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A study was conducted to analyze the influence of acute changes of extracellular osmolality on whole body protein and glucose metabolism. The tracer infusates were ultrafiltrated and examined using gas chromatography-mass spectrometry by an HP GC-MS model 5890/5790. Experimental results indicated that acute alterations of plasma osmolality affect whole body protein, glucose and lipid metabolism.

Purpose: In patients suffering from symptomatic peripheral artery disease (PAD), percutaneous revascularization is the treatment of choice. However, restenosis may occur in 10 to 60% in the first year depending on a variety of factors. Small dense low density lipoprotein (sdLDL) particles are associated with an increased risk for cardiovascular events, but their role in the process of restenosis is not known. We conducted a prospective study to analyze the association of sdLDL particles with the outcome of balloon angioplasty in PAD. The composite primary endpoint was defined as improved walking distance and absence of restenosis. Methods: Patients with angiographically documented PAD of the lower extremities who were scheduled for lower limb revascularization were consecutively recruited for the study. At baseline and at three month follow-up triglyceride, total cholesterol, LDL size and subclasses and HDL cholesterol and ankle-brachial index (ABI) were measured. Three months after the intervention duplex sonography was performed to detect restenosis. Results: Sixty-four patients (53% male) with a mean age of 68.6±9.9 years were included. The proportion of small- dense LDL particles (class III and IV) was significantly lower (33.1±11.0% vs. 39.4±12.1%, p = 0.038) in patients who reached the primary end-point compared with those who did not. Patients with improved walking distance and without restenosis had a significantly higher LDL size at baseline (26.6±1.1 nm vs. 26.1±1.1 nm, p = 0.046) and at follow-up (26.7±1.1 nm vs. 26.2±0.9 nm, p = 0.044) than patients without improvement. Conclusions: Small-dense LDL particles are associated with worse early outcome in patients undergoing percutaneous revascularization for symptomatic PAD. [ABSTRACT FROM AUTHOR]

Background: Travel to mountain areas is popular. However, the effects of acute exposure to moderate altitude on the cardiovascular system and metabolism are largely unknown. Objectives: To investigate the effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation. Methods: In 51 healthy male subjects with a mean (SD) age of 26.9 (9.3) years, oxygen saturation, blood pressure, heart rate, arterial stiffness, lipid profiles, low density lipoprotein (LDL) particle size, insulin resistance (HOMA-index), highly-sensitive C-reactive protein and pro-inflammatory cytokines were measured at 490 m (Zurich) and during two days at 2590 m, (Davos Jakobshorn, Switzerland) in randomized order. The largest differences in outcomes between the two altitudes are reported. Results: Mean (SD) oxygen saturation was significantly lower at 2590 m, 91.0 (2.0)%, compared to 490 m, 96.0 (1.0)%, p<0.001. Mean blood pressure (mean difference +4.8 mmHg, p<0.001) and heart rate (mean difference +3.3 bpm, p<0.001) were significantly higher at 2590 m, compared to 490 m, but this was not associated with increased arterial stiffness. At 2590 m, lipid profiles improved (median difference triglycerides −0.14 mmol/l, p = 0.012, HDL +0.08 mmol/l, p<0.001, total cholesterol/HDL-ratio −0.25, p = 0.001), LDL particle size increased (median difference +0.45 nm, p = 0.048) and hsCRP decreased (median difference −0.18 mg/l, p = 0.024) compared to 490 m. No significant change in pro-inflammatory cytokines or insulin resistance was observed upon ascent to 2590 m. Conclusions: Short-term stay at moderate altitude is associated with increased blood pressure and heart rate likely due to augmented sympathetic activity. Exposure to moderate altitude improves the lipid profile and systemic inflammation, but seems to have no significant effect on glucose metabolism. Trial Registration: ClinicalTrials.gov NCT01130948 [ABSTRACT FROM AUTHOR]

Objectives. Statins decrease cardiovascular events mainly by lowering cholesterol but anti-inflammatory effects also play a role. The effects of the cholesterol absorption inhibitor ezetimibe on markers of inflammation remain unclear. We performed an exploratory post-hoc analysis whether these drugs influence the pro-inflammatory markers interleukin-6 and high-sensitivity C-reactive protein in subjects with very-low cardiovascular risk. Design. Single center, randomized, parallel 3-group study in 72 healthy men without apparent cardiovascular disease (age 32 ± 9 years, BMI 25.7 ± 3.2 kg/m²). Each group of 24 subjects received a 14-day treatment with either simvastatin 40 mg, ezetimibe 10 mg, or their combination. Results. Baseline IL-6 and hsCRP concentrations in the total cohort were 0.72 ±0.57 ng/1 and 0.40 ±0.65 mg/1, respectively, with no differences between the 3 groups. Median changes (interquartile range) in IL-6 and hsCRP concentrations were -22% (-43 to 0%) and -30% (-44 to +19%) after simvastatin, -5% (-36 to +30%) and +9% (-22 to +107%) after ezetimibe, and +15% (-15 to +86%) and +1 (-30 to +49%) after the combination. Using a generalized linear model, the multivariable adjusted overall P-values for these changes were 0.008 (IL-6) and 0.1 (hsCRP). Conclusions. Simvastatin decreases the pro-inflammatory markers IL-6 and almost significantly hsCRP while ezetimibe monotherapy or the combination with simvastatin has no effect. [ABSTRACT FROM AUTHOR]

Higher plasma triglyceride levels and decreased HDL-cholesterol concentrations are usually accompanied by the presence of small, dense LDL in the so-called lipid triad or ‘atherogenic lipoprotein phenotype’. This phenotype is highly atherogenic and its prevalence may suggest an even higher overall burden of atherosclerotic disease as compared with that associated with hypercholesterolemia. As stated by the National Cholesterol Education Program Adult Treatment Panel III, there is evidence suggesting each component of this lipid triad is individually atherogenic. However, the relative contribution of each component cannot be easily determined. Therefore, it has been suggested to consider the atherogenic lipoprotein phenotype as a whole as a risk factor. This is supported by data from epidemiological studies considering high-risk populations, which showed that the contribution to cardiovascular risk of each individual component cannot be dissected from the sum of all factors. We recently investigated the prevalence of the atherogenic lipoprotein phenotype in different categories of patients at higher cardiovascular risk: with coronary and noncoronary forms of atherosclerosis or metabolic diseases, including Type 2 diabetes, polycystic ovary syndrome and growth hormone deficiency. Subjects with higher triglyceride levels, decreased HDL-cholesterol concentrations and increased levels of small, dense LDL (i.e., subjects with the atherogenic lipoprotein phenotype) are common in coronary and noncoronary forms of atherosclerosis. In the future, it may be possible to measure the presence of small, dense LDL to identify subgroups at higher cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background: Beyond total low-density-lipoproteins (LDL) levels, increasing evidence suggests that the 'quality' of LDL exerts a great influence on the cardiovascular risk. Several studies have also shown that the therapeutic modulation of LDL size is of benefit in reducing the risk of cardiovascular events. Hypolipidaemic treatment is able to alter LDL subclass distribution but strong variations have been noticed among different agents. Fibrates have a major impact on triglyceride metabolism and in modulating LDL size and subclasses, but variations exist among the different molecules.Methodology: A literature search (by Medline and Scopus) was performed using the following headings: 'small dense LDL', 'LDL size', 'LDL subfractions', 'LDL subclasses', 'LDL distribution' and 'fenofibrate', 'bezafibrate', 'ciprofibrate' and 'gemfibrozil' up to 20 January 2007. The authors also manually reviewed the references of selected articles for any pertinent material.Results: Analysis of all published studies revealed that treatment with fenofibrate, ciprofibrate, bezafibrate and gemfibrozil is usually beneficial, and fenofibrate may be more efficacious than the other molecules. This is supported by using all the available techniques in subjects with a very wide range of lipid alterations.Conclusion: Among the different agents, fenofibrate has been found to be particularly effective in modulating LDL size and subclasses in patients at higher cardiovascular risk, such as those with type 2 diabetes or the metabolic syndrome. [ABSTRACT FROM AUTHOR]

Small, dense low-density-lipoproteins (LDL) are associated with increased risk for cardiovascular diseases and diabetes mellitus and a reduction in LDL size has been reported in patients with coronary and non-coronary forms of atherosclerosis. LDL size has been accepted as an important predictor of cardiovascular events and progression of coronary artery disease as well as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III. Small, dense LDL, with elevated triglyceride levels and low HDL-cholesterol concentrations, constitute the 'atherogenic lipoprotein phenotype (ALP)', a form of atherogenic dyslipidemia that is a feature of type 2 diabetes and the metabolic syndrome. LDL size and subclasses show specific alterations in patients with the metabolic syndrome that probably significantly increase their cardiovascular risk; however, so far it has not been recommended to incorporate LDL size measurements in treatment plans, when hypolipidemic therapies are installed. Patients with type 2 diabetes are at high cardiovascular risk and it is still on debate if the treatment goals may be identical or whether there are distinct groups with different cardiovascular risks and hence with different treatment goals. Measurements beyond traditional lipids, such as measurements on the presence of small, dense LDL in patients with the metabolic syndrome, may help to identify cardiovascular risk subgroups. In addition, it might be possible in the future to individualize hypolipidemic treatments if more than the traditional lipids are taken into account. LDL size measurement may potentially help to assess cardiovascular risk within the metabolic syndrome and adapt the treatment goals thereafter. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Low to moderate sugar-sweetened beverage consumption impairs glucose and lipid metabolism and promotes inflammation in healthy young men: a randomized controlled trial," by I. Aeberli and colleagues in the 2011 issue.

The association of small, dense low-density lipoprotein (sdLDL) particles with an increased cardiovascular risk is well established. However, its predictive value with regard to glucose metabolism and arterial disease in patients with type 2 diabetes has not been thoroughly investigated. We conducted a prospective longitudinal cohort study in patients with (pre)diabetes who were seen at baseline and after two years. sdLDL particles were determined by gradient gel electrophoresis. Insulin resistance was estimated by using the homeostatic model assessment 2 (HOMA2). Intima media thickness (IMT) and flow-mediated dilation (FMD) were assessed by ultrasound measurements. Fifty-nine patients (mean age 63.0 ± 12.2 years) were enrolled and 39 were seen at follow-up. IMT increased in the whole cohort during follow-up. The change in IMT was predicted by the proportion of sdLDL particles at baseline (p=0.03), and the change in FMD was predicted by LDL-cholesterol levels at baseline (p=0.049). HOMA2 and changes in HOMA2 correlated with the proportion of sdLDL particles and changes in this proportion, respectively (p<0.05 for both). Serum resistin levels increased in parallel with the increasing sdLDL particle number, while serum adiponectin increased only in patients with unaltered sdLDL particle number at follow-up (p<0.01 for both). In conclusion, the proportion of small, dense LDL particles and changes in this proportion are predictive of changes in intima media thickness and insulin resistance, and are closely associated with other determinants of an adverse metabolic status. Thus, this parameter extends the individual risk assessment beyond the limitations of traditional risk markers in patients with dysglycemia. [ABSTRACT FROM AUTHOR]