LOX-1和CX3CR1与冠状动脉狭窄性疾病关系及其预后价值的探讨

Association of LOX-1 and CX3CR1 with coronary artery stenosis disease and its outcomes

目的探讨血凝素样氧化低密度脂蛋白（OX—LDL）受体-1（LOX-1）、CX3C趋化因子受体1（CX3CR1）与冠状动脉狭窄性疾病关系及其预后价值。方法临床病例对照研究。选取天津泰达国际心血管病医院心内科2011年5月至2013年4月收治的176例冠状动脉狭窄性疾病患者，均经冠状动脉造影（CAG）确认（冠状动脉血管狭窄达到或超过50％）。对照组为同期本院经CAG证实无冠状动脉病变的非冠心病的患者，均排除心脏疾病，肝、肾功能不全，脑部疾病，血液系统疾病以及其他导致动脉粥样硬化及栓塞类疾病。记录两组的-般资料及实验室指标，检测LOX-1、CX3CR1、尿酸（UA）、肌酐（CREA）。对各组检测指标进行比较，对病例组中单支病变与多支病变LOX—1、CX3CR1进行比较，对LOXtCX3CR1与Gensini积分及各变量进行相关分析。对随访1．5年发生主要心脏不良事件（MACE）组与无MACE组的LOX-1、CX3CR1进行比较，同时比较不同LOX-1、CX3CR1水平患者随访1．5年的MACE。采用SPSS16．0软件进行统计分析。运用独立样本t检验，Mann—WhitneyU检验，，检验，Spearman相关分析，Logistic回归分析，Kaplan—Meier概率对数据进行分析。结果病例组与对照组比较，LOX—1分别为：3．72（1．44，8．15）μg/L与0．75（0．50，1．19）μg／L，z=11．072，P〈0．001；CX3CR1分别为：（2．82±1．85）μg／L与（2．32±0．79）μg／L，t=2．021，P〈0．05：UA分别为：（351．34±94．82）μmo1／L与（326．74±79．51）μmo]／L，t=2．094，P〈0．05；CttEA分别为：（70．86±20．94）μmo1／L与（65．55±12．96）μmo1／L，t=2．077，P〈0．05。多支病变患者CX3CR1水平（2．84±1．78）μg／L明显高于单支病变患者（2．48±1．64）μg/L，差异有统计学意义（t=2．207，P〈0．05）。LOX-1、CX3CR1与Gensini积分均无相关性（尺分别为0．032、0．079，P均〉0．05）。LOX-1与左心室射血分数（LVEF）呈负相关（R。=0．272，P〈0．01），LOX-1与左心室舒张末期内径（LVDD）呈正相关（R=0．190，P〈0．05），LOX-1与UA呈正相关（R=-0．121，P〈0．05）。MACE组与无MACE组比较，LOX-1：7．38（4．97，11．88）μg／L与3．52（1．45，7．75）μg/L，z：2．762，P〈0．01；CX3CR1：（4．02±2．90）μg/L与（2．67±1．48）μg／L，t=3．086，P〈0．01。LOX-1、TG是冠状动脉狭窄性疾病发病的危险因素。高、低LOX-1组间比较，非MACE概率分别为：87．1％（115／132）和97．7％（43／44），Log—railK检验,X2=6．957，P〈0．01。高LOX-1水平组经皮冠状动脉介入治疗（PCI）术后1．5年内发生MACE风险增大。结论LOX-1、CX3CR1可能参与了冠状动脉狭窄性疾病的过程，且高水平LOX-1可能与左心室收缩功能受损相关。LOX-1升高与冠状动脉狭窄性疾病患者PCI术后远期MACE事件发生率密切相关。

Objective To explore the association of lectin-like oxidized low-density lipoprotein （ox- LDL） receptor -1 （LOX-1） , CX3C ehemokine receptor 1 （CX3CR1） with coronary artery stenosis disease and its outcomes. Methods A ease-control study was conducted. A total of 176 eases of coronary artery stenosis which were confirmed coronary artery stenosis ≥ 50% by coronary angiography（CAG） were served as ease group from department of cardiology of TEDA International Cardiovascular Hospital of Tianjin from May 2011 to April 2013. A total of 129 patients without coronary artery lesion by CAG from this hospital in the same period were served as control group, which has no history of heart disease, liver and kidney dysfuction, brain disease, hematological disease, other disorders that could bring out atherosclerosis and thrombosis. General information and laboratory parameters, LOX-I, CX3CR1, uric acid （UA） and ereatinine （CREA） were measured in 2 groups. These parameters of each group were compared ,the levels of LOX-1 and CX3CR1 in one-vessel stenosis were compared than that in multi-vessels stenosis in case group, the correlations between LOX-1, CX3 CR1 and Gensini score and other variables were analyzed. Comparison of the levels of LOX-1 and CX3CR1 between major adverse cardiovascular events （MACEs） group and non- major adverse cardiovascular event （MACE） group was made during follow up 1.5 years. MACEs in patients with different levels of LOX-1 and CX3CR1 were compared during 1.5-year follow up. All of the data were analyzed by SPSS 16. 0 software. The independent-samples T test, Mann-Whitney U test, Chi-square test, Spearman correlation, Binary Logistic Regression and Kaplan-Meier probability were adopted for data analysis. Results Comparison between ease group and control group, LOX-1 ： 3.72 （ 1.44,8. 15 ） μg/L vs 0. 75（0. 50,1.19） μg/L,z = 11. 072,P 〈0. 001 ;CX3CR1 ： （2. 82 ± 1.85） μg/L vs （2. 32 ±0.79） μg/L, t=2.021,P〈0.05;UA：（351.34±94.82） μmol/Lvs （326.74 ±79.51） μmol/L,t=2.094,P〈0.05; CREA ： （ 70. 86 ± 20. 94 ） μmol/L vs （ 65.55 ± 12. 96 ） μmol/L, t = 2. 077, P 〈 0. 05. CX3CR1 level was significantly higher in patients with multi-vessels stenosis （ 2. 84 ± 1.78 ） μg/L than that in one-vessel stenosis（2.48 _＋ 1.64） μg/L, there was significance in difference （t = 2. 207,P 〈 0.05 ）. There were no statistieally significant correlation between LOX-1, CX3CR1 and Gensini score （R was 0. 032, 0.079 respectively, P 〉 0. 05 ）. LOX-1 was negatively related to left ventricular ejection fraction （LVEF） （R = -0. 272, P 〈 0. 01 ）, but positively related to left ventricular end-diastolic diameter （LVDD） （R = 0. 190, P 〈0. 05） , positively related to UA （ R = 00. 121, P 〈 0. 05 ）. Comparison between MACE group and non- MACE group, LOX-1 ： 7. 38 （ 4. 97 ,11. 88 ） Ixg/L vs 3.52（1.45,7.75） μg/L, z =2.762,P 〈0.01; CX3CRl：（4.02 ^-2.90） μg/L ＇vs （2.67 ＋ 1.48） μg/L,t = 3. 086,P 〈0.01. LOX-1 and TG were independent risk effects of coronary artery stenosis disease. MACEs were increased in patients with high levels of LOX-1 after PCI during following up I. 5 years （ comparison between high-LOX-1 group and low- LOX-1 group, the probability of non-MACE was 87. 1% （115/132） vs 97.7% （43/44）, Log-ranK test, X2 =6. 957, P 〈 0. 01 ）. Conclusions LOX-1 and CX3CR1 may be involved in the process of coronary artery stenosis, and a high level of LOX-1 may be associated with left ventrieular systolic dysfunction in patients with coronary artery stenosis. Elevated LOX-1 level are closely related to afterwards MACE incidence after PCI in patients with coronary artery stenosis.