Low- and high-density lipoprotein cholesterol goal attainment in dyslipidemic women: The Lipid Treatment Assessment Project (L-TAP) 2

Background Differences between women and men have been documented for both diagnostic testing and treatment in cardiology. This analysis evaluates whether low-density lipoprotein cholesterol (LDL-C) success rates according to current guidelines and high-density lipoprotein cholesterol (HDL-C) levels differ by gender in the L-TAP 2 population. Methods Patients aged >= 20 years with dyslipidemia on stable lipid-lowering therapy were assessed in 9 countries between September 2006 and April 2007. Low-density lipoprotein cholesterol goal attainment by cardiovascular risk level and region and determinants of low HDL-C were compared between genders. Results Of 9,955 patients (45.3% women) evaluated, women had a significantly lower overall LDL-C success rate than men (71.5% vs 73.7%, P = .014), due entirely to the difference in the high-risk/coronary heart disease (CHD) group (LDL-C goal <100 mg/dL, 62.6% vs 70.6%, P < .0001) Among CHD patients with >= 2 additional risk factors, only 26.7% of women and 31.5% of men (P = .021) attained the optional LDL-C goal of <70 mg/dL. High-density lipoprotein cholesterol was <50 mg/dL in 32.2% of women and <40 mg/dL in 26.8% of men (P < .0001), including 38.2% of women and 29.8% of men in the high risk/CHD group (P < .0001). Predictors of low HDL-C in women included diabetes, smoking, waist circumference, and hypertension. Conclusions Cholesterol treatment has, improved substantially since the original L-TAP a decade ago, when only 39% of women attained their LDL-C goal. However, high-risk women are undertreated compared to men, and a substantial opportunity remains to reduce their cardiovascular risk. (Am Heart J 2009; 158:860-6.)

Brazil nut ingestion increased plasma selenium but had minimal effects on lipids, apolipoproteins, and high-density lipoprotein function in human subjects

The Brazil nut (Bertholletia excelsa) of the Amazon region is consumed worldwide. It is rich in both monounsaturated fatty acids and polyunsaturated fatty acids and is known for its high selenium content. This study tested the hypothesis whether the consumption of this nut could affect the plasma lipids and apolipoproteins and some functional properties of the antiatherogenic high-density lipoprotein (HDL). Fifteen normolipidemic subjects aged 27.3 +/- 3.9 years and with body mass index of 23.8 +/- 2.8 kg/m(2) consumed 45 g of Brazil nuts per day during a 15-day period. On days 0 and 15, blood was collected for biochemical analysis, determination of HDL particle size, paraoxonase 1 activity, and lipid transfer from a lipoprotein-like nanoparticle to the HDL fraction. Brazil nut ingestion did not alter HDL, low-density lipoprotein cholesterol, triacylglycerols, apolipoprotein A-1, or apolipoprotein B concentrations. HDL particle diameter and the activity of antioxidative paraoxonase 1, mostly found in the HDL fraction, Were also unaffected. Supplementation increased the reception of cholesteryl esters (P <.05) by the HDL yet did not alter the reception of phospholipids, free cholesterol, or triacylglycerols. As expected, plasma selenium was significantly increased. However, the consumption of Brazil nuts for short duration by normolipidemic subjects in comparable amounts to those tested for other nuts did not alter serum lipid profile. The only alteration in HDL function was the increase in cholesteryl ester transfer. This latter finding may be beneficial because it would improve the nonatherogenic reverse cholesterol transport pathway. (c) 2008 Elsevier Inc. All rights reserved.

Effect of Exercise Training on Plasma Levels and Functional Properties of High-Density Lipoprotein Cholesterol in the Metabolic Syndrome

Intense lifestyle modifications can change the high-density lipoprotein (HDL) cholesterol concentration. The aim of the present study was to analyze the early effects of short-term exercise training, without any specific diet, on the HDL cholesterol plasma levels and HDL functional characteristics in patients with the metabolic syndrome (MS). We studied 30 sedentary subjects, 20 with and 10 without the MS. The patients with the MS underwent moderate intensity exercise training for 3 months on bicycle ergometers. Blood was sampled before and after training for biochemical analysis, paraoxonase-1 activity, and HDL subfraction composition and antioxidative capacity. Lipid transfer to HDL was assayed in vitro using a labeled nanoemulsion as the lipid donor. At baseline, the MS group had greater triglyceride levels and a lower HDL cholesterol concentration and lower paraoxonase-1 activity than did the controls. Training decreased the plasma triglycerides but did not change the low-density lipoprotein or HDL cholesterol levels. Nonetheless, exercise training increased the HDL subfractions` antioxidative capacity and paraoxonase-1 activity. After training, the MS group had compositional changes in the smallest HDL subfractions associated with increased free cholesterol and cholesterol ester transfers to HDL, reaching normal values. In conclusion, the present investigation has added relevant information about the dissociation between the quantitative and qualitative aspects of HDL after short-term exercise training without any specific diet in those with the MS, highlighting the importance of evaluating the functional aspects of the lipoproteins, in addition to their plasma levels. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:1168-1172)

Aerobic exercise training improves the role of high-density lipoprotein antioxidant and reduces plasma lipid peroxidation in type 2 diabetes mellitus

In this study, we analyzed the effect of aerobic exercise training (AET) and of a single bout of exercise on plasma oxidative stress and on antioxidant defenses in type 2 diabetes mellitus (DM) and in healthy control subjects (C). DM and C did not differ regarding triglycerides, high-density lipoprotein cholesterol (HDL-c), insulin, and HOMA index at baseline and after AET. To measure the lag time for low-density lipoprotein (LDL) oxidation (LAG) and the maximal rate of conjugated diene formation (MCD), participants` plasma HDL(2) and HDL(3) were incubated with LDL from pooled healthy donors` plasma. In the presence of HDL(3), both LAG and MCD were similar in C and DM, but only in DM did AET improve LAG and reduce MCD. In the presence of HDL(2), the lower baseline LAG in DM equaled C after AET. MCD was unchanged in DM after AET, but was lower than C only after AET. Furthermore, after AET plasma thiobarbituric acid-reactive substances were reduced only in DM subjects. Despite not modifying the total plasma antioxidant status and serum paraoxonase-1 activity in both groups, AET lowered the plasma lipid peroxides, corrected the HDL(2), and improved the HDL(3) antioxidant efficiency in DM independent of the changes in blood glucose, insulin, and plasma HDL concentration and composition.

Natural, but not lyophilized, low density lypoproteins were an acceptable alternative to egg yolk for cryopreservation of ram semen

The objective was to evaluate the suitability of using natural or lyophilized low density lipoproteins (LDL), in lieu of whole egg yolk, in extenders for cryopreserving ram semen. Once extragonadal sperm reserves were depleted in 10 fertile Santa Ines cross rams, two ejaculates per ram were collected for cryopreservation. Nine extenders were used: Tris-16% egg yolk extender with 5% glycerol as a control (T1), and substitution of whole egg yolk with 8, 12, 16 or 20% natural LDL (T2-T5, respectively), or with 8, 12, 16, or 20% lyophilized LDL (T6-T9). Semen was diluted to 100 X 10(6) sperm/mL, packaged into 0.25 mL straws, cooled, held at 5 C for 3 h, and then frozen in liquid nitrogen vapor. Immediately after thawing (37 degrees C for 30 s), sperm total and progressive motility, and kinetic parameters were analyzed with computer assisted semen analysis (CASA). Percentage of sperm with plasma membrane functional integrity was assessed by the hypoosmotic swelling test (HOST), sperm membrane physical integrity with propidium iodide (PI), and acrosome integrity with FITC-PSA using an epifluorescent microscope. For all sperm end points, there was no difference between the control and natural LDL treatments (P > 0.05): total motility (T1: 20.9 +/- 11.9 and average of T2-T5: 25.9 +/- 13.6%; mean SD), progressive motility (T1: 6.6 +/- 4.2 and average of T2-T5: 11.7 +/- 7.5%), HOST(+) (T1: 23.7 +/- 6.9 and average of T2-T5: 23.2 +/- 8.7%) and PI(-)/PSA(-) (T1: 13.8 +/- 7.8 and average of T2-T5: 18.1 +/- 7.8%). However, lyophilization was apparently unable to preserve the protective function of LDL; every sperm end point was significantly worse than in the control and natural LDL groups. We concluded that natural LDL was appropriate for cryopreserving ram semen, as it yielded results similar to those obtained with whole egg yolk. (C) 2011 Elsevier Inc. All rights reserved.

High-density lipoprotein prevents SAA-induced production of TNF-α in THP-1 monocytic cells and peripheral blood mononuclear cells

In this study, we evaluated whether human serum and lipoproteins, especially high-density lipoprotein (HDL), affected serum amyloid A (SAA)-induced cytokine release. We verified the effects of SAA on THP-1 cells in serum-free medium compared to medium containing human serum or lipoprotein-deficient serum. SAA-induced tumour necrosis factor-alpha (TNF-α) production was higher in the medium containing lipoprotein-deficient serum than in the medium containing normal human serum. The addition of HDL inhibited the SAA-induced TNF-α release in a dose-dependent manner. This inhibitory effect was specific for HDL and was not affected by low-density lipoprotein or very low-density lipoprotein. In human peripheral blood mononuclear cells, the inhibitory effect of HDL on TNF-α production induced by SAA was less pronounced. However, this effect was significant when HDL was added to lipoprotein-deficient medium. In addition, a similar inhibitory effect was observed for interleukin-1 beta release. These findings confirm the important role of HDL and support our previous hypothesis that HDL inhibits the effects of SAA during SAA transport in the bloodstream. Moreover, the HDL-induced reduction in the proinflammatory activity of SAA emphasizes the involvement of SAA in diseases, such as atherosclerosis, that are characterized by low levels of HDL.

Effects of chlorogenic acid and bovine serum albumin on the oxidative stability of low density lipoproteins in vitro

The ability of chlorogenic acid to inhibit oxidation of human low-density lipoprotein (LDL) was studied by in vitro copper-induced LDL oxidation. The effect of chlorogenic acid on the lag time before LDL oxidation increased in a dose dependent manner by up to 176% of the control value when added at concentrations of 0.25 -1.0 μM. Dose dependent increases in lag time of LDL oxidation were also observed, but at much higher concentrations, when chlorogenic acid was incubated with LDL (up to 29.7% increase in lag phase for 10 μM chlorogenic acid) or plasma (up to 16.6% increase in lag phase for 200 μM chlorogenic acid) prior to isolation of LDL, and this indicated that chlorogenic acid was able to bind, at least weakly, to LDL. Bovine serum albumin (BSA) increased the oxidative stability of LDL in the presence of chlorogenic acid. Fluorescence spectroscopy showed that chlorogenic acid binds to BSA with a binding constant of 3.88 x 104 M-1. BSA increased the antioxidant effect of chlorogenic acid, and this was attributed to copper ions binding to BSA, thereby reducing the amount of copper available for inducing lipid peroxidation.

High density lipoprotein: guardian of the vascular system?

The role of low-density lipoprotein in the development of coronary heart disease (CHD) is well recognised. There is also growing evidence that high-density lipoprotein cholesterol (HDL-C) is a powerful inverse predictor for premature CHD and that maintaining a high HDL-C level may guard against atherosclerosis. Patients with low HDL-C levels often also have central obesity, insulin resistance and other features of the metabolic syndrome. This syndrome is both increasingly common and strongly implicated in the growing worldwide epidemic of type 2 diabetes. HDL-C may be increased by lifestyle changes, e.g. weight loss, physical activity and smoking cessation. Pharmacological agents such as fibrates, niacin and statins have also been shown significantly to elevate HDL-C. Although current guidelines are beginning to recognise the protective role of HDL-C level in preventing coronary events, HDL-C should be adopted soon as a target for intervention in its own right.

Investigation of the Europium Emission Spectra of the Europium-Oxytetracycline Complex in the Presence of Human Low-Density Lipoproteins

Low-Density Lipoprotein (LDL), often known as ""bad cholesterol"" is one of the responsible to increase the risk of coronary arterial diseases. For this reason, the cholesterol present in the LDL particle has become one of the main parameters to be quantified in routine clinical diagnosis. A number of tools are available to assess LDL particles and estimate the cholesterol concentration in the blood. The most common methods to quantify the LDL in the plasma are the density gradient ultracentrifugation and nuclear magnetic resonance (NMR). However, these techniques require special equipments and can take a long time to provide the results. In this paper, we report on the increase of the Europium emission in Europium-oxytetracycline complex aqueous solutions in the presence of LDL. This increase is proportional to the LDL concentration in the solution. This phenomenum can be used to develop a method to quantify the number of LDL particles in a sample. A comparison between the performances of the oxytetracycline and the tetracycline in the complexes is also made.

Centripetal cholesterol flux from extrahepatic organs to the liver is independent of the concentration of high density lipoprotein-cholesterol in plasma.

High density lipoproteins (HDLs) play a role in two processes that include the amelioration of atheroma formation and the centripetal flow of cholesterol from the extrahepatic organs to the liver. This study tests the hypothesis that the flow of sterol from the peripheral organs to the liver is dependent upon circulating HDL concentrations. Transgenic C57BL/6 mice were used that expressed variable amounts of simian cholesteryl ester-transfer protein (CETP). The rate of centripetal cholesterol flux was quantitated as the sum of the rates of cholesterol synthesis and low density lipoprotein-cholesterol uptake in the extrahepatic tissues. Steady-state concentrations of cholesterol carried in HDL (HDL-C) varied from 59 to 15 mg/dl and those of apolipoprotein AI from 138 to 65 mg/dl between the control mice (CETPc) and those maximally expressing the transfer protein (CETP+). There was no difference in the size of the extrahepatic cholesterol pools in the CETPc and CETP+ animals. Similarly, the rates of cholesterol synthesis (83 and 80 mg/day per kg, respectively) and cholesterol carried in low density lipoprotein uptake (4 and 3 mg/day per kg, respectively) were virtually identical in the two groups. Thus, under circumstances where the steady-state concentration of HDL-C varied 4-fold, the centripetal flux of cholesterol from the peripheral organs to the liver was essentially constant at approximately 87 mg/day per kg. These studies demonstrate that neither the concentration of HDL-C or apolipoprotein AI nor the level of CETP activity dictates the magnitude of centripetal cholesterol flux from the extrahepatic organs to the liver, at least in the mouse.

No relationship between low-density lipoproteins and endothelial function in hemodialysis patients

Background: Relationships between low-density lipoprotein cholesterol and endothelial function in hemodialysis patients have yet to be investigated. Furthermore, current reporting of endothelial function data using flow-mediated dilatation has recognised limitations. The aims of the study were to determine the relationship between low-density lipoproteins and endothelial function in hemodialysis patients and to investigate the validity of determining the area under the curve for data collected during the flow-mediated dilatation technique. Methods: Brachial artery responses to reactive hyperemia (endothelial-dependent) and glyceryl trinitrate (endothelial-independent) were assessed in 19 hemodialysis patients using high-resolution ultrasound. Lipid profiles and other factors known to effect brachial artery reactivity were also measured prior to the flow-mediated dilatation technique. Results: There were no significant relationships between serum low-density lipoproteins and endothelial-dependent or -independent vasodilation using absolute change (mm), relative change (%), time to peak change (s) or area under the curve (mm(.)s). In hemodialysis patients with atherosclerosis, area under the curve analysis showed a significantly (p < 0.05) decreased endothelial-dependent response (mean +/- S.D.: 19.2 +/- 17.4) compared to non-atherosclerotic patients (42.3 +/- 28.6). However, when analysing these data using absolute change, relative change or time to peak dilatation, there were no significant differences between the two groups. Conclusions: In summary, there was no relationship between low-density lipoproteins and endothelial function in hemodialysis patients. In addition, area under the curve analysis of flow-mediated vasodilatation data may be a useful method of determining the temporal vascular response during the procedure. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

Cu and Fe metallic ions-mediated oxidation of low-density lipoproteins studied by NMR, TEM and Z-scan technique

In this work we report on a study of the morphological changes of LDL induced in vitro by metallic ions (Cu(2+) and Fe(3+)). These modifications were characterized by transmission electron microscopy, nuclear magnetic resonance and the Z-scan technique. The degree of oxidative modification of LDL was determined by the TBARS and lipid hydroperoxides assays. It is shown that distinct pathways for modifying lipoproteins lead to different morphological transformations of the particles characterized by changes in size and/or shape of the resulting particles, and by the tendency to induce aggregation of the particles. There were no evidence of melting of particles promoted by oxidative processes with Cu and Fe. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Characterization of high density lipoprotein particles in familial apolipoprotein A-I deficiency

Our aim was to characterize HDL subspecies and fat-soluble vitamin levels in a kindred with familial apolipoprotein A-I (apoA-I) deficiency. Sequencing of the APOA1 gene revealed a nonsense mutation at codon 22, Q[22] X, with two documented homozygotes, eight heterozygotes, and two normal subjects in the kindred. Homozygotes presented markedly decreased HDL cholesterol levels, undetectable plasma apoA-1, tuboeruptive and planar xanthomas, mild corneal arcus and opacification, and severe premature coronary artery disease. In both homozygotes, analysis of HDL particles by two-dimensional gel electrophoresis revealed undetectable apoA-I, decreased amounts of small a-3 migrating apoA-II particles, and only modestly decreased normal amounts of slow a migrating apoA-IV- and apoE-containing HDL, while in the eight heterozygotes, there was loss of large alpha-1 HDL particles. There were no significant decreases in plasma fat-soluble vitamin levels noted in either homozygotes or heterozygotes compared with normal control subjects. Our data indicate that isolated apoA-I deficiency results in marked HDL deficiency with very low apoA-II alpha-3 HDL particles, modest reductions in the separate and distinct plasma apoA-IV and apoE HDL particles, tuboeruptive xanthomas, premature coronary atherosclerosis, and no evidence of fat malabsorption.

Alterations in lipid transfer to High-Density Lipoprotein (HDL) and activity of paraoxonase-1 in HIV+ patients

HIV+ patients often develop alterations of the plasma lipids that may implicate in development of premature coronary artery disease. High-density lipoprotein (HDL) has an important role in preventing atherogenesis and the aim of this study was to investigate aspects of HDL function in HIV+ patients. HIV+ patients (n = 48) and healthy control subjects (n = 45) of both sexes with similar age were studied. Twenty-five were not being treated with antiretroviral agents, 13 were under reverse transcriptase inhibitor nucleosidic and non-nucleosidic (NRTI+NNRTI) and 10 were under NRTI + protease inhibitors (NRTI+PI) treatment. Paraoxonase 1 (PON1) activity and the transfer of free and esterified cholesterol, tryglicerides and phospholipids from a lipidic nanoemulsion to HDL were analyzed. In comparison with healthy controls, HIV+ patients presented low PON-1 activity and diminished transfer of free cholesterol and tryglicerides. In contrast, phospholipid transfer was increased in those patients, whereas the transfer of cholesteryl esters was unchanged. NRTI+NNRTI increases the transfer of cholesteryl esters and triglycerides but in NRTI+PI there was no difference in respect to non-treated HIV+ patients. HDL from HIV+ patients has smaller antioxidant properties, as shown by lower PON-1 activity, and the transfer of lipids to this lipoprotein fraction is also altered, suggesting that HDL function is defective in those patients.

Links between body mass index, total body fat, cholesterol, high-density lipoprotein, and insulin sensitivity in patients with obesity related to depression, anger, and anxiety

OBJECTIVE: Define links between psychosocial parameters and metabolic variables in obese females before and after a low-calorie diet. METHOD: Nine female obese patients (age 36.1 +/- 7.1 years, body mass index [BMI] > 30 kg/m2) were investigated before and after a 6-week low-calorie diet accompanied by behavior therapy. Blood lipids, insulin sensitivity (Bergman protocol), fat distribution (by dual-energy X-ray absorptiometry [DEXA]), as well as psychological parameters such as depression, anger, anxiety, symptom load, and well-being, were assessed before and after the dieting period. RESULTS: The females lost 9.6 +/- 2.8 kg (p < .0001) of body weight, their BMI was reduced by 3.5 +/- 0.3 kg/m2 (p < .0001), and insulin sensitivity increased from 3.0 +/- 1.8 to 4.3 +/- 1.5 mg/kg (p = .05). Their abdominal fat content decreased from 22.3 +/- 5.5 to 18.9 +/- 4.5 kg (p < .0001). In parallel, psychological parameters such as irritability (p < .05) and cognitive control (p < .0001) increased, whereas feelings of hunger (p < .05), externality (p < .05), interpersonal sensitivity (p < .01), paranoid ideation (p < .05), psychoticism (p < .01), and global severity index (p < .01) decreased. Prospectively, differences in body fat (percent) were correlated to nervousness (p < .05). Waist-to-hip ratio (WHR) differences were significantly correlated to sociability (p < .05) and inversely to emotional instability (p < .05), whereas emotional instability was inversely correlated to differences in insulin sensitivity (p < .01). DISCUSSION: Weight reduction may lead to better somatic risk factor control. Women with more nervousness and better sociability at the beginning of a diet period may lose more weight than others.