Different Effects of Simvastatin and Losartan on Cytokine Levels in Coronary Artery Disease

BACKGROUND AND OBJECTIVE: Use of HMG-CoA reductase inhibitors (statins) and angiotensin II type 1 (AT(1)) receptor antagonists reduces the incidence of cardiovascular events. The cytokines macrophage colony-stimulating factor (M-CSF) and transforming growth factor (TGF)-beta may exert proatherogenic and antiatherogenic effects, respectively. In this study, we examined whether treatment with a statin or an AT(1) receptor antagonist alters M-CSF and TGF-beta levels in patients with coronary artery disease. METHODS: Twenty-seven consecutive patients with coronary artery disease were randomly assigned to the following three treatment groups for 8 weeks: simvastatin 5 mg/day (n = 10); losartan 50 mg/day (n = 9); or control (usual treatment; n = 8). Blood samples were collected before and after treatment. RESULTS: Clinical characteristics and baseline cytokine levels were comparable among the three groups. Serum levels of M-CSF were significantly decreased only in the simvastatin group (from 403 +/- 71 to 303 +/- 116 pg/mL; p = 0.009). Plasma levels of TGF-beta were significantly increased only in the losartan group (from 5.01 +/- 1.13 to 7.50 +/- 3.83 ng/mL; p = 0.021). Simvastatin decreased serum M-CSF levels independently of changes in total cholesterol or low-density lipoprotein-cholesterol. CONCLUSIONS: The results of this study indicate that simvastatin decreases serum levels of M-CSF while losartan increases plasma levels of TGF-beta, suggesting that the two drugs may have different anti-atherosclerotic properties.     

下肢动脉硬化与冠心病相关性的血管超声研究

目的:探讨下肢动脉硬化对冠状动脉粥样硬化性心脏病(冠心病)的发生及病变程度的预测意义。方法:选择住院患者353例,于冠状动脉(冠脉)造影前进行下肢的血管超声检查,观察斑块形成和血管内径(D),再行冠脉造影检查,并根据其结果分为对照组(N组)93例,冠状动脉病变组(CAD组)260例,CAD组中单支病变组(S组)62例,多支病变组(D组)198例。结果:CAD组患者股动脉斑块检出率明显高于对照组,单支病变组和多支病变组下肢动脉斑块检出率明显高于对照组,管腔内径小于对照组(股浅动脉远心端,腘动脉除外),冠状动脉病变支数与斑块检出呈正相关。结论:下肢动脉粥样硬化与冠心病之间有着较密切的联系,下肢血管动脉硬化对冠心病的发生有一定的预测价值。     

冠心病合并代谢综合征患者炎症因子水平与冠状动脉病变程度关系的研究

目的 探讨炎症因子在冠心病合并代谢综合征诊断中的意义.方法 收集2008年12月～2010年3月在我院经冠状动脉造影证实的冠心病患者204例,按有无代谢综合征分为冠心病合并代谢综合征组(101例)和单纯冠心病组(103例),测定血浆C-反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子(TNF-α)水平,根据冠状动脉造影结果评价冠状动脉病变严重程度.结果 冠心病合并代谢综合征组血浆CRP、IL-6、TNF-α显著高于单纯冠心病组(P＜0.01).CRP、IL-6、TNF-α与冠状动脉病变严重程度呈正相关(r值分别为0.50,0.51和0.51,P＜0.01).结论 CRP、IL-6、TNF-α升高是冠心病合并代谢综合征的危险因素,炎症在疾病发生发展过程中起重要作用.     

冠心病合并代谢综合征患者炎症因子水平与冠状动脉病变程度关系的研究

目的探讨炎症因子在冠心病合并代谢综合征诊断中的意义。方法收集2008年12月～2010年3月在我院经冠状动脉造影证实的冠心病患者204例,按有无代谢综合征分为冠心病合并代谢综合征组（101例）和单纯冠心病组（103例）,测定血浆C-反应蛋白（CRP）、白细胞介素-6（IL-6）、肿瘤坏死因子（TNF-α）水平,根据冠状动脉造影结果评价冠状动脉病变严重程度。结果冠心病合并代谢综合征组血浆CRP、IL-6、TNF-α显著高于单纯冠心病组（P〈0.01）。CRP、IL-6、TNF-α与冠状动脉病变严重程度呈正相关（r值分别为0.50,0.51和0.51,P〈0.01）。结论 CRP、IL-6、TNF-α升高是冠心病合并代谢综合征的危险因素,炎症在疾病发生发展过程中起重要作用。     

MTHFR基因多态性与冠心病的关系

目的研究天津地区人群N5,N10-亚甲基四氢叶酸还原酶(MTHFR)基因C 677 T多态性与冠心病的关系.方法应用聚合酶链反应(PCR)技术和限制性酶切片段长度多态性(RFLP)分析技术检测50例冠心病患者(冠心病组)和50例正常人(对照组)MTHFR基因C 677 T多态性,应用高效液相色谱法测定血浆同型半胱氨酸(Hcy)水平,采用125Ⅰ标记放免法测定血清叶酸浓度.结果(1)冠心病组与对照组MTHFR基因频率分布不同(P＜0 05),对照组CC型、TC型、TT型基因频率分别为52.0%,28.0%,20.0%;冠心病组分别为26.0%,44.0%,30.0%.冠心病组T等位基因频率为52.0%,C等位基因频率为48.0%,与对照组比较有显著性差异(P＜0.05).(2)两组的TT基因型者血浆Hcy浓度均明显高于CC和TC基因型者(P＜0.05),而后两者间无显著性差异(P＞0.05).(3)冠心病组Hcy浓度高于对照组(P＜0.05).两组叶酸水平无显著性差异(P＞0.05),血浆Hcy浓度与叶酸水平均呈显著负相关(r分别为-0.617和-0.588,P＜0.05).结论MTHFR基因C 677 T点突变与冠心病发病密切相关,MTHFR基因纯合突变是引起高Hcy血症的一个重要的遗传因素.     

基质金属蛋白酶基因多态性与冠心病的关系

目的：探讨基质金属蛋白酶基因MMP-3、MMP-9和MMP-12启动子基因多态性与冠心病及其血浆水平的关系.方法：对经冠状动脉（冠脉）造影证实的急性心肌梗死患者59例（AMI组）、稳定性心绞痛患者58例（SAP组）和99例经冠脉造影证实无冠状病变的对照组进行了研究.ELISA法检测血浆MMPs的水平,多聚酶链反应-限制性内切酶片段长度多态性法（PCR-RFLP法）分析MMP-3、MMP-9、MMP-12启动子的3个部位基因型变异状况和等位基因分布频率.结果：AMI组和SAP组血浆MMP-9水平明显高于对照组（P＜0.05）.各组基因型和等位基因频率分布差异无统计学意义（P＞0.05）.未检出MMP-12启动子的-82A/G变异的基因型.不同基因型之间血浆MMPs的水平差异无统计学意义（P＞0.05）.结论：MMP-3和MMP-9启动子区域两个位点的基因变异不影响其血浆水平的表达.未发现天津地区MMP-12的-82位A/G变异的基因多态现象,血浆MMP-9水平升高与冠心病发病有关.     

颈动脉粥样硬化超声表现与冠心病的相关性分析

目的:探究颈动脉粥样硬化超声表现和冠心病的相关性。方法:选取某院2013年1月~2015年2月收治的780例颈动脉超声检查的患者,包括390例冠心病患者,将其随机分成冠心病组和非冠心病组,进行回顾性分析,并探讨颈动脉粥样硬化和冠心病的相关性。结果:冠心病患者的颈动脉粥样硬化的发生率和板块发生率,均优于非冠心病患者,差异有统计学的意义。结论:颈动脉粥样硬化病变和冠心病有紧密的关系,对于冠心病发生的预测和临床早期干预方面均有重要的临床意义。     

高尿酸血症与冠脉造影确诊的冠心病的相关性

目的:探讨高尿酸血症(HUA)与冠脉造影确诊的冠心病(CAD)的发生及严重程度的相关性。方法:对647例接受冠脉造影的患者测定各项临床指标,根据冠脉造影结果分为CAD组和对照组,以发生病变的血管支数及Gen?sini积分反映冠心病严重程度,分性别进行对照研究。结果:(1)女性CAD组的HUA比例高于对照组(P=0.012)。(2)HUA仅在女性是冠心病发生的影响因素(OR=2.022,95%CI:1.098~3.723,P=0.023),但在对年龄进行调整后,HUA亦未入选冠心病影响因素(OR=1.513,95%CI:0.778~2.931,P=0.221)。两性患有HUA都不是冠心病发生的独立危险因素。(3)女性病变血管支数的分布在HUA组与非HUA组之间差异有统计学意义(Z=2.51,P=0.01)。女性HUA患者的Gensini积分高于非HUA患者(P=0.04),且在女性的全组、HUA组及非HUA组Gensini积分与血尿酸水平均呈正相关(rs分别为0.181、0.291和0.138,P<0.05或P<0.01)。结论:女性HUA与冠心病的发生有一定关联,但不是独立危险因素。临床诊断中似应重视高龄女性HUA患者发生冠心病的危险。     

Secondary Prevention of Coronary Artery Disease with Antimicrobials

Over the past several decades, coronary artery disease (CAD) has become the major health problem in the Western world with more than 50% of deaths attributed to its complications. The exact causes of atherosclerosis are not clearly known, although multiple risk factors (e. g. hypertension, hyperlipidemia, diabetes mellitus, family history, and smoking) have been well described. However, these risk factors account for only about 50% of the total risk of CAD. Consequently, an ongoing search is under way to discover new risk factors for atherosclerosis as well as the basic underlying causes of progression. Although the evidence is not yet definitive, recent studies have shown that chronic infection by such bacterial organisms as Chlamydia pneumoniae, Helicobacter pylori, and a variety of dental pathogens may play a causative role in atherosclerosis. If this is true, then antimicrobial therapy may be helpful in the secondary prevention of CAD. Indeed, several small studies have already been completed testing this hypothesis. This article reviews the evidence associating these bacterial pathogens to CAD and presently available information regarding the use of antibiotics in the setting. At present, most studies evaluating the potential efficacy antimicrobials in the secondary prevention of CAD have tested the use of macrolide antibodies. Although several small preliminary studies have reported promising results favoring a clinical benefit from even short (<3 months) courses of antimicrobial therapy, the first large clinical trial, the Weekly Intervention with Zithromax for Atherosclerosis and its Related Disorders (WIZARD) study, did not show a statistically significant beneficial effect of a 3 month course of azithromycin over placebo by the end of up to 4 years follow-up. However, a statistically significant (p = 0.03) 33% reduction in death and myocardial infarction was found at 6 months, 3 months after the discontinuation of antibiotics. This robust clinical benefit, however, was not sustained over the ensuing 3.5 years of follow-up. These disappointing long-term outcomes of short-term therapy with antimicrobials may be explained by the recently discovered difficulty found in eradicating chronic vascular infections such as C. pneumoniae. It remains possible that longer term antimicrobial therapy or short-term use of more potent single agents or combinations, capable ofeffectively eradicating the offending organisms might provide added clinical benefit in the fight against CAD. Further studies are ongoing or planned to evaluate this potential. In the meantime, it is not presently recommended that antimicrobials be routinely prescribed for the secondary prevention of CAD.     

动态心电图联合平板运动实验与冠脉造影的对比分析

目的探讨动态心电图与平板运动实验对冠心病的诊断价值。方法选择36例可疑冠心病患者,分组进行24h动态心电图与平板运动试验检查,以冠脉造影结果做对比,比较两种方法对冠心病心肌缺血阳性检出率,诊断冠心病心肌缺血的特异性。结果动态心电图检出冠脉病变的敏感性为77.8%,运动平板敏感性69.4%,差异有统计学意义。结论动态心电图与平板运动试验均可作为无创诊断冠心病的有效方法。     

异丙酚和异氟醚对非体外循环搭桥术患者围术期细胞因子的影响

目的:研究异丙酚和异氟醚对非体外循环搭桥术患者围术期炎性与抗炎性细胞因子平衡的影响。方法:择期非体外循环搭桥患者50例,随机分为2组。异丙酚组微量泵输入剂量为4～6mg·kg-·1h-1,异氟醚组吸入浓度为1%～1.5%。检测诱导前、打开心包、旁路血管开放30min,术后2h、24h血清白细胞介素6(IL-6)、白细胞介素10(IL-10)和肿瘤坏死因子α(TNF-α)的浓度。结果:2组患者旁路血管开放后IL-6浓度较术前升高(P<0.01),术后2h达高峰;术后2h异氟醚组高于异丙酚组(P<0.05)。IL-10浓度变化趋势与IL-6相似,旁路血管开放后、术后2h和24h异丙酚组高于异氟醚组(P<0.05)。2组患者TNF-α水平均无显著变化。结论:异丙酚麻醉促进IL-10的产生,抑制IL-6的产生,控制术中应激反应异丙酚优于异氟醚。     

MCP-1基因多态性与冠状动脉病变程度的关联性研究

目的:探讨苏南地区汉族人群单核细胞趋化蛋白-1(MCP-1)基因-2518MG单核苷酸多态性与冠状动脉病变程度的关系.方法:采用单荧光标记探针技术检测单核苷酸多态性的方法,检测经冠状动脉造影确诊的297例冠心病患者MCP-1基因-2518MG多态性位点的基因型和等位基因分布,分析不同冠状动脉狭窄程度人群中MCP-1的基因型和等位基因频率的差异.结果:MCP-1基因-2518A/G单核苷酸多态性的基因型在不同冠状动脉病变程度间的分布差异具有统计学意义(P=0.035),携AG基因型者发生严重冠脉狭窄的相对风险度是携AA基因型者的2.15倍(P=0.029,95%CI 1.10～4.22).结论:苏南地区汉族人群MCP一1-2518位点AA基因型可能有助于保护机体避免发生严重的冠脉狭窄,MCP-1-2518A/G基因多态性可能与冠状动脉病变程度相关.     

冠心病患者心率变异性与其冠脉病变严重程度的关系分析

目的 探析冠心病患者诊断评估中其机体冠状病变严重程度与心率变异性存在的相关性.方法 选取就诊且经冠状动脉造影确诊为冠心病患者70例,冠脉病变程度标准以Gensini评分加以判定后予以分组,划作轻度组(n=25例)、中度组(n=23例)及重度组(n=22例),行24h常规动态心电图监测三组心率变异性指标水平,涵盖相邻正常...     

非体外循环冠状动脉搭桥术后心肌损伤与炎症因子的关系

目的:探讨非体外循环冠状动脉搭桥术(OPCABG)后心肌损伤与炎症因子的关系。方法:根据患者术后24h肌钙蛋白(ITnI)水平分为2组,TnI<0.16μg/L者为A组,TnI≥0.16μg/L者为B组。集中通过液相芯片技术同期检测术前及术后1、4、24、72h细胞因子白细胞介素(IL)-6、IL-8和IL-10的表达水平。结果:2组患者术后1hIL-6、IL-8、IL-10水平达高峰,(IL-6 IL-8)/IL-10于术后24h达到高峰。2组组内(IL-6 IL-8)/IL-10水平各时间点比较差异有统计学意义(P<0.01),而组间比较差异无统计学意义(P>0.05),组内各时间点与处理分组的交互作用差异无统计学意义(P>0.05)。结论:OPCABG伴有炎症反应过程,可导致术后炎症因子水平的变化,(IL-6 IL-8)/IL-10水平与术后24h时心肌损伤状况无关。     

Platelet Glycoprotein IIb/IIIa Polymorphism and Coronary Artery Disease

Membrane glycoprotein (GP) IIb/IIIa plays a major role in platelet function; indeed it enables stimulated platelets to bind fibrinogen and related adhesive proteins, a process that is considered key in the development of thrombosis. The gene encoding GPIIIa (ITGB3, also known as GP3A) shows a common platelet antigen polymorphism [PL(A1)/PL(A2); expressed by alleles ITGB3*001 and ITGB3*002] that was variably associated with vascular disease. In 1996, the presence of the PL(A2) allele (ITGB3*001) was first reported to increase the risk of coronary heart disease. Shortly after, the interest in this study was increased by the publication of a case report on the death from myocardial infarction of an Olympic athlete who was found to be homozygous for the PL(A2) allele. Overviews of the published studies on the PL(A1)/PL(A2) polymorphism and coronary risk suggest an influence of the PL(A2) allele on the clinical phenotype and the interaction with other environmental factors. In particular, the strongest effect of the ITGB3 PL(A2) allele was expressed on the risk of occlusion after revascularization procedures, mainly after stent implantation, a condition in which platelet activation is more important as compared with other stenotic mechanisms. In the future, the identification of patients who are particularly responsive to GPIIb/IIIa antagonist therapy (e.g. those with the PL(A2) allele) might help to improve the treatment efficacy in this relatively small population. In a mechanism possibly unrelated to its effect on platelet reactivity to aggregating stimuli, the presence of the PL(A2) allele might influence the antiaggregatory effect of platelet inhibitory drugs such as aspirin (acetylsalicylic acid), clopidogrel, and GPIIb/IIIa antagonists. Although interesting, current data does not yet have direct clinical implications for patient risk identification and drug therapy tailoring. Larger studies are necessary to define the role of the PL(A2) allele in more homogeneous groups where platelet GPIIb/IIIa activation might be particularly relevant.     

Bioactive Sphingolipids as Major Regulators of Coronary Artery Disease

Atherosclerosis is the deposition of plaque in the main arteries. It is an inflammatory condition involving the accumulation of macrophages and various lipids (low-density lipoprotein [LDL] cholesterol, ceramide, S1P). Moreover, endothelial cells, macrophages, leukocytes, and smooth muscle cells are the major players in the atherogenic process. Sphingolipids are now emerging as important regulators in various pathophysiological processes, including the atherogenic process. Various sphingolipids exist, such as the ceramides, ceramide-1-phosphate, sphingosine, sphinganine, sphingosine-1-phosphate (S1P), sphingomyelin, and hundreds of glycosphingolipids. Among these, ceramides, glycosphingolipids, and S1P play important roles in the atherogenic processes. The atherosclerotic plaque consists of higher amounts of ceramide, glycosphingolipids, and sphingomyelin. The inhibition of the de novo ceramide biosynthesis reduces the development of atherosclerosis. S1P regulates atherogenesis via binding to the S1P receptor (S1PR). Among the five S1PRs (S1PR1-5), S1PR1 and S1PR3 mainly exert anti-atherosclerotic properties. This review mainly focuses on the effects of ceramide and S1P via the S1PR in the development of atherosclerosis. Moreover, it discusses the recent findings and potential therapeutic implications in atherosclerosis.     

澳门地区老年患者冠状动脉介入治疗术的临床评价

目的评估澳门地区75岁以上冠心病患者接受冠状动脉介入治疗术（PCI）的安全性和临床疗效。方法对医院自2004年1月至2007年6月共181例年龄≥75岁的冠心病患者临床特点、冠脉病变特点、PCI成功率、手术并发症进行回顾性分析，并与223例〈75岁患者作比较。其中3支冠脉病变68例（37.5%，复杂病变274处（88．1％），311处靶病变进行P丁CA、支架植入术。结果75岁以上病例成功率95.6％，小于75岁病例为96.8％，两组比较无显着性差异（P〉0.05）。病变的成功率为93.6％，48例急性心肌梗塞治疗犯罪血管开通率100%，慢性闭塞病变（CTO）22处，成功率77.3％，170例患者行冠脉支架植入术（93.9％），术前靶血管平均狭窄（87.6±10.4）％，术后平均残余狭窄（5.7±6.5）％。严重并发症5例（2.76％），死亡率2.76％，小于75岁病例严重并发症6例（2.69％），死亡率为2.69％，两组比较无显着性差异（P〉0.05）。结论高龄因素对冠心病患者选择性冠状动脉介入治疗术成功率和安全性无显着影响。     

Ambient Particulate Matter,C-Reactive Protein,and Coronary Artery Disease

Abstract

This article is a review of the scientific literature with respect to fine particulate matter (PM), 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, and coronary artery disease (CAD). The association between air pollution and respiratory diseases has been extensively investigated for decades; however, the role of air pollution in exacerbating heart disease has only recently become a focus of attention. It has been shown that for every 10-μg/m³ increase in fine PM in the air, there appears to be a 2.1% increase in the number of deaths related to ischemic heart disease. PM has been linked to increased levels of systemic inflammation biomarkers such as C-reactive proteins (CRP). Daily variation of ambient pollution is correlated with rises and falls in CRP levels. Increased CRP levels have been associated with increased morbidity and mortality in individuals with CAD. Seventy-five percent of patients with elevated CRP levels have reportedly experienced a major cardiac event despite low-density lipoproteins (LDL) levels that were below the threshold recommended for pharmacological intervention. HMG CoA reductase inhibitors (statins) have been shown to cause a reduction in coronary events by lowering LDL levels. However, recently it has been shown that statins have the effect of lowering CRP levels. This may explain why individuals with normal lipid levels may benefit from statin therapy. Ambient PM exposure levels and its effects on CRP are risk factors associated with coronary events and should be considered as a target for the treatment of CAD.