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. Following screening/drug washout and a 5-week single-blind placebo-run-in with diet stabilization, subjects were randomized 2:1 to daily ezetimibe 10 mg (n = 93) or placebo (n = 45) for 12 weeks. Lipid-altering efficacy and safety were assessed in all treated patients. RESULTS: Overall, mean age was 8.3 years, 57% were girls, 80% were white, mean baseline LDL-C was 228 mg/dL (5.9 mmol/L), and 91% had HeFH. After 12 weeks, ezetimibe significantly reduced LDL-C by 27% after adjustment for placebo (P < .001) and produced significant reductions in total cholesterol (21%), nonhigh-density lipoprotein cholesterol (26%), and apolipoprotein B (20%) (P < .001 for all). LDL-C lowering response in sex, race, baseline lipids, and HeFH/nonFH subgroups was generally consistent with overall study results. Ezetimibe was well tolerated, with a safety profile similar to studies in older children, adolescents, and adults. CONCLUSIONS: Ezetimibe monotherapy produced clinically relevant reductions in LDL-C and other key lipid variables in young children with primary HeFH or clinically important nonFH, with a favorable safety/tolerability profile. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00867165.

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. DESIGN, SETTING, AND PARTICIPANTS: We used a convenience sample of consecutive clinical lipid profiles obtained from 2009 through 2011 from 1,350,908 children, adolescents, and adults in the United States. Cholesterol concentrations were directly measured after vertical spin density-gradient ultracentrifugation, and triglycerides were directly measured. Lipid distributions closely matched the population-based National Health and Nutrition Examination Survey (NHANES). Samples were randomly assigned to derivation (n = 900,605) and validation (n = 450,303) data sets. MAIN OUTCOMES AND MEASURES: Individual patient-level concordance in clinical practice guideline LDL-C risk classification using estimated vs directly measured LDL-C (LDL-CD). RESULTS: In the derivation data set, the median TG:VLDL-C was 5.2 (IQR, 4.5-6.0). The triglyceride and non-high-density lipoprotein cholesterol (HDL-C) levels explained 65% of the variance in the TG:VLDL-C ratio. Based on strata of triglyceride and non-HDL-C values, a 180-cell table of median TG:VLDL-C values was derived and applied in the validation data set to estimate the novel LDL-C (LDL-CN). For patients with triglycerides lower than 400 mg/dL, overall concordance in guideline risk classification with LDL-CD was 91.7% (95% CI, 91.6%-91.8%) for LDL-CN vs 85.4% (95% CI, 85.3%-85.5%) for Friedewald LDL-C (LDL-CF) (P < .001). The greatest improvement in concordance occurred in classifying LDL-C lower than 70 mg/dL, especially in patients with high triglyceride levels. In patients with an estimated LDL-C lower than 70 mg/dL, LDL-CD was also lower than 70 mg/dL in 94.3% (95% CI, 93.9%-94.7%) for LDL-CN vs 79.9% (95% CI, 79.3%-80.4%) for LDL-CF in samples with triglyceride levels of 100 to 149 mg/dL; 92.4% (95% CI, 91.7%-93.1%) for LDL-CN vs 61.3% (95% CI, 60.3%-62.3%) for LDL-CF in samples with triglyceride levels of 150 to 199 mg/dL; and 84.0% (95% CI, 82.9%-85.1%) for LDL-CN vs 40.3% (95% CI, 39.4%-41.3%) for LDL-CF in samples with triglyceride levels of 200 to 399 mg/dL (P < .001 for each comparison). CONCLUSIONS AND RELEVANCE: A novel method to estimate LDL-C using an adjustable factor for the TG:VLDL-C ratio provided more accurate guideline risk classification than the Friedewald equation. These findings require external validation, as well as assessment of their clinical importance. The implementation of these findings into clinical practice would be straightforward and at virtually no cost. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01698489.

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. The database includes individuals who were referred for clinical purposes for a Vertical Auto Profile (Atherotech Inc., Birmingham, AL), which directly measures cholesterol concentrations of low-density lipoprotein, very low-density lipoprotein, intermediate-density lipoprotein, high-density lipoprotein, their subclasses, and lipoprotein(a). Individual Very Large Database of Lipids studies, ranging from studies of measurement accuracy, to dyslipidemia categorization, to biomarker associations, to characterization of rare lipid disorders, are investigator-initiated and utilize peer-reviewed statistical analysis plans to address a priori hypotheses/aims. In the first database harvest (Very Large Database of Lipids 1.0) from 2009 to 2011, there were 1 340 614 adult and 10 294 pediatric patients; the adult sample had a median age of 59 years (interquartile range, 49-70 years) with even representation by sex. Lipid distributions closely matched those from the population-representative National Health and Nutrition Examination Survey. The second harvest of the database (Very Large Database of Lipids 2.0) is underway. Overall, the Very Large Database of Lipids database provides an opportunity for collaboration and new knowledge generation through careful examination of granular lipid data on a large scale.

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. In multivariable adjusted models that included non-reproductive variables, mean percent dense breast volume (%DBV) decreased from 20.5 % in nulliparous women to 16.0 % in parous women, while mean absolute dense breast volume (ADBV) decreased from 85.3 to 62.5 cm(3). Breast density also was significantly inversely associated with the age women started using hormonal contraceptives, whereas it was significantly positively associated with duration of hormonal contraceptive use. In adjusted models, mean %DBV decreased from 21.7 % in women who started using hormones at 12-17 years of age to 14.7 % in those who started using hormones at 22-28 years of age, while mean ADBV decreased from 86.2 to 53.7 cm(3). The age at which women started using hormonal contraceptives and duration of hormone use were inversely correlated, and mean %DBV increased from 15.8 % in women who used hormones for not more than 2.0 years to 22.0 % in women who used hormones for more than 8 years, while mean ADBV increased from 61.9 to 90.4 cm(3) over this interval. CONCLUSIONS: Breast density in young women is inversely associated with parity and the age women started using hormonal contraceptives but positively associated with duration of hormone use.

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. METHODS: We assigned population percentiles to non-HDL-C and Friedewald-estimated LDL-C values of 1,310,440 U.S. adults with triglyceride levels <400 mg/dl who underwent lipid testing by vertical spin density gradient ultracentrifugation (Atherotech, Birmingham, Alabama) from 2009 to 2011. RESULTS: LDL-C cutpoints of 70, 100, 130, 160, and 190 mg/dl were in the same population percentiles as non-HDL-C values of 93, 125, 157, 190, and 223 mg/dl, respectively. Non-HDL-C values reclassified a significant proportion of patients within or to a higher treatment category compared with Friedewald LDL-C values, especially at LDL-C levels in the treatment range of high-risk patients and at triglyceride levels ≥150 mg/dl. Of patients with LDL-C levels <70 mg/dl, 15% had a non-HDL-C level ≥ 100 mg/dl (guideline-based cutpoint) and 25% had a non-HDL-C level ≥ 93 mg/dl (percentile-based cutpoint); if triglyceride levels were 150 to 199 mg/dl concurrently, these values were 22% and 50%, respectively. CONCLUSIONS: There is significant patient-level discordance between non-HDL-C and LDL-C percentiles at lower LDL-C and higher triglyceride levels, which has implications for the treatment of high-risk patients. Current non-HDL-C cutpoints for high-risk patients may need to be lowered to match percentiles of LDL-C cutpoints. Relatively small absolute reductions in non-HDL-C cutpoints result in substantial reclassification of patients to higher treatment categories with potential implications for risk assessment and treatment.

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. Hazard ratios (HRs) were used to evaluate the relationship between levels of apoA-1, apoB, and Lp(a), and CV events in each treatment group. RESULTS: Baseline apoB and the apoB/apoA-I ratio were significantly predictive of CV events only for the placebo group (HR: 1.17 [p = 0.018] and HR: 1.19 [p = 0.016]). Baseline and on-study Lp(a) were predictive of CV events in both simvastatin plus placebo (baseline HR: 1.24 [p = 0.002] and on-study HR: 1.21 [p = 0.017]) and the simvastatin plus ERN group (baseline HR: 1.25 [p = 0.001] and on-study HR: 1.18 [p = 0.028]). The ERN modestly increased 1-year apoA-1 (7%), decreased apoB (13%), decreased the ApoB/ApoA-1 ratio (19%), and decreased Lp(a) 21%, but did not reduce CV events. CONCLUSIONS: Lp(a) was associated with increased CV risk in both treatment groups indicating that it contributes to residual CV risk. However, there was no evidence that ERN reduced CV risk, despite favorable lipoprotein changes.

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. In the endogenous (hepatic) pathway, six disorders affect the activity of the LDLR and markedly increase LDL. These include FH, FDB, ARH, PCSK9 gain-of-function mutations, sitosterolemia and loss of 7 alpha hydroxylase. Hepatic overproduction of VLDL occurs in FCHL, hyperapoB, LDL subclass pattern B, FDH and syndrome X, often due to insulin resistance and resulting in high TG, elevated small LDL particles and low HDL-C. Defects in APOB-100 and loss-of-function mutations in PCSK9 are associated with low LDL-C, decreased CVD and longevity. An absence of MTP leads to marked reduction in chylomicrons and VLDL, causing abetalipoproteinemia. In the reverse cholesterol pathway, deletions or nonsense mutations in apoA-I or ABCA1 transporter disrupt the formation of the nascent HDL particle. Mutations in LCAT disrupt esterification of cholesterol in nascent HDL by LCAT and apoA-1, and formation of spherical HDL. Mutations in either CETP or SR-B1 and familial high HDL lead to increased large HDL particles, the effect of which on CVD is not resolved. The major goal is to prevent or ameliorate the major complications of many familial dyslipoproteinemias, namely, premature CVD or pancreatitis. Dietary and drug treatment specific for each inherited disorder is reviewed.

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.S. adults who underwent lipid profiling by vertical spin density gradient ultracentrifugation (Atherotech, Birmingham, Alabama) from 2009 to 2011. Following standard practice, Friedewald LDL-C was not estimated if triglyceride levels were ≥ 400 mg/dl (n = 30,174), yielding 1,310,440 total patients and 191,333 patients with Friedewald LDL-C <70 mg/dl. RESULTS: Patients were 59 ± 15 years of age and 52% were women. Lipid distributions closely matched those in the National Health and Nutrition Examination Survey. A greater difference in the Friedewald-estimated versus directly measured LDL-C occurred at lower LDL-C and higher triglyceride levels. If the Friedewald-estimated LDL-C was <70 mg/dl, the median directly measured LDL-C was 9.0 mg/dl higher (5th to 95th percentiles, 1.8 to 15.4 mg/dl) when triglyceride levels were 150 to 199 mg/dl and 18.4 mg/dl higher (5th to 95th percentiles, 6.6 to 36.0 mg/dl) when triglyceride levels were 200 to 399 mg/dl. Of patients with a Friedewald-estimated LDL-C <70 mg/dl, 23% had a directly measured LDL-C ≥ 70 mg/dl (39% if triglyceride levels were concurrently 150 to 199 mg/dl; 59% if triglyceride levels were concurrently 200 to 399 mg/dl). CONCLUSIONS: The Friedewald equation tends to underestimate LDL-C most when accuracy is most crucial. Especially if triglyceride levels are ≥ 150 mg/dl, Friedewald estimation commonly classifies LDL-C as <70 mg/dl despite directly measured levels ≥ 70 mg/dl, and therefore additional evaluation is warranted in high-risk patients.

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. As well, three studies using discordance analysis each demonstrated that apoB and LDL-P were superior to the cholesterol markers. Two approaches to resolve these differences are brought to bear in this article: first, which results are credible and second, how does taking the known differences in LDL composition into account, help resolve them. The best identification of individuals at risk of coronary artery disease or with coronary artery disease allows the most efficacious treatment of elevated LDL-P and will permit a more extensive use of some of the more novel LDL-lowering agents. SUMMARY: Much of the controversy vanishes once the physiologically driven differences in the composition of the apoB lipoprotein particles are taken into account, illustrating that epidemiology, not directed by physiology, is like shooting without aiming.

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. Of 103 infants studied at birth, 85 were sampled at FU at 2-3 months of age, along with 76 fathers. Lipids, lipoproteins, and their subclasses were determined by nuclear magnetic resonance spectroscopy. Correlations of lipid-related parameters were calculated using Spearman rank correlations. RESULTS: Female gender in infants and use of formula only were the only nonlipid variables associated with lipoprotein subfractions. LDL parameters were significantly correlated between infants at birth and FU. The largest high-density lipoprotein subfraction, H5C, was the only lipid variable significantly associated between mothers and infants at birth. Paternal low-density lipoprotein size was significantly correlated with that of infants at FU but not at birth. In each of the four groups, markedly inverse interrelationships were found between H5C and small LDL particles. At birth and at FU, apoC-I was strongly related with H5C but not TG. Conversely, apoC-I in the parents was strongly related with TG but not H5C. CONCLUSION: Significant relationships were found between lipoprotein subfractions within infants at birth and FU and their parents. ApoC-I and H5C levels very early in life may affect the development of dyslipidemia and obesity in childhood.

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). Diet was measured using 24-h recalls, and other health behaviors (physical activity, smoking) were assessed via self-report questionnaire. Results indicated a modest negative association between depressive symptoms and LDL-C levels. Higher levels of depressive symptoms were also associated with lower total and insoluble dietary fiber intake, both of which were associated with HDL-C and LDL-C. Mediational analyses indicated a significant indirect effect of depressive symptoms on LDL-C via total and insoluble dietary fiber in unadjusted analyses, but not in adjusted analyses. The present findings suggest that depressive symptoms are inversely associated with serum LDL-C levels in young adult women, but that these associations are not likely mediated by adverse lifestyle behaviors.

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. Cardiovascular risk factors present in youth often track into adulthood and are more predictive of future subclinical atherosclerosis than risk factors measured in young adulthood. Further, modification of risk factors beginning in childhood and young adulthood can lead to restoration to normal or improvement in measures of subclinical atherosclerosis measures both in those with genetic dyslipidemias and those with dyslipidemia secondary to obesity. Prior recommended selective lipid screening strategies based on family history or presence of other cardiovascular risk factors have failed to capture many with genetic dyslipidemia. Medium-term clinical trials of statin therapy for inherited dyslipidemias are safe and effective in lowering low-density lipoprotein cholesterol (LDL-C). Cholesterol screening in childhood is necessary to prevent cardiovascular morbidity in those with genetic dyslipidemias and to increase awareness of the need for behavioral intervention in those with multiple cardiovascular risk factors, often a result of the obesity epidemic.

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. Associations were evaluated using linear mixed-effects models. All tests of statistical significance are two-sided. RESULTS: Height was significantly positively associated with %DBV but not ADBV; for each standard deviation (SD) increase in height, %DBV increased by 18.7% in adjusted models. In contrast, all measures of adiposity and body fat distribution were significantly inversely associated with %DBV; a SD increase in body mass index (BMI), percentage fat mass, waist circumference and the android:gynoid fat mass ratio (A:G ratio) was each associated significantly with a 44.4 to 47.0% decrease in %DBV after adjustment for childhood BMI and other covariates. Although associations were weaker than for %DBV, all measures of adiposity and body fat distribution also were significantly inversely associated with ADBV before adjustment for childhood BMI. After adjustment for childhood BMI, however, only the DXA measures of percentage fat mass and A:G ratio remained significant; a SD increase in each was associated with a 13.8 to 19.6% decrease in ADBV. In mutually adjusted analysis, the percentage fat mass and the A:G ratio remained significantly inversely associated with %DBV, but only the A:G ratio was significantly associated with ADBV; a SD increase in the A:G ratio was associated with an 18.5% decrease in ADBV. CONCLUSION: Total adiposity and body fat distribution are independently inversely associated with %DBV, whereas in mutually adjusted analysis only body fat distribution (A:G ratio) remained significantly inversely associated with ADBV in young women. Research is needed to identify biological mechanisms underlying these associations.

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). SETTING: The study took place at six DISC clinical centers in the United States. PARTICIPANTS: A total of 230 (76%) DISC female participants who were 25-29 yr old and had not been pregnant or breastfeeding in the previous 3 months participated in the follow-up study. INTERVENTION: There was no intervention between the end of the DISC trial and the follow-up visit. MAIN OUTCOME MEASURE: Metabolic syndrome was the primary study endpoint planned before data collection and was hypothesized to be less common in the intervention group participants. RESULTS: Metabolic syndrome was uncommon, and its prevalence did not differ by treatment group. However, after adjustment for nondietary variables, mean systolic blood pressures of intervention and control group participants were 107.7 and 110.0 mm Hg, respectively (P = 0.03), whereas mean fasting plasma glucose levels were 87.0 and 89.1 mg/dl, respectively (P = 0.01). Intervention group participants also had lower concentrations of large very-low-density lipoprotein particles, a marker of hepatic insulin resistance, compared with control group participants. Adjustment for current diet did not materially alter results. CONCLUSION: Consumption of a diet lower in fat and higher in fiber during childhood and adolescence may benefit glycemic control and blood pressure long term.

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 144.2 to 155.8 mg/dL, compared with 108.8-109.1 mg/dL in those without MetS (all P < .001). The MetS prevalence ranged from 6.9% to 11.7% in youth with a non-HDL-C concentration of 120-144 mg/dL and from 21.5% to 23.4% in those with a concentration ≥ 145 mg/dL-both significantly higher than the prevalence of 1.9%-3.4% in youth with a concentration <120 mg/dL (all P < .001). After adjustment for potential confounders, youth with a non-HDL-C concentration ≥ 120 mg/dL or ≥ 145 mg/dL were about 3 or 4 times more likely to have MetS compared with those with a non-HDL-C <120 mg/dL or <145 mg/dL (all P < .001). CONCLUSIONS: Fasting non-HDL-C concentration was strongly associated with MetS in US youth. Our results support the use of non-HDL-C thresholds of 120 mg/dL and 145 mg/dL to indicate borderline and high MetS risk, respectively.