Normal HDL Research Articles

Prevalence of nonalcoholic fatty liver disease in an adult population in a rural community of Haryana, India.

Though nonalcoholic fatty liver disease (NAFLD) is increasingly becoming prevalent in the Indian population, knowledge regarding the burden and risk factors of NAFLD is limited, more so from rural areas. This study was thus conducted to estimate the prevalence of NAFLD among adults in a rural community of Haryana, India and to measure the association of diet, physical activity, and other selected risk factors with NAFLD. The present study was conducted in a rural community of Haryana, India among resident adults ≥35 years of age. Eight out of 28 villages were selected by probability proportion to size sampling. The number of eligible and consenting participants randomly selected from each village was 27. Out of 216 participants thus recruited, 184 participants reported for undergoing ultrasonography (USG) of the liver, anthropometry, blood pressure recording, and blood sample collection. Finally, 176 participants were analyzed. Prevalence of NAFLD was 30.7%. There was no significant difference in the calorie intake and average total physical activity between participants with and without NAFLD. On multivariate analysis, hypertension [adjusted odds ratio (OR): 2.3, 95% confidence interval (CI): 1.1-5.0, P 0.03] and an increased waist circumference (adjusted OR: 4.9, 95% CI: 1.5-7.0, P < 0.001) were independently associated with NAFLD. A normal high-density lipoprotein (HDL) level was protective against NAFLD (adjusted OR: 0.4, 95% CI: 0.2-0.8, P 0.001). The high prevalence of NAFLD is already a public health problem, even in the rural parts of India. Urgent public health interventions are required to prevent its development by controlling the cardiometabolic risk factors associated with it.

Analysis of lipoprotein profiles of healthy cats by gel-permeation high-performance liquid chromatography.

Density gradient ultracentrifugation (DGUC) and gel electrophoresis are conventionally used to obtain lipoprotein profiles of animals. We recently applied high-performance liquid chromatography with a gel permeation column (GP-HPLC) and an on-line dual enzymatic system to dogs for lipoprotein profile analysis. We compared the GP-HPLC with DGUC as a method to obtain a feline lipoprotein profile. The lipoprotein profiles showed large and small peaks, which corresponded to high-density lipoprotein (HDL) and low-density lipoprotein (LDL), respectively, whereas very low-density lipoprotein (VLDL) and chylomicron (CM) were only marginally detected. This profile was very similar to that of dogs reported previously. Healthy cats also had a small amount of cholesterol-rich particles distinct from the normal LDL or HDL profile. There was no difference in lipoprotein profiles between the sexes, but males had a significantly larger LDL particle size (P=0.015). This study shows the feasibility of GP-HPLC for obtaining accurate lipoprotein profiles with small sample volumes and provides valuable reference data for healthy cats that should facilitate diagnoses.

Transcription factor 7-like 2 (TCF7L2) Gene Polymorphism rs7903146 is Associated with Lipid Profile and Risk of Cardiovascular Disease in Metabolic Syndrome Subjects

Transcription factor 7-like 2 (TCF7L2) polymorphisms especially rs7903146(C/T) are related to type 2 diabetes (T2D) and other metabolic diseases; Metabolic Syndrome(MetS), atherosclerosis and cardiovascular disease (CVD) risk, this study is performed in order to evaluate the relationship between TCF7L2 polymorphism rs7903146 to Metabolic Syndrome (MetS) and CVD Blood samples were collected from the MetS (n=92) and control (n=80) subjects. The subjects were characterized according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP-III). Blood DNA was extracted and genotyped by mismatch PCR-RFLP. A logistic regression model was performed to analyze the data. T-TEST and ANOVA (Analysis Of Variance) were used to compare differences between CC and CT+TT rs7903146 genotypes. The biochemical factors showed that BMI, SBP, DBP, FBS, TG levels in the MetS subjects were meaningfully higher than Normal subjects (P=0.001, P=0.000, P=0.000, P=0.031, P=0.000) and HDL level in the MetS subjects was Lower than Normal subjects (P=0.003). The biochemical factors and genotype analysis indicated that FBS and TG levels in the CT+ TT genotypes were significantly higher than that of CC genotype in MetS subjects (P =0.000); The HDL level and BMI in CC genotype were higher (P=0.003, P=0.002). Furthermore, logistic regression analysis of the genotype frequencies for people with a history of cardiovascular disease and people without cardiovascular disease in metabolic syndrome subjects, showed that the odds ratios (OR) of CT+ TT genotypes carriers for CVD risk were higher than those of CC genotypes carriers (OR: 2.8889; 95 % CI : 1.0344 - 8.0680; P = 0.0429). There was relative risk for CT+ TT genotypes versus CC genotype (RR: 1.3542; 95 % CI: 1.0386 - 1.7656; P = 0.0251). Results of this study revealed that the CT+ TT genotypes carriers rs7903146 variation could be predisposed to CVD risk.

Majority of Elderly Sedentary Kenyans Show Unfavorable Body Composition and Cardio-Metabolic Fitness

Chronic disease, more prevalent among the elderly, is influenced by body composition and cardio-metabolic physiognomies. Aim: In this study, body composition, cardiovascular, and metabolic function in sedentary but healthy Kenyan individuals of = 50 years was determined. Methods: For 53 volunteers from Eldoret, Kenya, their biological, demographic characteristics, metabolic functions, cardiovascular performance, and body composition measurements were done before they were subjected to a Shuttle Run Test (SRT). Following SRT, their cardiovascular parameters were measured, and maximal oxygen consumption estimated. Fasting blood sugars and lipid profiles were measured after a 12-hour fast. Results: For males and females, respectively, the following parameters were recorded: average ages 55.5 ± 3.0 and 53.9 ± 3.0 years, BMI > 24.9 Kg/M2 in 67% and 88.5%, waist-to-height ratio = 0.5 in 70% and 88.5%, waist–hip ratio 78% ( = 0.90 ) and 38.5% (= 0.85), and blood pressure >140/90 mmHg in 22.2% and 23.1%. Pre-diabetic to diabetic values were found in 70.4% males and 88.5% females. The percent body fat was 22.3 ± 8.0 and 38.3 ± 4.69 in males and females, respectively. Lipid profile for males and females, respectively, showed high Total Cholesterol (TC) in 48.1% and 42.3%, anomalous Low Density Lipoproteins (LDL) in 29.6% and 26.9%, lower than normal HDL levels in 29.6% and 23.1%, elevated triglycerides in 22.2% and 7.7%, abnormal TC/HDL ratio in 44.4% and 38.5% females, higher LDL/HDL in 33.3% and 34.6%, and critical Triglycerides/HDL levels in 7.4% and 3.8%. Overall, 51.9% of males and 53.8% of females showed features consistent with metabolic syndrome. Conclusion: Majority of elderly sedentary Kenyans have body compositions and cardio-metabolic profiles below that for good cardiopulmonary fitness.

Efavirenz as component of initial combination antiretroviral therapy – Data from the Polish Observational Cohort of HIV/AIDS Patients (POLCA) Study Group

AimWe have investigated treatment effects among patients from Polish Observational Cohort of HIV/AIDS Patients (POLCA) who started efavirenz (EFV) in their first combination antiretroviral therapy (cART). BackgroundCombination antiretroviral therapy has dramatically influenced HIV epidemic and patients outcomes. With wider access to care and treatment and newer forms of cART HIV-positive persons’ prognosis continue to further improve, yet still strongly dependent on optimal adherence and virological efficacy. Materials and MethodsPOLCA is an observational cohort where information is collected in real-time from clinic database. Patients were included into analyses, if being naïve prior and starting EFV-based cART regimen and followed until 24 months, treatment modification or death whichever occurred first. ResultsIn total 285 patients started EFV-based cART and 55.1% continued the treatment after two years. Majority of patients were male (85.6%) and HIV infected through sexual contacts (97.5%). The median age at starting cART was 31.9 years. Baseline CD4 count was 228cells/μl. Thirty patients (10.5%) had treatment failure defined as <200copies/μl in two subsequent measurements and/or viral rebound above 500copies/μl. In terms of toxicities we have observed continuous increase in proportion of patients with normal urine protein level from 75.3% at baseline to 89.3% after 24 month of treatment. The proportion of patients with normal triglycerides, total cholesterol and LDL cholesterol decreased over time on efavirenz-based treatment, whereas proportion of those with normal HDL cholesterol increased. 16.4% of patients discontinued EFV due to CNS-related toxicities. ConclusionsEFV-based cART proved to be effective and safe treatment option for HIV-positive patients observed in POLCA study.

Proinflammatory high-density lipoprotein results from oxidized lipid mediators in the pathogenesis of both idiopathic and associated types of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by abnormal elaboration of vasoactive peptides, endothelial cell dysfunction, vascular remodeling, and inflammation, which collectively contribute to its pathogenesis. We investigated the potential for high-density lipoprotein (HDL) dysfunction (i.e., proinflammatory effects) and abnormal plasma eicosanoid levels to contribute to the pathobiology of PAH and assessed ex vivo the effect of treatment with apolipoprotein A-I mimetic peptide 4F on the observed HDL dysfunction. We determined the "inflammatory indices" HII and LII for HDL and low-density lipoprotein (LDL), respectively, in subjects with idiopathic PAH (IPAH) and associated PAH (APAH) by an in vitro monocyte chemotaxis assay. The 4F was added ex vivo, and repeat LII and HII values were obtained versus a sham treatment. We further determined eicosanoid levels in plasma and HDL fractions from patients with IPAH and APAH relative to controls. The LIIs were significantly higher for IPAH and APAH patients than for controls. Incubation of plasma with 4F before isolation of LDL and HDL significantly reduced the LII values, compared with sham-treated LDL, for IPAH and APAH. The increased LII values reflected increased states of LDL oxidation and thereby increased proinflammatory effects in both cohorts. The HIIs for both PAH cohorts reflected a "dysfunctional HDL phenotype," that is, proinflammatory HDL effects. In contrast to "normal HDL function," the determined HIIs were significantly increased for the IPAH and APAH cohorts. Ex vivo 4F treatment significantly improved the HDL function versus the sham treatment. Although there was a significant "salutary effect" of 4F treatment, this did not entirely normalize the HII. Significantly increased levels for both IPAH and APAH versus controls were evident for the eicosanoids 9-HODE, 13-HODE, 5-HETE, 12-HETE, and 15-HETE, while no statistical differences were evident for comparisons of IPAH and APAH for the determined plasma eicosanoid levels in the HDL fractions. Our study has further implicated the putative role of "oxidant stress" and inflammation in the pathobiology of PAH. Our data suggest the influences on the "dysfunctional HDL phenotype" of increased oxidized fatty acids, which are paradoxically proinflammatory. We speculate that therapies that target either the "inflammatory milieu" or the "dysfunctional HDL phenotype," such as apoA-I mimetic peptides, may be valuable avenues of further research in pulmonary vascular diseases.

HDL abnormalities in nephrotic syndrome and chronic kidney disease.

Normal HDL activity confers cardiovascular and overall protection by mediating reverse cholesterol transport and through its potent anti-inflammatory, antioxidant, and antithrombotic functions. Serum lipid profile, as well as various aspects of HDL metabolism, structure, and function can be profoundly altered in patients with nephrotic range proteinuria or chronic kidney disease (CKD). These abnormalities can, in turn, contribute to the progression of cardiovascular complications and various other comorbidities, such as foam cell formation, atherosclerosis, and/or glomerulosclerosis, in affected patients. The presence and severity of proteinuria and renal insufficiency, as well as dietary and drug regimens, pre-existing genetic disorders of lipid metabolism, and renal replacement therapies (including haemodialysis, peritoneal dialysis, and renal transplantation) determine the natural history of lipid disorders in patients with kidney disease. Despite the adverse effects associated with dysregulated reverse cholesterol transport and advances in our understanding of the underlying mechanisms, safe and effective therapeutic interventions are currently lacking. This Review provides an overview of HDL metabolism under normal conditions, and discusses the features, mechanisms, and consequences of HDL abnormalities in patients with nephrotic syndrome or advanced CKD.

Metabolic Dyslipidemia and Risk of Coronary Heart Disease in 28,318 Adults With Diabetes Mellitus and Low-Density Lipoprotein Cholesterol

The risk of future coronary heart disease (CHD) in subjects with diabetes and "metabolic dyslipidemia" (high triglyceride [TGs] and low high-density cholesterol levels) remains a matter of concern. Little is known regarding the risk of CHD for this phenotype with low-density lipoprotein cholesterol (LDL-C) levels <100 mg/dl. We analyzed a diabetes cohort of 28,318 members (aged 30 to 90 years) of Kaiser Permanente Northern California during 2002 to 2011 (192,356 person-years [p-y] follow-up), with LDL-C levels <100 mg/dl and without known CHD. We compared the incidence and hazard ratios (HRs) for CHD events in groups using Cox models: normal high-density lipoprotein (HDL) and TG (reference; n = 7,278, 25.7%); normal HDL and high TG (≥ 150 mg/dl; n = 4,484,15.8%); low HDL (≤ 50 mg/dl for women and ≤ 40 mg/dl for men) and normal TG (n = 4,048, 14.3%); low HDL and high TG (metabolic dyslipidemia; n = 12,508, 44%). Patients with metabolic dyslipidemia had the highest age-adjusted CHD events/1,000 p-y (12.7/1,000 p-y and 19.0/1,000 p-y for women and men, respectively). After multivariate adjustment for age, gender, ethnicity, hypertension, smoking, statin use, duration of diabetes, and hemoglobin A1c, we observed an increased CHD risk in women (HR 1.35, 95% confidence interval 1.14 to 1.60) and men (HR 1.62, 95% confidence interval 1.43 to 1.83) with metabolic dyslipidemia compared to those with normal HDL and TG. Even in subjects with an LDL-C <100 mg/dl, presence of metabolic dyslipidemia in adults with diabetes is associated with an increased risk of CHD. In conclusion, effective CHD prevention strategies are needed for adults with diabetes and metabolic dyslipidemia.

Do diethyl phthalate (DEP) and di-2-ethylhexyl phthalate (DEHP) influence the metabolic syndrome parameters? Pilot study.

The study objective was to determine if the healthy participants were exposed to diethyl phthalate (DEP) and di (2-ethylhexyl) phthalate (DEHP) and if this exposure could be linked to the development of metabolic syndrome. The study included 103 healthy volunteers of similar age with normal BMI values, waist circumference, total cholesterol, HDL, LDL, and triglycerides. DEP and DEHP were measured in the morning urine samples to detect monoethyl phthalate (MEP) and mono-2-ethylhexyl phthalate (MEHP). Two phthalate groups and a control group were formed. Both MEP group and control group had similar results. The correlations between MEP and the measured parameters were insignificant. The correlation between the MEHP group and the age was significantly negative, but between the MHEP group and the waist circumference the correlation was significantly positive. Lipids and lipoproteins were within the reference values and equal in both groups. The significant negative correlation was observed only between MEHP and HDL. Our population is exposed to DEP and DEHP. There was only a significant correlation between DEHP and the observed metabolic syndrome components. Its negative impact was higher as the participants were younger.

Cholesteryl ester transfer protein: ace of spades, queen of hearts, or the joker?

Cholesteryl ester transfer protein: ace of spades, queen of hearts, or the joker?

Significant abnormalities of the HDL phosphosphingolipidome in type 1 diabetes despite normal HDL cholesterol concentration.

Phospholipids and sphingolipids are major components of HDL. They play a critical role in HDL functionality and protective effects against atherosclerosis. As HDL are dysfunctional in type 1 diabetic patients, we ascertained whether they presented abnormalities in their phospholipid and sphingolipid profile, despite normal HDL cholesterol concentration. Using liquid chromatography-tandem mass spectrometry, we quantified the main species of phosphatidylcholines, sphingomyelins, lysophophatidylcholines, phosphatidylethanolamines, phosphatidylinositols, ceramides, plasmalogens and sphingosines 1-phosphate in the HDL2 and HDL3 from 54 type 1 diabetic patients and 50 controls. Serum HDL cholesterol was similar in the 2 groups of subjects. When data were expressed relative to the total amount of phospholipids and sphingolipids, sphingosines-1-phosphate (S1P) were 11.7% (NS) and 14.4% (p=0.0062) lower in HDL2 and HDL3, respectively, from type 1 diabetic patients than from controls. Ceramides were 23% (p=0.005) and 24% (borderline significance) lower in HDL2 and HDL3, respectively. The concentration of apolipoprotein M, the carrier of S1P, was similar in patients and controls. In type 1 diabetic patients compared to controls, the concentration of d18:1-S1P, the main S1P species, was decreased in total plasma (-17.0%, p<0.0001), HDL fraction (-21.9%, p<0.0001) and non-HDL fraction (-13.7%, p=0.012). The concentration of ceramides was decreased in total plasma (-24.4%, p<0.0001), HDL fraction (-27.9%, p=0.0006) and non-HDL fraction (-22.0%, p=0.0087). Despite normal HDL cholesterol level, the phospholipid+sphingolipid profile is impaired in HDL from type 1 diabetic patients. These abnormalities, especially the decrease in S1P, could contribute to the impaired HDL functionality observed in these patients.

Association of high-density lipoprotein with development of metabolic syndrome components: a five-year follow-up in adults.

BackgroundHigh-density lipoprotein (HDL) is associated with the incidence of metabolic syndrome (MetS). It is unclear whether subjects with different HDL levels develop different components of MetS over time. Our study aimed to determine what MetS components tend to emerge and change relative to different levels of HDL.MethodsDuring the period 2007 to 2012, 4,905 adults in Tongren and Xiaotangshan Hospitals in Beijing were included with no MetS, self-reported type 2 diabetes, or cardiovascular disease at baseline. An association rule was used to determine the changes of MetS components over time.ResultsThe incidence of MetS at follow-up was 3.40% for men and 1.50% for women in the high-normal HDL group; 6.65% and 4.55%, respectively, in the normal HDL group; and 11.05% and 6.45%, respectively, in the low HDL group. The most common transition was from healthy to healthy in normal-high or normal HDL groups (47.2% to 63.8%), whereas 11.7% to 39.9% of subjects with low HDL returned to healthy status or stayed unchanged in the low HDL group. The most common new-onset components were elevated blood pressure (9.2 to 10.0%), elevated high-density lipoprotein (5.5 to 11.0%), and raised fasting glucose (5.4 to 5.5%) in the groups with normal-high or normal HDL.ConclusionsThe incidence of MetS increased in parallel with the decrease in HDL. Adults with a low HDL level were more susceptible to developing MetS over time. Low HDL seemed to be a pre-existing phase of MetS and may be a crucial status for MetS prevention.

Serum Amyloid A 1.1 Forms a Conformational Temperature Sensor at the Lipid Surface

Serum amyloid A (SAA) is a natively unfolded acute-phase protein. Normally SAA circulates on plasma high-density lipoproteins (HDL) whose major protein is apoA-I. In inflammation SAA levels can increase 1000-fold and it becomes the major plasma protein that displaces up to 50% of apoA-I from HDL, forming SAA-HDL with altered metabolic properties. To determine whether SAA alters structural stability of HDL, human HDL were incubated with murine SAA 1.1 to obtain SAA-HDL. Calorimetric, spectroscopic and biochemical studies showed that HDL fusion and rupture, which were characterized in our previous work, occur at similar temperatures in normal HDL and in SAA-HDL. Therefore, the exchangeable fraction of apoA-I has little effect on HDL stability which, we propose, is determined by the apoA-I fraction that cannot be displaced. This apoA-I likely forms an antiparallel double-belt dimer around HDL. Our results argue against domain swapping among apoA-I molecules on HDL, which is important for HDL structure and function. Surprisingly, our results reveal helical unfolding in SAA-HDL circa 38°C. This novel transition was observed only in samples containing excess SAA and the lipid surface, but neither in lipid-free SAA nor in isolated SAA-HDL containing lipoproteins alone. The transition was invariant in a wide range of solvent conditions (pH 5.5-8.5, 10-150 mMol Na salt), upon lipolysis by PLA2, or upon lipoprotein rupture. In sum, SAA near the lipid surface undergoes folding/unfolding at physiologic temperatures. We propose that excess SAA forms a local conformational temperature sensor and suggest a new function for SAA in acute phase response. Funded by NIH GM067260.

Risk Factors Associated with Ischemic Heart Diseases in Different Age Groups Patients of Tertiary Care Hospitals of Peshawar

Objectives:To determine different risk factors associated with ischemic heart diseases in different age group patients of tertiary care hospitals of Peshawar.Methodology:A cross sectional study conducted on 350 patients of different age groups presented with ischemic heart diseases in tertiary care hospitals of Peshawar. Study was conducted for duration of 3 months from December 2013 to February 2014. Non probability convenient sampling technique was used. Sample size was calculated using standard sample size calculator. Semi structured questionnaire was used as data collection tool. Patient’s record and investigations were used as adding tools. Standard definition was made for ischemic heart disease. Different modifiable and non-modifiable factors were assessed and were analyzed using SPSS version 16.Results:This study contains 350 patients in which female patients were 133(38%) and male were 217(62%).The mean age was 57.23±11.36 years. The age of the patients ranges from 22 to 80 years. The frequencies of risk factors were stress (73.1%) followed by hypertension (65.7%), sedentary life style (59.4%), family history (57.1%), smoking (50.6%), over weight and obese (39.1%), below normal HDL (30.3%), high LDL (29.1%), hypertriglyceridemia (28%), hypercholesterolemia (23.7%). 64.3% patients were presenting with acute IHD and 35.7% were with chronic IHD. Stress, HTN, DM and sedentary life style were found to be significantly associated with male gender (p- value &lt;0.05). Age was divided into two groups, &lt;45 years and &gt;45 years. Stress, HTN, DM and hypercholesterolemia had a significant association with &gt;45 years of age group. (P-value &lt;0.05).Conclusion:Stress, HTN, DM, sedentary life styles were the major risk factors. And they were found to be more in male gender and in equal to more than 45 years of age group.

Remarkable quantitative and qualitative differences in HDL after niacin or fenofibrate therapy in type 2 diabetic patients

HDL-increasing drugs such as fenofibrate and niacin have failed to decrease the cardiovascular risk in patients with type 2 diabetes. Drug-mediated quantitative and qualitative HDL modifications could be involved in these negative results. To evaluate the quantitative and qualitative effects of niacin and fenofibrate on HDL in patients with type 2 diabetes, a prospective, randomised controlled intervention trial was conducted. Thirty type 2 diabetic patients with low HDL were randomised to receive either fenofibrate (FFB) or niacin + laropiprant (ERN/LPR) as an add-on to simvastatin treatment for 12 weeks according to a crossover design. At the basal point and after each intervention period, physical examinations and comprehensive standard biochemical determinations and HDL metabolomics were performed. Thirty nondiabetic patients with normal HDL were used as a basal control group. ERN/LRP, but not FFB, significantly increased HDL cholesterol. Neither ERN/LRP nor FFB reversed the HDL particle size or particle number to normal. ERN/LRP increased apoA-I but not apoA-II, whereas FFB produced the opposite effect. FFB significantly increased Preβ1-HDL, whereas ERN/LRP tended to lower Preβ1-HDL. CETP and LCAT activities were significantly decreased only by ERN/LRP. PAF-AH activity in HDL and plasma decreased with the use of both agents. Despite their different actions on antioxidant parameters, none of the treatments induced detectable antioxidant improvements.ERN/LRP and FFB had strikingly different effects on HDL quantity and quality, as well as on HDL cholesterol concentrations. When prescribing HDL cholesterol increasing drugs, this differential action should be considered.

Saquinavir/r containing initial antiretroviral therapy (ART)-long term evaluation in Polish Observational Cohort of HIV/AIDS Patients (POLCA) Study Group

BackgroundSince the introduction of highly active antiretroviral treatment significant decrease of HIV related morbidity and mortality has been noted. Ritonavir boosted saquinavir is an alternatively recommended protease inhibitor. Therefore we evaluated log term efficacy and safety of saquinavir/r (SQV/r) containing initial antiretroviral regimen on the basis of Polish Observational Cohort of HIV/AIDS Patients (POLCA).Materials and Methods The analysed data were prospectively collected in routine clinical practice and included ART naive patients starting SQV/r regiment as their first ART. ResultsFrom among 259 naive patients, who started SQV/r containing regimen 56.1% continued it for 24 months. Majority of the patients were male (74.9%). Similar proportion of patients was infected by IVDU (40.1%) and by sexual contact (47.1%). Median time from initial diagnosis was 2.16 years. Median baseline lymphocytes count was 210cells/mm3.Viral failure defined as HIV RNA>200copies/ml in at least two consecutive tests or>500copies/ml in one test was observed in 30 patients (11.5%). Analysing treatment related toxicities we found gradual decrease in proportion of patients with proteinuria (44.4–26%). Proportion of patients with normal total cholesterol, LDL and triglycerides decreased after 6 months of treatment and remained stable, whereas proportion of patients with normal HDL increased gradually to the end of observation. 23% of patients discontinued SQV/r containing regimen due to side effects, mainly gastrointestinal. ConclusionsSaquinavir/r containing regimen remains a valuable and safe option for patients with indications to protease inhibitor based antiretroviral treatment.

Cholesterol and lipoprotein metabolism: Early Career Committee contribution.

Cholesterol and lipoprotein metabolism: Early Career Committee contribution.

Identification of the Best Anthropometric Predictors of Serum High- and Low-Density Lipoproteins Using Machine Learning.

Serum high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels are associated with risk factors for various diseases and are related to anthropometric measures. However, controversy remains regarding the best anthropometric indicators of the HDL and LDL cholesterol levels. The objectives of this study were to identify the best predictors of HDL and LDL cholesterol using statistical analyses and two machine learning algorithms and to compare the predictive power of combined anthropometric measures in Korean adults. A total of 13,014 subjects participated in this study. The anthropometric measures were assessed with binary logistic regression (LR) to evaluate statistically significant differences between the subjects with normal and high LDL cholesterol levels and between the subjects with normal and low HDL cholesterol levels. LR and the naive Bayes algorithm (NB), which provides more reasonable and reliable results, were used in the analyses of the predictive power of individual and combined measures. The best predictor of HDL was the rib to hip ratio (p =< 0.0001; odds ratio (OR) = 1.895; area under curve (AUC) = 0.681) in women and the waist to hip ratio (WHR) (p =< 0.0001; OR = 1.624; AUC = 0.633) in men. In women, the strongest indicator of LDL was age (p =< 0.0001; OR = 1.662; AUC by NB = 0.653 ; AUC by LR = 0.636). Among the anthropometric measures, the body mass index (BMI), WHR, forehead to waist ratio, forehead to rib ratio, and forehead to chest ratio were the strongest predictors of LDL; these measures had similar predictive powers. The strongest predictor in men was BMI (p =< 0.0001; OR = 1.369; AUC by NB = 0.594; AUC by LR = 0.595 ). The predictive power of almost all individual anthropometric measures was higher for HDL than for LDL, and the predictive power for both HDL and LDL in women was higher than for men. A combination of anthropometric measures slightly improved the predictive power for both HDL and LDL cholesterol. The best indicator for HDL and LDL might differ according to the type of cholesterol and the gender. In women, but not men, age was the variable that strongly predicted HDL and LDL cholesterol levels. Our findings provide new information for the development of better initial screening tools for HDL and LDL cholesterol.

Corneal dystrophies related to cholesterol metabolism (fish eye and Schnyder dystrophy)

AbstractSchnyder corneal dystrophy (SCD) is a rare corneal dystrophy characterized by abnormally increased deposition of cholesterol and phospholipids in the cornea. SCD is inherited as an autosomal dominant trait with high penetrance and has been mapped to the UBIAD1 gene on chromosome 1p36.3. Diseases of systemic lipid metabolism that cause corneal opacification, such as lecithin‐ cholesterol acyltransferase (LCAT) deficiency and fish eye disease (FED), should be considered in the differential diagnosis. LCAT deficiency and FED are both entities that result from deficiency of the LCAT enzyme. LCAT deficiency is defined by deficient LCAT activity towards HDL and LDL whereas FED is defined by decreased LCAT activity against HDL only. When comparing LCAT deficiency and FED to SCD, there are numerous differences to help distinguish all 3 entities. Both LCAT deficiency and FED are inherited in an autosomal recessive manner while SCD has autosomal dominant inheritance. Systemically, SCD has a normal level of LCAT enzyme activity and normal HDL levels. Both LCAT deficiency and FED show abnormally low levels of HDL. SCD is often associated with a true arcus lipoides, unlike FED and LCAT deficiency.

Association of glucose transporter 4 gene polymorphism with hypoxia caused by obstructive sleep apnea syndrome and with related inflammatory factors

To investigate the relationship between genetic polymorphisms of glucose transporter 4 (GLUT4) and hypoxia caused by obstructive sleep apnea syndrome (OSAS) as well as with related inflammatory factors. Consecutive hypertension patients diagnosed at the People's Hospital of Xinjiang Uygur Autonomous Region were selected from January to December 2010. A total of 859 subjects with possible OSAS base on their histories and physical examination findings udner went the polysomnography and inflammatory factor determination, of whom 616 (72%) were diagnosed with moderate and severe hypoxia with OSAS (case group) and 243 (28%) without hypoxia or OASA (control group). Ninty-six patients from the case group underwent DNA sequencing at the functional domain of GLUT4 gene to screen for representative mutations. TaqMan PCR was used to genotyping then analyzed the relationship between locis of GLUT4 and hypoxia. GLUT4 genome sequencing was performed in 96 severe OSAS patients and 4 mutated sites were found, among which 3 mutated sites (rs5415, rs4517, and rs5435) were selected according to the principle of linkage disequilibrium (r² > 0.8) and minimum gene allele frequency > 5%. All of single nucleotide polymorphisms (SNP) satisfied Hardy-Weinberg equilibrium (P>0.05). A significant association of GLUT4 SNP rs5417 allele carried in control subjects, compared with moderate and severe hypoxia in OSAS patients (P<0.05); AA+AC genotype relative to CC with low oxygen levels in subjects significantly reduced. The difference existed in overweight and obese patients, as well as in those aged more than 50 years (P<0.05). AA was still an independent protective factor for hypoxia caused by OSAS (OR=0.385, 95%CI = 0.210-0.704, P=0.002). Male (OR=1.635, 95% CI=1.037-2.577, P=0.034) and total cholesterol (OR=1.600, 95% CI=1.287-1.987, P<0.001) were independent risk factors associated with hypoxia. Normal weight(OR=0.059, 95% CI=0.037-0.094, P<0.001) and high density lipoprotein cholesterol (OR=0.337, 95% CI=0.171-0.666, P=0.002)were independent protective factors for hypoxia. The levels of monocyte chemoattractant protein-1 and C-reaction protein above CC were significantly higher than AA+AC (P<0.05). Hypoxia caused by OSAS is associated with GLUT4 gene SNP rs5417.