Serum Apolipoprotein Concentrations Research Articles

Association between Serum Concentrations of Apolipoprotein A-I (ApoA-I) and Alzheimer's Disease: Systematic Review and Meta-Analysis.

Background: A wealth of experimental and epidemiological evidence suggest that Apolipoprotein A-I (ApoA-I), the main protein constituent of high-density lipoprotein (HDL), may protect against Alzheimer disease (AD). To investigate this potential role, we conducted a meta-analysis of the published studies on the relationship between serum ApoA-I and AD occurrence. Methods: We screened MEDLINE, EMBASE, Web of Science, and Scopus, for cross-sectional studies published from inception to 1 March 2021, comparing the ApoA-I serum levels between patients with AD and cognitively normal controls. Results: From an initial screening of 245 articles, 5 studies, including 397 AD patients (mean age 75.0 years, 234 females) and 367 controls (mean age 69.2 years, 182 females), met the inclusion criteria. Compared to healthy controls, AD subjects had a lower ApoA-I serum level. The pooled weighted mean difference from a random-effects model was −0.31 g/L (p < 0.0001) (95% Confidence Interval: [−0.62–0.01], with high heterogeneity (I2 = 100%). The Egger’s test confirmed an absence of publication bias (t = 0.62, p = 0.576). Conclusions: Our study showed that AD patients present lower serum levels of ApoA-I compared to cognitively normal individuals. Further studies on large population samples are required to support this finding.

Genetic predisposition and bioinformatics analysis of ATP-sensitive potassium channels polymorphisms with the risks of elevated apolipoprotein B serum levels and its related arteriosclerosis cardiovascular disease.

Serum concentration of apolipoprotein B (Apo B) is causally associated with arteriosclerosis cardiovascular disease (ASCVD) risk. Whether ATP-sensitive potassium channels (KATP) variants predict the risk of increased Apo B concentration (≥ 80 mg/dL) and related ASCVD remain less clear. We recruited 522 subjects with elevated Apo B concentration (≥ 80 mg/dL) and 522 counterpart subjects (< 80 mg/dL) from South China to assess the associations of KATP variants (rs11046182, rs78148713, rs145456027 and rs147265929) with the risks of increased Apo B serum concentration (≥ 80 mg/dL), carotid artery stenosis (CAS) ≥ 50% and new-onset ischemic stroke (IS). Our results showed that only KATP SNP rs11046182 (GG genotype) was associated with increased risk of Apo B ≥ 80 mg/dL (adjusted OR=2.17, P<0.001) and CAS ≥ 50% (adjusted OR=2.63, P=0.011). After median 50.6-months follow-up, subjects carrying GG genotype of rs11046182 were associated with higher risk of new-onset IS (adjusted HR=2.24, P=0.024). Further, the exosome-derived microRNAs (exo-miRs) expression profile was identified by next-generation sequencing. 41 exo-miRs were significantly differentially expressed under cross-talk status between high Apo B level (≥ 80 mg/dL) and KATP rs11046182. Our study demonstrated that KATP variant rs11046182 was associated with higher risks of elevated serum Apo B levels and its related ASCVD, and the possible mechanism was related to specific exo-miRs expression profile of KATP rs11046182.

Increased serum concentration of apolipoprotein B is associated with an increased risk of reaching renal replacement therapy in patients with diabetic kidney disease

Objective Few studies have investigated the association of apolipoprotein B (ApoB) with the progression of diabetic kidney disease (DKD) and the risk of renal replacement therapy (RRT). Method In this retrospective cohort study, a group of 258 DKD patients with stage 3–5chronic kidney disease(CKD)were divided into low ApoB (<1.1 g/L) and high ApoB (≥1.1 g/L) groups and followed-up for 20.51 ± 6.11 months. The association of the serum ApoB concentration with RRT was determined by Kaplan–Meier and Cox regression analysis. ApoB was measured in the serum. Results Ninety-three of the 258 DKD patients needed RRT during follow-up. Kaplan–Meier analysis showed that patients with high ApoB were significantly more likely to progress to RRT than those with low ApoB (log-rank = 16.62, p < 0.001). The presence of high ApoB increased the risk of RRT. Analysis of ApoB as either a categorical (<1.1 g/L or ≥1.1 g/l) or continuous variable by univariate and multivariate regression found that ApoB was an independent risk factor of DKD progression to RRT in this group of DKD patients with stage 3–5 CKD (p < 0.05). Conclusion Increased ApoB was an independent predictor of progression to RRT. A larger study is needed to confirm the unfavorable prognosis of increased ApoB in DKD patients.

Evaluation of Serum Apolipoprotein E as a Potential Biomarker for Pharmacological Therapeutic Efficacy Monitoring in Dopamine Dictated Disease Spectrum of Schizophrenia and Parkinson's disease: A Preliminary Study.

Aim of the Study:Parkinson’s disease and schizophrenia are disease end points of dopaminergic deficit and hyperactivity, respectively, in the mid brain. Accordingly, current medications aim to restore normal dopamine levels, overshooting of which results in adverse effects of psychosis and extra-pyramidal symptoms, respectively. There are currently no available laboratory tests to guide treatment decisions or help predict adverse side effects of the drugs. The aim was to therefore explore the possibility of using apolipoprotein E as a biomarker to monitor pharmacological intervention in dopamine dictated states of Parkinson’s disease and schizophrenia for optimum therapy.Methods:Naïve and treated, Parkinson’s disease and schizophrenic patients were recruited from neurology and psychiatry clinics. Serum of healthy volunteers was collected as controls. Serum concentrations of apolipoprotein E was estimated by enzyme-linked immunosorbent assay (ELISA). Pathway analysis was carried out to delineate the interactions of apolipoprotein E in Parkinson’s disease and schizophrenia.Results:Apolipoprotein E levels are higher in Parkinson’s disease patients as compared with schizophrenic samples (P < .05). Also, post-treatment apolipoprotein E levels in both disease states were at par with levels seen in healthy controls. The interactions of apolipoprotein E validate the results and place the differential expression of the protein in Parkinson’s disease and schizophrenia in the right perspective.Conclusion:Apolipoprotein E concentration across the dopaminergic spectrum suggests that it can be pursued not only as a potential biomarker in schizophrenia and Parkinson’s disease, but can also be an effective tool for clinicians to determine efficacy of drug-based therapy.

Analysis of the prevalence and risk factors of preoperative angiography confirmed coronary artery stenosis in patients with degenerative valvular heart disease

Objective: To estimate the prevalence and the risk factors of preoperative coronary angiography (CAG) confirmed coronary stenosis in patients with degenerative valvular heart disease. Methods: A total of 491 patients who underwent screening CAG before valvular surgery due to degenerative valvular heart disease were enrolled from January 2011 to September 2014 in our hospital, and clinical data were analyzed. According to CAG results, patients were divided into positive CAG result (PCAG) group or negative CAG (NCAG) group. Positive CAG result was defined as stenosis ≥50% of the diameter of the left main coronary artery or stenosis ≥70% of the diameter of left anterior descending, left circumflex artery, and right coronary artery.Risk factors of positive CAG result were analyzed by multivariable logistic regression analysis, and Bootstrap method was used to verify the results. Results: There were 47(9.57%)degenerative valvular heart disease patients with PCAG. Patients were older ((68.0±7.6)years vs.(62.6±7.1)years, P<0.001) and the prevalence of typical angina was significantly higher (14.89%(7/47)vs. 2.03%(9/444), P<0.001)in PCAG group than in NCAG group. Multivariable logistic regression analysis showed that age (OR=1.118, 95%CI 1.067-1.172, P<0.001), typical angina (OR=8.970, 95%CI 2.963-27.154, P<0.001), and serum concentration of apolipoprotein B (OR=20.311, 95%CI 4.774-86.416, P<0.001) were the independent risk factors of PCAG in degenerative valvular heart disease patients. Bootstrap method revealed satisfactory repeatability of multivariable logistic regression analysis results (age: OR=1.118, 95%CI 1.068-1.178, P=0.001; typical angina: OR=8.970, 95%CI 2.338-35.891, P=0.001; serum concentration of apolipoprotein B: OR=20.311, 95%CI 4.639-91.977, P=0.001). Conclusions: A low prevalence of PCAG before valvular surgery is observed in degenerative valvular heart disease patients in this patient cohort. Age, typical angina, and serum concentration of apolipoprotein B are independent risk factors of PCAG in this patient cohort.

Effects of gender and menopausal status on serum apolipoprotein concentrations

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Effects of gender, age and menopausal status on serum apolipoprotein concentrations.

To undertake a comprehensive evaluation of apolipoprotein risk markers for cardiovascular disease (CVD) according to gender, age and menopausal status. Cross-sectional analysis of independent associations of gender, age and menopause with serum apolipoproteins. Apparently healthy Caucasian premenopausal (n = 109) and postmenopausal (n = 252) women not taking oral contraceptives or hormone replacement, and Caucasian men (n = 307). Serum apolipoprotein (apo) B, A-I and A-II concentrations were measured, plus serum total cholesterol, low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively), triglycerides, cholesterol in HDL subfractions and the apoB/apoA-I, LDL-C/apoB, HDL-C/apoA-I and HDL-C/apoA-II ratios. Analyses were undertaken with and without standardization for confounding characteristics and in 5-year age ranges. Overall, apoB concentrations were highest in men but in women rose with age and menopause to converge, in the age range of 50-55 years, with concentrations in men. The LDL-C/apoB ratio was generally higher in women than in men. ApoA-I concentrations were highest in postmenopausal women and lowest in men (standardized median (IQR) 144 (130, 158) vs 119 (108, 132) g/l, respectively, P < 0·001). ApoA-II concentrations were also highest in postmenopausal women but were lowest in premenopausal women (40·3 (37·5, 44·5) vs 32·9 (30·5, 35·7) g/l, respectively, P < 0·001). Nevertheless, postmenopausal women had HDL-C/apoA-I and HDL-C/apoA-II ratios approaching the lowest ratios, which were seen in men. Consistent with adverse effects on CVD risk, male gender, ageing in women and menopause were associated with increased apoB concentrations, and menopause and male gender were associated with a decreased cholesterol content of HDL particles.

Apolipoprotein B/Apolipoprotein A-I Ratio and Apolipoprotein B

We investigated whether serum concentrations of apolipoprotein (apo) B and apoA-I and the apoB/apoA-I ratio provided predictive information on myocardial infarction (MI) and ischemic stroke during 13 years of follow-up in a group of initially clinically healthy 58-year-old men, free from previous cardiovascular disease, diabetes, other established disease, or treatment with cardiovascular drugs. Multivariate logistic regression analysis showed that the apoB/apoA-I ratio and apoB were significant and independent determinants of MI (exponentiation of the B coefficient [Exp(β)] 3.1, 95% confidence interval [CI] 1.6-6.3, P=.001, Exp(β) 2.8, 95% CI 1.1-7.7, P=.045, respectively). The area under the receiver-operating characteristics curve as a relative measure of test efficiency was highest and significant for both apoB/apoA-I ratio and apoB (area under the curve=0.75, P<.001). In conclusion, the apoB/apoA-I ratio and apoB are independent risk factors for MI and has the highest efficiencies for predicting MI in initially healthy middle-aged men.

Association of Apolipoprotein B and Nuclear Magnetic Resonance Spectroscopy–Derived LDL Particle Number with Outcomes in 25 Clinical Studies: Assessment by the AACC Lipoprotein and Vascular Diseases Division Working Group on Best Practices

The number of circulating LDL particles is a strong indicator of future cardiovascular disease (CVD) events, even superior to the concentration of LDL cholesterol. Atherogenic (primarily LDL) particle number is typically determined either directly by the serum concentration of apolipoprotein B (apo B) or indirectly by nuclear magnetic resonance (NMR) spectroscopy of serum to obtain NMR-derived LDL particle number (LDL-P). To assess the comparability of apo B and LDL-P, we reviewed 25 clinical studies containing 85 outcomes for which both biomarkers were determined. In 21 of 25 (84.0%) studies, both apo B and LDL-P were significant for at least 1 outcome. Neither was significant for any outcome in only 1 study (4.0%). In 50 of 85 comparisons (58.8%), both apo B and LDL-P had statistically significant associations with the clinical outcome, whereas in 17 comparisons (20.0%) neither was significantly associated with the outcome. In 18 comparisons (21.1%) there was discordance between apo B and LDL-P. In most studies, both apo B and LDL-P were comparable in association with clinical outcomes. The biomarkers were nearly equivalent in their ability to assess risk for CVD and both have consistently been shown to be stronger risk factors than LDL-C. We support the adoption of apo B and/or LDL-P as indicators of atherogenic particle numbers into CVD risk screening and treatment guidelines. Currently, in the opinion of this Working Group on Best Practices, apo B appears to be the preferable biomarker for guideline adoption because of its availability, scalability, standardization, and relatively low cost.

Increased Serum Cholesterol Esterification Rates Predict Coronary Heart Disease and Sudden Death in a General Population

Lecithin:cholesterol acyltransferase (LCAT) is thought to be important in reverse cholesterol transport. However, its association with coronary heart disease (CHD) and sudden death is controversial. We prospectively studied 1927 individuals from the general population. Serum concentrations of apolipoprotein A-I, A-II, B, C-II, C-III, E, and LCAT activity measured as a serum cholesterol esterification rate were evaluated. We documented 61 events of CHD and sudden death during 10.9 years of follow-up. After adjustment for age and sex, LCAT activity was significantly associated with the risk of CHD and sudden death (hazard ratio, 3.02; 95% confidence interval, 1.49-6.12; P=0.002). In multivariate analysis adjusted for age, sex, current smoking status, history of diabetes mellitus, body mass index, systolic blood pressure, serum total cholesterol, and serum high-density lipoprotein cholesterol concentrations, the hazard ratio of LCAT activity for the risk of CHD and sudden death remained significant (hazard ratio, 3.07; 95% confidence interval, 1.35-7.01; P=0.008). However, when it was analyzed for men and women separately, this association remained significant only in women. Increased LCAT activity measured as a serum cholesterol esterification rate was a risk for CHD and sudden death in a Japanese general population.

Association of Apolipoproteins with Symptoms of Asthma and Atopy among Schoolchildren

Background: There is evidence for an association between serum cholesterol concentrations and asthma, but little is known about the underlying mechanisms. We explored the associations between serum apolipoprotein concentrations and symptoms of asthma and atopy. Methods: In a population-based cross-sectional study among 10-year-old schoolchildren (n = 462), plasma concentrations of apolipoprotein AI (apoAI) and apolipoprotein B (apoB) were measured. Information on disease symptoms and diagnoses was collected by parental questionnaire. Multivariate logistic regression models were used to analyse the data. Results: High plasma apoAI concentrations (≥1.74 g/l) were associated with high prevalence of wheeze (OR 3.65; 95% CI 1.43–9.33), and a trend was seen with asthma (OR 3.35; 95% CI 0.94–11.93). In linear analyses, plasma apoAI concentrations were positively related to wheeze (β-coefficient = 3.20; p = 0.045) and non-atopic wheeze (β-coefficient = 4.47; p = 0.036), and a trend was found for asthma (β-coefficient = 3.29; p = 0.099). Overall, plasma apoB concentrations were not associated with either symptoms of asthma or allergy. Conclusion: Our results support the hypothesis that high apoAI is associated with the manifestation of asthma and atopy. The underlying pathomechanism still remains to be fully elucidated, but suggests that immune mechanisms may play a central role. However, our results are based on a small study sample and larger studies are warranted to confirm these observations.

Heritability of Serum Apolipoprotein Concentrations in Middle-Aged Japanese Twins

BackgroundStudies of the genetic and environmental influences on apolipoproteins have been conducted, but few have used data from Japanese twins. The aim of this study was to quantify and compare the genetic and environmental causes of individual differences in the serum concentrations of apolipoproteins in Japanese middle-aged twins.MethodsApo A-I, apo A-II, apo B, apo C-II, apo C-III, and apo E were studied. A total of 142 twin pairs, aged 45 through 65 years, were enrolled: 85 monozygotic pairs (59 male, 26 female) and 57 same-sexed dizygotic pairs (43 male, 14 female). The intraclass correlation coefficient and structural equation modeling were used to estimate the best-fitting model and heritability.ResultsSixteen percent to 75% of the total variances of apo A-I, apo C-II, and apo C-III were attributable to genetic influence; apo A-I and apo C-II were influenced by dominant genetic factors. Twenty percent to 73% of the total variances of apo A-II, apo B, and apo E were attributable to additive genetic influence; apo B was clearly influenced by common environmental factors. Furthermore, the heritability of all apolipoproteins was higher among females than among males.ConclusionsGenetic factors, including additive genetic effects (A) and dominant effects (D), influence apolipoprotein levels. However, a common environment does not influence the variances of these apolipoproteins, with the exception of apo B. Furthermore, the heritability of apolipoprotein phenotypes differs by sex.

ApoB/apoA-I ratio is related to femoral artery plaques in 64-year-old women also in cases with low LDL cholesterol

Introduction The apolipoproteinB (apoB)/apolipoproteinA-I (apoA-I) ratio mirrors the number of pro-atherogenic and anti-atherogenic lipoprotein particles. This ratio may carry more information on risk for atherosclerosis than LDL in cohorts with impaired glucose tolerance. The aim was to examine the association between the apoB/apoA-I ratio and ultrasound-assessed atherosclerosis in the carotid and femoral arteries in women with varying degrees of glucose tolerance. Methods Plaque occurrence, and intima-media thickness in the carotid and femoral arteries were examined by B-mode ultrasound in a random sample of 64-year-old women ( n = 646) living in Gothenburg, Sweden, representing different degrees of glucose intolerance (diabetes ( n = 234), impaired ( n = 212) and normal glucose tolerance ( n = 200)). Traditional risk factors and serum concentrations of apolipoproteins were analysed. Results For subjects in the lowest LDL tertile, the risk of having a plaque in the femoral artery was three times greater for subjects in the highest apoB/apoA-I tertile compared to subjects in the lowest tertile (OR: 3.0, 95% CI: 1.2–7.5). A clear increase in the occurrence of femoral plaque was observed already at a cut-off value of 0.63 (OR: 1.8, 95% CI: 1.2–2.6). ApoB/apoA-I was also related to femoral plaque occurrence in women with low HbA1c. ApoB/A-I ratio was associated with carotid and femoral IMT but not carotid plaques. Conclusion The apoB/apoA-I ratio improved the identification of cases with femoral artery atherosclerosis in a cohort of women with varying degrees of glucose tolerance. Such cases could also be identified in women with normal LDL and HbA1c levels. The results indicate that an apoB/apoA-I ratio above 0.63 should be used as a marker of increased risk.

Apolipoprotein B/apolipoprotein A-I in relation to the metabolic syndrome and change in carotid artery intima-media thickness during 3 years in middle-aged men.

The apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) ratio is a measure of the relationship between different lipoprotein particles and a powerful predictor of coronary death. The aim was to examine whether apoB/apoA-I was associated with the metabolic syndrome (MetS) at baseline and also with the future change in carotid artery intima-media thickness (IMT). In 313 58-year-old men, carotid artery IMT was measured bilaterally by high-resolution B-mode ultrasound at baseline and after 3 years of follow-up. Serum apolipoprotein concentrations and the components of MetS were measured at study entry. ApoB/apoA-I showed statistically significant associations with body mass index, waist-to-hip ratio, high-density lipoprotein (HDL) cholesterol, triglycerides, low-density lipoprotein (LDL) particle size, insulin, and diastolic blood pressure. Two thirds of the patients with MetS had high apoB/apoA-I ratios (>0.90) compared with one third of those without the syndrome (P<0.001). The IMT change was associated with apoB, total cholesterol, LDL cholesterol, triglycerides, and inversely with HDL cholesterol and LDL particle size at entry, and there was a strong colinearity between these variables. The subjects with apoB/apoA-I above the first tertile (0.74) had a 20-microm-higher (95% CI, 7 to 33) annual increase in IMT compared with those below this level after adjustment for blood pressure and smoking. The apoB/apoA-I ratio was strongly associated with MetS and its components at baseline. ApoB/apoA-I at baseline was related to the change in carotid artery IMT during 3 years of follow-up. There was a strong colinearity between apoB/apoA and the atherogenic lipids.

Hypocholesterolaemic effects of an ethanol precipitate of Kabosu juice in stroke-prone spontaneously hypertensive rats fed a cholesterol-free diet.

1. We have previously identified strong inhibitory effects of Kabosu (Citrus sphaerocarpa Hort.) juice precipitate (KJP) on cholesterol elevation in stroke-prone spontaneously hypertensive rats (SHRSP) fed a cholesterol diet. In the present study, to elucidate the hypocholesterolaemic mechanism, we examined the effect of dietary KJP on lipid metabolism by using SHRSP fed a cholesterol-free diet. 2. Compositions of the experimental diet containing 10% KJP powder were adjusted to those of the control diet. Seven-week-old male SHRSP were fed control or experimental diet for 2 weeks with free access to the diet and water. 3. Serum levels of cholesterol, phospholipid and triglyceride of the KJP group were significantly reduced, which was due to decreases in the very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) fractions. 4. Serum concentrations of apolipoproteins A-I and E (apoA-I and E) of the KJP group were significantly lower than those of the control group, whereas no significant differences were observed in serum apoB and apoA-IV between the two groups. 5. In liver, there were no significant differences in the contents of lipids or relative liver weight between the two groups. The activity of microsomal cholesterol 7alpha-hydroxylase of the KJP group tended to increase, whereas that of microsomal acyl-coenzyme A : cholesterol acyltransferase was significantly reduced, compared with the control group. 6. These results indicate that dietary KJP produces reductions of serum lipid levels, which are due to reductions in VLDL, apoE HDL and apoA-I HDL, and may promote catabolism and excretion of hepatic cholesterol in SHRSP fed a cholesterol-free diet.

Association Between Serum Concentration of Apolipoproteins A-I and B with Gallbladder Disease

Background. A total of 1,255 subjects attending a private health care facility in Mexico City were studied to evaluate the association of serum concentration of Apo A-I and Apo B with presence of gallbladder disease (gallstones or cholecystectomy). Methods. A cross-sectional study was carried out. All participants provided data on sociodemographic status and previous diagnoses of type 2 diabetes, hypertension, cardiovascular events, alcohol consumption, and smoking habits. Women additionally reported their obstetric-gynecologic history. Weight and height were measured; liver and biliary tract ultrasound assessed gallbladder disease. Plasma levels of total cholesterol, triglycerides, high-density lipoproteins (HDL) cholesterol, and apolipoproteins A-I (Apo A-I) and B (Apo B) were determined after a 12-h fasting period. Results. In multivariate models, Apo A-I ≥120 mg/dL was positively associated with gallbladder disease with odds ratio (OR) = 1.64, 95% confidence interval (95% CI) = 1.03–2.62, whereas Apo B ≥120 mg/dL showed an inverse association (OR = 0.71, 95% CI = 0.48–1.05). Ratio of Apo B/Apo A-I ≥1 was inversely associated with risk of gallbladder disease (OR = 0.54, 95% CI = 0.37–0.80). All models were adjusted for age, gender, body mass index (BMI), previous diagnosis of type 2 diabetes, triglycerides, alcohol consumption, tobacco, and contraceptive use, as well as for total cholesterol in HDL-cholesterol and Apo A-I models. Conclusions. Our results suggested the relationship between serum concentration of apolipoproteins and gallbladder disease. These findings support the hypothesis of increased biliary catabolism of cholesterol in subjects with gallbladder disease characterized by lower Apo B and higher Apo A-I serum concentrations.

Fibrinolysis Defect in Long-Term Hemodialysis Patients with Type 2 Diabetes mellitus and Its Relation to Metabolic Disorders

Background/Aims: Patients with chronic renal failure (CRF) secondary to diabetes mellitus show a high incidence of atherosclerosis with its thrombotic complications. Both CRF and type 2 diabetes mellitus (DM2) results in fibrinolysis defects causally related to atherogenesis and thrombogenesis. It is not well known whether or not and, if so, how fibrinolysis is altered in patients with both CRF and DM2. Our study was designed (1) to identify the fibrinolysis defect present in patients with DM2-mediated CRF and treated by long-term hemodialysis (DM2HD), and (2) to establish whether the fibrinolysis defect is related to the metabolic abnormalities observed in CRF or DM2. Methods: Sixteen DM2HD patients and 23 healthy individuals (HI) had their euglobulin clot lysis time (ECLT), and tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) activities (act) and concentrations (ag) assessed before and after standard fibrinolytic stimulus (i.v. administration of 0.4 µg/kg BW 1-deamino-8-D-arginine vasopressin, DDAVP) along with metabolic status markers. Results: DDAVP caused a significant shortening of ECLT, rises in tPA act and ag, and a significant decrease in PAI-1 act. PAI-1 ag declined significantly in HI, but not in DM2HD. A comparison of responses to DDAVP revealed the groups differed significantly in the change in PAI-1 ag. Whereas, in HI, PAI-1 ag decreased by 11.8 ng/ml, no decrease was seen in DM2HD (0.0 ng/ml) (p < 0.0001; medians given; unpaired Wilcoxon’s test). Stepwise regression analysis showed the change in PAI-1 ag was highly group-specific (DM2HD vs. HI, regression coefficient 21.22; partial correlation 0.58; p < 0.0001) and, also dependent on the serum concentrations of apolipoprotein A-I (–32.41; –0.46; p < 0.01) and homocysteine (0.35; 0.36; p < 0.05). Conclusions: Patients with type 2 DM and CRF on long-term hemodialysis have a fibrinolysis defect manifesting itself after standard fibrinolytic stimulus by an insufficient decrease in PAI-1 concentrations. The defect is related to decreased serum levels of apolipoprotein A-I and increased serum levels of homocysteine. The defect might be a factor contributing to accelerated atherosclerosis and thrombotic complications in these patients.

Coronary artery disease is associated with the ratio of apolipoprotein A-I/B and serum concentration of apolipoprotein B, but not with paraoxonase enzyme activity in Iranian subjects

To determine the association of serum apolipoprotein (apo) A-I and B concentrations, and paraoxonase (PON) high-density lipoprotein (HDL) associated enzyme activity with angiographically determined coronary artery disease (CAD) in Iranian diabetic and non-diabetic CAD patients and non-diabetic control subjects, 251 subjects aged 30–70 years, who underwent their first coronary angiography were matched and randomly assigned into three groups: CAD +DM +, CAD +DM −, and CAD −DM − (control). Stenosis of ≥50% in one or more coronary arteries was classified as CAD +. CAD − was defined as a maximum stenosis of 10% in any coronary artery. Fasting serum concentrations of cholesterol (TC), triglycerides (TGs), LDL-C, HDL-C, apo A-I/B and PON activity were determined. Apolipoprotein concentrations were measured in a fasting serum sample by immunoturbidometric assay and paraoxonase/arylesterase activities by spectrophotometric assay of p-nitrophenol/phenol production following addition of paraoxon/phenylacetate. Information concerning non-lipid risk factors were collected by questionnaires. No significant difference was observed in HDL-C, LDL-C, apo A-I, and PON/arylesterase activity between the study groups. The values of TC (213±38 vs 196±45, P<0.05), TGs (209±187 vs 151±113, P<0.01), apo B (99±22 vs 96±24, P<0.0001), TC/HDL-C (4.8±1.5 vs 4.0±1.3, P<0.001) and LDL-C/HDL-C (2.9±1.1 vs 2.4±1.1, P<0.05) were higher and apo A-I/B (1.7±0.4 vs 2.0±0.6, P<0.01) was lower in CAD +DM + patients than in control subjects. In CAD +DM − group, only the level of apo B (96±24 vs 85±18, P<0.01), and the ratio of apo A-I/B (1.8±0.4 vs 2.0±0.6, P<0.01), were significantly higher than those of control group. On multiple logistic regression analysis, the best markers for discrimination between CAD + groups and CAD − control subjects were the ratio of apo A-I/B in diabetic and apo B in non-diabetic patients. The results suggest that in Iranian diabetic and non-diabetic patients with CAD the concentration of apolipoproteins are better markers than traditional lipid parameters in discriminating between CAD + and CAD − subjects. Lack of significant difference in PON activity between CAD patients and CAD − controls supports the concept of interethnic variability in PON polymorphism and unimodal distribution of its activity in non-Europid populations observed in other studies.

Reference intervals for serum apolipoproteins A-I, A-II, B, C-II, C-III, and E in healthy Japanese determined with a commercial immunoturbidimetric assay and effects of sex, age, smoking, drinking, and Lp(a) level

Background: Apolipoproteins, which are contained in lipoprotein particles, play important roles in the transport of lipids. Methods: Serum levels of apolipoproteins (apo) A-I, A-II, B, C-II, C-III, and E were determined by immunoturbidimetry in a healthy Japanese study population (1018 men and 1167 women, age 20–69 years) to establish reference intervals. Results: Among the 2185 subjects examined, the mean serum value for apoA-I was 1.42±0.20 g/l, for apoA-II was 0.30±0.05 g/l, for apoB was 0.87±0.18 g/l, for apoC-II was 29±13 mg/l, for apoC-III was 75±20 mg/l, and for apoE was 36±9 mg/l. A sex difference was detected in the mean serum concentrations of all six apolipoproteins. Alcohol consumption and cigarette use had a slight effect on serum apolipoprotein concentrations. Age effects were observed among women in apoB, apoC-II, and apoC-III concentrations. Moreover, individuals with elevated serum lipoprotein (a) [Lp(a), >300 mg/l] also displayed increased serum apoB and apoC-II levels and an increased apoB/apoA-I ratio. Conclusion: The reference intervals for apolipoproteins in Japanese adults that we established, using commercially available reagents for automated analyzers, will be helpful for assessing risk of coronary heart disease and pathological conditions of patients with hyperlipidemia. We recommend use of these reference intervals for the clinical interpretation of serum apolipoprotein concentrations.

Reference intervals of Apo A-1 , Apo B and Apo B/Apo A-1 ratio in sample of macedonian population

The disorders of serum concentration of Apolipoproteins A-1 and B (Apo A-1 and Apo B), as well as of Apolipoprotein B/Apoliporotein A-1 ratio (Apo B/ Apo A-1) are considered to be independent risk factors for coronary heart disease. It is recommended that each laboratory should asign its own reference intervals for Apo A-1 and Apo B, as well as for Apo B/Apo A-1 ratio, as these depend on the geographical location. For this purpose we determined the serum concentration of Apo A-1 and Apo B and we calculated the Apo B/Apo A-1 ratio in 122 healthy individuals from Macedonian population (70 women and 52 men), aged 18-60 years. We used commercial, standardized manual immunoturbidimetric assay (Randox). The obtained concentrations (x ± SD) were: Apo A-1 = 1.39 ± 0.28 g/l in the female population and 1.42 ± 0.27 g/l in the male population, Apo B = 0.95 ± 0.24 g/l in the female and 1.00 ± 0.23 g/l in the male population. The calculated Apo B/Apo A-1 ratio was 0.70 ± 0.17 in the female subgroup and 0.72 ± 0.18 in the male subgroup. Student's t-test detected no significant difference (p&gt;0.05) in mean values for Apolipoproteins A-1 and B and for Apo B/Apo A-1 ratio between female and male subgroups, which lead to the conclusion that division according to sex is not necessary from diagnostic point of view. The Apo A-1 and Apo B concentrations estimated for the mixed group (N=122) were 1.40 ± 0.28 g/l and 0.97 ± 0.23 g/l. The Apo B/Apo A-1 ratio estimated for whole group was 0.71 ± 0.17. The type of distribution of values for Apo A-1, Apo B and Apo B/A-1 ratio was tested by calculating the values of coefficient of asymetry (Skewness), coefficient of flatness (Kurtosis) and standard deviations of these coefficients. The distribution of values was according to Gaussian curve for all three parameters. Therefore, according to the normal distribution reference intervals for Apo A-1, Apo B and Apo B/Apo A-1 ratio was estimated parametrically (mean ± 2 standard deviations). Reference intervals for Apo A-1 were 0.84 - 1.96 g/l, 0.51 - 1.43 g/l for Apo B and 0.37- 1.05 for Apo B/Apo A-1 ratio.