冠状动脉粥样硬化斑块消退研究进展

冠状动脉粥样硬化的发生与低密度脂蛋白及炎症反应、内皮功能减退等有关。近年来多项临床试验证实早期强化应用他汀类药物可以通过降低低密度脂蛋白、抗炎、改善内皮功能等途径改善急性冠脉综合征患者的预后。其中他汀类药物发挥的抗炎症反应、改善内皮功能等多效性作用日益受到重视。而应用血管内超声的研究发现强化他汀类治疗能够显著遏制甚至消退冠状动脉粥样斑块。     

多排计算机体层成像在冠状动脉检查中的应用进展

多排计算机体层成像在临床应用范围越来越广泛,除了用于因胸痛怀疑冠状动脉粥样硬化性心脏病患者的筛查、冠状动脉支架术后、冠状动脉搭桥术后及心脏移植术后等经典的应用领域,近年来采用冠状动脉计算机体层成像血管造影评价冠状动脉病变斑块特性,以及与单光子发射断层显像术结合评价病变危险分层等一些新领域。     

冠状动脉计算机体层成像血管造影在冠状动脉疾病的临床应用

冠状动脉计算机体层成像血管造影是诊断冠状动脉疾病的一个优秀无创评价测试工具。虽然冠状动脉造影是冠状动脉粥样硬化性心脏病的金标准,但有充分的证据来支持冠状动脉计算机体层成像血管造影的性价比,而且它的临床应用范围广。本次综述的目的是对冠状动脉计算机体层成像血管造影在冠状动脉疾病临床应用中的诊断准确性和预测价值的概述;对冠状动脉计算机体层成像血管造影的新兴领域,包括双源计算机体层成像、多排螺旋计算机体层成像进行讨论,以及冠状动脉计算机体层成像血管造影的局限性和突出展示其未来的发展方向。     

ASCVD患者逆转斑块他汀治疗专家共识

他汀降低低密度脂蛋白胆固醇(LDL-C)可以显著减少动脉粥样硬化性心血管疾病(ASCVD)事件。分析6项他汀治疗冠心病患者血管内超声(IVUS)评价冠状动脉(冠脉)斑块体积变化的临床试验:他汀治疗后LDL-C显著降低到1.4~2.1mmol/L(53~79 mg/dl)冠脉斑块体积保持稳定,若同时升高载脂蛋白A1(ApoA1)9%(达到1.35~1.5g/L)和高密度脂蛋白胆固醇(HDL-C)8%(达到1.2~1.4mmol/L)(45~55mg/dl),可以观察到冠脉斑块的逆转。这可以作为他汀类药物治疗减少胆固醇流入斑块和增加胆固醇流出斑块的目标值,对ASCVD防治具有重要指导意义。     

他汀类药物的作用多向性效应及其临床应用

他汀类药物能显著降低总胆固醇、低密度脂蛋白胆固醇和升高高密度脂蛋白胆固醇,在急性冠状动脉综合征的治疗中发挥着稳定粥样硬化斑块、降低急性冠状动脉综合征患者急性期病死率的作用。近年来的临床和实验研究证实,他汀类具有作用多向性效应,可以防治20余种疾病,其中多数与调脂作用无关。     

冠状动脉易损斑块的识别和防治进展

易损斑块的早期识别对于治疗及预后具有重要的价值,现有的影像学诊断方法包括靶向分子荧光成像、冠状动脉(冠脉)计算机断层摄影术(CT)造影、磁共振、血管内超声(包括虚拟组织学成像)、光学相干断层成像及血管内窥镜等,而血清学检查还没有一个很好的指标提示易损斑块。易损斑块的治疗主要是他汀类药物治疗,强化降脂治疗可以起到逆转斑块的作用,而其它稳定易损斑块的治疗方法还需要进一步研究证实。     

冠状动脉斑块计算流体力学研究进展

为了探究冠状动脉斑块发生发展的具体影响因素,研究人员将目光投向了计算流体力学。病理状态下管壁切应力营造促进斑块发生、进展的环境,诱导斑块趋于易损,甚至破裂,增加远期不良心血管事件风险。以往研究多采用血管内超声或光学相干断层成像的侵入性成像方法对切应力进行计算评估。近年来,冠状动脉CT血管造影(CCTA)技术在图像质量上的进步则使基于CT计算管壁切应力与斑块轴向应力成为可能。基于无创影像学斑块检测技术的发展以及多种血管内血流应力的联合评价方式,都将进一步提高CCTA对于斑块转归与临床结局的预测价值。     

冠状动脉斑块计算流体力学研究进展

为了探究冠状动脉斑块发生发展的具体影响因素,研究人员将目光投向了计算流体力学。病理状态下管壁切应力营造促进斑块发生、进展的环境,诱导斑块趋于易损,甚至破裂,增加远期不良心血管事件风险。以往研究多采用血管内超声或光学相干断层成像的侵入性成像方法对切应力进行计算评估。近年来,冠状动脉CT血管造影(CCTA)技术在图像质量上的进步则使基于CT计算管壁切应力与斑块轴向应力成为可能。基于无创影像学斑块检测技术的发展以及多种血管内血流应力的联合评价方式,都将进一步提高CCTA对于斑块转归与临床结局的预测价值。     

降脂治疗逆转冠状动脉粥样硬化

目的通过血管内超声了解氟伐他汀和阿托伐他汀降脂治疗对冠状动脉粥样斑块退缩及其成分的影响。方法经冠状动脉造影(CAG)证实至少有一支主要冠状动脉存在20%～50%狭窄(目测)的70名患者,利用Excel表格按1∶1比例随机分为阿托伐他汀(20mg/d,35例)组和氟伐他汀(80mg/d,35例)组。通过血管内超声灰阶成像(C-IVUS)和虚拟组织学成像(VH-IVUS)脱机分析软件分别测量降脂治疗12个月前后冠状动脉粥样硬化斑块、血管、管腔体积及成分的变化。结果 56例(80%)患者完成全部随访过程,阿托伐他汀组及氟伐他汀组各28例。经过12个月的降脂治疗,阿托伐他汀组低密度脂蛋白胆固醇(LDL-C)由(3.43±0.65)mmol/L降至(2.11±0.41)mmol/L(P0.001),下降(36.9±14.7)%;氟伐他汀组LDL-C由(3.36±0.69)mmol/L降至(2.75±0.85)mmol/L(P=0.002),下降(16.1±30.3)%,两组间LDL-C下降幅度差异有统计学意义(P=0.002)。阿托伐他汀组斑块体积由(351.0±152.2)mm3减至(314.4±112.9)mm3(P=0.001),下降(8.5±12.9)%;氟伐他汀组斑块体积由(294.6±87.6)mm3增至(308.4±91.5)mm3(P=0.001),增加(4.7±9.2)%,组间斑块体积变化的百分比差异有统计学意义(P0.001)。阿托伐他汀组斑块体积下降百分比与LDL-C下降百分比呈正相关(r=0.586,P=0.001)。坏死核心(NC)比例阿托伐他汀组由(13.8±3.9)%下降至(10.8±6.9)%(P=0.023),而氟伐他汀组由(12.7±3.4)%增至(15.0±7.8)%(P=0.111),组间NC比例变化差异有统计学意义(P=0.006)。结论阿托伐他汀20mg降脂治疗可显著缩小冠状动脉粥样斑块体积,并可减少斑块坏死核心比例,斑块体积下降百分比与LDL-C下降百分比呈正相关,而氟伐他汀80mg不能阻止冠状动脉粥样硬化进展。     

高强度他汀类治疗对冠状动脉粥样硬化的消退作用

背景与目的血管内超声试验证明应用他汀类药物能减慢或延迟动脉粥样硬化的发展,但是,使用粥样瘤体积百分比法还没有找到确凿证据证明疾病进展减慢或消退,后者比血管内超声试验更准确。此项研究旨在评定高强度他汀类药物治疗是否如血管内超声成像显示的那样能延缓冠状动脉粥样硬     

冠状动脉斑块消退的调脂治疗策略

4项他汀类药物治疗冠心病患者,以血管内超声评价冠状动脉(冠脉)斑块变化的临床试验(RE-VERSAL、ASTEROID、COSMOS和SATURN)结果一致显示,他汀治疗显著降低LDL-C,同时升高Apo-A1和HDL-C,才能观察到冠脉粥样硬化斑块的消退。适度调脂指通过他汀类药物治疗,达到减少胆固醇流入斑块的目标值:降低LDL-C>45%(达到1.81～2.46mmol/L),同时达到增加胆固醇流出斑块的目标值:升高Apo-A1>9%(达到3.50～3.89mmol/L)和HDL-C>8%(达到1.17～1.42mmol/L),实现冠脉斑块的消退。     

多层螺旋CT评估血脂在冠状动脉粥样斑块变化中的作用

目的:以多层螺旋CT观察血脂,尤其是TG与冠心病患者冠状动脉斑块的变化情况的关系。方法:选择多层螺旋CT及血脂化验检查并复查的患者,观察冠状动脉斑块CT图像的变化并分析与血脂尤其是TG的关系。结果:本组患者中,冠状动脉斑块面积减少者TG水平和LDL-C水平均明显低于斑块面积增加者[1.42(0.92,1.88)vs.1.63(1.26,2.75)mmol/L,P=0.0443;(2.04±0.49)vs.(2.45±0.7)mmol/L,P=0.0091]。逐步回归分析斑块面积增加与TG、LDL-C水平正相关(B=-1.7193,P=0.0014;B=-2.4409,P=0.0352)。结论:TG与LDL-C均与冠状动脉斑块进展有关,LDL-C影响较TG更为明显,但是在当前强调强化控制LDL-C后,TG逐渐成为心血管病剩余风险的重要原因,在临床工作中应该得到重视。     

他汀类非调脂作用在稳定急性冠脉综合征病变斑块的机制

急性冠脉综合征主要由斑块破裂、血栓形成所致。他汀类属羟甲基戊二酸辅酶A还原酶抑制剂,除调脂作用之外尚有非调脂作用,即多向性效应。它包括抗炎作用,逆转内皮功能失调,降低动脉粥样硬化斑块的脆性,抗血小板凝聚和减少血栓形成等效应,在稳定急性冠脉综合征病变斑块方面发挥着重要作用。     

他汀类药物对老年冠心病患者冠状动脉粥样硬化斑块的影响

目的评价他汀类药物对轻度胆固醇升高的老年冠心病患者冠状动脉粥样硬化斑块的影响。方法将LDL-C为2.6~3.6 mmol/L的57例冠心病患者分为>65岁组(Ⅰ组,30例)和≤65岁组(Ⅱ组,27例)。每例患者选取一处狭窄50%~70%的斑块为靶病变。分别于治疗前和治疗后12个月行冠状动脉造影(CAG)和靶病变的血管内超声(IVUS),比较血管、管腔和斑块体积,并观察斑块钙化情况。结果Ⅰ组和Ⅱ组患者12个月后LDL-C平均降至2.39 mmol/L和2.23 mmol/L,较基线下降32.1%和33.2%。两组患者血管、管腔和斑块体积在治疗前无显著差异。治疗12个月后,Ⅰ组血管、管腔和斑块体积无显著变化,Ⅱ组血管体积无变化;管腔体积由(68.8±14.4)mm3增加至(83.6±22.5)mm3(P<0.05),斑块体积由(80.1±18.6)mm3缩小至(69.9±21.7)mm3(P<0.05)。钙化斑块比例Ⅰ组明显高于Ⅱ组(56.7%vs25.9%,P<0.05)。结论他汀类药物可以阻止LDL-C轻度升高的老年冠心病患者冠状动脉斑块的进展。     

Effect of early statin therapy after acute coronary syndromes: a concise review of the recent data

HMG Co-A reductase inhibitors(statins) have been shown, in three large randomized trials, to decrease adverse cardiac events in patients with clinically evident coronary artery disease. All of these trials have excluded patients with an acute coronary syndrome within the three months prior to enrollment. Statin therapy is thought to stabilize coronary plaque and decrease the risk of plaque rupture. Statins have been shown to quickly reduce levels of LDL-C in addition to altering systemic inflammatory responses, improving endothelial function, and reducing platelet aggregation and activation. These mechanisms are potentially beneficial in the setting of acute coronary syndromes, a time of profound plaque instability. There is a growing body of evidence supporting the early initiation of statin therapy in the setting of acute coronary syndromes. This paper reviews the available data from randomized-controlled trials and observational studies evaluating the effect of early statin initiation during, or soon following, an acute coronary syndrome.     

Stabilization of carotid atheroma assessed by quantitative ultrasound analysis in nonhypercholesterolemic patients with coronary artery disease.

OBJECTIVES: This study examined whether intensive cholesterol-lowering therapy with statins in nonhypercholesterolemic patients is effective in improving echolucency of vulnerable plaques assessed by ultrasound with integrated backscatter (IBS) analysis. BACKGROUND: Atherosclerotic plaque stabilization is a promising clinical strategy to prevent cardiovascular events in patients with coronary artery disease (CAD). There is a correlation between coronary and carotid plaque instability, and echolucent plaques are recognized as vulnerable plaques. METHODS: Consecutive nonhypercholesterolemic patients with CAD were randomly assigned Adult Treatment Panel-III diet therapy (diet group; n = 30) or pravastatin (statin group; n = 30). Echolucent carotid plaques were monitored by measuring intima-media thickness (IMT) and echogenicity by IBS for six months. RESULTS: Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein were significantly decreased in the statin group (from 197 +/- 15 mg/dl to 170 +/- 18 mg/dl [p < 0.001]; from 131 +/- 14 mg/dl to 99 +/- 14 mg/dl [p < 0.001]; and from 0.11 [0.04 to 0.22] mg/dl to 0.06 [0.04 to 0.11] mg/dl [p < 0.05]; respectively), whereas only total cholesterol was moderately reduced (from 193 +/- 24 mg/dl to 185 +/- 22 mg/dl [p < 0.05]) and LDL-C and triglycerides insignificantly reduced in the diet group. Significant increases of echogenicity of carotid plaques were noted in the statin group but not in the diet group (from -18.5 +/- 4.1 dB to -15.9 +/- 3.7 dB [p < 0.001] and from -18.2 +/- 4.0 dB to -18.9 +/- 3.5 dB [p = 0.13]; respectively) without significant regression of plaque-IMT values in both groups. CONCLUSIONS: Statin therapy is rapidly effective in increasing echogenicity of vulnerable plaques without regression of plaque size in nonhypercholesterolemic patients with CAD. Quantitative assessment of carotid plaque quality by ultrasound with IBS is clinically useful for monitoring atherosclerotic lesions by evaluating vulnerability of atheroma.     

Comparison of the effects of pitavastatin versus pravastatin on coronary artery plaque phenotype assessed by tissue characterization using serial virtual histology intravascular ultrasound

Thin-cap fibroatheroma (TCFA) is the most common type of vulnerable plaque and is the precursor of plaque rupture. However, rupture of a TCFA is not the only mechanism underlying thrombus formation or acute coronary syndrome. Although statin therapy changes the composition of coronary artery plaques, the effects of statins, particularly different types of statins, on plaque phenotype have not been fully examined. This study compared the effects of pitavastatin versus pravastatin on coronary artery plaque phenotype assessed by virtual histology (VH) intravascular ultrasound (IVUS) in patients with angina pectoris (AP). Coronary atherosclerosis in nonculprit lesions was evaluated using VH-IVUS at baseline and 8 months after statin therapy; analyzable IVUS data were obtained from 83 patients with stable AP (39 patients treated with pitavastatin and 44 with pravastatin) and 36 patients with unstable AP (19 patients treated with pitavastatin and 17 with pravastatin). Pitavastatin had a strong effect on reducing pathologic intimal thickening (PIT), especially in patients with unstable AP, but had no impact on VH-TCFA or fibroatheroma (FA). By contrast, pravastatin had weak effects on reducing PIT, VH-TCFA, or FA. Increases in the number of calcified plaques were observed for both statins. In conclusion, pitavastatin and pravastatin changed coronary artery plaque phenotype as assessed by VH-IVUS in patients with AP. However, the effects of these statins on coronary artery plaque phenotype were different.     

Effect of statins on cholesterol crystallization and atherosclerotic plaque stabilization

Pleiotropic effects of statins have not been fully elucidated. Recently we demonstrated that cholesterol expands when crystallizing and may trigger plaque rupture. The present study evaluated the potential direct effects of statins in altering cholesterol crystallization as a possible mechanism for plaque stabilization independent of cholesterol lowering. Cholesterol powder was dissolved in oil with and without pravastatin, simvastatin, or atorvastatin (10 to 90 mg) and then allowed to crystallize to measure peak volume expansion (ΔVE) in graduated cylinders. Effect of ΔVE on fibrous membrane damage was also evaluated. Human coronary, carotid, and peripheral arterial plaques (65 plaques from 55 patients) were incubated with statin or saline solution using matched plaque segments to evaluate direct effects of statins on preformed crystals. Also, the effect of in vivo use of oral statins on crystal structure was examined by scanning electron microscopy and crystal content in plaques scored from 0 to +3. For all statins, ΔVE decreased significantly in a dose-dependent fashion (0.76 ± 0.1 vs 0 ml at 60 mg, p <0.001). By scanning electron microscopy crystal structure with statins had loss of pointed tip geometries, averting fibrous membrane damage. Cholesterol crystal density was markedly decreased and appeared dissolved in human plaques incubated with statins (+2.1 ± 1.1 vs +1.3 ± 1.0, p = 0.0001). Also, plaques from patients taking oral statins compared to controls had significantly more dissolving crystals (p = 0.03). In conclusion, statins decreased ΔVE by altering cholesterol crystallization and blunting sharp-tipped crystal structure and dissolving cholesterol crystals in human arteries in vivo and in vitro, providing plaque stabilization.     

Atheroma stabilizing effects of simvastatin due to depression of macrophages or lipid accumulation in the atheromatous plaques of coronary plaque-prone WHHL rabbits

Clinical studies showed that both hydrophilic and lipophilic statins reduce coronary events although in vitro studies demonstrated that lipophilic statins inhibited proliferation of arterial smooth muscle cells. Therefore, we examined whether lipophilic simvastatin reduces smooth muscle cells in atheromatous plaque and how simvastatin affects stability of atheroma in vivo. Coronary atherosclerosis-prone WHHLCA rabbits aged 10 months were given simvastatin (15 mg/kg) orally for 52 weeks and examined the serum lipid levels, plasma drug concentration, and aortic and coronary atherosclerosis. Compared to the placebo group, the plasma cholesterol levels decreased by about 20%. In the simvastatin group, the lipid component (macrophages+extracellular lipids) was decreased in the coronary and aortic atheroma, despite no decrease in the fibromuscular components. Consequently, the frequency of vulnerable plaque decreased. In the coronary plaque of the simvastatin group, PCNA-positive cells (which appeared to be macrophages) of the plaques decreased but the TUNEL-positive cells did not show significant change. Finally, fully differentiated smooth muscle cells increased in the aortic lesions of the simvastatin group. In conclusion, our results suggest that simvastatin did not depress the fibromuscular components in atheromatous plaques and the plaque-stabilizing effects were due to the reduction of macrophages/lipid deposits.