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Favorable effects of hydroxychloroquine on serum low density lipid in patients with systemic lupus erythematosus: A systematic review and meta-analysis.
Babary, H, Liu, X, Ayatollahi, Y, Chen, XP, Doo, L, Uppaluru, LK, Kwak, MK, Kulaga, C, Modjinou, D, Olech, E, et al
International journal of rheumatic diseases. 2018;(1):84-92
Abstract
AIMS: Hydroxychloroquine (HCQ) has shown to have significant immunomodulatory effects in the treatment of systemic lupus erythematosus (SLE). Current studies show favorable effects of HCQ on traditional cardiac risk factors in patients with SLE. This review examined the effects of HCQ on serum low-density lipoprotein (LDL) level in patients with SLE. METHODS A systematic search of seven major literature search databases from their inception until 3 April, 2017 identified nine studies. Random-effects pooled mean difference with corresponding 95% confidence intervals (CI) were estimated. Heterogeneity was measured by I2 . Publication bias was assessed by visual inspection of funnel plots. Sensitivity analysis examined whether HCQ effect on serum total cholesterol level was similar to the main analysis. The Grading of Recommendations Assessment, Development, and Evaluation system was used to assess the overall quality of evidence. RESULTS Pooled study participants were 559 patients from eight observation studies (two before-after studies; six case-control studies) examining the effects of HCQ on serum LDL. Pooled study participants' characteristics were as follows: mean age 45.719, female 95.262%, and prednisone use 58.366%. HCQ reduced mean LDL levels by 24.397 mg/dL (95% CI 8.921-39.872; P = 0.002). The number of studies identifying statin use was too few to perform meta-regression analysis of statin use. Heterogeneity was extensive (I2 = 94.739%). Symmetrical funnel plot visualized no evidence of publication bias. CONCLUSION HCQ was associated with serum LDL level reduction by mean 24.397 mg/dL in patients with SLE. Future prospective studies are need to fully characterize the treatment effect.
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Effectiveness of Low to Moderate Physical Exercise Training on the Level of Low-Density Lipoproteins: A Systematic Review.
Albarrati, AM, Alghamdi, MSM, Nazer, RI, Alkorashy, MM, Alshowier, N, Gale, N
BioMed research international. 2018;:5982980
Abstract
BACKGROUND Regular exercise reduces risk factors associated with cardiovascular disease (CVD). Elevated low-density lipoprotein (LDL) contributes to atherosclerosis formation, which is associated with an increased risk of CVD. The relationship between exercise therapy and lipid levels has been widely studied, but it is established that high-intensity exercise improves lipid profile. However, the effectiveness of low- to moderate-intensity exercise in altering LDL levels is controversial. This review aims to identify the current evidence and existing gaps in literature in this area. METHODS We searched and reviewed various randomized controlled clinical trials in the electronic databases EMBASE, CINAHL, the Web of Science, Cochrane, Pedro, Medline (PubMed), and Google Scholar using the keywords "low and moderate aerobic training," "exercise", "low-density lipoproteins," "cholesterol," "atherosclerosis," and "coronary artery diseases markers." We included studies that involved low- and/or moderate-intensity exercise training in apparently healthy adults over a period of 8 weeks and its effect on LDL levels. We selected a total of 11 studies from 469; nine were randomized controlled trials and two were systematic reviews. RESULTS Aerobic exercise of both low and moderate intensity resulted in a significant reduction of total cholesterol. Effects on low-density lipoprotein levels were significant, and most of the studies showed changes in the level without significant relation to the type of exercise. At the same time, exercise improved the health status and physical fitness of all the participants in the included studies. CONCLUSION This study found that low- and moderate-intensity exercise and low-density lipoprotein levels were not proven to be significantly related, except in a few studies that were limited to dyslipidemia population.
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OxLDL plasma levels in patients with Alzheimer's disease.
Grossi, MF, Carvalho, MDG, Silveira, JN, Gonçalves, GS, Gomes, KB, Bicalho, MA, Silva, IFO
Arquivos de neuro-psiquiatria. 2018;(4):241-246
Abstract
OBJECTIVE The objective of this study was to characterize the conventional lipid profile, oxLDL levels and ApoE polymorphism in patients with Alzheimer's disease (AD) and in elderly individuals without cognitive impairment. METHODS Eighty elderly individuals were selected and the levels of oxLDL were determined using the ELISA kit, and ApoE gene polymorphism was investigated using polymerase chain reaction-restriction fragment length polymorphism. RESULTS Significantly reduced levels of oxLDL were observed in patients with AD compared to the control group. A higher frequency of the ApoE ε4 allele was observed in patients with AD compared to controls. No difference was observed for total cholesterol, HDL-C, and LDL-C levels between the two groups, while triglyceride levels were higher in controls compared with patients with AD. CONCLUSION The data analyzed together did not reveal significant differences in lipid profiles, including oxLDL levels. However, the importance of lipid changes in the genesis of the disease cannot be ruled out. Nevertheless, the ApoE ε4 allele was significantly more frequent in patients with Alzheimer's dementia in agreement with previous findings in the literature, but this genetic component did not change the levels of oxLDL.
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Incretins and Lipid Metabolism.
Tsimihodimos, V, Elisaf, M
Current medicinal chemistry. 2018;(18):2133-2139
Abstract
BACKGROUND Recent findings indicate that incretin hormones and incretin-based therapies may affect the metabolism of lipoproteins, although the corresponding mechanisms are not clearly defined. OBJECTIVE To summarize the available data on the mechanisms linking incretins with the characteristics of serum lipoproteins and discuss the clinical implications of these relationships. METHODS PubMed was searched using the terms "incretins", "GLP-1", "GIP" and "lipids", "dyslipidemia", "triglycerides", "apolipoprotein B48". All articles published in the English language until June 2016 were assessed and the relevant information is presented here. RESULTS GLP-1, and therapies that increase its activity, exert a beneficial effect on lipoprotein metabolism that is translated in a reduction in the fasting and postprandial concentration of triglycerides and a small improvement in the concentration and function of HDLs. In addition, a shift towards larger, less atherogenic particles usually follows the administration of GLP-1 receptor agonists. The mechanisms that underlie these changes involve a direct effect of GLP- 1 on the hepatic and intestinal production of triglyceride-rich lipoproteins, the GLP-1 induced increase in the production and function of insulin, the activation of specific areas of central nervous system as well as the increase in the peripheral utilization of triglycerides for energy production. On the other hand, GLP-2 increases the absorption of dietary fat and the production of triglyceride-rich lipoproteins while the role of GIP on lipid metabolism remains indeterminate. CONCLUSION GLP-1 and incretin-based therapies favorably affect lipid metabolism. These effects may contribute to the beneficial effects of incretin-based therapies on atherosclerosis and fatty liver disease.
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Oxidized Low-Density Lipoprotein and Cell Adhesion Molecules Following Exercise Training.
Koh, Y, Park, J, Carter, R
International journal of sports medicine. 2018;(2):83-88
Abstract
Elevated oxidized low-density lipoprotein (ox-LDL) and cell adhesion molecules are associated with inflammation and atherosclerosis. The role of exercise in circulating ox-LDL, enzyme mediators, and cell adhesion molecules are not clearly understood in obesity. As a randomized controlled design, 27 obese (BMI>30 kg/m2) sedentary men (N=13) and women (N=14) were randomly assigned to either an exercise (N=15) or a control (N=12) group. The exercise group performed a 60-min supervised treadmill exercise at moderate intensity (70% of HRmax) for 3 days per week for 4 weeks, while the control group did not exercise. Overnight fasting blood samples were collected before and after the study period to analyze serum lipids, lipoprotein-cholesterol, ox-LDL, 12- and 15-lipoxygenases, myeloperoxidase (MPO), and soluble vascular cell adhesion molecules-1 and intercellular adhesion molecule-1. Moderate-intensity exercise training lowered both ox-LDL (from 44.76±1.99 to 38.51±1.99 U/L, p=0.032) and MPO (from 31.48±2.20 to 23.09±2.20 ng/mL, p=0.010), without significantly altering body weight, other parameters of serum lipids and lipoproteins, or soluble cell adhesion molecules. Moderate intensity exercise training reduced the levels of ox-LDL and MPO, indicating a reduced risk for developing CVD and additional protection to the possible metabolic complications associated with obesity.
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A Single Bout of Exercise Reduces Postprandial Lipemia but Has No Delayed Effect on Hemorheological Variables.
Chiu, CH, Yang, TJ, Liang, HJ, Chang, CK, Wu, CL
The Chinese journal of physiology. 2018;(3):181-187
Abstract
High plasma triglyceride (TG) concentration in fasting state could cause hemorheological abnormality, thus increasing the incidence of metabolic diseases. Exercise has been reported to effectively reduce postprandial TG response. This study aimed to investigate whether a single bout of pre-prandial exercise can affect lipemia and hemorheological variables after a high-fat meal. Nine healthy young male subjects completed two experimental trials. The subjects walked for 1 h at 50% maximal oxygen uptake (V̇O₂max) (the exercise, EX trial), or rested (the control, CON trial). In the next morning, the subjects consumed a high-fat meal, and the postprandial lipemia and hemorheological responses were monitored for 6 h. The results showed that postprandial plasma TG concentrations were significantly lower in the EX trial compared to the CON trial. The postprandial low-density lipoproteins (LDL) concentration declined in the first 2 h and then gradually returned to the baseline level in both trials. The postprandial blood viscosity also decreased in the CON trial. There was no significant difference in postprandial blood viscosity, red blood cell (RBC) deformation index and aggregation degree between the trials. There was no significant correlation between plasma TG concentration and blood viscosity. In conclusion, brisk walking effectively reduced postprandial TG concentration, but has no significant impact on postprandial blood viscosity, RBC deformation index and RBC aggregation index.
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The enigmatic membrane fatty acid transporter CD36: New insights into fatty acid binding and their effects on uptake of oxidized LDL.
Jay, AG, Hamilton, JA
Prostaglandins, leukotrienes, and essential fatty acids. 2018;:64-70
Abstract
The scavenger receptor CD36 binds numerous small biomolecules, including fatty acids, and even large ligands such as oxidized LDL, for which it is considered a receptor. Although CD36 has often been postulated to "transport" fatty acids across the plasma membrane, fatty acids translocation (mass transport or kinetics) was not affected by expression of CD36 in HEK293 cells; however, esterification of fatty acids (cellular uptake) was increased. These recent results from our lab are consistent with the established mechanism of fatty acid entry into cells by passive diffusion (flip-flop) and also with the well-documented enhancement of uptake of fatty acids by CD36 in other cell types. A fascinating new discovery is that CD36 has multiple fatty acid binding sites on the extracellular domain of CD36. As illuminated by new methodologies that we have applied, these sites have high affinity and exhibit rapid exchange with the medium. In an initial study of functional consequences of binding, several dietary fatty acids enhanced uptake of oxidized LDL into HEK293 cells expressing CD36. This is the first established link between physical binding of fatty acids and a function of CD36, and has implications for obesity and atherosclerosis. New methods as those used in our study could also be applied to elucidate other functional roles of fatty acid binding to CD36.
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Effect of short-term hazelnut consumption on DNA damage and oxidized LDL in children and adolescents with primary hyperlipidemia: a randomized controlled trial.
Guaraldi, F, Deon, V, Del Bo', C, Vendrame, S, Porrini, M, Riso, P, Guardamagna, O
The Journal of nutritional biochemistry. 2018;:206-211
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Abstract
Children with primary hyperlipidemia are prone to develop premature atherosclerosis, possibly associated with increased oxidative stress. Nutritional therapy is the primary strategy in the treatment of hyperlipidemia and associated conditions. Dietary interventions with bioactive-rich foods, such as nuts, may contribute to the modulation of both lipid profile and the oxidative/antioxidant status. Our study aimed to assess the impact of a dietary intervention with hazelnuts on selected oxidative stress markers in children and adolescents with primary hyperlipidemia. A single-blind, 8-week, randomized, controlled, three-arm, parallel-group study was performed. Children and adolescents diagnosed with primary hyperlipidemia (n=60) received dietary guidelines and were randomized into three groups: group 1 received hazelnuts with skin (HZN+S), and group 2 hazelnuts without skin (HZN-S), at equivalent doses (15-30 g/day, based on body weight); group 3 (controls) received only dietary recommendations (no nuts). At baseline and after 8 weeks, plasma oxidized low-density lipoprotein (ox-LDL) concentrations, oxidative levels of DNA damage in PBMCs and potential correlation with changes in serum lipids were examined. A reduction of endogenous DNA damage by 18.9%±51.3% (P=.002) and 23.1%±47.9% (P=.007) was observed after HZN+S and HZN-S, respectively. Oxidatively induced DNA strand breaks decreased by 16.0%±38.2% (P=.02) following HZN+S treatment. Ox-LDL levels did not change after HZN+S intervention but positively correlated with total cholesterol and LDL cholesterol. A short-term hazelnut intervention improves cell DNA protection and resistance against oxidative stress but not ox-LDL in hyperlipidemic pediatric patients. The trial was registered at ISRCTN.com, ID no. ISRCTN12261900.
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An intensive lifestyle intervention reduces circulating oxidised low-density lipoprotein and increases human paraoxonase activity in obese subjects.
Russo, A, Pirisinu, I, Vacca, C, Reginato, E, Tomaro, ES, Pippi, R, Aiello, C, Talesa, VN, De Feo, P, Romani, R
Obesity research & clinical practice. 2018;(Suppl 2):108-114
Abstract
OBJECTIVE Obesity has a great impact on cardiovascular morbidity and mortality, the treatment of this pathological state is important given the significant health consequences. Lifestyle and behaviour changes play a significant role in weight management. The purpose of this study was to investigate the impact of an intensive multidisciplinary lifestyle intervention on well-known atherogenic factors in a group of overweight and obese subjects. METHODS A total of 44 people with overweight/obesity underwent a lifestyle intervention based on nutritional education, psychological support and a 3-month exercise training program with a frequency of twice a week. Several anthropometric and biochemical parameters were measured before and after the lifestyle intervention. RESULTS Lifestyle intervention led to a significant reduction in metabolic profile including body mass index (BMI), waist circumference, systolic and diastolic blood pressure, plasma glucose, and plasma triglycerides. These reductions were also accompanied by a significant increase in maximal oxygen consumption and muscle strength. Furthermore, paraoxonase and lactonase activities and the concentration of Apoliproteins A1 (APO A1) were significantly increased and the serum levels of oxLDL reduced without any changes in the circulating levels of LDL and HDL. CONCLUSION In conclusion, our study suggests that an intensive lifestyle intervention in obese subjects promotes a series of beneficial antiatherogenic changes which included increased enzyme activites of paraoxonase and lactonase, concentration of Apoliproteins A1 and decreased circulating levels of oxLDL.
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The relationship between oxidized low-density lipoprotein and related ratio and acute cerebral infarction.
Yan, Z, Fu, B, He, D, Zhang, Y, Liu, J, Zhang, X
Medicine. 2018;(39):e12642
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Abstract
This study aimed to study the value of oxidized low-density lipoprotein (OX-LDL) and related ratio in the diagnosis of acute cerebral infarction and the classification of acute cerebral infarction.Of the 129 patients enrolled in this study, 94 patients with acute cerebral infarction were assigned to the case group, and 35 healthy subjects were enrolled as control group (n = 35). And then the case group were divided into large-artery atherosclerosis (LAA) group (n = 61) and small-artery occlusion (SAO) group (n = 33) according to the TOAST classification standard. Plasma OX-LDL levels were determined by enzyme-linked immunosorbent assay. OX-LDL/total cholesterol (OX-LDL/TC), OX-LDL/high-density lipoprotein (OX-LDL/HDL), OX-LDL/LDL were calculated.There were significant differences in OX-LDL, OX-LDL/TC, OX-LDL/HDL, and OX-LDL/LDL in patients with acute cerebral infarction and those in control group (P < .001). The area under the receiver-operating characteristic curve of OX-LDL and related ratio was >0.7 (P < .001). There was a slight positive correlation between OX-LDL/TC and National Institutes of Health Stroke Scale score at admission (r = 0.265, P = .039) in the LAA group.OX-LDL, OX-LDL/TC, OX-LDL/HDL, and OX-LDL/LDL were closely related to acute cerebral infarction, especially with large atherosclerotic cerebral infarction. OX-LDL/TC can reflect the severity of acute cerebral infarction for LAA, but it cannot predict the short-term prognosis of acute cerebral infarction.