主动脉夹层患者脂蛋白相关磷脂酶A_2浓度水平及临床意义的研究

正主动脉夹层(aortic dissection,AD)在急性期致残率及病死率高,是一种灾难性血管性疾病,因此早期确诊极其重要。目前,其诊断主要依靠影像学检查,尚缺乏特异性较强的血液检查指标。因而,寻找一种方便且敏感度较高的诊断筛选方法显得尤为迫切。高血压、动脉粥样硬化均是AD的重要病因,而脂蛋白相关磷脂酶A_2(Lp-PLA_2)是近年来炎症反应介质的热点,其具有促进动脉粥样硬化作用,且与高血压病密切相关,而Lp-PLA_2与AD之间是否存在联系目前尚无报道。为此笔者检测358例急性胸背痛患者血清中Lp-PLA_2水平,探讨其对AD的诊断预测价值。     

慢性肾衰竭患者幽门螺旋杆菌感染与血浆脂蛋白相关磷脂酶A2及颈动脉粥样硬化的关系

目的探讨慢性肾衰竭(CRF)患者幽门螺旋杆菌(Hp)感染与血浆脂蛋白相关磷脂酶A_2(Lp-PLA_2)水平及颈动脉粥样硬化(CAS)的关系。方法选取CRF患者200例,根据~(14)C尿素呼气试验分为CRF合并Hp感染组(CRF-Hp组,n=119)和CRF未合并Hp感染组(CRF-nHp组,n=81)。将CRF-Hp组按CAS程度又分为3个亚组:颈动脉内膜中膜厚度(CIMT)增厚组、稳定性斑块组和不稳定性斑块组。采用酶联免疫吸附法测定血浆Lp-PLA_2水平,用高分辨二维超声技术检测CIMT、粥样硬化斑块。分析CRF患者Hp感染与血浆Lp-PLA_2水平、CIMT、粥样硬化斑块稳定性的关系。结果 CRF-Hp组血浆Lp-PLA_2水平、CIMT与CRF-nHp组比较差异均有统计学意义(P0.01)。CRF-Hp组和CRF-nHp组CAS类型的构成比差异有统计学意义(χ~2=15.637,P=0.0004)。在CRF-Hp组3个亚组中,不稳定性斑块组、稳定性斑块组、CIMT增厚组血浆Lp-PLA_2水平比较差异均有统计学意义(P0.01)。Pearson相关分析显示,CRF-Hp组血浆Lp-PLA_2水平与CIMT呈正相关(r=0.649,P0.01)。结论CRF患者Hp感染可能通过影响血浆Lp-PLA_2水平使CIMT增厚,并导致CAS斑块的不稳定性增加,从而促进CAS的发生和发展。     

Lp-PLA_2预测急性心梗患者PCI预后的价值

目的探讨脂蛋白相关磷脂酶A_2(Lp-PLA_2)对行直接经皮冠状动脉介入治疗(PCI)的急性ST段抬高性心肌梗死(STEMI)患者预后的预测价值。方法连续入选2014年6月至2015年6月在河北省涿州市医院心内科住院治疗的首次急性心肌梗死患者共220例。入院根据PCI术前检测Lp-PLA_2水平分为高、低水平两组,随访6个月,观察住院期间及随访期间心血管事件发生情况。结果高Lp-PLA_2组在前壁心肌梗死、心功能killip≥Ⅱ分级比例、血肌酐(Cr)水平及冠脉病变支数高于低Lp-PLA_2组,左室射血分数(LVEF)明显低于低Lp-PLA_2组,6个月内预后比较有统计学意义(p0.05)。结论脂蛋白相关磷脂酶A_2对行直接PCI的急性STEMI患者6个月内发生心血管事件的预测有一定的价值。     

90例冠心病不同中医证型病人Lp-PLA_2、eGFR与冠状动脉病变的相关性分析

目的探讨冠心病不同中医证型与血浆脂蛋白相关磷脂酶A_2(Lp-PLA_2)、肾小球滤过率(eGFR)及冠状动脉病变严重程度的关系。方法选取经冠状动脉造影确诊为冠心病的病人,按照其中医辨证分型分为痰浊证组、血瘀证组、非瘀非痰证组,每组30例。对比不同中医辨证分型组Lp-PLA_2、eGFR水平和冠状动脉病变严重程度,并分析其相关性。结果 Lp-PLA_2在冠心病血瘀证、痰浊证病人表达水平较高(P0.05),冠状动脉Gensini积分随着Lp-PLA_2水平升高而增加(P0.05)。eGFR水平与Lp-PLA_2水平及中医证型无明显相关性(P0.05),与冠状动脉病变程度存在相关性,随着eGFR水平下降,冠状动脉Gensini积分增加(P0.05)。结论中医证型、Lp-PLA_2、eGFR水平均与冠状动脉病变程度相关。中医辨证和Lp-PLA_2、eGFR检测相结合的方式可以较准确地推断冠心病病人冠状动脉病变情况,能在早期防治冠心病方面发挥作用。     

荷丹片联合阿托伐他汀对老年冠心病病人斑块稳定性的影响

目的观察荷丹片联合阿托伐他汀治疗后老年动脉粥样硬化病人基质金属蛋白酶-1(MMP-1)、妊娠相关蛋白A(PAPP-A)、脂蛋白相关磷脂酶A_2(Lp-PLA_2)水平的变化,推测其对斑块稳定性的影响。方法随机选取2015年2月10日—2015年8月10日在潍坊市益都中心医院保健老年病科住院的老年冠心病病人76例,并随机分为两组:阿托伐他汀治疗组、荷丹片联合阿托伐他汀组,观察时间为8周,观察前后测定血中基质金属蛋白酶-1、妊娠相关蛋白A、脂蛋白相关磷脂酶A_2水平。结果治疗8周后,两组基质金属蛋白酶-1、妊娠相关蛋白A、脂蛋白相关磷脂酶A_2水平均较治疗前降低(P0.05);与阿托伐他汀治疗组相比,荷丹片联合阿托伐他汀组基质金属蛋白酶-1、妊娠相关蛋白A、脂蛋白相关磷脂酶A_2水平降低更为明显(P0.05)。结论荷丹片联合阿托伐他汀治疗可以进一步提高动脉粥样硬化病人的斑块稳定性。     

冠心病患者血浆Lp-PLA_2水平与冠状动脉病变的临床关系探讨

目的探讨冠心病患者血浆脂蛋白相关磷脂酶A_2(Lp-PLA_2)水平与冠状动脉病变的临床关系。方法选取146例冠心病患者和100例健康志愿者,分别记为疾病组和健康组。所有受试者均采用酶联免疫法测定血浆Lp-PLA_2水平,并对疾病组患者实施冠状动脉造影检查,根据检查结果对冠状动脉进行Gensini积分。对比疾病组和健康组血浆Lp-PLA_2水平,并对比Gensini积分≤19分、20-39分和≥40分3个亚组血浆Lp-PLA_2水平。结果疾病组患者血浆Lp-PLA_2水平明显高于健康组(P0.05),Gensini积分≤19分、20-39分和≥40分3个亚组血浆Lp-PLA_2水平对比差异显著(P0.05),且Gensini积分≥40分者血浆Lp-PLA_2水平均远高于Gensini积分≤19分、20-39分者(P0.05),且Gensini积分20-39分者血浆LP-PLA_2水平远高于Gensini积分≤19分者(P0.05)。结论冠心病患者血浆Lp-PLA_2水平明显高于正常人群,且冠状动脉狭窄越严重,该因子水平越高,可用以评估冠状动脉病变程度。     

冠状动脉粥样硬化性心脏病合并慢性肾病与慢性炎症因子的关系探讨

目的探讨冠状动脉粥样硬化性心脏病(CHD)病人血清脂蛋白磷脂酶A_2(Lp-PLA_2)、超敏C反应蛋白(hs-CRP)、同型半胱氨酸(Hcy)与CHD合并慢性肾病(CKD)病人的关系。方法选取2016年9月—2017年11月在我院心血管内科行冠状动脉造影检查后确诊的CHD病人286例,收集所有病人的相关病例资料,包括一般情况、临床症状、实验室检查(包括Lp-PLA_2、hs-CRP、Hcy、血清尿酸等)。比较CHD组与CHD合并CKD组Lp-PLA_2、hs-CRP、Hcy水平,并分析其与各种实验室指标的关系。结果 CHD合并CKD组hs-CRP、Lp-PLA_2和Hcy水平明显高于CHD组(P0.05)。Logistic回归分析结果显示,hs-CRP、Lp-PLA_2和Hcy是CHD合并CKD的危险因素(P0.05)。hs-CRP、Lp-PLA_2和Hcy的ROC曲线下面积分别为0.749、0.757和0.644。结论 hs-CRP、Lp-PLA_2、Hcy是CHD合并CKD的危险因素,Lp-PLA_2和hs-CRP对CHD合并CKD的预测具有一定的诊断价值,并可作为CHD合并CKD的临床指标指导诊治和评估预后。     

冠心病病人冠状动脉斑块性质与Lp-PLA_2、Hcy和D-二聚体水平的相关性分析

目的探讨脂蛋白相关磷脂酶A_2(Lp-PLA_2)、同型半胱氨酸(Hcy)和D-二聚体水平与冠心病病人冠状动脉斑块性质的相关性。方法选取2016年1月—2018年10月延安大学附属医院经血管内超声和冠状动脉造影检查的病人132例,按照检查结果分为对照组、稳定斑块组、易损斑块组。比较3组血清Lp-PLA_2、Hcy及血浆D-二聚体水平。采用Pearson法分析Lp-PLA_2、Hcy及D-二聚体水平与血管重构指数、斑块偏心指数及纤维帽厚度的关系。采用Logistic回归法分析Lp-PLA_2、Hcy及D-二聚体水平与斑块性质的相关性。结果易损斑块组Lp-PLA_2、Hcy和D-二聚体水平高于稳定斑块组,差异有统计学意义[(401.01±143.11)μg/L与(319.68±108.14)μg/L,(59.43±22.82)μmol/L与(31.91±16.58)μmol/L,(618.53±178.67)μg/L与(308.17±102.91)μg/L,P均0.05]。Pearson相关分析显示:Lp-PLA_2与血管重构指数及斑块偏心指数呈正相关(OR值分别为0.883、0.756,P均0.05),与纤维帽厚度呈负相关(OR=-0.618,P0.05);Hcy与血管重构指数及斑块偏心指数呈正相关(OR值分别为0.697、0.603,P均0.05),与纤维帽厚度呈负相关(OR=-0.618,P0.05);D-二聚体与血管重构指数及斑块偏心指数呈正相关(OR值分别为0.926、0.883,P均0.05),与纤维帽厚度呈负相关(OR=-0.742,P0.05)。Logistic回归分析显示:Lp-PLA_2、Hcy和D-二聚为斑块不稳定的独立危险因素(均P0.05)。结论冠心病病人血清Lp-PLA_2、Hcy及血浆D-二聚体水平与冠状动脉斑块的性质相关,其水平升高可能是冠状动脉易损斑块不稳定的独立危险因素。     

脂蛋白相关性磷脂酶A2与冠心病的研究现状

脂蛋白相关性磷脂酶A2（1ipoprotein-associated phospholipase A2,Lp-PLA2）是近年来被广泛关注的与动脉粥样硬化和缺血性心脑血管病密切相关的磷脂酶家族分子,本文对Lp-PLA2的生物学特征及其与动脉粥样硬化形成与发展的相关研究进展做一综述.     

脂蛋白相关性磷脂酶A_2与冠心病及其预后的相关性分析

目的探讨血浆脂蛋白相关性磷脂酶A_2(Lp-PLA_2)水平对冠心病及其预后的预测价值。方法选择2016年3月—2016年6月因胸闷胸痛症状入院行冠状动脉造影检查的病人166例,造影正常者36例为对照组;造影确诊为冠心病者130例为冠心病组[稳定型心绞痛(SAP)组32例、不稳定型心绞痛(UAP)组53例、急性心肌梗死(AMI)组45例]。记录各组病人的一般资料及心血管不良事件发生情况,分析其对Lp-PLA_2水平的影响。结果 Lp-PLA_2与低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)呈正相关(r=0.163,P <0.05; r=0.082,P <0.05),与高密度脂蛋白胆固醇(HDL-C)呈负相关(r=-0.105,P <0.05)。冠心病心血管不良事件病人Lp-PLA_2高于无心血管不良事件病人[(295.36±247.2) ng/m L与(262.98±16.89) ng/m L,P <0.01]。结论 Lp-PLA_2参与冠心病的发病过程,是冠心病及其预后的一个重要预测因子。     

维生素D与脑血管疾病的关系

维生素D是一种类固醇衍生物,其经典生物效应是调节钙磷代谢。目前研究发现,维生素D具有保护血管内皮完整性、抗动脉粥样硬化、抗氧化应激、抗炎、抑制肾素-血管紧张素-醛固酮系统活性等作用。维生素D与缺血性脑卒中呈负相关,但与脑小血管疾病的关系尚不明确。本文通过综述维生素D与脑血管疾病的研究现状,以期为脑血管疾病的预防及治疗提供相关依据。     

Gene transfer and hepatic overexpression of the HDL receptor SR-BI reduces atherosclerosis in the cholesterol-fed LDL receptor-deficient mouse

HDL cholesterol levels in humans are inversely correlated with the risk of atherosclerosis. The class B scavenger receptor type I (SR-BI) is the first molecularly well-defined HDL receptor, and hepatic overexpression of SR-BI in normal mice has been shown to result in decreased plasma HDL cholesterol levels. To determine whether SR-BI overexpression is proatherogenic or is protective against atherosclerosis, LDL receptor-deficient mice were placed on a high-fat/high-cholesterol diet for 2 or 12 weeks to induce atherosclerotic lesions of different stages and then were injected with a recombinant adenovirus encoding murine SR-BI. Transient hepatic overexpression of SR-BI in mice with both early and advanced lesions significantly decreased atherosclerosis. SR-BI expression was associated with markedly decreased HDL cholesterol and either unchanged or only modestly reduced non-HDL cholesterol levels; in all experiments, the mean HDL cholesterol levels were significantly correlated with atherosclerotic lesion size. These data suggest that interventions that promote HDL cholesterol transport and lower plasma HDL cholesterol levels can suppress atherosclerosis, even when initiated after significant lesion development. Thus, stimulation of hepatic SR-BI activity may provide a novel target for therapeutic intervention in atherosclerotic cardiovascular disease.     

Antioxidant therapy and atherosclerosis: animal and human studies.

Oxidation of LDL cholesterol appears to play a central role in the pathogenesis of atherosclerosis. Animal models of atherosclerosis have elucidated this process and have demonstrated an antioxidant effect of vitamin administration that has been correlated with delayed progression or regression of atherosclerosis. However, clinical trials of antioxidants present a confused picture. Explanations proposed for the discrepancy in results include differences in patient characteristics, the antioxidant content of their diets and dose selection. However, a striking feature of these trials is the absence of a biochemical basis for patient inclusion or dose selection. Reliable, quantitative indices of free radical induced modification of lipids, such as F2-isoprostanes have emerged. Future trials of anti-oxidant therapy in cardiovascular disease should be targeted toward patients with high levels of oxidant stress or patients with depletion of endogenous antioxidants. The dose of anti-oxidant should be chosen based on a surrogate readout, such as F2 isoprostanes, that is a reliable, reproducible and easily obtainable in vivo measure of oxidant stress.     

Proinflammatory cytokines,antibodies to Chlamydia pneumoniae and age-associated diseases in Danish centenarians: is there a link?

Plasma levels of tumour necrosis factor (TNF)-alpha levels increase with age. High levels are associated with dementia and atherosclerosis in centenarians. Chlamydia pneumoniae induces the production of proinflammatory cytokines and has been related to the pathogeneses of Alzheimer's disease and cardiovascular diseases. The purpose of this study was to test the hypothesis that circulating levels of TNF-alpha represent a link between C. pneumoniae, high prevalences of dementia and cardiovascular diseases in 126 Danish centenarians. IgA antibody titres against C. pneumoniae were linearly correlated with high plasma levels of TNF-alpha in centenarians. However, both parameters were also correlated with total IgA in the blood and the association between C. pneumoniae IgA and TNF-alpha was not significant when total IgA was included in a multiple linear regression model. Accordingly, the association between C. pneumoniae-specific IgA and TNF-alpha may reflect immune activation rather than a specific antibody response. No associations were found between antibodies to C. pneumoniae and dementia or cardiovascular diseases. Although TNF-alpha is likely to be involved in the pathogenesis of atherosclerosis and dementia, the present study does not support the hypothesis that TNF-alpha represents a link between chronic C. pneumoniae infection and these disorders.     

动脉粥样硬化性疾病与肿瘤发生的相关性及机制研究进展

动脉粥样硬化性疾病和肿瘤严重威胁人类健康.临床研究显示,动脉粥样硬化性疾病和肿瘤的发生显著相关,动脉粥样硬化患者中肿瘤的发生率高于非动脉粥样硬化者,同时,肿瘤人群中动脉粥样硬化性疾病的发生率亦显著高于非肿瘤人群.动脉粥样硬化性疾病和肿瘤看似是两个独立的疾病,但是在发病机制上存在不同水平的关联,二者不仅存在共同的危险因素...     

治疗高血脂症药物的研究进展

血脂代谢异常是动脉粥样硬化和冠心病的重要危险因素,血清总胆固醇(TC)、三酰甘油(TG)、极低密度脂蛋白-胆固醇(VLDL-C)、低密度脂蛋白-胆固醇(LDL-C)、脂蛋白a[Lp(a)]升高与冠心痛发病呈正相关,高密度脂蛋白-胆固醇(HDL-C)升高与冠心病发病呈负相关.调脂药物通过调控脂质的代谢来降低血脂,进而降低心血管疾病的发生.一直以来,降脂药物都是通过一定的靶点起到降血脂作用.近几年,人们发现了几种新的药物作用靶点,通过对这些新靶点的研究,有助于人们研发出更行之有效的药物,为人类的健康作出贡献.     

Telomere shortening of peripheral blood mononuclear cells in coronary disease patients with metabolic disorders

OBJECTIVE: Telomere shortening is correlated with cell turnover and aging, but it has been recently suggested to occur not only by aging but by several biochemical factors of metabolic disorders predisposing to atherosclerosis. PATIENTS AND METHODS: We compared telomere length of peripheral blood mononuclear cells of patients with the metabolic disorders, hypercholesterolemia (HC) and diabetes mellitus (DM), according to the presence or absence of coronary diseases. RESULTS: The results demonstrated that HC and/or DM patients with coronary diseases have significantly shorter telomere length than healthy controls (p = 0.0014). CONCLUSION: Telomere shortening may be involved in the mechanisms that promote coronary diseases under some circumstances of metabolic disorders.     

Age-dependent variations of human PMNL elastase activity as a function of pH, ionic strength and calcium concentration

Human leukocyte elastase (HLE) has been implicated in the pathomechanism of various diseases, such as emphysema and atherosclerosis. The incidence of these diseases is increasing with aging. Therefore, it can be supposed that the HLE activity is changing with aging according to the well known age-related physiological alterations. Thus, the effects of pH, NaCl and calcium concentrations on HLE activity, separated from polymorphonculear leucocytes (PMNLs) of healthy, young (<35 years) and elderly (>75 years) subjects, were studied by measuring the activity with synthetic substrate and with bovine and human atherosclerotic and non-atherosclerotic aortic elastin. From our results, it may be concluded, that the elastolytic activity of HLE separated from PMNLs of elderly subjects is more sensitive to ionic strength, to pH and to the calcium concentration of the medium, than the HLE activity of young subjects. The elastolytic activity of HLE, of both young and old subjects, increases dramatically on atherosclerotic aortic elastin in the presence of calcium. These findings might explain, at least partly, the increased incidence of atherosclerosis with aging.     

Risk factors for asymptomatic atherosclerosis in Japanese type 2 diabetic patients without diabetic microvascular complications

Atherosclerotic vascular diseases are frequently associated with diabetes mellitus. There has been increasing evidence showing that the atherosclerotic diseases in diabetic patients are distinct from diabetic microvascular complications as to their pathophysiology and epidemiology. However, we have no information on the prevalence of asymptomatic atherosclerosis in diabetic patients before the onset of microvascular diseases. In the present investigation, we aimed to evaluate risk factors for the atherosclerosis in type 2 diabetic patients without the microvascular diseases. For this purpose, we evaluated atherosclerotic change of carotid arteries in 125 Japanese type 2 diabetic patients who had neither atherosclerotic vascular diseases nor diabetic microvascular complications. When atherosclerotic change was defined as the mean intima-media thickness (IMT) of >/= 1.1 mm and/or the presence of plaque lesion, 50% of patients had atherosclerosis of the carotid arteries. Risk factors for the carotid atherosclerosis were age, low-density lipoprotein (LDL)-cholesterol, hypertension, and diabetes treatment. Age and LDL-cholesterol were associated with mean IMT. Age, diabetes treatment, LDL-cholesterol, and hypertension were positively associated with plaque lesion, while high-density lipoprotein (HDL)-cholesterol was negatively associated with it. Fasting plasma glucose, glycosylated hemoglobin (HbA(1c)), and known diabetes duration remained unassociated with any parameters of asymptomatic atherosclerosis of the carotid arteries. These results indicate that glycemic control is unrelated with asymptomatic atherosclerosis in type 2 diabetic patients without diabetic microvascular complications. Conventional risk factors and diabetes treatment are independently associated with atherosclerosis of the carotid arteries in these patients.     

动脉弹性指数与老年人冠状动脉粥样硬化的相关性研究

目的 观察老年冠状动脉粥样硬化患者和冠心病患者大动脉弹性指数(C1)和小动脉弹性指数(C2)的变化,探讨C1、C2与老年冠状动脉粥样硬化狭窄病变Gensini积分的相关性。 方法 入选160例行选择性冠状动脉造影的老年患者,分为3组：冠状动脉正常组（正常组）、冠状动脉粥样硬化组（硬化组）和冠心病组。应用桡动脉舒张期脉搏波形分析仪测定入选者的动脉弹性,得到C1和C2;冠状动脉造影后对所有入选者的冠状动脉狭窄病变程度应用Gensini积分法进行定量评定;分别对硬化组和冠心病组的C1、C2与Gensini积分间的相关性进行直线相关分析。 结果 硬化组的C2低于正常组（P＜0.01）,冠心病组的C2低于硬化组(P＜0.05),3组间的C1比较,差异无统计学意义;硬化组和冠心病组患者Gensini积分分别为（5.4±2.6）分与（51.3±32.1）分,两组比较差异有统计学意义（t= 10.574,P＜0.01）;冠状动脉狭窄病变Gensini积分均与C2呈负相关,与C1无相关性。 结论在老年冠状动脉粥样硬化这一亚临床阶段,C2已开始下降,并随着冠状动脉粥样硬化病变程度的加重而降低,测定C2有助于老年冠状动脉粥样硬化患者的早期发现。