冠心病家族史少年儿童血清脂蛋白（a）的研究

对５４例有冠心病（ＣＨＤ）家族史和１０７例无ＣＨＤ家族史（作对照组）少年儿童检测血清脂蛋白（ａ）［Ｌｐ（ａ）］、载脂蛋白Ａ－Ｉ（ａｐｏＡ－Ｉ）、载脂蛋白Ｂ（ａｐｏＢ）水平及身高、体重五项指标。结果显示：（１）有ＣＨＤ家族史组Ｌｐ（ａ）平均值为１９８．６ｍｇ／Ｌ，对照组则为１３６．０３ｍｇ／Ｌ，两组有差异显著性（Ｐ＜０．０１）；（２）有ＣＨＤ家族史组Ｌｐ（ａ）增高的频率也明显高于对照组；（３）Ｌｐ（ａ）水平与体重无显著相关，与ａｐｏＡ－Ｉ、ａｐｏＢ、年龄和身高也均无相关性。     

脂蛋白(a)和载脂蛋白(a)多态性与女性冠心病的相关性研究

冠心病在病因、发病年龄等诸多方面存在性别差异。载脂蛋白（ａ）多态性与脂蛋白（ａ）血浆水平对女性冠心病影响的资料甚少。我们通过检测３５例女性冠心病患者和４５例女性正常对照者的载脂蛋白（ａ）多态表型及脂蛋白（ａ）水平，并与相应的男性组对比分析，发现含有等位基因Ｓ１、Ｓ２、Ｂ的载脂蛋白（ａ）低分子量表型的冠心病患者，女性占３７．１４％，显著高于对照组；而男性仅占２５．７１％，与对照组比较差异无显著性。在女性体内载脂蛋白（ａ）低分子量表型发生冠心病的危险度为对照组的４．７倍；在男性中仅为１．４倍。结果提示：载脂蛋白（ａ）低分子量表型对女性冠心病的影响大于男性。脂蛋白（ａ）水平在两性冠心病患者中均明显高于对照组，而两性之间的差异无显著性。     

冠心病患者血清脂蛋白（a）浓度变化

观察不同类型冠心病（ＣＨＤ）患者３１０例和正常对照１４０例血清脂蛋白（ａ）［Ｌｐ（ａ）］等变化。结果：血清Ｌｐ（ａ）水平，在各类ＣＨＤ及正常对照组中的分布均呈正偏态，对数及平方根变量变换可使其分布正态化；在ＣＨＤ各种临床类型中均显著高于正常对照；心肌梗塞患者中急性期高于陈旧性者，且前者在第１４天组最高；在心绞痛患者中劳力型高于自发型者。对陈旧心肌梗塞、心绞痛及正常对照者的生理参数、病史及血脂等诸因素，进行多元逐步回归后仅发现Ｌｐ（ａ）水平只与冠状动脉狭窄程度明显相关（Ｂｅｔａ＝０．５８１）。另外，ＣＨＤ合并脂肪肝者Ｌｐ（ａ）水平降低。     

载脂蛋白A多态性在老年冠心病中检测的临床意义

目的探讨老年冠心病（ＣＨＤ）和健康老年人载脂蛋白Ａ（ＡｐｏＡ）异构体多态性表型、脂蛋白（ａ）［Ｌｐ（ａ）］及血脂水平的临床关系。方法检测１０４例老年ＣＨＤ患者（陈旧性心肌梗塞３１例，稳定型心绞痛３８例，心律失常型２０例，心力衰竭型１５例）血清ＡｐｏＡ异构体多态性表型和血清Ｌｐ（ａ）及血脂水平，并与６８例健康老年人对照分析。结果ＣＨＤ组Ｌｐ（ａ）和血脂水平明显高于对照组（Ｐ＜０．０５或Ｐ＜０．０１）。ＣＨＤ组ＡｐｏＡ表型检出率为８２．７％，对照组为７５％。ＡｐｏＡ表型频率分布与ＡｐｏＡ表型分子量呈非常显著正相关（ＣＨＤ组ｒ＝０．９９２７，对照组ｒ＝０．９６９７，Ｐ＜０．０１）。结论ＡｐｏＡ多态性表型在临床上比Ｌｐ（ａ）及血清脂质更具有参考价值。     

脂蛋白(a)的生化特征与动脉粥样硬化

血清高浓度的脂蛋白（ａ）［Ｌｐ（ａ）］是动脉粥样硬化（ＡＳ）形成的独立危险因素，它与低密度脂蛋白（ＬＤＬ）有许多不同，作为Ｌｐ（ａ）特征性结构的载脂蛋白（ａ）［ａｐｏ（ａ）］与纤维蛋白溶酶原（ｐｌｇ）非常相似，Ｌｐ（ａ）是血脂与纤溶系统之间的桥梁。本文将对Ｌｐ（ａ）的结构、理化特征、基因、代谢、与ＡＳ形成的关系、检测方法及其临床意义等问题作一综述。     

老年缺血性心脑血管疾病患者脂蛋白（a）的观察

本文测定１６２例老年住院患者和３８例健康老人血清脂蛋白（ａ）［Ｌｐ（ａ）］水平。分析结果显示老年冠心病（ＣＨＤ）、脑梗塞（ＣＭ）患者Ｌｐ（ａ）浓度明显高于健康组和其他疾病组（Ｐ＜０．０１或Ｐ＜０．０５）。高Ｌｐ（ａ）血症的检出率ＣＨＤ组、ＣＭ组亦分别高于健康组及其他疾病组（Ｐ＜０．０１或Ｐ＜０．０５）。Ｌｐ（ａ）水平不受饮食和降脂药物等影响。认为脂蛋白（ａ）是缺血性心脑血管疾病的独立危险因素之一。提出Ｌｐ（ａ）可作为临床缺血性心脑血管疾病的重要预测指标。     

脂蛋白（a）的研究进展

脂蛋白（ａ）的研究进展广州市第一人民医院心内科罗义综述郭南山审校自从Ｂｅｒｇ于１９６３年发现脂蛋白（ａ）［Ｌｐ（ａ）］以来，大量的流行病学资料表明［１－４］，血浆Ｌｐ（ａ）水平高与冠心病（ＣＨＤ）的发病密切相关，但至今只报道了四个前瞻性研究［５］。Ｌ...     

脂蛋白（a）与冠心病

１９６３年Ｂｅｒｇ应用免疫吸附技术研究不同个体间脂蛋白差异时发现一种新的抗原，它在血浆中的浓度受单基因控制，按免疫基因学命名为脂蛋白（ａ）［Ｌｐ（ａ）］。Ｌｐ（ａ）分子量（４～６）×１０６，密度１．０５０～１．１２ｇ／ｍｌ，基因位于６号染色体长臂。Ｌ...     

陈旧性心肌梗塞者血胆固醇低水平的临床意义

本文观察了１９８例老年及老年前期陈旧性心肌梗塞患者的血脂质和载脂蛋白的变化，重点探讨血胆固醇不高患者的致病因素，特别是脂蛋白（ａ）〔Ｌｐ（ａ）〕的临床意义。结果显示，Ｉ组（ＴＣ＞３．８８ｍｍｏｌ／Ｌ）的ＴＣ、ＴＧ、ＬＤＬ－Ｃ和ＡｐｏＢ水平均高于Ⅱ组（ＴＣ≤３．８８ｍｍｏｌ／Ｌ）（Ｐ＜０．０５～０．００１），但Ｌｐ（ａ）水平却明显低于Ⅱ组（Ｐ＜０．０５），高脂蛋白血症［Ｌｐ（ａ）＞０．３ｇ／Ｌ］的发生率也明显低于Ⅱ组（２７．４％比４８．２％）。ＨＤＬ－Ｃ和ＡｐｏＡ１水平在２组间无显著差异。由此提示，Ｌｐ（ａ）作为心肌梗塞的危险因素，可能不依赖于ＴＣ、ＬＤＬ－Ｃ而发挥作用。因此对血胆固醇不高的心肌梗塞患者应特别注意监测Ｌｐ（ａ）水平，在心肌梗塞后的二级预防中对于高脂蛋白血症者宜采取适当措施。     

老年急性心肌梗塞患者脂蛋白（a）、脂质过氧化物及红细胞变形能力的变化

观察老年急性心肌梗塞（ＡＭＩ）患者３２例、心绞痛患者４５例和对照组５０例的血清脂蛋白（ａ）［Ｌｐ（ａ）］、过氧化脂质（ＬＰＯ）及红细胞变形能力（ＲＣＤ）的变化．结果表明：ＡＭＩ组的血清Ｌｐ（ａ）、ＬＰＯ及ＲＣＤ均高于其他两组，且具明显性差异。相关分析表明，Ｌｐ（ａ）的变化与ＬＰＯ、ＲＣＤ无关，而ＬＰＯ的升高与ＲＣＤ的降低呈一定的线性相关（Ｐ＜０．０１），进一步证实了Ｌｐ（ａ）是冠心病的独立危险因素，ＬＰＯ、ＲＣＤ的变化亦是冠心病加重的重要因素。Ｌｐ（ａ）、ＬＰＯ及ＲＣＤ的检测对ＡＭＩ的诊断及预防有一定的指导意义。降低Ｌｐ（ａ）、清除ＬＰＯ、改善ＲＣＤ是治疗ＡＭＩ及改善其预后的重要手段。     

Apolipoprotein (a) phenotypes and lipoprotein (a) concentrations in patients with type III hyperlipoproteinaemia

Abstract. Objectives . The familial lipoprotein disorder type III hyperlipoproteinaemia (HLP) carries a marked increase in the risk of accelerated and premature atherosclerosis, but there is considerable variation amongst affected individuals in their susceptibility to cardiovascular disease (CVD). Therefore, it was the aim of our study to investigate the possible influence of lipoprotein (a) [Lp(a)] in the pathogenesis of type III HLP. Design . Apolipoprotein (a) [apo(a)] phenotypes and Lp(a) concentrations were determined in patients with the disease and in an appropriate control group. Setting . University out-patient lipid disorder clinic. Subjects . Seventy-six apoE-2 homozygous patients with type III HLP and 76 normolipidaemic and healthy age- and sex-matched controls. Main outcome measures . The frequencies of different apo(a) phenotypes and their correlations with Lp(a) serum concentrations were determined in patients and controls. Results . Lp(a) concentrations were not significantly different in type III HLP patients (14.1±19.1 mg dl^-1) as compared with the controls (13.3±16.2 mg dl^-1; P = 0.549, NS). In addition, there was no significant difference in apo(a) phenotype frequencies amongst both groups (0.2 > P > 0.1). Conclusions . We conclude that the apo(a) polymorphism does not participate (to a significant extent) in the phenotypical expression of type III HLP.     

Serum lipoprotein(a) concentrations and apolipoprotein(a) phenotypes in the families of NIDDM patients

Summary We studied the quantitative and qualitative characteristics of lipoprotein(a) [Lp(a)] as a function of apolipoprotein(a) [apo(a)] phenotype in 87 members (42 males, 45 females) of 20 diabetic families, 26 of whom were diagnosed with non-insulin-dependent diabetes mellitus (NIDDM) with moderate glycaemic control (HbA_1c7.1±1.2%). Apo(a) phenotyping was performed by a sensitive, high-resolution technique using SDS-agarose/gradient PAGE (3–6%). To date, 26 different apo(a) phenotypes, including a null type, have been identified. Serum Lp(a) levels of NIDDM patients and non-diabetic members of the same family who had the same apo(a) phenotypes were compared, while case control subjects were chosen from high-Lp(a) non-diabetic and low-Lp(a) non-diabetic groups with the same apo(a) phenotypes in the same family. Serum Lp(a) levels were significantly higher in NIDDM patients than in non-diabetic subjects (39.8±33.3 vs 22.3±19.5 mg/dl, p<0.05). The difference in the mean Lp(a) level between the diabetic and non-diabetic groups was significantly (p<0.05) greater than that between the high-Lp(a) non-diabetic and low-Lp(a) non-diabetic groups. An analysis of covariance and a least square means comparison indicated that the regression line between serum Lp(a) levels [log Lp(a)] and apo(a) phenotypes in the diabetic patient group was significantly (p<0.01) elevated for each apo(a) phenotype, compared to the regression line of the control group. These data, together with our previous findings that serum Lp(a) levels are genetically controlled by apo(a) phenotypes, suggest that Lp(a) levels in diabetic patients are not regulated by smaller apo(a) isoforms, and that serum Lp(a) levels are greater in diabetic patients than in non-diabetic family members, even when they share the same apo(a) phenotypes.Abbreviations Lp(a) Lipoprotein(a) - apo(a) apolipoprotein(a) - NIDDM non-insulin-dependent diabetes mellitus - TC total cholesterol - LDL low density lipoprotein - TG triglycerides - HDL-C high density lipoprotein-cholesterol - LDL-C low density lipoprotein-cholesterol - PBS phosphate buffered saline The first two authors contributed equally to this work     

Single nucleotide polymorphisms in the apo(a) kringle IV type 8 domain are not associated with atherothrombotic serum lipoprotein (a) concentration, in a Portuguese paediatric population

Lipoprotein (a) (Lp[a]) is a complex of apolipoprotein (a) (apo[a]) and low-density lipoprotein (LDL), associated with atherothrombotic disease. Most of the interindividual variations in plasma levels of Lp(a) can be attributed to sequence differences linked to the apo(a) gene locus. The aim of this study was to investigate a possible link between single nucleotide polymorphisms (SNPs) in the apo(a) kringle (K) IV type 8 domain and atherothrombotic serum Lp(a) concentrations. Direct sequencing of the two exons and flanking intronic sequences of the apo(a) K IV type 8 domain was performed in a group of 97 paediatric patients, 51 with serum Lp(a) concentration above and 46 with concentration below 30 mg/dl,. We found three SNPs, two in exon 1 (c.66A>C and c.133G>A) and one in intron 1 (c.160+1G>A). The c.66A>C polymorphism was the most common with a heterozygosity frequency of 15.46%. The c.133G>A and c.160+1G>A polymorphisms were found at a frequency of 5.15% and 1.03%, respectively. No statistically significant difference was found in the genotype distribution between the two groups of patients. Our results suggest that these SNPs in the apo(a) K IV 8 domain are not directly associated with atherothrombotic serum Lp(a) concentration in our population.     

老年2型糖尿病患者血清脂蛋白(a)水平与载脂蛋白(a)基因多态性分析

本文对老年 2型糖尿病患者血清脂蛋白 (a)水平及载脂蛋白 (a)多态性进行了分析 ,以探讨老年糖尿病与高脂蛋白 (a)血症的关系及其载脂蛋白 (a)遗传表型的分布特点 ,同时分析脂蛋白 (a)与糖尿病并发症的相关性。用酶联免疫吸附法测定脂蛋白 (a)水平 ,用十二烷基磺酸钠 -聚丙烯酰胺凝胶电泳和Westernblot技术测定脂蛋白(a)遗传表型。结果发现 :① 3组 (老年 2型糖尿病、非老年 2型糖尿病与老年健康对照组 )脂蛋白 (a)浓度差异无统计学意义 (P >0 .0 5 ) ,脂蛋白 (a)与血清总胆固醇、甘油三酯、高密度脂蛋白胆固醇及其亚型、低密度脂蛋白胆固醇、载脂蛋白A和B水平无相关性 (P >0 .1) ;②老年 2型糖尿病组合并高血压、糖尿病性视网膜病变和糖尿病肾病者的血清脂蛋白 (a)浓度明显高于无合并相应疾病者 (P <0 .0 5或P <0 .0 0 1) ;③ 3组共检出 13种载脂蛋白 (a)基因型 ,在老年 2型糖尿病合并症患者中 ,低分子质量的S1和S2基因型明显多于其它组及无合并症者     

Lipoprotein (a) Immunapheresis in the Treatment of Familial Lipoprotein (a) Hyperlipoproteinemia in a Patient with Coronary Heart Disease

Abstract: This paper reports 2 years' experience with lipoprotein (a) (Lp[a]) immunapheresis which was successfully handled on a now 40-year-old patient with familial Lp(a) hyperlipoproteinemia inducing severe coronary heart disease with 2 myocardial infarctions and diffuse coronary sclerosis. Continued treatment by Lp(a) immun-absorption with specific sheep antibodies reduced stenosis in coronary vessels more than 50% and stopped the progression of coronary heart disease. A special apheresis technique and the results of continued absorption effects are described.     

脂蛋白(a)与心血管疾病的关系

脂蛋白(a)[Lp(a)]结构类似于低密度脂蛋白(LDL),高水平Lp(a)是一种公认的心血管疾病危险因子。体内存在氧化型Lp(a)更易于促进动脉粥样硬化的发生发展。Lp(a)中的载脂蛋白(a)[apo(a)]存在异质性,研究显示其危险性可能是由于apo(a)等位基因水平差异引起的,而且apo(a)的多态性影响到Lp(a)水平的临床测定,如何降低apo(a)对结果的影响还需要更多深入研究。目前针对高Lp(a)水平的人群尚无统一的治疗标准,但降脂治疗有益于预防心脑血管疾病的发生。     

脂蛋白(a)的研究进展

脂蛋白(a)是动脉粥样硬化形成与进展的高危因素,外周血中高浓度的脂蛋白(a)已成为冠心病公认的预测因子。由于它主要受遗传调控,饮食、运动、生活方式、传统降脂药物等对脂蛋白(a)水平的影响很小。随着研究的深入,脂蛋白(a)的代谢、致病机制和危害逐渐被人们了解,氧化修饰后的脂蛋白(a)具有更强的致动脉粥样硬化作用。此外,可降低脂蛋白(a)的新型降脂药物已经被研发出来,它们降低脂蛋白(a)的强度和作用靶点各不相同,对疾病的预后的影响也仍有待观察。本文就脂蛋白(a)的代谢、遗传调控、氧化修饰、临床干预手段等研究进展作一综述。     

脂蛋白(a)与动脉粥样硬化研究进展

脂蛋白(a)由低密度脂蛋白和载脂蛋白(a)组成.高血浆脂蛋白(a)水平是动脉粥样硬化和心血管疾病的独立危险因素.脂蛋白(a)不但能参与动脉粥样硬化斑块的形成,还能影响抗炎机制和血管壁中促凝与抗凝因子的平衡.血浆脂蛋白(a)水平的个体差异很大,主要受遗传因素控制.血浆脂蛋白(a)水平对药理和非药理因素都不敏感,临床上缺乏高效安全降低脂蛋白(a)水平的治疗方法.近年,科研工作者发现反义寡核苷酸链和人工合成的肽链等可以降低脂蛋白(a)水平,但用于临床治疗还需进一步研究.本文拟对近年来脂蛋白(a)与动脉粥样硬化研究的新进展进行综述.     

Urinary excretion of apo(a) fragments in NIDDM patients

Summary Lp(a), one of the most atherogenic lipoproteins, is believed to contribute significantly to vascular diseases in non-insulin-dependent diabetic (NIDDM) patients. Contradictive data have been published on these patients concerning plasma concentrations of Lp(a) and their relation to renal function. Since apo(a) fragments appear in urine, we measured urinary apo(a) in 134 NIDDM patients and 100 matched controls and related urinary apo(a) concentrations to plasma Lp(a) levels and kidney function. Plasma Lp(a) values were found to be significantly higher in NIDDM patients. NIDDM patients also secreted significantly more apo(a) into their urine as compared to control subjects. There was no correlation between creatinine clearance or albumin excretion and urinary apo(a) concentrations. Patients with macroalbuminuria exhibited a twofold higher apparent fractional excretion of apo(a) in comparison to patients with normal renal function. Urinary apo(a) values in both patients and control subjects were highly correlated to plasma Lp(a), yet no correlation was found with HbA_{1 c} or serum lipoproteins. It is concluded that urinary apo(a) excretion is correlated to plasma Lp(a) levels but not to creatinine clearance in patients suffering from NIDDM. [Diabetologia (1997) 40: 1455–1460] Received: 26 May 1997 and in revised form: 21 July 1997