Association of the Low-Density Lipoprotein Cholesterol/High-Density Lipoprotein Cholesterol Ratio and Body Mass Index with Coronary Plaque Regression

Background

The change (D) in the low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio (DLDL-C/HDL-C) and obesity are known to play important roles in the progression of coronary atherosclerosis. We hypothesized that a reasonable predictive model of coronary plaque regression could be constructed using DLDL-C/HDL-C and the body mass index (BMI).

Objective

The purpose of this study was to establish a predictive model of coronary plaque regression using DLDL-C/HDL-C and BMI.

Methods and Results

A 6-month prospective observational study was conducted among 114 patients with coronary artery disease (CAD) who were treated with pravastatin. The plaque volume, as assessed using volumetric intravascular ultrasound, decreased significantly by 9.9% (p<0.0001 vs baseline). In a multi-variate regression analysis with traditional risk factors, ΔLDL-C/HDL-C (β: 0.473, p = 0.0001) and the baseline BMI (β: 0.249, p = 0.004) were identified as independent predictors of the Δplaque volume. The patients were divided using the 50th percentile of the baseline BMI and the 50th percentile of the ΔLDL-C/HDL-C ratio as cutoffs, and a model for predicting coronary atherosclerotic regression was prepared using a combination of the two variables. The Δplaque volumes were -18.3%, -14.1%, -4.8%, and -2.2% for the groups with ΔLDL-C/HDL-C ≤22.2% and a BMI ≤ 24.1 kg/m², ΔLDL-C/HDL-C ≤22.2% and ΔBMI >24.1 kg/m², ΔLDL-C/HDL-C >-22.2% and BMI ≤ 24.1 kg/m², and ΔLDL-C/HDL-C >-22.2% and BMI >24.1 kg/m², respectively (p = 0.003).

Conclusion

A predictive model for coronary plaque regression based on a combination of ΔLDL-C/HDL-C and the baseline BMI may be a useful clinical tool in patients with CAD.     

Candidate Mechanisms for Regression of Coronary Atherosclerosis with High-Dose Statins

Animal models and serial imaging studies in humans have shown that atherosclerosis is a potentially reversible disease. Several drug classes have been tested to determine whether they can promote reversal of atherosclerosis. Of these, HMG-CoA reductase inhibitors (statins) have been consistently proven to have anti-atherosclerotic effects in large-scale clinical trials. In this article, we review the lipid- and non-lipid-based mechanisms of statin-induced disease regression using the information provided by the recent intravascular ultrasonography trials. We conclude that, despite several potential mechanisms, reduction of low-density lipoprotein cholesterol appears to be the dominant mechanism responsible for regression of atherosclerosis.     

抗氧化低密度脂蛋白自身抗体与冠心病的关系

目的:研究抗氧化低密度脂蛋白自身抗体对冠心病发病的影响.方法:对稳定型心绞痛(SAP组,30例)、不稳定型心绞痛(UAP组,32例)、急性心肌梗死(AMI组,28例)和对照组(38例)采用7%聚乙二醇(PEG6000)沉淀法分离血清中抗氧化低密度脂蛋白免疫复合物(OX-LDL-IC).建立抗氧化低密度脂蛋白自身抗体酶联免疫测定方法,同时测定氧化低密度脂蛋白(OX-LDL)、血清上清中游离的OX-LDL-Ab和沉淀里OX-LDL-IC的OX-LDL-Ab.结果:氧化低密度脂蛋白组OX-LDL、游离OX-LDL-Ab以及OX-LDL-IC水平及其阳性率均高于对照组(P<0.01);AMI组游离OX-LDL-Ab和OX-LDL-IC水平及其阳性率均高于SAP组和UAP组(P<0.05);SAP组和UAP组OX-LDL和OX-LDL-Ab水平及其阳性率差异无统计学意义(P>0.05),而OX-LDL-IC的水平及其阳性率UAP组比SAP组增高(P<0.05).结论:检测患者OX-LDL-IC比单纯测定游离OX-LDL-Ab能更好地判定冠心病病变的严重程度,指导临床治疗.     

Add-on Ezetimibe Reduces Small Dense Low-Density Lipoprotein Cholesterol Levels Without Affecting Absorption of Eicosapentaenoic Acid in Patients with Coronary Artery Disease: A Pilot Study

Background

Residual risk of cardiovascular disease from increased small dense low-density lipoprotein (sdLDL)-cholesterol levels and low n-3 polyunsaturated fatty acid (PUFA) levels is a considerable therapeutic issue. The purpose of this study was to evaluate the effect of ezetimibe as an add-on to statins and supplemental eicosapentaenoic acid (EPA) on sdLDL cholesterol and absorption of EPA in patients with coronary artery disease.

Methods

The study population consisted of ten male patients who were concurrently receiving statins and EPA 1,800 mg/day. Serum lipids and PUFAs, including EPA and arachidonic acid, were measured in blood samples collected before ezetimibe (baseline), 4 weeks after starting 10-mg/day ezetimibe, and 4 weeks after discontinuing ezetimibe.

Results

Ezetimibe significantly decreased sdLDL-cholesterol levels after 4 weeks of treatment (baseline 35 ± 13 mg/dl; treatment 27 ± 9 mg/dl), but the levels returned to baseline after discontinuation of ezetimibe (37 ± 13 mg/dl). The concentration of EPA did not significantly change during the study.

Conclusion

Ezetimibe shows great promise as an add-on therapy to statins to reduce sdLDL-cholesterol-related residual risk of cardiovascular disease without affecting absorption of supplemental EPA in patients with coronary artery disease.     

血清凝集素样氧化低密度脂蛋白受体-1水平与急性冠脉综合征关系的研究

目的:探讨血清中凝集素样氧化低密度脂蛋白受体-1(LOX-1)水平与急性冠脉综合征(ACS)的关系。方法:经冠状动脉造影(CAG)确诊的冠心病患者121例,其中ACS组75例,稳定型心绞痛组(SAP)46例;另设经CAG证实冠脉无狭窄者50例为对照组。采用酶联免疫吸附法(ELISA)测定3组入选者入院即刻,ACS组与SAP组经皮冠状动脉介入治疗(PCI)术后即刻、对照组CAG术后即刻,ACS组与SAP组PCI术后1周血清sLOX-1浓度。结果:入院即刻及术后即刻,ACS组外周血清sLOX-1水平高于SAP组和对照组,SAP组高于对照组(P<0.05或P<0.01);PCI术后1周,ACS组与SAP组之间差异无统计学意义(P>0.05)。各组内比较,3组术后即刻血清sLOX-1水平与入院即刻相比,差异均无统计学意义(P>0.05);PCI术后1周血清sLOX-1水平较入院即刻有所降低,但差异无统计学意义(P>0.05)。结论:ACS患者外周血清LOX-1浓度明显升高,其水平与冠状动脉内粥样硬化斑块的稳定性密切相关,其可作为动脉粥样硬化斑块不稳定的血清学指标。     

辛伐他汀对氧化型低密度脂蛋白及葡萄糖诱导的LOX-1表达的不同作用

【摘要】目的研究辛伐他汀干预对于氧化型低密度脂蛋白（ox-LDL）及葡萄糖诱导的巨噬细胞表面血清凝集素样氧化型低密度脂蛋白受体（LOX）-1表达的影响,以及核因子（NF）-κB的作用。方法U937细胞经佛波酯诱导分化后,将含有50mg/L ox-LDL和（或）25mmol/L葡萄糖的培养液与上述细胞共同孵育,应用吡咯烷二硫氨基甲酸（PDTC）及不同浓度辛伐他汀（1、10μmol/L）干预上述细胞,干预前后用ELISA检测LOX-1蛋白的表达及NF-κB的活性,RT-PCR检测LOX-1mRNA含量。结果ox-LDL、高糖及联合组均上调LOX-1表达,NF-κB的抑制剂PDTC可以抑制其作用,辛伐他汀可以下调ox-LDL诱导的LOX-1表达增加,且高浓度下调明显;但辛伐他汀对于高糖诱导LOX-1表达无明显影响。各组间NF-κB活性改变与LOX-1表达基本一致。结论辛伐他汀可以下调ox-LDL诱导的巨噬细胞LOX-1表达,但对葡萄糖诱导的LOX-1表达无明显影响,LOX-1表达调控与NF-κB信号途径有关。     

冠心病患者小而密低密度脂蛋白与血浆同型半胱氨酸水平的关系

目的:探讨小而密低密度脂蛋白(sLDL)和血浆同型半胱氨酸(Hcy)与冠心病的发生及冠状动脉病变程度的关系.方法:根据冠状动脉造影的结果依冠状动脉病有无狭窄分为冠心病组和对照组,检测其血浆Hcy、血清胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆同醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)水平,并测定sLDL在低密度脂蛋白中所占的比例,观察冠脉病变程度与Hcy及sLDL的关系.结果:冠心病组血浆Hcy、TC、TG、LDL-C及sLDL水平明显高于对照组,HDL-C低于对照组,差异有统计学意义(P＜0.05),Hcy与sLDL水平随冠状动脉病变支数增加而升高(P＜0.05).sLDL和血浆Hcy水平与冠状动脉病变程度有关,sLDL和血浆Hcy水平呈正相关.结论:sLDL和血浆Hcy水平呈正相关,且与冠心病发病及病变严重程度有关.     

低密度脂蛋白血液净化研究进展

冠心病与低密度脂蛋白(IDL)浓度过高有着密切关系，低密度脂蛋白血液净化已成为一种有效的治疗严重高胆固醇血症方法被广泛采用的。文章综述了低密度脂蛋白血液净化的方法及其净化材料研究概况。     

Modeling of Corticosteroid Effects on Hepatic Low-Density Lipoprotein Receptors and Plasma Lipid Dynamics in Rats

Purpose This study examines methylprednisolone (MPL) effects on the dynamics of hepatic low-density lipoprotein receptor (LDLR) mRNA and plasma lipids associated with increased risks for atherosclerosis. Materials and methods Normal male Wistar rats were given 50 mg/kg MPL intramuscularly (IM) and sacrificed at various times. Measurements included plasma MPL and CST, hepatic glucocorticoid receptor (GR) mRNA, cytosolic GR density and hepatic LDLR mRNA, and plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), and triglycerides (TG). Results MPL showed bi-exponential disposition with two first-order absorption components. Hepatic GR and LDLR mRNA exhibited circadian patterns which were disrupted by MPL. Down-regulation in GR mRNA (40–50%) was followed by a delayed rebound phase. LDLR mRNA exhibited transient down-regulation (60–70%). Cytosolic GR density was significantly suppressed but returned to baseline by 72 h. Plasma TC and LDLC showed increases (55 and 142%) at 12 h. A mechanistic receptor/gene pharmacokinetic/pharmacodynamic model was developed to describe CS effects on hepatic LDLR mRNA and plasma cholesterols. Conclusions Our PK/PD model was able to satisfactorily capture the MPL effects on hepatic LDLR, its relationship to various plasma cholesterols, and builds the foundation to explore this area in the future. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

冠心病患者血清胆红素和低密度脂蛋白胆固醇水平的临床研究

目的通过对35~55岁中年男性冠心病(CHD)患者与男性健康体检者血清胆红素(BIL)和低密度脂蛋白胆固醇(LDL-C)水平进行回顾性分析,探讨中年男性血清BIL和LDL-C水平与CHD发生的关系及血清BIL和LDL-C水平的相关性,为临床CHD的预防和治疗提供理论基础和实验依据。方法选择2012年1月至2012年11月到阜新市第二医院就诊并确诊为CHD的72例35-55岁中年男性患者作为实验组,72例相同年龄段的男性健康体检者作为对照组。采用全自动生化仪检测各组研究对象血清BIL和LDL-C水平,进行统计学分析。结果 CHD患者组血清TBIL、DBIL、IBIL浓度均低于对照组,LDL-C浓度高于对照组,差异具有统计学意义(P<0.05)。血清TBIL、DBIL、IBIL水平与LDL-C浓度均成负相关关系(-1相似文献   

Modifications in Lipoprotein Surface Charge Alter Cyclosporine A Association with Low-Density Lipoproteins

Purpose. The purpose of this study was to examine the influence of lipoprotein surface charge on the plasma distribution of cyclosporine A (CSA). Methods. Phosphatidylinositol (PI; 40 mol) was administered intravenously to rabbits. Blood was removed 10 min after injection and plasma was retrieved. Radiolabeled CSA ([³H] CSA) at a concentration of 1000 ng/mL was incubated for 60 min at 37°C in control and PI-treated rabbit plasma. After incubation, plasma was separated into its lipoprotein and lipoprotein-deficient plasma (LPDP) fractions by density gradient ultracentrifugation, and the percentage of [³H]CSA recovered in each fraction was determined by radioactivity. To determine lipoprotein surface charge within control and PI-treated plasma, the zeta potential of each lipoprotein fraction was measured. The effect of PI on lipoprotein surface charge was further confirmed by gel electrophoresis. Results. PI treatment caused low-density lipoprotein (LDL) fraction to migrate further on the agarose gel, indicative of an increased negative surface charge. Zeta potential analysis further showed that LDL particles had a surface potential of –11.4 ± 1.9 mV and –17.4 ± 3 mV in control and PI-treated groups, respectively. A greater percentage of [³H]CSA was recovered within the LDL (16.4 ±1.1% vs. 7.7 ± 2.1%; n = 3; p < 0.05) fraction after incubation in PI treated than in control plasma, respectively. Conclusion. These findings suggest that modifications in lipoprotein surface charge alter CSA distribution within the LDL plasma fraction.     

脂蛋白（a）在动脉粥样硬化患者中的变化及血脂康干预的影响

目的：探讨冠心病（CHD）患者及脑梗死患者血清脂蛋白（a）[Lp(a)]水平及药物干预的影响。方法：151例CHD病人，其中急民生心肌梗死（AMI）20例，陈旧性心肌梗死（OMI）49例，心绞痛（AP）82例；脑梗死患者42例及正常对照组30例，测定其血清Lp(a)浓度。对高Lp(a）水平随机分组用血脂康胶囊及维生素C治疗。结果：CHD及脑梗死组其血清Lp(a)水平明显高于对照组（均P＜0.01)；CHD组高于脑梗死组（P＜0.01)。CHD组中，AMI组＞AP组＞OMI组（P＜0.01或P＜0.05）。用血脂康胶囊4粒/日治疗40例，12周末血清Lp(a)下降19.66%，与治疗前比较差异显著（P＜0.05)。结论：提示Lp(a)有致动脉粥样硬化的作用；血脂康胶囊对高血清Lp(a)水平安全有效。     

不同他汀类治疗老年冠心病伴高胆固醇血症的疗效比较

目的:比较不同他汀类治疗老年冠心病伴高胆固醇血症的疗效.方法:选择2016年11月—2019年11月在河南省人民医院治疗的360例老年冠心病伴高胆固醇血症患者,随机分为A、B、C三组进行不同他汀类治疗,向A组(n=120)提供普伐他汀,B组(n=120)提供瑞舒伐他汀,C组(n=120)提供阿托伐他汀,比较三组不同他汀类治疗后的效果.结果:在血脂水平比较上,三组在治疗后的各项血脂指标上均表现好于治疗前;B组总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)上的表现较A、C两组更好,差异具有统计学意义,P<0.05.结论:不同他汀类药物在治疗老年冠心病上都能够取得较好疗效,安全性有保障,但相对来说,瑞舒伐他汀的疗效更佳,在临床应用更广.     

不同他汀类药物的降脂作用及对冠心病患者炎症指标的疗效

目的:分析不同他汀类药物的降脂作用及对冠心病患者炎症指标的疗效。方法:选取2019年12月~2020年12月来某院开展治疗的冠心病患者66例作为观察对象,选择红蓝双色球法进行分组,分为对照组(阿托伐他汀钙片10mg)和实验组(辛伐他汀片40mg)各33例,对比分析两组的血脂水平、炎症指标,统计动脉粥样硬化程度与不良反应。结果:在甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)与高密度脂蛋白(HDL)水平上,实验组优于对照组(P<0.05)。在肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)、白细胞介素-6(IL-6)以及基质金属蛋白酶-9(MMP-9)水平上,实验组低于对照组(P<0.05)。在颈动脉内-中膜厚度、冠状动脉狭窄程度评分以及颈动脉斑块积分上,实验组低于对照组(P<0.05)。在不良反应发生率上,实验组略低于对照组(P>0.05)。结论:相较于阿托伐他汀,辛伐他汀用于冠心病的治疗效果理想,对于血脂水平与炎症反应的改善具有促进作用,可有效减轻动脉粥样硬化程度,临床可进一步推广运用。     

新型胆固醇吸收抑制剂依泽替米贝与他汀类联合应用评价

目的:评价新型胆固醇吸收抑制剂依泽替米贝及其与他汀类联合应用的临床疗效.方法:采用近期国内外文献进行综述、评价.结果与结论:依泽替米贝是一个新型的胆固醇吸收抑制剂,具有优良.的药理活性和安全性,是调血脂领域中药理作用比较新颖的一类,具有广泛的市场前景,目前尚未在我国上市.     

The Effects of Phthalimide and Saccharin Derivatives on Low-Density Lipoprotein (LDL) and High-Density Lipoprotein (HDL) Receptor Activity and Related Enzyme Activities

The hypolipidemic agents, phthalimide, saccharin, o-(N-phthalimido) acetophenone, N-(p-chlorobenzoyl) sulfamate, and o-chlorobenzylsulfonamide affected low-density lipoprotein (LDL) and high-density lipoprotein (HDL) receptor activity and lipoprotein degradation. In isolated rat hepatocytes, rat aorta foam cells, and human fibroblasts, LDL receptor activity, which is dependent on apo-B and -E, was inhibited by the drugs in a dose-dependent manner. LDL degradation was accelerated in the hepatocytes, while it was inhibited in aorta cells and fibroblasts. The drugs enhanced HDL receptor activity, dependent on apo-E and -Al, and HDL degradation in the hepatocytes, whereas in fibroblasts and aorta cells HDL receptor binding and degradation were suppressed. In parallel, activities of acyl Co A acyl transferase, sn-glycerol-3-phosphate acyl transferase, and heparin-induced lipoprotein lipase decreased and activities of HMG–CoA reductase and cholesterol oleate-ester hydrolase increased. In fibroblasts the presence of drugs enhanced HDL binding of intracellular cholesterol. In vivo studies demonstrated that phthalimide and saccharin treatment enhanced the clearance of HDL and decreased the clearance of LDL from the serum of rats. The results suggest that the mode of action of the agents is to modulate the lipoprotein receptor and, thereby, the clearance of lipids from peripheral tissue as part of the hypolipidemic activity.     

异丹叶大黄素在体外对Cu2+介导的人低密度脂蛋白过氧化的抑制作用

目的研究异丹叶大黄素(Iso)对Cu2 介导的人低密度脂蛋白(LDL)过氧化及氧化LDL(ox-LDL)对小鼠巨噬细胞毒性的抑制作用.方法用序贯超离心法分离血脂正常的供血者血清LDL,分离的LDL 1 mg·mL-1 磷酸缓冲液(pH 7.4), 与10 μmol·L-1 CuSO4于37℃水浴温育10 h 以引起LDL过氧化,给药组预先加入不同浓度Iso,对照组加等量生理盐水,测定丙二醛(MDA)的生成量、维生素E的耗竭以及LDL电泳迁移率.另外测定用ox-LDL处理小鼠腹腔巨噬细胞线粒体的膜电位、吞噬刚果红及释放NO的量.结果 1-100 μmol·L-1 Iso 剂量依赖性地抑制Cu2 引起的人LDL氧化时MDA的生成量、维生素E的耗竭及电泳迁移率的升高.10 μmol·L-1 Iso能防止0.1 mg·mL-1 ox-LDL与小鼠腹腔巨噬细胞温育4 h 后线粒体膜电位的损伤、吞噬刚果红功能以及NO释放量的降低.结论 Iso在体外对Cu2 介导的LDL过氧化以及ox-LDL对小鼠巨噬细胞的毒性有保护作用.     

他汀类调脂药对冠状动脉粥样硬化斑块炎症的影响

急性冠脉综合征是冠脉斑块破裂后激发的一个由中性粒细胞介导的与血栓形成有关的急性炎症过程 ,在细胞黏附分子、肿瘤坏死因子、巨细胞移动抑制因子、金属蛋白酶、核转录因子 -κB等多种炎性因子中 ,C反应蛋白水平的升高不但与急性冠脉事件高度相关 ,还与疗效及预后相关 ;他汀类调脂药对冠心病患者的保护远超出其血脂下降本身 ,他汀类抗炎机制可能与降脂作用无关 ,新近研究发现大剂量他汀类如阿托伐他汀 ( 80 mg·d- 1有快速炎症抑制作用和消退斑块作用 ,其炎症抑制效价与剂量相关 ,而且非常安全     

早期应用他汀类药物对经皮冠状动脉介入治疗患者预后的影响

目的：评价早期应用他汀类药物对行经皮冠状动脉介入治疗（PCI）患者随访结果的影响。方法：选择2001年7月1日～2002年6月30日、2003年7月1日～2004年6月30日在北京安贞医院接受PCI的患者，记录其临床与造影特征、血运重建情况和住院临床结果等。根据住院期间及出院时是否服用他汀类药物，将患者分为他汀组和非他汀组。采用Kaplan—Meier方法、单因素和多因素Cox回归模型分析，观察住院期间及出院时应用他汀类药物对主要不良心血管事件（MACE）及死亡率的影响。采用Cox回归模型分析对死亡、主要不良心血管事件的影响因素。结果：共入选3289例患者，随访成功3005例，随访率91．4％。他汀组入选2082例，非他汀组入选1207例。随访时间中位数678d。两组无MACE事件生存率差异有显著性，他汀组发生MACE事件绝对危险性较非他汀组下降7％，相对危险度下降44．3％；两组无全因死亡事件生存率差异有显著性，他汀组全因死亡事件绝对危险性较非他汀组下降0.7％，相对危险度下降23．3％。随访MACE事件的单因素Cox回归分析显示，两组差异有显著性。随访MACE事件的多因素Cox回归分析，两组差异有显著性。随访全因死亡临床结果的单因素Cox、多因素Cox回归分析显示，两组差异有显著性。结论：行经皮冠状动脉介入治疗的患者早期服用他汀类药物可显著减少MACE事件及死亡率。     

瑞舒伐他汀对老年冠心病患者动脉硬化、炎性反应与同型半胱氨酸的影响研究

目的探讨瑞舒伐他汀对老年冠心病患者动脉硬化、炎性反应与同型半胱氨酸的影响。方法选取我院(2017年1月至2018年1月)收治的90例冠心病患者,根据不同治疗入院序号分为两组,两组患者均给予控制血糖、血压和低盐低脂饮食、冠心病健康宣教以及适量运动等常规治疗,对照组(n=45)给予阿托伐他汀钙片治疗,观察组(n=45)给予瑞舒伐他汀治疗,对比两组患者治疗前后血脂水平和同型半胱氨酸(Hcy)、炎性反应、动脉硬化程度和不良事件发生率。结果两组患者HDL-C、LDL-C、TG、TC水平对比差异明显,具有统计学意义(P<0.05)。两组患者Hcy、TNF-α、hs-CRP水平对比差异明显,具有统计学意义(P<0.05)。两组患者FMD、IMT对比差异明显,具有统计学意义(P<0.05)。两组患者心血管不良事件发生率对比差异不明显,无统计学意义(P>0.05)。结论瑞舒伐他汀对老年冠心病患者不仅有较好的治疗效果,还具有较高的安全性。