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Elevated C-reactive Protein and Depressed High-density Lipoprotein Cholesterol are Associated with Poor Function Outcome After Ischemic Stroke.
Zheng, X, Zeng, N, Wang, A, Zhu, Z, Zhong, C, Xu, T, Xu, T, Peng, Y, Peng, H, Li, Q, et al
Current neurovascular research. 2018;(3):226-233
Abstract
AIMS: C-reactive protein is an established marker of inflammation that can impair the protective function of High Density Lipoprotein Cholesterol (HDL-C). The combined effect of Creactive protein and HDL-C on long-term outcomes in patients with stroke remains uncertain. METHODS A total of 3124 acute ischemic stroke subjects from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) were included in this analysis. Participants were divided into four groups according to CRP and HDL-C levels on admission. The primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at one year after stroke. RESULTS Compared to participants with low CRP/ high HDL-C, adjusted odd ratios for primary outcome for those with low CRP /low HDL-C, high CRP /high HDL-C and high CRP /low HDL-C were 1.06(0.81-1.39),1.78(1.31-2.41) and 2.03(1.46-2.80), respectively, after multiple adjustments. Adding serum CRP and HDL-C status to a model containing conventional stroke risk factors significantly improve risk reclassification for the combined outcome of death and major disability (NRI: 6.85%, P=0.005; IDI: 2.57%, P=0.002). Moreover, no interaction was observed between CRP and HDL-C in relation to stroke outcomes (P-interaction >0.05 for all). CONCLUSIONS High CRP with low HDL-C levels was associated with death and major disability within one year after ischemic stroke. The findings suggest that the ischemic patients with both high CRP and low HDL-C should be treated with reducing CRP and promoting HDL-C levels.
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Exercise intervention alters HDL subclass distribution and function in obese women.
Woudberg, NJ, Mendham, AE, Katz, AA, Goedecke, JH, Lecour, S
Lipids in health and disease. 2018;(1):232
Abstract
BACKGROUND Obesity 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. METHODS Thirty-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. RESULTS Exercise 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. CONCLUSIONS These results demonstrate the potential for exercise training to modify HDL subclass distribution and HDL function in obese women. TRIAL REGISTRATION Clinical trials number: PACTR201711002789113 .
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Polyunsaturated fatty acids supplementation impairs anti-oxidant high-density lipoprotein function in heart failure.
Wurm, R, Schrutka, L, Hammer, A, Moertl, D, Berger, R, Pavo, N, Lang, IM, Goliasch, G, Huelsmann, M, Distelmaier, K
European journal of clinical investigation. 2018;(9):e12998
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Abstract
BACKGROUND The underlying reasons for the highly inconsistent clinical outcome data for omega-3-polyunsaturated fatty acids (n3-PUFAs) supplementation in patients with cardiac disease have not been understood yet. The aim of this prospective, randomized, double-blind, placebo controlled study was to determine the effects of oral treatment with n3-PUFAs on the anti-oxidant capacity of HDL in heart failure (HF) patients. METHODS A total of 40 patients with advanced HF of nonischaemic origin, defined by NT-proBNP levels of >2000 pg/mL, NYHA class III or IV and a LVEF <35% who were on stable optimized medical therapy for ≥3 months, were consecutively enrolled into this prospective, double-blind, placebo-controlled trial and randomized in a 1:1:1 fashion to receive 1 g/day or 4 g/day of n3-PUFA, or placebo, respectively, for 12 weeks. RESULTS After 12 weeks of treatment, the anti-oxidant function of HDL, measured by the HDL inflammatory index, was found significantly impaired in the treatment group in a dose-dependent fashion with 0.67 [IQR 0.49-1.04] for placebo vs 0.71 [IQR 0.55-1.01] for 1 g/day n3-PUFA vs 0.98 [IQR 0.73-1.16] for 4 g/day n3-PUFA (P for trend = 0.018). CONCLUSION We provide evidence for an adverse effect of n3-PUFA supplementation on anti-oxidant function of HDL in nonischaemic heart failure patients, establishing a potential mechanistic link for the controversial outcome data on n3-PUFA supplementation.
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4.
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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Circulating LECT2 levels in newly diagnosed type 2 diabetes mellitus and their association with metabolic parameters: An observational study.
Zhang, Z, Zeng, H, Lin, J, Hu, Y, Yang, R, Sun, J, Chen, R, Chen, H
Medicine. 2018;(15):e0354
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Abstract
Leukocyte cell-derived chemotaxin 2 (LECT2) is a hepatokine expressed in hepatocytes and appears to be involved in energy metabolism. The aim of this study was to determine plasma LECT2 levels in newly diagnosed type 2 diabetic patients and to correlate the results with various metabolic parameters.A total of 93 newly diagnosed type 2 diabetic patients and 80 age- and sex-matched nondiabetes mellitus ones were enrolled in the study. Plasma LECT2 levels were measured by enzyme-linked immunosorbent assay.Circulating LECT2 levels were approximately 1.3 times higher in newly diagnosed type 2 diabetic patients than in controls (mean 30.30 vs 23.23 ng/mL, P < .001). Correlation analysis showed that LECT2 was negatively associated with high-density lipoprotein-cholesterol (HDL-C) levels in type 2 diabetic patients and obese subjects (P < .05). In multiple stepwise regression analysis, HDL-C, HOMA-IR, BMI, FINS, and TG were significantly independent determinants for LECT2 (P < .05).Our study showed that circulating LECT2 concentrations are significantly higher in newly diagnosed type 2 diabetic patients and further elevated in obese type 2 diabetic patients. LECT2 concentrations are significantly negatively associated with HDL-cholesterol levels in newly diagnosed type 2 diabetic patients and obese subjects.
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Effects of Freeze-Dried Grape Powder on High-Density Lipoprotein Function in Adults with Metabolic Syndrome: A Randomized Controlled Pilot Study.
Millar, CL, Duclos, Q, Garcia, C, Norris, GH, Lemos, BS, DiMarco, DM, Fernandez, ML, Blesso, CN
Metabolic syndrome and related disorders. 2018;(9):464-469
Abstract
BACKGROUND High-density lipoprotein (HDL) particles are protective against atherosclerosis. However, HDL function is impaired in metabolic syndrome (MetS) due to low-grade inflammation and dyslipidemia. Foods containing polyphenols, such as grapes, may prevent HDL dysfunction via antioxidant or anti-inflammatory effects. We evaluated the effects of grape powder ingestion on measures of HDL function in adults with MetS. METHODS Twenty adults (age: 32-70 years; body mass index: 25.3-45.4 kg/m2) consumed either 60 grams/day of freeze-dried grape powder (GRAPE) or a placebo for 4 weeks, separated by a 3-week washout period, in a randomized, double-blind crossover study. The primary outcome was serum paraoxonase-1 (PON1) arylesterase activity, a measure of HDL antioxidant function. Secondary outcomes included PON1 lactonase activity, plasma lipids, metabolic markers, cholesterol efflux capacity, and other HDL functional markers. RESULTS After 4 weeks, GRAPE did not alter the serum PON1 activity or other markers of HDL function compared with placebo. Measures of HDL function were positively correlated with each other and inversely with measures of insulin resistance and inflammation. GRAPE intake led to a significant reduction in fasting plasma triglycerides compared with placebo (P = 0.032). No other significant effects of GRAPE were observed for other plasma lipids, anthropometrics, or metabolic measures. CONCLUSIONS Grape powder consumption did not impact HDL function in this cohort of adults with MetS. However, it was shown to improve fasting triglycerides, a risk factor for cardiovascular disease.
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Neutrophil-lymphocyte ratio, gamma-glutamyl transpeptidase, lipase, high-density lipoprotein as a panel of factors to predict acute pancreatitis in pregnancy.
Zhang, L, Wang, Y, Han, J, Shen, H, Zhao, M, Cai, S
Medicine. 2018;(26):e11189
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Abstract
Acute pancreatitis in pregnancy (APIP) is a rare but dangerous complication. APIP has common symptoms with acute abdomen. Assessment of an acute abdomen is more complicated during pregnancy because the gravid uterus could mask most of symptomatic signs. It has been a challenge to diagnose APIP by physical examination or diagnostic imaging. Case studies on APIP are also limited for analysis on the risk factors associated with the disease. This retrospective study evaluated a series of risk factors from a relatively substantial number of APIP cases to determine early predictors or prognosis markers for APIP.Fifty-nine APIP patients together with 179 random normal pregnant women in Shengjing Affiliated Hospital of China Medical University were included for this retrospective study. Medical parameters of blood test in biochemistry and hematology were compared between 2 groups using t test. Multivariate logistic regression analysis was performed to investigate the relationship between various factors and APIP using Statistical Applied Software (SAS student version).Compared with normal pregnant women, APIP patients have elevated values in alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen, creatinine, C-reactive protein, direct bilirubin, fibrin degradation products, gamma-glutamyl transpeptidase (GGT), glucose, lipase, pH and decreased values in albumin, fibrinogen, high-density lipoprotein (HDL), hemoglobin, low-density lipoprotein cholesterol (LDL-D), and total proteins from their blood tests. In addition, APIP patients have decreased numbers in red cells but increased numbers in white blood cells and increased ratio of neutrophil/lymphocyte (N/L). Among these factors, N/LR, GGT, lipase, and HDL are significantly associated with APIP. This study suggests that the combination of those factors serve as a panel of indicators for early-onset prognosis of APIP.GGT, lipase, HDL, and N/LR can serve as a panel of factors to predict APIP. More case studies are important to further evaluate the predicting power of this panel factors in APIP.
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CETP and LCAT Gene Polymorphisms Are Associated with High-Density Lipoprotein Subclasses and Acute Coronary Syndrome.
Vargas-Alarcon, G, Perez-Mendez, O, Herrera-Maya, G, Garcia-Sanchez, C, Martinez-Rios, MA, Peña-Duque, MA, Posadas-Sanchez, R, Posadas-Romero, C, Escobedo, G, Fragoso, JM
Lipids. 2018;(2):157-166
Abstract
We evaluated whether CETP and LCAT gene polymorphisms are statistically associated with the high-density lipoprotein (HDL) size distribution, the cholesterol level of HDL subclasses, and the acute coronary syndrome (ACS) susceptibility. Two CETP gene polymorphisms (rs4783961 and rs708272) and one LCAT polymorphism (rs2292318) were genotyped by 5' exonuclease TaqMan assays in 619 patients with ACS and 607 control individuals. For HDL analysis, a subgroup of 100 healthy individuals was recruited; the HDL subclasses were separated via ultracentrifugation and polyacrylamide gradient gel electrophoresis under native conditions. Under a dominant model, the G allele of the rs708272 polymorphism was associated with an increased risk of ACS (odds ratios [OR] = 1.45, corrected p-value [pCDom ] = 0.036). The linkage disequilibrium analysis showed that one of the eight possible combinations was associated with the risk of developing ACS (OR = 1.52, pC = 0.02), which suggests that it may contribute to coronary atherosclerosis. The rs708272 G allele carriers had a lower concentration of cholesterol associated with the HDL2a and HDL3a subclasses when compared with subjects carrying the A allele. Carriers of LCAT rs2292318 A allele showed a lower concentration of high-density lipoprotein-cholesterol (HDL-C) in comparison to the GG genotype; the cholesterol associated with the each one of the five HDL subclasses was significantly lower in rs2292318 A than in GG subjects. In summary, this study demonstrates that the rs708272 polymorphism is associated with a heightened risk of developing ACS. In addition, we report the association of the rs708272 and rs2292318 polymorphisms with HDL-C levels and HDL subclasses.
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JCL roundtable: High-density lipoprotein function and reverse cholesterol transport.
Cuchel, M, Rohatgi, A, Sacks, FM, Guyton, JR
Journal of clinical lipidology. 2018;(5):1086-1094
Abstract
High-density lipoproteins (HDL) have been known since the 1960s to be associated with protection from atherosclerotic cardiovascular disease. However, the mechanisms of this protection are unclear. The extent to which HDL per se vs other correlated metabolic factors may mitigate atherosclerosis has been seriously questioned. In fact, new epidemiologic studies have found that in some clinical settings, very high HDL cholesterol levels correlate with increased atherosclerotic risk. Most importantly, over the past 2 decades, randomized clinical trials targeting HDL have failed to reproduce the usual epidemiologic inverse relation of HDL cholesterol to atherosclerotic events. In this roundtable discussion, we bring together 3 expert investigators working in the HDL field to elucidate questions of HDL function. One area of agreement is that reverse cholesterol transport remains a primary hypothesis for an anti-atherogenic role of HDL. Bioassays that measure cholesterol efflux capacity of HDL (or of apolipoprotein [apo] B-depleted plasma) have emerged as potentially accurate surrogates for reverse cholesterol transport. ApoA-I is the major functional apoprotein of HDL, but apoE- and apoC-III-containing subpopulations of HDL may have significant roles. Anti- and pro-inflammatory functions of various HDL particles, as well as the role of oxidative and other modifications, are gaining attention.
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High-Density Lipoproteins: Effects on Vascular Function and Role in the Immune Response.
Haghikia, A, Landmesser, U
Cardiology clinics. 2018;(2):317-327
Abstract
The focus in studies of high-density lipoproteins was on their capacity to remove excess cholesterol and deliver it to the liver. Other functions and vascular effects have been described. Clinical trials and translational/genetic studies have led to a refined understanding of the role of high-density lipoprotein; it is likely not a causal cardiovascular risk factor. In healthy subjects, it limits lipid oxidation, protects endothelial cell functions/integrity, and exerts antiinflammatory/antiapoptotic effects. In patients with coronary disease or diabetes, it undergoes modifications/remodeling, resulting in dysfunctional high-density lipoprotein. We summarize recent findings about the regulation of its function and discuss the clinical implications.