Changes In High-density Lipoprotein Research Articles

The association between the SLCO1B1, apolipoprotein E, and CYP2C9 genes and lipid response to fluvastatin: a meta-analysis.

The aim of this study was to determine the impact of the SLCO1B1, apolipoprotein E (ApoE), and CYP2C9 genotypes on the lipid-lowering efficacy of fluvastatin. We performed electronic searches on the PubMed, Embase, and Cochrane Library databases to identify studies published through October 2017. Studies that reported the effect estimates with 95% confidence intervals (CIs) of total cholesterol (TC), triglyceride, low-density lipoprotein (LDL), and high-density lipoprotein were included so that the different genotype categories could be compared. Weighted mean difference (WMD) was used to summarize the effect estimates. Six studies, involving a total of 1171 individuals, were included in the final analysis. We noted that the patient carrier SLCO1B1 521TT was associated with greater change in TC (WMD: -2.98; 95% CI: -5.12 to -0.84; P=0.006) and LDL (WMD: -5.58; 95% CI: -10.64 to -0.52; P=0.031) compared with 521TC or CC. Furthermore, the patient carrier ApoE*2/*3 showed more change in high-density lipoprotein compared with ApoE*3/*3 (WMD: 18.76; 95% CI: 8.97-28.55; P<0.001) and ApoE*3/*4 or *4/*4 (WMD: 22.51; 95% CI: 0.98-44.04; P=0.040). Finally, the CYP2C9 genotypes showed no correlation with the effects of fluvastatin on TC, triglyceride, and LDL. The findings of this study suggested that the SLCO1B1 and ApoE polymorphisms could influence the lipid-lowering effect of fluvastatin, whereas the CYP2C9 genotypes were not associated with the therapeutic effects of fluvastatin.

Exercise intervention alters HDL subclass distribution and function in obese women

BackgroundObesity is associated with a change in high-density lipoprotein (HDL) function and subclass. Exercise training reduces cardiovascular risk in obese patients. We aimed to explore the effect of an exercise training stimulus on HDL functionality and subclass in obese women.MethodsThirty-two obese black South African women were randomly assigned to exercise (combined aerobic and resistance exercise) or control (no exercise) conditions for 12-weeks. Pre- and post-testing included venous blood sampling for analysis of lipid profile and HDL functionality, by measuring cellular cholesterol efflux capacity, reduction in endothelial vascular cell adhesion molecule (VCAM) expression (anti-inflammatory function), paraoxonase (PON) (antioxidative function) and platelet activating factor acetylhydrolase (PAF-AH) activities (anti-thrombotic function). PON-1 and PAF-AH expression were determined in serum and in isolated HDL using Western blotting. Levels of large, intermediate and small HDL subclasses were measured using the Lipoprint® system.ResultsExercise training resulted in a decrease in body mass index (− 1.0 ± 0.5% vs + 1.2 ± 0.6%, p = 0.010), PON activity (− 8.7 ± 2.4% vs + 1.1 ± 3.0%, p = 0.021), PAF-AH serum expression (− 22.1 ± 8.0% vs + 16.9 ± 9.8, p = 0.002), and the distribution of small HDL subclasses (− 10.1 ± 5.4% vs + 15.7 ± 6.6%, p = 0.004) compared to controls. Exercise did not alter HDL cellular cholesterol efflux capacity and anti-inflammatory function.ConclusionsThese results demonstrate the potential for exercise training to modify HDL subclass distribution and HDL function in obese women.Trial registrationClinical trials number: PACTR201711002789113.

Hypoxis hemerocallidea alters metabolic parameters and hepatic histomorphology in streptozotocin-nicotinamide-induced diabetic male rats under antiretroviral therapy.

IntroductionHighly active antiretroviral therapy (HAART) and HIV/AIDS have been demonstrated to induce endocrine/metabolic dysfunction with a consequential increase in morbidity/mortality due to organ toxicities. This study aimed at investigating the possible protective effect of Hypoxis hemerocallidea (HH) against metabolic and hepatic histomorphology of diabetic rats under HAART.Material and methodsSixty-two adult male Sprague-Dawley rats were divided into a normoglycemic group A (n = 6) and 7 diabetic (110 mg/kg nicotinamide + 45 mg/kg streptozotocin) groups (B–H) (n = 8) and treated according to protocols. Concomitant treatment with adjuvant HH and HAART resulted in the least %body weight gain as the liver weight decreased in all treated animals.ResultsSignificant changes in serum lipids were aggravated by treatment with HH and HAART, triglycerides and total cholesterol levels were elevated (p < 0.001/0.05), but changes in high-density lipoprotein (HDL) and total protein levels were insignificant. While artherosclerotic and cardiopulmonary indexes remained insignificant, concomitant use of HH with HAART in diabetes resulted in reduction of low-density lipoprotein (LDL) (p < 0.001), and increased triglyceride (p < 0.05) and total cholesterol (p < 0.001). The parameters of liver injury showed a significant (p < 0.05) increase in ALT of animals treated with HH alone, HAART + HH and melatonin; however, an insignificant decline in AST level was recorded. Treatment with adjuvant HAART, HH and melatonin resulted in significant (p < 0.005/0.0001) up-regulation of ALP and total bilirubin levels. Histopathology derangement ranged from severe hepatocellular distortions, necrosis with reduced glycogen expression following co-treatment of HAART+melatonin, HH and HAART alone in diabetes.ConclusionsPresumptive hypoglycemic use of HH with HAART by people living with HIV/AIDS requires caution as implications for hepatocellular injuries are suspected with further uncontrolled metabolic disorder.

Genomic Influence in the Prevention of Cardiovascular Diseases with a Sterol-Based Treatment.

Raised serum cholesterol concentration is a well-established risk factor in cardiovascular disease. In addition, genetic load may have an indirect influence on cardiovascular risk. Plant-based sterol-supplemented foods are recommended to help reduce the serum low-density lipoprotein cholesterol level. The objective was to analyse the influence of different polymorphisms in hypercholesterolemia patients following a dietary treatment with plant sterols. A randomised double-blind cross-over controlled clinical trial was carried out in 45 people (25 women). Commercial milk, containing 2.24 g of sterols, was ingested daily during a 3-week period, and then the same amount of skim milk, without sterols, was consumed daily during the 3-week placebo phase. Both phases were separated by a washout period of 2 weeks. At the beginning and end of each phase, blood draws were performed. Genes LIPC C-514T and APOA5 C56G are Ser19Trp carriers and greatly benefit from sterol intake in the diet. LIPC C-514T TT homozygous carriers had lower low-density lipoprotein cholesterol (LDL-c) levels than CC homozygote and CT heterozygote carriers after the ingestion of plant sterols (p = 0.001). These two genes also showed statistically significant changes in total cholesterol levels (p = 0.025; p = 0.005), and no significant changes in high-density lipoprotein (HDL) cholesterol levels (p = 0.032; p = 0.003), respectively. No statistically significant differences were observed for other genes. Further studies are needed to establish which genotype combinations would be the most protective against hypercholesterolemia.

Proteomic characterization of high-density lipoprotein particles in patients with non-alcoholic fatty liver disease

BackgroundMetabolic diseases such as obesity and diabetes are associated with changes in high-density lipoprotein (HDL) particles, including changes in particle size and protein composition, often resulting in abnormal function. Recent studies suggested that patients with non-alcoholic fatty liver disease (NAFLD), including individuals with non-alcoholic steatohepatitis (NASH), have smaller HDL particles when compared to individuals without liver pathologies. However, no studies have investigated potential changes in HDL particle protein composition in patients with NAFLD, in addition to changes related to obesity, to explore putative functional changes of HDL which may increase the risk of cardiovascular complications.MethodsFrom a cohort of morbidly obese females who were diagnosed with simple steatosis (SS), NASH, or normal liver histology, we selected five matched individuals from each condition for a preliminary pilot HDL proteome analysis. HDL particles were enriched using size-exclusion chromatography, and the proteome of the resulting fraction was analyzed by liquid chromatography tandem mass spectrometry. Differences in the proteomes between the three conditions (normal, SS, NASH) were assessed using label-free quantitative analysis. Gene ontology term analysis was performed to assess the potential impact of proteomic changes on specific functions of HDL particles.ResultsOf the 95 proteins identified, 12 proteins showed nominally significant differences between the three conditions. Gene ontology term analysis revealed that severity of the liver pathology may significantly impact the anti-thrombotic functions of HDL particles, as suggested by changes in the abundance of HDL-associated proteins such as antithrombin III and plasminogen.ConclusionsThe pilot data from this study suggest that changes in the HDL proteome may impact the functionality of HDL particles in NAFLD and NASH patients. These proteome changes may alter cardio-protective properties of HDL, potentially contributing to the increased cardiovascular disease risk in affected individuals. Further validation of these protein changes by orthogonal approaches is key to confirming the role of alterations in the HDL proteome in NAFLD and NASH. This will help elucidate the mechanistic effects of the altered HDL proteome on cardioprotective properties of HDL particles.

Metabolomic Analysis of N-acetylcysteine Protection of Injury from Gadolinium-DTPA Contrast Agent in Rats with Chronic Renal Failure.

Gadolinium-based contrast agents (GBCAs) are frequently used to enhance the diagnostic efficacy of magnetic resonance imaging. On the other hand, the association between GBCA administration in patients with advanced renal disease and nephrogenic systemic fibrosis (NSF) was also noted. NSF is a systemic disorder characterized by widespread tissue fibrosis that may lead to death. N-acetylcysteine (NAC) protects rats from injury induced by gadolinium-based contrast agents, but the underlying mechanisms remain unclear. In this study, a nuclear magnetic resonance-based metabolomic approach was used to systematically investigate the protective effects of NAC on Gd-DTPA-induced injury. Thirty-two male Sprague-Dawley rats were given adenine (200 mg·kg-1 body weight) by oral gavage once a day for 3 weeks to induce chronic renal failure (CRF). NAC (600 mg/L in drinking water for 9 days) pretreatment was initiated 2 days before Gd-DTPA injection (a single tail vein injection, 2 mmol/kg body weight). Serum and liver samples were collected on day 7 after Gd-DTPA injection. By study design, the serum and hepatic metabolic changes of rats were measured in four groups of eight each: CRF, CRF-Gd, CRF-Gd-NAC, and CRF-NAC. Gd-DTPA administration to rats with CRF resulted in disturbances of several metabolic pathways, including glucose, lipid, glutamate, choline, gut microbiota, one-carbon, and purine metabolism. NAC pretreatment reversed the abundance changes of high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, glutamate, glutamine, oxidized glutathione, choline, phosphocholine, glycerophosphocholine, trimethylamine, and trimethylamine-N-oxide induced by Gd-DTPA. It is noteworthy, however, that the ameliorating effects of NAC on the disturbance of glutamate, choline, and gut microbiota metabolism may be specific to Gd-DTPA. In all, these findings could be potentially useful to decipher the underlying mechanisms of NAC protective effects from the injury induced by gadolinium-based contrast agents.

A Walking Intervention Among Men With Prostate Cancer: A Pilot Study.

Men diagnosed with prostate cancer have increased risk for disease progression, cardiovascular events, and impairments in quality of life. This pilot study evaluated the feasibility of a randomized walking group intervention to improve quality of life, circulating biomarkers, and morbidity among men with newly diagnosed prostate cancer. Men were recruited at Örebro University Hospital, Sweden, and randomized to an 11-week walking group intervention (n= 21) or usual care (n= 20). The intervention included weekly 1-hour walking group sessions and maintenance of 10,000 steps/day. Outcomes were changes in body composition, clinical factors, biomarkers of cardiovascular health, and quality of life between baseline and end of study. Analysis of covariance was used to compare outcomes in each group adjusted for baseline values. All 41 men randomized completed the 11-week trial. Men assigned to the intervention walked on average 10,644 steps/day, and 92% reported missing 2 or fewer sessions. Both groups experienced similar weight loss at 11 weeks. Men in the intervention had a significant adjusted mean change in high-density lipoprotein of 0.14mmol/L (95% confidence interval [CI], 0.01-0.27; P= .04), and suggestive adjusted mean changes in low-density lipoprotein of-0.22mmol/L (95% CI,-0.47 to 0.03; P= .08) and in systolic blood pressure of-8.5mm Hg (95% CI,-21.2 to 4.2; P= .18), compared with the usual care group. A walking group intervention among men with recent diagnosis of prostate cancer is feasible and potentially effective in improving cardiovascular health. A larger randomized trial of longer duration is required to elucidate its potential for improvement in longer term outcomes.

Association of Air Pollution Exposures With High-Density Lipoprotein Cholesterol and Particle Number: The Multi-Ethnic Study of Atherosclerosis.

The relationship between air pollution and cardiovascular disease may be explained by changes in high-density lipoprotein (HDL). We examined the cross-sectional relationship between air pollution and both HDL cholesterol and HDL particle number in the MESA Air study (Multi-Ethnic Study of Atherosclerosis Air Pollution). Study participants were 6654 white, black, Hispanic, and Chinese men and women aged 45 to 84 years. We estimated individual residential ambient fine particulate pollution exposure (PM2.5) and black carbon concentrations using a fine-scale likelihood-based spatiotemporal model and cohort-specific monitoring. Exposure periods were averaged to 12 months, 3 months, and 2 weeks prior to examination. HDL cholesterol and HDL particle number were measured in the year 2000 using the cholesterol oxidase method and nuclear magnetic resonance spectroscopy, respectively. We used multivariable linear regression to examine the relationship between air pollution exposure and HDL measures. A 0.7×10-6 m-1 higher exposure to black carbon (a marker of traffic-related pollution) averaged over a 1-year period was significantly associated with a lower HDL cholesterol (-1.68 mg/dL; 95% confidence interval, -2.86 to -0.50) and approached significance with HDL particle number (-0.55 mg/dL; 95% confidence interval, -1.13 to 0.03). In the 3-month averaging time period, a 5 μg/m3 higher PM2.5 was associated with lower HDL particle number (-0.64 μmol/L; 95% confidence interval, -1.01 to -0.26), but not HDL cholesterol (-0.05 mg/dL; 95% confidence interval, -0.82 to 0.71). These data are consistent with the hypothesis that exposure to air pollution is adversely associated with measures of HDL.

Treatment of hyperprolactinaemia reduces total cholesterol and LDL in patients with prolactinomas

Previous studies suggest that hyperprolactinaemia might have adverse effects on lipid and glucose metabolism. We therefore aimed to evaluate whether dopamine agonist treatment with cabergoline has significant effects on blood lipids, fasting glucose and HbA1c levels in patients with micro- or macroprolactinoma. In this retrospective observational study the main outcome measures are changes in parameters of glucose and lipid metabolism compared at hyperprolactinaemia and after achievement of normoprolactinaemia by cabergoline treatment. We enrolled 53 study participants (22 females; median [interquartile range] age: 40.0 [27.5 to 50.0] years), 22 (41.5 %) with micro-, and 31 (58.5 %) with macroprolactinomas. After a median follow-up of 9 months, prolactin levels decreased from 220.6 (80.7–913.4) to 11.2 (3.5–18.7) ng/mL (p < 0.001). There was a significant decrease in median levels of low-density lipoprotein (LDL) from 121.6 (±39.4) to 110.6 mg/dl (±37.6, p = 0.005) and total cholesterol from 191 (168.5–241) to 181 mg/dl (162–217, p < 0.001), but no change in high-density lipoprotein (HDL), triglycerides, fasting glucose and HbA1c. We observed a significant increase in testosterone in men and in oestradiol in women. In linear regression analyses using the change in total cholesterol or LDL as dependent, and the change in prolactin, oestradiol, and testosterone as independent variables, no significant predictor of the change in total cholesterol or LDL was identified. In patients with prolactinomas, normalisation of elevated prolactin levels by cabergoline treatment was accompanied by significant reductions in LDL and total cholesterol. Further studies are warranted to confirm our findings and to evaluate the clinical implications of lipid levels in the monitoring and treatment of patients with prolactinomas.

Abstract 625: Targeting of Heparin Binding EGF-like Growth Factor (HBEGF) Suppresses Hyperlipidemia and Atherosclerosis in LDL Receptor Deficient Mice

Objective: Elevation of apoB-containing lipoproteins is a well-established risk factor for the development of atherosclerosis. Previous reports showed that expression of heparin-binding EGF-like growth factor (HBEGF), a ligand of epidermal growth factor receptor (EGFR), is associated with atherosclerosis development. In this study, we examined in vivo effects of HBEGF targeting on hyperlipidemia-induced atherosclerosis by suppressing HBEGF expression using antisense oligonucleotide (ASO). Methods and Results: Female and male LDLR deficient mice were fed a high fat diet (HFD; 21% fat, 0.2% cholesterol) throughout the study. After 8 weeks of HFD feeding, mice were injected intraperitoneally with either control or HBEGF ASOs weekly for 12 weeks. At termination, we measured circulating lipid concentrations and atherosclerotic lesion size in the aorta. Compared to control ASO group, HBEGF ASO group had a significant reduction of circulating total cholesterol, triglyceride, and apoB-containing lipoprotein concentrations but no change of high-density lipoprotein (HDL) concentration. Importantly, HBEGF ASO injection significantly suppressed atherosclerosis in the aortic arch, thoracic, and abdominal aorta. HBEGF ASO suppressed sterol synthetic gene expression in the liver but elevated lipid contents in the liver. HBEGF gene silencing in a liver cell system induced downregulation of sterol regulatory element binding protein (SREBP) target genes including LDLR and Insig1. Conclusion: Targeting HBEGF using ASOs is an efficient approach to suppress dyslipidemia and hyperlipidemia-induced atherosclerosis. The differential gene expression analysis suggests that HBEGF ASO administration suppresses SREBP-regulated gene expression in the liver leading to downregulation of circulating cholesterol and TG concentrations.

Influence of uvulopalatopharyngoplasty on serum uric acid level in obstructive sleep apnea patients

Abstract Background: The objective of this study was to determine whether there is an association between successful uvulopalatopharyngoplasty (UPPP) and serum uric acid in patients with obstructive sleep apnea (OSA), and identify the risk markers for successful UPPP in OSA patients. Methods: We performed a prospective cohort study of 73 adult patients with OSA who underwent surgery (nasal or UPPP) at a major, urban, academic hospital in Huaian from 2011 to 2014 who had preoperative and postoperative clinical and laboratory profiles. Demographic, clinical, laboratory, and PSG parameters were carefully recorded. Logistic regression was used for the multivariate analysis of independent risk factors. Results: Changes of uric acid (UA), changes of C-reactive protein (CRP), changes of triglyceride, changes of high density lipoprotein before and after UPPP were significantly higher in OSA patients with successful UPPP than in those with unsuccessful UPPP (p&lt;0.05). Among these patients, multiple logistic analyses indicated the independent risk factors for successful UPPP in the OSA subjects included changes of UA and CRP before and after UPPP. The diagnosis analysis showed that changes of UA and CRP before and after UPPP had a significant ability to reflect UPPP success in the OSA patients. Conclusions: The novel finding of this study is that the successful UPPP in OSA patients is strongly related to changes of serum UA level, CRP before and after operation. These results might be helpful for providing valuable information to reflect the effect of UPPP operation, regardless of UA and CRP before operation.

Association of Variants in Candidate Genes with Lipid Profiles in Women with Early Breast Cancer on Adjuvant Aromatase Inhibitor Therapy

Aromatase inhibitors can exert unfavorable effects on lipid profiles; however, previous studies have reported inconsistent results. We describe the association of single-nucleotide polymorphisms (SNP) in candidate genes with lipid profiles in women treated with adjuvant aromatase inhibitors. We conducted a prospective observational study to test the associations between SNPs in candidate genes in estrogen signaling and aromatase inhibitor metabolism pathways with fasting lipid profiles during the first 3 months of aromatase inhibitor therapy in postmenopausal women with early breast cancer randomized to adjuvant letrozole or exemestane. We performed genetic association analysis and multivariable linear regressions using dominant, recessive, and additive models. A total of 303 women had complete genetic and lipid data and were evaluable for analysis. In letrozole-treated patients, SNPs in CYP19A1, including rs4646, rs10046, rs700518, rs749292, rs2289106, rs3759811, and rs4775936 were significantly associated with decreases in triglycerides by 20.2 mg/dL and 39.3 mg/dL (P < 0.00053), respectively, and with variable changes in high-density lipoprotein (HDL-C) from decreases by 4.2 mg/dL to increases by 9.8 mg/dL (P < 0.00053). Variants in CYP19A1 are associated with decreases in triglycerides and variable changes in HDL-C in postmenopausal women on adjuvant aromatase inhibitors. Future studies are needed to validate these findings, and to identify breast cancer survivors who are at higher risk for cardiovascular disease with aromatase inhibitor therapy.

Correlation between the High Density Lipoprotein and its Subtypes in Coronary Heart Disease

Background/Aims: To detect the changes of high density lipoprotein (HDL) and its subtypes in serum of patients with coronary heart disease (CHD). Methods: 337 hospitalized patients were selected from our hospital during August, 2014 - January, 2015, and divided into CHD group (n = 190) and control group (n = 127). Lipoprint lipoprotein analyzer was used to classify low density lipoprotein (LDL) particle size and its sub-components, as well as HDL particle size and its sub-components. The changes of the subtypes in patients with CHD were statistically analyzed. The possible mechanism was explored. Results: (1) Compared with the control group, the concentration of HDL in CHD patients reduced, HDLL significantly decreased (P < 0.001), while HDLS increased (P < 0.001); (2) In the patients with HDL less than 1.04 mmol/L among CHD, all HDL subtypes reduced, but HDLL had the most significant decreased; (3) HDL and all HDL subtypes were positively correlated with apolipoprotein A-I (apoA-I), of which, HDLL had the biggest correlation with apoA-I (P < 0.001); (4) HDL subtypes had good correlation with HDL, of which, HDLM had a maximum correlation with HDL (P < 0.001). Conclusion: HDL maturation disorders existed in the serum of CHD patients, HDLL may be protected factor for CHD, whose decrease was closely related wit the risk increase of CHD. The cardiovascular protection function of HDLL may be related with apoA-I content.

HIV infection induces structural and functional changes in high density lipoproteins

Background and aimsCoronary artery disease is a growing clinical problem in HIV-infected subjects. The increased risk of coronary events in this population has been linked to low levels of HDL, but the effects of HIV infection and anti-retroviral treatment (ART) on HDL structure and function remain unknown. Here, we aimed to determine the composition and function of HDL particles isolated from ART-naive and ART-positive HIV-infected patients. Methods and resultsProteomic profiling revealed decreased levels of paraoxonase (PON) 1 and PON 3 in HDL from HIV patients relative to HDL from uninfected controls (p < 0.0001), and PON activity of HDL from control group (0.13 ± 0.01 U/μl) was significantly higher than PON activity of HDL from HIV-infected untreated subjects (0.12 ± 0.01 U/μl, p = 0.0035), subjects treated with non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy (0.11 ± 0.01 U/μl, p < 0.0001), subjects treated with protease inhibitor (PI)-based therapy with detectable viral load (0.11 ± 0.01 U/μl, p < 0.0001), and PI-treated patients with undetectable viral load (0.12 ± 0.01 U/μl, p = 0.0164). Lipidomic profiling uncovered a negative correlation between CD4 T cell counts and particle sphingomyelin, lyso-phosphatidylcholine and ether-linked phosphatidylserine content in the ART-naive (R2 = 0.2611, p < 0.05; R2 = 0.2722, p < 0.05; and R2 = 0.3977, p < 0.05, respectively) but not treated HIV-infected subjects. Functional analysis demonstrated a negative correlation between cholesterol efflux capacity of HDL and viral load in the ART-naive HIV-infected group (R2 = 0.26, p = 0.026). ConclusionsTaken together, these results indicate that HIV infection associates with a number of both protein and lipid compositional changes in HDL particles. Moreover, HIV infection affects cholesterol efflux function of HDL, thus contributing to an increased risk of atherosclerosis in this patient population.

Oxidative stress and paraoxonase 1 status in acute ischemic stroke patients.

The connection of oxidative stress with dyslipidemia creates a newly-emerging atherosclerosis risk factor involved in acute ischemic stroke development. This study analyzed the influence of oxidative stress on structural changes of high-density lipoprotein (HDL) particles connected with modification in protective paraoxonase 1 (PON1) activity. This study used 185 patients with acute ischemic stroke and 185 apparently healthy controls. Oxidative stress status, PON1 status, lipids and high-sensitivity C-reactive protein (hsCRP) were determined. In isolated HDL lipoprotein fraction we determined selected markers of oxidative stress (malondialdehyde, MDA) and the content of total sulfhydryl (SH) groups. The capability of oxidative and PON1 status parameters to discriminate patients according to survival status was evaluated. Stroke patients had lower HDL-cholesterol than controls and a remarkable fall in PON1 activity (control group-227U/L, survivors-42U/L, lethal outcome group-61U/L, p<0.001), along with more prominent inflammation. Pronounced oxidative stress and impaired antioxidative protection was present among patients. HDL fraction analysis revealed a significant decrease of SH groups content (control group vs. patients, p<0.05) and increased in MDA content in patients (lethal outcome vs. control group, p<0.05). According to logistic regression analysis, the best predictor of disease outcome was oxidative stress marker - prooxidative-antioxidative balance (PAB). Pronounced oxidative stress in this group of acute ischemic stroke patients probably led to HDL structural changes, which could further cause an alteration or decrease of PON1 activity. Evidence of increased prooxidant level associated with decreased protective, antioxidative factors suggests their mutual involvement in this complex pathology.

Abstract 314: HIV infection iIduces Structural and Functional Changes in High Density Lipoproteins

Coronary artery disease is a growing clinical problem in HIV-infected subjects. Increased risk of coronary events in this population has been linked to low levels of HDL, but the effects of HIV infection and anti-retroviral treatment (ART) on HDL structure and function are poorly characterized. Here, we determined the composition and function of HDL particles isolated from plasma collected from ART-naive and ART-positive HIV-infected patients and compared them to HDL from a convenience control group. Proteomic profiling revealed decreased paraoxonase (PON) 1 and PON 3 in HDL from both treated and untreated HIV-positive patients, and PON activity of HDL from HIV-infected subjects was significantly lower than in control group. Lipidomic profiling found sphingomyelin and ether-linked glycerophospholipid species in the HDL particles correlated positively with viral load and negatively with CD4+ T cell counts in ART-naive subjects. Consistent with analysis of lipids, the level of PLTP showed a significant positive correlation with viral load and negative correlation with CD4+ T cell counts in ART-naïve HIV-positive samples. Given the low PON1 and 3 levels in HDL from HIV-infected subjects, we tested for the level of oxidized phospholipids in the HDL particles from a subset of HIV+ ART-naïve and treated subjects with completely suppressed viremia. No significant differences in oxidized lipids were found between HDL from control and untreated or PI-treated subjects, but a significant increase was detected in the NNRTI-treated samples. Similarly, the ratio of oxidized LDL to total LDL was significantly increased in the NNRTI-treated samples. These results suggest that reduced PON levels in HDL of HIV-infected subjects do not translate to increased levels of oxidized lipids, however, low PON may contribute to increased oxidation in NNRTI-treated patients. Finally, a negative correlation between cholesterol efflux capacity of HDL and viral load in ART-naive HIV-infected group was detected. Thus, HIV infection associates with a number of both protein and lipid compositional changes in HDL particles. Moreover, HIV infection affects cholesterol efflux function of HDL, and this may increase risk of atherosclerosis in this patient population.

Interleukin-6, vitamin D & diabetes risk-factors modified by a short-term yoga-based lifestyle intervention in overweight/obese individuals.

Background & objectives:Several diabetes prevention programmes have demonstrated a reduction in incidence of diabetes in individuals with prediabetes through weight loss. Short-term yoga-based lifestyle intervention programmes have also been shown to be efficacious in weight loss. This study was undertaken to investigate if interleukin (IL)-6, vitamin D, neopterin, vaspin, and diabetes risk factors can be modified by a short-term yoga-based lifestyle intervention in overweight/obese subjects.Methods:In this pilot study, 34 overweight/obese [body mass index (BMI) ≥23 to <35 kg/m2 per Asian cut-off values] individuals were enrolled, and received directly supervised intervention for 10 days. Thereafter, they were advised to follow this yoga-based lifestyle at home for one month, and were reassessed for study variables at day 30.Results:There was a reduction from baseline to day 10 in weight (P<0.001), BMI (P<0.001), waist/hip-ratio (P<0.05), blood glucose (P<0.01), and a significant improvement in lipid profile. There was a decrease in median fasting insulin (P<0.05), homeostatic model assessment-insulin resistance (P<0.01), and IL-6 (P<0.05). A non-significant increase in 25-OH-vitamin D, and a decrease in neopterin and vaspin were observed. Twenty subjects returned for follow up assessments. At day 30, weight loss was sustained while systolic blood pressure also showed reduction (P<0.05). Changes in vitamin D levels were significantly and negatively correlated with changes in weight, BMI and fasting blood glucose, and positively with change in high density lipoprotein. Changes in body weight and BMI significantly and positively correlated with insulin. Changes in IL-6 levels positively and significantly correlated with change in neopterin levels.Interpretation & conclusions:The findings showed that IL-6, vitamin D, and diabetes risk factors were favourably modified by a short-term yoga-based lifestyle intervention in obesity. This study also highlighted the challenges in compliance associated with the follow up of subjects following an aggressive supervised intervention of 10 days.

Structural and functional changes in high-density lipoprotein induced by chemical modification.

Reconstituted high-density lipoprotein (rHDL), a natural nanoparticle consisting of apolipoprotein A-I and phospholipids, was modified with a hydrophobic fluorescent dye before (pre-rHDL) and after (post-rHDL) reconstitution. Pre-rHDL particles had a similar size to unmodified rHDL, but post-rHDL particles were significantly larger and their avidity for a HDL receptor was 2.6 times of that shown by pre-rHDL.

Glucocorticoid use is associated with increase in HDL and no change in other lipids in rheumatoid arthritis patients.

The aim of this article was to examine the association of glucocorticoid use and dose and changes in the lipid profile in rheumatoid arthritis (RA) patients. RA patients between January 1, 2001, and November 30, 2011, who received oral or intravenous glucocorticoids and who had lipid levels within 1 year before and 1 year after ongoing (at least 3 months) glucocorticoids use along with RA patients who did not take glucocorticoids (controls) were included. Glucocorticoid exposure was calculated as a weighted daily dose in prednisone equivalents and analyzed using as cutoff dose prednisone equivalent of 7.5 mg/day. Outcomes were changes in high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), triglycerides, and TC/HDL ratio and were calculated in linear regression models adjusting for relevant confounders. In total, 202 subjects on glucocorticoids and 436 controls were included. The glucocorticoid group of ≥7.5 mg/day had the greatest increase in HDL of 6.0 mg/dL (p = 0.003 compared to controls) with lower increases of 3.1 and 2.4 mg/dL in the glucocorticoid group of <7.5 mg/day and controls, respectively. There were no significant differences in other parameters of the lipid profile between the two glucocorticoid groups and controls. In this RA cohort, glucocorticoid dose equivalent of prednisone ≥7.5 mg/day was associated with increased HDL and no change in LDL or TC/HDL ratio compared to no glucocorticoid use These results suggest that this glucocorticoid dose is not associated with an atherogenic lipid profile in RA, a finding that is important in this patient population at high risk for cardiovascular disease.

Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor.

The existence of an independent association between elevated triglyceride (TG) levels, cardiovascular (CV) risk and mortality has been largely controversial. The main difficulty in isolating the effect of hypertriglyceridemia on CV risk is the fact that elevated triglyceride levels are commonly associated with concomitant changes in high density lipoprotein (HDL), low density lipoprotein (LDL) and other lipoproteins. As a result of this problem and in disregard of the real biological role of TG, its significance as a plausible therapeutic target was unfoundedly underestimated for many years. However, taking epidemiological data together, both moderate and severe hypertriglyceridaemia are associated with a substantially increased long term total mortality and CV risk. Plasma TG levels partially reflect the concentration of the triglyceride-carrying lipoproteins (TRL): very low density lipoprotein (VLDL), chylomicrons and their remnants. Furthermore, hypertriglyceridemia commonly leads to reduction in HDL and increase in atherogenic small dense LDL levels. TG may also stimulate atherogenesis by mechanisms, such excessive free fatty acids (FFA) release, production of proinflammatory cytokines, fibrinogen, coagulation factors and impairment of fibrinolysis. Genetic studies strongly support hypertriglyceridemia and high concentrations of TRL as causal risk factors for CV disease. The most common forms of hypertriglyceridemia are related to overweight and sedentary life style, which in turn lead to insulin resistance, metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM). Intensive lifestyle therapy is the main initial treatment of hypertriglyceridemia. Statins are a cornerstone of the modern lipids-modifying therapy. If the primary goal is to lower TG levels, fibrates (bezafibrate and fenofibrate for monotherapy, and in combination with statin; gemfibrozil only for monotherapy) could be the preferable drugs. Also ezetimibe has mild positive effects in lowering TG. Initial experience with en ezetimibe/fibrates combination seems promising. The recently released IMPROVE-IT Trial is the first to prove that adding a non-statin drug (ezetimibe) to a statin lowers the risk of future CV events. In conclusion, the classical clinical paradigm of lipids-modifying treatment should be changed and high TG should be recognized as an important target for therapy in their own right. Hypertriglyceridemia should be treated.