Apolipoprotein Phenotypes Research Articles

Significance of apolipoprotein(a) phenotypes in acute coronary syndromes: relation with clinical presentation

Background High lipoprotein(a) [Lp(a)] levels and small-sized apolipoprotein(a) [apo(a)] phenotypes have been linked to acute coronary syndromes (ACS). We sought to determine whether Lp(a) concentrations and apo(a) phenotypes may be related to the clinical syndrome of presentation among ACS patients. Methods Two hundred ten ACS patients and 105 controls were enrolled. One hundred thirteen patients presented with acute myocardial infarction (AMI) and 97 with unstable angina pectoris (UAP). Lp(a) concentrations were determined by ELISA and apo(a) isoforms were detected with a high-resolution immunoblotting method. Results Lp(a) levels and the percentage of subjects with at least one small-sized apo(a) isoform were significantly higher both in AMI patients and in UAP subjects as compared with controls. Among ACS patients, the percentage of subjects with at least one small apo(a) phenotype was significantly higher in patients who presented with AMI than in those with UAP ( p<0.001). Multivariate logistic regression analysis showed that the presence of at least one small-sized apo(a) isoform was associated with AMI as the patient's clinical syndrome of presentation (OR=2.51, 95% CI: 1.38–4.58, p<0.01). Conclusions Among ACS patients, apo(a) isoforms of low molecular weight were associated with AMI onset. High-resolution apo(a) phenotyping might be helpful to identify individuals at high risk for developing AMI.

Apolipoprotein(a) phenotypes are reliable biomarkers for familial aggregation of coronary heart disease

Lipoprotein(a) [Lp(a)] is an atherogenic and prothrombotic molecule formed by the covalent binding of the highly polymorphic apolipoprotein(a) [apo(a)] to apoprotein B-100 of LDL. High Lp(a) concentrations are a recognized genetic risk factor for coronary heart disease (CHD) and have been shown to be related with a familial clustering of ischemic cardiac events. Nevertheless, the association between apolipoprotein(a) isoforms and a positive familial history of CHD has received far less attention. In this report, we explored the distribution of apo(a) phenotypes in 127 CHD subjects with a family history of coronary events and in 92 CHD patients without such a history. Twenty-two apo(a) isoforms were detected by a high-resolution immunoblotting method. In univariate analysis, the percentage of subjects with at least one small sized apo(a) isoform was significantly higher in CHD patients with a positive family history than in those without (P<0.01). Multivariate analysis showed that apo(a) isoforms of low molecular weight were the best predictors of familial aggregation of cardiac ischemia. We conclude that apo(a) size polymorphism is strongly associated with a familial history of CHD and is more efficient than Lp(a) plasma concentrations in predicting the familial clustering of coronary disease. When detected by high-resolution techniques, apo(a) phenotypes are objective laboratory markers that can substitute for a knowledge of a positive family history of CHD and should be used, together with Lp(a) levels, to better assess the familial predisposition to coronary events.

Relationship between plasma lipoprotein (a), apolipoprotein (a) phenotypes, and other coronary heart disease risk factors in a Melbourne South Asian population

Background: High plasma lipoprotein(a) [Lp(a)] level is a strong and important risk factor for cardiovascular disease (CVD). Small-sized apolipoprotein(a) [apo(a)] isoforms (F, B, S1, and S2) are inversely correlated with the high levels of Lp(a) in plasma and significantly associated with CVD. Although the effects of apo(a) phenotypes and various risk factors on Lp(a) status in South Asian population may have been studied in other countries, there are no reports involving these risk factors in Australia. Methods and results: Factors contributing to variation in Lp(a) were surveyed in 402 (216 males and 186 females) South Asian Melburnians. There was a negative relationship between low alcohol beer per day and Lp(a) in men ( P < 0.05). Approximately 21% of the variance of Lp(a) concentration in men and 6% in women were explained by age. Age was positively associated with Lp(a) concentrations in men but negatively in women. The most commonly occurring phenotype was apo(a) S3. In this phenotype, Lp(a) concentrations ranged from non-detectable to 811 mg/l. After adjusting for age, an inverse correlation was observed between Lp(a) concentration and apo(a) phenotypes ( P < 0.01). Conclusions: Although Lp(a) has been reported to be genetically determined, there are clearly other factors contributing to variations in Lp(a) concentrations in a South Asian population.

Apolipoprotein E Polymorphism Is Related to Plasma Lipids and Apolipoproteins in Mexican Adolescents

Previous studies in the Mexican population have failed to show an effect of apolipoprotein E (APOE) polymorphism on the lipid profile. The purpose of the present study was to determine the frequencies of APOE phenotypes, and their influence on lipid and apolipoprotein levels in a random sample of Mexican adolescents living in Mexico City. APOE polymorphism, fasting insulin levels, lipid levels, and apolipoprotein levels were determined in 420 adolescents. We found a high frequency of APOE*3 subjects (89.5%) and a low frequency of APOE*2 (3.0%) and APOE*4 (7.5%) subjects. The APOE*4 subjects (including APOE 4,3 and APOE 4,4) showed the highest concentrations of total cholesterol, low-density lipoprotein cholesterol, and apoB and the lowest high-density lipoprotein cholesterol levels, whereas carriers of the APOE*2 allele (APOE 3,2 and APOE 2,2) had the lowest values for total and low-density lipoprotein cholesterol and the highest concentrations of high-density lipoprotein cholesterol. No significant differences in triglyceride and insulin levels among subjects with different APOE polymorphisms were observed. Unlike previous studies in the Mexican population, our results show that lipid and lipoprotein levels are under the influence of APOE polymorphism. As in whites, APOE*4 may be a cardiovascular risk factor in the Mexican population.

Hypertriglyceridemia and Hypercholesterolemia Induced by L-Asparaginase

Hypertriglyceridemia and Hypercholesterolemia Induced by L-Asparaginase

Restenosis after intracoronary stent placement: can apolipoprotein(a) polymorphism play a role?

Background: The relationship between lipoprotein(a) and restenosis after intracoronary stent implantation has been analysed by two specific studies, but the role of apoliprotein(a) polymorphism was not considered. The aim of the present prospective study was to evaluate whether lipoprotein(a) levels and apolipoprotein(a) phenotypes are predictors of restenosis after elective stent implantation in patients with de novo lesions of coronary arteries. Methods: We recruited 182 patients with a new lesion successfully treated with elective placement of one or two Palmaz–Schatz stents. Follow-up angiography was scheduled at 6 months or earlier if clinically indicated. Nine patients were lost to the follow up. Among 173 patients enrolled, restenosis was present in 52 (30.0%) and absent in 121 (70.0%). Results: Lipoprotein(a) levels were higher in the restenosis than in the nonrestenosis group (29.5±17.2 versus 27.4±20.2 mg/dl), even if the difference did not attain statistical significance ( P=0.067). The restenosis group had a percentage of subjects with at least one apolipoprotein(a) isoform of low molecular weight significantly greater than the nonrestenosis group (82.7 versus 66.9%; P=0.035). A multiple logistic regression analysis showed that multiple stenting (RR: 4.01; CI 95%: 1.65–13.91; P=0.004), presence of diabetes (RR: 3.96; CI 95%: 1.67–9.37; P=0.002) and presence of multivessel disease (RR: 2.71; CI 95%: 1.19–6.16; P=0.017) were predictors of restenosis after stent placement. Lipoprotein(a) and apolipoprotein(a) polymorphism did not enter the model as predictive variables. Conclusions: Our study confirms that multiple stenting, diabetes and multivessel disease are powerful predictors of restenosis after intracoronary stent implantation. On the contrary, lipoprotein(a) and apolipoprotein(a) polymorphism do not appear to be reliable markers of restenosis in patients with stent implantation.

Effects of genetic factors on the response to hormone replacement therapy

Hormone Replacement Therapy (HRT) is currently recognized as the potential tool for menopause medicine. But it is also well known that the effects of HRT on bones and blood vessels show interindividual variances. Among the candidate factors to explain these variances, genetic factors may play an important role. Several reports have shown associations between some genetic markers, such as polymorphisms of estrogen receptor alpha gene, and the effect of HRT on bone mineral density. Phenotype of apolipoprotein B, E, and angiotensin-converting enzyme, as well as polymorphisms of estrogen receptor alpha gene, have been reported to influence the lipid metabolic or vasodilatic response to HRT. This information can be applicable to tailor-made therapy. But the results of reports are conflicting and relationships between genetic markers and the response to HRT are still controversial. Further investigations will reveal the potential of genetic markers in disease managements near future.

Intracerebral haemorrhage in previously healthy adults following aerobic and anaerobic exercise

Primary objective : Intracerebral haemorrhage (ICH) without demonstrated tissue pathology in previously healthy adults has not been previously linked to anaerobic or aerobic exercise. The possible mechanisms and risk factors for ICH that may be found in a young, 'healthy' adult are described. Research design : Case reports of two patients who suffered a frontal lobe ICH following aerobic and anaerobic exercise are presented. A review of the literature was carried out to elucidate the risk factors for ICH in previously healthy adults. Main outcomes : Hypocholesterolemia below 4.14 mmol/l, phenylpropanolamine use above 75mg per day and certain apolipoprotein phenotypes (Apo E2 and Apo E4), which can all be found in young, healthy adults have all been described in the literature as contributors to the risk of ICH. Conclusions : There is a need for these risk factors to be researched in more detail, given that potential risk modifiers may help decrease their posed threat.

Relation of Apolipoprotein (a) Phenotypes to Diabetic Retinopathy in Elderly Type 2 Diabetes.

The aim of this study was to clarify the relationship between apolipoprotein (a) (apo (a) ) phenotypes and diabetic retinopathy in elderly type 2 diabetes. Serum Lp (a) concentrations and apo (a) phenotypes were analyzed in 250 diabetic patients aged 60 to 88 years old. Apo (a) phenotypes were classified into 7 subtypes (F, B, S1, S2, S3, S4, O (Null) ) by the method SDS electrophoresis with Western blotting. Patients were divided into two groups according to their apo (a) phenotypes:a low molecular weight (LMW) Lp (a) group, and a high molecular weight (HML) Lp (a) group. Patients were classified as having one of 4 types of diabetic retinopathy: no retinopathy (R0), simple retinopathy (R1), pre-proliferative retinopathy (R2), and proliferative retinopathy (R3). There was a significant association between serum Lp (a) levels and severity of diabetic retinopathy (p<0.001). A gradual trend toward increasing serum Lp (a) levels was observed across the groups (from R0 to R3). A significantly greater percentage of LMW Lp (a) was observed in the R1, R2, and R3 groups than in the R0 group (42.9% (p<0.001), 27.0% (p<0.01), and 27.3% (p<0.05) vs. 10.4%). Multiple logistic regression analysis revealed that duration of diabetes and LMW Lp (a) are independent risk factors for diabetic retinopathy. These results provide significant evidence that LMW Lp (a) contributes to an increased risk of diabetic retinopathy in elderly type 2 diabetes.

Associations between apolipoprotein E phenotype, glucose metabolism and cognitive function in men. An explorative study in a population sample.

To investigate the associations of the apolipoprotein E phenotype (apoE) and disturbed glucose metabolism with cognitive function in a random population sample. A cross-sectional study was conducted, in which 528 men aged 54 or 60 years were recruited randomly from a larger population-based sample of 1516 men. A subject was defined as having abnormal glucose tolerance (AGT), if he had a clinical diagnosis of diabetes, with either dietary or oral antidiabetic treatment or showed impaired glucose tolerance in an oral glucose tolerance test. The subjects were divided into three groups according to apolipoprotein E phenotypes: (a) E2/4, E3/4 or E4/4 (apoE E4); (b) E 3/3 (apoE E3); and (c) E2/2 or E2/3 (apoE E2). Memory function was examined using a word-list learning with Buschke's selective reminding method and test. Executive functions were assessed with the Trail Making Test A and B. Those subjects with apoE E2 and abnormal glucose metabolism demonstrated the worst cognitive executive control compared to other groups. Simple cognitive speed did not differ between the groups. The exploratory analyses revealed that subjects with apoE E2 allele and AGT had worse glycaemic control and cognitive executive control compared to other groups. Different apolipoprotein phenotypes together with impaired glucose tolerance may have different cumulative adverse effects on age-related cognitive performance. Some subgroups of subjects may be especially vulnerable to cognitive impairment.

Protease inhibitor related type III hyperlipoproteinaemia is common and not associated with apolipoprotein-E E2/E2 phenotype

Objective: To determine the prevalence of type III hyperlipoproteinaemia in a cohort of HIV infected patients taking protease inhibitors and its correlation with the apolipoprotein-E2 isoform. Design: Cross sectional study...

Association of lipoprotein(a) levels and apolipoprotein(a) phenotypes with coronary artery disease in Type 2 diabetic patients and in non-diabetic subjects.

We investigated whether in Type 2 diabetic patients lipoprotein(a) (Lp(a)) levels and apolipoprotein(a) (apo(a)) polymorphism are associated with angiographically documented coronary artery disease (CAD). We also examined whether there are differences in the distributions of Lp(a) levels and apo(a) phenotypes between CAD patients with and without diabetes. A hundred and seven diabetic patients with CAD, 274 diabetic patients without CAD, 201 non-diabetic patients with CAD, and 358 controls were enrolled. Diabetic patients with CAD showed Lp(a) levels (21.2 +/- 17.7 vs. 15.1 +/- 17.8 mg/dl; P = 0.0018) and a percentage of subjects with at least one apo(a) isoform of low molecular weight (MW) (67.2% vs. 27.7%; P = 0.0000) significantly greater than diabetic patients without CAD. Multivariate analysis showed that in diabetic patients Lp(a) levels and apo(a) phenotypes were significantly associated with CAD; odds ratios (ORs) of high Lp(a) levels for CAD were 2.17 (1.28-3.66), while ORs of the presence of at least one apo(a) isoform of low MW were 5.35 (3.30-8.60). Lp(a) levels (30.2 +/- 23.7 vs. 21.2 +/- 17.7 mg/dl; P = 0.0005) and the percentage of subjects with at least one apo(a) isoform of low MW (87.0% vs. 67.2%; P = 0.0001) were significantly higher in CAD patients without than in those with diabetes. Our data suggest that Lp(a) levels and apo(a) phenotypes are independently associated with CAD in Type 2 diabetic patients; thus both these parameters may be helpful in selecting diabetic subjects at high genetic cardiovascular risk. However, Lp(a) levels and apo(a) polymorphism seem to be cardiovascular risk factors less important in diabetic than in non-diabetic subjects. Diabet. Med. 18, 589-594 (2001)

Influence of apolipoprotein-E phenotypes on postprandial lipoprotein metabolism after three different fat loads

The aim of this study was to evaluate the postprandial response to three fat-loading tests in healthy subjects with different apolipoprotein E (apoE) phenotypes. Thirty-four subjects were studied: 15 with apoE3/3 (7 men and 8 women), 12 with apoE4/3 (5 men and 7 women), and 7 with apoE2/3 (4 men and 3 women). All received three oral fat loads at 1-wk intervals in meals rich in monounsaturated fatty acid, polyunsaturated fatty acid, and saturated fatty acid, with retinyl palmitate (60000 IU/m 2 of aqueous vitamin A) to quantify lipoproteins secreted by the intestine. No significant differences in postprandial lipoproteins were found between the three different fat loads. Peaks and incremental areas under the curve of retinyl palmitate in non-chylomicron fractions were higher in the apoE2/3- than in the apoE3/3- and apoE4/3-phenotype groups in meals rich in monounsaturated and polyunsaturated fatty acids ( P < 0.05). When the three fat loads were analyzed together, the incremental area under the curve of retinyl palmitate was much higher in the apoE2/3- than in the other apoE-phenotype groups ( P = 0.0004). In conclusion, the magnitude of intestinal lipoproteins after fat load, especially with monosaturated and polyunsaturated fatty acids, is higher in subjects with apoE2/3 than in those with apoE3/3 and apoE4/3 phenotypes.

Phenotype of apolipoprotein E influences the lipid metabolic response of postmenopausal women to hormone replacement therapy

Objectives: We investigated whether the phenotype of apolipoprotein E (apo E) would influence the response of postmenopausal Japanese women to hormone replacement therapy (HRT). Methods: We measured the plasma levels of lipoprotein and apolipoprotein in 242 postmenopausal women at baseline and again after 12 months of HRT. Patients were divided into three groups according to apo E phenotype: E2+ (E2/2 and E2/3, n=21), E3/3 ( n=176), E4+ (E3/4 and E4/4, n=45). Results: We found that the E4+ group had the highest levels of total and low density lipoprotein (LDL) cholesterol and apolipoprotein B, being significantly higher than in the E2+ group at baseline. The plasma levels of total and LDL cholesterol showed a significant decrease only in the E2+ and E3/3 groups after 12 months of HRT (E2+ group, total cholesterol −8.9% and LDL cholesterol −21.5%; E3/3 group, total cholesterol −2.9% and LDL cholesterol −9.5%). No significant difference in the reduction of total and LDL cholesterol was found in the E4+ group. Other lipid parameters did not differ in the three groups. Conclusions: These data show that the apo E phenotype influenced the response of lipid metabolism in postmenopausal women to HRT, especially in the reduction of LDL cholesterol. Therefore, apo E phenotyping may be important in predicting the cholesterol-lowering effect of HRT.

Impact of apolipoprotein(a) phenotypes on long-term renal transplant survival.

The long-term success of renal transplantation is limited because of chronic rejection (CR), which shows histologic parallels to atherosclerosis. Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerosis, but its role in CR has not been investigated. Plasma levels of Lp(a) are determined mainly by the inherited isoform (phenotype) of apolipoprotein(a) [apo(a)] and show an inverse correlation with the molecular weight of apo(a). Apo(a) isoforms were identified in frozen sera of 327 patients who received a renal transplant during 1982 to 1992. Long-term graft survival in recipients with high molecular weight (HMW) or low molecular weight (LMW) apo(a) phenotypes were compared retrospectively. Mean (95% confidence interval) transplant survival was 12.8 yr (range, 11.9 to 13.6 yr) in patients with HMW and 11.9 yr (range, 10.8 to 13.1 yr) in patients with LMW apo(a) phenotypes (P = 0.2065). In patients who were 35 yr or younger at the time of transplantation, mean transplant survival was more than 3 yr longer in recipients with HMW apo(a) phenotypes compared with those with LMW apo(a) phenotypes (13.2 yr [range, 12.1 to 14.4 yr] versus 9.9 yr (range, 8.5 to 11.5 yr); P = 0.0156). In a Cox's proportional hazards regression model, the presence of LMW phenotypes-but not gender, immunosuppression, or HLA mismatches-in young patients was associated with a statistically significant risk of CR (P = 0.0434). These retrospective data indicate that young renal transplant recipients with LMW apo(a) phenotypes have a significantly shorter long-term graft survival, regardless of the number of HLA mismatches, gender, or immunosuppressive treatment.

Apolipoprotein-E phenotype and basal activity of low-density lipoprotein receptor are independent of changes in plasma lipoprotein subfractions after cholesterol ingestion in japanese subjects

We investigated whether the apolipoprotein-E (apoE) phenotype and the basal activity of low-density lipoprotein (LDL) receptor, which were reported to be the major determinants for increase in plasma LDL levels by cholesterol ingestion, have the same role in Japanese subjects whose diet is low in fat and cholesterol. Cholesterol (750 mg/d) was added to the ordinary diet as a dried egg-yolk supplement for 4 wk to 110 subjects. Plasma levels of lipids, apolipoproteins, and cholesterol in lipoprotein subfractions were measured at the beginning and end of the test period. Phenotyping of apoE was determined by an isoelectric focusing-immunoblotting method, and LDL receptor activity in lymphocytes was determined by flow cytometry. Plasma levels of cholesterol in less-dense LDL (LDL 1) and less-dense high-density lipoprotein (HDL 2) were slightly but significantly increased, 3.4% and 4.1%, respectively, by cholesterol ingestion, but the increases were not statistically significant in any of E2, E3, and E4 groups. The distribution of the apoE phenotype was equivalent in all three LDL-cholesterol groups (no change, increase, and decrease by cholesterol ingestion). Plasma levels of LDL, LDL 1, and LDL 2 cholesterol were not significantly increased in the three groups of subjects with lymphocyte LDL-receptor activities (low, medium, and high). As with apoE phenotype, LDL-receptor activities were the same in all three LDL-cholesterol groups. In addition, there were no significant correlations between LDL-receptor activity and changes in plasma levels of lipids, apolipoproteins, and cholesterol in lipoprotein subfractions. Therefore, we concluded that cholesterol ingestion significantly increases plasma levels of less-dense LDL and HDL, but neither apoE phenotype nor basal LDL-receptor activity explain the variability in changes in plasma lipoprotein subfractions by cholesterol ingestion in Japanese subjects.

Lipoprotein(a) changes during natural menstrual cycle and ovarian stimulation with recombinant and highly purified urinary FSH

This prospective, randomized, controlled study compared the effects of recombinant human FSH (r-hFSH) and highly purified urinary FSH (u-hFSH HP) on lipoprotein(a) [Lp(a)] concentrations in women undergoing ovarian stimulation. Fifty infertile women were randomly allocated into two equally sized treatment groups (n = 25 per group). Thirty normal ovulation women were recruited as controls. The infertile women received u-hFSH or r-hFSH 150 IU/day starting on cycle day 2. From cycle day 6 the dose was adjusted according to ovarian response. Human chorionic gonadotrophin 10,000 IU was administered once there was at least one follicle > or =18 mm in diameter. The luteal phase was supported with progesterone 50 mg/day for at least 15 days. Repeated measurements of Lp(a) concentrations were performed during both stimulated and natural cycles. A significant increase in luteal phase Lp(a) concentrations was detected in the stimulated cycles, whereas no significant changes in serum Lp(a) concentrations were observed during natural cycles. There were no significant differences between the urinary and recombinant FSH effects on serum Lp(a). The luteal Lp(a) increase was transitory because after 1 month Lp(a) concentrations returned to baseline values if pregnancy failed to occur; in pregnant women persistent increased Lp(a) concentrations were found at the 8th week. The percentage changes in serum Lp(a) were positively correlated with the luteal progesterone increase (r = 0.40, P < 0.05), but not with follicular or luteal oestradiol increase. The women with low baseline Lp(a) (< or =5 mg/dl) had a greater increase of the Lp(a) concentrations at midluteal phase than women with baseline Lp(a) >5 mg/dl. In conclusion, the recombinant or urinary hFSH administration does not directly influence Lp(a) concentrations. The luteal Lp(a) increase in stimulated cycles is not related to gonadotrophin treatment per se, but appears to be related to the high luteal progesterone concentrations, physiologically or pharmacologically determined. Our results also suggest that the sensitivity to the progesterone changes could be related to apolipoprotein(a) phenotype.

Lipoprotein (a), Apolipoprotein (a) Phenotypes, and Thyroid Autoimmunity in Uremic Patients

Lipoprotein (a), Apolipoprotein (a) Phenotypes, and Thyroid Autoimmunity in Uremic Patients

Plasma lipoprotein (a) concentrations and apolipoprotein (a) phenotypes in an Aboriginal population from Western Australia

Factors contributing to the variation in plasma lipoprotein (a) (Lp(a)) concentration were surveyed in an Aboriginal population (175 men and 219 women), aged 24-86 years, from Western Australia. The plasma Lp(a) levels were highly skewed towards low levels in this population, with a median of 84 mg/L and a mean of 166 mg/L. Approximately 20% had plasma Lp(a) above the threshold value of 300 mg/L, while 52% had Lp(a) levels below 100 mg/L. The most commonly occurring phenotype was apolipoprotien(a) S4. In this phenotype, Lp(a) concentrations ranged from not detectable to 468 mg/L. There was a positive relationship between cigarette smoking and plasma Lp(a) concentration in men. Apolipoprotein A1 and bilirubin were positively associated with Lp(a) in the 40-60 age group and a positive relationship between weight and Lp(a) concentrations was observed in those aged 60 years or over. Thus, although Lp(a) is mainly genetically determined, there are clearly other factors which contribute to variations in Lp(a) concentrations.

Apolipoprotein(a) phenotype and retinopathy in diabetic patients

Apolipoprotein(a) phenotype and retinopathy in diabetic patients