本文選題：阿司匹林 + 冠狀動脈血流��； 參考：《浙江大學(xué)》2015年博士論文

【摘要】：第一部分阿司匹林對冠脈造影正�；颊吖诿}血流速度的影響及作用 背景：血管內(nèi)皮功能下降及血小板功能紊亂是冠狀動脈慢血流現(xiàn)象最為主要的發(fā)病機(jī)制。阿司匹林具有抑制血小板聚集,改善血管內(nèi)皮細(xì)胞功能等有益的藥理作用機(jī)制,但阿司匹林對冠狀動脈血流速度的影響及作用尚未闡明。因此,本研究旨在評價阿司匹林對冠狀動脈造影正常人群冠狀動脈血流速度的影響及作用 方法：本研究共入選了563例浙江大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院冠脈造影注冊研究數(shù)據(jù)庫中冠脈造影正常的患者,根據(jù)造影前阿司匹林服用與否分為服用阿司匹林組與未服用阿司匹林組兩組。采用TIMI幀計(jì)數(shù)(Thrombolysis in Myocardial Infarction frame counts, TFC)作為冠狀動脈血流速度的評價指標(biāo)；使用逐步個案配對、傾向性評分以及多元線性回歸分析等多種方法校正相應(yīng)的混雜因素后比較兩組TFC差異,評判阿司匹林對冠脈造影正常人群冠脈血流速度的影響。 結(jié)果：患者基線特征中除了年齡,高血壓病,低密度脂蛋白膽固醇,凝血酶原時間以及ACEI/ARB、鈣離子拮抗劑、他汀使用率具有顯著差異,其他基線特征兩組具有可比性。無論配對與否,平均TFC在服用阿司匹林組均低于未服用阿司匹林組(配對之前：29.61+5.12vs31.64±7.91；配對年齡后：29.28士5.20vs31.12士7.49；配對年齡與LDL-C后：29.15±5.60vs31.55±7.89；傾向性評分配對后：29.11±5.52vs31.61土8.71；所有P0.05)。亞組分析發(fā)現(xiàn),服用與未服用阿司匹林兩組間TFC差值,服用他汀類藥物組較未服用他汀類藥物組有縮小的趨勢。多元線性回歸分析發(fā)現(xiàn),服用阿司匹林是TFC的獨(dú)立影響因素,與TFC呈負(fù)相關(guān)關(guān)系(β：-2.641；95%CI：-4.059-1.223),這種關(guān)系并不會因?yàn)樾Ｕ挲g、高血壓、ACEI/ARB、鈣離子拮抗劑、他汀使用率,低密度脂蛋白膽固醇以及凝血酶原時間而發(fā)生改變,并且在配對年齡組(β:-1.599;95％CI:-3.091-0.108)以及配對年齡與低密度脂蛋白膽固醇組(β:-2.025;95％CI:-3.938-0.112),這種關(guān)系依然存在。 結(jié)論：盡管包括他汀在內(nèi)的影響因素可能干預(yù)阿司匹林對冠狀動脈血流速度的作用,但阿司匹林與TFC呈獨(dú)立負(fù)相關(guān)關(guān)系,提示阿司匹林可以加快冠脈正常人群的冠脈血流速度,可能是治療冠脈慢血流的選擇之一。 第二部分冠狀動脈造影正�；颊咧械兔芏戎鞍啄懝檀寂c冠脈血流速度的研究中文摘要 背景：冠狀動脈微血管內(nèi)皮受損是冠狀動脈慢血流最為主要的發(fā)病機(jī)制。盡管低密度脂蛋白膽固醇(low-density lipoprotein cholesterol, LDL-C)損傷內(nèi)皮細(xì)胞功能的具體作用機(jī)制復(fù)雜,但已經(jīng)明確LDL-C具有損傷內(nèi)皮的作用,由此LDL-C可能對冠脈血流速度產(chǎn)生不利的影響。然而,目前尚無LDL-C與冠脈血流速度間關(guān)系的相關(guān)研究。我們擬校正干擾LDL-C與冠脈血流速度間關(guān)系的因素后,尤其是他汀類降脂藥物后,評價LDL-C與冠狀動脈造影正�；颊吖跔顒用}血流速度的相關(guān)性。 方法：本研究共入選了563例浙江大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院冠狀造影注冊研究數(shù)據(jù)庫中冠脈造影完全正常的患者作為研究對象,根據(jù)LDL-C界值2.6mmol/l將入選對象劃分為低LDL-C與高LDL-C組。采用TIMI幀計(jì)數(shù)(Thrombolysis in Myocardial Infarction frame counts, TFC)作為冠狀動脈血流速度的觀察指標(biāo)；在納入對象整體及服用與未服用他汀類亞組中,通過統(tǒng)計(jì)比較、相關(guān)分析、曲線擬合等方法分析LDL-C與TFC間關(guān)系,多元回歸方程校正相應(yīng)的混雜因素,確定LDL-C對冠脈造影正�；颊吖诿}血流速度的影響。 結(jié)果：臨床基線特征中年齡、體重指數(shù)、甘油三脂、阿司匹林及他汀使用率兩組間具有顯著差異(P值0.05),其他基線特征兩組間均衡可比。無論是任一單支冠脈TFC測值還是平均TFC測值,低LDL-C組中均顯著低于高LDL-C組(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與TFC間呈Person正相關(guān)關(guān)系,但當(dāng)采用偏相關(guān)分析校正年齡、體重指數(shù)、甘油三脂、阿司匹林及他汀使用率等在組間不匹配變量后,LDL-C與TFC間相關(guān)系數(shù)有所下降。曲線擬合發(fā)現(xiàn)LDL-C與TFC間呈非完全線性直線關(guān)系而是反“S”曲線關(guān)系。他汀對LDL-C與TFC間關(guān)系有負(fù)向效應(yīng),但并不能逆轉(zhuǎn)。多元線性回歸分析發(fā)現(xiàn),在整體納入對象中LDL-C是平均TFC的獨(dú)立影響因素,與TFC呈正相關(guān)關(guān)系(p：1.099；95%CI：0.240～-1.958),這種關(guān)系并不會因?yàn)樾Ｕ挲g、體重指數(shù)、甘油三脂、阿司匹林及他汀使用率而發(fā)生改變,在未服用他汀亞組這種關(guān)系依然存在(β：1.337；95%CI：0.271-2.402),而在服用他汀亞組不再具有統(tǒng)計(jì)學(xué)意義的獨(dú)立正相關(guān)關(guān)系(β:1.38;95%CI:-0.157～2.916)。 結(jié)論：LDL-C與TFC呈非完全線性直線正相關(guān)關(guān)系,他汀可以負(fù)向降低這種相關(guān)性,但并不能逆轉(zhuǎn)。提示LDL-C對冠脈血流速度有負(fù)向影響,他汀治療可能有益于改善冠脈慢血流的血流速度,尤其是在LDL-C相對更高的患者中可能獲益更大。
[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.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2015
【分類號】：R541.4

【共引文獻(xiàn)】

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