LIPOPROTEIN(a) CONCENTRATION AND MOLECULAR WEIGHT OF APOLIPOPROTEIN(a) IN PATIENTS WITH CEREBROVASCULAR DISEASE AND DIABETES MELLITUS

Plasma lipoprotein(a) [Lp(a)] concentrations are genetically determined, and hyper-Lp(a)-emia is an independent risk factor for atherosclerosis and thrombosis. To study the implications of Lp(a) in cerebrovascular disease (CVD) and diabetes mellitus (DM), we examined plasma Lp(a) levels and molecular weights of apolipoprotein(a) [apo(a)] in 118 patients with CVD, and 125 cases with DM. Although mean Lp(a) concentrations were higher in those cases with atherothrombotic brain infarction than in those with brain hemorrhage and lacunar infarction, the difference was not statistically significant. Lp(a) levels were significantly higher in the DM cases treated with insulin and in those treated with oral hypoglycemic agents than in those on diet therapy alone, suggesting that insulin and oral agents modulate apo(a) expression. Lp(a) concentrations correlated significantly with the low-molecular-weight isoforms of apo(a) in all CVD and DM groups. © 1997 Elsevier Science Ltd     

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).     

Does Lp(a) lipoprotein inhibit the fibrinolytic system?

Lp(a) lipoprotein contains a unique apolipoprotein, apolipoprotein (a), that has a striking homology with plasminogen. This homology has brought forward speculations as to an inhibitory effect of Lp(a) lipoproteins on fibrinolysis. The present investigation was undertaken to study the influence of Lp(a) lipoprotein on the fibrinolytic system. In an in vitro model, we have studied the influence of purified Lp(a) lipoprotein on plasminogen activation by tissue plasminogen activator (t-PA) in the presence of soluble fibrin. Increasing concentrations of Lp(a) lipoprotein (0-32 mg/dl) did not inhibit plasminogen activation by t-PA in the presence of thrombin or bathroxobin digested fibrinogen. When purified Lp(a) lipoprotein was added to whole blood, the degree of fibrin degradation obtained following standardized coagulation, as evaluated by the generation of D-dimer, was not reduced. D-dimer levels in plasma and in serum after standardized coagulation, as well as conventional parameters for evaluation of the fibrinolytic system, were determined in 10 individuals with high and 10 individuals with low levels of Lp(a) lipoprotein. No differences in the fibrinolytic parameters were observed between the groups. Thus, we found no evidence that Lp(a) lipoprotein interferes with the fibrinolytic process in the present experiments.     

Comparison of lipid and lipoprotein values in men and women differing in training status

The aim of this study was to compare plasma lipid and lipoprotein concentrations of male and female subjects in different training levels and to examine the risks of cardiovascular diseases. For this purpose, 20 male athletes from the National Turkish Wrestling Team (age 23.5 +/- 1.25 years) and 44 male and 51 female students (ages 21.7 +/- 1.72 and 20.20 +/- 1.68 years, respectively) from physical education and sports department and 40 sedentary females (ages 21.14 +/- 1.72 years) participated in this study. Trigliceride (TG), total cholesterol (TC), HDL-C and LDL-C levels were determined by a Hitachi 717 Autoanalyser. Apo A-l, Apo B, and Lp(a) levels were determined by Behringer Nephelometer 100. Maximum Oxygen Consumption (VO(2) max) values were determined by 12-min run test and the anaerobic power values were measured by Jump Meter Instrument. Energy consumption of basal metabolic rates were for males 1 kcal for an hour and 0.9 kcal for females. There were no significant differences in plasma TC, TG, and small lipoprotein a (Lp(a)) values between four groups (p > .05). No significant differences were found in HDL-C, LDL-C, apolipoprotein Al (Apo-Al), and apolipoprotein B100 (Apo-B) values between wrestlers and male students, and between female students and sedentary females (p > .05). HDL-C values of female students and sedentary females were significantly higher when compared with the same values of wrestlers and male students (41.52 and 40.93 mg/100 ml versus 51.92 and 50.10 mg/100 ml). However, LDL-C values were found to be lower in females than males (121.83 and 101.10 mg/100 ml as opposed to 97.7 and 98.4 mg/100 ml) but only significantly lower than in wrestlers (p < .05). Although the wrestlers' training levels were always higher than male students, the lipid and lipoprotein values were not different. These variables were not different between female groups either. But the lipid and lipoprotein profile of female subjects was found to be better than that of males. These results showed that medium and high level of exercises did not cause significant differences in lipid and lipoprotein levels, but the sex differences were very pronounced. Lipid and lipoprotein values of the four groups have indicated that the individuals in these groups would not be exposed to danger of cardiovascular diseases.     

Elevated plasma levels of lipoprotein(a) in psychiatric patients: a possible contribution to increased vascular risk.

An increased incidence of adverse cardiovascular events has been reported in psychiatric patients, but the exact mechanisms underlying this association are still uncertain. Elevated plasma level of lipoprotein(a) [Lp(a)] is an independent risk factor for atherothrombotic disease in the general population. To study the implications of Lp(a) in psychiatric patients, we measured the plasma levels of Lp(a) in 74 patients with psychiatric disorders (39 schizophrenia, 10 major depression, 13 bipolar disorder and 12 personality disorder) and 74 healthy controls. The Lp(a) levels of the patient groups with schizophrenia, major depression and bipolar disorder were significantly higher than that of the control group. The median Lp(a) value of these diagnostic groups was comparable with those reported in patients with prior atherothrombotic events. On the other hand, no differences were found among personality disorder and controls. Our findings suggest that the elevation of plasma Lp(a) may contribute to increased cardiovascular risk in several patients with psychiatric disorders.     

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.     

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.     

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。     

Effect of Antiepileptic drugs on plasma lipoprotein (a) and other lipid levels in childhood

Antiepileptic drugs may alter plasma lipid status in epileptic patients. We conducted a study to assess the effect of phenobarbital, carbamazepine, and valproate on plasma levels of lipoprotein (a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A, and apolipoprotein B in 22 epileptic children. The children were separated as group 1, seven children, mean age 1.6+/-0.2 years, treated with phenobarbital, 5 mg/kg/day, twice daily; group 2, seven children, mean age 9.8+/-1.2 years, treated with carbamazepine, 20 mg/kg/day, twice daily; and group 3, eight children, mean age 6.8+/-0.6 years, treated with valproate, 20 mg/kg/day, twice daily. Plasma lipoprotein (a) and other lipid levels were studied before (pretreatment) and at 3 and 6 months of treatment. Friedman two-way analysis of variance and Wilcoxon's signed-rank test were used for statistical analysis, and the results were expressed as the mean and standard error of the mean. The mean age of children in group 1 was significantly low, compared with groups 2 and, 3 (P < .001). The mean pretreatment lipid levels between the groups were not significant. The increase in lipoprotein (a) at 3 and 6 months and high-density lipoprotein cholesterol at 6 months was statistically significant in group 1 (P < .025). We suggest a careful monitoring of plasma levels of lipoprotein (a) and other lipids in epileptic children treated with antiepileptic drugs.     

Chlamydia pneumoniae antibodies and high lipoprotein(a) levels do not predict ischemic cerebral infarctions. Results from a nested case-control study in Northern Sweden.

BACKGROUND AND PURPOSE: An association between high lipoprotein(a) [Lp(a)] levels and positive Chlamydia pneumoniae IgG titers in coronary artery disease has been described. The possibility of predicting ischemic stroke by measurements of plasma Lp(a) and C pneumoniae antibodies was investigated. METHODS: This incident case-control study included 101 case subjects (cases) who had suffered ischemic cerebral infarctions and 201 matched control subjects (controls). The study population was nested within the V?sterbotten Intervention Program or the WHO MONICA project. Plasma samples were measured for C pneumoniae-specific IgG and IgA antibodies and Lp(a). RESULTS: A significantly higher mean Lp(a) level was found in female cases than in female controls. However, plasma Lp(a) was unable to predict ischemic cerebral infarctions in either women or men. The proportion of individuals with positive C pneumoniae-specific IgG or IgA titers did not differ between cases and controls. Antibody titers were unable to predict a future stroke. The proportion of individuals with a positive C pneumoniae IgG titer in combination with a high Lp(a) level did not differ significantly between cases and controls. CONCLUSIONS: These data suggest that there is no association between baseline plasma Lp(a) levels, presence of C pneumoniae antibodies, and future ischemic cerebral infarctions. Furthermore, no evidence of an interactive effect between high Lp(a) levels and C pneumoniae IgG titers was found. However, selection bias and a recent C pneumoniae epidemic may have influenced the results.     

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。     

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.     

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.     

Euglobulin clot lysis induced by tissue-type plasminogen activator is reduced in subjects with increased levels of lipoprotein (a).

Several reports have evaluated the in vitro effect of lipoprotein(a) [Lp(a)] levels on the fibrinolytic system, suggesting that high Lp(a) levels may inhibit fibrinolysis by competing for plasminogen binding in different systems. We have studied plasminogen activation induced by tissue-type plasminogen activator (t-PA), as well as other fibrinolytic parameters, in 25 subjects with Lp(a) levels greater than 30 mg/dl and the results were compared with those found in 23 subjects with Lp(a) less than 30 mg/dl. Both groups were similar in age, sex distribution, living habits and lipid pattern. Plasminogen activation, when measured by t-PA-induced euglobulin clot lysis, was significantly decreased in the group with elevated Lp(a) levels (lysis time, 16.7 +/- 3.3 min) compared with the group with low Lp(a) levels (11.8 +/- 2.0 min), although 8 of the 25 subjects with high Lp(a) levels showed plasminogen activation within the range of the control group. A positive significant correlation between Lp(a) levels and t-PA-induced euglobulin clot lysis time was found. No statistical differences were demonstrated between groups for the other fibrinolytic parameters studied. Addition of purified Lp(a) to the euglobulin fraction or to plasma resulted in a decrease in euglobulin clot lysis. The present study shows that t-PA induced plasminogen activation is decreased in individuals with high circulating levels of Lp(a) supporting the hypothesis that Lp(a) may interfere with the physiological functions of plasminogen.     

Plasma lipids and lipoproteins in subtypes of stroke

We determined plasma lipid and lipoprotein concentrations in 131 patients (95 males, 36 females, mean age 71 years) 6 months after acute stroke onset. Compared to a reference population, the alterations of plasma lipid concentrations in stroke patients were moderate. However, the stroke patients had higher levels of triglyceride and lipoprotein (a) and lower concentrations of cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol. Patients with different subtypes of stroke showed significant differences when compared with each other by analysis of covariance (with adjustment for age, sex, smoking, hypertension and diabetes). Patients with carotid or vertebral artery disease had the higher levels of cholesterol, triglyceride and apolipoprotein B, whereas high density lipoprotein triglyceride concentrations were higher in patients with cardioembolic infarcts.     

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.     

Lipid metabolism in cognitive decline and dementia

This review will focus on the current knowledge on circulating serum and plasma risk factors of cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD) linked to cholesterol homeostasis and lipoprotein disturbances, i.e. total cholesterol (TC), 24S-hydroxy-cholesterol, lipoprotein(a) (Lp(a)), or apolipoprotein E (APOE). These measures linked to lipoprotein metabolism appear to be altered in AD, VaD, or predementia syndrome relative to controls, but with contrasting results. At present, several studies have demonstrated the dependence of APOE serum levels upon the APOE genotype, nonetheless serum APOE levels seems not to be a credible risk factor or a biochemical marker for AD instead of APOE genotyping. In fact, there was no consistent association of serum or plasma apoE protein levels with the disease when controlled for APOE genotype. In addition, there are some evidence that higher Lp(a) levels could be linked with AD, although there are studies suggesting an increased presence of low molecular weight apo(a) in AD, VaD, and frontotemporal dementia, that are associated with elevated Lp(a) levels. In fact, the apo(a) gene is highly polymorphic in length due to variation in the numbers of a sequence encoding the apo(a) kringle 4 domain, and plasma levels of Lp(a) are inversely correlated with apo(a) size. Furthermore, although serum/plasma levels of TC and 24S-hydroxycholesterol are not credible diagnostic markers for AD and cognitive decline, the current evidence suggests that they may be modifiable risk/protective factors. The prevailing wisdom is that high TC is a risk factor for dementia. However, the relationship between TC and dementia may vary considerably depending on when cholesterol is measured over the life course or, alternatively, in relation to the underlying course of the disease. Several observational studies have suggested that statins, which are effective in lowering cholesterol, may reduce the risk of dementia, but the results of these reports are inconclusive. Thus, more studies with long-term follow-up and serial assessments of TC are needed to further clarify the causal relationship between cholesterol and dementia.     

Lipoprotein(a) in ischemic cerebrovascular disease: a new approach to the assessment of risk for stroke

We estimated the serum levels of lipoprotein(a) [Lp(a)] of 87 patients suffering from ischemic cerebrovascular disease (ICVD) (50 men, 37 women; mean age, 66.7 +/- 10.9 years; median, 66) and of 66 healthy controls (33 men, 33 women; mean age, 62.2 +/- 11.1; median, 63). The Lp(a) serum levels of the ICVD group (mean, 20.5 +/- 23 mg/dl; median, 9.5) were significantly elevated compared with those of controls (mean, 14.2 +/- 23.1 mg/dl; median, 5). In a smaller subgroup, limiting the age range to 30 to 60 years, the difference in the Lp(a) serum levels between the ICVD patients and the controls was even highly significant (p less than 0.001).     

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.     

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。