David S. Freedman

The Relation of Overweight to Cardiovascular Risk Factors Among Children and Adolescents: The Bogalusa Heart Study

Background. Although overweight and obesity in childhood are related to dyslipidemia, hyperinsulinemia, and hypertension, most studies have examined levels of these risk factors individually or have used internal cutpoints (eg, quintiles) to classify overweight and risk factors. Objective. We used cutpoints derived from several national studies to examine the relation of overweight (Quetelet index, >95th percentile) to adverse risk factor levels and risk factor clustering. Design. The sample consisted of 9167 5- to 17-year-olds examined in seven cross-sectional studies conducted by the Bogalusa Heart Study between 1973 and 1994. Results. About 11% of examined schoolchildren were considered overweight. Although adverse lipid, insulin, and blood pressure levels did not vary substantially with the Quetelet index at levels <85th percentile, risk factor prevalences increased greatly at higher levels of the Quetelet index. Overweight schoolchildren were 2.4 times as likely as children with a Quetelet index <85th percentile to have an elevated level of total cholesterol. Odds ratios for other associations were 2.4 (diastolic blood pressure), 3.0 (low-density lipoprotein cholesterol), 3.4 (high-density lipoprotein cholesterol), 4.5 (systolic blood pressure), 7.1 (triglycerides), and 12.6 (fasting insulin). Several of these associations differed between whites and blacks, and by age. Of the 813 overweight schoolchildren, 475 (58%) were found to have at least one risk factor. Furthermore, the use of overweight as a screening tool could identify 50% of schoolchildren who had two or more risk factors. Conclusions. Because overweight is associated with various risk factors even among young children, it is possible that the successful prevention and treatment of obesity in childhood could reduce the adult incidence of cardiovascular disease.overweight, lipids, blood pressure, insulin, children, adolescents.

Relation of serum lipoprotein levels and systolic blood pressure to early atherosclerosis. The Bogalusa Heart Study.

Abstract We assessed the relation of risk factors for cardiovascular disease to early atherosclerotic lesions in the aorta and coronary arteries in 35 persons (mean age at death, 18 years). Aortic involvement with fatty streaks was greater in blacks than in whites (37 vs. 17 percent, P<0.01). However, aortic fatty streaks were strongly related to antemortem levels of both total and low-density lipoprotein cholesterol (r = 0.67, P<0.0001 for each association), independently of race, sex, and age, and were inversely correlated with the ratio of high-density lipoprotein cholesterol to low-density plus very-low-density lipoprotein cholesterol (r = -0.35, P = 0.06). Coronary Artery fatty streaks were correlated with very-low-density lipoprotein cholesterol (r=0.41, P = 0.04). Mean systolic blood-pressure levels also tended to be higher in the four subjects with coronary-artery fibrous plaques than in those without them: 112 mm Hg as compared with 104 (P = 0.09). These results document the importance of risk-fa...

The relation of childhood BMI to adult adiposity: the Bogalusa Heart Study.

Objective. Although many studies have found that childhood levels of body mass index (BMI; kg/m2) are associated with adult levels, it has been reported that childhood BMI is not associated with adult adiposity. We further examined these longitudinal associations. Design. Cohort study based on examinations between 1973 and 1996. Setting. Bogalusa, Louisiana. Participants. Children (2610; ages 2-17 years old) who were followed to ages 18 to 37 years; the mean follow-up was 17.6 years. Main Outcome Measures. BMI-for-age and triceps skinfold thickness (SF) were measured in childhood. Subscapular and triceps SFs were measured among adults, and the mean SF was used as an adiposity index. Adult obesity was defined as a BMI ≥ 30 kg/m2 and adult overfat as a mean SF in the upper (gender-specific) quartile. Results. Childhood levels of both BMI and triceps SF were associated with adult levels of BMI and adiposity. The magnitude of these longitudinal associations increased with childhood age, but the BMI levels of even the youngest (ages 2-5 years) children were moderately associated (r = 0.33-0.41) with adult adiposity. Overweight (BMI-for-age ≥ 95th centile) 2- to 5-year-olds were >4 times as likely to become overfat adults (15 of 23 [65%]), as were children with a BMI < 50th centile (30 of 201 [15%]). Even after accounting for the triceps SF of children, BMI-for-age provided additional information on adult adiposity. Conclusions. Childhood BMI is associated with adult adiposity, but it is possible that the magnitude of this association depends on the relative fatness of children.

Low-Density Lipoprotein and High-Density Lipoprotein Particle Subclasses Predict Coronary Events and Are Favorably Changed by Gemfibrozil Therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial

Background— Changes in conventional lipid risk factors with gemfibrozil treatment only partially explain the reductions in coronary heart disease (CHD) events experienced by men in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT). We examined whether measurement of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle subclasses provides additional information relative to CHD risk reduction. Methods and Results— This is a prospective nested case-control study of 364 men with a new CHD event (nonfatal myocardial infarction or cardiac death) during a 5.1-year (median) follow-up and 697 age-matched controls. Nuclear magnetic resonance (NMR) spectroscopy was used to quantify levels of LDL and HDL particle subclasses and mean particle sizes in plasma obtained at baseline and after 7 months of treatment with gemfibrozil or placebo. Odds ratios for a 1-SD increment of each lipoprotein variable were calculated with adjusted logistic regression models. Gemfibrozil treatment increased LDL size and lowered numbers of LDL particles (−5%) while raising numbers of HDL particles (10%) and small HDL subclass particles (21%). Concentrations of these LDL and HDL particles achieved with gemfibrozil were significant, independent predictors of new CHD events. For total LDL and HDL particles, odds ratios predicting CHD benefit were 1.28 (95% CI, 1.12 to 1.47) and 0.71 (95% CI, 0.61 to 0.81), respectively. Mean LDL and HDL particle sizes were not associated with CHD events. Conclusions— The effects of gemfibrozil on NMR-measured LDL and HDL particle subclasses, which are not reflected by conventional lipoprotein cholesterol measures, help to explain the demonstrated benefit of this therapy in patients with low HDL cholesterol.

Racial and Ethnic Differences in Secular Trends for Childhood BMI, Weight, and Height

Objectives: The prevalence of childhood overweight in the United States has markedly increased over the last 30 years. We examined differences in the secular trends for BMI, weight, and height among white, black, and Mexican‐American children.

Relation of Lipoprotein Subclasses as Measured by Proton Nuclear Magnetic Resonance Spectroscopy to Coronary Artery Disease

Although each of the major lipoprotein fractions is composed of various subclasses that may differ in atherogenicity, the importance of this heterogeneity has been difficult to ascertain owing to the labor-intensive nature of subclass measurement methods. We have recently developed a procedure, using proton nuclear magnetic resonance (NMR) spectroscopy, to simultaneously quantify levels of subclasses of very low density (VLDL), low density (LDL), and high density (HDL) lipoproteins; subclass distributions determined with this method agree well with those derived by gradient gel electrophoresis. The objective of the current study of 158 men was to examine whether NMR-derived lipoprotein subclass levels improve the prediction of arteriographically documented coronary artery disease (CAD) when levels of lipids and lipoproteins are known. We found that a global measure of CAD severity was positively associated with levels of large VLDL and small HDL particles and inversely associated with intermediate size HDL particles; these associations were independent of age and standard lipid measurements. At comparable lipid and lipoprotein levels, for example, men with relatively high (higher than the median) levels of either small HDL or large VLDL particles were three to four times more likely to have extensive CAD than were the other men; the 27 men with high levels of both large VLDL and small HDL were 15 times more likely to have extensive CAD than were men with low levels. In contrast, adjustment for levels of triglycerides or HDL cholesterol greatly reduced the relation of small LDL particles to CAD. These findings suggest that large VLDL and small HDL particles may play important roles in the development of occlusive disease and that their measurement, which is not possible with routine lipid testing, may lead to more accurate risk assessment.

Relation of BMI to fat and fat-free mass among children and adolescents

OBJECTIVE:Although the body mass index (BMI, kg/m2) is widely used as a surrogate measure of adiposity, it is a measure of excess weight, rather than excess body fat, relative to height. We examined the relation of BMI to levels of fat mass and fat-free mass among healthy 5- to 18-y-olds.METHODS AND PROCEDURES:Dual-energy X-ray absorptiometry was used to measure fat and fat-free mass among 1196 subjects. These measures were standardized for height by calculating the fat mass index (FMI, fat mass/ht2) and the fat-free mass index (FFMI, fat-free mass/ht2).RESULTS:The variability in FFMI was about 50% of that in FMI, and the accuracy of BMI as a measure of adiposity varied greatly according to the degree of fatness. Among children with a BMI-for-age ≥85th P, BMI levels were strongly associated with FMI (r=0.85–0.96 across sex–age categories). In contrast, among children with a BMI-for-age <50th P, levels of BMI were more strongly associated with FFMI (r=0.56–0.83) than with FMI (r=0.22–0.65). The relation of BMI to fat mass was markedly nonlinear, and substantial differences in fat mass were seen only at BMI levels ≥85th P.DISCUSSION:BMI levels among children should be interpreted with caution. Although a high BMI-for-age is a good indicator of excess fat mass, BMI differences among thinner children can be largely due to fat-free mass.

Health risks of obesity.

Evidence implicating obesity as a risk-factor disease is critically reviewed. Possible reasons for the many conflicting findings are addressed. The classification of obesity, based upon the site of body fat distribution, and possible biologic mechanisms associating regional adiposity with morbidity, are discussed.

Relations of lipoprotein subclass levels and low-density lipoprotein size to progression of coronary artery disease in the pravastatin limitation of atherosclerosis in the coronary arteries (PLAC-I) trial☆

Lipoprotein subclass measurements may enhance the prediction of coronary artery disease (CAD) risk, but clinical application of such information has been hindered by the relatively laborious and time-consuming nature of laboratory measurement methods. In this study, lipoprotein subclass analyses were performed on frozen plasma samples from 241 participants in the Pravastatin Limitation of Atherosclerosis in the Coronary arteries Trial using an automated nuclear magnetic resonance technique. The objective was to determine if levels of these subclasses provided additional information on the progression of CAD, based on the change in the minimum lumen diameter, over a 3-year period. After adjustment for race, sex, age, treatment group, baseline lumen diameter, and chemically measured levels of triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol, on-trial predictors (p <0.05) of progression included an elevated LDL particle number, and levels of small LDL and small HDL. Within treatment groups, CAD progression was most strongly related to the LDL particle number (placebo) and levels of small HDL (pravastatin). In logistic regression models that adjusted for chemically determined lipid levels and other covariates, a small LDL level > or = 30 mg/dl (median) was associated with a ninefold increased risk of CAD progression (p <0.01) in the placebo group. These results indicate that levels of various lipoprotein subclasses may provide useful information on CAD risk even if levels of traditional risk factors are known.

The Validity of BMI as an Indicator of Body Fatness and Risk Among Children

PURPOSE OF REVIEW: Although the prevalence of childhood obesity, as assessed by BMI (kg/m2), has tripled over the last 3 decades, this index is a measure of excess weight rather than excess body fatness. In this review we focus on the relation of BMI to body fatness and health risks, particularly on the ability of BMI for age ≥95th Centers for Disease Control and Prevention [CDC] percentile to identify children who have excess body fatness. We also examine whether these associations differ according to race/ethnicity and whether skinfold and circumference measurements provide additional information on body fatness or health risks. RESULTS: The accuracy of BMI varies according to the degree of body fatness. Among relatively fat children, BMI is a good indicator of excess adiposity, but differences in the BMIs of relatively thin children can be largely due to fat-free mass. Although the accuracy of BMI in identifying children with excess body fatness depends on the chosen cut points, we have found that a high BMI-for-age has a moderately high (70%–80%) sensitivity and positive predictive value, along with a high specificity (95%). Children with a high BMI are much more likely to have adverse risk factor levels and to become obese adults than are thinner children. Skinfold thicknesses and the waist circumference may be useful in identifying children with moderately elevated levels of BMI (85th to 94th percentiles) who truly have excess body fatness or adverse risk factor levels. CONCLUSION: A BMI for age at ≥95th percentile of the CDC reference population is a moderately sensitive and a specific indicator of excess adiposity among children.