218 results on '"Kwiterovich PO"'
Search Results
2. An HphI polymorphism in the E-selectin gene is associated with premature coronary artery disease
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Zheng, F, primary, Chevalier, JA, additional, Zhang, LQ, additional, Virgil, D, additional, Ye, SQ, additional, and Kwiterovich, PO, additional
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- 2001
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3. Applicability of LDLR flanking microsatellite polymorphisms for prenatal diagnosis of homozygous state for familial hypercholesterolemia
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Suva, ER De Oliveirae, primary, Haddad, L., additional, Kwiterovich, PO, additional, Humphries, SE, additional, and Day, INM, additional
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- 1998
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4. Association of plasma triglyceride concentration and LDL particle diameter, density, and chemical composition with premature coronary artery disease in men and women
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Coresh, J, primary, Kwiterovich, PO, additional, Smith, HH, additional, and Bachorik, PS, additional
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- 1993
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5. Non-High-Density Lipoprotein Cholesterol Concentration is Associated with the Metabolic Syndrome among US Youth Aged 12-19 Years.
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Li C, Ford ES, McBride PE, Kwiterovich PO, McCrindle BW, and Gidding SS
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- 2011
6. Effect of soy protein-containing isoflavones on lipoproteins in postmenopausal women.
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Allen JK, Becker DM, Kwiterovich PO, Lindernstruth KA, and Curtis C
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- 2007
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7. Higher self-reported physical activity is associated with lower systolic blood pressure: the Dietary Intervention Study in Childhood (DISC)
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Gidding SS, Barton BA, Dorgan JA, Kimm SYS, Kwiterovich PO, Lasser NL, Robson AM, Stevens VJ, Van Horn L, and Simons-Morton DG
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- 2006
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8. A large high-density lipoprotein enriched in apolipoprotein C-I: a novel biochemical marker in infants of lower birth weight and younger gestational age.
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Kwiterovich PO Jr., Cockrill SL, Virgil DG, Garrett ES, Otvos J, Knight-Gibson C, Alaupovic P, Forte T, Zhang L, Farwig ZN, Macfarlane RD, Kwiterovich, Peter O Jr, Cockrill, Steven L, Virgil, Donna G, Garrett, Elizabeth S, Otvos, James, Knight-Gibson, Carolyn, Alaupovic, Petar, Forte, Trudy, and Zhang, Lin
- Abstract
Context: Low birth weight is associated with increased cardiovascular disease in adulthood, and differences in the molecular weight, composition, and quantity of lipoprotein subclasses are associated with coronary artery disease.Objective: To determine if there are novel patterns of lipoprotein heterogeneity in low-birth-weight infants.Design, Setting, and Participants: Prospective study at a US medical center of a representative sample of infants (n = 163; 70 white and 93 black) born at 28 or more weeks of gestational age between January 3, 2000, and September 27, 2000. This sample constituted 20% of all infants born during the study period at this site.Main Outcome Measures: Plasma levels and particle sizes of lipoprotein subclasses and plasma concentrations of lipids, lipoproteins (high-density lipoprotein [HDL] and low-density lipoprotein [LDL]), and apolipoproteins.Results: An elevated lipoprotein peak of a particle with density between 1.062 and 1.072 g/mL was identified using physical-chemical methods. This subclass of large HDL was enriched in apolipoprotein C-I (apo C-I). Based on the amount of the apo C-I-enriched HDL peak, 156 infants were assigned to 1 of 4 groups: 0 (none detected), 17%; 1 (possibly present), 41%; 2 (probably present), 22%; 3 (elevated), 19%. Infants in group 3, compared with those in the other 3 groups, had significantly (P<.001) lower mean birth weight (2683.7 vs 3307.1 g) and younger mean gestational age (36.2 vs 39.3 wk). After correction for age, infants in group 3 had significantly higher levels of total and large HDL cholesterol and of total and large LDL cholesterol and LDL particle number. However, infants in group 3 had lower levels of small HDL, very low-density lipoproteins, and triglycerides than infants in the other 3 groups. This lipoprotein profile differed from that in infants born small for gestational age, who had significantly higher triglyceride (P<.001) and apo B (P = .04) levels, but lower levels of total and large HDL cholesterol (P<.001) and apo A-I (P<.001).Conclusions: Because apo C-I-enriched HDL, and purified apo C-I alone, promotes apoptosis in vitro, increased amounts of this particle may have physiological significance and identify a novel group of low-birth-weight infants apparently distinct from traditionally classified small-for-gestational-age infants. [ABSTRACT FROM AUTHOR]- Published
- 2005
9. Long-term safety and efficacy of a cholesterol-lowering diet in children with elevated low-density lipoprotein cholesterol: seven-year results of the Dietary Intervention Study in Children (DISC)
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Obarzanek E, Kimm SYS, Barton BA, Van Horn L, Kwiterovich PO Jr., Simons-Morton DG, Hunsberger SA, Lasser NL, Robson AM, Franklin FA Jr., Lauer RM, Stevens VJ, Friedman LA, Dorgan JF, Greenlick MR, and DISC Collaborative Research Group
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- 2001
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10. Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia: a randomized controlled trial.
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Stein EA, Illingworth DR, Kwiterovich PO Jr., Liacouras CA, Siimes MA, Jacobson MS, Brewster TG, Hopkins P, Davidson M, Graham K, Arensman F, Knopp RH, DuJovne C, Williams CL, Isaacsohn JL, Jacobsen CA, Laskarzewski PM, Ames S, Gormley GJ, and Stein, E A
- Abstract
Context: Heterozygous familial hypercholesterolemia (HeFH) is a common disorder associated with early coronary artery disease, especially in men. The age at which drug therapy should be started is still controversial, as is the use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins).Objective: To assess the lipid-lowering efficacy, biochemical safety, and effect on growth and sexual development of lovastatin in adolescent boys with HeFH.Design: One-year, double-blind, placebo-controlled, balanced, 2-period, 2-arm randomized trial. In the first period (24 weeks), lovastatin was increased at 8 and 16 weeks and the dosage remained stable during the second period (24 weeks). The study was conducted between 1990 and 1994.Setting: Fourteen pediatric outpatient clinics in the United States and Finland.Patients: Boys aged 10 to 17 years with HeFH. Of 132 randomized subjects (67 intervention, 65 placebo), 122 (63 intervention, 59 placebo) and 110 (61 intervention, 49 placebo) completed the first and second periods, respectively.Intervention: Lovastatin, starting at 10 mg/d, with a forced titration at 8 and 16 weeks to 20 and 40 mg/d, respectively, or placebo.Main Outcome Measures: The primary efficacy outcome measure was low-density lipoprotein cholesterol (LDL-C). Primary safety measures were growth and sexual development.Results: Compared with placebo, LDL-C levels of patients receiving lovastatin decreased significantly (P<.001) by 17%, 24%, and 27% receiving dosages of 10, 20, and 40 mg/d, respectively, and remained 25 % lower than baseline at 48 weeks. Growth and sexual maturation assessed by Tanner staging and testicular volume were not significantly different between the lovastatin and placebo groups at 24 weeks (P = .85) and 48 weeks (P = .33); neither were serum hormone levels or biochemical parameters of nutrition. However, the study was underpowered to detect significant differences in safety parameters. Serum vitamin E levels were reduced with lovastatin treatment consistent with reductions in LDL-C, the major carrier of vitamin E in the circulation.Conclusions: This study in adolescent boys with HeFH confirmed the LDL-C-reducing effectiveness of lovastatin. Comprehensive clinical and biochemical data on growth, hormonal, and nutritional status indicated no significant differences between lovastatin and placebo over 48 weeks, although further study is required. [ABSTRACT FROM AUTHOR]- Published
- 1999
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11. Comparison of the effects of lean red meat vs lean white meat on serum lipid levels among free-living persons with hypercholesterolemia: a long-term, randomized clinical trial.
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Davison MH, Hunninghake D, Maki KC, Kwiterovich PO Jr., and Kafonek S
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- 1999
12. Safety of a fat-reduced diet: the Dietary Intervention Study in Children (DISC)
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Obarzanek E, Hunsberger SA, Van Horn L, Hartmuller VV, Barton BA, Stevens VJ, Kwiterovich PO, Franklin FA, Kimm SYS, Lasser NL, Simons-Morton DG, and Lauer RM
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- 1997
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13. The East Baltimore study: the relationship of lipids and lipoproteins to selected cardiovascular risk factors in an inner city Black adult population
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Haigh, NZ, primary, Salz, KM, additional, Chase, GA, additional, Jenkins, JA, additional, Bachorik, PS, additional, and Kwiterovich, PO, additional
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- 1983
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14. Clinical relevance of the biochemical, metabolic, and genetic factors that influence low-density lipoprotein heterogeneity.
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Kwiterovich PO Jr. and Kwiterovich, Peter O Jr
- Abstract
Traditional risk factors for coronary artery disease (CAD) predict about 50% of the risk of developing CAD. The Adult Treatment Panel (ATP) III has defined emerging risk factors for CAD, including small, dense low-density lipoprotein (LDL). Small, dense LDL is often accompanied by increased triglycerides (TGs) and low high-density lipoprotein (HDL). An increased number of small, dense LDL particles is often missed when the LDL cholesterol level is normal or borderline elevated. Small, dense LDL particles are present in families with premature CAD and hyperapobetalipoproteinemia, familial combined hyperlipidemia, LDL subclass pattern B, familial dyslipidemic hypertension, and syndrome X. The metabolic syndrome, as defined by ATP III, incorporates a number of the components of these syndromes, including insulin resistance and intra-abdominal fat. Subclinical inflammation and elevated procoagulants also appear to be part of this atherogenic syndrome. Overproduction of very low-density lipoproteins (VLDLs) by the liver and increased secretion of large, apolipoprotein (apo) B-100-containing VLDL is the primary metabolic characteristic of most of these patients. The TG in VLDL is hydrolyzed by lipoprotein lipase (LPL) which produces intermediate-density lipoprotein. The TG in intermediate-density lipoprotein is hydrolyzed further, resulting in the generation of LDL. The cholesterol esters in LDL are exchanged for TG in VLDL by the cholesterol ester tranfer proteins, followed by hydrolysis of TG in LDL by hepatic lipase which produces small, dense LDL. Cholesterol ester transfer protein mediates a similar lipid exchange between VLDL and HDL, producing a cholesterol ester-poor HDL. In adipocytes, reduced fatty acid trapping and retention by adipose tissue may result from a primary defect in the incorporation of free fatty acids into TGs. Alternatively, insulin resistance may promote reduced retention of free fatty acids by adipocytes. Both these abnormalities lead to increased levels of free fatty acids in plasma, increased flux of free fatty acids back to the liver, enhanced production of TGs, decreased proteolysis of apo B-100, and increased VLDL production. Decreased removal of postprandial TGs often accompanies these metabolic abnormalities. Genes regulating the expression of the major players in this metabolic cascade, such as LPL, cholesterol ester transfer protein, and hepatic lipase, can modulate the expression of small, dense LDL but these are not the major defects. New candidates for major gene effects have been identified on chromosome 1. Regardless of their fundamental causes, small, dense LDL (compared with normal LDL) particles have a prolonged residence time in plasma, are more susceptible to oxidation because of decreased interaction with the LDL receptor, and enter the arterial wall more easily, where they are retained more readily. Small, dense LDL promotes endothelial dysfunction and enhanced production of procoagulants by endothelial cells. Both in animal models of atherosclerosis and in most human epidemiologic studies and clinical trials, small, dense LDL (particularly when present in increased numbers) appears more atherogenic than normal LDL. Treatment of patients with small, dense LDL particles (particularly when accompanied by low HDL and hypertriglyceridemia) often requires the use of combined lipid-altering drugs to decrease the number of particles and to convert them to larger, more buoyant LDL. The next critical step in further reduction of CAD will be the correct diagnosis and treatment of patients with small, dense LDL and the dyslipidemia that accompanies it. [ABSTRACT FROM AUTHOR]
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- 2002
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15. Lipoprotein heterogeneity: diagnostic and therapeutic implications.
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Kwiterovich PO Jr. and Kwiterovich, Peter O Jr
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- 2002
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16. A symposium: Current Concepts in Lipoprotein-Modulated Disease.
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Kwiterovich PO Jr.
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- 2002
17. The metabolic pathways of high-density lipoprotein, low-density lipoprotein, and triglycerides: a current review.
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Kwiterovich PO Jr. and Kwiterovich, P O Jr
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Three major interconnected pathways are involved in lipoprotein metabolism: (1) the transport of dietary or exogenous fat; (2) the transport of hepatic or endogenous fat; and (3) reverse cholesterol transport. These pathways are interdependent and disruptions in one will affect the function and products of the others. For example, a mutation such as one in the ABC1 protein can disrupt normal transport and processing of cholesterol. High-density lipoprotein cholesterol (HDL-C) appears to have cardioprotective properties because of its involvement in certain processes such as reverse cholesterol transport and inhibition of low-density lipoprotein cholesterol (LDL-C) oxidation. Certain agents, such as niacin, which increases HDL-C, lowers lipoprotein (a), and targets specific enzymes or receptors, may be highly beneficial for patients at risk of cardiovascular disease. [ABSTRACT FROM AUTHOR]
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- 2000
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18. A symposium: new advances in dyslipidemia.
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Guyton JR and Kwiterovich PO Jr.
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- 1998
19. The effect of dietary fat, antioxidants, and pro-oxidants on blood lipids, lipoproteins, and atherosclerosis... Reducing dietary fat: putting theory into practice, December 10-11, 1996, New York, NY.
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Kwiterovich PO Jr.
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- 1997
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20. Long-term safety and efficacy of a once-daily niacin/lovastatin formulation for patients with dyslipidemia.
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Kashyap ML, McGovern ME, Berra K, Guyton JR, Kwiterovich PO Jr., Harper WL, Toth PD, Favrot LK, Kerzner B, Nash SD, Bays HE, Simmons PD, Kashyap, Moti L, McGovern, Mark E, Berra, Kathleen, Guyton, John R, Kwiterovich, Peter O, Harper, Wayne L, Toth, Phillip D, and Favrot, Laurence K
- Abstract
Combination therapy is increasingly recommended for patients with multiple lipid disorders, especially those at high risk for coronary events. We investigated the long-term safety and effectiveness of a new drug formulation containing once-daily extended-release niacin and lovastatin. A total of 814 men and women (mean age 59 years) with dyslipidemia were enrolled in a 52-week multicenter, open-label study. We used 4 escalating doses (niacin/lovastatin in milligrams): 500/10 for the first month, 1,000/20 for the second, 1,500/30 for the third, and 2,000/40 for the fourth month through week 52. Dose-dependent effects were observed for all major lipid parameters. At week 16, mean low-density lipoprotein (LDL) cholesterol and triglycerides were reduced by 47% and 41%, respectively; mean high-density lipoprotein (HDL) cholesterol was increased by 30% (all p <0.001). LDL/HDL cholesterol and total/HDL cholesterol ratios were also decreased by 58% and 48%, respectively. These effects persisted through week 52, except for the mean increase in HDL cholesterol, which had increased to 41% at 1 year. Lipoprotein (a) and C-reactive protein also decreased in a dose-related manner (by 25% and 24%, respectively, on 2,000/40 mg; p <0.01 vs baseline). Treatment was generally well tolerated. The most common adverse event was flushing, which caused 10% of patients to withdraw. Other adverse events included gastrointestinal upset, pruritus, rash, and headache. Drug-induced myopathy did not occur in any patient. The incidence of elevated liver enzymes to >3 times the upper limit of normal was 0.5%. Once-daily niacin/lovastatin exhibits substantial effects on multiple lipid risk factors and represents a significant new treatment option in the management of dyslipidemia. [ABSTRACT FROM AUTHOR]
- Published
- 2002
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21. Efficacy and safety of ezetimibe monotherapy in children with heterozygous familial or nonfamilial hypercholesterolemia.
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Kusters DM, Caceres M, Coll M, Cuffie C, Gagné C, Jacobson MS, Kwiterovich PO, Lee R, Lowe RS, Massaad R, McCrindle BW, Musliner TA, Triscari J, and Kastelein JJ
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- Anticholesteremic Agents adverse effects, Azetidines adverse effects, Child, Double-Blind Method, Ezetimibe, Female, Heterozygote, Humans, Hypercholesterolemia genetics, Male, Single-Blind Method, Treatment Outcome, Anticholesteremic Agents therapeutic use, Azetidines therapeutic use, Hypercholesterolemia drug therapy
- Abstract
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., (Copyright © 2015 Elsevier Inc. All rights reserved.)
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- 2015
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22. Comparison of a novel method vs the Friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile.
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Martin SS, Blaha MJ, Elshazly MB, Toth PP, Kwiterovich PO, Blumenthal RS, and Jones SR
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- Adolescent, Adult, Child, Female, Humans, Hypercholesterolemia diagnosis, Male, Practice Guidelines as Topic, Random Allocation, Reference Values, Risk Assessment, Cholesterol, LDL analysis, Cholesterol, VLDL analysis, Models, Theoretical, Triglycerides analysis
- Abstract
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.
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- 2013
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23. 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).
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Elshazly MB, Martin SS, Blaha MJ, Joshi PH, Toth PP, McEvoy JW, Al-Hijji MA, Kulkarni KR, Kwiterovich PO, Blumenthal RS, and Jones SR
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- Cardiovascular Diseases blood, Female, Humans, Male, Middle Aged, Treatment Outcome, Cardiovascular Diseases prevention & control, Cholesterol, LDL blood, Hypolipidemic Agents therapeutic use, Practice Guidelines as Topic, Secondary Prevention methods
- Abstract
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., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
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- 2013
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24. Very large database of lipids: rationale and design.
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Martin SS, Blaha MJ, Toth PP, Joshi PH, McEvoy JW, Ahmed HM, Elshazly MB, Swiger KJ, Michos ED, Kwiterovich PO, Kulkarni KR, Chimera J, Cannon CP, Blumenthal RS, and Jones SR
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- Adolescent, Adult, Aged, Biomarkers blood, Child, Data Interpretation, Statistical, Data Mining, Dyslipidemias diagnosis, Dyslipidemias drug therapy, Dyslipidemias epidemiology, Female, Humans, Hypolipidemic Agents therapeutic use, In Vitro Techniques, Male, Middle Aged, Predictive Value of Tests, Treatment Outcome, United States epidemiology, Young Adult, Databases as Topic statistics & numerical data, Dyslipidemias blood, Lipids blood, Research Design statistics & numerical data
- Abstract
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., (© 2013 Wiley Periodicals, Inc.)
- Published
- 2013
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25. Menstrual and reproductive characteristics and breast density in young women.
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Dorgan JF, Klifa C, Deshmukh S, Egleston BL, Shepherd JA, Kwiterovich PO Jr, Van Horn L, Snetselaar LG, Stevens VJ, Robson AM, Lasser NL, and Hylton NM
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- Adult, Age Factors, Breast Neoplasms diagnosis, Breast Neoplasms prevention & control, Contraception statistics & numerical data, Contraceptives, Oral, Hormonal administration & dosage, Cross-Sectional Studies, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging methods, Multivariate Analysis, Surveys and Questionnaires, Time Factors, Breast anatomy & histology, Menarche physiology, Menstruation physiology, Reproduction physiology
- Abstract
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.
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- 2013
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26. 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).
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Albers JJ, Slee A, O'Brien KD, Robinson JG, Kashyap ML, Kwiterovich PO Jr, Xu P, and Marcovina SM
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- Aged, Biomarkers blood, Cardiovascular Diseases drug therapy, Cardiovascular Diseases epidemiology, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Hypertriglyceridemia blood, Hypertriglyceridemia drug therapy, Hypertriglyceridemia epidemiology, Hypoalphalipoproteinemias blood, Hypoalphalipoproteinemias drug therapy, Hypoalphalipoproteinemias epidemiology, Male, Metabolic Syndrome drug therapy, Metabolic Syndrome epidemiology, Middle Aged, Niacin administration & dosage, Prospective Studies, Simvastatin administration & dosage, Treatment Outcome, Apolipoprotein A-I blood, Apolipoproteins B blood, Cardiovascular Diseases blood, Cholesterol, HDL blood, Lipoprotein(a) blood, Metabolic Syndrome blood, Triglycerides blood
- Abstract
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., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
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27. Response to the letter from Okada et al.
- Author
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Kwiterovich PO
- Subjects
- Female, Humans, Male, Pregnancy, Apolipoprotein C-I blood, Lipoproteins, HDL blood
- Published
- 2013
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28. Friedewald-estimated versus directly measured low-density lipoprotein cholesterol and treatment implications.
- Author
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Martin SS, Blaha MJ, Elshazly MB, Brinton EA, Toth PP, McEvoy JW, Joshi PH, Kulkarni KR, Mize PD, Kwiterovich PO, Defilippis AP, Blumenthal RS, and Jones SR
- Subjects
- Adult, Aged, Apolipoproteins B blood, Blood Chemical Analysis methods, Centrifugation, Density Gradient, Cholesterol, HDL blood, Female, Humans, Male, Middle Aged, Reproducibility of Results, Risk Assessment, Triglycerides blood, Cholesterol, LDL blood
- Abstract
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., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
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29. Diagnosis and management of familial dyslipoproteinemias.
- Author
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Kwiterovich PO Jr
- Subjects
- Apolipoprotein A-I blood, Apolipoprotein A-V, Apolipoprotein C-II blood, Apolipoproteins A blood, Apolipoproteins B blood, Cardiovascular Diseases blood, Cardiovascular Diseases therapy, Cholesterol, HDL blood, Cholesterol, LDL blood, Coronary Artery Disease blood, Coronary Artery Disease therapy, Dyslipidemias blood, Dyslipidemias therapy, Female, Humans, Male, Pancreatitis blood, Pancreatitis therapy, Peptide Fragments blood, Proprotein Convertase 9, Proprotein Convertases blood, Receptors, Lipoprotein blood, Serine Endopeptidases blood, Triglycerides blood, Cardiovascular Diseases prevention & control, Coronary Artery Disease prevention & control, Dyslipidemias diagnosis, Pancreatitis prevention & control
- Abstract
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.
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- 2013
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30. Author's response. Universal lipid screening: in response to ongoing debate.
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McCrindle BW, Kwiterovich PO, McBride PE, Daniels SR, and Kavey RE
- Subjects
- Humans, Male, Cardiovascular Diseases prevention & control, Guideline Adherence, Hypercholesterolemia diagnosis, Mass Screening
- Published
- 2013
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31. Update on the detection and treatment of atherogenic low-density lipoproteins.
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Sniderman A and Kwiterovich PO
- Subjects
- Atherosclerosis drug therapy, Biomarkers blood, Cholesterol, LDL blood, Diet, Fat-Restricted, Female, Humans, Male, Predictive Value of Tests, Prospective Studies, Randomized Controlled Trials as Topic, Risk Assessment, Risk Factors, Apolipoproteins B blood, Atherosclerosis blood, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Lipoproteins, LDL blood
- Abstract
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.
- Published
- 2013
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32. Depressive symptoms and serum lipid levels in young adult women.
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Fang CY, Egleston BL, Gabriel KP, Stevens VJ, Kwiterovich PO Jr, Snetselaar LG, Longacre ML, and Dorgan JF
- Subjects
- Adult, Biomarkers blood, Female, Follow-Up Studies, Health Behavior, Humans, Life Style, Young Adult, Cholesterol blood, Cholesterol, HDL blood, Cholesterol, LDL blood, Depression blood, Depression psychology
- Abstract
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.
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- 2013
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33. 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.
- Author
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Kwiterovich PO, Virgil DG, Chu AY, Khouzami VA, Alaupovic P, and Otvos JD
- Subjects
- Adult, Blood Chemical Analysis, Body Mass Index, Cardiovascular Diseases blood, Cardiovascular Diseases pathology, Female, Follow-Up Studies, Gestational Age, Hospitals, Community, Humans, Infant, Infant, Newborn, Lipoproteins, HDL chemistry, Magnetic Resonance Spectroscopy, Male, Mothers, Parents, Pregnancy, Prospective Studies, Risk Factors, Triglycerides blood, Apolipoprotein C-I blood, Lipoproteins, HDL blood
- Abstract
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., (Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
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34. Universal screening of cholesterol in children.
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Kwiterovich PO and Gidding SS
- Subjects
- Adolescent, Adult, Age of Onset, Biomarkers blood, Cardiovascular Diseases genetics, Cardiovascular Diseases prevention & control, Child, Child, Preschool, Cholesterol, HDL blood, Cholesterol, LDL blood, Early Diagnosis, Genetic Predisposition to Disease, Genetic Testing, Humans, Hyperlipoproteinemia Type II blood, Hyperlipoproteinemia Type II epidemiology, Hyperlipoproteinemia Type II genetics, Hyperlipoproteinemia Type II therapy, Infant, Middle Aged, Obesity epidemiology, Phenotype, Predictive Value of Tests, Prognosis, Risk Assessment, Risk Factors, Young Adult, Cardiovascular Diseases epidemiology, Hyperlipoproteinemia Type II diagnosis, Mass Screening methods
- Abstract
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., (© 2012 Wiley Periodicals, Inc.)
- Published
- 2012
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35. Guidelines for lipid screening in children and adolescents: bringing evidence to the debate.
- Author
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McCrindle BW, Kwiterovich PO, McBride PE, Daniels SR, and Kavey RE
- Subjects
- Adolescent, Adult, Arteriosclerosis epidemiology, Arteriosclerosis genetics, Arteriosclerosis prevention & control, Cardiovascular Diseases epidemiology, Cardiovascular Diseases genetics, Child, Child, Preschool, Cholesterol, LDL blood, Evidence-Based Medicine, Genetic Carrier Screening, Genetic Predisposition to Disease genetics, Humans, Hypercholesterolemia epidemiology, Hypercholesterolemia genetics, Infant, Male, Middle Aged, Risk Factors, Young Adult, Cardiovascular Diseases prevention & control, Guideline Adherence, Hypercholesterolemia diagnosis, Mass Screening
- Published
- 2012
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36. Height, adiposity and body fat distribution and breast density in young women.
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Dorgan JF, Klifa C, Shepherd JA, Egleston BL, Kwiterovich PO, Himes JH, Gabriel K, Horn L, Snetselaar LG, Stevens VJ, Barton BA, Robson AM, Lasser NL, Deshmukh S, and Hylton NM
- Subjects
- Adult, Age Factors, Body Weights and Measures, Breast Neoplasms pathology, Cross-Sectional Studies, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Risk Factors, Absorptiometry, Photon, Adiposity, Body Fat Distribution, Body Height, Mammary Glands, Human
- Abstract
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.
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- 2012
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37. Adolescent diet and metabolic syndrome in young women: results of the Dietary Intervention Study in Children (DISC) follow-up study.
- Author
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Dorgan JF, Liu L, Barton BA, Deshmukh S, Snetselaar LG, Van Horn L, Stevens VJ, Robson AM, Lasser NL, Himes JH, Shepherd JA, Pourfarzib R, Pettee Gabriel K, Kriska A, and Kwiterovich PO Jr
- Subjects
- Adolescent, Adult, Blood Pressure physiology, Child, Dietary Fats, Dietary Fiber, Female, Follow-Up Studies, Humans, Insulin Resistance physiology, Longitudinal Studies, Metabolic Syndrome etiology, Randomized Controlled Trials as Topic, Treatment Outcome, Diet, Feeding Behavior, Metabolic Syndrome metabolism
- Abstract
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.
- Published
- 2011
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38. Clinical implications of the molecular basis of familial hypercholesterolemia and other inherited dyslipidemias.
- Author
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Kwiterovich PO Jr
- Subjects
- Adolescent, Child, Child, Preschool, Cholesterol blood, Cholesterol, LDL blood, Dyslipidemias genetics, Humans, Hyperlipoproteinemia Type II blood, Mutation, Receptors, LDL genetics, Hyperlipoproteinemia Type II genetics
- Published
- 2011
- Full Text
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39. The use of lipid-lowering drugs in children.
- Author
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Brown WV, Wilson DP, Freemark M, and Kwiterovich PO
- Subjects
- Cardiovascular Diseases drug therapy, Child, Cholesterol, LDL blood, Humans, Risk Factors, Triglycerides blood, Hypolipidemic Agents therapeutic use
- Published
- 2010
- Full Text
- View/download PDF
40. 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.
- Author
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Dorgan JF, Liu L, Klifa C, Hylton N, Shepherd JA, Stanczyk FZ, Snetselaar LG, Van Horn L, Stevens VJ, Robson A, Kwiterovich PO Jr, Lasser NL, Himes JH, Pettee Gabriel K, Kriska A, Ruder EH, Fang CY, and Barton BA
- Subjects
- Adolescent, Adult, Child, Cholesterol, LDL blood, Diet, Estradiol blood, Female, Follow-Up Studies, Humans, Mammography, Progesterone blood, Sex Hormone-Binding Globulin metabolism, Young Adult, Bone Density, Breast anatomy & histology, Breast Neoplasms prevention & control, Diet, Fat-Restricted, Gonadal Hormones blood
- Abstract
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. Participants were 25 to 29 years old at follow-up visits. All tests of statistical significance are two-sided., Results: In analyses that did not take account of diet at the time of the follow-up visit, the only statistically significant treatment group difference was higher bone mineral content in intervention group participants compared with usual care group participants; their mean bone mineral contents were 2,444 and 2,377 g, respectively. After adjustment for current diet, the intervention group also had statistically significantly higher bone mineral density and luteal phase serum estradiol concentrations. Serum progesterone concentrations and breast density did not differ by treatment group in unadjusted or adjusted analyses., Conclusions: Results do not support the hypothesis that consumption of a lower fat diet during adolescence reduces breast cancer risk via effects on subsequent serum estradiol and progesterone levels, breast density, or bone mineral density. It remains unclear, however, if the results are specific to the DISC intervention or are more broadly applicable., Impact: Modest reductions in fat intake during adolescence are unlikely to lower later breast cancer risk via long-term effects on the biomarkers measured., (Copyright 2010 AACR.)
- Published
- 2010
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41. Recognition and management of dyslipidemia in children and adolescents.
- Author
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Kwiterovich PO Jr
- Subjects
- Adolescent, Atherosclerosis blood, Atherosclerosis mortality, Cardiovascular Diseases blood, Cardiovascular Diseases mortality, Child, Cholesterol blood, Coronary Disease epidemiology, Dyslipidemias blood, Dyslipidemias complications, Humans, Hypercholesterolemia blood, Hypercholesterolemia epidemiology, Lipoproteins blood, Mass Screening, Obesity complications, Risk Factors, United States epidemiology, Atherosclerosis epidemiology, Cardiovascular Diseases epidemiology, Dyslipidemias diagnosis, Dyslipidemias therapy, Obesity diagnosis, Obesity therapy
- Abstract
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., Evidence Acquisition: A detailed literature search from 1985-2008 was performed using PubMed and subsequent reference searches of retrieved articles. Selection of included articles was based on rigor of scientific design, adequate sample size, quality of the data, statistical analysis, and hypothesis testing., Evidence Synthesis: CVD risk factors in children predict pathological lesions of atherosclerosis in young adults, and their clinical manifestations, as judged by carotid intima medial thickness, coronary artery calcium, or brachial flow-mediated dilatation. About half the offspring of a parent with premature CVD have a primary dyslipidemia. However, use of family history to identify such youth will miss the majority of children with dyslipidemia. Treatment of dyslipidemia starts with a low-fat diet supplemented with water-soluble fiber, plant stanols, and plant sterols, weight control, and exercise. Drug therapy with inhibitors of hydroxymethylglutaryl coenzyme A reductase, bile acid sequestrants (BAS), and cholesterol absorption inhibitors can be considered in adolescents with a positive family history of premature CVD and a low-density lipoprotein cholesterol of more than 160 mg/dL. Such dietary and drug therapy appears safe and efficacious and is likely to retard atherosclerosis., Conclusions: Early identification and treatment of youth at risk for early atherosclerosis will require an integrated assessment of predisposing CVD risk factors and a comprehensive universal screening and treatment program.
- Published
- 2008
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42. Clinical and laboratory assessment of cardiovascular risk in children: Guidelines for screening, evaluation, and treatment.
- Author
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Kwiterovich PO
- Abstract
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. Treatment starts with a diet low in total and saturated fat and cholesterol, use of water-soluble fiber, plant stanols and plant sterols, weight control, and exercise. Drug therapy, for example, with inhibitors of hydroxymethylglutaryl-CoA reductase, bile acid sequestrants, and cholesterol absorption inhibitors, can be considered in those with a positive family history of premature CVD and low-density lipoprotein cholesterol >160 mg/dL after dietary and hygienic measures. Candidates for drug therapy often include those with familial hypercholesterolemia, familial combined hyperlipidemia, the metabolic syndrome, polycystic ovarian syndrome, type 1 diabetes, and the nephrotic syndrome. Such dietary and drug therapy appears safe and efficacious. Early identification and treatment of youth with CVD risk factors and dyslipidemia are likely to retard the atherosclerotic process. Optimal detection and treatment of high-risk children either from the general population or from families with premature CVD will require a comprehensive universal screening and evaluation program.
- Published
- 2008
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43. Cut points for lipids and lipoproteins in children and adolescents: should they be reassessed?
- Author
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Kwiterovich PO
- Subjects
- Adolescent, Cardiovascular Diseases genetics, Child, Dyslipidemias genetics, Humans, Hypercholesterolemia genetics, Lipoproteins blood, Risk Factors, Sensitivity and Specificity, Dyslipidemias diagnosis, Lipids blood
- Published
- 2008
- Full Text
- View/download PDF
44. Primary and secondary disorders of lipid metabolism in pediatrics.
- Author
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Kwiterovich PO
- Subjects
- Adolescent, Adult, Atherosclerosis, Cardiovascular Diseases, Child, Diabetes Mellitus, Type 1, Diet, Female, Humans, Life Style, Lipoproteins, Male, Metabolic Syndrome, Nephrotic Syndrome, Polycystic Ovary Syndrome, Lipid Metabolism Disorders diagnosis, Lipid Metabolism Disorders etiology, Lipid Metabolism Disorders therapy, Pediatrics
- Abstract
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. familial hypercholesterolemia [FH]) or secondary to other diseases or conditions (e.g. insulin resistance) and can be clinically significant; for example, elevated low-density lipoprotein cholesterol levels are a major risk factor for future cardiovascular disease. Patients with primary lipid disorders in childhood such as FH can exhibit early atherosclerotic lesions in childhood. Other risk factors for cardiovascular disease, such as obesity and type 2 diabetes mellitus, are increasingly common in the pediatric population, and are often associated with dyslipidemia. Thus, pediatricians should be aware of how to screen, diagnose and treat dyslipidemia. The majority of lipid disorders in children can be managed with diet and lifestyle modification. Pharmacologic therapy (e.g. statins) may be added if target lipoprotein levels are not achieved. Clinicians may be guided in patient management by recent scientific statements from the American Heart Association; however, existing National Cholesterol Education Program treatment guidelines should be urgently updated to incorporate new evidence regarding atherosclerosis pathophysiology, obesity and the metabolic syndrome, emerging cardiovascular risk factors, and pharmacologic therapy in pediatric patients.
- Published
- 2008
45. Beyond low-density lipoprotein cholesterol: defining the role of low-density lipoprotein heterogeneity in coronary artery disease.
- Author
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Mudd JO, Borlaug BA, Johnston PV, Kral BG, Rouf R, Blumenthal RS, and Kwiterovich PO Jr
- Subjects
- Apolipoprotein A-I blood, Apolipoproteins B blood, Biomarkers blood, Coronary Artery Disease blood, Coronary Artery Disease prevention & control, Humans, Particle Size, Predictive Value of Tests, Risk Factors, Coronary Artery Disease etiology, Lipoproteins, LDL physiology
- Abstract
Recent clinical trials in patients with coronary artery disease (CAD) provide evidence that low-density lipoprotein cholesterol (LDL-C) levels should be lowered even further to prevent recurrent CAD. However, despite more aggressive interventions for lowering LDL-C levels, the majority of CAD events go undeterred, perhaps related to the fact that intervention was not started earlier in life or that LDL-C levels represent an incomplete picture of atherogenic potential. Nevertheless, LDL-C remains the contemporary standard as the primary goal for aggressive LDL reduction. If triglycerides are >200 mg/dl, the measurement of non-high-density lipoprotein cholesterol (HDL-C) is recommended. Measurement of apolipoprotein (apo)B has been shown in nearly all studies to outperform LDL-C and non-HDL-C as a predictor of CAD events and as an index of residual CAD risk. This is because apoB reflects the total number of atherogenic apoB-containing lipoproteins and is a superior predictor of the number of low-density lipoprotein particles (LDL-P). Estimates of LDL-P and size can also be made by nuclear magnetic resonance spectroscopy, density gradient ultracentrifugation, and gradient gel electrophoresis. Although a number of studies show that such estimates predict CAD, LDL-P, and size often accompany low HDL-C and high triglyceride levels, and therefore such additional lipoprotein testing has not been recommended for routine screening and follow-up. Because apoB is a superior predictor of LDL-P, we recommend that apoB and the apoB/apoA-I ratio be determined after measurement of LDL-C, non-HDL-C, and the ratio of total cholesterol/HDL-C to better predict CAD and assess efficacy of treatment.
- Published
- 2007
- Full Text
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46. Diet and sex hormones in boys: findings from the dietary intervention study in children.
- Author
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Dorgan JF, McMahon RP, Friedman LA, Van Horn L, Snetselaar LG, Kwiterovich PO Jr, Lauer RM, Lasser NL, Stevens VJ, Robson A, Cooper SF, Chandler DW, Franklin FA, Barton BA, Patterson BH, Taylor PR, and Schatzkin A
- Subjects
- Androstenedione blood, Child, Cholesterol, LDL blood, Dihydrotestosterone blood, Estradiol blood, Humans, Male, Sex Hormone-Binding Globulin analysis, Testosterone blood, Diet, Gonadal Steroid Hormones blood, Puberty blood
- Abstract
Context: Diet reportedly alters serum sex hormone concentrations in adults, but little is known about the influence of diet during puberty on these hormones., Objective: We aimed to determine whether an intervention to lower fat intake during adolescence alters serum sex hormone concentrations and progression through puberty., Design: In 1990-1997, we conducted an ancillary study to the Dietary Intervention Study in Children, a multicenter, randomized, controlled clinical trial to test the safety and efficacy of a cholesterol-lowering dietary intervention in children., Participants: Healthy, prepubertal, 8 to 10 yr olds with elevated low-density lipoprotein cholesterol were randomized to usual care or a behavioral intervention. Of 362 randomized Dietary Intervention Study in Children boys, 354 participated in the ancillary study. Eighty-four percent of boys attended last visits when their median time on trial was 7.1 yr., Intervention: The behavioral intervention continued throughout the duration of the trial and promoted a diet with 28% energy from total fat, less than 8% from saturated fat, 9% or less from polyunsaturated fat, and less than 75 mg cholesterol per 1000 kcal., Outcome Measures: The main outcome measure for boys formulated before study initiation was non-SHBG bound testosterone concentration. Secondary outcomes included serum total testosterone, dihydrotestosterone, androstenedione, estradiol, estrone, SHBG, and Tanner stage., Results: There were no significant treatment group differences in boys' serum hormone levels, SHBG, or Tanner stages at any individual visit or over the course of the trial when evaluated by longitudinal models., Conclusion: Modest reductions in total fat, saturated fat, and possibly energy intake do not alter progression through puberty or serum sex hormone concentrations in adolescent boys.
- Published
- 2006
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47. Treatment of dyslipidemia in children and adolescents.
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Holmes KW and Kwiterovich PO Jr
- Subjects
- Adolescent, Atherosclerosis etiology, Atherosclerosis prevention & control, Child, Dyslipidemias complications, Humans, Risk Factors, Diet, Fat-Restricted, Dyslipidemias therapy, Exercise Therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use
- Abstract
The early lesions of atherosclerosis begin in childhood, and are related to antecedent cardiovascular disease risk factors. Environmental and genetic factors such as diet, obesity, exercise, and certain inherited dyslipidemias influence the progression of such lesions. The identification of youth at risk for atherosclerosis includes an integrated assessment of these predisposing factors. Treatment starts with a diet low in total and saturated fat and cholesterol, the use of water-soluble fiber and plant sterols, weight control, and exercise. Drug therapy, for example, with inhibitors of hydroxymethylglutaryl CoA reductase, bile acid sequestrants, and cholesterol absorption inhibitors, can be considered in those with a positive family history of premature coronary artery disease and a low-density lipoprotein cholesterol above 160 mg/dL, after dietary and hygienic measures. Candidates for drug therapy often include those with familial hypercholesterolemia, familial combined hyperlipidemia, the metabolic syndrome, polycystic ovarian syndrome, type I diabetes, and the nephrotic syndrome. We review the safety and efficacy of dietary and drug therapy, and propose an updated diagnostic and therapeutic algorithm that includes the metabolic syndrome. The early identification and treatment of youth with dyslipidemias is likely to retard the atherosclerotic process.
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- 2005
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48. Efficacy and safety of lovastatin therapy in adolescent girls with heterozygous familial hypercholesterolemia.
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Clauss SB, Holmes KW, Hopkins P, Stein E, Cho M, Tate A, Johnson-Levonas AO, and Kwiterovich PO
- Subjects
- Adolescent, Anticholesteremic Agents adverse effects, Apolipoproteins blood, Child, Cholesterol, LDL blood, Female, Growth drug effects, Heterozygote, Hormones blood, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Hyperlipoproteinemia Type II blood, Hyperlipoproteinemia Type II genetics, Lipids blood, Lipoproteins blood, Lovastatin adverse effects, Anticholesteremic Agents therapeutic use, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Hyperlipoproteinemia Type II drug therapy, Lovastatin therapeutic use
- Abstract
Objective: The present study was designed to evaluate the lipid-altering efficacy, safety, and tolerability of lovastatin treatment in adolescent girls with heterozygous familial hypercholesterolemia., Methods: A total of 54 postmenarchal girls, aged 10 to 17 years, were enrolled in a 24-week, double-blind, randomized, placebo-controlled study. After a 4-week diet/placebo run-in period, patients were randomized to 1 of 2 groups: (1) treatment with diet plus lovastatin 20 mg/day for 4 weeks, followed by diet plus lovastatin 40 mg/day for 20 weeks, or (2) diet plus placebo for 24 weeks., Results: Baseline values of lipids, lipoproteins, and apolipoproteins (apo) were comparable between treatment groups. Lovastatin treatment was efficacious at reducing low-density lipoprotein cholesterol by 23% to 27%, total cholesterol by 17% to 22%, and apo B by 20% to 23% at weeks 4 and 24, respectively. Between-treatment group differences were not statistically significant for triglycerides, very-low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or apo A-I. Lovastatin was generally safe and well tolerated. There were no clinically significant alterations in vital signs (blood pressure and pulse rate), anthropomorphic measurements (height, weight, and BMI), hormone levels (luteinizing hormone, follicle-stimulating hormone, dehydroepiandrosterone sulfate, estradiol, and cortisol), menstrual cycle length, or tests of liver and muscle function., Conclusions: Lovastatin offers an efficacious and well-tolerated treatment option for improving lipid profiles in adolescent girls with familial hypercholesterolemia.
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- 2005
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49. Lipoprotein heterogeneity at birth: influence of gestational age and race on lipoprotein subclasses and Lp (a) lipoprotein.
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Kwiterovich PO Jr, Virgil DG, Garrett ES, Otvos J, Driggers R, Blakemore K, Cockrill SL, and Macfarlane RD
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- Age Factors, Apolipoprotein A-I blood, Apolipoprotein A-II blood, Apolipoprotein C-II, Apolipoproteins genetics, Apolipoproteins C blood, Cholesterol, HDL blood, Cholesterol, LDL blood, Female, Humans, Infant, Newborn, Lipoproteins genetics, Lipoproteins, HDL blood, Lipoproteins, LDL blood, Male, Maryland, Prospective Studies, Risk Factors, Sex Factors, Triglycerides genetics, Black or African American, Apolipoproteins blood, Black People genetics, Gestational Age, Lipoproteins blood, Triglycerides blood, White People genetics
- Abstract
Objective: To determine the influence of gestational age, gender, and race, on lipoprotein heterogeneity at birth., Design: Prospective study of representative sample of infants., Setting: The Johns Hopkins Hospital., Participants: 163 infants (70 White and 93 Black) >28 weeks gestational age., Intervention: None., Main Outcome Measures: Lipids, lipoprotein subclasses, apolipoproteins, Lp (a) lipoprotein., Results: The number of low-density lipoprotein (LDL) particles, large LDL subclass, and LDL cholesterol level, were all significantly higher in the younger infants. The large high-density lipoprotein (HDL) subclass was significantly higher, while the small HDL subclass was significantly lower in the younger infants. Female infants had a greater HDL size than did males (P=.03). There were no differences between the age groups for HDL cholesterol, very low-density lipoprotein subclasses, or levels of triglycerides, or apolipoproteins B and A-I. White infants had a notably higher mean (SD) level (nmol/L) of total LDL particles (476 [251]), compared to the Black infants (372 [177]) (P=.009). The Black infants had a significantly (P=.02) higher mean (SD) Lp (a) lipoprotein level (mg/dL), compared to the White infants, 2.8 (3.2) vs 1.7 (2.4). Black small-for-gestational age infants had significantly higher levels of very low and intermediate density lipoproteins and apolipoprotein B, compared to appropriate-for-gestational age infants., Conclusions: Gestational age has a significant effect on both LDL and HDL subclasses. Differences in LDL particle number and Lp (a) between White and Black infants mirror those seen later in life.
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- 2004
50. A summary of results of the Dietary Intervention Study in Children (DISC): lessons learned.
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Van Horn L, Obarzanek E, Barton BA, Stevens VJ, Kwiterovich PO Jr, Lasser NL, Robson AM, Franklin FA Jr, Lauer RM, Kimm SY, Dorgan JF, and Greenlick MR
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- Biomarkers blood, Body Mass Index, Child, Child Nutritional Physiological Phenomena, Cholesterol, HDL blood, Cholesterol, LDL blood, Diet Records, Female, Ferritins blood, Follow-Up Studies, Humans, Learning, Male, Nutritional Status physiology, Predictive Value of Tests, Psychological Tests, Sexual Maturation physiology, Socioeconomic Factors, Time Factors, Treatment Outcome, United States, Vitamin E administration & dosage, Zinc administration & dosage, Dietary Fats administration & dosage, Dietary Fats metabolism
- Abstract
Prevention of cardiovascular disease must begin in childhood, preferably before risk factors develop. Elevated low-density lipoprotein cholesterol levels in children are likely to track over time and become high-risk levels in adults. The Dietary Intervention Study in Children (DISC) was a multicenter, collaborative randomized trial in pre-adolescent children designed to test the efficacy and safety of a dietary intervention to lower saturated fat and cholesterol intake among growing children with elevated low-density lipoprotein cholesterol. Numerous DISC results, which include findings on lipids-lipoproteins, genetics, and nutrient adequacy, as well as descriptions of the behavioral intervention strategies, have been reported. A summary of practical findings and their potential clinical applications have not previously been published. Highlights of key lessons learned from DISC and translational applications of potential interest to nurses and other health care providers are presented., (Copyright 2003 CHF, Inc.)
- Published
- 2003
- Full Text
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