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冠心病(coronary heart disease,CHD)是指冠状动脉粥样硬化使血管腔狭窄或阻塞,和/或因冠状动脉功能性改变(痉挛)导致心肌缺血缺氧或坏死而引起的心脏病。糖尿病(diabetes mellitus,DM)是目前已知的心血管疾病的主要危险因素,尤其是CHD的“等危症”,持续存在的高血糖状态可通过血管内皮功能失调、一氧化氮合成及生物利用度降低、血管平滑肌细胞功能障碍、血小板功能紊乱、血管炎症反应增强等机制对动脉粥样硬化起到“帮凶”作用[1-2]。此外,冠状动脉硬化进展期易发生冠状动脉钙化(coronary artery calcification,CAC),主要为斑块进展到一定程度,平滑肌细胞及泡沫细胞发生矿化使得钙盐在斑块中沉积而形成。CAC是CHD的重要影像特征,与粥样硬化严重程度呈明显相关关系[3]。DM与CAC亦密切相关,临床常用CT获得冠状动脉钙化积分(coronary artery calcium score,CACS)评估CAC的严重程度,是预测心肌梗死、冠心病和全因死亡的重要指标[4]。内皮抑素(endostatin, ES)是体内产生的一种强效血管生成抑制剂,是血管壁弹力纤维的重要组成成分。其可抑制内皮细胞迁移,诱导内皮细胞凋亡[5],在内皮细胞粘附中发挥重要作用[6]。研究显示,糖尿病[7]、运动[8]、炎症、肥胖均可影响ES水平,血清ES水平的改变与脑血管疾病[9]、高血压靶器官损伤[10]及老年人心血管死亡[11]均有关。因此,本研究探讨ES与CHD合并2型糖尿病(type 2 diabetes mellitus,T2DM)病人冠状动脉钙化的关系。现作报道。
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2组病人年龄、性别、BMI、病史、血压、冠脉阻塞血管数及用药情况差异均无统计学意义(P>0.05),Crea、TC、TG、HDL-C、LDL-C、LVEF差异亦均无统计学意义(P>0.05),观察组FBG、HbA1c、HOMA-IR及hs-CRP均高于对照组(P < 0.05~P < 0.01)(见表 1)。
分组 n 年龄/岁 男 女 高血压 高血脂 吸烟史 BMI/(kg/m2) SBP/mmHg DBP/mmHg FBG/(mmol/L) HbA1c/% HOMA-IR hs-CRP/(mg/L) 对照组 55 58.67±10.05 34 21 29(52.7) 34(61.8) 26(47.3) 23.71±2.73 125.38±14.93 81.64±11.51 5.06±0.64 5.30±0.47 2.76±0.78 4.43±0.84 观察组 60 57.98±9.04 36 24 29(48.3) 35(58.3) 27(45.0) 23.91±3.10 128.87±16.53 85.57±8.84 9.37±2.74 8.70±2.03 3.13±0.78 7.79±1.04 t — 0.42* 0.04* 0.22* 0.15* 0.06* 0.36 1.18 1.78 8.68 8.42 2.45 9.24 P — >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 <0.01 <0.01 <0.05 <0.01 分组 n Crea/(μmol/L) TC/(mmol/L) TG/(mmol/L) HDL-C/(mmol/L) LDL-C/(mmol/L) LVEF/% 对照组 55 75.80±17.30 4.64±0.80 2.68±0.84 1.09±0.15 3.04±0.30 53.05±6.91 观察组 60 74.45±19.44 4.70±0.88 2.84±0.93 1.06±0.17 3.07±0.33 52.58±7.28 t — 0.43 0.43 0.96 1.26 P — <0.05 <0.01 >0.05 >0.05 分组 n 冠脉阻塞涉及血管数 用药情况 单支病变 双支病变 三支病变 血管紧张素转换酶抑制剂/血管紧张素受体Ⅱ拮抗剂 血小板聚集 他汀类药物 对照组 55 6(10.9) 3(5.5) 8(14.5) 49 (89.1) 48 (87.3) 38 (69.1) 观察组 60 9(15.0) 8(13.3) 12(20) 52 (86.7) 53 (88.3) 43 (71.7) t — 0.59 0.34 0.58# 0.16* 0.03* 0.09* P — >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 *示χ2值;#示uc值 表 1 2组病人一般资料比较(x±s)
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对照组血清ES水平为(50.49±11.49)ng/mL,观察组血清ES水平为(85.61±17.41)ng/mL,2组差异有统计学意义(t=8.18, P < 0.01)。根据冠状动脉是否阻塞分布,对照组病人中0支、单支、双支及三支病变的血清ES水平差异无统计学意义(P>0.05),观察组病人0支、单支、双支及三支病变的血清ES水平间差异有统计学意义(P < 0.01)(见表 2)。
分组 n 总CHD 0支 单支 双支 三支 Hc P 对照组 55 49.69(43.09, 58.93) 49.69(40.22, 59.11) 51.03(45.99, 53.11) 49.66(43.26, 56.07) 57.72(44.08, 75.61) 2.34 >0.05 观察组 60 81.34(74.41, 94.12) 76.69(69.09, 84.33) 87.03(72.35, 96.64) 87.74(76.51, 106.05) 109.69(77.39, 123.41) 14.85 <0.01 Hc — 8.19 — — P — <0.01 — — 表 2 2组病人血清ES水平比较
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对照组病人CACS(314.87±121.97)分,观察组病人CACS为(473.63±214.38)分,2组差异具有统计学意义(t=3.80,P < 0.01)。根据CACS等级分布,观察组病人各级血清ES水平均高于对照组(P < 0.05~P < 0.01)(见表 3)。
CACS/分 血清ES/(ng/mL) uc P 对照组(n=55) 观察组(n=60) 0 43.26(34.21, 65.30) 69.78(63.59, 81.73) 2.50 <0.05 1~100 50.28(37.38, 58.92) 72.31(65.27, 85.69) 4.17 <0.01 101~400 49.69(43.45, 59.64) 92.82(77.93, 115.58) 5.26 <0.01 >400 53.59(47.37, 59.35) 85.52(76.04, 96.35) 3.87 <0.01 表 3 2组病人血清ES与CACS的相关性
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对所有CHD病人进行CACS评分,其中0分17例,1~100分28例,101~400分23例,>400分47例;无明显钙化病人共45例(39.13%),明显钙化病人70例(60.87%)。以CACS评分为标准,绘制ES预测明显钙化的ROC曲线,确定ES预测的最佳截断值为69.18 ng/mL,预测的灵敏度为62.9%,特异度为75.6%,ROC曲线下面积为0.700,95%CI为0.604~0.796。
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血清ES水平与CACS、FBG、HbA1C及hs-CRP均呈明显正相关关系(r=0.642、0.576、0.571、0.467,P < 0.01)。以是否明显钙化(CACS>100分)为应变量,血清ES水平为自变量引入logistic回归分析,结果显示,血清ES水平为总CHD及观察组病人冠状动脉明显钙化的独立危险因素(P < 0.01)。而以冠状动脉是否阻塞为应变量,将血清ES水平为自变量引入logistic分析,结果显示,血清ES水平为总CHD及观察组病人预测冠状动脉阻塞的独立危险因素(P < 0.01)(见表 4)。
分组 是否明显钙化 是否阻塞血管 B SE Waldχ2 P OR(95%CI) B SE Waldχ2 P OR(95%CI) 总CHD 0.064 0.018 13.283 <0.01 1.066(1.030~1.104) 0.042 0.015 8.192 <0.01 1.043(1.013~1.074) 对照组 0.051 0.029 3.165 >0.05 1.052(0.995~1.113) 0.038 0.029 1.646 >0.05 1.038(0.980~1.100) 观察组 0.095 0.033 8.133 <0.01 1.100(1.030~1.174) 0.061 0.023 7.068 <0.01 1.063(1.016~1.112) 表 4 血清ES水平与冠状动脉明显钙化及阻塞的logistic回归分析
血清内皮抑素与冠心病合并2型糖尿病病人冠状动脉病变严重程度的关系研究
Relationship between serum endostatin and severity of coronary artery lesions in patients with coronary heart disease complicated with type 2 diabetes mellitus
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摘要:
目的探讨血清内皮抑素(ES)与冠心病(CHD)合并2型糖尿病(T2DM)病人冠状动脉钙化程度的关系。 方法纳入115例CHD病人,其中合并T2DM者60例(观察组),无T2DM者55例(对照组)。采用酶联免疫吸附试验测定2组病人血清ES水平,通过CT获得冠状动脉钙化积分(CACS)。 结果观察组血清ES水平明显高于对照组(P < 0.01)。观察组0支、单支、双支及三支病变病人的血清ES水平差异有统计学意义(P < 0.01),而对照组0支、单支、双支及三支病变病人血清ES水平差异无统计学意义(P>0.05)。观察组病人CACS明显高于对照组(P < 0.01)。根据CACS等级分布,观察组病人各级血清ES水平均高于对照组(P < 0.05~P < 0.01)。ROC曲线分析显示,ES预测CACS>100分的最佳截断值为69.18 ng/mL,预测灵敏度为62.9%,特异度为75.6%,AUC为0.700,95%CI为0.604~0.796(P < 0.01)。多因素logistic回归分析显示,血清ES水平为观察组病人冠状动脉明显钙化(P < 0.01)及冠状动脉阻塞(P < 0.01)的独立危险因素。 结论血清ES水平与CHD合并T2DM病人的冠状动脉病变血管支数和钙化程度密切相关,可能作为冠脉动脉粥样硬化进展的监测指标。 Abstract:ObjectiveTo assess the relationship between serum endostatin(ES) and coronary artery calcification(CAC) in coronary heart disease(CHD) complicated with type 2 diabetes mellitus(T2DM) patients. MethodsAmong 115 patients with CHD, 60 cases complicated with T2DM and 55 cases complicated without T2DM were divided into the observation group and control group, respectively.The serum ES levels in two groups were detected using enzyme-linked immunosorbent assay, and the coronary artery calcium score(CACS) scores were obtained using CT. ResultsThe serum ES level in observation group was significantly higher than that in control group(P < 0.01).The differences of the serum ES levels among the patients with 0, single, double and triple branches lesions in observation group were statistically significant(P < 0.01), while the differences of those in control group were not statistically significant(P>0.05).The CACS in observation group was significantly higher than that in control group(P < 0.01).According to the CACS distribution, the serum ES levels in observation group were higher than that in control group(P < 0.05 to P < 0.01).The optimal cutoff value of ES for CACS >100 points was 69.18 ng/mL, and the sensitivity, specificity, AUC and 95%CI were 62.9%, 75.6%, 0.700 and 0.604 to 0.796, respectively(P < 0.01).The results of multiple logistic regression analysis showed that the ES level was an independent risk factors of significant calcification and obstruct of coronary artery. ConclusionsThe serum ES level is closely related to the number of coronary artery lesions and the degree of calcification in patients with CHD complicated with T2DM, which may be used as a monitoring index for the progression of coronary atherosclerosis. -
Key words:
- coronary heart disease /
- type 2 diabetes mellitus /
- coronary calcification /
- endostatin
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表 1 2组病人一般资料比较(x±s)
分组 n 年龄/岁 男 女 高血压 高血脂 吸烟史 BMI/(kg/m2) SBP/mmHg DBP/mmHg FBG/(mmol/L) HbA1c/% HOMA-IR hs-CRP/(mg/L) 对照组 55 58.67±10.05 34 21 29(52.7) 34(61.8) 26(47.3) 23.71±2.73 125.38±14.93 81.64±11.51 5.06±0.64 5.30±0.47 2.76±0.78 4.43±0.84 观察组 60 57.98±9.04 36 24 29(48.3) 35(58.3) 27(45.0) 23.91±3.10 128.87±16.53 85.57±8.84 9.37±2.74 8.70±2.03 3.13±0.78 7.79±1.04 t — 0.42* 0.04* 0.22* 0.15* 0.06* 0.36 1.18 1.78 8.68 8.42 2.45 9.24 P — >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 <0.01 <0.01 <0.05 <0.01 分组 n Crea/(μmol/L) TC/(mmol/L) TG/(mmol/L) HDL-C/(mmol/L) LDL-C/(mmol/L) LVEF/% 对照组 55 75.80±17.30 4.64±0.80 2.68±0.84 1.09±0.15 3.04±0.30 53.05±6.91 观察组 60 74.45±19.44 4.70±0.88 2.84±0.93 1.06±0.17 3.07±0.33 52.58±7.28 t — 0.43 0.43 0.96 1.26 P — <0.05 <0.01 >0.05 >0.05 分组 n 冠脉阻塞涉及血管数 用药情况 单支病变 双支病变 三支病变 血管紧张素转换酶抑制剂/血管紧张素受体Ⅱ拮抗剂 血小板聚集 他汀类药物 对照组 55 6(10.9) 3(5.5) 8(14.5) 49 (89.1) 48 (87.3) 38 (69.1) 观察组 60 9(15.0) 8(13.3) 12(20) 52 (86.7) 53 (88.3) 43 (71.7) t — 0.59 0.34 0.58# 0.16* 0.03* 0.09* P — >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 *示χ2值;#示uc值 表 2 2组病人血清ES水平比较
分组 n 总CHD 0支 单支 双支 三支 Hc P 对照组 55 49.69(43.09, 58.93) 49.69(40.22, 59.11) 51.03(45.99, 53.11) 49.66(43.26, 56.07) 57.72(44.08, 75.61) 2.34 >0.05 观察组 60 81.34(74.41, 94.12) 76.69(69.09, 84.33) 87.03(72.35, 96.64) 87.74(76.51, 106.05) 109.69(77.39, 123.41) 14.85 <0.01 Hc — 8.19 — — P — <0.01 — — 表 3 2组病人血清ES与CACS的相关性
CACS/分 血清ES/(ng/mL) uc P 对照组(n=55) 观察组(n=60) 0 43.26(34.21, 65.30) 69.78(63.59, 81.73) 2.50 <0.05 1~100 50.28(37.38, 58.92) 72.31(65.27, 85.69) 4.17 <0.01 101~400 49.69(43.45, 59.64) 92.82(77.93, 115.58) 5.26 <0.01 >400 53.59(47.37, 59.35) 85.52(76.04, 96.35) 3.87 <0.01 表 4 血清ES水平与冠状动脉明显钙化及阻塞的logistic回归分析
分组 是否明显钙化 是否阻塞血管 B SE Waldχ2 P OR(95%CI) B SE Waldχ2 P OR(95%CI) 总CHD 0.064 0.018 13.283 <0.01 1.066(1.030~1.104) 0.042 0.015 8.192 <0.01 1.043(1.013~1.074) 对照组 0.051 0.029 3.165 >0.05 1.052(0.995~1.113) 0.038 0.029 1.646 >0.05 1.038(0.980~1.100) 观察组 0.095 0.033 8.133 <0.01 1.100(1.030~1.174) 0.061 0.023 7.068 <0.01 1.063(1.016~1.112) -
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