SciCombinator

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Concept: Lipoprotein

167

The present study was designed to verify the influence of acute fat loading on high density lipoprotein (HDL) composition, and the involvement of liver and different segments of small intestine in the changes observed.

Concepts: Cholesterol, Liver, Lipoprotein, High-density lipoprotein, Lipoproteins, Small intestine, Lipid, Olive oil

167

Aim: To determine the effect of a 12-month intent-to-treat tesosterone replacement therapy (TRT) trial on QTa interval variability (QTaVI) in hypogonadal (HG) men with spinal cord injury (SCI). Method: A prospective, controlled, 12-month TRT trial was completed in twenty-two healthy, chronic, non-ambulatory men with SCI. Based on serum T concentration, subjects were designated as HG (≤11.3 nmol/l) or eugonadal (EG, ≥11.4 nmol/l). Digital 3-lead electrocardiograms were performed. Heart rate (RR), heart rate variability [(HRV), including total power (TP(RR)), low frequency (LF(RR)) and high freguency (HF(RR))], QTa, QTe, and RT intervals, QTC (Bazett), QTVN, and QTaVI were calculated and evaluated at baseline and 12 months. Lipoprotein profiles (triglycerides, total cholesterol, low density and high-density lipoproteins) were obtained at the respective time points. Results: Based on serum T concentration, 13 subjects were designated as HG and 11 EG. During the trial, there were no group differences for RR, QTa, QTe or RT intervals, QTC, TP(RR), HF(RR), or lipoproteins. The HG was older (p < 0.05) and LF(RR) was lower (p < 0.05) at baseline. At baseline, QTaVI was significantly greater in HG compared to EG [-0.17 (0.92) vs. -1.07 (0.90); p < 0.05]. After TRT, this group difference was no longer present [-0.44 (0.87) vs. -0.65 (0.85)] and the change in HG was significant (p < 0.05). Conclusion: Hypogonadism in men with SCI was associated with elevated QTaVI at baseline. After 12 months of physiological TRT, the QTaVI improved in association with raising T into the normal range. These findings occurred independently from the prolongation of the QT interval.

Concepts: Cholesterol, Cardiology, Lipoprotein, Lipoproteins, Cardiac electrophysiology, Testosterone, QT interval, Hypogonadism

166

The prognostic importance of high-density lipoprotein cholesterol (HDL-C) as a specific risk factor for cardiovascular (CV) disease has been challenged by recent clinical trials and genetic studies.

Concepts: Cholesterol, Epidemiology, Atherosclerosis, Medical statistics, The Canon of Medicine, Cardiovascular disease, Avicenna, Lipoprotein

166

Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL), in addition to having a prognostic value in patients with cardiovascular disease, seems to interact with adiposity, insulin resistance and other cardiovascular risk factors. However, the results of previous clinical studies, focused on the association of TRAIL with selected metabolic or anthropometric indices were inconclusive. The aim of this study was to further investigate how soluble TRAIL concentrations independently correlate with major cardiovascular risk factors, including lipid, glycemic and anthropometric features. MATERIALSMETHODS: We examined the associations between serum soluble TRAIL concentrations, measured by ELISA, and lipid, glycemic and anthropometric features in 199 subjects recruited at our Metabolic Outpatient Clinic.

Concepts: Myocardial infarction, Atherosclerosis, Blood vessel, Cardiovascular disease, Low-density lipoprotein, Insulin resistance, Lipoprotein, The Association

55

Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies can reduce low-density lipoprotein cholesterol (LDL-C) to very low levels when added to background lipid-lowering therapy.

Concepts: Cholesterol, Atherosclerosis, Cardiovascular disease, Low-density lipoprotein, Atheroma, Niacin, Lipoprotein

54

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in regulating the levels of plasma low-density lipoprotein cholesterol (LDL-C). Here, we demonstrate that the compound PF-06446846 inhibits translation of PCSK9 by inducing the ribosome to stall around codon 34, mediated by the sequence of the nascent chain within the exit tunnel. We further show that PF-06446846 reduces plasma PCSK9 and total cholesterol levels in rats following oral dosing. Using ribosome profiling, we demonstrate that PF-06446846 is highly selective for the inhibition of PCSK9 translation. The mechanism of action employed by PF-06446846 reveals a previously unexpected tunability of the human ribosome that allows small molecules to specifically block translation of individual transcripts.

Concepts: Cholesterol, Protein, Atherosclerosis, Low-density lipoprotein, Atheroma, Lipoprotein, Protein biosynthesis, Enzyme inhibitor

48

Calorie restriction or changes in dietary composition can enhance healthy aging, but the inability of most subjects to adhere to chronic and extreme diets, as well as potentially adverse effects, limits their application. We randomized 100 generally healthy participants from the United States into two study arms and tested the effects of a fasting-mimicking diet (FMD)-low in calories, sugars, and protein but high in unsaturated fats-on markers/risk factors associated with aging and age-related diseases. We compared subjects who followed 3 months of an unrestricted diet to subjects who consumed the FMD for 5 consecutive days per month for 3 months. Three FMD cycles reduced body weight, trunk, and total body fat; lowered blood pressure; and decreased insulin-like growth factor 1 (IGF-1). No serious adverse effects were reported. After 3 months, control diet subjects were crossed over to the FMD program, resulting in a total of 71 subjects completing three FMD cycles. A post hoc analysis of subjects from both FMD arms showed that body mass index, blood pressure, fasting glucose, IGF-1, triglycerides, total and low-density lipoprotein cholesterol, and C-reactive protein were more beneficially affected in participants at risk for disease than in subjects who were not at risk. Thus, cycles of a 5-day FMD are safe, feasible, and effective in reducing markers/risk factors for aging and age-related diseases. Larger studies in patients with diagnosed diseases or selected on the basis of risk factors are warranted to confirm the effect of the FMD on disease prevention and treatment.

Concepts: Nutrition, Death, Senescence, Atherosclerosis, Obesity, Cardiovascular disease, Lipoprotein, Body mass index

36

To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization.

Concepts: Cholesterol, Atherosclerosis, Heart, Atheroma, Lipid disorders, Lipoprotein, Heart disease, Artery

32

The extent to which a high intake of saturated fat (SFA) increases the risk of cardiovascular disease (CVD) has become a highly controversial topic. Dietary SFA primarily raises low-density lipoprotein cholesterol, while having a relatively neutral impact on other key CVD risk factors. Recent epidemiological data also challenge the concept that SFA increases the risk of CVD. This short review provides arguments for the urgency to re-assess the association between dietary SFA and CVD risk in light of recent data on the subject.

Concepts: Cholesterol, Epidemiology, Nutrition, Atherosclerosis, Cardiovascular disease, Low-density lipoprotein, Atheroma, Lipoprotein

32

BACKGROUND Although current guidelines recommend measuring lipid levels in a fasting state, recent studies suggest that nonfasting lipid profiles change minimally in response to food intake and may be superior to fasting levels in predicting adverse cardiovascular outcomes. The objective of this study was to investigate the association between fasting times and lipid levels. METHODS Cross-sectional examination of laboratory data, including fasting duration (in hours) and lipid results, was performed over a 6-month period in 2011 in a large community-based cohort. Data were obtained from Calgary Laboratory Services, Calgary, Alberta, Canada, the sole supplier of laboratory services for Calgary and surrounding areas (source population, 1.4 million persons). The main outcome measures were mean levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, and triglycerides for fasting intervals from 1 hour to more than 16 hours. After differences in individual ages were controlled for, linear regression models were used to estimate the mean levels of cholesterol subclasses at different fasting times. RESULTS A total of 209 180 individuals (111 048 females and 98 132 males) were included in the study. The mean levels of total cholesterol and high-density lipoprotein cholesterol differed little among individuals with various fasting times. The mean calculated low-density lipoprotein cholesterol levels showed slightly greater variations of up to 10% among groups of patients with different fasting intervals, and the mean triglyceride levels showed variations of up to 20%. CONCLUSION Fasting times showed little association with lipid subclass levels in a community-based population, which suggests that fasting for routine lipid levels is largely unnecessary.

Concepts: Cholesterol, Regression analysis, Linear regression, Atherosclerosis, Low-density lipoprotein, Triglyceride, Lipoprotein, Lipid