Mean ApoA1 Research Articles

Pretreatment HDL-C and ApoA1 are predictive biomarkers of progression-free survival in patients with EGFR mutated advanced non-small cell lung cancer treated with TKI.

BackgroundWe aimed to explore the correlation between blood lipids (high density lipoprotein cholesterol [HDL‐C] and apolipoprotein A1 [ApoA1]) and epidermal growth factor receptor (EGFR) T790M mutation, as well as its predictive role in clinical efficacy and progression‐free survial (PFS) in advanced non‐small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (EGFR‐TKI).MethodsWe retrospectively collected information of 153 patients with advanced NSCLC harboring exon EGFR mutation and receiving EGFR‐TKI.ResultsThe best cutoff value for HDL‐C and ApoA1 was determined to be 1.15 and 1.14 mmol/l. The overall response rate (ORR) was 67.7% in the high HDL‐C group and 46.6% in the low HDL‐C group, respectively. The ORR of the high ApoA1 group showed a significant increase than that of the low ApoA1 group (68.1% vs. 38.5%). The mean ApoA1 level of the EGFR T790M mutation‐positive group was significantly higher than that of the EGFR T790M mutation‐negative group (1.13 g/l vs. 1.01 g/l). Patients with high ApoA1 levels were related to the EGFR T790M mutation (r = 0.324). (3) The median progression‐free survival (PFS) of the high HDL‐C group and low HDL‐C group were 13.00 months and 10.20 months. The median PFS of the high ApoA1 group and the low ApoA1 group were 12.10 and 10.00 months, respectively. Multivariate Cox stepwise regression model analysis demonstrated ECOG PS, pathological type and HDL‐C were confirmed as critical and independent predictors of PFS.ConclusionsPatients with EGFR T790M mutations often show higher ApoA1 levels. Peripheral serum HDL‐C and ApoA1 before treatment can be used as potential significant factors for predicting clinical efficacy and PFS in advanced NSCLC patients treated with EGFR‐TKI.

High-density lipoprotein functionality in patients with hyperbaric oxygen therapy

High-density lipoprotein (HDL) cholesterol levels are associated with decreased risk of atherosclerotic disease, but also not all HDL are functionally equivalent. The functional status of HDL is closely linked to its primary protein component, apolipoprotein A-1 (ApoA-I) levels and paraoxonase 1 (PON1) enzyme. Functional changes of HDL may arise from hyperbaric oxygen therapy (HBO) induced posttranslational modification of ApoA-1 and PON1 levels. A total of 41 patients who met the research criteria were included in the study. On average, 30 sessions of HBO therapy were performed (range: 20-39). Laboratory measurements were performed at the beginning and at the end of HBO treatment in two groups of the same patients. We measured serum levels of Apo A-1, PON1, oxidized LDL (OxLDL) and routine lipid laboratory parameters to determine possible changes in HDL function with HBO therapy. As unexpected, long term HBO treatment have no effect on OxLDL and also on PON1 enzyme. However, the mean ApoA-1 values in the second group were statistically significantly increased than their pre-treatment values (P < 0.003). This preliminary study showed that HBO therapy increased the amount of serum ApoA-1. Actually, it can be assumed that the treatment of HBO does not have a negative effect on HDL functionality. The increase in ApoA-1 with HBO therapy is probably aimed at protecting against oxidative stress in patients. As a result, there is a need for larger clinical trials to determine the possible effects of HBO therapy on HDL functionality.

Decreased Cholesterol Efflux Capacity and Atherogenic Lipid Profile in Young Women With PCOS

Women with polycystic ovary syndrome (PCOS) have a high prevalence of cardiovascular disease (CVD) risk factors including dyslipidemia. Lipoproteins are heterogeneous, and measurement of serum lipids provides only the size of the pool and does not predict their function or composition. Recently, high-density lipoprotein cholesterol (HDL-C) function, as determined by cholesterol efflux capacity from macrophages, has been shown to be an independent predictor of subclinical CVD. The aim of the study was to comprehensively evaluate lipoprotein profile including lipid particle size and number and cholesterol efflux capacity in PCOS to better define CVD risk. A case control study was performed at an academic PCOS center. Women with PCOS (n = 124) and geographically matched controls (n = 67) were included in the study. The primary outcome was to measure HDL-C efflux capacity by an ex vivo system involving the incubation of macrophages with apolipoprotein (Apo) B-depleted serum from subjects, and the secondary outcome was to measure lipid particle size and number using nuclear magnetic resonance spectroscopy. Women with PCOS had significantly higher body mass index and blood pressure but similar HDL-C and low-density lipoprotein cholesterol levels compared to controls. The mean ApoA1 levels were lower, and the ApoB/ApoA1 ratio was higher in PCOS subjects compared to controls (P < .01). There were no differences in ApoB levels. Women with PCOS had an 7% decrease in normalized cholesterol efflux capacity compared to controls (P < .003). Cholesterol efflux capacity in PCOS correlated with body mass index, ApoA1, HDL-C, and the presence of metabolic syndrome. In a multivariable regression model, PCOS was significantly associated with diminished cholesterol efflux. PCOS was also associated with an atherogenic profile including an increase in large very low-density lipoprotein particles, very low-density lipoprotein (VLDL) size, and small low-density lipoprotein cholesterol particles (P < .01). Our novel findings of decreased cholesterol efflux and an atherogenic lipid particle number and size pattern in women with PCOS, independent of obesity, further substantiate the increased risk of CVD in this population.

Role of Serum Lipoprotein at the Site of Iloprost Therapy in the Treatment of Painful Bone Marrow Edema

The authors hypothesized that the emergence of painful bone marrow edema occurs through microembolisms in the bone marrow that may be reflected in elevated plasma parameters of hypofibrinolysis or a disturbance of the lipid metabolism and that treatment with iloprost may lead to a decrease in or normalization of the elevated serum parameters and, therefore, to pain reduction. Twenty-one patients (12 men and 9 women; mean age, 50 years [range, 22-70 years]) with painful bone marrow edema and elevated lipoprotein(a) (Lp[a]) serum values were treated with intravenous iloprost. Before and 6 weeks after iloprost therapy, the serum concentrations of Lp(a), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB) were determined. At 6-week follow-up, 17 patients reported complete resolution of their symptoms. For these patients, complete bone marrow edema resolution was observed on magnetic resonance imaging. Four patients reported that their symptoms were either the same or had worsened but had partial bone marrow edema resolution on magnetic resonance imaging. In these patients, Lp(a) values either increased or remained the same. Hence, the total success rate of iloprost treatment was 86% at a mean follow-up of 17 months (range, 3-45 months). Before iloprost therapy, mean ApoA1, ApoB, and Lp(a) values were 159.8, 108.3, and 69.1 mg/dL, respectively. Six weeks after iloprost therapy, mean ApoA1, ApoB, and Lp(a) values decreased to 147.6 (P=.011), 98.4 (P=.042), and 38.3 (P<.001) mg/dL, respectively. The results of this study indicate a possible role of hypofibrinolysis or a disturbance in the lipid metabolism in the emergence of painful bone marrow edema.

Proteomic Serum Profile of Fatigued Men Receiving Localized External Beam Radiation Therapy for Non-Metastatic Prostate Cancer

ContextFatigue is the most distressing side effect of radiation therapy, and its progression etiology is unknown. ObjectivesThis study describes proteome changes from sera of fatigued men with non-metastatic prostate cancer receiving external beam radiation therapy (EBRT). MethodsFatigue scores, measured by the Functional Assessment of Chronic Illness Therapy-Fatigue, and serum were collected from 12 subjects at baseline (before EBRT) and at midpoint (Day 21) of EBRT. Depleted sera from both time points were analyzed using two-dimensional difference gel electrophoresis, and up/down regulated proteins were identified using liquid chromatography-tandem mass spectrometry. Western blot analyses confirmed the protein changes observed. ResultsResults showed that apolipoprotein (Apo)A1, ApoE, and transthyretin (TTR) consistently changed from baseline (Day 0) to midpoint (Day 21). The mean ApoE level of subjects with high change in fatigue (HF: n = 9) increased significantly from baseline to midpoint and were higher than in subjects with no change in fatigue. The mean ApoA1 level was higher in HF subjects at baseline and at midpoint than in no fatigue subjects at both time points. The mean TTR level of no fatigue subjects was higher at baseline and midpoint than in HF subjects. ConclusionThese ApoE, ApoA1, and TTR results may assist in understanding pathways that can explain fatigue progression etiology in this clinical population.

Prevalence of apolipoprotein E genotypes in ischaemic cerebrovascular disease in end-stage renal disease patients.

Several studies have demonstrated that atherosclerotic complications are the major cause of morbidity and mortality in end-stage renal disease (ESRD) patients on dialysis. The allele epsilon 4 of apolipoprotein E (ApoE) gene has been associated with an increased risk for ischaemic cerebrovascular disease (ICVD) in general populations in recent preliminary cross-sectional studies. The aim of our study was to prospectively investigate the risk of ischaemic cerebrovascular disease with respect to the presence of Apo epsilon 4 allele in 157 Chinese uraemic patients. During the 2 year follow-up, the incidence of stroke was 6.4% and the cumulative occurrence of ischaemic cerebrovascular disease was 9.6%. Further analysis showed that the cumulative occurrence of ischaemic cerebrovascular disease was 5.6% in subjects with no ApoE epsilon 4 allele and 36.8% in those with one or two ApoE epsilon 4 alleles. Univariate analysis showed that the prevalence of ischaemic cerebrovascular disease was significantly higher in the subjects with ApoE epsilon 4 allele. The mean ApoA1 plasma concentrations was significantly lower in those with ApoE epsilon 4 allele. A stepwise regression analysis showed that the presence of stroke was significantly related to the ApoE epsilon 4 genotype (P < 0.001). The ApoE epsilon 4 allele can be regarded as an important risk factor for ischaemic cerebrovascular disease in uraemic patients.

Effects of probucol on plasma cholesterol, high and low density lipoprotein cholesterol, and apolipoproteins A1 and A2 in adults with primary familial hypercholesterolemia

This double-blind crossover study was designed to assess the safety, utility, and effectiveness of probucol (1000 mg/day) as an agent for reduction of total and low density lipoprotein plasma cholesterol (C-LDL) in 19 adults with primary familial hypercholesterolemia. The study was also designed to evaluate the effects of probucol on high density lipoprotein cholesterol (C-HDL) and its two major apolipoproteins, Apo A1 and Apo A2. After stabilization on a diet that provided < 200 mg cholesterol/day with a P S ratio of 1.2:1, the subjects were randomized into the following drug-placebo sequences: 9 subjects received 24 wk of probucol followed by 24 wk of placebo, while 10 received 24 wk of placebo followed by 24 wk of probucol, with weight maintained ± 1 kg, and dietary cholesterol and P S intake stable. In all 19 subjects on probucol total plasma cholesterol was reduced 10.7% and C-LDL 8.4% beyond the effects of diet alone; plasma triglyceride, the ratio of C-HDL to Apo A1, and the ratio of Apo A1 Apo A2 were not significantly changed. In all 19 subjects, the C-LDL C-HDL ratio during probucol therapy was 22% higher than during placebo, with an overall 26% reduction in C-HDL on probucol as compared to placebo. In the group of 9 subjects, whose plasma C-HDL levels fell 19% on probucol, mean HDL apolipoprotein A1 (Apo A1) levels fell 6%, Apo A2 levels did not change. In the group of 10 subjects whose mean plasma C-HDL levels fell 30% on probucol, mean Apo A1 fell 34%, and Apo A2 fell 20%. The probucol was well tolerated, with mean adherence of 93%. Of the 19 subjects, the only drug-related side effects were diarrhea in two subjects, and fetid perspiration in another. The relevance of the simultaneous reduction in C-HDL in the face of a mean 8.4% reduction in C-LDL is unknown. Better long-term information about the prognostic significance for atherosclerotic disease of the reductions in C-HDL, Apo A1, and Apo A2 need to be obtained, in view of the inverse association of C-HDL with coronary heart disease.