Debate: "How low should LDL cholesterol be lowered for optimum prevention of vascular disease?" Viewpoint: "Below 100 mg/dl"

Arteriosclerotic vascular disease manifests as heart disease, stroke, aortic aneurysms, and peripheral vascular disease, and is a growing problem world-wide. The preventive efforts made so far have demonstrated that lowering LDL-C is one action that individuals and populations can do with significant success in delaying the onset of clinical events. Epidemiological studies and small clinical trials suggest that more aggressive and sustained lowering to LDL-C below 100 mg/dl could result in 50 to 70% reductions in vascular death. The full benefit of reducing LDL-C is only now being tested in adequate clinical trials

Metabolic studies in an unusual case of asymptomatic familial hypobetalipoproteinemia with hypoalphalipoproteinemia and fasting

A B S T R A C T A new kindred with asymptomatic hypobetalipoproteinemia is reported. The proband, age 67, differs from previously described cases in several respects: (a) unusually low levels of low density lipoprotein (LDL) cholesterol (4-8 mg/dl); (b) normal triglyceride levels; (c

Metabolism and proteomics of large and small dense LDL in combined hyperlipidemia: effects of rosuvastatin

Small dense LDL (sdLDL) has been reported to be more atherogenic than large buoyant LDL (lbLDL). We examined the metabolism and protein composition of sdLDL and lbLDL in six subjects with combined hyperlipidemia on placebo and rosuvastatin 40 mg/day. ApoB-100 kinetics in triglyceride-rich lipoproteins (TRLs), lbLDL (density [d] = 1.019-1.044 g/ml), and sdLDL (d = 1.044-1.063 g/ml) were determined in the fed state by using stable isotope tracers, mass spectrometry, and compartmental modeling. Compared with placebo, rosuvastatin decreased LDL cholesterol and apoB-100 levels in TRL, lbLDL, and sdLDL by significantly increasing the fractional catabolic rate of apoB-100 (TRL, +45%; lbLDL, +131%; and sdLDL, +97%), without a change in production. On placebo, 25% of TRL apoB-100 was catabolized directly, 37% was converted to lbLDL, and 38% went directly to sdLDL; rosuvastatin did not alter these distributions. During both phases, sdLDL apoB-100 was catabolized more slowly than lbLDL apoB-100 (

Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation.

Familial hypercholesterolaemia (FH) is a dominantly inherited disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL) cholesterol and causes premature coronary heart disease. There are at least 20million people with FH worldwide, but the majority remain undetected and current treatment is often suboptimal. To address this major gap in coronary prevention we present, from an international perspective, consensus-based guidance on the care of FH. The guidance was generated from seminars and workshops held at an international symposium. The recommendations focus on the detection, diagnosis, assessment and management of FH in adults and children, and set guidelines for clinical purposes. They also refer to best practice for cascade screening and risk notifying and testing families for FH, including use of genetic testing. Guidance on treatment is based on risk stratification, management of non-cholesterol risk factors, and safe and effective use of LDL lowering therapies. Recommendations are given on lipoprotein apheresis. The use of emerging therapies for FH is also foreshadowed. This international guidance acknowledges evidence gaps, but aims to make the best use of contemporary practice and technology to achieve the best outcomes for the care of FH. It should accordingly be employed to inform clinical judgement and be adjusted for country-specific and local health care needs and resources

Integrated Guidance on the Care of Familial Hypercholesterolaemia from the International FH Foundation: Executive Summary

Familial hypercholesterolaemia (FH) is a dominantly inherited disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL) cholesterol and causes premature coronary heart disease. There are at least 20 million people with FH worldwide, but the majority remains undetected and current treatment is often suboptimal. To address this major gap in coronary prevention we present, from an international perspective, consensus-based guidance on the care of FH. The guidance was generated from seminars and workshops held at an international symposium. The recommendations focus on the detection, diagnosis, assessment and management of FH in adults and children, and set guidelines for clinical purposes. They also refer to best practice for cascade screening and risk notifying and testing families for FH, including use of genetic testing. Guidance on treatment is based on risk stratification, management of non-cholesterol risk factors and safe and effective use of LDL lowering therapies. Recommendations are given on lipoprotein apheresis. The use of emerging therapies for FH is also foreshadowed. This international guidance acknowledges evidence gaps, but aims to make the best use of contemporary practice and technology to achieve the best outcomes for the care of FH. It should accordingly be employed to inform clinical judgment and be adjusted for country-specific and local healthcare needs and resources

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Original Articles National Lipid Association recommendations for patient-centered management of dyslipidemia: Part 1 -executive summary E M B A R G O E D

Abstract: Various organizations and agencies have issued recommendations for the management of dyslipidemia. Although many commonalities exist among them, material differences are present as well. The leadership of the National Lipid Association (NLA) convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. The current Executive Summary highlights the major conclusions in Part 1 of the recommendations report of the NLA Expert Panel and includes: (1) background and conceptual framework for formulation of the NLA Expert Panel recommendations; (2) screening and classification of lipoprotein lipid levels in adults; (3) targets for intervention in dyslipidemia management; (4) atherosclerotic cardiovascular disease risk assessment and treatment goals based on risk category; (5) atherogenic cholesterol-non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol-as the primary targets of therapy; and (6) lifestyle and drug therapies intended to reduce morbidity and mortality associated with dyslipidemia. Ó 2014 National Lipid Association. All rights reserved. Various organizations and agencies have issued recommendations for the management of dyslipidemia. The current Executive Summary highlights the major conclusions in Part 1 of the recommendations report of the NLA Expert Panel. The Executive Summary does not include a comprehensive reference list, but citations have been included for several key publications. The full report will include additional details on the rationale for the recommendations and citations to published research considered in the panel's deliberations. A presentation containing the main elements of these recommendations was made available to the public and other organizations involved with the prevention of atherosclerotic cardiovascular disease (ASCVD) to solicit input during an open comment period. Comments and suggestions were received from many members of the NLA as well as other individuals and organizations and were collated for consideration and adjudication by the panel in formulating the final set of recommendations contained herein. Part 1 of the NLA Expert Panel Recommendations for Patient-Centered Management of Dyslipidemia, will cover: Background and conceptual framework for formulation of the NLA Expert Panel recommendations; Screening and classification of lipoprotein lipid levels in adults; Targets for intervention in dyslipidemia management; ASCVD risk assessment and treatment goals based on risk category; Atherogenic cholesterol-non-high-density lipoprotein cholesterol (non-HDL-C) and low-density lipoprotein cholesterol (LDL-C)-as the primary targets of therapy; and Lifestyle and drug therapies intended to reduce morbidity and mortality associated with dyslipidemia

Original Articles National Lipid Association recommendations for patient-centered management of dyslipidemia: Part 1 -executive summary

Abstract: Various organizations and agencies have issued recommendations for the management of dyslipidemia. Although many commonalities exist among them, material differences are present as well. The leadership of the National Lipid Association (NLA) convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. The current Executive Summary highlights the major conclusions in Part 1 of the recommendations report of the NLA Expert Panel and includes: (1) background and conceptual framework for formulation of the NLA Expert Panel recommendations; (2) screening and classification of lipoprotein lipid levels in adults; (3) targets for intervention in dyslipidemia management; (4) atherosclerotic cardiovascular disease risk assessment and treatment goals based on risk category; (5) atherogenic cholesterol-non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol-as the primary targets of therapy; and (6) lifestyle and drug therapies intended to reduce morbidity and mortality associated with dyslipidemia. Ó 2014 National Lipid Association. All rights reserved. Various organizations and agencies have issued recommendations for the management of dyslipidemia. The current Executive Summary highlights the major conclusions in Part 1 of the recommendations report of the NLA Expert Panel. The Executive Summary does not include a comprehensive reference list, but citations have been included for several key publications. The full report will include additional details on the rationale for the recommendations and citations to published research considered in the panel's deliberations. A presentation containing the main elements of these recommendations was made available to the public and other organizations involved with the prevention of atherosclerotic cardiovascular disease (ASCVD) to solicit input during an open comment period. Comments and suggestions were received from many members of the NLA as well as other individuals and organizations and were collated for consideration and adjudication by the panel in formulating the final set of recommendations contained herein. Part 1 of the NLA Expert Panel Recommendations for Patient-Centered Management of Dyslipidemia, will cover: Background and conceptual framework for formulation of the NLA Expert Panel recommendations; Screening and classification of lipoprotein lipid levels in adults; Targets for intervention in dyslipidemia management; ASCVD risk assessment and treatment goals based on risk category; Atherogenic cholesterol-non-high-density lipoprotein cholesterol (non-HDL-C) and low-density lipoprotein cholesterol (LDL-C)-as the primary targets of therapy; and Lifestyle and drug therapies intended to reduce morbidity and mortality associated with dyslipidemia

Original Articles National Lipid Association recommendations for patient-centered management of dyslipidemia: Part 1 -executive summary

Abstract: Various organizations and agencies have issued recommendations for the management of dyslipidemia. Although many commonalities exist among them, material differences are present as well. The leadership of the National Lipid Association (NLA) convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. The current Executive Summary highlights the major conclusions in Part 1 of the recommendations report of the NLA Expert Panel and includes: (1) background and conceptual framework for formulation of the NLA Expert Panel recommendations; (2) screening and classification of lipoprotein lipid levels in adults; (3) targets for intervention in dyslipidemia management; (4) atherosclerotic cardiovascular disease risk assessment and treatment goals based on risk category; (5) atherogenic cholesterol-non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol-as the primary targets of therapy; and (6) lifestyle and drug therapies intended to reduce morbidity and mortality associated with dyslipidemia. Ó 2014 National Lipid Association. All rights reserved. Various organizations and agencies have issued recommendations for the management of dyslipidemia. The current Executive Summary highlights the major conclusions in Part 1 of the recommendations report of the NLA Expert Panel. The Executive Summary does not include a comprehensive reference list, but citations have been included for several key publications. The full report will include additional details on the rationale for the recommendations and citations to published research considered in the panel's deliberations. A presentation containing the main elements of these recommendations was made available to the public and other organizations involved with the prevention of atherosclerotic cardiovascular disease (ASCVD) to solicit input during an open comment period. Comments and suggestions were received from many members of the NLA as well as other individuals and organizations and were collated for consideration and adjudication by the panel in formulating the final set of recommendations contained herein. Part 1 of the NLA Expert Panel Recommendations for Patient-Centered Management of Dyslipidemia, will cover: Background and conceptual framework for formulation of the NLA Expert Panel recommendations; Screening and classification of lipoprotein lipid levels in adults; Targets for intervention in dyslipidemia management; ASCVD risk assessment and treatment goals based on risk category; Atherogenic cholesterol-non-high-density lipoprotein cholesterol (non-HDL-C) and low-density lipoprotein cholesterol (LDL-C)-as the primary targets of therapy; and Lifestyle and drug therapies intended to reduce morbidity and mortality associated with dyslipidemia