冠心病患者血浆LCAT水平与HDL亚类组成的关系

摘要目的：探讨冠心病(coronaryheartdisease,CHD)患者血浆卵磷脂胆固醇酰基转移酶(lecithincholesterolacyltransferase,LCAT)与高密度脂蛋白(high-densitylipoprotein,HDL)亚类分布的关系。方法：采用双向电泳-免疫印记法分析了73例正常对照者和144例冠心病患者HDL亚类的组成、含量及分布特征,用酶联免疫法测定其LCAT浓度。冠心病患者按血浆LCAT浓度进行四分位数（19.22、36.39和55.32mg/L）分层（Q1：LCAT<19.22mg/L;Q2：19.22≤LCAT<36.39mg/L;Q3：36.39≤LCAT<55.32mg/L;Q4：LCAT≥55.32mg/L）。结果：随着LCAT浓度的降低,冠心病患者血浆总胆固醇（TC）、甘油三酯（TG）水平和载脂蛋白B-100/A-I(apoB-100/A-I)比值呈增加趋势,高密度脂蛋白胆固醇（HDL-C）和apoA-I水平呈减少趋势。与最高四分位数组相比,第三、第二和最低四分位数组中preβ1-HDL含量增加,HDL2a和HDL2b含量减少(P<0.05或P<0.01)。与正常TC组比较,高TC组LCAT浓度降低,且preβ1-HDL含量增加,HDL2a和HDL2b含量减少(P<0.01)。直线相关和多元回归分析中发现,血浆LCAT水平与preβ1-HDL浓度呈负相关,与HDL2a和HDL2b浓度呈正相关。结论：CHD患者血浆HDL颗粒呈变小趋势,并且随着LCAT水平的降低,其HDL颗粒的变小程度更加明显。     

Influence of acute maximal exercise on lecithin: cholesterol acyltransferase activity in healthy adults of differing aerobic performance

Summary To document the possible influence of a single episode of maximal aerobic stress on the serum lecithin: cholesterol acyltransferase (LCAT) activity in subjects with differing histories of training, two groups of healthy male adults [controls (C),n = 18, 28.6 years, SD 5.2, 50.1 ml · kg^–1 · min^–1 maximal O₂ uptake (VO_2max), SD 5.3; endurance trained athletes (T),n = 18, 31.4 years, SD 8.8, 65.0 ml · kg^–1 · min^–1 VO_2max, SD 2.8] were examined in a maximal aerobic stress test. In addition to the routine assessment of lipid status, LCAT activity was measured immediately before and after exercise. At rest nearly identical LCAT activity values were found in both groups: C 64.4 nmol · ml^–1 · h^–1, SD 16.7 vs T 65.0 nmol · ml^–1 · h^–1, SD 20.9. The post-exercise LCAT values induced by the maximal stress test increased significantly to (C) 95.7 nmol · ml^–1 · h^–1, SD 23.5, +48.6%,P<0.001; (T) 83.5 nmol · ml^–1 · h^–1, SD 24.3, +29.1%,P<0.01. Neither the pre nor the post-exercise individual LCAT activity values showed any significant correlation to the corresponding data on physical performance.     

卵磷脂胆固醇酰基转移酶基因单核苷酸多态性与冠心病脂代谢易感性的关联研究

目的：检测卵磷脂胆固醇酰基转移酶（lecithin cholesterol acyltransferase,LCAT）基因3个编码区单核苷酸多态位点在中国人群中的分布频率，并初步探讨它们与脂代谢和冠状动脉粥样硬化性心脏病（coronary atherosclerotic heart disease,CHD）易感性的关系。方法：采用聚合酶链反应－限制性片段长度多态性方法，分析209名正常人和203例CHD患者中608C／T、911T／C和1188C／T（参照序列：NM_000229）3个位点的多态性。结果：608C和608T等位基因频率分布符合Hardy-Weinberg平衡。CHD患者组608T频率显著低于正常人群（P＝0．034）。与无608T CHD患者相比，具有608T的CHD患者的血浆高密度脂蛋白胆固醇显著升高（P＝0．015）。911T／C和1188C/T在两组中均未检出。结论：LCAT基因608T等位基因与CHD患者较高的血浆高密度脂蛋白胆固醇水平相关联，可能与中国人CHD相关。911T／C和1188C／T在中国人群中非常罕见。     

Genetic variations of the apolipoprotein B gene in Turkish patients with coronary artery disease

Background:?The results of studies that clarify the association of genetic markers at the apolipoprotein B (apo?B) gene (EcoRI and XbaI polymorphisms) with coronary artery disease (CAD) are not consistent and suggest that the effect is context dependent (dependent on ethnicity and sex). The present study represents the first investigation of the apo B gene polymorphisms in Turkish patients with CAD and their influence on lipid levels.

Aim:?The study investigated the association of apo B gene EcoRI and XbaI polymorphisms with CAD and with variation in lipid levels (total cholesterol (T-Chol), high-density lipoprotein cholesterol (HDL-Chol), low-density lipoprotein cholesterol (LDL-Chol), and triacylglycerol (TAG)).

Subjects and methods:?The study group was composed of 150 individuals with angiographically documented CAD and 100 angiographically proven to be healthy controls. PCR-RFLP was used to determine the DNA polymorphisms of the apo B gene.

Results:?The frequencies of apo B genotypes detected with EcoRI (AA, AG, GG) and XbaI (CC, CT, TT) did not differ significantly between case and control subjects. A significant association between EcoRI genotypes and T-Chol (p?≤?0.05), and LDL-Chol (p?≤?0.001) was observed only in CAD patients. Patients with the AA genotype had higher levels of serum T-Chol and LDL-Chol compared with AG. With logistic regression analysis the XbaI TT genotype was found to be associated with CAD prevention. However, no significant differences in lipid variables were determined for the XbaI polymorphisms in the patients with CAD.

Conclusions:?Apo B EcoRI genotypes were not found as risk factors for CAD, whereas XbaI TT genotype was detected to prevent against CAD in our study group.

Résumé. Arrière plan: Les résultats des études qui clarifient l’association des marqueurs génétiques du gène B (apo B) de l’alipoprotéine (polymorphismes EcoRI et XbaI) avec la maladie coronarienne (MC), ne sont pas satisfaisants et suggèrent que l’effet est dépendant du contexte (dépendance par rapport au sexe et à l’ethnicité). Cette étude est la première recherche sur les polymorphismes EcoRI et XbaI du gène apo B chez des patients turcs souffrant de MC et sur leur influence sur les niveaux lipidiques.

But: L’étude explore l’association des polymorphismes EcoRI et XbaI du gène apo B avec la MC et avec la variation des niveaux lipidiques?: cholestérol total (Chol-T), cholestérol de lipoprotéines de haute densité (Chol-LHD), cholestérol de lipoprotéines de basse densité (Chol-LBD) et glycéroltriacyl (GTA)

Sujets et méthodes. Le groupe étudié est composé de 150 individus présentant une angiographie de MC et de 100 individus a angiographie saine. La technique de RFLP-PCR a été utilisée pour déterminer les polymorphismes d’ADN du gène apo B.

Résultats: Les fréquences des génotypes de apo B détectées avec EcoRI (AA, AG, GG) et XbaI (CC, CT, TT) ne diffèrent pas significativement entre patients et contrôles. Une association significative entre génotypes EcoRI et Chol-T (p?≤?0,05) ainsi qu’avec Chol-LBD (p?≤?0,001) n’a été observée que chez les patients à MC. Les patients de génotype AA ont un niveau plus élevé que ceux de génotype AG pour les niveaux de Chol-T et de Chol-LBD dans le sérum. Par analyse de régression logistique, on trouve que le génotype XbaI TT est associé à la prévention de la MC. On n’a cependant pas trouvé de différence significative des variables lipidiques qui serait déterminée par les polymorphismes XbaI chez les patients MC.

Conclusion: Les génotypes apo B EcoRI n’apparaissent pas être des facteurs de risque pour la MC, tandis qu’il apparaît que le génotype XbaI TT protège de la MC dans le groupe étudié.

Zusammenfassung. Hintergrund: Die Ergebnisse von Studien, die die Beziehung zwischen genetischen Markern auf dem Apolipoprotein B (Apo B)-Gen und koronarer Herzkrankheit (coronary artery disease, CAD) klären, sind nicht vereinbar und legen nahe, dass der Einfluss vom Zusammenhang abhängt (je nach ethnischer Zugehörigkeit und Geschlecht). Die vorliegende Studie ist die erste Untersuchung von Apo B-Gen-Polymorphismen und ihrem Einfluss auf Lipidspiegel bei Türkischen Patienten mit CAD.

Ziel: Die Studie untersuchte die Beziehung von Apo B-Gen EcoRI- und XbaI-Polymorphismen mit CAD und mit der Schwankung der Lipidspiegel (Gesamtcholesterin (total cholesterol, T-Chol), High-density lipoprotein Cholesterin (HDL-Chol), Low-density lipoprotein Cholesterin (LDL-Chol) und Triacylglycerol (TAG)).

Probanden und Methoden: Die Studiengruppe bestand aus 150 Personen mit angiographisch dokumentierter CAD und 100 angiographisch gesicherten gesunden Kontrollen. PCR-RFLP wurden benutzt um DNS-Polymorphismen des Apo B-Gens zu bestimmen.

Ergebnisse: Die Häufigkeiten der Apo B-Genotypen, die mit EcoRI (AA, AG, GG) und XbaI (CC, CT, TT) bestimmt wurden, unterschieden nicht signifikant zwischen Patienten und Kontrollpersonen. Eine signifikante Beziehung zwischen EcoRI-Genotypen und T-Chol (p?≤?0,05) und LDL-Chol (p?≤?0,001) wurde nur bei CAD-Patienten beobachtet. Patienten mit dem Genotyp AA hatten höhere Serumspiegel von T-Chol und LDL-Chol, verglichen mit AG. Unter Verwendung einer logistischen Regressionsanalyse fand sich, dass der XbaI TT-Genotyp vor CAD schützt. Allerdings wurden keine signifikanten Unterschiede bei den Lipidvariablen hinsichtlich von XbaI-Polymorphismen bei Patienten mit CAD gefunden.

Zusammenfassung: Es wurde nicht gefunden, dass Apo B EcoRI-Genotypen Risikofaktoren für das Auftreten einer CAD darstellen, allerdings zeigte sich in unserer Studiengruppe, dass der XbaI TT-Genotyp gegen CAD schützt.

Resumen. Antecedentes: Los resultados de los estudios que tratan de aclarar la asociación de los marcadores genéticos en el gen de la apolipoproteína B (apo B) (polimorfismos EcoRI y XbaI) con la enfermedad arterial coronaria (EAC), no son consistentes y sugieren que el efecto depende del contexto (es dependiente de la etnicidad y del sexo). El presente estudio constituye la primera investigación sobre los polimorfismos del gen apo B en pacientes turcos con EAC y su influencia sobre los niveles lipídicos.

Objetivo: El estudio investigó la asociación de los polimorfismos EcoRI y XbaI del gen apo B con la EAC y con la variación en los niveles lipídicos (colesterol total (Col-T), colesterol asociado a lipoproteínas de alta densidad (Col-HDL), colesterol asociado a lipoproteínas de baja densidad (Col-LDL) y triacilglicerol (TAG)).

Sujetos y Métodos: El grupo estudiado estaba compuesto por 150 individuos con EAC documentada angiográficamente y 100 controles sanos, comprobados mediante un angiograma. Se utilizó la PCR-RFLP para determinar los polimorfismos del ADN del gen apo B.

Resultados: Las frecuencias de los genotipos apo B detectados con EcoRI (AA, AG, GG) y XbaI (CC, CT, TT) no diferían significativamente entre los casos y los controles. Se observó una asociación significativa entre los genotipos EcoRI y los niveles de Col-T (p?≤?0,05) y Col-LDL (p?≤?0,001), sólo en pacientes con EAC. Los pacientes con el genotipo AA tenían niveles más altos de Col-T y de Col-LDL séricos comparados con los de genotipo AG. Mediante un análisis de regresión logística se encontró que el genotipo XbaI TT estaba asociado con la prevención de la EAC. Sin embargo, en los pacientes con EAC no se encontraron diferencias significativas en las variables lipídicas para los polimorfismos XbaI.

Conclusiones: No se ha encontrado que los genotipos apo B EcoRI sean factores de riesgo para la EAC, mientras que se detectó que el genotipo XbaI TT prevenía contra la EAC en el grupo estudiado.     

Presence of autoantibodies to apolipoprotein A-1 in patients with acute coronary syndrome further links autoimmunity to cardiovascular disease

Anti-apolipoprotein A-1 (Apo A-1) autoantibodies were described in autoimmune disorders such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) and might be involved in the genesis of arterial and venous thrombotic events. To investigate the presence of these autoantibodies in patients with acute coronary syndrome (ACS) without other features of autoimmunity, we set up an enzyme-linked immunosorbent assay (ELISA) for anti-Apo A-1 antibodies. We used it to investigate their prevalence in ACS as compared to SLE and APS and correlated them to plasma Apo A-1 and serum amyloid A protein (SAA) concentrations. The prevalence of anti-Apo A-1 autoantibodies in the healthy control group was 1% (1/92), but was significantly higher in other groups: 21% (11/53) in ACS group (P=0.001), 13% (12/92) in SLE and/or APS group (P=0.005). Multiple linear regression revealed a significant correlation between plasma Apo A-1 (r=-0.72, P=0.013), plasma SAA concentration (r=0.76, P=0.0066) and anti-Apo A-1 IgG titre in ACS patients. The presence of anti-Apo A-1 autoantibodies in patients with ACS highlights an additional link between autoimmunity, inflammation and atherosclerosis.     

内脂素通过上调ACAT1诱导THP-1源性泡沫细胞形成

目的:观察酰基辅酶A:胆固醇酰基转移酶1(ACAT1)在内脂素(visfatin)诱导THP-1源性泡沫细胞形成中的作用,以初步探讨visfatin诱导泡沫细胞形成的分子机制。方法:THP-1单核细胞诱导分化为巨噬细胞,予不同浓度的visfatin(1×10-7~1×10-5mol/L)分别作用0~48小时,运用油红O染色观察细胞浆脂滴变化,酶荧光法检测细胞内总胆固醇(TC)和游离胆固醇(FC)含量,TC与FC之差为胆固醇酯(CE)含量。分别运用RT-PCR和Western blot检测ACAT1 mRNA和蛋白表达。结果:与对照组比较,visfatin干预组细胞浆脂滴明显增多,CE与TC的比值明显增加(>50%)。visfatin呈浓度和时间依赖性地上调ACAT1 mRNA和蛋白表达(P<0.05)。结论:ACAT1表达上调是visfatin诱导THP-1源性泡沫细胞形成的机制之一,这可能为visfatin致动脉粥样硬化发病机制的研究提供一个新的理论依据。     

Levels of plasma and aortic lipids in young exercised rats with a diminished weight gain

Summary Young exercised rats with a diminished weight gain had a decrease in high density lipoprotein (HDL) cholesterol and phospholipid levels in the plasma and augmented free cholesterol and phosphatide in the aorta. When the weight gain in the trained rats paralleled the gain in non-exercised animals, the values of these lipids were not altered. The levels of aortic free cholesterol in the non-exercised and exercised groups were inversely associated with concentrations of HDL-cholesterol, but were not related to the activities of lecithin cholesterol acyltransferase. In addition, the total cholesterol and phospholipid contents in the aorta negatively correlated with HDL-cholesterol concentrations. We propose that in young exercised rats with a diminished weight gain, the removal of aortic lipids is hampered due to a reduction in HDL-cholesterol.     

Lecithin:Cholesterol Acyltransferase (LCAT) Deficiency: Renal Lesions with Early Graft Recurrence

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a rare metabolic disease with lipid deposition in several organs. The authors report a man with hypertension and proteinuria. Renal biopsy revealed glomerular changes, including peculiar thrombus-like deposits, consistent with LCAT deficiency. He was found to be compound heterozygous for two mutations of the LCAT gene. He received a kidney graft from his father. The authors also describe LCAT deficiency-related lesions in the explanted native kidneys and in biopsies at 2 days, 6 weeks, and 1 year after transplantation. The morphology of this disease is characteristic, and the diagnosis should be suspected from the ultrastructural findings.     

冠心病患者来源HDL对小鼠腹腔巨噬细胞脂质沉积及凋亡的影响

目的:探讨冠心病(CAD)患者来源的高密度脂蛋白(HDL)对小鼠腹腔巨噬细胞脂质沉积及凋亡的影响。方法:分离提取健康人群、稳定型冠心病(SCAD)及急性心肌梗死(AMI)患者的HDL,并观察其对氧化型低密度脂蛋白(ox-LDL)诱导的泡沫细胞内脂质沉积及细胞凋亡的影响。采用油红O检测细胞内脂质沉积,用DCFH-DA检测活性氧簇(ROS)的水平,annexin V/PI检测巨噬细胞凋亡率,Western blot检测巨噬细胞ATP结合盒转运体(ABC)A1、ABCG1、Bcl-2和Bax的表达。结果:ox-LDL处理后巨噬细胞脂质沉积增加, ABCA1和ABCG1表达上调(P<0.05);与单纯ox-LDL处理组相比,联合健康人HDL(HDL_healthy)处理后巨噬细胞脂质沉积减少,ABCA1和ABCG1表达上调(P<0.05),而联合SCAD患者HDL(HDL_SCAD)或AMI患者HDL(HDL_AMI)处理后巨噬细胞脂质沉积进一步增加,ABCA1和ABCG1表达下调(P<0.05);与HDL_...     

Serum protein profiles predict coronary artery disease in symptomatic patients referred for coronary angiography

Background

More than a million diagnostic cardiac catheterizations are performed annually in the US for evaluation of coronary artery anatomy and the presence of atherosclerosis. Nearly half of these patients have no significant coronary lesions or do not require mechanical or surgical revascularization. Consequently, the ability to rule out clinically significant coronary artery disease (CAD) using low cost, low risk tests of serum biomarkers in even a small percentage of patients with normal coronary arteries could be highly beneficial.

Methods

Serum from 359 symptomatic subjects referred for catheterization was interrogated for proteins involved in atherogenesis, atherosclerosis, and plaque vulnerability. Coronary angiography classified 150 patients without flow-limiting CAD who did not require percutaneous intervention (PCI) while 209 required coronary revascularization (stents, angioplasty, or coronary artery bypass graft surgery). Continuous variables were compared across the two patient groups for each analyte including calculation of false discovery rate (FDR ≤ 1%) and Q value (P value for statistical significance adjusted to ≤ 0.01).

Results

Significant differences were detected in circulating proteins from patients requiring revascularization including increased apolipoprotein B100 (APO-B100), C-reactive protein (CRP), fibrinogen, vascular cell adhesion molecule 1 (VCAM-1), myeloperoxidase (MPO), resistin, osteopontin, interleukin (IL)-1β, IL-6, IL-10 and N-terminal fragment protein precursor brain natriuretic peptide (NT-pBNP) and decreased apolipoprotein A1 (APO-A1). Biomarker classification signatures comprising up to 5 analytes were identified using a tunable scoring function trained against 239 samples and validated with 120 additional samples. A total of 14 overlapping signatures classified patients without significant coronary disease (38% to 59% specificity) while maintaining 95% sensitivity for patients requiring revascularization. Osteopontin (14 times) and resistin (10 times) were most frequently represented among these diagnostic signatures. The most efficacious protein signature in validation studies comprised osteopontin (OPN), resistin, matrix metalloproteinase 7 (MMP7) and interferon γ (IFNγ) as a four-marker panel while the addition of either CRP or adiponectin (ACRP-30) yielded comparable results in five protein signatures.

Conclusions

Proteins in the serum of CAD patients predominantly reflected (1) a positive acute phase, inflammatory response and (2) alterations in lipid metabolism, transport, peroxidation and accumulation. There were surprisingly few indicators of growth factor activation or extracellular matrix remodeling in the serum of CAD patients except for elevated OPN. These data suggest that many symptomatic patients without significant CAD could be identified by a targeted multiplex serum protein test without cardiac catheterization thereby eliminating exposure to ionizing radiation and decreasing the economic burden of angiographic testing for these patients.

     

Relationship between diabetes mellitus and degree of coronary artery disease in uraemic patients investigated with coronary angiography

Prevalence of cardiovascular disease is high in diabetic patients on renal replacement therapy (RRT); therefore we examined the role of diabetes mellitus on determining the degree of coronary artery stenosis. Twenty-five patients underwent coronary angiography, 12 were awaiting kidney transplantation and the examination was performed regardless of cardiac symptoms, 13 were affected by ischaemic heart disease (IHD). Diabetic and nondiabetic status together with the other risk factors for cardiovascular disease such as age, sex, length of time on RRT, smoking and elevated phosphorus levels history, clinical diagnosis of IHD, cerebrovascular and peripheral vascular disease, mean blood pressure, cholesterol, triglycerides, calcium, phosphate, albumin, haemoglobin, haematocrit and weekly dose of erythropoietin were derived from clinical records. All investigated parameters were matched in diabetic (group 1, n=10) and nondiabetic patients (group 2, n=15) and showed no differences. Clinical evidence of IHD was detected in 80% of patients in group 1 and 46% in group 2 and the percentage of patients on the renal transplant waiting list was not statistically different in the two groups (30 vs 60%). In 60% of patients in group 1 there were 3 or more stenotic lesions equal or greater than 75% of normal reference segment in the major coronary arteries, whilst in 53% in group 2 there were no haemodynamically significant narrowings. Narrowing percentage of the coronaries in group 1 and 2 were: right coronary artery 83 +/- 30 vs 32 +/- 41 (p<0.05), left anterior descending artery 80 +/- 25 vs 44 +/- 34 (p<0.05), left circumflex artery 46 +/- 37 vs 18 +/- 29 (p=0.05) respectively. Our study confirms that IHD is a clinical feature of uraemic diabetic patients and that diabetes is the main cardiovascular risk factor for determining the degree of coronary stenosis.     

冠心病患者心电图ST段改变与多排螺旋CT冠状动脉成像的关系分析

目的:通过对心电图ST段改变及多排螺旋CT冠状动脉成像（MSCTCA）检查在冠心病诊断中的比较分析,探讨冠心病诊断中心电图和MSCTCA检查的方法和作用,为临床诊断提供更多有效的信息。方法:选取临床诊断疑似或确诊为冠心病患者64例,进行心电图和MSCTCA检查,比较两种方法的一致性,不同部位、不同程度及不同类型病变检查的阳性率。结果:与MSCTCA方法相比,心电图ST段改变检查的灵敏度为56.82%,特异度为50%,总体符合率为54.69%,Kappa值为0.061,两种方法检查一致性较差,差异具有显著性（P<0.05）;I/avL/V1-5导联ST段改变阳性患者与Ⅱ/Ⅲ/avF导联ST段改变阳性患者相比,以MSCTCA检查的阳性率更高（P<0.05）;冠状动脉重度狭窄患者与轻度患者相比,心电图ST段改变阳性率显著升高（P<0.05）;中度狭窄患者与轻度患者相比,心电图ST段改变阳性率差异不显著（P>0.05）;多支冠状动脉病变患者心电图ST段改变阳性率显著高于单支管状动脉病变患者（P<0.05）。结论:心电图与MSCTCA检查一致性较差,临床上不宜单独使用单一检查方法;在重度冠状动脉狭窄患者及多支冠状动脉病变患者中,心电图ST段改变检出率较高,结果具有参考价值;I/avL/V1-5导联ST段改变阳性患者相比Ⅱ/Ⅲ/avF导联ST段改变阳性患者,MSCTCA检查阳性率更高,更具有检测意义。     

Testosterone and coronary artery disease in men

Coronary artery disease (CAD) is the leading cardiovascular cause of death, and in men, endogenous testosterone concentrations are inversely related to the extent and severity of CAD. Testosterone is known to affect a number of risk factors for CAD and has effects on vascular tone, vasoreactivity and blood flow of blood vessels beyond the reproductive system, indicating that testosterone may be involved in the pathogenesis of CAD. In this review we will present and discuss the actions of endogenous testosterone and testosterone treatment on risk factors for CAD, on the blood vessel wall and blood flow, and on atheroma development and progression, and discuss the potential for testosterone use in men with CAD.     

Beta-blocker induced changes in the cholesterol: High-density lipoprotein cholesterol ratio and risk of coronary heart disease

Summary The lowering of blood pressure with beta-blocking drugs has had a low impact on coronary heart disease (CHD) mortality and the question has been raised whether adverse changes in plasma lipoproteins offset the benefits of blood pressure reduction. Comparison of plasma lipoprotein concentrations in hypertensive patients treated with commonly used beta-blockers with lipoprotein concentrations in patients with coronary heart disease shows that these drugs cause clinically important shifts in the cholesterol ratio [total cholesterol (TC): high-density lipoprotein cholesterol (HDLC)] and reductions in the atheroprotective lipoprotein HDLC. The magnitude of these changes is sufficient to increase the risk of heart attack two- to four-fold depending on the initial cholesterol ratio and the duration of treatment. Only beta-blockers with marked intrinsic sympathomimetic agonist activity (pindolol) or combined alpha-beta-blocking properties (Labetalol) appear free of adverse effects on plasma lipoproteins and triglycerides. Chronic treatment with other betablockers should be accompanied by cholesterol and HDLC measurements at the beginning of therapy. Plasma lipoprotein measurements at 3–6 month intervals seem mandatory in patients with cholesterol values greater than 6 mmol/l (230 mg/dl) and (TC):HDLC ratios above 5 at the start of treatment. The risk of a coronary event must be regarded as unacceptable when the cholesterol ratio exceeds a critical value of about 6. Further controlled studies are needed to evaluate the effects of beta-blockers in hypertension when administered for periods of up to a year or more. More information is required on the behaviour of lipoprotein subspecies and apoproteins. Since the changes in lipoproteins reported in studies referred to in this review may have been submaximal the risks and the benefits from beta-blocker therapy must be carefully considered.     

Carotid artery stenting in patients with symptomatic coronary artery disease

Carotid artery stenting has been accepted as a potential alternative to carotid endarterectomy in patients with significant carotid artery stenosis. The objective of this study was to evaluate the feasibility, safety and long-term outcome of percutaneous stenting of carotid artery stenosis in patients with coexisting symptomatic coronary disease. Between May 1996 and May 1999, we performed carotid artery stenting at 48 lesions in 36 patients with carotid stenosis of 60% and symptomatic coronary artery stenosis. Twenty-one patients (58%) had neurologic symptoms. Carotid stenting was performed in 43 internal, 2 external and 3 common carotid lesions. We used Wallstent in 46 lesions, Palmaz stent in 2 lesions and Microstent II in 1 lesion. Staged or combined coronary intervention was performed in 18 patients (50%) and staged coronary artery bypass surgery was performed in 6 patients (17%). In the other 12 patients (33%), medical treatments were performed. Carotid stenting was successful in all lesions. Simultaneous bilateral carotid stenting was performed in 11 patients (31%). One major and 1 minor stroke developed during the procedure. There were no deaths during the procedures and within 30 days post-procedure. During the follow-up of 14 +/- 7 (3 to 40) months, there were no deaths or neurological events. On follow-up (6 +/- 1 months) angiography and/or duplex sonography of 44 eligible lesions in 32 patients, there were 2 cases of asymptomatic restenosis (4.5%) which developed in Palmaz stents implanted at the external carotid artery and the common carotid artery, respectively. In conclusion, carotid artery stenting in patients with coexistent carotid and coronary artery disease is feasible, safe and shows favorable follow-up outcomes.     

Risk factor reduction in progression of angiographic coronary artery disease

Introduction

To investigate differences between outpatients with progressive and nonprogressive coronary artery disease (CAD) measured by coronary angiography.

Material and methods

Chart reviews were performed in patients in an outpatient cardiology practice having ≥ 2 coronary angiographies ≥ 1 year apart. Progressive CAD was defined as 1) new non-obstructive or obstructive CAD in a previously disease-free vessel; or 2) new obstruction in a previously non-obstructive vessel. Coronary risk factors, comorbidities, cardiovascular events, medication use, serum low-density lipoprotein cholesterol (LDL-C), and blood pressure were used for analysis.

Results

The study included 183 patients, mean age 71 years. Mean follow-up duration was 11 years. Mean follow-up between coronary angiographies was 58 months. Of 183 patients, 108 (59%) had progressive CAD, and 75 (41%) had nonprogressive CAD. The use of statins, β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and aspirin was not significantly different in patient with progressive CAD or nonprogressive CAD Mean arterial pressure was higher in patients with progressive CAD than in patients with nonprogressive CAD (97±13 mm Hg vs. 92±12 mm Hg) (p<0.05). Serum LDL-C was insignificantly higher in patients with progressive CAD (94±40 mg/dl) than in patients with nonprogressive CAD (81±34 mg/dl) (p=0.09).

Conclusions

Our data suggest that in addition to using appropriate medical therapy, control of blood pressure and serum LDL-C level may reduce progression of CAD.     

正常中国人及内源性高甘油三酯血症患者酰基辅酶A:胆固醇酰基转移酶基因多态性的研究

目的 研究酰基辅酶A:胆固醇酰基转移酶1(acyl-coenzyme A:cholesterol acyltransferase 1,ACAT1)基因rs1044925多态性是否与正常汉族中国人及内源性高甘油三酯血症(hypertriglyceridemia,HTG)患者血脂及载脂蛋白水平存在关联.方法 应用聚合酶链反应-限制性片段长度多态性分析法,对成都地区372名汉族人(267名正常人和105例内源性高甘油三酯血症患者)ACAT1基因rs1044925多态位点进行分析.结果 中国人ACAT1基因rs1044925多态位点C等位基因频率为0.137,显著低于中部和南部欧洲人的0.354(P＜0.05);HTG组和对照组C等位基因频率分别为0.153和0.137,两者之间差异无统计学意义.对照组AA基因型携带者血清低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)和非高密度脂蛋白胆固醇(non-high density lipoprotein cholesterol,nHDL-C)水平均较C等位基因携带者(Ac和CC基因型者)显著升高[(3.25±0.68)mmol/L vs(3.03±0.87)mmol/L,P＜0.05;(3.80±0.71)mmol/L vs(3.23±0.82)mmol/L,P＜0.05],HTG组AA基因型携带者血清高密度脂蛋白胆固醇(high density lipoprotein-cholesterol,HDL-c)水平较C等位基因携带者显著升高[(1.00±0.28)mmol/L vs(0.87±0.17)mmoL/L,P＜0.05].结论 ACAT1 基因rs1044925多态性不仅与正常中国成都地区汉族人血清LDL-C、nHDL-C含量有关,而且还与内源性高甘油三酯血症患者血清HDL-C水平相关联.