Efficacy and safety of ezetimibe monotherapy in children with heterozygous familial or nonfamilial hypercholesterolemia.

Objectives: To evaluate the lipid-altering efficacy and safety of ezetimibe monotherapy in young children with heterozygous familial hypercholesterolemia (HeFH) or nonfamilial hypercholesterolemia (nonFH).

Study Design: One hundred thirty-eight children 6-10 years of age with diagnosed HeFH or clinically important nonFH (low-density lipoprotein cholesterol [LDL-C] ≥ 160 mg/dL [4.1 mmol/L]) were enrolled into a multicenter, 12-week, randomized, double-blind, placebo-controlled study.

Comparison of a novel method vs the Friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile.

Importance: In clinical and research settings worldwide, low-density lipoprotein cholesterol (LDL-C) is typically estimated using the Friedewald equation. This equation assumes a fixed factor of 5 for the ratio of triglycerides to very low-density lipoprotein cholesterol (TG:VLDL-C); however, the actual TG:VLDL-C ratio varies significantly across the range of triglyceride and cholesterol levels.

Objective: To derive and validate a more accurate method for LDL-C estimation from the standard lipid profile using an adjustable factor for the TG:VLDL-C ratio.

Very large database of lipids: rationale and design.

Blood lipids have major cardiovascular and public health implications. Lipid-lowering drugs are prescribed based in part on categorization of patients into normal or abnormal lipid metabolism, yet relatively little emphasis has been placed on: (1) the accuracy of current lipid measures used in clinical practice, (2) the reliability of current categorizations of dyslipidemia states, and (3) the relationship of advanced lipid characterization to other cardiovascular disease biomarkers. To these ends, we developed the Very Large Database of Lipids (NCT01698489), an ongoing database protocol that harnesses deidentified data from the daily operations of a commercial lipid laboratory.

Non-high-density lipoprotein cholesterol, guideline targets, and population percentiles for secondary prevention in 1.3 million adults: the VLDL-2 study (very large database of lipids).

Objectives: This study sought to examine patient-level discordance between population percentiles of non-high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C).

Background: Non-HDL-C is an alternative to LDL-C for risk stratification and lipid-lowering therapy. The justification for the present guideline-based non-HDL-C cutpoints of 30 mg/dl higher than the LDL-C cutpoints remains largely untested.

Relationship of apolipoproteins A-1 and B, and lipoprotein(a) to cardiovascular outcomes: the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes).

Objectives: This study sought to examine the relationship between baseline and on-study apolipoproteins (apo) A-1 and B and lipoprotein(a) [Lp(a)] levels and the development of subsequent cardiovascular (CV) events in the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes) trial.

Background: Niacin has been reported to lower apoB and Lp(a) and to raise apoA-1.

Methods: Individuals with CV disease and low baseline levels of high-density lipoprotein cholesterol were randomized to simvastatin plus placebo or simvastatin, plus extended-release niacin ([ERN], 1,500 to 2,000 mg/day), with ezetimibe added as needed, in both groups, to maintain an on-treatment low-density lipoprotein cholesterol in the range of 40 to 80 mg/dl.

Menstrual and reproductive characteristics and breast density in young women.

Purpose: Breast density is strongly related to breast cancer risk, but determinants of breast density in young women remain largely unknown.

Methods: Associations of reproductive and menstrual characteristics with breast density measured by magnetic resonance imaging were evaluated in a cross-sectional study of 176 healthy women, 25-29 years old, using linear mixed effects models.

Results: Parity was significantly inversely associated with breast density.

Diagnosis and management of familial dyslipoproteinemias.

The three major pathways of lipoprotein metabolism provide a superb paradigm to delineate systematically the familial dyslipoproteinemias. Such understanding leads to improved diagnosis and treatment of patients. In the exogenous (intestinal) pathway, defects in LPL, apoC-II, APOA-V, and GPIHBP1 disrupt the catabolism of chylomicrons and hepatic uptake of their remnants, producing very high TG.

Friedewald-estimated versus directly measured low-density lipoprotein cholesterol and treatment implications.

Objectives: The aim of this study was to compare Friedewald-estimated and directly measured low-density lipoprotein cholesterol (LDL-C) values.

Background: LDL-C is routinely estimated by the Friedewald equation to guide treatment; however, compatibility with direct measurement has received relatively little scrutiny, especially at levels <70 mg/dl now targeted in high-risk patients.

Methods: We examined 1,340,614 U.

Update on the detection and treatment of atherogenic low-density lipoproteins.

Purpose Of Review: To explain why epidemiological studies have reached such diverse views as to whether apolipoprotein B (apoB) and/or low-density lipoprotein particle number (LDL-P) are more accurate markers of the risk of cardiovascular disease than LDL-C or non-high-density lipoprotein cholesterol (HDL-C) and to review the treatment options to lower LDL.

Recent Findings: The Emerging Risk Factor Collaboration, a large prospective participant level analysis, a meta-analysis of statin clinical trials, and the Heart Protection Study have each reported that apoB does not add significantly to the cholesterol markers as indices of cardiovascular risk. By contrast, a meta-analysis of published prospective studies demonstrated that non-HDL-C was superior to LDL-C, and apoB was superior to non-HDL-C.

Interrelationships between the concentration and size of the largest high-density lipoprotein subfraction and apolipoprotein C-I in infants at birth and follow-up at 2-3 months of age and their parents.

Background: Lipoprotein subfractions in infants may predict the risk of cardiovascular disease factors in children.

Objective: To examine the relationships between lipid and nonlipid factors and lipoprotein subfractions in infants at birth and follow-up (FU) and in their parents.

Methods: Prospective study in a community-based hospital of 103 families ascertained through a pregnant mother at 36 weeks gestation or older.

Universal screening of cholesterol in children.

Atherosclerosis begins in childhood, and these early lesions are related to cardiovascular risk factors, including non-high-density lipoprotein cholesterol (HDL-C). Genetic disorders of lipid metabolism, principally familial hypercholesterolemia, have a high frequency in the population (about 1:300-1:500), and cause cardiovascular morbidity beginning in the third decade of life. The current obesity epidemic in children has worsened cardiovascular risk status.

Height, adiposity and body fat distribution and breast density in young women.

Introduction: Breast density is one of the strongest risk factors for breast cancer, but determinants of breast density in young women remain largely unknown.

Methods: Associations of height, adiposity and body fat distribution with percentage dense breast volume (%DBV) and absolute dense breast volume (ADBV) were evaluated in a cross-sectional study of 174 healthy women, 25 to 29 years old. Adiposity and body fat distribution were measured by anthropometry and dual-energy X-ray absorptiometry (DXA), while %DBV and ADBV were measured by magnetic resonance imaging.

Depressive symptoms and serum lipid levels in young adult women.

Accumulating data suggest that depression is associated with risk factors for cardiovascular disease, but few studies have investigated potential behavioral mediators of such associations, particularly among women. In this study of healthy young adult women (n = 225), we examined associations among depressive symptoms, health behaviors, and serum lipid levels. Depressive symptoms were assessed with the 20-item Center for Epidemiologic Studies-Depression scale, and a fasting blood sample was obtained for serum lipid levels, including total cholesterol, high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C).

Adolescent diet and metabolic syndrome in young women: results of the Dietary Intervention Study in Children (DISC) follow-up study.

Context: Childhood diet is hypothesized to influence development of chronic disease in adulthood.

Objective: Our objective was to evaluate the long-term effects of a dietary intervention to reduce fat and increase fiber intake during childhood and adolescence on the prevalence of metabolic syndrome in young adult women.

Design: A follow-up study was conducted in 2006-2008, 9 yr after termination of the Dietary Intervention Study in Children (DISC).

Non-high-density lipoprotein cholesterol concentration is associated with the metabolic syndrome among US youth aged 12-19 years.

Objective: To test the hypothesis that the concentration of non-high-density lipoprotein cholesterol (non-HDL-C) is associated with the metabolic syndrome (MetS) in youth.

Study Design: Data on children and adolescents aged 12-19 years (n = 2734) from the cross-sectional National Health and Nutrition Examination Survey 1999-2004 were analyzed.

Results: Depending on the definition of MetS used, the mean non-HDL-C concentration among youth with MetS ranged from 144.

Adolescent diet and subsequent serum hormones, breast density, and bone mineral density in young women: results of the Dietary Intervention Study in Children follow-up study.

Background: Adolescent diet is hypothesized to influence breast cancer risk. We evaluated the long-term effects of an intervention to lower fat intake among adolescent girls on biomarkers that are related to breast cancer risk in adults.

Methods: A follow-up study was conducted on 230 girls who participated in the Dietary Intervention Study in Children (DISC), in which healthy, prepubertal, 8 to 10 year olds were randomly assigned to usual care or to a behavioral intervention that promoted a reduced fat diet.

Recognition and management of dyslipidemia in children and adolescents.

Context: Cardiovascular disease (CVD) remains the number one cause of death in the United States. The origins of atherosclerosis and CVD begin in childhood. Dyslipidemia and obesity are endemic in American youth and require urgent action.

Clinical and laboratory assessment of cardiovascular risk in children: Guidelines for screening, evaluation, and treatment.

The early lesions of atherosclerosis begin in childhood and are related to antecedent cardiovascular disease (CVD) risk factors. Environmental and genetic factors (eg, diet, obesity, exercise, and certain inherited dyslipidemias) influence progression of such lesions. Identification of youth at risk for atherosclerosis includes an integrated assessment of these predisposing factors.

Primary and secondary disorders of lipid metabolism in pediatrics.

In the circulation, cholesterol and triglycerides are enveloped in apolipoproteins and phospholipids, and transported as complex particles called lipoproteins. Abnormal levels of lipoproteins occur in children either because of a genetic defect in lipid metabolism pathways (primary lipid disorders, e.g.