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Elevated remnant lipoprotein cholesterol (RLP-C) levels increase cardiovascular disease risk. However, RLP-C measurement methods are not standardized, leading to variations across studies.To evaluate the effect of ezetimibe (Eze) + statins vs statin monotherapy on RLP-C using immunoseparation (IM), vertical auto profile (VAP) ultracentrifugation, and calculated RLP-C measurement methods.This post hoc analysis evaluated data pooled from 3 first-line (all-statin [simvastatin 10/20/40/80 mg] vs Eze + statin [Eze 10 mg + simvastatin]) and 2 second-line (statin [atorvastatin uptitrated to 40/80 mg] vs statin + Eze [atorvastatin 20/40 mg + Eze 10 mg]) studies. Similarity of RLP-C methods was evaluated using Pearson correlation coefficients and Bland-Altman plots. RLP-C changes and percent changes from baseline were measured by all 3 methods in first-line and VAP and calculated methods in second-line studies.Correlations between methods were generally moderate to strong for RLP-C levels, changes, and percent changes across treatment groups (r = 0.29-0.79) but with little evidence of agreement by Bland-Altman plots. Baseline RLP-C levels for Eze + statin vs all-statin groups were lower by IM (14.0 vs 14.0) compared with VAP (36.9 vs 35.9) and calculated (32.8 vs 33.3) methods. RLP-C changes (mg/dL) and percent changes from baseline were significantly greater (P .01) with Eze + statins vs statins by VAP, calculated, and IM methods (between-treatment differences: -5.0 and -12.0, -2.0 and -5.4, and -1.5 and -12.1, respectively) in first-line, and VAP and calculated methods (between-treatment differences: -5.0 and -19.9 and -2.0 and -7.3) in second-line studies.Although the 3 methods showed little agreement, each supported Eze + statins for achieving greater RLP-C reductions vs statin monotherapy; variability of results reinforces urgent need to standardize RLP-C measurements.

Background Little is known regarding relationships between high-sensitivity C-reactive protein (hsCRP) and lipoproteins other than low-density lipoprotein cholesterol (LDL-C). High-density lipoprotein (HDL), with both anti-inflammatory and cholesterol-mediating effects, is of particular interest. This exploratory analysis assessed associations between hsCRP and lipids in older (>65 years) patients with moderate and/or high cardiovascular disease risk, before and after treatment with ezetimibe/simvastatin (E/S) or atorvastatin (ATV). Methods An analysis of a multicenter, randomized, double-blind, 12-week study. Correlations were assessed in 1054 patients with both baseline and 12-week hsCRP ≤10 mg/L, pooled across doses of E/S (10/20 and 10/40 mg) and ATV (10, 20, and 40 mg), and combined E/S + ATV treatments. Because of multiple comparisons, observed relationships were considered significant only if P values were Results Correlations between baseline levels of hsCRP and either LDL-C, non–HDL-C, or apolipoprotein B were weak and nonsignificant in the E/S, ATV, and E/S + ATV groups. After 12 weeks of treatment, these correlations increased slightly and significantly in all groups, except for LDL-C in the ATV group. HDL-C was significantly but inversely correlated with hsCRP in the ATV and E/S + ATV groups at baseline, and in all groups at 12 weeks. Only with HDL-C did change correlate with change in hsCRP in both the E/S and combined groups. Conclusions Relationships between hsCRP and lipid factors in older patients were weak at baseline and somewhat stronger after treatment. HDL-C was inversely and consistently correlated with baseline and 12-week on-treatment hsCRP and with therapy-induced changes in HDL-C and hsCRP.

The roundtable this month will involve a discussion of two new drugs that have been approved by the Food and Drug Administration for the reduction of low-density lipoprotein cholesterol (LDL-C). The Food and Drug Administration approved the first of these, alirocumab as an "adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL [low-density lipoprotein]-cholesterol." Evolucumab has similar indications plus an indication specifically for treatment of homozygous familial hypercholesterolemia. This sets the stage for their clinical use and in this roundtable, we will discuss with two experts, the implications of these indications for the practicing physician. Dr McKenney and Dr Moriarty have had extensive experience in the conduct of clinical trials that provided the evidence of safety and efficacy of these so called PCSK9 inhibitors.

Preview Of the lipid-lowering agents, niacin (nicotinic acid) has been available the longest. Its efficacy in lowering LDL cholesterol and triglyceride levels and in raising HDL cholesterol levels makes it very useful for many patients. However, the frequency of adverse reactions in persons taking niacin has inhibited physicians from using the agent optimally in practice. In this article, Dr Brown examines its current role in the treatment of dyslipidemia.

The first efforts to uncover the causes of cardiovascular disease focused on the behavioral, now called lifestyle habits of populations. Diet, exercise, and smoking were recognized as important issues with strong relationships in community-based observational studies such as the Seven Countries study, the Framingham Heart Study, and the Western Electric Study in Chicago. The first meaningful intervention in the United States was the dietary recommendations made by the American Heart Association in 1963 and the Surgeon General's Report on Smoking and Health in 1964. The American public listened and a very large change occurred in food consumption data and cigarette smoking over the next decade. These changes were mainly focused on men because the incidence of myocardial infarction was much higher in middle aged and older men than women. As smoking prevalence has decreased in men and increased in women and the population has aged, the differences in major vascular events have virtually disappeared. Women still enjoy a longer period of low rates but eventually the incidence rates approach those of men. As we constantly attempt to demonstrate ways of reducing risk by improved lifestyle it behooves us to re-evaluate the potential differences in gender response and adjust our expectations accordingly as clinicians.

The availability of food quickly prepared at lower cost and with consistent quality and convenience has made a variety of restaurant chains extremely popular. Commonly referred to as the fast food industry, these companies have stores on virtually every street corner in cities large and small. Fast foods contribute to energy intake, and depending on the food choices made, provide foods and nutrients that should be decreased in the diet. As Americans have become more conscious of their risk factors for heart disease and recognized eating patterns as a contributor to blood cholesterol levels, high blood pressure, obesity, and diabetes, the fast food industry has attempted to adjust their menus to provide more healthful choices. The Roundtable discussion in this issue of the Journal will focus on the importance of this industry as a source of foods that could help address our population-wide efforts to reduce cardiovascular disease.

Elderly population; Blood cholesterol; Lipid drugs; Vascular disease; Atherosclerosis Abstract: Using drugs in the elderly requires some special considerations; however, there is no ques- tion that our older patients benefit tremendously from the use of agents that prevent and/or control many of the risk factors for vascular disease that are most prevalent in the latter years of life. Recently, the American College of Cardiology and the American Heart Association issued guidelines for the management of blood cholesterol elevations. For the first time, little specific guidance was given for the age group older than 75 years of age. The rationale given for this approach was primarily that the data from randomized trials comparing drug therapy to treatment with placebos were inadequate for such recommendations. There was also concern regarding safety in this group. This Roundtable will consider this lack of recommendations in a broader context than statin trials. 2014 National Lipid Association. All rights reserved.

There are several inherited disorders that involve abnormal storage of lipids in tissues leading to severe compromise of organs. Sadly, these are often accompanied by lifelong morbidity and early mortality. Disorders such as Gaucher, Fabry, and lysosomal acid lipase deficiencies (Wolman and cholesteryl ester storage diseases) have been known for many years, and provide a difficult and frustrating set of problems for patients, their families, and their physicians. With recombinant methods of protein synthesis, it is now possible to literally replace the defective enzymes that underlie the basic pathophysiology of many such disorders. The delivery of these enzymes into the affected cells is possible because of their location in the lysosomes where the natural degradation of their lipid substrates occurs. I have asked 2 well-known investigators to join us for this Roundtable. These are professors who have been involved with the research that has made this type of therapy possible and who have participated in the clinical trials that demonstrated the value of enzyme replacement therapy. They are Dr. Robert Desnick, dean of Genetic and Genomic Medicine and professor and chairman emeritus of the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai in New York City, and Dr. Gregory Grabowski, professor of Microbiology, Biochemistry, and Pediatrics, at the University of Cincinnati College of Medicine. Dr. Grabowski recently retired from that school to become the chief science officer of Synageva, a company involved in producing enzymes for this type of therapy.

Our topic is the evaluation and treatment of obesity in the practice of medicine. I am joined by Dr. Harold Bays who has carried out many studies of dietary and medical interventions in patients with obesity. I am also honored to have Dr. George Bray who is known for his many years of research into causes of obesity and its therapy. Our goal is bring this clinical and research experience to bear on the office practice of medicine.

One of the most serious challenges to all physicians is the maintenance of therapy for those chronic disorders that at present cannot be cured. Elevations of low-density lipoprotein and very low-density lipoprotein are among the most common of those disorders. We are now in an era in which 2 fundamental developments of modern technology have come together. These are the supply of effective and safe lipid-lowering drugs as well as the ability to closely monitor pertinent measures in our patients. The rapid conversion of our health care systems into large teams of professionals with direct support from third-party payers has made it possible to coordinate chronic care through electronic medical records and electronic communication. As a result, with effective planning and organization, we can guide our patients toward better adherence to successful medical regimens. These issues are evolving rapidly and have been presented in some detail in the December 2013 issue of the Journal. I was joined in this Roundtable discussion by 3 health professionals who have had extensive experience with the application of health information technology. They are Dr. Karen Aspry and Dr. Alan Brown, both clinical cardiologists, and Dr. Matthew Ito, a Doctor of Pharmacy.

During the American Heart Association's Scientific Sessions in November 2014, this Editor had the opportunity to interview Dr. Scott Grundy regarding the new recommendations for guideline development that was issued by the International Atherosclerosis Society. (The full document is published in this issue of the journal). In developing this report, Dr. Grundy chaired a panel of international experts who spent 1 year in consideration of new evidence and regional concerns regarding the clinical management of lipoprotein disorders and vascular disease prevention. His experience in developing the Adult Treatment Panel Reports from the National Cholesterol Education Program in the United States and his extensive research in lipoprotein physiology and related disorders makes him unique in offering the expertise for worldwide leadership in this effort.

Familial hypercholesterolemia (FH) is a dominantly inherited disorder present from birth that markedly elevates plasma low-density lipoprotein 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 noncholesterol risk factors, and the safe and effective use of low-density lipoprotein-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 used to inform clinical judgment and be adjusted for country-specific and local healthcare needs and resources. (C) 2014 National Lipid Association. All rights reserved.

Clinical lipidologists are often asked to manage patients with severely elevated low-density lipoprotein cholesterol (LDL-C) and other apolipoprotein B-containing lipoproteins. Statins at maximum doses and in combination with other drugs may not achieve adequate reductions in LDL-C in such patients. The most dramatic elevations are usually in patients with genetic abnormalities in the LDL receptor gene on both chromosome pairs. LDL-C values well in excess of 400 mg/dL are not fully responsive to current treatments. In the past few months, the Food and Drug Administration has approved 2 new drugs for special use in such patients; these are mipomersen and lomitapide. During the National Lipid Association's Scientific Sessions, 2 highly experienced clinician scientists who have completed research studies with these agents agreed to answer questions pertinent to the prescription use of these agents. These scientists are Dr Anne Goldberg from Washington University in St. Louis and Dr Daniel Rader from the University of Pennsylvania.

Many factors enter into the decision by the Food and Drug Administration (FDA) to approve a new drug for use by physicians and other health care providers in treating diseases. Initially, the FDA authority was restricted to issues of safety and only later did the documentation of efficacy become part of the review process required for approval. However, all drugs have the potential for causing harm at some dose level to all and at lower doses in certain patients with vulnerability to the particular pharmacology of the agent. As new drugs have been designed to manage disorders that are uncommon, but of significant consequence, they may have adverse effects that are acceptable only because they are so uniquely beneficial to these specific conditions. The risk of these adverse effects may be acceptable since the benefit can outweigh the harm in most patients and the adversity can be predicted and managed. The approval of this category of drugs has grown rapidly since definition of a mechanism of action to manage and modify the risk has been provided by a process known as known as Risk Evaluation and Mitigation Strategy or "REMS." In 2007, the Food and Drug Administration Amendments Act (FDAAA) allowed the FDA to require postmarketing studies and the authority to mandate the implementation of a REMS for drugs with efficacy but documented potential for harm. Two relatively new drugs useful in the management of severe elevations of low-density lipoprotein cholesterol have been approved under a requirement for a REMS. These are lomitapide, an inhibitor of microsomal triglyceride transfer protein and mipomersen, an antisense oligonucleotide which reduces the synthesis of apolipoprotein B.

The HIV-AIDS epidemic has provided one of the more challenging problems in treatment of infectious diseases. As antiretroviral drugs made a very marked improvement in controlling the immunodeficiency state and patients gained in their longevity, the concern with lipid abnormalities came to the fore. The initial drugs produced a form of metabolic syndrome accompanied by very elevated plasma triglyceride concentrations. Furthermore, the drugs used to control the virus were often metabolized in a manner that interfered with lipid lowering drug therapy. The antiviral agents have improved in many respects and the experience in managing the lipid disorders has added greatly to our ability to control these problems as well. This roundtable discussion has been conducted with 4 physicians who have been involved in management of large cohorts of patients with HIV infection and who have had a special interest in reduction of vascular disease risk.

The diagnosis of familial hypercholesterolemia is usually straightforward. The severely elevated low-density lipoprotein cholesterol and the occurrence of high concentrations of low-density lipoprotein cholesterol in the parents provide the diagnosis. The presence of tendon xanthomata is confirmation but not necessary. However, this relatively simple picture becomes much more complicated when one attempts to define the genetic variants that actually produced this clinical syndrome. In this Roundtable discussion, I am joined by two experts in the identification of genetic abnormalities discovered in those with phenotypic familial hypercholesterolemia. Dr. John Kane from the University of California, San Francisco, and Dr. Daniel Rader from the University of Pennsylvania share their knowledge in and experience with this topic.

Editor–in–Chief, The Journal of Clinical Lipidology, Charles Howard Candler Professor of Internal Medicine Emeritus, Emory University School of Medicine, 1670 Clairmont Road, Atlanta, GA 30033 USA (Dr. Brown); Department of Internal Medicine, Texas AM and Pediatric Cardiology, Nemours Cardiac Center, Alfred I. duPont Hospital for Children, Wilmington, DE 19899 USA (Dr. Gidding)

BACKGROUND Peripheral arterial compliance (PAC) is a measure of the ability of the vascular tree to dilate in response to a pressure wave. Reduced PAC is seen in patients with psychiatric diagnoses and has been associated with increased risk for stroke, myocardial infarction, and mortality. The objective of this pilot study was to identify predictors of reduced PAC in subjects with psychiatric diagnoses. METHODS Male psychiatric subjects (N = 77) were studied in a cross-sectional study of medication effects on PAC conducted from August 2005 to February 2010. Calf and thigh compliance were modeled in separate linear regressions. The models were adjusted for age, race, smoking status, presence or absence of the metabolic syndrome, current treatment with a statin, diagnosis of schizophrenia or schizoaffective disorder, current antipsychotic treatment, and body mass index (BMI). RESULTS Of the 77 subjects (mean ± SD age of 53.7 ± 8.8 years), 41 were white, 36 were black, and 27 were diagnosed with schizophrenia or schizoaffective disorder (DSM-IV criteria). Fifty participants were being treated with an antipsychotic medication, while the remaining 27 were off of antipsychotics for at least 2 months. Our model explained 27% of the variance in calf compliance. Black subjects had reduced calf compliance compared to white subjects (P = .02). Having metabolic syndrome was associated with reduced PAC at a trend level (P < .08), and BMI (P = .004) and BMI2 (P = .011) were significant predictors of calf compliance. Schizophrenia versus other psychiatric diagnoses and antipsychotic treatment were not significantly associated with calf compliance. CONCLUSIONS In this pilot study, significant predictors of calf compliance were race (black vs white) and BMI. PAC is a noninvasive measure that may be a predictor of cardiovascular risk in psychiatric patients. The reduced PAC seen in patients with psychiatric diagnoses does not appear to be directly related to their diagnosis or antipsychotic treatment but rather to other characteristics inherent to the subject. Future studies are warranted to better understand the pathophysiology of PAC including but not limited to inflammation in psychiatric patients.

The focus of this Roundtable discussion is the mysterious lipoprotein Lp(a). There is growing evidence that it confers significant risk of vascular disease at high plasma concentrations. The concentration in plasma is highly variable from person to person but relatively stable in any given individual. The issue of defining this as a target of treatment has many facets, which have stymied clinicians in their management of this risk factor. The pertinent questions are many such as: "How does one obtain the most meaningful measure as there are so many components?" "What agents are truly effective in lowering this lipoprotein particle?" "Does direct treatment with reduction affect risk?" "How does low-density lipoprotein–cholesterol relate to the risk?" "If low-density lipoprotein-cholesterol is reduced, is there residual risk related directly to Lp(a)?" and "Are there effective therapies under development?" For this Roundtable, I am fortunate to have three experts that have studied these questions in various settings and have agreed to answer my questions relevant to these clinical issues. These include Dr Moriarty from the University of Kansas, Dr Remaley from the National Institutes of Health, and Dr Tsimikas from the University of California San Diego.

Editor–in–Chief, The Journal of Clinical Lipidology, Charles Howard Candler Professor of Internal Medicine, Emeritus, Emory University School of Medicine, 1670 Clairmont Road, Atlanta, GA 30033, USA (Dr. Brown); Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA (Dr. Brook); Harvard School of Medicine, Massachusetts General Hospital, Boston, MA, USA (Dr. Hemphill); and Division of Clinical Pharmacology, University of Kansas Medical Center, Kansas City, KS, USA (Dr. Moriarty)

In clinical lipidology, we have focused our major efforts in defining risk status and specifying the targets of therapy by using the cholesterol content of the lipoproteins. However, we now know that these measures are variable and that they may not reveal all the valuable information that can be used to treat our patients. The amount of cholesterol in each lipoprotein can be quite different in different patients. The number of particles containing apolipoprotein B (apoB) can be abnormally high with a value for low-density lipoprotein cholesterol, which is within our guidelines. Furthermore, the content of apoC3 in apoB-containing lipoproteins can predict risk without a close association with triglycerides or cholesterol. The genome-wide association studies and studies in special families with known genetic polymorphisms have been particularly revealing relationships between these vascular risk.

Editor–in–Chief, The Journal of Clinical Lipidology, Charles Howard Candler Professor of Internal Medicine Emeritus, Emory University School of Medicine, 3208 Habersham Road, Atlanta, GA 30305, USA (Dr. Brown); Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY, USA (Dr. Bays); Clinical Professor and Director of Preventive Cardiology, and President, Chief Executive Officer and Executive Medical Director, Chicago Center for Clinical Research, Radiant Research, Chicago, IL, USA (Dr. Davidson); and Associate Professor of Medicine, Washington University School of Medicine, St. Louis, MO, USA (Dr. Goldberg)

Editor–in–Chief, The Journal of Clinical Lipidology, Charles Howard Candler Professor of Internal Medicine, Emory University School of Medicine, 1670 Clairmont Road, Atlanta, GA 30033, USA (Dr. Brown); Director, Division of Pediatric Endocrinology and Diabetes, Phoenix Children’s Hospital and Clinical Professor of Pediatrics, University of Arizona College of Medicine, Phoenix, AZ, USA (Dr. Wilson); Chief, Pediatric Endocrinology and Diabetes and Robert C. and Veronica Atkins Professor of Pediatrics, Duke University Medical Center, Durham, NC, USA (Dr. Freemark); and Chief, Lipid Research and Atherosclerosis Division and Director, Johns Hopkins Lipid Clinic and Professor of Pediatrics and Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA (Dr. Kwiterovich)

Editor–in–Chief, The Journal of Clinical Lipidology, Charles Howard Candler Professor of Medicine Emeritus, Emory University School of Medicine, 1670 Clairmont Road, Atlanta, GA 30033, USA (Dr. Brown); Professor of Medicine, Emory University School of Medicine and Chief of Cardiology, Grady Memorial Hospital, Atlanta, GA, USA (Dr. Wenger); Professor of Medicine, University of Alabama School of Medicine, Birmingham, AL, USA (Dr. Bittner); and Professor of Medicine and Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA (Dr. Brinton)

Summary: Statins are powerful agents for the reduction of low‐density lipoprotein cholesterol (LDL‐C) and reduction of cardiovascular risk. Newly developed statins with increased potency, such as rosuvastatin (Crestor(TM)) and NK‐104 (in earlier clinical development), are capable of achieving marked LDL‐C reductions. Cholesterol‐lowering agents with mechanisms of action distinct from those of the statins are in active development. These include bile transport inhibitors. such as improved bile acid‐absorbing resins and specific inhibitors of the ileal Na(+)/bile acid cotransporter. There are also specific inhibitors of cholesterol absorption, such as ezetimibe, which may provide cholesterol lowering that is additive to that achieved with statin treatment. Another approach is to reduce cardiovascular risk by modifying atherosclerotic processes within the arterial wall, as represented by the acyl CoA:cholesterol acyltransferase (ACAT) inhibitor avasimibe; ACAT inhibitors may reduce atherosclerotic lesions by inhibiting macrophage cholesterol storage.

Editor–in–Chief, The Journal of Clinical Lipidology, Charles Howard Candler Professor of Internal Medicine Emory University School of Medicine, 1670 Clairmont Road, Atlanta, GA 30033 (Dr. W.V. Brown); Director, Midwest Heart Disease Prevention Center and Interventional Cardiologist Midwest Heart Specialists, Naperville, IL, USA and Clinical Associate Professor of Medicine, Loyola Stritch School of Medicine (Dr. A.S. Brown); Professor of Medicine and Radiology Director Cardiac Imaging Center, Emory University, Atlanta, GA, USA (Dr. Raggi); Director of Preventive Cardiology, Emory Clinic and Associate Professor of Medicine (Cardiology), Emory University School of Medicine, Atlanta, GA, USA (Dr. Sperling)

Patients with diabetes or metabolic syndrome frequently have higher triglycerides, lower high-density lipoprotein (HDL) cholesterol, and more particles containing apolipoprotein B (ApoB); this combination contributes significantly to their cardiovascular risk. Optimal management of dyslipidemia and increased atherosclerotic risk requires a fundamental understanding of diabetic dyslipidemia, the clinical evidence for different interventional strategies, and the potential benefit of achieving therapeutic targets. For this review, we considered guidelines, recent reviews, and clinical trial results. The features of dyslipidemia in type 2 diabetes and the metabolic syndrome are linked metabolically and are related to central adiposity and insulin resistance. Levels of ApoB and HDL cholesterol are particularly important markers of risk. Guidelines broadly agree that low-density lipoprotein (LDL) cholesterol should be reduced below population average levels. Additional or secondary strategies in patients with diabetes or the metabolic syndrome are to decrease non-HDL cholesterol, ApoB and/or LDL particle concentration, to increase HDL cholesterol, and to reduce triglycerides. Lifestyle changes and statins are the bedrock of treatment, although second-line treatment using fibrates or niacin will likely benefit many patients with residual risk. Ezetimibe, too, has a favorable effect on lipid profile and inflammatory biomarkers of risk. Dyslipidemia in type 2 diabetes and metabolic syndrome has a distinct profile, suggesting the need for a tailored therapy that targets the key features of lowered HDL cholesterol and raised triglycerides, in addition to the primary antiatherogenic strategy of lowering ApoB-containing lipoproteins, such as LDL. With the prominent failure of some recent intervention trials, new therapeutic strategies-particularly safe and effective means to raise HDL-are needed to manage dyslipidemia in this high-risk population.

Cardiovascular disease (CVD) is the number one cause of mortality in men and women. Currently, two thirds of US adults are overweight or obese. CVD and obesity are closely linked and together take a substantial toll on the health of individuals and the community. It is creating a growing burden on public health and financial difficulties in both personal and institutional funding of health care. A review of recent scientific literature reveals that modest weight loss of 5% to 10% ameliorates cardiometabolic risk factors and improves health outcomes. To date, successful weight-loss interventions have been elusive. The choice of weight-loss medications is limited, and the risks of surgical intervention demand that this option be reserved for those patients with extreme obesity. Research has elucidated an improved understanding of the mechanisms leading to obesity and disease. The potential role of hormones, such as leptin and adiponectin, in altering metabolism and vascular disease is better understood. The endocannabinoid system is now recognized as a potentially viable pathway to modulate appetite and energy, lipid, and glucose metabolism.

The National Lipid Association (NLA) Annual Summary of Clinical Lipidology is a yearly updated summary of principles important to the patient-centered evaluation, management, and care of patients with dyslipidemia. This summary is intended to be a "living document," with future annual updates based on emerging science, clinical considerations, and new NLA Position, Consensus, and Scientific Statements, thus providing an ongoing resource that applies the latest in medical science towards the clinical management of patients with dyslipidemia. Topics include the NLA Recommendations for Patient-Centered Management of Dyslipidemia, genetics, Familial Hypercholesterolemia, secondary causes of dyslipidemia, biomarkers and advanced lipid testing, nutrition, physical activity, obesity, adiposopathy, metabolic syndrome, diabetes mellitus, lipid pharmacotherapy, lipid-altering drug interactions, lipoprotein apheresis, dyslipidemia management and treatment based upon age (children, adolescents, and older individuals), dyslipidemia considerations based upon race, ethnicity and gender, dyslipidemia and human immune virus infection, dyslipidemia and immune disorders, adherence strategies and collaborative care, and lipid-altering drugs in development. Hyperlinks direct the reader to sentinel online tables, charts, and figures relevant to lipidology, access to online atherosclerotic cardiovascular disease risk calculators, worldwide lipid guidelines, recommendations, and position/scientific statements, as well as links to online audio files, websites, slide shows, applications, continuing medical education opportunities, and patient information.

The Roundtable in this issue of the journal has to do with a very important topic that has generated much debate and confusion over the years. Do women and men need and receive the same type and intensity of drug therapy to appropriately reduce the incidence of major vascular events? Second, do women respond to lipid-lowering medications with similar changes in lipoprotein levels and with equivalent reduction in major cardiovascular clinical events? I am very pleased to have 3 experts in different aspects of this issue. Dr Rachel Mackey is a cardiovascular epidemiologist in the University of Pittsburgh who is now actively involved in analyzing large data sets from community-based observational studies. Dr Thomas Pearson has many years of cardiovascular experience in clinical trials and observational studies that go to the issues faced by physicians in practice. He is the current Executive Vice President for Research and Education at the University of Florida Health Science Center. Dr Carl Orringer is a professor at the University of Miami School of Medicine who has years of experience in teaching preventive cardiology.

The leadership of the National Lipid Association convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. An Executive Summary of those recommendations was previously published. This document provides support for the recommendations outlined in the Executive Summary. The major conclusions include (1) an elevated level of cholesterol carried by circulating apolipoprotein B-containing lipoproteins (non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol [LDL-C], termed atherogenic cholesterol) is a root cause of atherosclerosis, the key underlying process contributing to most clinical atherosclerotic cardiovascular disease (ASCVD) events; (2) reducing elevated levels of atherogenic cholesterol will lower ASCVD risk in proportion to the extent that atherogenic cholesterol is reduced. This benefit is presumed to result from atherogenic cholesterol lowering through multiple modalities, including lifestyle and drug therapies; (3) the intensity of risk-reduction therapy should generally be adjusted to the patient's absolute risk for an ASCVD event; (4) atherosclerosis is a process that often begins early in life and progresses for decades before resulting a clinical ASCVD event. Therefore, both intermediate-term and long-term or lifetime risk should be considered when assessing the potential benefits and hazards of risk-reduction therapies; (5) for patients in whom lipid-lowering drug therapy is indicated, statin treatment is the primary modality for reducing ASCVD risk; (6) nonlipid ASCVD risk factors should also be managed appropriately, particularly high blood pressure, cigarette smoking, and diabetes mellitus; and (7) the measurement and monitoring of atherogenic cholesterol levels remain an important part of a comprehensive ASCVD prevention strategy.

Objectives: Dyslipidemia has become a common problem in HIV disease, especially in patients on combination antiretroviral (ARV) therapy. However, little data are available to evaluate lipid abnormalities in women on ARV therapy. Methods: Using a cross-sectional design, the prevalence of abnormal plasma lipid and lipoprotein concentrations as well as other biomarkers for vascular disease was determined in 184 HIV-positive women from 2 HIV clinics in Atlanta during 2002. Results: Most of the women were African American (89%), with median age of 41 years (range 21-72); 6% were diabetic, 44% smoked, and 67% were overweight. ARV therapy defined the comparison groups that included treatment with a protease inhibitor (PI)-based regimen for more than 3 months in 76 (41%), treatment with a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen for more than 3 months in 38 (20%), and no ARV therapy for the past 3 months in 70 (38%). Women being treated with a PI or NNRTI had higher total cholesterol and triglyceride levels than patients on no therapy (P < 0.05 for each). Women treated with either PIs or NNRTIs had significantly higher apolipoprotein B and apolipoprotein C-III levels than patients on no therapy (P < 0.01 for each). Conclusions: In this cross-sectional study of HIV-infected women, either PI or NNRTI therapy elevated levels of total cholesterol and specific apolipoproteins. These findings, on a background of an older population with additional risk factors of smoking, obesity, and diabetes, may lead to future atherosclerotic events in these patients.

Dose-associated effects of rosuvastatin on the metabolism of apolipoprotein (apo) B-100 in triacylglycerol rich lipoprotein (TRL, d

This study examined the relation between arterial compliance of the lower extremities and aerobic capacity in patients with a broad spectrum of cardiovascular risk but without overt coronary heart disease (CHD). Local arterial compliance was noninvasively measured in the thigh and calf in 104 men and 99 women using air plethysmography. Subjects also underwent maximal exercise treadmill testing as a measure of aerobic capacity. In univariate analysis, age (r = -0.49, p0.001), systolic blood pressure at rest (r = -0.27, p0.001), pulse pressure (r = -0.39, p0.001), total cholesterol (r = -0.25, p0.001), triglycerides (r = -0.025, p0.001), non-high-density lipoprotein cholesterol (r = -0.23, p0.001), high-sensitivity C-reactive protein (r = -0.21, p = 0.002), and low-density lipoprotein cholesterol (r = -0.15, p = 0.03) all demonstrated a significant inverse association with treadmill time. Thigh and calf compliance demonstrated a significant positive association with treadmill time (r = 0.48, p0.001; r = 0.46, p0.001). In multivariate analysis, thigh compliance (p = 0.003), age (p0.001), gender (p = 0.005), and triglycerides (p = 0.017) were independent predictors of treadmill time. In conclusion, thigh compliance measured with a simple-to-use, fully automated device independently predicts aerobic fitness in patients with a wide range of cardiovascular risk but without CHD.

Aim We investigated the associations of apolipoprotein C-III (apoCIII) protein and apoCIII gene variation with microvascular disease complications in Type 1 diabetes. Methods The serum apoCIII concentration, and both a T −455 →C and a Sac I gene polymorphisms were determined in 409 patients in the DCCT/EDIC cohort of patients with Type 1 diabetes. Correlations with albumin excretion rate (AER) and the severity of retinopathy were investigated. Results Higher apoCIII concentrations were associated ( P r =.78), total ( r =.61) and LDL ( r =.40) cholesterol, apoAI ( r =.26), and apoB ( r =.50), AER ( r =.08), and the severity of retinopathy (ETDRS score, r =.11), and these relationships persisted after controlling for age, gender, body mass index (BMI), and HbA1c level. The apoCIII concentration was significantly higher in the group of patients with macroalbuminuria (AERs 300 mg/24 h) compared to the groups with microalbuminuria (AER 40–299 mg/24 h; P P P P −455 →C polymorphism nor a Sac I polymorphism in the 3′ UTR were associated with circulating apoCIII concentrations, nor the severity of nephropathy or retinopathy. Conclusions Elevated apoCIII levels have been associated with increased macrovascular disease risk. In the DCCT/EDIC cohort of patients, there was an independent positive association of apoCIII level with microvascular complications of Type 1 diabetes.