Particle Cholesterol Research Articles

Discordance of Low-Density Lipoprotein (LDL) Cholesterol With Alternative LDL-Related Measures and Future Coronary Events

Low-density lipoprotein cholesterol (LDL-C) is the traditional measure of risk attributable to LDL. Non-high-density lipoprotein cholesterol (NHDL-C), apolipoprotein B (apoB), and LDL particle number (LDL-P) are alternative measures of LDL-related risk. However, the clinical utility of these measures may only become apparent among individuals for whom levels are inconsistent (discordant) with LDL-C. LDL-C was measured directly, NHDL-C was calculated, apoB was measured with immunoassay, and LDL-P was measured with nuclear magnetic resonance spectroscopy among 27 533 healthy women (median follow-up 17.2 years; 1070 incident coronary events). Participants were grouped by median LDL-C (121 mg/dL) and each of NHDL-C, apoB, and LDL-P. Discordance was defined as LDL-C greater than or equal to the median and the alternative measure less than the median, or vice versa. Despite high LDL-C correlations with NHDL-C, apoB, and LDL-P (r=0.910, 0.785, and 0.692; all P<0.0001), prevalence of LDL-C discordance as defined by median cut points was 11.6%, 18.9%, and 24.3% for NHDL-C, apoB, and LDL-P, respectively. Among women with LDL-C less than the median, coronary risk was underestimated for women with discordant (greater than or equal to the median) NHDL-C (age-adjusted hazard ratio, 2.92; 95% confidence interval, 2.33-3.67), apoB (2.48, 2.01-3.07), or LDL-P (2.32, 1.88-2.85) compared with women with concordant levels. Conversely, among women with LDL-C greater than or equal to the median, risk was overestimated for women with discordant (less than the median) NHDL-C (0.40, 0.29-0.57), apoB (0.34, 0.26-0.46), or LDL-P (0.42, 0.33-0.53). After multivariable adjustment for potentially mediating factors, including HDL cholesterol and triglycerides, coronary risk remained underestimated or overestimated by ≈20% to 50% for women with discordant levels. For women with discordant LDL-related measures, coronary risk may be underestimated or overestimated when LDL-C alone is used. http://www.clinicaltrials.gov. Unique identifier: NCT00000479.

Are We Moving Towards Concordance on the Principle That Lipid Discordance Matters?

In this issue of Circulation , Samia Mora, Julie Buring, and Paul Ridker publish an elegant and clinically-relevant analysis examining discordance of low-density lipoprotein cholesterol (LDL-C) with related laboratory measures and the risk implications.1 The article should attract attention from a diverse set of contingents, such as those based in preventive cardiology, clinical lipidology, and laboratory medicine, to name just a few. The study addresses the underappreciated concept of discordance between different lipid and lipoprotein measures in individual patients. The investigators address the prevalence of such discordance and its association with long-term incidence of coronary events. Article see p 553 Dr Mora and colleagues analyze participants in the prospective Women’s Health Study. With necessary lipid measurements captured on nearly all of the women, the analysis is large, involving 27 533 women aged ≥45 years. This is a primary prevention population—these women were all free of self-reported cardiovascular disease and cancer at baseline. After baseline risk factor measurements, the women underwent follow-up over a median of 17.2 years for incident coronary events, including nonfatal myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting, and coronary death. An Endpoints Committee adjudicated events, which occurred in 1070 women. A unique aspect of this analysis is the simultaneous availability of directly measured LDL-C, Friedewald-estimated LDL-C, nonhigh-density lipoprotein cholesterol (non– HDL-C), apolipoprotein B (apoB), and low-density lipoprotein particle concentration (LDL-P). Essentially, these are related, but distinct, measures of the atherogenic lipid burden. Given that LDL-C is commonly the first parameter considered in clinical practice, in line with international guidelines,2–4 having this study center its primary analyses on LDL-C makes the results particularly relevant to daily practice. Another strength of the study is that the laboratory performing the measurements participates in the Centers for Disease Control and Prevention’s Lipid Standardization Program. Ultimately, …

Luffa cylindrica and phytosterols bioconversion: from shake flask to jar bioreactor

Bioconversion of lipophilic compounds poorly soluble in water, such as sterols, required the use of chemicals and solubilizing agents. On the other hand, it was shown that immobilization of Mycobacterium species on the dried fruit of Luffa cylindrica (DFLC) allows a close interaction between immobilized cells and cholesterol particles and increases by then the product's yield. In this work, the use of DFLC in a 5-l jar bioreactor with phytosterols mixture (1g/l) as substrate was assessed without addition of any chemicals or solubilizing agents. DFLC increased by a factor of four the volumetric productivity of androstenones (0.08g/lday). Products were accumulated in the aqueous medium while substrates remained on the fibers of DFLC. This observation lets envisage a green semi-continuous process of androstenone production. DFLC has no influence on cell growth, and is moreover natural, inexpensive, non-toxic, and mechanically strong.

Non-invasive measurement of cholesterol in human blood by impedance technique: an investigation by 2D finite element field modelling

This paper concerns detection of solid particles suspended in conductive media by impedance technique. The technique is based on changes in impedance measured between two electrodes placed across a given volume of conducting medium. It presents a methodology for modelling and investigation of the feasibility of such a technique for particle detection by 2D finite element (FE) field modelling. This is based on modelling and computation of electric field distribution between the above electrodes. It establishes the modelling approach, the complexity involved and justifies the need for modelling in 3D to incorporate some of the effects that cannot be taken into account in 2D models. It reports on the modelling investigation for a specific case of detecting, by impedance technique cholesterol particles suspended in human blood and points to a possible instrument for non-invasive measurement of blood cholesterol level.

Cholesterol reduction by Lactococcus lactis KF147

Lactococcus lactis from yoghurt sample was confirmed based on alignment of 16S rRNA gene sequence in gene bank. The degree of acid and bile tolerance of strain L. lactissubsp. lactis KF147 was evaluated. The L. lactis KF147 was able to maintain viability for 2 h at pH 2 and growth in a medium with 0.4% (w/v) of bile acids. The maximum cholesterol reduction was 66.8% from the mMRS culture medium supplemented with 100 mg/L cholesterol. The tested strain was capable of binding cholesterol and removing 13% cholesterol from the medium. The growth of bacteria was affected by the presence of cholesterol in the medium. The growing bacterial cells had cholesterol reducing activity more than resting and dead cells. Transmission electron microscopy and IR analysis detected the cholesterol binding activity between L. lactis KF147 cells and the cholesterol. The fatty acid composition of the cells of L. lactis KF147 was altered by reducing cholesterol from the MRS medium that indicated incorporation of the cholesterol particles into cell membrane. According to these results, L. lactis KF147 revealed the probiotic potential in hypocholesterolemic effect on rats. Key words: Cholesterol reduction, cholesterol binding, probiotic, hypocholesterolemic,Lactococcus lactis KF147.

A new enzyme-linked immunosorbent assay system for human hepatic triglyceride lipase

BackgroundThe objective of this study was to establish a new sandwich based enzyme linked immunosorbent assay (ELISA) for measuring the protein mass of human hepatic triacylglyceride lipase (HTGL). MethodTwo mouse monoclonal antibodies raised against human HTGL were used for the sandwich ELISA. The post-heparin plasma (PHP) samples obtained at a heparin dose of 50unit/kg from 124 normolipidemic subjects were used for this ELISA. ResultsThe dynamic assay range of the developed ELISA for the HTGL was from 0.47 to 30ng/ml. The CV was <7% in both intra- and inter-assays, and it did not cross-react with lipoprotein lipase or endothelial lipase (EL). The HTGL concentration in PHP showed a strong correlation with HTGL activity [n=121, r=0.778, p<0.001]. There was a weak relation of HTGL concentration against high-density lipoprotein cholesterol (HDL-C) [n=123, r=−0.229, p=0.011] but no relations against total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), small dense LDL, remnant like particles cholesterol (RLP-C) and RLP-TG were confirmed. Interestingly, a weak but positive correlation between HTGL concentration and EL concentration was shown [n=122, p=0.013, r=0.224]. ConclusionThese results indicate that this new sandwich ELISA for measuring HTGL concentration in PHP can be applied in a daily clinical practice.

Efficacy and Safety of a Novel Dual Modulator of Adenosine Triphosphate-Citrate Lyase and Adenosine Monophosphate-Activated Protein Kinase in Patients With Hypercholesterolemia: Results of a Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial

The aim of this study was to assess the lipid-altering efficacy and safety of ETC-1002 in subjects with hypercholesterolemia. ETC-1002 is a small molecule that modulates pathways of cholesterol, fatty acid, and carbohydrate metabolism and may have therapeutic benefits in treating hypercholesterolemia and other cardiometabolic risk factors. This multicenter, randomized, double-blind, placebo-controlled, parallel-group trial evaluated patients (n = 177) with elevated low-density lipoprotein cholesterol (LDL-C) (130 to 220 mg/dl), who were stratified by baseline triglycerides (not elevated [<150 mg/dl] or elevated [150-<400 mg/dl]) and randomized to receive 40, 80, or 120 mg of ETC-1002 or placebo once daily for 12 weeks. Outcomes included changes in LDL-C (primary endpoint), other lipids, and cardiometabolic risk factors; and safety. ETC-1002 40, 80, and 120 mg lowered least-squares mean ± SE LDL-C levels by 17.9 ± 2.2%, 25.0 ± 2.1%, and 26.6 ± 2.2%, respectively, versus a reduction of 2.1 ± 2.2% with placebo (all, p < 0.0001); LDL-C lowering was similar between the subgroups with nonelevated and elevated triglycerides. ETC-1002 also lowered non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, and LDL particle number (all, p < 0.0001) in a dose-dependent manner; HDL-C and triglyceride levels were relatively unchanged. Post-hoc analyses suggest that ETC-1002 may have favorable effects on other cardiometabolic risk factors. The ETC-1002 and placebo groups did not demonstrate clinically meaningful differences in adverse events or other safety assessments. ETC-1002 significantly lowered LDL-C levels up to 27% across a broad range of baseline triglycerides and was generally safe and well tolerated. ETC-1002 has a novel mechanism of action and may be useful for reducing LDL-C. (A Study to Assess the Efficacy and Safety of ETC-1002 in Subjects With Elevated Blood Cholesterol and Either Normal or Elevated Triglycerides; NCT01262638).

Higher levels of small dense low‐density lipoprotein (LDL) are associated with cardiac autonomic neuropathy in patients with Type 2 diabetes

To investigate the relationship between small dense LDL cholesterol and cardiac autonomic neuropathy among patients with Type 2 diabetes. A total of 175 patients who had not taken lipid-lowering agents previously were enrolled consecutively in this study. Small dense LDL cholesterol level was measured using polyacrylamide tube gel electrophoresis, which fractionates LDL cholesterol into seven components according to particle size and charge. We analysed the mean LDL cholesterol particle size and the proportion of small dense LDL cholesterol. The mean (± sd) patient age was 56 (± 14) years, the mean (± sd) duration of diabetes was 10.3 (± 8.3) years, the mean (± sd) proportion of small dense LDL cholesterol was 21.3 (± 17.6)% and the mean (± sd) LDL cholesterol size was 26.33 (± 0.8) nm. Men with cardiac autonomic neuropathy had a longer duration of diabetes compared with those without cardiac autonomic neuropathy. Women with cardiac autonomic neuropathy had a larger waist circumference, higher plasma triglyceride levels, smaller mean (± sd) LDL cholesterol size [26.8 (± 4.3) nm vs 26.4 (± 6.9) nm; P < 0.01] and larger mean (± sd) proportion of small dense LDL cholesterol [10.1 (± 9.9)% vs 19.1 (± 16.8)%; P < 0.01] compared with those without cardiac autonomic neuropathy. After adjusting for other confounding risk factors, the triglyceride/ HDL cholesterol ratio (odds ratio = 1.698, 95% CI: 1.07-2.69; P = 0.025) and mean LDL cholesterol size (odds ratio = 0.873, 95% CI: 0.77-0.99; P = 0.038) remained as independent risk factors for cardiac autonomic neuropathy in women. A more atherogenic lipid profile such as the triglyceride: HDL cholesterol ratio and a smaller mean LDL cholesterol particle size were related to the prevalence of cardiac autonomic neuropathy in women with Type 2 diabetes.

Role of enterocytes in dyslipidemia of insulin-resistant states

The increase in cardiovascular morbidity and mortality associated to insulin resistance (IR) states (obesity, metabolic syndrome, type 2 diabetes) represents a major public health problem. In IR, dyslipidemia typically include hypertriglyceridemia, low high density lipoprotein cholesterol, increased small and dense low density lipoprotein particles, and post-prandial hyperlipidemia, which play a direct or indirect role in the mechanisms of atherosclerosis. Dyslipidemia is mainly due to accumulation of circulating triglyceride-rich lipoproteins from the liver and bowel. The bowel has traditionally been seen as a passive organ, but current evidence confirms that it is an active organ subject to regulation by free fatty acids, insulin, incretins, and inflammation. Two new concepts have emerged: intestinal IR and overproduction of chylomicrons in hyperinsulinemic/IR states. A better understanding of intestinal IR may make the enterocyte a therapeutic target.

Modeling of precipitation of ultra-fine particles by pressure reduction over CO2-expanded liquids

A mathematical model has been developed to describe the process of precipitation of ultrafine particles by pressure reduction over gas (CO2)-expanded liquids. A rapid pressure reduction over a CO2-expanded organic solution, from 30–70 to 1bar at 303K decreases the solution temperature by 30–80K in a very short span of time (0.5–1.5min), which generates a rapid, high, and uniform supersaturation of the dissolved solute in the solution and facilitates precipitation of ultrafine particles. The model developed in this work estimates the supersaturation attained, nucleation and growth rates obtained during the pressure reduction over CO2-expanded organic solutions, and the particle size distribution of the precipitated particles. Cholesterol has been chosen as a model solute to be precipitated, and acetone has been chosen as a solvent. A new method has been developed for prediction of equilibrium solubility of solute which is affected by a decrease in CO2 mole fraction as well as a simultaneous decrease in solution temperature during pressure reduction. This method combines the semi-empirical approach of using the partial molar volume fraction of solvent in a CO2-solvent binary mixture and solid–liquid equilibrium data for a solute–solvent system. Size distributions of the precipitated particles have been calculated assuming primary nucleation (homogeneous as well as heterogeneous nucleation) and diffusion-limited growth kinetics. The predicted mean average particle sizes are then compared with the size of cholesterol particles precipitated by pressure reduction of a CO2-expanded acetone solution of cholesterol. The particle sizes predicted assuming heterogeneous nucleation are found to be closer to the experimentally observed particle sizes, indicating that the heterogeneous nucleation could be the main mechanism of nucleation, which could occur at the gas–liquid interface of the CO2 bubbling out of CO2-expanded solution during pressure reduction.

Low-Density Lipoprotein Cholesterol versus Particle Number in Middle School Children

To characterize lipids and lipoproteins in a diverse school-based cohort and identify features associated with discordance between low-density lipoprotein cholesterol (LDL-C) and LDL particle (LDL-P). Sixth-grade children enrolled in the HEALTHY trial (n = 2384; mean age 11.3 ± 0.6 years; 54.2% female) were evaluated for standard lipids, lipoprotein particles measured by nuclear magnetic resonance, and homeostatic model of insulin resistance. Characteristics of subgroups with values of LDL-C and LDL-P discordant by >20 percentile units, an amount reasoned to be clinically significant, were compared. Four-hundred twenty-eight (18%) of children were in the LDL-P < LDL-C subgroup and 375 (16%) in the LDL-P > LDL-C subgroup. Those with LDL-P > LDL-C had significantly greater body mass index, waist circumference, homeostatic model of insulin resistance, triglycerides, systolic and diastolic blood pressure, and reflected a greater Hispanic ethnic composition but fewer of black race than both the concordant (LDL-P ≅ LDL-C) and opposite discordant (LDL-P < LDL-C) subgroups. There is as much lipoprotein cholesterol compositional heterogeneity in sixth graders as has been described in adults and a discordant atherogenic phenotype of LDL-P > LDL-C, common in obesity, is often missed when only LDL-C is considered. Conversely, many children with moderate-risk cholesterol measures (75th to 99th percentile) have a lower LDL-P burden.

Non-HDL cholesterol, ApoB and LDL particle concentration in coronary heart disease risk prediction and treatment

LDL cholesterol has been identified as the primary therapeutic target for lipid management to reduce the future risk of coronary events. Despite the use of LDL cholesterol-targeted therapy with statins and other lipid-altering agents, many patients still suffer coronary events. Residual risk for such events has been attributed, at least in part, to persistently elevated atherogenic particle concentration. When patients are found to have elevated non-HDL cholesterol, ApoB-100 or LDL particle concentrations, they are presumed to be at increased risk and are often prescribed more aggressive lipid-altering therapy. This review examines the evidence that these biomarkers provide additional clinically useful information both in coronary risk prediction and in lipid management decision-making.

Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200–500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study

BackgroundIcosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. ANCHOR was a 12-week, phase 3 study that evaluated the efficacy and safety of IPE in patients (N = 702) with residual high fasting TG levels (≥200 and <500 mg/dL) despite having optimized low-density lipoprotein cholesterol (LDL-C) levels (≥40 and <100 mg/dL) on statin therapy. Among patients randomized to IPE (4 g/day or 2 g/day) or placebo, 514 (73%) had diabetes mellitus.MethodsA post hoc subgroup analysis of the ANCHOR study was conducted to assess the effects of IPE on median placebo-adjusted percent change from baseline in efficacy end point parameters in 3 subgroups: total (all subjects with diabetes—overall median baseline glycosylated hemoglobin A1c [A1c] = 6.8%), better-controlled diabetes (below median baseline A1c), and less-controlled diabetes (above median baseline A1c).ResultsBaseline efficacy parameters were similar among all groups except high-sensitivity C-reactive protein (hsCRP), which was higher in the total and less-controlled diabetes groups. Compared with placebo, IPE 4 g/day significantly reduced TG, non-high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol (VLDL-C), lipoprotein-associated phospholipase A2, apolipoprotein B (Apo B), total cholesterol, high-density lipoprotein cholesterol, VLDL-TG, oxidized LDL, and remnant-like particle cholesterol in all 3 diabetes groups, LDL-C in the total diabetes group, and hsCRP in the total and less-controlled diabetes groups. Decreases in hsCRP and Apo B were much greater in patients with less-controlled diabetes. There were no significant increases in fasting plasma glucose, A1c, insulin, or homeostasis model assessment-estimated insulin resistance in any group.ConclusionIPE 4 g/day significantly improved lipid and lipid-related parameters without worsening glycemic control in patients with diabetes and mixed dyslipidemia, with possibly greater effects among those with less-controlled diabetes.Trial registrationClinicaltrials.gov Identifier NCT01047501

Combination Lipid Therapy on Lipid Profiles in Patients with Impaired Glucose Tolerance

Objective: This study compared the effects of combination statin and fibrate therapy with either statin or fibrate monotherapy on lipid profiles in patients with impaired glucose tolerance (IGT) and a high risk for cardiovascular disease. Methods & Patients: Forty-five patients with IGT and dyslipidemia (men 25, women 20, mean age 61.7 ± 2.4 yrs) were assigned randomly to the 3 treatment groups for a 6-month period. Results: After 6 months of treatment, low density lipoprotein levels decreased in every group, especially the statin and statin + fibrate groups. Triglyceride levels also decreased in all three groups, especially the fibrate and statin + fibrate groups. High density lipoprotein cholesterol and fasting blood glucose levels did not change in any group. The levels of remnant like cholesterol particles decreased in the fibrate and statin + fibrate groups. There was no change during the study in the levels of creatine phosphokinase, lactate dehydrogenase, or creatinine. Conclusion: Combination statin and fibrate therapy results in greater improvement in lipid profiles than monotherapy with either drug. No marked adverse effects were observed with combination therapy during the study.

Increased oxidative stress in normal-weight postmenopausal women with metabolic syndrome compared with metabolically healthy overweight/obese individuals

ObjectiveThe purpose of this study was to assess whether the metabolically healthy overweight/obese phenotype is associated with decreased oxidative stress compared with normal-weight individuals with metabolic syndrome (MetS). Materials/MethodsPlasma oxidized LDL (ox-LDL) and urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) were analyzed in a cross-sectional study of 1846 healthy postmenopausal women. Participants were classified by presence (n=569) or absence (n=1277) of MetS and by BMI (18.5–24.9kg/m2=normal weight, n=1254; ≥25kg/m2=overweight/obese, n=592). MetS was diagnosed with the modified National Cholesterol Education Program Adult Treatment Panel III criteria. ResultsCompared to normal weight women with MetS (n=296), metabolically healthy overweight/obese women (n=319) showed lower blood pressure, triglyceride, and glucose and higher HDL cholesterol, adiponectin, and LDL particle size. Ox-LDL was higher in overweight/obese women without MetS than in normal weight women without MetS (n=958) but was lower than in women with MetS. Urinary 8-epi-PGF2α level was about 11% lower in women without MetS than in women with MetS. Normal weight women with MetS had greater odds of having ox-LDL (multivariate odds ratio [OR] 2.42, 95% CI: 1.65–3.55) and 8-epi-PGF2α (OR 1.49; CI: 1.03–2.14) levels in the top quartile compared to normal weight women without MetS after adjusting for age, drinking, smoking, total- and LDL-cholesterol, and high sensitivity C-reactive protein. Additionally, there was no significant correlation between ox-LDL and 8-epi-PGF2α. ConclusionsThe metabolically healthy overweight/obese phenotype was associated with a better overall metabolic profile and less oxidative stress than that observed in normal weight individuals with MetS. Furthermore, there was a lack of association between ox-LDL and 8-epi-PGF2α.

P 17: Analysis of the relationship between parameters of total and abdominal obesity, levels of lipoproteins and occurrence of coronary heart disease in type 2 diabetes

Atherosclerosis is the commonest and the most important cause of coronary heart disease (CHD). Among the risk factors for its occurrence the key ones are diabetes mellitus, obesity and dyslipidemia. Therefore, the aim of this study was to determine the connection between the parameters of total and abdominal obesity, level of lipoproteins and the occurrence of CHD in type 2 diabetes (T2D). The research was conducted on 85 patients, 39 diabetics and 46 nondiabetics divided into the following groups: 18 patients with T2D and previously diagnosed CHD (group 1), 21 patients with T2D but without CHD (group 2), 24 nondiabetics with previously diagnosed CHD (group 3) and 22 nondiabetics without CHD (group 4). As an indicator of total obesity we calculated the body mass index (BMI). As parameters of abdominal obesity waist circumference (WC) and waist to hip ratio (WHR) were used. Total cholesterol (ch), HDL-ch, LDL-ch and Triglycerides (Tg) levels were determined by chromatography. We used also Tg/ HDL-ch ratio as an indicator of structural changes in subfractions of cholesterol particles and an independent risk factor for CHD. We found there is no difference in BMI in group 1 vs group 2 (28.09+/−0.82 vs 28.07+/−0.92 kg/m 2 , p=NS) neither in group 3 vs group 4 (27.58+/−0.97 vs 27.16+/−0.71 kg/m 2 , p=NS). WC and WHR values were significantly higher in group 1 vs group 2 (103.06+/−1.88 vs 97.60+/−1.99 cm, 0.98+/−0.01 vs 0.91+/−0.01; p<0.05 respectively) and in group 3 vs group 4 (95.15+/−2.42 vs 90.10+/−2.55 cm, 0.89+/−0.01 vs 0.83+/−0.01, p<0.05 respectively). Comparing the diabetics and nondiabetics, we have found that WC and WHR were significantly higher in diabetics (100.25+/−1.89 vs 92.50+/−2.53; 0.95+/−0.01 vs 0.86+/−0.01; p<0.05 respectively). There was no difference in levels of total ch between groups 1 and 2 (6.59+/−0.33 vs 6.32+/−0.37 mmol/L; p=NS), but total ch levels were significantly higher in group 3 compared to group 4 (6.27+/−0.20 vs 5.70+/−0.16 mmol/L, p<0.05). LDL-ch levels and Tg levels were significantly higher in group 1 vs group 2 (LDL-ch: 4.39+/−0.32 vs 3.61+/−0.24 mmol/L, p<0.05, Tg: 3.68+/−0.59 vs 3.08+/−0.60 mmol/L, p<0.05) and in group 3 vs group 4 (LDL-ch: 4.05+/−0.2 vs 3.59+/−0.17 mmol/L, p<0.05, Tg: 2.55+/−0.35 vs 1.58+/−0.16 mmol/L, p<0.05). There were no difference in HDL-ch levels between these groups (1: 1.04+/−0.06; 2: 1.14+/−0.08; 3: 1.25+/−0.08; 4: 1.25+/−0.07; 1 vs 2 and 3 vs 4 p=NS). However, Tg/HDL ratio was significantly higher in group 1 vs group 2 (4.11+/−0.88 vs 2.87+/−0.67, p<0.01) and in group 3 vs group 4 (2.18+/−0.34 vs 1.40+/−0.19, p<0.05). Also, by method of correlation, we found that in patients with CHD BMI significantly correlate with Tg and Tg/HDL ratio (r=0.338, p<0.05; r=0.388, p<0.05 respectively), while WC and WHR significantly correlate with Tg (r=0.387, p<0.05; r=0.410, p<0.01 respectively), Tg/HDL ratio (r=0.505, p<0.01; r=0.497, p<o.01 respectively) and HDL-ch (r=-0.450, p<0.01; r=-0.494, p<0.01 respectively). Our results have demonstrated that abdominal obesity disrupts cholesterol reverse path, leading to changes in the structure and composition of the HDL subfraction of cholesterol, which is one of the possible pathogenetic mechanisms of atherogenic effects of abdominal obesity. Also, this suggest that parameters of abdominal obesity could be an useful screening test for detecting people with dyslipidemia and high risk of developing CHD, especially diabetics.

Increase in Standard Cholesterol and Large HDL Particle Subclasses in Antiretroviral-Naïve Patients Prescribed Efavirenz Compared to Atazanavir/Ritonavir

Background: Cardiovascular risk in HIV-infected patients is related, at least in part, to serum lipid alterations before and after HAART. Lipoprotein-particle subclasses may also have an effect, but comparative data after standard HAART regimens are limited.Methods: This was a substudy of a trial in 91 antiretroviral-naïve patients randomized to tenofovir + emtricitabine + atazanavir/ritonavir (ATV/r) or efavirenz (EFV). Over-time trends from baseline to week 48 in total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), HDL particles (HDLp), and TC:HDL-C and TG:HDL-C ratios were analyzed by analysis of covariance (ANCOVA). Furthermore, confidence intervals for differences between the 2 groups at week 48 were calculated. Indications for lipid-lowering interventions and low HDL-C were also studied.Results: ANCOVA showed that, with respect to patients receiving ATV/r, those prescribed efavirenz (EFV) had greater increases reported as mean differences in lipid values at week 48: 14 mg/dL (95% CI, 0.2 to 27) for TC, 14 mg/dL (95% CI, 4 to 25) for LDL-C, 5 mg/dL (95% CI, 2 to 9) for HDL-C, and 2.2 mg/dL (95% CI, 0.4 to 4) for large HDLp. Proportions of subjects with indications for lipid-lowering interventions and with HDL-C <40 mg/dL did not differ significantly.Conclusions: Patients prescribed EFV had greater increases in TC, LDL-C, and HDL-C. Although no significant differences were detected between the 2 groups for the TC:HDL ratio and for indications to start lipid-lowering interventions, large HDLp increased more in the EFV group compared to the ATV/r group, suggesting a protective effect associated with EFV use.

New treatments on the horizon for familial hypercholesterolemia

Patients with familial hypercholesterolemia (FH) have higher baseline LDL cholesterol (LDLc) levels and are at high risk of developing premature cardiovascular disease. Disease is attributed to mutations in the LDLR gene, which encodes the LDL receptor protein and whose deficiency results in decreased uptake of apoB-containing cholesterol particles by the liver and elevated serum LDLc levels. Heterozygous FH is inherited in an autosomal-dominant pattern and has an incidence of 1:500 in the general population. These patients usually present with premature cardiovascular disease at 30–40 years of age and have baseline LDLc levels ranging from 190 to 230 mg/dl. Homozygous FH, however, is much rarer, occurring in one in a million births; those afflicted present with severe cardiovascular disease in childhood and have baseline LDLc levels greater than 300 mg/dl. Often FH patients do not reach their target LDLc levels on conventional therapies such as statins. Even with combination therapy, the percent of FH patients reaching target cholesterol levels is less than 30% and while apheresis is a therapeutic option for those with the most severe disease, many FH patients seek less invasive therapeutic strategies. New classes of cholesterol medications, aimed at either lowering LDLc levels or altering the progression of intra-arterial plaque, are currently in clinical development and may offer alternative or adjunctive therapies for this high-risk population.

Rol del enterocito en la dislipemia de la resistencia insulínica

The increase in cardiovascular morbidity and mortality associated to insulin resistance (IR) states (obesity, metabolic syndrome, type 2 diabetes) represents a major public health problem. In IR, dyslipidemia typically include hypertriglyceridemia, low high density lipoprotein cholesterol, increased small and dense low density lipoprotein particles, and post-prandial hyperlipidemia, which play a direct or indirect role in the mecanisms of atherosclerosis. Dyslipidemia is mainly due to accumulation of circulating triglyceride-rich lipoproteins from the liver and bowel. The bowel has traditionally been seen as a passive organ, but current evidence confirms that it is an active organ subject to regulation by free fatty acids, insulin, incretins, and inflammation. Two new concepts have emerged: intestinal IR and overproduction of chylomicrons in hyperinsulinemic/IR states. A better understanding of intestinal IR may make the enterocyte a therapeutic target.

Exercise effects on lipids in persons with varying dietary patterns—does diet matter if they exercise? Responses in Studies of a Targeted Risk Reduction Intervention through Defined Exercise I

The standard clinical approach for reducing cardiovascular disease risk due to dyslipidemia is to prescribe changes in diet and physical activity. The purpose of the current study was to determine if, across a range of dietary patterns, there were variable lipoprotein responses to an aerobic exercise training intervention. Subjects were participants in the STRRIDE I, a supervised exercise program in sedentary, overweight subjects randomized to 6 months of inactivity or 1 of 3 aerobic exercise programs. To characterize diet patterns observed during the study, we calculated a modified z-score that included intakes of total fat, saturated fat, trans fatty acids, cholesterol, omega-3 fatty acids, and fiber as compared with the 2006 American Heart Association diet recommendations. Linear models were used to evaluate relationships between diet patterns and exercise effects on lipoproteins/lipids. Independent of diet, exercise had beneficial effects on low-density lipoprotein cholesterol particle number, low-density lipoprotein cholesterol size, high-density lipoprotein cholesterol, high-density lipoprotein cholesterol size, and triglycerides (P < .05 for all). However, having a diet pattern that closely adhered to American Heart Association recommendations was not related to changes in these or any other serum lipids or lipoproteins in any of the exercise groups. We found that even in sedentary individuals whose habitual diets vary in the extent of adherence to AHA dietary recommendations, a rigorous, supervised exercise intervention can achieve significant beneficial lipid effects.