Combined statin and niacin therapy remodels the high-density lipoprotein proteome.

Background: Boosting low high-density lipoprotein (HDL) levels is a current strategy for preventing clinical events that result from cardiovascular disease. We previously showed that HDL(3) of subjects with coronary artery disease is enriched in apolipoprotein E and that the lipoprotein carries a distinct protein cargo. This observation suggests that altered protein composition might affect the antiatherogenic and antiinflammatory properties of HDL.

Lipoprotein(a) level as a predictor of cardiovascular disease and small apoliprotein(a) isoforms in dialysis patients: assay-related differences are important.

Background: Lipoprotein(a) assays sensitive to apolipoprotein(a) size may underestimate associations of lipoprotein(a) with cardiovascular disease (CVD) and low molecular weight (LMW) apolipoprotein(a) isoforms. This study among 629 dialysis patients compares the value of two lipoprotein(a) assays in predicting CVD events and small isoforms.

Methods: Lipoprotein(a) level was measured by an apolipoprotein(a) size-insensitive ELISA and apolipoprotein(a) size-sensitive immunoturbidometric (IT) assay; and apolipoprotein(a) size by Western blot.

Enhanced cellular uptake of remnant high-density lipoprotein particles: a mechanism for high-density lipoprotein lowering in insulin resistance and hypertriglyceridemia.

A low level of high-density lipoprotein (HDL) cholesterol is characteristic of insulin resistance and hypertriglyceridemia and likely contributes to the increased risk of cardiovascular disease associated with these conditions. One pathway involves enhanced clearance of lipolytically modified HDL particles, but the underlying mechanisms remain poorly understood. Here, we examine the effect of triglyceride enrichment and hepatic lipase hydrolysis on HDL binding, internalization, and degradation in cultured liver and kidney cells.

Adiponectin, change in adiponectin, and progression to diabetes in the Diabetes Prevention Program.

Objective: To determine whether baseline adiponectin levels or intervention-associated change in adiponectin levels were independently associated with progression to diabetes in the Diabetes Prevention Program (DPP).

Research Design And Methods: Cox proportional hazards analysis was used to evaluate the contribution of adiponectin and treatment-related change in adiponectin to risk of progression to diabetes.

Results: Baseline adiponectin was a strong independent predictor of incident diabetes in all treatment groups (hazard ratio per approximately 3 microg/ml higher level; 0.

Prevalence and determinants of elevated apolipoprotein B and dense low-density lipoprotein in youths with type 1 and type 2 diabetes.

Objective: The objective of the study was to assess the prevalence and determinants of elevated apolipoprotein B (apoB) and dense low-density lipoprotein (LDL) in United States youth with type 1 or type 2 diabetes.

Methods: We conducted cross-sectional analyses of apoB concentrations, LDL density, and prevalence of elevated apoB levels and dense LDL from the SEARCH for Diabetes in Youth study, a six-center U.S.

Effects of adding extended-release niacin and colesevelam to statin therapy on lipid levels in subjects with atherosclerotic disease.

Background: The use of combination therapies is needed to treat dyslipidemia in patients with both elevated low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol (HDL-C). We conducted a study to assess the efficacy and safety of combination therapy with statin plus extended-release (ER) niacin and colesevelam, aimed at lowering LDL-C and raising HDL-C, in subjects with atherosclerotic disease.

Methods: This 1-year study randomized 123 subjects with atherosclerotic disease to atorvastatin alone, double therapy with atorvastatin plus ER niacin, or triple therapy with atorvastatin, plus ER niacin and colesevelam.

The dipeptidyl peptidase-4 inhibitor vildagliptin improves beta-cell function and insulin sensitivity in subjects with impaired fasting glucose.

Objective: To evaluate the effect of treatment with the dipeptidyl peptidase (DPP)-4 inhibitor vildagliptin on insulin sensitivity and beta-cell function in subjects with impaired fasting glucose (IFG).

Research Design And Methods: A total of 22 subjects with IFG (11 female and 11 male, mean +/- SD age 59.6 +/- 11.

Higher prevalence of elevated albumin excretion in youth with type 2 than type 1 diabetes: the SEARCH for Diabetes in Youth study.

Objective: To estimate the prevalence of an elevated albumin-to-creatinine ratio (ACR) (> or = 30 microg/mg) among youth with type 1 or type 2 diabetes and to identify factors associated with elevated ACR and their effect on the relationship between elevated ACR and type of diabetes.

Research Design And Methods: Cross-sectional data were analyzed from 3,259 participants with onset of diabetes at < 20 years of age in the SEARCH for Diabetes in Youth, a multicenter observational study of diabetes in youth. Multiple logistic regression was used to explore determinants of elevated ACR and factors accounting for differences in this prevalence between type 2 and type 1 diabetes.

Novel and traditional cardiovascular risk factors for peripheral arterial disease in incident-dialysis patients.

Peripheral arterial disease (PAD), which threatens limb viability and patient survival, is increasing in frequency in the dialysis population, but associated risk factors remain poorly defined. We conducted a cross-sectional analysis of the association of novel and traditional cardiovascular risk factors with PAD in incident-dialysis patients enrolled in the CHOICE study by application of multivariate logistic-regression models with adjustment for confounders. Risk factors were determined by interview, record review, and laboratory analysis of frozen specimens.

Incidence of diabetes in youth in the United States.

Context: Data on the incidence of diabetes mellitus (DM) among US youth according to racial/ethnic background and DM type are limited.

Objective: To estimate DM incidence in youth aged younger than 20 years according to race/ethnicity and DM type.

Design, Setting, And Participants: A multiethnic, population-based study (The SEARCH for Diabetes in Youth Study) of 2435 youth with newly diagnosed, nonsecondary DM in 2002 and 2003, ascertained at 10 study locations in the United States, covering a population of more than 10 million person-years.

Release of glutamate decarboxylase-65 into the circulation by injured pancreatic islet beta-cells.

The enzyme glutamate decarboxylase-65 (GAD65) is a major autoantigen in autoimmune diabetes. The mechanism whereby autoreactivity to GAD65, an intracellular protein, is triggered is unknown, and it is possible that immunoreactive GAD65 is released by injured pancreatic islet beta-cells. There is a great need for methods by which to detect and monitor ongoing islet injury.

Evidence mounts for a role of the kidney in lipoprotein(a) catabolism.

Numerous studies have suggested a role of the kidney in lipoprotein(a) (Lp(a)) catabolism, but direct evidence is still lacking. Frischmann et al. demonstrate that the marked elevation of Lp(a) observed in hemodialysis patients results from a decrease in Lp(a) clearance rather than an increase in Lp(a) production, consistent with the notion that the kidney degrades Lp(a).

Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL.

HDL lowers the risk for atherosclerotic cardiovascular disease by promoting cholesterol efflux from macrophage foam cells. However, other antiatherosclerotic properties of HDL are poorly understood. To test the hypothesis that the lipoprotein carries proteins that might have novel cardioprotective activities, we used shotgun proteomics to investigate the composition of HDL isolated from healthy subjects and subjects with coronary artery disease (CAD).

Biochemical and bioimaging markers for risk assessment and diagnosis in major cardiovascular diseases: a road to integration of complementary diagnostic tools.

This report from the first International Course on Integrated Biomarkers, Biochemical and Bioimaging Endpoints in Cardiovascular Diagnosis, Prevention, Therapy and Drug Development provides the basis for optimizing diagnostic, prognostic and therapeutic information in four areas of cardiovascular medicine: primary prevention of cardiovascular diseases, acute coronary syndromes, heart failure and stroke. Risk stratification and treatment strategies can be refined and enhanced through integration of bioimaging and biochemical markers to characterize sub-clinical and clinical atherosclerosis. For the integrative approach to be useful, each of the biomarkers must be validated and cost-effective.

Plasma lipoprotein(a) indicates risk for 4 distinct forms of vascular disease.

Background: Increased lipoprotein(a) [Lp(a)] concentrations are predictive for coronary artery disease (CAD). The risk conferred by Lp(a) for other types of vascular disease compared with CAD has not been investigated within a single population. This study aimed to investigate Lp(a) risk association for 4 different types of vascular disease (including CAD) within a predominantly white population.

Serum lipids and glucose control: the SEARCH for Diabetes in Youth study.

Objective: To assess the relationship of serum lipid concentrations with glucose control in youth with diabetes mellitus.

Design: Cross-sectional analyses of data from the SEARCH for Diabetes in Youth study.

Setting: Multicenter study of youth with diabetes onset at younger than 20 years.

Standardization of insulin immunoassays: report of the American Diabetes Association Workgroup.

Background: Circulating insulin concentration in serum or plasma provides important information for the estimation of insulin secretion and insulin resistance. Currently, lack of standardization of insulin assays hinders efforts to achieve consistent measures for treatment guidelines.

Methods: A Workgroup convened by the American Diabetes Association evaluated 12 different commercial insulin methods from 9 manufacturers.

Rosiglitazone increases LDL particle size and buoyancy and decreases C-reactive protein in patients with type 2 diabetes on statin therapy.

A substantial number of individuals with type 2 diabetes mellitus (T2DM) demonstrate a predominance of small dense low-density lipoprotein (sdLDL), which is associated with an increased risk of cardiovascular disease (CVD). In some cases, sdLDL persists after treatment with a statin to reduce levels of LDL. The effect of the addition of a thiazolidinedione, rosiglitazone (RSG) (4 mg/day or 8 mg/day) to statin therapy on LDL phenotype and C reactive protein (CRP) levels was investigated in a 12- week, placebo-controlled study of 72 T2DM patients who were well controlled and on a statin, but who had persistently predominant sdLDL.

Apolipoprotein A1 and B.

This article reviews the evidence showing that apolipoprotein (apo) B and A-1 are superior to the conventional cholesterol indices as analytes in laboratory practice, indices of the lipoprotein-related risk for vascular disease, and measures of the adequacy of low-density lipoprotein-lowering therapy.

Lp(a) enhances coronary atherosclerosis in transgenic Watanabe heritable hyperlipidemic rabbits.

Elevated plasma levels of LDL and lipoprotein (a) [Lp(a)] are associated with an increased risk of atherosclerosis and coronary heart disease. However, it is not known whether Lp(a) would enhance the atherogenic effect of LDL on coronary atherosclerosis and myocardial infarction. To address this issue, we cross-bred human Lp(a) transgenic (Tg) rabbits with Watanabe heritable hyperlipidemic (WHHL) rabbits and evaluated the long-term (at the age of 2 years) effects of Lp(a) on the development of coronary atherosclerosis.

The burden of diabetes mellitus among US youth: prevalence estimates from the SEARCH for Diabetes in Youth Study.

Objective: Our goal was to estimate the prevalence of diabetes mellitus in youth <20 years of age in 2001 in the United States, according to age, gender, race/ethnicity, and diabetes type.

Methods: The SEARCH for Diabetes in Youth Study is a 6-center observational study conducting population-based ascertainment of physician-diagnosed diabetes in youth. Census-based denominators for 4 geographically based centers and enrollment data for 2 health plan-based centers were used to calculate prevalence.

Reference distributions for apolipoproteins AI and B and B/AI ratios: comparison of a large cohort to the world's literature.

Limiting the clinical utility of apolipoproteins AI (apo AI) and B (apo B) and the apo B/AI ratios until the last decade has been the lack of satisfactory methods for quantifying serum levels and credible reference materials. Great technological strides have been made in the last few years. The remaining barrier to more relevant and cost-effective use of serum protein data for diagnosis and prognosis has been the availability of widely recognized reliable reference intervals from birth to old age for both males and females.

Reference distributions for apolipoproteins AI and B and the apolipoprotein B/AI ratios: a practical and clinically relevant approach in a large cohort.

The two serum apolipoproteins in the highest concentrations, apolipoprotein (apo) AI and apolipoprotein B, and the apolipoprotein B/AI ratio are measured to assess clinical risk for atherosclerotic heart and peripheral vascular diseases. The study is based on a cohort of over 37,000 Caucasian individuals from northern New England measured in one laboratory by immunonephelometry using standardized reference materials. All samples received for protein analyses were accepted provided adequate identifying information was available.

Statins of different brain penetrability differentially affect CSF PLTP activity.

Background/aims: Phospholipid transfer protein (PLTP) and apolipoprotein E (apoE) are key proteins involved in lipoprotein metabolism in the peripheral circulation and in the brain. Several epidemiological studies suggested that use of 3-hydroxyl-3-methylglutaryl-coenzyme A reductase inhibitors (statins) reduces risk of Alzheimer's disease (AD). However, the effects of statins of differing blood-brain barrier (BBB) penetrability on brain-derived molecules in cognitively normal individuals are largely unknown.

Lipid abnormalities are prevalent in youth with type 1 and type 2 diabetes: the SEARCH for Diabetes in Youth Study.

Objective: Assessment of the prevalence of serum lipid abnormalities in US youth with type 1 or type 2 diabetes.

Study Design: The SEARCH for Diabetes in Youth Study was a cross-sectional, population-based study, conducted in six centers. Subjects were 2448 youth with diabetes who had a study examination.