Association of levels of lipoprotein (a) and other lipoproteins with cerebrovascular disease in the Turkish population

Lipoprotein (a) [Lp (a)] is a cholesterol-rich lipoprotein that structurally resembles the low density lipoprotein cholesterol (LDL-C) particles, but contains a molecule of apolipoprotein (a) attached to apolipoprotein B by disulfide bond. Because of the fact that high plasma levels of Lp (a) have been shown to be associated with cerebrovascular disease (CVD), we determined plasma Lp (a) levels in CVD for the Turkish population, and compared them with previous findings of some developed countries. Plasma Lp (a) levels were evaluated in CVD and control groups. The mean plasma Lp (a) levels in the CVD group was found to be approximately two-fold higher than that of the control group (0.21 g/1 vs 0.38 g/1). Also, it was found to be higher than the mean levels of CVD group in the other populations described in previous reports. But CVD prevalence in the Turkish population is lower than in those of developed countries, especially United States and Japan. Therefore, we believe that each of those populations should determine their plasma Lp (a) levels to observe the risk for CVD.     

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.     

Lipoprotein(a) phenotypes in patients with vascular dementia

We tried to examine if there is a particular distribution pattern of lipoprotein(a) [Lp(a)] phenotypes specific for patients with vascular dementia (VD). Fourteen cases of VD (9 males and 5 females), 18 cases of dementia of the Alzheimer type (DAT)(7 males and 11 females), 29 cases of cerebrovascular disease (CVD) in the chronic phase (18 males and 11 females) and 47 healthy individuals as controls (25 males and 22 females) were examined for serum Lp(a). Serum concentrations and phenotypes of Lp(a) were assessed by ELISA and a test kit for the Lp(a) phenotype, respectively. Serum concentrations of Lp(a) were significantly higher in patients with VD (p < 0.05) as well as patients with CVD (p < 0.01) compared with those in healthy individuals. Serum concentrations of Lp(a) did not significantly differ between patients with DAT and healthy individuals. The incidences of Lp(a) phenotypes containing relatively low-molecular-weight apolipoprotein(a) isoforms were significantly higher in patients with CVD in the chronic phase (p < 0.05) or those with VD (p < 0.01) compared with those in healthy individuals. Distribution patterns of Lp(a) phenotypes did not differ between patients with DAT and healthy individuals. Thus, high serum levels of Lp(a) could be considered a clinical hallmark to distinguish VD from DAT. Abnormally high serum levels of Lp(a) in patients with CVD and VD seemed to be due to specific increases in low-molecular-weight apolipoprotein(a) isoforms in Lp(a).     

Lp(a) Lipoprotein in Cerebrovascular Disease and Dementia

Abstract: Lp(a) lipoprotein has been considered an independent risk factor in the development of coronary heart disease (CHD). We examined the role of Lp(a) in patients with cerebrovascular disease (CVD) and those with dementia.
The Lp(a) concentration in patients with CHD, those with cerebral infarction due to a large artery occlusion and those with vascular dementia (VD) was significantly higher than that of age-matched control subjects. However, the Lp(a) concentration was not high in cerebral infarction due to a small artery occlusion, intracerebral hemorrhage and dementia of the Alzheimer type (DAT).
The present results suggest that Lp(a) should cause VD as well as CVD, and that Lp(a) should be one of the indicators that distinguish VD from DAT.     

Cryptogenic cerebral infarction in a young patient with very high lipoprotein(a) serum level as the only risk factor

Abstract Lipoprotein(a) [Lp(a)] is a plasma lipoprotein that consists of a low-density lipoprotein (LDL)-like particle containing APO B-100 and apolipoprotein(a), linked by a disulphide bridge. There is evidence that higher serum level of Lp(a) is a predictor of various vascular diseases, such as myocardial infarction, coronary stenosis, re-occlusion of aortocoronary bypass vein grafts, peripheral atherosclerosis and cerebral infarction [1–4]. We describe a young man with a cryptogenic stroke with very high serum level of Lp(a) as the only vascular risk factor.     

载脂蛋白（a）蛋白多态性与皮质脑梗塞相关性研究

目的在蛋白亚基水平上阐明载脂蛋白（ａ）［ａｐｏ（ａ）］多态性与脑梗塞的关系。方法８５名健康对照者和４２例皮质脑梗塞患者以ＥＬＩＳＡ法检测血Ｌｐ（ａ）水平、ＳＤＳ－ＰＡＧＥ／免疫印迹结合银染法检测ａｐｏ（ａ）蛋白大小多态性。结果得出脑梗塞患者血Ｌｐ（ａ）水平显著高于对照组；病人组低分子量ａｐｏ（ａ）表型频率明显高于对照组；但即使是相同ａｐｏ（ａ）表型个体间，病人的血Ｌｐ（ａ）水平仍显著高于对照者。结论研究在进一步证实高水平血Ｌｐ（ａ）是ＡＳ性脑梗塞危险因素的基础上，发现脑梗塞与决定Ｌｐ（ａ）高水平的低分子量ａｐｏ（ａ）表型密切关联，且提示除ａｐｏ（ａ）大小多态性外，尚有其它因素影响血Ｌｐ（ａ）水平。     

Lipoprotein(a) and the risk of thromboembolism in Thai children

High lipoprotein(a) [Lp(a)] level was identified as a risk factor of both venous and arterial thromboembolism (TE), especially in Caucasian children. The Lp(a) level is affected by apo(a) gene. The genetic polymorphisms that associated with Lp(a) level are the size of apo(a) gene, pentanucleotide repeat (TTTTA )_n and + 93 C/T at promoter region. The increasing size of apo(a) gene, more than 8 pentanucleotide repeats and + 93 C > T polymorphisms are associated with low level of Lp(a) in African and Caucasian populations. This cross - sectional, case control study, aims to identify the association of Lp(a) level and the risk for TE in Thai children. Forty-nine patients and 116 healthy children were enrolled. Mean ± SD for age of patients and controls were 7.6 ± 4.7 and 11.2 ± 1.7 years, with female:male ratios of 1:1.2 and 1.8:1, respectively. The median Lp(a) levels in patients was 8.2 (0-87.3) mg/dL and 7.9 (0-74.9) mg/dL in controls, which were not statistically different, P = 0.65. The frequencies of 8 pentanucleotide repeats and + 93 C/T were different compared to Caucasian and African populations but similar to Chinese population. However, both polymorphisms did not affect the level of Lp(a).     

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。     

血清脂蛋白a在缺血性脑卒中患者中含量的变化

目的　研究血清脂蛋白a[lipoprotein(a) ,LP(a) ]在脑梗死形成中的作用及意义。 方法　采用双抗体夹心法检测血清中LP(a)的浓度。结果　与动脉粥样硬化有关的脑梗死 (atherothromboticbraininfarc tion ,ABI)组 (n =6 2 )LP(a)浓度显著高于对照组 (n =37)及脑栓塞组 (n =15 ) (P <0 .0 5 )。ABI组、脑栓塞组及对照组中不同性别及不同年龄的LP(a)水平无显著差异 (P >0 .0 5 )。脑梗死组在有无糖尿病患者中 ,LP(a)水平无显著差异 (P >0 .0 5 )。结论　LP(a)是与遗传有关的血浆脂蛋白 ,通过血清LP(a)的水平的测定 ,一方面可作为脑血栓形成和脑栓塞的鉴别 ;另一方面对于有缺血性脑卒中发生倾向者 ,可推断其患病风险 ,也可作为脑卒中预测的一个指标 ,对于已经发生脑梗死的患者 ,可推断其再发生的可能性。     

Relation of apolipoprotein(a) size to alzheimer's disease and vascular dementia

Lipoprotein(a) [Lp(a)] level is a newly established vascular risk factor which has been suggested to play a role in dementia. However, the majority of Lp(a) cell-to-cell interactions are mediated by its specific apolipoprotein(a) [apo(a)] moiety. This suggests that the size polymorphism of apo(a) may be of importance in conveying the Lp(a)-related risk. Specifically, we postulated that variation in apo(a) isoform size may lead to increased risk of vascular dementia (VaD), Alzheimer's disease (AD), stroke, or all three of them. Under a case-control design we compared Lp(a) plasma levels and the distribution of apo(a) phenotypes in groups of subjects consisting of 50 VaD patients, 162 sporadic AD patients, 95 non-demented stroke patients (NDS), and 105 normal controls. The prevalence of small-sized apo(a) isoforms in the VaD group was significantly higher than that in the stroke and normal control groups, with an odds ratio of 5.29 (95% CI 2.24-12.49, p = 0.0001) for the development of VaD for individuals with at least one apo(a) isoform of low molecular weight (LMW). Furthermore, the possession of at least one small-sized apo(a) isoform significantly increased the risk of AD to 1.92 (95% CI 1.02-3.61, p = 0.0434). Our results demonstrate that possession of at least one LMW apo(a) isoform is significantly associated with dementia and specifically offer new evidence of a strong association between the lipoprotein system and post-stroke dementia.     

Lp(a) lipoprotein in cerebrovascular disease and dementia

Lp(a) lipoprotein has been considered an independent risk factor in the development of coronary heart disease (CHD). We examined the role of Lp(a) in patients with cerebrovascular disease (CVD) and those with dementia. The Lp(a) concentration in patients with CHD, those with cerebral infarction due to a large artery occlusion and those with vascular dementia (VD) was significantly higher than that of age-matched control subjects. However, the Lp(a) concentration was not high in cerebral infarction due to a small artery occlusion, intracerebral hemorrhage and dementia of the Alzheimer type (DAT). The present results suggest that Lp(a) should cause VD as well as CVD, and that Lp(a) should be one of the indicators that distinguish VD from DAT.     

Early and persistent increase in serum lipoprotein (a) concentrations in epileptic children treated with carbamazepine and sodium valproate monotherapy

PURPOSE: The aim of this study was to investigate by a prospective, self-controlled method, whether treatment with carbamazepine (CBZ) and sodium valproate (VPA) monotherapy may alter serum lipoprotein (a) [Lp(a)] concentrations in epileptic children. METHODS: Serum Lp(a) concentrations have been determined in 18 epileptic children before and at 6, 12 and 24 months of treatment with CBZ monotherapy and in 30 epileptic children before and at 6, 12 and 24 months of treatment with VPA monotherapy. Serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoproteins A-I and B concentrations and serum concentrations of biochemical markers of liver and renal function were also measured in the study participants. RESULTS: Serum Lp(a) concentrations were significantly increased at 6, 12 and 24 months of CBZ and VPA monotherapy. There were no significant correlations between serum Lp(a) and serum lipids, lipoproteins, apolipoproteins, concentrations of biochemical markers of liver and renal function or antiepileptic-drugs concentrations. CONCLUSIONS: Children who receive CBZ or VPA monotherapy may have significant and persistent increase in serum lipoprotein (a) concentrations, occuring early in the course of therapy. It may be useful to measure serum Lp(a) concentrations routinely in epileptic children taking these antiepileptic drugs, especially in those that are already at higher atherosclerotic risk.     

Elevated plasma concentrations of lipoprotein(a) in medicated epileptic patients

Lipoprotein(a) [Lp(a)] has been identified as an independent risk factor for vascular diseases. There are no data on Lp(a) levels in patients on long-term medication with carbamazepine, phenytoin, phenobarbital, or valproate. To investigate the effects of such treatment on Lp(a) levels and common carotid artery intima media thickness we studied 51 epileptic outpatients on long-term antiepileptic medication and 51 age- and sex-matched controls. Lp(a) levels above 45 mg/dl were found in 11 of 50 patients, but in only 4 of 51 controls (P<0.05). The mean serum concentration of Lp(a) was 33.0±7.0 mg/dl in patients and 16.9±2.7 mg/dl in controls (P<0.05). Epileptic patients also had a thicker intima media of the common carotid artery (0.79±0.04 mm) than controls (0.69±0.02 mm, P<0.05) as measured by B-mode ultrasonography. Our results suggest an untoward effect of long-term antiepileptic medication on Lp(a) serum concentrations. Elevated Lp(a) levels might be a risk factor for arteriosclerosis in epileptic patients. Received: 26 November 1999/Received in revised form: 16 March 2000/Accepted: 9 April 2000     

中青年人脑卒中与血脂关系的研究

目的 探讨血脂与中青年人脑卒中的关系。方法 检测了206例中青年脑卒中患者及80例对照者的甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL－C）、低密度脂蛋白胆固醇（LDL－C）、载脂蛋白A－I（ApoA-I)、载脂蛋白B100（ApoB100)和脂蛋白（a)[Lp(a)]血清含量。结果 脑梗死组TG、TC、LD-L－C、ApoB100及Lp(a)水平显著高于对照组,Lp(a)水平亦高于脑出血组,异常的血脂成分随年龄变化而发生改变;皮层动脉区脑梗死组Lp(a)水平显著高于穿通动脉区脑梗死组;脑出血组血脂指标与对照组比较差异无显著。结论 血脂代谢紊乱是中青年人脑梗死的危险因素。     

Lipoprotein(a) levels and isoforms and fibrinolytic activity in postmenopause--influence of hormone replacement therapy.

Epidemiological studies suggest that hormone replacement therapy (HRT) decreases the risk of cardiovascular disease in postmenopausal women via several mechanisms, including modifications in the fibrinolytic system and lipoprotein(a) [Lp(a)] levels. The aim of this study was to examine the influence of the levels and isoforms of Lp(a) on fibrinolytic activity in 91 postmenopausal women in comparison with premenopause and analyze the effect of HRT on those parameters. In postmenopause, an increase in plasma Lp(a) and plasminogen activator inhibitor-1 (PAI-1) levels was found. A significant inverse correlation was observed between Lp(a) or PAI-1 levels and plasmin generation. Plasma samples with low molecular weight (MW) apo(a) isoforms showed higher plasmin inhibition than plasmas with high MW apo(a) isoforms and similar levels of total Lp(a) and PAI-1. HRT induced a significant decrease in Lp(a) and PAI-1 levels and an increase in estradiol levels, as well as an increase in fibrinolytic activity. A significant correlation was found between the percentages of variation in Lp(a) levels and in plasmin generation and between the percentages of variation in PAI-1 levels and in the euglobulin lysis time under HRT. In conclusion, the increase in fibrinolytic activity observed in women under HRT could be explained by two independent mechanisms: (a) the decrease in PAI-1 and (b) the decrease in the inhibition of plasmin generation due to the decrease in Lp(a) levels.     

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。     

脑梗死患者血尿酸、脂蛋白(a)含量的研究

目的探讨脑梗死患者血尿酸、血清脂蛋白(a)含量的变化及其意义。方法对85例脑梗死患者测定其血总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、脂蛋白(a)及血尿酸(UA)水平,与对照组40例结果进行比较。结果脑梗死患者TC、TG、HDL水平与对照组相比无明显差异(P>0.05),UA、LDL、Lp(a)水平较对照组明显升高(P<0.01);其中脑梗死合并糖尿病者较无糖尿病者,血UA、Lpo(a)亦有明显升高(P<0.05),两组与正常对照组比较均有显著性差异(P<0.05)。结论血尿酸、Lpo(a)含量增高与脑梗死存在一定关系,是脑梗死的重要危险因素。     

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.     

The elevated plasma lipoprotein(a) concentrations in preeclampsia do not precede the development of the disorder

We sought to determine whether maternal plasma lipoprotein(a) [Lp(a)] levels are elevated in the second trimester, before the development of preeclampsia and other obstetrical complications, in women at risk. In the first part of the study (cross-sectional), plasma concentrations of Lp(a) were compared among 16 women with preeclampsia, 35 normotensive pregnant women and 18 healthy nonpregnant women. In the second part (nested case-control), blood samples were collected prospectively from 82 women at risk of preeclampsia, at 14-24 weeks of gestation, and Lp(a) levels were compared between those in whom preeclampsia or other obstetrical complications developed and those in whom they did not. In the cross-sectional study, plasma concentrations of Lp(a) were significantly higher in women with preeclampsia than in normotensive pregnant and healthy nonpregnant women (41 +/- 31 vs. 24 +/- 16 and 15 +/- 10 mg/dl, respectively; P=.001). Of the 82 women in the second part of the study, 9 (11%) developed preeclampsia and 19 (23%) had complications such as intrauterine growth restriction, preterm delivery and fetal or neonatal loss. There were no differences in plasma Lp(a) concentrations between the women with preeclampsia and those without complications, though Lp(a) levels were significantly higher in women with other complications than in those with either preeclampsia or uncomplicated pregnancies (40 +/- 29 vs. 17 +/- 13 or 28 +/- 18 mg/dl, respectively; P=.05). In conclusion, elevated plasma levels of Lp(a), associated with clinically established preeclampsia, are not detected before the appearance of the disorder in pregnant women at risk.     

Lipoprotein(a) as a strong indicator for cerebrovascular disease

To evaluate the role of lipoprotein(a) (Lp(a] in patients with cerebrovascular disease (CVD), lipid parameters were compared with a control group (CO). Additionally, the Lp(a) serum levels were investigated in a coronary artery disease (CAD) group. The CO was made up of 37 healthy persons (age: 54.5 +/- 7.7, 26 males and 11 females), the CVD group included 46 patients with sustained transient ischemic attack (TIA) prolonged reversible ischemic neurologic deficits (PRIND) and cerebral infarction (CI) (age: 53.6 +/- 9.7, 32 males and 14 females), and the CAD group was made up of 28 survivors of myocardial infarctions (age: 52.5 +/- 8.1, 18 males and 10 females). The median values of Lp(a) in CVD were significantly higher than in the CO (p less than 0.01) and did not differ significantly from the CAD. Total TC, HDL-C, TG, LDL-C and the ratio of LDL-C/HDL-C did not show any significant difference between the control and cerebrovascular disease group. For quantification of the vascular lesions of the carotid system, a Duplex Doppler score system was used. The score correlated with Lp(a) in patients between 40 to 65 years of age (r = 0.34, p less than 0.01). Thus, we conclude that Lp(a) is not only a risk factor for CAD but also for CVD.