oxLDL,Lp（a）与脑血管疾病的关系

测定５１例脑血管病和２０例对照组的血浆ｏｘＬＤＬ和血清Ｌｐ（ａ）。结果脑血管病组明显高于对照组，脑血管病各分组（脑出血、脑栓塞、蛛网膜下腔出血）的ｏｘＬＤＬ亦高于对照组，脑出血、脑梗塞分组的Ｌｐ（ａ）高于对照组。ｏｘＬＤＬ及Ｌｐ（ａ）异常与患者的性别、年龄、病程及常规血脂检查异常率无相关。结论：ｏｘＬＰＬ、Ｌｐ（ａ）升高与脑血管病发病密切相关，是估价中风危险因素重要的、独立的脂蛋白参数之一。     

Lipoprotein (a), LPA Ile4399Met,and Fibrin Clot Properties

Introduction

Elevated lipoprotein(a) (Lp(a)) levels were reported to be associated with dense fibrin clots. The apo(a) component of Lp(a) is encoded by LPA, and the Met allele of the LPA Ile4399Met polymorphism is associated with elevated Lp(a) levels and cardiovascular disease risk. We investigated whether Ile4399Met was associated with fibrin clot properties.

Materials and Methods

We determined plasma Lp(a) levels, fibrin clot permeability and lysis time for 64 LPA 4399Met carriers and 128 noncarriers matched for age, sex, ethnicity, and enrollment site.

Results

Elevated Lp(a) levels were associated with reduced clot permeability and prolonged lysis time (P < 0.0001). Carriers of 4399Met had higher Lp(a) levels compared with noncarriers (P = 0.0003). However, this association differed by ethnicity (P = 0.003 for interaction between genotype and ethnicity): compared with noncarriers, 4399Met carriers had 2.89 fold higher Lp(a) levels among Caucasians while no difference was observed among non-Caucasians (primarily East Asians and Hispanics). Among all subjects, no association was observed between Ile4399Met and clot properties, but this relationship also differed by ethnicity: among non-Caucasians, 4399Met carriers had increased clot permeability and shorter lysis time; whereas among Caucasians, the trend was for decreased permeability and longer lysis time (P < 0.01 for interactions between genotype and ethnicity).

Conclusions

We confirmed that elevated Lp(a) levels are associated with dense fibrin clots, and found that the association of LPA 4399Met carriers and clot permeability as well as lysis time differ by ethnicity.     

脑梗塞患者血清脂蛋白（a）测定及其临床意义

应用酶标法测定58例脑梗塞患者和56例健康对照者血清脂蛋白(a)[LP(a)]含量,并同时测定了其他脂代谢指标,对其中26例脑梗塞患者还测定了血浆纤维蛋白溶解(简称纤溶)指标。结果表明脑梗塞组存在显著的脂代谢和纤溶功能紊乱。LP(a)含量增高,与所测脂代谢、纤溶指标无显著相关,是脑梗塞发病独立的危险因素。     

Combination of High-Density Lipoprotein Cholesterol and Lipoprotein(a) as a Predictor of Collateral Circulation in Patients With Severe Unilateral Internal Carotid Artery Stenosis or Occlusion

Background and PurposeCollateral circulation is considered an important factor affecting the risk of stroke, but the factors that affect collateral circulation remain unclear. This study was performed to identify the factors associated with collateral circulation, especially blood lipids.MethodsThe study involved patients who had undergone digital subtraction angiography and were confirmed as having severe unilateral stenosis or occlusion of the internal carotid artery (ICA). We classified the collateral circulation status of each patient as good (Grade 3 or 4) or poor (Grade 0, 1, or 2) according to the grading system of the American Society of Interventional and Therapeutic Neuroradiology/American Society of Interventional Radiology. We collected data on patients’ characteristics and identified the factors that affect collateral circulation.ResultsThis study included 212 patients. The multivariate logistic regression analysis showed that the high-density lipoprotein cholesterol (HDL-C) concentration and a complete anterior half of the circle of Willis were independent protective factors for good collateral circulation, whereas elevated lipoprotein(a) [Lp(a)] and serum creatinine concentrations were independent risk factors for good collateral circulation. The area under the receiver operating characteristics curve (AUC) was 0.68 (95% confidence interval [CI], 0.61–0.76) for HDL-C and 0.69 (95% CI, 0.62–0.76) for Lp(a). A binary logistic regression model analysis of the joint factor of HDL-C and Lp(a) yielded an AUC of 0.77 (95% CI, 0.71–0.84).ConclusionsIn patients with severe unilateral ICA stenosis or occlusion, the combination of HDL-C and Lp(a) is a useful predictor of collateral circulation.     

血清脂蛋白（a）与缺血性脑卒中关系的临床研究

目的探讨脂蛋白（a）（Lp（a））是否为缺血性卒中的危险因素,以及Lp（a）水平与缺血性脑卒中类型和预后的关系。方法将缺血性脑卒中患者按急性卒中治疗低分子肝素试验．TOAST）分型标准分为心源性脑栓塞（CE）、大动脉粥样硬化性卒中（LAA）、小动脉卒中（SAA）、其他原因引发的缺血性卒中（SOE）和原因不明的缺血性卒中（SUE）。以同期入院的非脑卒中患者（经头颅CT或磁共振排除）作为对照组。病例组和对照组均于入院次日清晨空腹抽取静脉血,测定Lp（a）及其他各项血脂指标,并于入院及病程两周时分别行NHISS评分评估神经功能缺损程度,分析Lp（a）与卒中类型及NIHSS评分之间的关系。结果缺血性脑卒中组Lp（a）浓度及异常率均高于对照组（P〈0．05）,Lp（a）进入大动脉粥样硬化卒中患病因素的回归方程Lp（a）水平与卒中患者的NIHSS评分无相关性（P〉0．05）。结论高浓度Lp（a）可能参与了缺血性脑卒中的发生,并且可能是大动脉粥样硬化性卒中发生的危险因素,但与神经功能缺失程度和早期功能修复无关。     

缺血性脑血管病患者颈动脉斑块与TXB2、OxLDL、Lp(a)、Hcy相关性分析

目的探讨缺血性脑血管病的颈动脉斑块与TXB2、OxLDL、Lp(a)、Hcy的相关性,以更好的对该病进行预防、治疗。方法35例急性缺血性卒中患者和20名正常对照组行颈动脉血管彩色多普勒超声检测颈动脉斑块,采用ELISA双抗体夹心法测定血浆TXB2、OxLDL、Lp(a),采用荧光偏振免疫分析法测定Hcy的含量,两组相比,并作相关性分析。结果斑块最大厚度、血浆TXB2、OxLDL、Lp(a)、Hcy的含量均高于正常对照组(P<0.01)。斑块最大厚度与TXB2、OxLDL、Lp(a)呈正相关。结论颈动脉斑块,血浆TXB2、OxLDL、Lp(a)、Hcy可能与缺血性脑血管病相关;TXB2、OxLDL、Lp(a)可能参与促进颈动脉粥样硬化斑块的形成。     

Lipoprotein (a) in patients with spontaneous venous thromboembolism

INTRODUCTION: Elevated lipoprotein (a) (Lp (a)) has been established as a risk factor of coronary heart disease and stroke. Findings concerning the risk of venous thromboembolism (VTE) in adults are contradictory. The aim of our study was to investigate, whether elevated Lp (a) levels are an independent risk factor of spontaneous symptomatic venous thromboembolism (VTE). Our study was further designed to detect differences in risk profiles between thrombosis patients with and without symptomatic PE. MATERIALS AND METHODS: We investigated Lp (a) in 128 patients with spontaneous symptomatic deep vein thrombosis (DVT, group 1), 105 with spontaneous symptomatic pulmonary embolism with or without DVT (PE, group 2) and 122 healthy controls. Lp (a) was measured with an immunoturbidimetric assay (Tina-quant(R), Roche, Grenzach-Wyhlen, Germany) on a Hitachi-Modular system. RESULTS: Lp (a) levels (mg/L) were not significantly different among groups, median levels (25th-75th percentiles) were 170 (51-386) in group 1, 140 (<20-427) in group 2 and 126 (54-331) in controls, respectively. As continuous variable, odds ratios for VTE for a 100 mg/L increase of Lp (a) were 1.1 [95% confidence interval 0.98-1.2] for group 1 versus controls and 1.1 [0.95-1.2] for group 2 versus controls. The prevalence of Lp (a) above 300 mg/L was not significantly different among patients and controls (group 1: 30%, group 2: 32% and controls: 25%, p=0.4, p=0.2, respectively). CONCLUSIONS: In conclusion we found no association between Lp (a) and VTE regardless whether DVT occurred together with PE or not.     

Apolipoprotein (a) mediates the lipoprotein (a)-induced biphasic shift in human platelet cyclic AMP

Lipoproteins are known to influence platelet cyclic adenosine monophosphate (c-AMP) levels. Lipoprotein (a) (Lp(a))'s impact on platelet c-AMP levels has never been assessed. Increasing levels of purified human Lp(a) (1–100) mg/dl were incubated with washed human platelets. Lp(a) concentrations of 1–25 mg/dl resulted an initial statistically significant increase of platelet c-AMP above basal levels and decreased collagen-stimulated platelet aggregation levels. Higher concentrations progressively returned the platelet c-AMP concentrations to basal levels accompanied by further decreases in platelet aggregation. Increasing concentrations of purified apolipoprotein (a) (apo(a)) also resulted in a similar biphasic c-AMP response while Lp(a) without apo(a) was without impact. One antibody directed against apo(a) in intact Lp(a) removed the biphasic c-AMP pattern and eliminated Lp(a) platelet aggregation. Antibodies directed against apo B in intact Lp(a) gave results similar to intact Lp(a) in terms of the biphasic response of c-AMP upon platelet exposure to increasing levels of Lp(a). It is concluded that apo(a) mediates the Lp(a)-induced biphasic response in platelet c-AMP as the result of platelet exposure to increasing levels of Lp(a). The biphasic response in c-AMP assists in platelet aggregation decreases up to a concentration of 25 mg/dl Lp(a), such assistance being lost at higher Lp(a) concentrations.     

Focal Atrophy and Cerebrovascular Disease Increase Dementia Risk among Cognitively Normal Older Adults

BACKGROUND AND PURPOSE: This study investigated the association of medial temporal lobe (MTL) atrophy and cerebrovascular disease (white matter hyperintensities [WMH], subclinical infarcts) with the risk of developing Alzheimer's disease (AD) among cognitively normal older adults. METHODS: Risk of developing AD was examined for 155 cognitively normal older adults (77.4 years, 60% women, 81% white). The MTL volumes and the presence of WMH and of subclinical infarcts were determined from brain magnetic resonance imaging (MRI) at the beginning of the study. Follow-up cognitive evaluations (average 4.3 years) identified those who developed AD. RESULTS: The presence of either MTL atrophy or subclinical infarcts was independently and significantly associated with a greater risk to develop AD (OR [95% CI]: 4.4 [1.5, 12.3] and 2.7 [1.0, 7.1], respectively). In addition, those participants with both MTL atrophy and at least one brain infarct had a 7-fold increase in the risk of developing AD (OR [95% CI]: 7.0 [1.5, 33.1]), compared to those who had neither of these conditions. CONCLUSIONS: In cognitively normal older adults, markers of neurodegeneration (as reflected by MTL atrophy) and of cerebrovascular disease (as reflected by infarcts on MRI) independently contribute to the risk to develop AD.     

Dual inverse effects of lipoprotein(a) on the dementia process in Japanese late-onset Alzheimer's disease

Background: The role of lipoprotein metabolism in the dementia process has attracted increasing attention. It is universally accepted that apolipoprotein E4 (ApoE) is a risk factor for late‐onset Alzheimer's disease, however, the role of lipoprotein(a) (Lp(a)) remains unclear. Therefore, we conducted the present study to clarify the association between Lp(a) and dementia. Methods: Lipoprotein(a) serum concentrations were examined in relation to ApoE phenotypes and periventricular lucency (PVL) on brain computed tomography in 150 patients with late‐onset Alzheimer's disease (AD group), compared with 46 patients with vascular dementia (VaD group) and 150 controls without dementia. Results: The incidences of hypertension, hypercholesterolaemia, and severe PVL were significantly higher in the VaD group than in the AD group. The distributions of Lp(a) concentrations showed left‐skewed deviation in each group, but we found the concentration of 40 mg/dL to be the best cut‐off point to distinguish the frequency of Alzheimer's disease from that of the controls. Compared with the frequency of high Lp(a) concentrations of 40 mg/dL or more in the controls (16.7%), that in the AD group (10.0%) was significantly lower, while that in the VaD group (45.7%) was significantly higher. Separating the AD group according to the presence or absence of ApoE4, the same findings were recognized. However, severe PVL was more frequent in the AD group with high Lp(a) concentrations (53.3%) than in the AD group without high Lp(a) concentrations (7.4%) (P < 0.01). Conclusions: These findings suggest the possibility of dual inverse effects of Lp(a) on the occurrence of Japanese late‐onset Alzheimer's disease, via suppression of Alzheimer's related processes and promotion of PVL formation presumably caused by ischemia.     

小剂量阿司匹林对血浆脂蛋白(a)浓度的影响

目的观察小剂量阿司匹林(ASA)对血浆脂蛋白(a)Lp(a)浓度的影响.方法采用酶联免疫双抗体夹心法分别检测了101例服用ASA(100mg/d)前后的脑梗死患者的血浆Lp(a)浓度和50例对照者服用安慰剂前后血浆Lp(a)水平.结果血浆Lp(a)浓度升高患者及不高者服用阿司匹林前所测Lp(a)浓度分别为(534±56)mg/L和(136±68)mg/L,Lp(a)浓度升高患者服用阿司匹林后Lp(a)浓度平均大约下降了14%(P＜0.01),而且持续3个月后所测Lp(a)浓度仍继续下降,为(433±58)mg/L,而Lp(a)浓度不高者服用阿司匹林后Lp(a)浓度无明显变化.对照组中血浆Lp(a)浓度升高者及不高者服用安慰剂后血浆Lp(a)水平均无明显变化.结论小剂量阿司匹林能有效降低Lp(a)浓度较高患者的Lp(a)水平.但对Lp(a)浓度正常患者的Lp(a)水平无明显影响.     

203例急性脑血管病患者血清脂蛋白(a)水平的研究

目的探讨血清脂蛋白(a)水平与脑血管病的关系.方法采用速率散射比浊法检测203例急性脑血管病患者(脑梗死组151例、脑出血组52例)和83例健康对照组血清脂蛋白(a)水平,并进行比较.结果脑梗死组和脑出血组血清脂蛋白(a)水平(分别为380.72±214.51mg/L和315.59±184.38mg/L)较健康对照组(206.49±115.44mg/L)显著升高(P＜0.01).脑梗死组和脑出血组血清脂蛋白(a)水平的异常率(分别为35.10%和19.23%)较健康对照组(4.82%)有显著升高(P＜0.01).脑梗死组血清脂蛋白(a)水平及其异常率显著高于脑出血组(P＜0.05).血清脂蛋白(a)水平与高血压、糖尿病、心脏病、吸烟等其他脑血管病危险因素无相关性.结论高脂蛋白(a)水平与脑血管病密切相关,是脑血管病的重要独立危险因素.     

急性脑梗死患者血清氧化型低密度脂蛋白水平变化及其与TOAST分型的关系

目的：探讨脑梗死患者血清氧化型低密度脂蛋白（oxLDL）水平变化及其与脑梗死的TOAST病因学分型之间的关系。方法：应用酶联免疫吸附法（ELISA）检测70例急性脑梗死患者血清oxLDL水平，按TOAST分型进行分组，对各亚组与52例健康对照组进行比较。结果：所有急性脑梗死患者、大动脉粥样硬化性卒中组及小动脉闭塞性卒中组血清oxLDL均较对照组显著增高（P均〈0．01）；大动脉粥样硬化性卒中组血清oxLDL水平显著高于其他亚组（P均〈0．01）。结论：血清oxLDL在脑梗死急性期升高，并与TOAST分型中的大动脉粥样硬化性卒中等类型关系紧密，可作为脑梗死急性期的血清标志物之一，提示斑块不稳定。     

糖尿病性脑梗死与非糖尿病性脑梗死患者血清脂蛋白(a)水平的比较

目的 比较糖尿病性脑梗死与非糖尿病性脑梗死患者血清脂蛋白（a）水平,探讨Lp（a）糖尿病及脑梗死之间的关系。方法 采用ELISA双抗体夹心法检测脑梗死患者的血清Lp（a）水平,并分别比较脑梗死组与对照组、糖尿病性脑梗死组与非糖尿病性脑梗死组、动脉粥样硬化性脑梗死与腔隙性脑梗死组之间Lp（a）水平变化。结果 脑梗死患组与对照组比较,脂蛋白（a）血浆浓度明显增高;糖尿病性脑梗死组与非糖尿病性脑梗死组脂蛋白（a）水平、动脉粥样硬化性脑梗死与腔隙性脑梗死组之间Lp（a）水平差异均具有显著性意义（P〈0．01）。结论 Lp（a）是缺血性脑卒中的一个危险因素,在动脉粥样硬化斑块的形成中起重要作用,脑梗死患者Lp（a）与糖尿病有一定的关联性。     

长期糖皮质激素治疗对特发性炎性肌病Lp(a)和hs-CRP水平的影响

目的通过检测特发性炎性肌病(IIM)患者糖皮质激素(简称"激素")治疗前、后不同时期血清脂蛋白(a)〔Lp(a)〕、超敏C反应蛋白(hs-CRP)水平变化,观察激素对IIM患者体内炎性状态的影响。方法选择确诊IIM患者25例(肌炎组),分别在泼尼松片治疗前及治疗后第3、6、9、12个月采用免疫散色比浊法和免疫透射比浊法检测其血清Lp(a)和hs-CRP水平,同时检测血总胆固醇(CHO)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL)、低密度脂蛋白胆固醇(LDL-C)、尿酸、同型半胱氨酸(HCY)水平。另选择15名作者医院门诊体检的健康人员检测其上述指标,作为健康对照,进行比较分析。结果肌炎组治疗前Lp(a)、hs-CRP、CHO、LDL-C、HDL、血尿酸、HCY水平与对照组比较差异均无统计学意义(均P0.05)。肌炎组患者治疗后第3、6、9、12个月Lp(a)、hs-CRP水平均较治疗前及对照组明显升高(均P0.05),治疗后第6个月与第9、12个月比较无明显差异(P0.05)。肌炎组治疗后各观察月CHO、LDL-C、HDL、血尿酸、HCY水平及治疗后第3个月TG水平与治疗前及对照组比较差异无统计学意义(均P0.05);TG在治疗后第6、9、12月水平较对照组、治疗前及治疗后第3月时高(P0.05)。结论长期激素治疗的IIM患者可出现血清Lp(a)、hs-CRP水平升高。     

脑梗塞患者血LP(a)、ox-LDL、D-D、Fbg含量的研究

本研究按不同年龄组分别测定了110例正常人和123例脑梗塞患者急性期和恢复期血中LP（a）、ox-LDL、D-D、Fbg的含量，结果显示：脑梗塞患者血中LP（a）、ox-LDL、D-D、Fbg较正常对照组显著升高（P＜0．01），并且LP（a）、ox-LDL、D-D在脑梗塞人血中呈正相关（r=0.876，P＜0．05）。正常人D-D的含量随年龄的增高有增长趋势，低年龄组与高年龄组有显著性差异（q=4．82，P＜0．01）。LP（a）、OX-LDL、Fbg含量各年龄组无差异（P＞0．05）。D-D随年龄增长塔高明显（R=0．596P＜0．01）并且与梗塞面积正相关（r=0．819，P＜0．01），而LP（a）、OX-LDL、Fbg与梗塞面积无关。同时发现D-D在脑梗塞恢复期明显降低（P＜0．05），证实了脑梗塞急性期确实存在高凝状态和内源性纤溶功能活跃。     

老年多梗塞性痴呆的性激素变化及相关因素的探讨

目的 :研究老年多梗塞性痴呆 (MID)的性激素。方法 :采取放射免疫法测定老年多梗塞痴呆 46例 ,老年非痴呆脑梗塞 (CI) 6 2例 ,正常老年健康对照组 38例。结果 :男性 MID组和 CI组分别与对照组的比较 ,T值下降 ,E2 /T增高 ,均有显著性差异 (P <0 .0 5 ) ,MID组 E2 高于对照组 ,有显著性差异 (P <0 .0 5 ) ,CI组与对照组 E2 比较无显著差异 (P >0 .0 5 )。女性 MID组和 CI组分别与对照组比较 ,T值下降 ,有显著性差异 (P <0 .0 5 ) ,E2 更明显下降 ,有高度显著差异 (P <0 .0 0 1) ,PRL和 PRO及 E2 / T值无显著性差异。男女性老年多梗塞性痴呆与非痴呆性脑梗塞组分别比较 T、PRO、E2 / T、均无显著性差异 (P >0 .0 5 )。结论 :老年多梗塞性痴呆与非痴呆性脑梗塞都存在着性激素失衡 ,其中 ,男性 E2 / T增高 ,女性以 E2 降低最为明显。表明适当地调节性激素水平会有利于老年多梗塞痴呆及非痴呆性脑梗塞的防治。     

Lipoprotein(a) concentration increases during treatment with carbamazepine

PURPOSE: Treatment with carbamazepine (CBZ) is known to affect apolipoprotein B-containing lipoprotein concentrations in serum. However, little is known about the effects of anticonvulsant drugs (AEDs) on lipoprotein(a) [Lp(a)], although Lp(a) has been characterized as independent cardiovascular risk factor. We investigated prospectively the effect of CBZ on lipoprotein(a) concentration in normolipidemic healthy adults. METHODS: Twenty male volunteers were included in the study. Lp(a) levels were determined before and 69 +/- 19 days after CBZ administration by using an enzyme-linked immunoassay. RESULTS: CBZ (mean plasma concentration, 6.6 +/- 0.6 microg/ml) caused a significant increase in Lp(a) concentrations, with a median change of +19.5% (95% CI: +8.2, +53.3; p < 0.001). Total cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides also increased significantly. CONCLUSIONS: Although the precise mechanism of action of CBZ on Lp(a) elevation remains uncertain, it might be related to its enzyme-inducing properties. During treatment with CBZ, special focus should be given to elevated LDL cholesterol and Lp(a) concentrations with regard to increased risk for atherosclerotic vascular diseases.