP水平呈正相关关系(r=0.733、0.908,P < 0.05),血清hs-CRP与Gensini评分呈正相关关系(r=0.708,P < 0.05)。CHD组血清NGAL的浓度高于CON组(P < 0.05)。当截断值为59.02 ng/mL,血清NGAL诊断冠心病的ROC曲线下面积为0.875,95%CI 0.820~0.929,灵敏度为74.8%,特异度为96.0%。 结论血清NGAL与hs-CRP及冠状动脉粥样硬化的病变严重程度相关,可作为诊断冠心病的辅助指标。 -
关键词:
- 冠心病 /
- 中性粒细胞明胶酶相关载脂蛋白 /
- 超敏-C反应蛋白
Abstract:ObjectiveTo study the value of serum neutrophil gelatinase-associated apolipoprotein(NGAL)in assessing the severity of coronary atherosclerosis, and its diagnostic value in coronary heart disease. MethodsOne hundred and thirty-five patients with coronary heart disease(CHD)diagnosed by coronary angiography and 30 patients without coronary heart disease diagnosed by coronary angiography were divided into the coronary heart disease group(CHD group), and control group(CON group).The CHD patients were subdivided into the stable angina pectoris group(SAP group), unstable angina pectoris group(UA group)and acute myocardial infarction group(AMI group).The clinical data, general biochemical indicators and serum high sensitive C-reactive protein hs-CRP level were compared among all groups.The correlations among NGAL, hs-CRP and Gensini score in all cases were analyzed.The value of serum NGAL in the diagnosis of coronary heart disease was analyzed by receiver operating(ROC)characteristic curve. ResultsThe serum levels of hs-CRP in SAP group, UA group and AMI group were higher than that in CON group(P < 0.05), and the differences of hs-CRP level among SAP group, UA group and AMI group were statistically significant(P < 0.05).The serum levels of NGAL and hs-CRP increased gradually with the increasing of Gensini score(P < 0.01).The differences of serum levels of NGAL and hs-CRP were statistically significant among the Gensini score < 30 group, 30-60 group and >60 group(P < 0.05~P < 0.01).The serum level of NGAL was positively correlated with Gensini score and hs-CRP level(r=0.733, 0.908, P < 0.05), and the serum level of hs-CRP was positively correlated with Gensini score(r=0.708, P < 0.05).The concentration of NGAL in CHD group was higher than that in CON group(P < 0.05).When the cut-off value was 59.02 ng/mL, the area under ROC curve of serum NGAL in the diagnosis of coronary heart disease was 0.875, the 95%CI was 0.820-0.929, the sensitivity was 74.8%, and the specificity was 96.0%. ConclusionsThe serum NGAL is correlated with the hs-CRP level and severity of coronary atherosclerosis, and can be used as an auxiliary index in the diagnosis of coronary heart disease. -
表 1 一般临床资料比较(x±s)
指标 SAP(n=40) UA(n=50) AMI(n=45) CON(n=30) F P MS组内 年龄/岁 61.98±9.52 62.11±8.95 63.96±10.03 59.63±9.90 1.24 >0.05 91.480 性别(男/女) 26/14 28/22 22/23 17/13 6.48# >0.05 — BMI/(kg/m2) 25.80±3.47 25.62±3.86 25.95±3.51 25.11±3.70 50.34 >0.05 13.284 吸烟史 21(52.50) 22(44.00) 26(57.80) 13(43.30) 7.32# >0.05 — 糖尿病病史 7(17.50) 10(20.00) 12(26.70) 5(16.70) 9.82# >0.05 — 高血压病史 25(62.50) 29(58.00) 27(60.00) 16(53.30) 6.89# >0.05 — TC/(mmol/L) 3.98±0.83 3.86±1.02 4.05±1.02 3.91±0.89 0.34 >0.05 0.911 TG/(mmol/L) 1.66±0.67 1.68±0.89 1.70±0.87 1.42±0.56 0.93 >0.05 0.613 HDL-C/(mmol/L) 1.20±0.33 1.23±0.35 1.21±0.35 1.37±0.37 1.68 >0.05 0.122 LDL-C/(mmol/L) 2.49±0.53 2.51±0.62 2.54±0.60 2.21±0.46 2.41 >0.05 13.640 SCr/(mol/L) 67.26±10.87 68.55±10.21 68.63±9.84 64.08±9.82 1.49 >0.05 104.180 hs-CRP /(mg/L) 3.24±1.67Δ 5.06±2.11Δ* 8.39±3.45Δ*& 1.89±1.07 56.53 < 0.01 5.490 #示χ2值;q检验:与CON组比较ΔP < 0.05;与SAP组比较*P < 0.05;与UA组比较&P < 0.05 表 2 不同冠状动脉Gensini评分病人血清NGAL和hs-CRP水平比较(x±s)
分组 n NGAL/(ng/mL) hs-CRP/(mg/L) Gensini评分/分 < 30 41 55.49±18.47 3.03±1.51 30~60 56 83.52±26.61** 5.35±1.93** >60 38 100.64±36.22**# 8.95±2.99**## F — 27.09 73.73 P — < 0.01 < 0.01 MS组内 — 76.661 4.749 q检验:与30分组比较**P < 0.01;与30~60分组比较#P < 0.05,##P < 0.01 -
[1] AKBOGA MK, CANPOLAT U, SAHINARSLAN A, et al. Association of serum total bilirubin level with severity of coronary atherosclerosis is linked to systemic inflammation[J]. Atherosclerosis, 2015, 240(1): 110. doi: 10.1016/j.atherosclerosis.2015.02.051 [2] SHAH P, BAJAJ S, VIRK H, et al. Rapid progression of coronary atherosclerosis: a review[J]. Thrombosis, 2015, 2015(2): 1. [3] MACDONALD SPJ, BOSIO E, NEIL C, et al. Resistin and NGAL are associated with inflammatory response, endothelial activation and clinical outcomes in sepsis[J]. Inflamm Res, 2017, 66(7): 611. doi: 10.1007/s00011-017-1043-5 [4] RAJAPPA M, GOSWAMI B, BALASUBRAMANIAN A, et al. Interplay between inflammation and hemostasis in patients with coronary artery disease[J]. Indian J Clin Biochem, 2015, 30(3): 281. doi: 10.1007/s12291-014-0438-0 [5] ZHUANG Q, SHEN C, CHEN Y, et al. Association of high sensitive C-reactive protein with coronary heart disease: a mendelian randomization study[J]. BMC Med Genet, 2019, 20(1): 170. doi: 10.1186/s12881-019-0910-z [6] TAYEFI M, TAJFARD M, SAFFAR S, et al. Hs-CRP is strongly associated with coronary heart disease(CHD): a data mining approach using decision tree algorithm[J]. Comput Meth Prog Bio, 2017, 141(3): 105. [7] SOYLU K, NAR G, AKSAN G, et al. Serum neutrophil gelatinase-associated lipocalin levels and aortic stiffness in noncritical coronary artery disease[J]. Cardiorenal Med, 2014, 4(3/4): 147. [8] SAVIC-RADOJEVIC A, PLJESA-ERCEGOVAC M, MATIC M, et al. Novel biomarkers of heart failure[J]. Adv Clin Chem, 2016, 79(5): 93. [9] LI C, ZHANG Z, PENG Y, et al. Plasma neutrophil gelatinase-associated lipocalin levels are associated with the presence and severity of coronary heart disease[J]. PLoS One, 2019, 14(8): e0220841. doi: 10.1371/journal.pone.0220841 [10] MA CY, XU ZY, WANG SP, et al. Change of inflammatory factors in patients with acute coronary syndrome[J]. Chinese Med J, 2018, 131(12): 1444. doi: 10.4103/0366-6999.233953 [11] KARADENIZ M, DURAN M, AKYEL A, et al. High sensitive CRP level is associated with intermediate and high syntax score in patients with acute coronary syndrome[J]. Int Heart J, 2015, 56(4): 377. doi: 10.1536/ihj.14-299 [12] YAGHOUBI A, GHOJAZADEH M, ABOLHASANI S, et al. Correlation of serum levels of vitronectin, malondialdehyde and hs-CRP with disease severity in coronary artery disease[J]. J Cardiovasc Thorac Res, 2015, 7(3): 113. doi: 10.15171/jcvtr.2015.24 [13] AKCAY AB, OZLU MF, SENEN N, et al. Prognostic significance of neutrophil gelatinase-associated lipocalin in ST-segment elevation myocardial infarction[J]. J Investig Med, 2012, 60(2): 508. doi: 10.2310/JIM.0b013e31823e9d86 [14] KATAGIRI M, TAKAHASHI M, DOIK, et al. Serum neutrophil gelatinase-associated lipocalin concentration reflects severity of coronary artery disease in patients without heart failure and chronic kidney disease[J]. Heart Vessels, 2015, 31(10): 1. [15] YNDESTAD A, LANDRO L, UELAND T, et al. Increased systemic and myocardial expression of neutrophil gelatinase-associated lipocalin inclinical and experimental heart failure[J]. Eur Heart J, 2009, 30(10): 1229. doi: 10.1093/eurheartj/ehp088 [16] BIELECKA-DABROWA A, GLUBA-BRZOZKA A, MICHALSKA-KASICZAK M, et al. The multi-biomarker approach for heart failure in patients with hypertension[J]. Int J Mol Sci, 2015, 16(5): 10715. [17] 马续祥, 陈卫东, 纵晓英, 等. 血清NGAL在早期2型糖尿病肾脏疾病诊断中的作用[J]. 蚌埠医学院学报, 2018, 43(5): 595. [18] HEMDAHL AL, GABRIELSEN A, ZHU C, et al. Expression of neutrophil gelatinase-associated lipocalin in atherosclerosis and myocardial infarction[J]. Arterioscler Thromb Vasc Biol, 2006, 26(1): 136. doi: 10.1161/01.ATV.0000193567.88685.f4