Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events

Lipid Droplets in Atherosclerotic Fatty Streaks of Human Aorta

A B S T R A C T Preparations of lipid droplets and droplet-free tissue residue (cytoplasm + membranes + nuclei) were obtained by homogenization and centrifugal separation from intimal fatty streak lesions of aortic atherosclerosis of 21 adults who had died suddenly. Neutral lipids and phospholipids were analyzed by quantitative thin-layer chromatography and cholesteryl ester fatty acids by gas-liquid chromatography. Optical properties of droplets were evaluated by differential counting and sizing procedures with the polarizing microscope. The droplets occurred in mixtures of two forms distinguished by their optical properties, anisotropic (i.e. liquid crystals) and isotrop c (true liquids). Both forms had average diameters of about 1.8 1A, with a range of 0.55 ,.. The proportions of the two forms varied with temperature as individual droplets changed their form; anisotropic forms averaged 83.7% at 220C and 37.8% at 370C, with isotropic forms being 16.3 and 62.2% respectively. The proportions of anisotropic forms at 220C decreased with age. These forms were not separated for chemical analysis. The droplets contained about half the lipid in the lesions. The composition of the lipids of the droplet mixture was remarkably uniform and strikingly different from that of the droplet-free residue. respectively: cholesteryl esters 94.9% vs. 38.7%, free cholesterol 1.7% vs. 18.6%. total phospholipids 1.0% vs. 38.6%, and triglycerides 2.4% vs. 4.0%. The proportions of individual phospholipids, with the exception of lysolecithin, were also different between the preparations. In the droplets only the proportions of lecithin correlated positively with the proportion of anisotropi

Combination of niacin extended-release and simvastatin results in a less atherogenic lipid profile than atorvastatin monotherapy

Objective: To compare the effects of combination niacin extended-release + simvastatin (NER/S) versus atorvastatin alone on apolipoproteins and lipid fractions in a post hoc analysis from SUPREME, a study which compared the lipid effects of niacin extended-release + simvastatin and atorvastatin in patients with hyperlipidemia or mixed dyslipidemia. Patients and methods: Patients (n = 137) with dyslipidemia (not previously receiving statin therapy or having discontinued any lipid-altering treatment 4-5 weeks prior to the study) received NER/S (1000/40 mg/day for four weeks, then 2000/40 mg/day for eight weeks) or atorvastatin 40 mg/day for 12 weeks. Median percent changes in apolipoprotein (apo) A-1, apo B, and the apo B: A-I ratio, and nuclear magnetic resonance lipoprotein subclasses from baseline to week 12 were compared using the Wilcoxon rank-sum test and Fisher's exact test. Results: NER/S treatment produced significantly greater percent changes in apo A-I and apo B: A-I, and, at the final visit, apo B < 80 mg/dL was attained by 59% versus 33% of patients, compared with atorvastatin treatment (P = 0.003). NER/S treatment resulted in greater percent reductions in calculated particle numbers for low-density lipoprotein (LDL, 52% versus 43%; P = 0.022), small LDL (55% versus 45%; P = 0.011), very low-density lipoprotein (VLDL) and total chylomicrons (63% versus 39%; P < 0.001), and greater increases in particle size for LDL (2.7% versus 1.0%; P = 0.007) and VLDL (9.3% versus 0.1%; P < 0.001), compared with atorvastatin. Conclusion: NER/S treatment significantly improved apo A-I levels and the apo B: A-I ratio, significantly lowered the number of atherogenic LDL particles and VLDL and chylomicron particles, and increased the mean size of LDL and VLDL particles, compared with atorvastatin

Bile Acid Sequestrants for Lipid and Glucose Control

Bile acids are generated in the liver and are traditionally recognized for their regulatory role in multiple metabolic processes including bile acid homeostasis, nutrient absorption, and cholesterol homeostasis. Recently, bile acids emerged as signaling molecules that, as ligands for the bile acid receptors farnesoid X receptor (FXR) and TGR5, activate and integrate multiple complex signaling pathways involved in lipid and glucose metabolism. Bile acid sequestrants are pharmacologic molecules that bind to bile acids in the intestine resulting in the interruption of bile acid homeostasis and, consequently, reduction in low-density lipoprotein cholesterol levels in hypercholesterolemia. Bile acid sequestrants also reduce glucose levels and improve glycemic control in persons with type 2 diabetes mellitus (T2DM). This article examines the mechanisms by which bile acid–mediated activation of FXR and TGR5 signaling pathways regulate lipid and glucose metabolism and the potential implications for bile acid sequestrant–mediated regulation of lipid and glucose levels in T2DM

Lipid droplets in atherosclerotic fatty streaks of human aorta

Preparations of lipid droplets and droplet-free tissue residue (cytoplasm + membranes + nuclei) were obtained by homogenization and centrifugal separation from intimal fatty streak lesions of aortic atherosclerosis of 21 adults who had died suddenly. Neutral lipids and phospholipids were analyzed by quantitative thin-layer chromatography and cholesteryl ester fatty acids by gas-liquid chromatography. Optical properties of droplets were evaluated by differential counting and sizing procedures with the polarizing microscope. The droplets occurred in mixtures of two forms distinguished by their optical properties, anisotropic (i.e. liquid crystals) and isotropic (true liquids). Both forms had average diameters of about 1.8 μ, with a range of 0.5-5μ. The proportions of the two forms varied with temperature as individual droplets changed their form; anisotropic forms averaged 83.7% at °C and 37.8% at 37°C, with isotropic forms being 16.3 and 62.2% respectively. The proportions of anisotropic forms at 22°C decreased with age. These forms were not separated for chemical analysis. The droplets contained about half the lipid in the lesions. The composition of the lipids of the droplet mixture was remarkably uniform and strikingly different from that of the droplet-free residue, respectively: cholesteryl esters 94.9% vs. 38.7%, free cholesterol 1.7% vs. 18.6%, total phospholipids 1.0% vs. 38.6%, and triglycerides 2.4% vs. 4.0%. The proportions of individual phospholipids, with the exception of lysolecithin, were also different between the preparations. In the droplets only the proportions of lecithin correlated positively with the proportion of anisotropic forms (at 22°C). Droplet cholesteryl esters were particularly rich in oleic acid and when compared to residue esters had more palmitoleic (+0.7%), oleic (+12.3%), and eicosatrienoic (+2.4%) and less palmitic (-2.2%), linoleic (-12.4%), and arachidonic (-1.6%) acids. The proportions of most individual fatty acids of droplets and residue correlated positively. The lipids of the residue closely resemble those reported for the normal intima. The observations that these droplets are prominent in the morphology of the fatty streak lesions, and that their high content of oleate-rich cholesteryl esters is similar to that reported for analysis of the whole lesions, suggest that the droplets may be involved in the pathogenesis of the fatty streak lesions of artherosclerosis in man

Surgical inclination in senior medical students from the University of Auckland: results of the 2005 Senior Students Survey.

AIMS: To determine the proportion of senior medical students who are surgically inclined and to assess whether gender differences exist in surgical inclination. STUDY DESIGN: Cross-sectional survey. Twenty-five point questionnaire. Likert scale response ranking. SETTING: University of Auckland Medical School, New Zealand. PARTICIPANTS: 218 surveys were emailed to functioning addresses of fourth and fifth year students.156 students emailed responses (71.60% response rate). RESULTS: Twenty percent of students were found to be surgically inclined (95% CI 0.15-0.26). The proportion of surgically inclined males was significantly higher than females (p<0.01). A greater proportion of surgically inclined students found time spent in the operating theatre educationally valuable than non-surgically inclined students (p<0.01). No difference exists in the number of different procedures undertaken by students (p<0.05). CONCLUSION: Males are significantly more likely to be surgically inclined than females at the University of Auckland Medical School