阿司匹林、低密度脂蛋白胆固醇与冠脉造影正常患者冠脉血流速度的关系及作用

发布时间：2018-05-19 10:17

本文选题：阿司匹林 + 冠状动脉血流　；参考：《浙江大学》2015年博士论文

【摘要】：第一部分阿司匹林对冠脉造影正常患者冠脉血流速度的影响及作用背景：血管内皮功能下降及血小板功能紊乱是冠状动脉慢血流现象最为主要的发病机制。阿司匹林具有抑制血小板聚集,改善血管内皮细胞功能等有益的药理作用机制,但阿司匹林对冠状动脉血流速度的影响及作用尚未阐明。因此,本研究旨在评价阿司匹林对冠状动脉造影正常人群冠状动脉血流速度的影响及作用方法：本研究共入选了563例浙江大学医学院第二附属医院冠脉造影注册研究数据库中冠脉造影正常的患者,根据造影前阿司匹林服用与否分为服用阿司匹林组与未服用阿司匹林组两组。采用TIMI帧计数(Thrombolysis in Myocardial Infarction frame counts, TFC)作为冠状动脉血流速度的评价指标；使用逐步个案配对、倾向性评分以及多元线性回归分析等多种方法校正相应的混杂因素后比较两组TFC差异,评判阿司匹林对冠脉造影正常人群冠脉血流速度的影响。结果：患者基线特征中除了年龄,高血压病,低密度脂蛋白胆固醇,凝血酶原时间以及ACEI/ARB、钙离子拮抗剂、他汀使用率具有显著差异,其他基线特征两组具有可比性。无论配对与否,平均TFC在服用阿司匹林组均低于未服用阿司匹林组(配对之前：29.61+5.12vs31.64±7.91；配对年龄后：29.28士5.20vs31.12士7.49；配对年龄与LDL-C后：29.15±5.60vs31.55±7.89；倾向性评分配对后：29.11±5.52vs31.61土8.71；所有P0.05)。亚组分析发现,服用与未服用阿司匹林两组间TFC差值,服用他汀类药物组较未服用他汀类药物组有缩小的趋势。多元线性回归分析发现,服用阿司匹林是TFC的独立影响因素,与TFC呈负相关关系(β：-2.641；95%CI：-4.059-1.223),这种关系并不会因为校正年龄、高血压、ACEI/ARB、钙离子拮抗剂、他汀使用率,低密度脂蛋白胆固醇以及凝血酶原时间而发生改变,并且在配对年龄组(β:-1.599;95％CI:-3.091-0.108)以及配对年龄与低密度脂蛋白胆固醇组(β:-2.025;95％CI:-3.938-0.112),这种关系依然存在。结论：尽管包括他汀在内的影响因素可能干预阿司匹林对冠状动脉血流速度的作用,但阿司匹林与TFC呈独立负相关关系,提示阿司匹林可以加快冠脉正常人群的冠脉血流速度,可能是治疗冠脉慢血流的选择之一。第二部分冠状动脉造影正常患者中低密度脂蛋白胆固醇与冠脉血流速度的研究中文摘要背景：冠状动脉微血管内皮受损是冠状动脉慢血流最为主要的发病机制。尽管低密度脂蛋白胆固醇(low-density lipoprotein cholesterol, LDL-C)损伤内皮细胞功能的具体作用机制复杂,但已经明确LDL-C具有损伤内皮的作用,由此LDL-C可能对冠脉血流速度产生不利的影响。然而,目前尚无LDL-C与冠脉血流速度间关系的相关研究。我们拟校正干扰LDL-C与冠脉血流速度间关系的因素后,尤其是他汀类降脂药物后,评价LDL-C与冠状动脉造影正常患者冠状动脉血流速度的相关性。方法：本研究共入选了563例浙江大学医学院第二附属医院冠状造影注册研究数据库中冠脉造影完全正常的患者作为研究对象,根据LDL-C界值2.6mmol/l将入选对象划分为低LDL-C与高LDL-C组。采用TIMI帧计数(Thrombolysis in Myocardial Infarction frame counts, TFC)作为冠状动脉血流速度的观察指标；在纳入对象整体及服用与未服用他汀类亚组中,通过统计比较、相关分析、曲线拟合等方法分析LDL-C与TFC间关系,多元回归方程校正相应的混杂因素,确定LDL-C对冠脉造影正常患者冠脉血流速度的影响。结果：临床基线特征中年龄、体重指数、甘油三脂、阿司匹林及他汀使用率两组间具有显著差异(P值0.05),其他基线特征两组间均衡可比。无论是任一单支冠脉TFC测值还是平均TFC测值,低LDL-C组中均显著低于高LDL-C组(LAD:33.39±9.14vs35.99±10.00; LCX:27.19±7.40vs28.87±7.51; RCA:28.75±8.39vs30.63±8.56; Mean:29.78±6.72vs31.83±7.36;所有P值0.05)。LDL-C与TFC间呈Person正相关关系,但当采用偏相关分析校正年龄、体重指数、甘油三脂、阿司匹林及他汀使用率等在组间不匹配变量后,LDL-C与TFC间相关系数有所下降。曲线拟合发现LDL-C与TFC间呈非完全线性直线关系而是反“S”曲线关系。他汀对LDL-C与TFC间关系有负向效应,但并不能逆转。多元线性回归分析发现,在整体纳入对象中LDL-C是平均TFC的独立影响因素,与TFC呈正相关关系(p：1.099；95%CI：0.240～-1.958),这种关系并不会因为校正年龄、体重指数、甘油三脂、阿司匹林及他汀使用率而发生改变,在未服用他汀亚组这种关系依然存在(β：1.337；95%CI：0.271-2.402),而在服用他汀亚组不再具有统计学意义的独立正相关关系(β:1.38;95%CI:-0.157～2.916)。结论：LDL-C与TFC呈非完全线性直线正相关关系,他汀可以负向降低这种相关性,但并不能逆转。提示LDL-C对冠脉血流速度有负向影响,他汀治疗可能有益于改善冠脉慢血流的血流速度,尤其是在LDL-C相对更高的患者中可能获益更大。
[Abstract]:Part 1 Effect of aspirin on coronary blood flow velocity in patients with normal coronary angiography
Background: the decline of vascular endothelial function and platelet dysfunction are the most important pathogenesis of slow flow of coronary artery. Aspirin has beneficial pharmacological mechanisms to inhibit platelet aggregation and improve vascular endothelial cell function, but the effect and effect of aspirin on the velocity of coronary artery blood flow has not been elucidated. The aim of this study was to evaluate the effect of aspirin on coronary blood flow velocity in healthy subjects with normal coronary angiography.
Methods: 563 patients with normal coronary angiography in the database of coronary angiography of the Second Affiliated Hospital of Zhejiang University medical college were enrolled in this study. The patients were divided into two groups, taking aspirin group and non aspirin group according to pre contrast aspirin, using TIMI frame count (Thrombolysis in Myocardial Infarction FR). Ame counts, TFC) was used as an evaluation index for the velocity of coronary artery blood flow, and the effect of aspirin on coronary flow velocity in normal coronary angiography group was evaluated by using a variety of methods such as progressive case pairing, tendency score and multiple linear regression analysis to correct the corresponding confounding factors and compare the difference between the two groups of TFC.
Results: in the baseline features of the patients, except age, hypertension, low density lipoprotein cholesterol, prothrombin time, ACEI/ARB, calcium antagonists, and statins, there were significant differences in the use of other baseline features in two groups. The average TFC in the aspirin group was lower than that in the non aspirin group. Before: 29.61+5.12vs31.64 + 7.91; paired age: 29.28 MW 5.20vs31.12 7.49; paired age and LDL-C: 29.15 + 5.60vs31.55 + 7.89, 29.11 + 5.52vs31.61 soil 8.71, all P0.05). The subgroup analysis found that the difference between the 29.28 groups of aspirin and aspirin, which was not taken with aspirin, was taken by the statin group. Multiple linear regression analysis found that taking aspirin was an independent factor in TFC and was negatively correlated with TFC (beta: -2.641; 95%CI:-4.059-1.223), and this relationship was not due to correction of age, hypertension, ACEI/ ARB, calcium antagonists, statins use, low density lipoprotein Cholesterol and prothrombin time changed, and the relationship remained in the paired age group (beta: -1.599; 95%CI:-3.091-0.108) and the paired age and low density lipoprotein cholesterol group (beta: -2.025; 95%CI:-3.938-0.112).
Conclusion: Although the influence factors including statins may interfere with the effect of aspirin on the velocity of coronary artery blood flow, aspirin and TFC are negatively correlated, suggesting that aspirin can accelerate coronary flow velocity in normal coronary arteries and may be one of the options for the treatment of slow coronary blood flow.
The second part is the study of low density lipoprotein cholesterol and coronary blood flow velocity in patients with normal coronary angiography.
Background: coronary microvascular endothelial damage is the most important pathogenesis of slow coronary artery blood flow. Although the specific mechanism of low-density lipoprotein cholesterol (LDL-C) damage endothelial cell function is complex, it is clear that LDL-C has the effect of damaging the endothelium, thus the LDL-C may be on the coronary artery. However, there is no related study of the relationship between the LDL-C and the coronary flow velocity. We should correct the correlation between the LDL-C and the coronary flow velocity, especially after the statins, and evaluate the correlation between the LDL-C and the coronary flow velocity in the patients with normal coronary artery angiography.
Methods: 563 patients with completely normal coronary angiography in the Second Affiliated Hospital of Zhejiang University medical college were selected. The subjects were divided into low LDL-C and high LDL-C group according to the LDL-C boundary value 2.6mmol/l. The Thrombolysis in Myocardial Infarction frame (Thrombolysis in Myocardial Infarction frame) was used. Counts, TFC) as the observation index of the velocity of coronary artery blood flow; the relationship between LDL-C and TFC was analyzed by statistical comparison, correlation analysis and curve fitting in the whole and the non taking statins subgroups, and the multiple regression equation was used to correct the corresponding melange, and the coronary blood flow of the patients with normal coronary angiography was determined by LDL-C. The influence of speed.
Results: the age, body mass index, glycerin three fat, aspirin and statin use rate were significantly different among the two groups (P value 0.05), and the other baseline characteristics were comparable in two groups. No matter any single coronary TFC or TFC, the low LDL-C group was significantly lower than that of the high LDL-C group (LAD:33.39 + 9.14vs35.99 + 10) LCX:27.19 + 7.40vs28.87 + 7.51; RCA:28.75 + 8.39vs30.63 + 8.56; Mean:29.78 + 6.72vs31.83 + 7.36; all P value 0.05).LDL-C and TFC showed a positive correlation between Person, but when using partial correlation analysis to correct age, body mass index, glycerin three fat, aspirin and statins, the relationship between LDL-C and TFC The number of LDL-C and TFC showed a non complete linear relationship between the curve and the inverse "S" curve. Statins had a negative effect on the relationship between LDL-C and TFC, but it could not be reversed. The multivariate linear regression analysis found that LDL-C was the independent factor of the average TFC in the overall inclusion object, and there was a positive correlation with TFC (p:1.099). 95%CI:0.240 to -1.958), this relationship did not change due to the correction of age, body mass index, glycerin three fat, aspirin and statin use, which still existed in the non - Taking group (beta: 1.337; 95%CI:0.271-2.402) and no statistically significant independent positive correlation in the statin subgroup. Beta: 1.38; 95%CI:-0.157 to 2.916).
Conclusion: LDL-C and TFC have a non complete linear linear correlation. Statins can negatively reduce this correlation, but it can not be reversed. It suggests that LDL-C has a negative effect on the velocity of coronary blood flow. Statin therapy may be beneficial to improve the blood flow velocity of slow coronary blood flow, especially in patients with higher LDL-C.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R541.4

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