Inhibition of microsomal triglyceride transfer protein alone or with ezetimibe in patients with moderate hypercholesterolemia.

Background: Many patients with coronary heart disease do not achieve recommended LDL-cholesterol levels, due to either intolerance or inadequate response to available lipid-lowering therapy. Microsomal triglyceride transfer protein (MTP) inhibitors might provide an alternative way to lower LDL-cholesterol levels. We tested the safety and LDL-cholesterol-lowering efficacy of an MTP inhibitor, AEGR-733 (Aegerion Pharmaceuticals Inc.

Low-carbohydrate diets, obesity, and metabolic risk factors for cardiovascular disease.

Given the increased prevalence of obesity in the United States (and its associated cardiovascular risk) despite reduced fat intake, there has been increasing interest in the effect of low-carbohydrate diets on obesity. Recent prospective trials have demonstrated equivalent weight loss on low-carbohydrate versus low-fat diets, but with significantly different effects on metabolic risk factors for cardiovascular disease. Low-carbohydrate diets have more favorable effects on metabolic abnormalities found in insulin resistance syndromes, including serum triglyceride levels, high-density lipoprotein cholesterol levels, and small, dense low-density lipoprotein particles.

Adipocytokine changes caused by low-carbohydrate compared to conventional diets in obesity.

Modest weight loss causing a decrease in insulin resistance has been linked to favorable changes in the adipocyte cytokines leptin, adiponectin, and tumor necrosis factor-alpha (TNF-alpha), three emerging risk factors of cardiovascular disease. We previously observed a significant reduction in insulin resistance with weight loss in obese subjects on a low-carbohydrate diet. Based on these previous findings, we hypothesize that a low-carbohydrate diet would be more beneficial in changing leptin, TNF-alpha, and adiponectin than a conventional diet.

Social support and self-care of patients with heart failure.

Background: Social support can influence treatment adherence of patients with chronic illnesses, which may explain the positive effects of social support on heart failure (HF) outcomes.

Purpose: To investigate the effects of social support among patients with HF, we examined whether aspects of social support were associated with self-care, including medication adherence, dietary adherence, and HF symptom monitoring functions.

Methods: We recruited 74 patients with HF from cardiology clinics of a Veterans Affairs Medical Center and a university-affiliated hospital, and tested the relationships between social support and the patients' self-care.

Clinical exacerbations as a surrogate end point in heart failure research.

Background: We examined the utility of an index of clinical exacerbations of heart failure (HF) as a surrogate measure of outcome for use in modestly sized clinical trials and observational studies.

Methods: Electronic records of 189 outpatients with HF in a US Veterans Affairs Medical Center were examined over a 2- to 3-year period. Data collected included patient characteristics, clinical exacerbations of HF, hospitalizations, and deaths.

Adherence to warfarin assessed by electronic pill caps, clinician assessment, and patient reports: results from the IN-RANGE study.

Background: Patient adherence to warfarin may influence anticoagulation control; yet, adherence among warfarin users has not been rigorously studied.

Objective: Our goal was to quantify warfarin adherence over time and to compare electronic medication event monitoring systems (MEMS) cap measurements with both self-report and clinician assessment of patient adherence.

Design: We performed a prospective cohort study of warfarin users at 3 Pennsylvania-based anticoagulation clinics and assessed pill-taking behaviors using MEMS caps, patient reports, and clinician assessments.

Dyslipidemia in type 2 diabetes mellitus.

Cardiovascular disease is a significant cause of morbidity and mortality in patients with diabetes mellitus (DM). DM is now recognized as a risk equivalent for coronary heart disease. The lipid profile in patients with type 2 DM is characterized by elevated triglycerides, low levels of high-density lipoprotein cholesterol, and small dense low-density lipoprotein cholesterol (LDLC) particles and is believed to be a key factor promoting atherosclerosis in these patients.

Warfarin and cytochrome P450 2C9 genotype: possible ethnic variation in warfarin sensitivity.

Introduction: Warfarin is a widely prescribed, efficacious oral anticoagulant. S-warfarin, the more active form, is metabolized by the cytochrome P450 (CYP)2C9 enzyme. The aim was to evaluate the influence of two CYP2C9 functional polymorphisms (*2 and *3) on warfarin dose in African-Americans, an unstudied population and Caucasians, and also to assess the effect of these polymorphisms on anticoagulation response after accounting for nongenetic factors and genetic factors that might also impact the dose-response relationship of warfarin.

The influence of patient adherence on anticoagulation control with warfarin: results from the International Normalized Ratio Adherence and Genetics (IN-RANGE) Study.

Background: Warfarin sodium is a highly efficacious drug, but proper levels of anticoagulation are difficult to maintain. Conflicting data exist on the influence of patient adherence on anticoagulation control.

Methods: We performed a prospective cohort study at 3 anticoagulation clinics to determine the effect of adherence on anticoagulation control.

Novel platelet and vascular roles for immunoreceptor signaling.

The immunoreceptor signaling pathway has classically been defined by its role in mediating intracellular signals downstream of immune receptors on circulating cells, but recent studies have revealed new and unexpected roles for this pathway in vascular biology. In platelets the immunoreceptor signaling pathway is coupled to 2 structurally distinct platelet collagen receptors, glycoprotein VI and integrin alpha2beta1, and is required for the activation of platelets after exposure to vessel wall collagen during plaque rupture. During vascular development immunoreceptor signaling is required for proper formation of the lymphatic system, a role that has revealed the contribution of hematopoietic endothelial progenitors to that process.

Effects of rosiglitazone on lipids, adipokines, and inflammatory markers in nondiabetic patients with low high-density lipoprotein cholesterol and metabolic syndrome.

Background: PPAR-gamma agonists improve insulin sensitivity and glycemic control in type 2 diabetes and may reduce atherosclerosis progression. Thus, PPAR-gamma agonists may be an effective therapy for metabolic syndrome. However, the full spectrum of potentially antiatherogenic mechanisms of PPAR-gamma agonists have not been fully tested in nondiabetic patients with metabolic syndrome.

Cost-effectiveness of a low-carbohydrate diet and a standard diet in severe obesity.

Objective: Low-carbohydrate diets have become a popular alternative to standard diets for weight loss. Our aim was to compare the cost-effectiveness of these two diets.

Research Methods And Procedures: The patient population included 129 severely obese subjects (BMI = 42.

Effects of pioglitazone on lipoproteins, inflammatory markers, and adipokines in nondiabetic patients with metabolic syndrome.

Objective: The purpose of this research was to evaluate the short-term effects of pioglitazone (PIO) on high-density lipoprotein cholesterol (HDL-C) and other metabolic parameters in nondiabetic patients with metabolic syndrome (MetSyn).

Methods And Results: Sixty nondiabetic adults with low HDL-C and MetSyn were randomized to PIO or matching placebo for 12 weeks. PIO increased HDL-C by 15% and 14% at 6 and 12 weeks, respectively, compared with placebo (P<0.

Effect of very high-fat diets on body weight, lipoproteins, and glycemic status in the obese.

Given the increased prevalence of obesity in the United States, despite reduced fat intake, there has been increasing interest in the effect of dietary fat on body weight, lipoproteins, and glycemic status. Despite predictions from epidemiologic and physiologic studies, recent prospective trials have demonstrated equivalent weight loss on high-fat versus low-fat diets. Nevertheless, the type of dietary fat consumed has substantially different effects on lipoproteins.

Free fatty acids, insulin resistance, and corrected qt intervals in morbid obesity: effect of weight loss during 6 months with differing dietary interventions.

Objective: To assess whether shortening of the corrected QT (QTc) interval is most closely associated with changes in weight, insulin resistance, or free fatty acids (FFAs) (or some combination of these factors).

Methods: We randomized 75 severely obese subjects without diabetes to either a low-carbohydrate or a conventional low-fat weight-loss diet for 6 months. We measured QTc, insulin sensitivity, body mass index, and FFAs at baseline and at 6 months.

Density of platelet collagen receptors glycoprotein VI and alpha2beta1 and prior myocardial infarction in human subjects, a pilot study.

Background: Prior studies evaluating whether platelet collagen receptors affect risk of myocardial infarction (MI) have used common polymorphisms thought to affect receptor density, and have yielded conflicting results. Our objective in the current pilot study was to obtain preliminary information on the relationship between platelet collagen receptor density and prior MI.

Material/methods: We measured glycoprotein VI (GPVI) and integrin alpha2beta1 density by flow cytometry using FITC-conjugated monoclonal antibodies in consecutive subjects from an outpatient cardiology practice.

A randomized study comparing the effects of a low-carbohydrate diet and a conventional diet on lipoprotein subfractions and C-reactive protein levels in patients with severe obesity.

Purpose: To compare the effects of a low-carbohydrate diet and a conventional (fat- and calorie-restricted) diet on lipoprotein subfractions and inflammation in severely obese subjects.

Methods: We compared changes in lipoprotein subfractions and C-reactive protein levels in 78 severely obese subjects, including 86% with either diabetes or metabolic syndrome, who were randomly assigned to either a low-carbohydrate or conventional diet for 6 months.

Results: Subjects on a low-carbohydrate diet experienced a greater decrease in large very low-density lipoprotein (VLDL) levels (difference = -0.

The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year follow-up of a randomized trial.

Background: A previous paper reported the 6-month comparison of weight loss and metabolic changes in obese adults randomly assigned to either a low-carbohydrate diet or a conventional weight loss diet.

Objective: To review the 1-year outcomes between these diets.

Design: Randomized trial.

Functional polymorphism in the carboxyl terminus of the alpha-subunit of the human epithelial sodium channel.

A common human epithelial sodium channel (ENaC) polymorphism, alphaT663A, is present in the cytoplasmic C terminus of the alpha-subunit, although it is unclear whether this polymorphism segregates with blood pressure. We examined whether this polymorphism was associated with differences in functional Na(+) channel expression. Whole cell amiloride-sensitive currents in Xenopus oocytes expressing wild type channels (alphaT663betagamma) were significantly approximately 1.

Cystic fibrosis transmembrane conductance regulator differentially regulates human and mouse epithelial sodium channels in Xenopus oocytes.

The cystic fibrosis transmembrane conductance regulator (CFTR), in addition to its well defined Cl- channel properties, regulates other ion channels. CFTR inhibits murine or rat epithelial Na+ channel (mENaC or rENaC) currents in many epithelial and non-epithelial cells, whereas murine or rat ENaC increases CFTR functional expression. These regulatory interactions are reproduced in Xenopus oocytes where both the open probability and surface expression of wild type CFTR Cl- channels are increased when CFTR is co-expressed with alphabetagamma mENaC, and conversely the activity of mENaC is inhibited after wild type CFTR activation.

A low-carbohydrate as compared with a low-fat diet in severe obesity.

Background: The effects of a carbohydrate-restricted diet on weight loss and risk factors for atherosclerosis have been incompletely assessed.

Methods: We randomly assigned 132 severely obese subjects (including 77 blacks and 23 women) with a mean body-mass index of 43 and a high prevalence of diabetes (39 percent) or the metabolic syndrome (43 percent) to a carbohydrate-restricted (low-carbohydrate) diet or a calorie- and fat-restricted (low-fat) diet.

Results: Seventy-nine subjects completed the six-month study.