Discordance between high non-HDL cholesterol and high LDL-cholesterol among US adults.

Background: Although low-density lipoprotein cholesterol (LDL-C) is recommended as the primary marker to guide lipid-lowering therapy, some data suggest non-high-density lipoprotein cholesterol (non-HDL-C) may better reflect coronary heart disease risk. Discordance between these measures has not been evaluated.

Methods: We used data from the National Health and Nutrition Examination Surveys 2005-2010 (n = 4986) to examine the discordance between these lipid parameters.

Endothelial shear stress and blood viscosity in peripheral arterial disease.

This review examines the emerging role of endothelial shear stress (ESS) and blood viscosity on the initiation and progression of atherosclerosis in peripheral arterial disease. Among the variables determining ESS, blood viscosity has to date been the most overlooked by clinical researchers. Blood viscosity is a laboratory assessment that is minimally invasive and modifiable using pharmacologic therapy as well as by hemodilution.

Design and rationale of the GAUSS-2 study trial: a double-blind, ezetimibe-controlled phase 3 study of the efficacy and tolerability of evolocumab (AMG 145) in subjects with hypercholesterolemia who are intolerant of statin therapy.

Statins effectively lower low-density lipoprotein cholesterol (LDL-C), reducing cardiovascular morbidity and mortality. Most patients tolerate statins well, but approximately 10% to 20% experience side effects (primarily muscle-related) contributing to diminished compliance or discontinuation of statin therapy and subsequent increase in cardiovascular risk. Statin-intolerant patients require more effective therapies for lowering LDL-C.

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial.

Importance: Secretory phospholipase A2 (sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2 inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown.

Objective: To determine the effects of sPLA2 inhibition with varespladib on cardiovascular outcomes.

High-density lipoproteins: a consensus statement from the National Lipid Association.

For >4 decades it has been recognized that elevated serum levels of high-density lipoprotein cholesterol (HDL-C) are associated with reduced risk of cardiovascular disease (CVD) and its sequelae. Many prospective observational studies performed around the world have confirmed an inverse relationship between HDL-C and cardiovascular risk in people irrespective of sex, race, or ethnicity. Consequently, it was assumed that, by extension, raising HDL-C through lifestyle modification and pharmacologic intervention would reduce risk of CVD.

Systematic review: Evaluating the effect of lipid-lowering therapy on lipoprotein and lipid values.

Purpose: This systematic review was performed to summarize published experience using low density lipoprotein particle number (LDL-P) to monitor the efficacy of lipid-lowering pharmacotherapies.

Methods: Studies were identified from a literature search of MEDLINE (January 1, 2000 - June 30, 2012); and abstract searches of select conferences. All accepted studies reported mean (or median) nuclear magnetic resonance (NMR)-based LDL-P values for at least 10 subjects receiving lipid lowering pharmacotherapy.

Trends in the prevalence, awareness, treatment and control of high low density lipoprotein-cholesterol among United States adults from 1999-2000 through 2009-2010.

Marked increases in the awareness, treatment, and control of high low-density lipoprotein (LDL) cholesterol occurred among United States (US) adults from 1988-1994 to 1999-2004. An update to the Third Adult Treatment Panel guidelines was published in 2004, and it is unknown if these improvements have continued since the publication of these revised treatment recommendations. The aim of this study was to determine trends in the awareness, treatment, and control of high LDL cholesterol among US adults from 1999-2000 to 2009-2010 using nationally representative samples of US adults aged ≥20 years from 6 consecutive National Health and Nutrition Examination Surveys (NHANES) in 1999-2000 (n = 1,659), 2001-2002 (n = 1,897), 2003-2004 (n = 1,698), 2005-2006 (n = 1,692), 2007-2008 (n = 2,044), and 2009-2010 (n = 2,318).

Emerging anti-inflammatory drugs for atherosclerosis.

Introduction: Cardiovascular disease is the most common cause of morbidity and mortality worldwide. Inflammation is responsible for initiation and progression of atherosclerosis, and leads to plaque vulnerability. Evidence-based therapies reduce the risk of initial and recurrent cardiovascular events but many patients experience recurrent events due to the failure of conventional therapies to adequately address inflammation.

Awareness, treatment, and control of LDL cholesterol are lower among U.S. adults with undiagnosed diabetes versus diagnosed diabetes.

Objective: Diabetes is often undiagnosed, resulting in incorrect risk stratification for lipid-lowering therapy. We conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) 2005-2010 to determine the prevalence, awareness, treatment, and control of elevated LDL cholesterol (LDL-C) among U.S.

Shear rate specific blood viscosity and shear stress of carotid artery duplex ultrasonography in patients with lacunar infarction.

Background: This study describes a new method for determining site-specific vascular shear stress using dynamic measures of shear rate and blood viscosity (BV) in the carotid arteries, and examines characteristics of carotid arterial shear stress among patients with lacunar infarction.

Methods: Vascular shear stress measurements were conducted in 37 patients (17 lacunar infarction patients and 20 control subjects) using duplex ultrasonography. Vessel wall diameters and velocities were measured in each arterial segment at peak-systolic (PS) and end-diastolic (ED) phases, for calculation of PS/ED shear rates.

Biomarkers and sustainable innovation in cardiovascular drug development: lessons from near and far afield.

Future innovative therapies targeting cardiovascular disease (CVD) have the potential to improve health outcomes and to contain rising healthcare costs. Unsustainable increases in the size, cost and duration of clinical trial programs necessary for regulatory approval, however, threaten the entire innovation enterprise. Rising costs for clinical trials are due in large part to increasing demands for hard cardiovascular clinical endpoints as measures of therapeutic efficacy.

Elevated coronary whole blood viscosity in acute coronary syndrome patients.

Objectives: As most clinical studies measure whole blood viscosity (WBV) from peripheral samples, potential differences in WBV obtained from the coronary arteries are often ignored. This study investigated differences in WBV measured from coronary artery specimens in patients with and without acute coronary syndrome (ACS).

Methods And Results: Consecutive patients with chest pain who underwent diagnostic coronary angiography were divided into two groups [non-ACS (n = 16), ACS (n = 22)].

Attainment of goal/desirable lipid levels in patients with mixed dyslipidemia after 12 weeks of treatment with fenofibric acid and rosuvastatin combination therapy: a pooled analysis of controlled studies.

Background: Goal/desirable lipid levels are underachieved in patients with mixed dyslipidemia. These patients may have substantial residual risk of cardiovascular disease even while receiving optimal LDL-C-lowering therapy and may require additional therapy to improve multiple lipid/lipoprotein levels.

Objective: To evaluate attainment of goal/desirable levels of lipids/lipoproteins after 12-week treatment with combination rosuvastatin + fenofibric acid versus rosuvastatin monotherapy.

Colesevelam improved lipoprotein particle subclasses in patients with prediabetes and primary hyperlipidaemia.

Background: A randomised, double-blind, placebo-controlled study evaluated lipid- and glucose-lowering effects of colesevelam in patients with prediabetes and primary hyperlipidaemia. We report the effect of colesevelam on lipoprotein particle concentration and particle size (determined by nuclear magnetic resonance spectroscopy) in these patients.

Methods: Adults with prediabetes (World Health Organization criteria), low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (≥2.

Modulating peroxisome proliferator-activated receptors for therapeutic benefit? Biology, clinical experience, and future prospects.

Clinical trials of cardiovascular disease (CVD) prevention in patients with type 2 diabetes mellitus primarily have been directed at the modification of a single major risk factor; however, in trials that enroll patients with and without diabetes, the absolute risk in CVD events remains higher in patients with diabetes. Efforts to reduce the macrovascular and microvascular residual risk have been directed toward a multifactorial CVD risk-factor modification; nonetheless, long-term complications remain high. Dual-peroxisome proliferator-activated receptor (PPAR) α/γ agonists may offer opportunities to lower macrovascular and microvascular complications of type 2 diabetes mellitus beyond the reductions achieved with conventional risk-factor modification.

Initial combination therapy with metformin plus colesevelam improves lipoprotein particles in patients with early type 2 diabetes mellitus.

Background: The bile acid sequestrant colesevelam has been shown to significantly reduce low-density lipoprotein particle concentration (LDL-P) in adults with primary hyperlipidemia or type 2 diabetes mellitus (T2DM).

Objective: To assess the effect of initial combination therapy with metformin plus colesevelam on lipoprotein particles in patients with T2DM (secondary efficacy variables).

Methods: This 16-week, randomized, double-blind, placebo-controlled study enrolled drug-naïve adults with T2DM, glycated hemoglobin 6.

Importance of blood rheology in the pathophysiology of atherothrombosis.

Elevated blood viscosity is an integral component of vascular shear stress that contributes to the site specificity of atherogenesis, rapid growth of atherosclerotic lesions, and increases their propensity to rupture. Ex vivo measurements of whole blood viscosity (WBV) is a predictor of cardiovascular events in apparently healthy individuals and studies of cardiovascular disease patients. The association of an elevated WBV and incident cardiovascular events remains significant in multivariate models that adjust for major cardiovascular risk factors.

Phospholipase A2 enzymes and the risk of atherosclerosis.

Certain members of the phospholipase A(2) superfamily of enzymes have established causal involvement in atherosclerosis, thus at least two groups of this family of enzymes have been considered potential candidates for the prevention of cardiovascular events. Recently completed experimental animal studies, human biomarker data, vascular imaging studies, and genome-wide atherosclerosis studies provide the rationale for proceeding with clinical outcome trials directed at inhibition of secretory phospholipase A(2) and lipoprotein-associated phospholipase A(2). A clinical trial with the sPLA(2) inhibitor varespladib methyl was recently terminated, while clinical trials with the Lp-PLA(2) inhibitor darapladib are being conducted in coronary heart disease patients.

Modulation of oxidative stress, inflammation, and atherosclerosis by lipoprotein-associated phospholipase A2.

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), also known as platelet-activating factor acetylhydrolase (PAF-AH), is a unique member of the phospholipase A(2) superfamily. This enzyme is characterized by its ability to specifically hydrolyze PAF as well as glycerophospholipids containing short, truncated, and/or oxidized fatty acyl groups at the sn-2 position of the glycerol backbone. In humans, Lp-PLA(2) circulates in active form as a complex with low- and high-density lipoproteins.

Study design, rationale, and baseline characteristics: evaluation of fenofibric acid on carotid intima-media thickness in patients with type IIb dyslipidemia with residual risk in addition to atorvastatin therapy (FIRST) trial.

Purpose: Elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) levels contribute to cardiovascular disease risk and can be effectively treated with fenofibric acid. A trial is under way to evaluate the effect of once-daily fenofibric acid or placebo on carotid intima-media thickness (CIMT) progression in patients with controlled low-density lipoprotein cholesterol (LDL-C) levels achieved through atorvastatin treatment, but with high TG and low HDL-C levels.

Methods: In this multicenter, double-blind study, 682 patients were randomized to once-daily delayed-release capsules of choline fenofibrate 135 mg (fenofibric acid [Trilipix(®); Abbott, North Chicago, IL]) or placebo plus atorvastatin treatment after a 2- to 10-week diet and atorvastatin run-in period.