Mean Apolipoprotein Research Articles

DIFFERENCES OF APOLIPOPROTEIN A1 AND APOLIPOPROTEIN B LEVELS IN TYPE 2 DIABETES MELLITUS (T2DM) PATIENTS WITH DIABETIC RETINOPATHY AND WITHOUT DIABETIC RETINOPATHY

Introduction Apolipoprotein A1 are antiatherogenic in blood serum and have an anti-inflammatory while Apolipoprotein B describes a protein structure that is potentially atherogenic.. Meanwhile, the inflammatory process plays a role in the diabetic retinopathy process. The aim of this study was to determine whether there were differences in the levels of apolipoprotein A1 and B in diabetic retinopathy patients and without diabetic retinopathy.
 Methods: This study used a cross sectional design. The subjects of this study were type 2 diabetes mellitus patients with diabetic retinopathy and without diabetic retinopathy at Dr. Sardjito General Hospital from July to September 2020. Subjects consisted of 32 patients in the group with diabetic retinopathy and 31 patients without diabetic retinopathy. The levels of apolipoprotein A1 and apolipoprotein B were analyzed using independent T test. The factors affecting apolipoprotein A1 and apolipoprotein B were analyzed using multiple regression tests.
 Result: There were no significant differences (p> 0.05) in age, gender, duration of diabetes, HDL, triglycerides, HbA1c, BMI, physical activity, and smoking history. The mean apolipoprotein A1 level in the diabetic retinopathy group was 1.46 ± 0.177 mg / dL higher than the non-diabetic retinopathy group, namely 1.44 ± 0.27 mg / dL (p = 0.699). The mean level of apolipoprotein B in the diabetic retinopathy group was 1.26 ± 0.289 mg / dl higher than the non-diabetic retinopathy group 1.01 ± 0.26 mg / dL (p = 0.001). The mean LDL levels were 162.5 ± 48.38 mmol / L in the diabetic retinopathy group and 127 ± 38.45 mmol / L in the group without diabetic retinopathy (p = 0.012).
 Conclusion: Apolipoprotein B levels were found to be higher in the group with diabetic retinopathy than in the group without diabetic retinopathy and there was a significant difference between the two assumed due to an atherogenic process in the diabetic retinopathy group. Further research is needed to assess the causal relationship between elevated levels of Apo B and the incidence of diabetic retinopathy by calculating the ratio of apolipoprotein B to apolipoprotein A1.
 Keywords: Apolipoprotein A1, Apolipoprotein B, Diabetic Retinopathy

Malaria parasite density and plasma apolipoprotein A1 in symptomatic and asymptomatic infections in Nigerian children.

Alterations in plasma apolipoproteins in individuals with malaria infection and their potential roles in the pathogenesis are known but the link between the malaria parasite density and apolipoprotein A1 (apo-A1) level is insufficiently understood. This study was conducted to determine whether the plasma apo-A1 level is influenced by the degree of parasitaemia in malaria infections. In a case-control study, a convenient sample of children aged 2-10 years with uncomplicated malaria cases (UMC), asymptomatic parasitaemia cases (APC) and healthy children without parasitaemia (HCP) was recruited. The cases consisted of 61 UMC and 21 APC, while the controls consisted of 24 HCP. Levels of apo-A1 was determined using immunoturbidimetric assay and compared among the different degrees of parasite density. Of the 82 participants with parasitaemia, density was ≤1000/μL in 12, 1001-10000/μL in 21 and >10000/μL in 49 children. There was significant difference among the mean values of apolipoprotein A1 of the three groups, viz: UMC [91.4 (95% CI: 81.3, 101.5) mg/dL], APC [67.0 (95% CI: 48.9, 84.9) mg/dL] and HCP [99.0 (95% CI: 76.6, 121.3) mg/dL], p=0.029. Post-hoc analysis revealed that the mean plasma level of apo-A1 in HCP was significantly higher than APC by 32.0±12.4 mg/dL and UMC by 7.5±4.2 mg/dL. However, there were no differences in the mean apolipoprotein A1 levels among the three groups of parasite density. The presence of parasitaemia causes a remarkable reduction in apolipoprotein A1 level that was not influenced by the degree of parasitaemia.

Egg consumption may improve factors associated with glycemic control and insulin sensitivity in adults with pre- and type II diabetes.

Without appropriate interventions, prediabetes is typically followed by type II diabetes. Eggs are a rich source of important nutrients including protein, vitamins, minerals, carotenoids and lecithin. In this 12-week, parallel, randomized controlled trial, 42 overweight or obese individuals between the ages of 40 and 75 years with pre- and type II-diabetes were included. Participants were randomly assigned to receive either one large egg per day or an equivalent amount of egg substitute for 12 weeks. Blood samples were obtained to analyze lipid profile and biomarkers associated with glycemic control at all time points. Regular egg consumption resulted in improvements of fasting blood glucose, which was significantly (P = 0.05) reduced by 4.4% at the final visit in the egg group. Participants in the egg group had significantly (P = 0.01) lower levels of homeostatic model assessment of insulin resistance (HOMA-IR) at all visits. In the egg group, ATP-binding cassette protein family A1 (ABCA1) was significantly higher at the 6-week visit (0.78 ± 0.21 vs. 0.28 ± 0.05 mg dL-1, P < 0.001) and tended to be higher at the final visit (0.62 ± 0.11 vs. 0.55 ± 0.18 mg dL-1, P = 0.1). The mean apolipoprotein A1 (apo A1) level was also significantly higher at the final visit in the egg group compared to the control (147.43 ± 5.34 vs. 142.81 ± 5.09 mg dL-1, P = 0.01). There were no significant changes in total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels. Daily consumption of one large egg may reduce the risk of diabetes without having any adverse effects on lipid profiles in individuals with pre- and type II diabetes.

Dyslipidaemia for patients with low-energy femoral neck fractures after the treatment of cancellous screws: a retrospective study with a 3-year minimum follow-up

BackgroundAvascular necrosis of the femoral head (AVNFH) occurs infrequently following femoral neck fracture. The association between AVNFH and dyslipidaemia remains controversial. Although major risk factors for AVNFH have been proposed, most of them remain under discussion. Our purpose herein was to evaluate the association between dyslipidaemia and AVNFH following low-energy femoral neck fractures treated with cancellous screws in elderly patients in our tertiary care centre.MethodsFour hundred and seventy-two consecutive patients (472 hips) with low-energy femoral neck fractures were identified and treated with cancellous screws from July 2007 to April 2013. Patients underwent evaluations preoperatively and each subsequent postoperative visit (months 1, 6, 12, 18, 24, 30, and 36). Clinical and radiographic evaluations were documented at each visit. The risk factors of AVNFH were assessed by multivariate binary logistic analysis.ResultsFollow-up was available for 277 patients, which included 135 patients diagnosed with AVNFH (AVNFH group) and 142 patients without AVNFH (control group). The median follow-up for patients alive at the time of analysis was 40 months (range, 37 to 46 months). The mean total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and apolipoprotein B (Apo-B) values were considerably higher in the AVNFH group compared with those in the control group. The mean high density lipoprotein cholesterol (HDL-C) and apolipoprotein A1(Apo-A1) values were significantly lower in the AVNFH group compared with those in the control group. A multivariate logistic backward regression model showed that HDL-C and LDL-C were the only variables associated with the development of postoperative AVNFH in patients with a femoral neck fracture (Odds ratio[OR] 33.09, 95% Confidence Interval[CI]: 2.65–19.42, p < 0.001 and OR 45.94, 95% CI: 0.47–27.75, p < 0.001, respectively).ConclusionOur results suggest that both low HDL-C and high LDL-C have a tendency to result in the occurrence of AVNFH in elderly patients with low-energy femoral neck fractures treated with cancellous screws.

The association between the apolipoprotein B/A-I ratio and coronary calcification may differ depending on kidney function in a healthy population.

BackgroundThe apolipoprotein B/A-1 ratio has been reported to be one of the strongest risk predictors of cardiovascular events. However, its prognostic value for cardiovascular disease is still uncertain, especially in patients with chronic kidney disease. This study aimed to investigate whether the association between the apolipoprotein B/A-I ratio and coronary artery calcification differed according to kidney function in a healthy population.MethodsOf the data from 7,780 participants from the medical records database in Gangnam Severance Hospital from 2005 through 2016, a cross-sectional analysis included participants with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 determined based on the Chronic Kidney Disease -Epidemiology Collaboration equation (n = 1,800). Mild renal insufficiency was defined as an eGFR of 60–90 mL/min/1.73 m2. Coronary artery calcification measured with computed tomography was defined as an above-zero score. Logistic regression analyses were used to determine the association between coronary calcification and the apolipoprotein B/A-I ratio according to eGFR by adjusting for the influence of confounders.ResultsThe mean apolipoprotein B/A-I level was significantly higher in the participants with coronary artery calcification than in the participants without coronary artery calcification. The apolipoprotein B/A-I ratio was significantly different according to coronary artery calcification in the participants with normal kidney function, but in the participants with mild renal insufficiency, it was not different. After adjusting for age, male sex, systolic blood pressure, body mass index, current smoking status, and fasting plasma glucose, the apolipoprotein B/A-I ratio was significantly associated with an increased risk of coronary artery calcification in participants with normal kidney function (odds ratio = 2.411, p = 0.011), while in the participants with mild renal insufficiency, the apolipoprotein B/A-I ratio was not associated with coronary artery calcification.ConclusionOur study showed that the predictive value of apolipoprotein B/A-I ratio for coronary artery calcification may differ according to kidney function.

Open-label therapy with alirocumab in patients with heterozygous familial hypercholesterolemia: Results from three years of treatment

BackgroundPCSK9 inhibition with alirocumab significantly reduced LDL-C levels in trials of up to 78weeks' duration in patients with heterozygous familial hypercholesterolemia (HeFH). We report results from 3years of an ongoing open-label treatment extension (NCT01576484) to a 12-week double-blind trial in HeFH patients (NCT01266876). MethodsPatients who completed the parent study and were receiving stable daily statin±ezetimibe could enter the open-label extension, where they received alirocumab 150mg every 2 weeks (Q2W) subcutaneously (n=58). The primary endpoint was safety (treatment-emergent adverse events, TEAEs). Efficacy endpoints included the percentage change in LDL-C from baseline at Week 24. Safety and efficacy data were available up to Weeks 156 and 148, respectively. ResultsMean baseline LDL-C was 150.7mg/dL (3.9mmol/L), despite all patients being on a statin (76% on high-intensity statin; 72% also receiving ezetimibe). Over 156weeks, 54 (93.1%) patients experienced a TEAE, 12 (20.7%) experienced a serious TEAE, and two (3.4%) discontinued due to a TEAE. Injection site reactions occurred in 21 (36.2%) patients. Mean (SD) reduction in LDL-C from baseline to Week 24 was 65.4 (21.1)%, with reductions maintained through 148weeks (Week 148 reduction: 56.0 [23.8]%). Mean apolipoprotein B reduction was 50.9% and median lipoprotein (a) reduction was 22.5% at Week 24 (46.1% and 25.6% at Week 148, respectively). ConclusionsOpen-label treatment for 3years with alirocumab 150mg Q2W, administered with background statin±ezetimibe, was generally well-tolerated and had a safety profile comparable with that seen in the overall alirocumab clinical trial program. Alirocumab provided significant, sustained LDL-C reductions.

Correlation of lipoprotein(a) with the extent of coronary artery disease in patients with established coronary atherosclerosis: gender differences

To assess the gender differences in correlation lipoprotein(a) concentration with the extent of coronary artery disease in patients with established coronary artery disease. Blood lipids and lipoprotein(a) concentrations were measured in 351 consecutive patients (256 men and 95 women) who underwent coronary angiography between January and May 2010, and who had established coronary atherosclerosis (angiography score >1). A modified angiographic Gensini Score was used. Mean angiographic score was 19.6 in men and 15.0 in women. Men had lower mean high-density lipoprotein cholesterol level than women (1.05 vs. 1.18 mmol/l) and lower mean apolipoprotein A level (1.41 vs. 1.53 g/l). Mean lipoprotein(a) level was higher in men than women (307.1 vs. 282.7 mg/l). Significant inverse correlation between high-density lipoprotein cholesterol and apoA with angiographic score was identified in women (r = -0.23, p = 0.028 and r = -0.26, p = 0.025), but not in men. Lipoprotein(a) level correlated significantly with angiographic score only in men (r = 0.168, p = 0.0185). Gender differences were identified in patients with established coronary atherosclerosis in the relation of blood lipids and lipoprotein(a) levels with the extent of coronary artery disease.

Serum Lipid Profile in Preterm and Term Appropriate for Gestational Age Indian Newborns: A Hospital Based Comparative Study

Background: Cardiovascular disease is a common cause of death in developed countries and also is a rising trend in developing countries. Aim: The objective of this study was to compare lipid profile and atherogenic indices in term and preterm neonates. Methods: A total of 60 neonates were selected which were grouped on the basis of gestational age and birth weight. Umbilical venous blood was collected from them. Lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, VLDL cholesterol, triglycerides), apolipoproteins (apo B and apo A-I) and atherogenic index were evaluated and compared. Student- t test (unpaired) was applied to test the significance. Results: Mean serum cholesterol and LDL was significantly high in preterm .Mean TC / LDL ratio of preterm group 3.17, term 2.64 (p< 0.006).Mean Apolipoprotein A-1 in preterm 78.37 mg/dl, term 76.51 mg/dl (P<0.67). Mean apolipoprotein B / A-1 ratio in preterm 0.45, term 0.39, (p<0.11) showing worse profile in preterm. Conclusions: These findings demonstrate a trend towards worse lipid profile in preterm SGA new-borns. There is a need to investigate if this atherogenic lipid profile is a marker for future cardiovascular diseases.

Increased apoB/A‐I ratio independently associated with Type 2 diabetes mellitus: cross‐sectional study in a Korean population

The aim of this study was to investigate whether increased apolipoprotein B/apolipoprotein A-I ratio is associated with Type 2 diabetes mellitus independent of other risk factors for Type 2 diabetes. A total of 70,063 subjects (41,391 men and 28,672 women; mean age 41.5 years) who visited the Health Screening Center at Kangbuk Samsung Hospital for a routine medical check-up between January 2009 and December 2009 were enrolled in this study. The mean apolipoprotein B/apolipoprotein A-I ratio in the study subjects was 0.66 ± 0.18. The prevalence of Type 2 diabetes increased across the apolipoprotein B/apolipoprotein A-I ratio quartiles (1.0%, 1.6%, 2.9%, and 4.8% for the 1st through 4th quartiles, respectively, P < 0.001) and homeostasis model assessment-insulin resistance (HOMA2-IR) also showed an increasing tendency by quartile (P < 0.001). The apolipoprotein B/apolipoprotein A-I ratio was correlated with age, adiposity, blood pressure, HOMA2-IR value, fasting glucose levels, and other inflammatory marker, including high-sensitivity C-reactive protein, and lipoprotein (a) levels (all P < 0.001). In a multiple logistic regression model, the highest apolipoprotein B/apolipoprotein A-I ratio quartile was associated with Type 2 diabetes, even after controlling for other risk factors for diabetes, such as age, gender, BMI, systolic blood pressure, HOMA2-IR values, high-sensitivity C-reactive protein levels, family history of diabetes, presence of metabolic syndrome, and conventional lipid parameters (odds ratio 1.31; 95% confidence interval 1.17-1.46, P < 0.001). The apolipoprotein B/apolipoprotein A-I ratio was found to be associated with Type 2 diabetes independent of other risk factors for diabetes and conventional lipid parameters.

Abstract 104: Serum from Patients with Aortic Valvular Stenosis Shows Decreased Cholesterol Efflux Capacities Despite Similar High-Density Lipoprotein Cholesterol Levels

Background: Studies have shown that low HDL-cholesterol levels may be associated with the progression of aortic valvular calcium and aortic valvular stenosis (AVS), but whether patients with AVS have impaired cholesterol efflux capacities is unknown. Methods and results: We have measured four parameters of cholesterol efflux capacity in apolipoprotein B-depleted serum samples from 48 patients with (aortic jet velocity ≥2.5 m/s, mean age = 72 ± 7 years and 72.7% men) and 51 patients without AVS (aortic jet velocity ≤ 1.7 m/s, mean age 71 ± 7 years and 70.6% men). Cholesterol efflux capacity was measured using J774 macrophages with and without stimulation of ABCA1 expression by cAMP (non-stimulated efflux, total efflux and ABCA1-mediated efflux), and HepG2 hepatocytes to measure SR-BI-mediated efflux. Mean HDL-cholesterol and apolipoprotein A-I levels as well as efflux are shown in the table for patients with vs. without AVS. The Pearson correlation coefficient between HDL-cholesterol levels and SR-B1-dependent efflux was 0.39 (p=0.007) in patients with AVS and 0.68 (&lt;0.0001) in controls (P-value for the difference between the correlation coefficients obtained with Fisher’s test = 0.04). Conclusions: This study provides evidence that serum from patients with AVS may have impaired cholesterol efflux capacities, especially through the SR-B1 pathway. Table. Mean HDL-cholesterol and apolipoprotein A-I levels as well as non-stimulated-, total-, ABCA1-, and SR-B1-dependent cholesterol efflux obtained from patients’ serum with vs. without AVS. Data is shown as mean ± SD. Differences between categories were assessed using a Student unpaired t-test.

Association of Cholesteryl Ester Transfer Protein Genotypes With CETP Mass and Activity, Lipid Levels, and Coronary Risk

The importance of the cholesteryl ester transfer protein (CETP) pathway in coronary disease is uncertain. Study of CETP genotypes can help better understand the relevance of this pathway to lipid metabolism and disease risk. To assess associations of CETP genotypes with CETP phenotypes, lipid levels, and coronary risk. Studies published between January 1970 and January 2008 were identified through computer-based and manual searches using MEDLINE, EMBASE, BIOSIS, Science Citation Index, and the Chinese National Knowledge Infrastructure Database. Previously unreported studies were sought through correspondence with investigators. Relevant studies related principally to 3 common (TaqIB [rs708272], I405V [rs5882], and -629C>A [rs1800775]) and 3 uncommon (D442G [rs2303790], -631C>A [rs1800776], and R451Q [rs1800777]) CETP polymorphisms. Information on CETP genotypes, CETP phenotypes, lipid levels, coronary disease, and study characteristics was abstracted from publications, supplied by investigators, or both. Ninety-two studies had data on CETP phenotypes, lipid levels, or both in 113,833 healthy participants, and 46 studies had data on 27,196 coronary cases and 55,338 controls. For each A allele inherited, individuals with the TaqIB polymorphism had lower mean CETP mass (-9.7%; 95% confidence interval [CI], -11.7% to -7.8%), lower mean CETP activity (-8.6%; 95% CI, -13.0% to -4.1%), higher mean high-density lipoprotein cholesterol (HDL-C) concentrations (4.5%; 95% CI, 3.8%-5.2%), and higher mean apolipoprotein A-I concentrations (2.4%; 95% CI, 1.6%-3.2%). The pattern of findings was very similar with the I405V and -629C>A polymorphisms. The combined per-allele odds ratios (ORs) for coronary disease were 0.95 (95% CI, 0.92-0.99) for TaqIB, 0.94 (95% CI, 0.89-1.00) for I405V, and 0.95 (95% CI, 0.91-1.00) for -629C>A. Three CETP genotypes that are associated with moderate inhibition of CETP activity (and, therefore, modestly higher HDL-C levels) show weakly inverse associations with coronary risk. The ORs for coronary disease were compatible with the expected reductions in risk for equivalent increases in HDL-C concentration in available prospective studies.

Cord blood lipid profile and associated factors: baseline data of a birth cohort study

The cord blood lipid profile may be associated with lifelong changes in the metabolic functions of the individual. The aim of the present study was for the first time in Iran to assess the cord blood lipid profile of neonates, as well as some of its environmental influencing factors. The subjects were 442 (218 boys and 224 girls) normal vaginal delivery newborns. Overall, 14.4% of neonates were preterm and the rest were full-term. In total, 9.2% (n = 35) of the full-term newborns were small-for-gestational-age (SGA), of which 16 had a ponderal index (PI) below the 10th percentile (SGA I) and 19 had a PI above the 10th percentile (SGA II), 5.5% (n = 21) were large-for-gestational-age (LGA), and the remainder were appropriate-for-gestational-age (AGA).Before becoming pregnant, 6.9% of mothers were underweight, 49.3% had normal body mass index (BMI), 39.4% were overweight and 4.4% were obese. Total and high-density lipoprotein cholesterol (HDL-C) in girls were significantly higher than in boys (80.3 +/- 33.3 and 31.1 +/- 9.9 vs. 73.3 +/- 23.1 and 28.8 +/- 8.7 mg/dL, respectively, P < 0.05). The mean apolipoprotein A (apoA) of neonates with underweight mothers was significantly lower, and the mean apoB level of those with overweight mothers was significantly higher than other neonates. The mean low-density lipoprotein cholesterol (LDL-C), HDL-C and apoA of the LGA newborns were significantly lower, and their apoB was significantly higher compared with AGA and SGA neonates. The SGA I neonates had significantly lower total cholesterol, LDL-C, HDL-C and apoA, as well as higher triglycerides, lipoprotein a and apoB than the SGA II group. The mean cord blood triglycerides of full-term neonates was significantly higher than preterm neonates (69.4 +/- 11.9 vs. 61.4 +/- 12.7 mg/dL, respectively, P = 0.04). A preconception maternal BMI of > or =25 kg/m(2) correlated significantly with the cord triglycerides (OR = 1.3, [95% CI 1.07, 1.5]) and with apoB (OR = 1.4, [95% CI 1.1, 1.5]). The BMI <18 of mothers before pregnancy correlated with low HDL-C (OR = 1.3, [95% CI 1.04, 1.7]). Birthweight correlated with high cord triglyceride level (SGA: OR = 1.4, [95% CI 1.1, 1.7]; LGA: OR = 1.6, [95% CI 1.3, 1.7] compared with AGA). These associations remained significant even after adjusting for the preconception BMI of mothers. Our findings reflect the possible interaction of environmental factors and fetal growth and the in utero lipid metabolism. Long-term longitudinal studies in different ethnicities would help to elucidate the relationship.

Ezetimibe is effective when added to maximally tolerated lipid lowering therapy in patients with HIV

To determine the efficacy and safety of adding ezetimibe to maximally tolerated lipid lowering therapy in patients with HIV dyslipidemia.Retrospective analysis of lipid parameters was conducted for 33 patients with HIV who had been prescribed ezetimibe 10 mg per day.Mean total cholesterol was reduced 21% (p < 0.001). Mean LDL was reduced 35% (p < 0.001). Mean HDL increased 8% (p = 0.038). Mean triglyceride was reduced 34% (p = 0.006). Mean Apolipoprotein B100 was reduced 33% (p = 0.043). No adverse events occurred.Ezetimibe appears safe and effective in patients with HIV when added to maximally tolerated doses of lipid lowering therapy.

Body composition, lipid and lipoprotein levels in childhood‐onset systemic lupus erythematosus

Objectives: Systemic inflammation, corticosteroid therapy, and reduced physical activity are risk factors for altered body composition in patients with systemic lupus erythematosus (SLE). The aim of this study was to assess whether body composition differs between childhood‐onset SLE patients and healthy controls, and to investigate the impact of disease characteristics and lifestyle factors on body fat mass, serum lipids, and lipoproteins.Methods: Fat mass and lean tissue mass were measured in a cross‐sectional study of 68 childhood‐onset SLE patients and 68 matched healthy controls by dual‐energy X‐ray absorptiometry (DXA). The influence of disease, glucocorticosteroids, disease activity and severity, physical activity, and dietary intake on fat mass was evaluated by multiple linear regression analysis. Serum lipid and lipoprotein levels were measured.Results: Patients had a significantly higher fat mass [mean (SD) 35.3 (10.8) vs. 30.9 (11.1)%; p = 0.024] and lower lean mass [39.7 (9.8) vs. 44.4 (1.5) kg; p = 0.003] than controls. Corticosteroid use and the disease itself were significant independent predictors of greater fat mass, while disease activity, physical activity, and dietary intake had only a minor influence. Mean high density lipoprotein (HDL) cholesterol and apolipoprotein A1 (apo A1) levels were significantly lower (p<0.001), and the mean apo B/apo A1 ratio significantly higher (p = 0.004), in patients than in controls.Conclusion: Childhood‐onset SLE patients had a higher fat mass and lower lean mass than healthy controls and corticosteroid use was an independent predictor of increased fat mass. Patients had a more proatherogenic lipid profile, which will contribute to the increased risk of coronary heart disease in SLE patients.

Effects of raloxifene and low-dose simvastatin coadministration on plasma lipids in postmenopausal women with primary hypercholesterolemia

Raloxifene and low-dose simvastatin can each reduce low-density lipoprotein (LDL) cholesterol without affecting high-density lipoprotein (HDL) cholesterol and triglycerides. The objective of this double-blind, 12-week study is to determine whether raloxifene and simvastatin coadministration gives added benefit beyond either monotherapy in affecting fasting lipoproteins and apolipoproteins. Ninety-five postmenopausal women with moderately elevated LDL cholesterol (mean, 146 mg/dL) were randomized to placebo, raloxifene 60 mg/d, simvastatin 10 mg/d, or raloxifene 60 mg/d coadministered with simvastatin 10 mg/d. Raloxifene, simvastatin, and coadministration therapy reduced mean LDL cholesterol by 10.5%, 23.3%, and 31.0% from baseline, respectively ( P < .003 vs baseline; P < .02 vs placebo), and mean apolipoprotein B by 10.4%, 24.2%, and 30.0% from baseline, respectively ( P < .003 vs baseline; P < .02 vs placebo). Each active treatment decreased non-HDL cholesterol compared with placebo ( P < .01). Coadministration treatment was more effective than either monotherapy in reducing LDL cholesterol ( P < .05). Coadministration treatment reduced mean apolipoprotein B ( P < .001) and non-HDL cholesterol ( P < .001) when compared with raloxifene, but was not significantly different when compared with simvastatin. Coadministration therapy increased HDL cholesterol and apolipoprotein A1 levels compared with placebo ( P < .02). No significant effect on triglycerides, very low density lipoprotein cholesterol, and lipoprotein (a) occurred with any active treatment. Raloxifene, simvastatin, and the coadministration therapy were generally well tolerated with clinical adverse effects similar to placebo. No woman had clinically significant elevated liver function tests requiring drug discontinuation. Further data on safety and lipid-lowering effects are needed before raloxifene and statin coadministration may be considered as therapeutic interventions for treating postmenopausal women to achieve National Cholesterol Education Program–Adult Treatment Panel III treatment guidelines.

Interaction between angiotensin-converting enzyme genotype and glycaemic control influences lipoprotein levels in type 2 diabetes mellitus.

To evaluate the influence of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on lipid levels in patients with Type 2 diabetes. 109 patients with Type 2 diabetes were included. The patients were not on any lipid-lowering treatment. The groups with different ACE genotypes had similar ages, sex distributions, body mass indices, systolic blood pressures and indices of glycaemic control. ACE gene I/D polymorphism was determined using polymerase chain reaction. The mean apolipoprotein B (apoB) level was significantly higher in the group of DD homozygotes compared with the subjects with at least one insertion allele (DD: 1.21 +/- 0.25 g/l vs. ID + II: 1.04 +/- 0.27 g/l; P = 0.007). Significant correlations between glycated haemoglobin (HbA1c) and both apoB and cholesterol levels were found (r = 0.27; P < 0.01). For the apoB, this correlation was highly significant in the DD-genotype subgroup (r = 0.54; P < 0.01), and was not significant in the subgroup of patients with genotypes ID or II. In the multivariate analysis, HbA1c and the interaction of genotype DD with HbA1c were significant independent predictors of apoB (r2 = 0.17) and cholesterol levels. The present study showed that the interaction between the DD genotype of angiotensin-converting enzyme and chronic hyperglycaemia (expressed by HbA1c level) is related to higher plasma levels of atherogenic lipoproteins, such as apoB and cholesterol, in patients with Type 2 diabetes.

Increased levels of lipoprotein (a) in Crohn's disease: a relation to thrombosis?

Lipoprotein (a) is recognized as a risk factor for arterial and venous thrombosis, a property that might be related to its structural similarity to plasminogen. Since patients with inflammatory bowel disease frequently suffer from thromboembolic events, we studied the role of lipoprotein (a) in conjunction with lipids and apolipoproteins in Greek patients with ulcerative colitis and Crohn's disease. Lipoprotein (a), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein A-1 and apolipoprotein B-100 were determined in sera from 129 consecutive fasting Greek patients with inflammatory bowel disease (66 with ulcerative colitis and 63 with Crohn's disease) and from 66 matched healthy controls. In Crohn's disease patients, the mean serum lipoprotein (a) level was significantly higher than in control patients (41.2 mg/dl vs 22.9 mg/dl; P = 0.005). Mean apolipoprotein A-1 and apolipoprotein B-100 levels were significantly lower in Crohn's disease patients than in the controls. In ulcerative colitis patients the mean levels of lipoprotein (a) and apolipoprotein A-1 were not significantly different to the controls, but the levels of apolipoprotein B-100 were significantly lower. Raised levels of lipoprotein (a) of > 30 mg/dl were found in 29 Crohn's disease patients (46%), 15 ulcerative colitis patients (23%) and 11 control patients (17%). Patients with active Crohn's disease had significantly higher mean lipoprotein (a) and lower apolipoprotein A-1 than patients with non-active disease. Our results suggest that Crohn's disease patients have different lipoprotein (a) and apolipoprotein patterns compared to ulcerative colitis patients and healthy controls. These changes in Crohn's disease patients may possibly expose them to a higher risk of thrombosis.

Effectiveness of Colesevelam Hydrochloride in Decreasing LDL Cholesterol in Patients With Primary Hypercholesterolemia: A 24-Week Randomized Controlled Trial

To evaluate the efficacy, tolerability, and safety of colesevelam hydrochloride, a new nonsystemic lipid-lowering agent. In this double-blind, placebo-controlled trial performed in 1998, 494 patients with primary hypercholesterolemia (low-density lipoprotein [LDL] cholesterol level > or = 130 mg/dL and < or = 220 mg/dL) were randomized to receive placebo or colesevelam (2.3 g/d, 3.0 g/d, 3.8 g/d, or 4.5 g/d) for 24 weeks. Fasting serum lipid profiles were measured to assess efficacy. Adverse events were monitored, and discontinuation rates and compliance rates were analyzed. The primary outcome measure was the mean absolute change of LDL cholesterol from baseline to the end of the 24-week treatment period. Colesevelam lowered mean LDL cholesterol levels 9% to 18% in a dose-dependent manner (P<.001), with a median LDL cholesterol reduction of 20% at 4.5 g/d. The reduction in LDL cholesterol levels was maximal after 2 weeks and sustained throughout the study. Mean total cholesterol levels decreased 4% to 10% (P<.001), while median high-density lipoprotein cholesterol levels increased 3% to 4% (P<.001). Median triglyceride levels increased by 5% to 10% in placebo and colesevelam treatment groups relative to baseline (P<.05), but none of these differences were significantly different from placebo. Mean apolipoprotein B levels decreased 6% to 12% in an apparent dose-dependent manner (P<.001). No significant differences occurred in adverse events or discontinuation rates between groups, and compliance rates were between 88% and 92% for all groups. Colesevelam was efficacious, decreasing mean LDL cholesterol levels by up to 18%, and well tolerated without serious adverse events.

Lipoprotein abnormalities in patients with secondary renal amyloidosis.

The prevalance of hyperlipidemia in chronic renal failure (CRF) patients is higher than in general population. Secondary amyloidosis is a common cause of CRF in Turkey. In this study, 25 patients with CRF due to secondary renal amyloidosis (amyloid-CRF), 15 patients with CRF without amyloidosis-CRF and 17 healthy controls were studied for serum lipid parameters. The mean serum lipoprotein (a) [LP(a)] level in the patients with amyloid-CRF was significantly higher than in the controls (p < 0.01). The mean serum apolipoprotein B (Apo B), apolipoprotein E (Apo E) and triglyceride levels in the patients with amyloid-CRF were very significantly higher than in the controls (p < 0.001). The mean serum total cholesterol, low-density lipoprotein (LDL) levels in the patients with amyloid-CRF were higher than in the controls (p < 0.05). The mean serum apo AI levels in the patients with amyloid-CRF was very significantly lower than in the controls (p < 0.001). The mean serum high-density lipoprotein (HDL) in the patients with amyloid-CRF was lower than in the controls (p < 0.05). The mean serum Lp (a), Apo AI, Apo B and Apo E levels in the patients with amyloid-CRF were significantly higher than in the patients with CRF (p < 0.01). The mean serum total cholesterol, trigliserides, LDL and HDL levels in the patients with amyloid-CRF were higher than in the patients with CRF (p < 0.05). There was not any correlation with serum lipid parameters and serum albumin and urine protein levels (p > 0.05). Our study suggests that serum lipid parameters are abnormal and might be the risk factor of atherosclerotic vascular disease and contribute to renal disease progression in the patients with secondary renal amyloidosis and lipid abnormalities were different from CRF with various etiology, without amyloidosis.

Apolipoprotein A-IV polymorphism in Saami and Finns: frequency and effect on serum lipid levels

Apolipoprotein A-IV (apoA-IV) is a glycoprotein constituent of triglyceride-rich and high-density lipoproteins (HDL) and may thus play an important role in lipid metabolism. In Finland two common isoforms (A-IV-1 and A-IV-2) of apoA-IV have been found. The isoforms are the result of the G to T substitution in the third base of the codon 360 in the apoA-IV-2 allele of the apoA-IV gene. The purpose of the study was to determine the apoA-IV allele frequencies in the Saami and the Finns, and to relate the apoA-IV phenotypes to serum lipids. The sample was drawn in connection with a Reindeer Herders' Health Survey performed in northern Finland in 1989. The study group included 248 men with known ethnic origin, Saami and Finns, who lived in the area of the nine northernmost municipalities of Finland. ApoA-IV phenotypes from 71 Saami (both parents Saami) and 177 Finns (both parents Finns) were determined by isoelectric focusing and Western blotting. Serum lipids were determined enzymatically. ApoA-IV allele frequencies in the Saami and the Finns were for A-IV-1 0.894 vs 0.944 and for A-IV-2 0.106 vs 0.056, respectively (χ2-test, P < 0.05). The effect of the apoA-IV phenotype on serum HDL-cholesterol levels differed significantly between the Saami and the Finns (two-way ANCOVA, interaction between ethnicity and apoA-IV phenotype, P < 0.02). In the Saami, HDL-cholesterol levels were significantly higher in the apoA-IV-2/1 than in the apoA-IV-1/1 phenotypes (ANCOVA, P < 0.05). Mean total cholesterol, low-density lipoprotein (LDL)-cholesterol, apolipoprotein B, HDL-cholesterol and triglyceride levels did not differ statistically significantly between the Saami and the Finns. Yet, there was a trend in the Saami of having higher mean total cholesterol, LDL-cholesterol and apolipoprotein B levels than the Finns among the apoA-IV-2/1 phenotypes, while there was only a small difference in these parameters between the Saami and the Finns among the apoA-IV-1/1 phenotypes. In conclusion, the Saami have a higher frequency of the apoA-IV-2 allele than the Finns and most of the other studied populations.