Aggressive management of obesity in children and young adults: the known challenges and potential opportunities.

The world is confronted with an impending epidemic of premature cardiovascular disease (CVD) that is being fueled by an increase in the prevalence of central obesity.

Estimating the consequences of anti-psychotic induced weight gain on health and mortality rate.

Many anti-psychotic medications produce marked weight gain. In this study, we estimate the expected impact of degrees of antipsychotic-induced weight gain on selected mortality rate and incidence rates of impaired glucose tolerance (IGT) and hypertension (HTN) among US adults. Using raw data from 5209 respondents from the Framingham Heart Study's public use data set and national statistics on population demographics, we estimated the expected effect of weight gain on number of deaths and incident cases of IGT and HTN for a 10-year period commencing in 1999. Results indicated that the estimated deleterious effects of weight gain were greater for people with higher BMIs at baseline, for greater degrees of weight gain, for men than women, and for older than younger persons. Because there is a 'U-shaped' relation between BMI and mortality rate, small to moderate weight gains among people with baseline BMIs less than 23 were predicted to decrease mortality rates, whereas weight gains among people with baseline BMIs above that level were expected to increase mortality rates. However, the relations of IGT and HTN with BMI are monotonically increasing. Thus, the anticipated effect of weight gain on IGT and HTN is deleterious regardless of baseline BMI. Because it is unclear whether the beneficial effects of the atypical agents on, for example, reducing suicide mortality, outweigh the putative increase in mortality due to weight gain, we estimate the beneficial effects due to decreased death from suicide with the potential deleterious effects due to a 10-kg weight gain. We found that 492 suicide deaths per 100,000 schizophrenic patients would be prevented over 10 years with the use of clozapine compared to 416 additional deaths due to antipsychotic induced weight gain. Although this estimate is rather crude and should be seen only as offering a sense of the likely situation, results suggest that the lives saved via clozapine may essentially be offset by the deaths due to weight gain. As we discuss, it is not possible to provide definitive estimates of the effect of antipsychotic-induced weight gain on health and mortality, but our findings suggest that the magnitude of weight gains induced by many antipsychotic agents is likely to have important deleterious effects on mortality and health.

Expanded Clinical Evaluation of Lovastatin (EXCEL) study results: two-year efficacy and safety follow-up.

The Expanded Clinical Evaluation of Lovastatin study, a randomized, double-blind, placebo- and diet-controlled multicenter trial, evaluated the efficacy and tolerability of lovastatin over 48 weeks in 8,245 patients with moderately severe hypercholesterolemia. During year 1 of follow-up of the full cohort, lovastatin at 20 or 40 mg/day, or 20 or 40 mg twice daily, produced dose-dependent decreases in low-density lipoprotein (LDL) cholesterol (24% to 40%) and triglyceride levels (10% to 19%), and increases in high-density lipoprotein (HDL) cholesterol (6.6% to 9.5%). In all, 977 patients continued their original blinded treatment for an additional year. In year 2, the LDL cholesterol response to lovastatin was maintained, the triglyceride reductions were somewhat less, and the increases in HDL cholesterol were moderately greater than in year 1. Successive transaminase elevations > 3 times the upper limit of normal were observed in only 1 patient in year 2, yielding a cumulative 2-year incidence of from 0.1% (placebo or lovastatin 20 mg/day) to 1.9% (lovastatin 80 mg/day). Myopathy occurred in only 1 patient during year 2, and over the 2-year study was observed rarely and only at lovastatin dosages of 40 and 80 mg/day. This study indicates that lovastatin maintains its efficacy over long-term follow-up, particularly in effectively lowering LDL cholesterol, is generally well tolerated, and has a favorable safety profile.

Efficacy and tolerability of lovastatin in 3390 women with moderate hypercholesterolemia.

OBJECTIVE: To evaluate the efficacy and safety of lovastatin in women with moderate hypercholesterolemia. DESIGN: The Expanded Clinical Evaluation of Lovastatin (EXCEL) Study, a multicenter, double-blind, diet- and placebo-controlled trial, in which participants were randomly assigned to receive placebo or lovastatin at doses of 20 or 40 mg once daily, or 20 or 40 mg twice daily for 48 weeks. SETTING: Ambulatory patients recruited by 362 participating centers throughout the United States. PATIENTS: Women (n = 3390) from the total cohort of 8245 volunteers. MEASUREMENTS: Plasma total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, and triglycerides; and laboratory and clinical evidence of adverse events monitored periodically throughout the study. RESULTS: Among women, lovastatin (20 to 80 mg/d) produced sustained (12- to 48-week), dose-related changes (P < 0.001): decreases in LDL cholesterol (24% to 40%) and triglycerides (9% to 18%), and increases in HDL cholesterol (6.7% to 8.6%). Depending on the dose, from 82% to 95% of lovastatin-treated women achieved the National Cholesterol Education Program goal of LDL cholesterol levels less than 4.14 mmol/L (160 mg/dL), and 40% to 87% achieved the goal of 3.36 mmol/L (130 mg/dL). Successive transaminase elevations greater than three times the upper limit of normal occurred in 0.1% of women and were dose dependent above the 20-mg dose. Myopathy, defined as muscle symptoms with creatine kinase elevations greater than 10 times the upper limit of normal, was rare and associated with the highest recommended daily dose of lovastatin (80 mg). Estrogen-replacement therapy appeared to have no effect on either the efficacy or safety profile of lovastatin. CONCLUSION: Lovastatin is highly effective and generally well tolerated as therapy for primary hypercholesterolemia in women.

The case for unstable angina pectoris as a primary end point in primary prevention studies.

Coronary artery disease (CAD) primary end point definitions used in previous prevention trials are reviewed, as well as trends over time for CAD mortality, incidence and hospital discharges to see if new primary end points should be considered. CAD mortality has shown a dramatic decline in the U.S. in the last 20 years, whereas the decrease in the incidence of acute myocardial infarction (AMI) is less consistent. The decline in CAD incidence and mortality has been attributed to changes in lifestyle and increased medical/surgical intervention. Hospital discharge rates for CAD have risen during the past decade. In addition, although the rate of discharge for AMI appears to have stabilized, the rates for angina, and more dramatically for unstable angina, have increased. Unstable angina made up 4% of CAD discharges in 1980, and increased to 25% of CAD discharges in 1989. Because of these trends, future trials that rely solely on AMI as a primary end point will not reflect the actual experience with CAD presentation in the U.S. Given the greater availability of methods to diagnose unstable angina more accurately, and because of its high risk pathology, it is concluded that unstable angina should receive serious consideration as a primary end point in future primary prevention trials.

Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. Effect of patient characteristics on lovastatin-induced changes in plasma concentrations of lipids and lipoproteins.

BACKGROUND: Lovastatin produces consistent dose-related reductions in plasma levels of low density lipoprotein (LDL) cholesterol along with variable decreases in triglycerides and increases in high density lipoprotein (HDL) cholesterol. Patient characteristics from the Expanded Clinical Evaluation of Lovastatin (EXCEL) study were examined to determine their association with the magnitude of lovastatin-induced changes in these lipids and lipoproteins. METHODS AND RESULTS: After a baseline period consisting of dietary therapy, 8,245 patients with moderate hypercholesterolemia were randomized to five groups that received 48 weeks of treatment with either placebo or daily doses of lovastatin ranging from 20 to 80 mg. By use of linear statistical models, 20 different patient characteristics were examined for modification of the dose-dependent responses observed. For LDL cholesterol, the following were associated with enhanced lowering (p less than 0.05; percent changes are placebo-corrected, adjusted mean changes from baseline for the 80-mg/day lovastatin group): full drug compliance (-41.9%) versus 80% compliance (-20.3%); an age of 65 (-43.4%) versus 45 years (-38.1%) for women; white race (-40.9%) versus black race (-38.0%); and 4.5-kg weight gain (-42.6%) versus 4.5-kg weight loss (-37.9%). Similar relations for enhanced triglyceride lowering were found with older age and weight gain. Patients with initially low HDL cholesterol (less than 0.91 mmol/l) and high triglycerides (greater than 2.26 mmol/l) had enhanced responses for these parameters: placebo-corrected percent changes at 80 mg/day were -27.4% for triglycerides and +12.3% for HDL cholesterol. CONCLUSIONS: Overall, patient characteristics had very little impact of clinical importance on the dose-dependent LDL cholesterol lowering found with lovastatin. In patients with initially high levels of triglycerides and low levels of HDL cholesterol, the elevation of HDL cholesterol produced by lovastatin appears to be enhanced.

Lovastatin and coadministered antihypertensive/cardiovascular agents.

Hypertension and hypercholesterolemia frequently coexist and may require concomitant drug treatments. The efficacy and safety profile of lovastatin given in the presence of antihypertensive medication was evaluated using patient subgroups identified in the Expanded Clinical Evaluation of Lovastatin (EXCEL) Study. The EXCEL study examined 8,245 patients with moderate hypercholesterolemia randomly assigned either to a group treated with lovastatin (20-80 mg daily) or to a group given placebo for 48 weeks. After adjustment for patient characteristics, pairwise comparisons were made between patients taking no antihypertensive agents (n = 3,772) and those taking either calcium antagonists (n = 446), selective beta 1-adrenergic receptor blockers (n = 326), nonselective beta-adrenergic receptor blockers (n = 219), potassium-sparing diuretics (n = 187), thiazide diuretics (n = 126), or angiotensin converting enzyme inhibitors (n = 171). The placebo-corrected dose-dependent effect of lovastatin on the percent change from baseline in low-density lipoprotein cholesterol was not attenuated in any subgroup and was slightly enhanced in the calcium antagonist subgroup (-29% to -44%, p = 0.06) when compared with patients taking no antihypertensive agents (-24% to -40%); this difference, however, was only of borderline significance. Patterns of lovastatin-induced increase in high-density lipoprotein cholesterol and decrease in triglycerides were not consistently different among the subgroups. Examination of mean changes in serum transaminases, mean changes in creatine kinase, and the proportion of patients discontinuing therapy for clinical adverse experiences did not indicate the presence of an interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Expanded clinical evaluation of lovastatin (EXCEL) study results: III. Efficacy in modifying lipoproteins and implications for managing patients with moderate hypercholesterolemia.

In the multicenter, double-blind EXCEL (Expanded Clinical Evaluation of Lovastatin) study the efficacy of lovastatin in modifying plasma lipids and lipoproteins in 8,245 participants with moderate primary hypercholesterolemia was evaluated. Patients were randomly assigned to 48 weeks of treatment with diet and placebo or diet and lovastatin 20 or 40 mg once a day, or 20 or 40 mg twice a day. At all of these dosages, lovastatin produced substantial dose-dependent reductions in low-density-lipoprotein (LDL)-cholesterol levels, averaging 24% (20 mg/day) to 40% (80 mg/day). The magnitude of the effect of this lipoprotein was further reflected by the percentage of patients who achieved National Cholesterol Education Program (NCEP) goals. In the absence of coronary artery disease (CAD) or two other CAD risk factors, the LDL-cholesterol goal of 4.14 mmol/L (160 mg/dL) was attained by 22% of patients in the placebo group and between 81% (20 mg/day) and 96% (80 mg/day) of those treated with lovastatin. For those with CAD or at least two other CAD risk factors, the LDL-cholesterol goal of 3.36 mmol/L (130 mg/dL) was attained by 4% of placebo patients and between 38% (20 mg/day) and 83% (80 mg/day) of those treated with lovastatin. Lovastatin also increased high-density-lipoprotein cholesterol (7-10%) and decreased triglycerides (10-19%) in a dose-dependent manner. Thus, when used as an adjunct to a prudent diet, lovastatin produces favorable changes in the entire lipoprotein profile and is a highly effective agent for managing patients with primary hypercholesterolemia.

Expanded clinical evaluation of lovastatin (EXCEL) study results: IV. Additional perspectives on the tolerability of lovastatin.

This randomized, double-blind, multicenter, diet-and-placebo-controlled study was designed to clarify the dose-response relationship of lovastatin therapy to lipid-modifying efficacy and drug-related adverse events. Exclusion criteria were minimized so that study patients were representative of the majority of patients with moderate hypercholesterolemia seen in medical practice. After 6 weeks on the American Heart Association Step 1 Diet, a total of 8,245 patients were randomly assigned to 48 weeks of treatment with diet and placebo or lovastatin at dosages of 20 or 40 mg once a day or 20 or 40 mg twice a day. All adverse events were monitored, with particular attention to evaluation of liver and muscle. Liver transaminase elevations suggestive of possible hepatotoxicity, defined as successive elevations in either aspartate transaminase or alanine aminotransferase greater than 3 times the upper limit of normal, occurred in equal numbers of placebo and lovastatin 20 mg/day treated patients (0.1%). The frequencies were higher in lovastatin 40 mg/day and 80 mg/day patient groups (0.9 and 1.5%, respectively). No patient was diagnosed as having clinically symptomatic hepatic dysfunction. Creatinine kinase (CK) elevations above the upper limit of normal occurred frequently in placebo- (29%), as well as lovastatin-treated patients (29-35%), and muscle symptoms were reported with similar frequency in all groups (7-9%). The combination of muscle symptoms with marked CK elevations (greater than 10 times the upper limit of normal) was seen in only five patients: one in a 40 mg/day dose group and four in the 80 mg/day dose group. No patient developed rhabdomyolysis. The incidence of clinical and laboratory adverse events requiring discontinuation was 6% for the placebo group and from 7% (20 mg/day) to 9% (80 mg/day) for lovastatin treatment groups. No new types of adverse experiences related to lovastatin treatment were reported. Lovastatin, as an adjunct to diet for the reduction of elevated LDL cholesterol, was generally very well tolerated.

Expanded clinical evaluation of lovastatin (EXCEL) study results. II. Assessment of the human lens after 48 weeks of treatment with lovastatin.

The crystalline lenses of hypercholesterolemic patients were assessed before and after 48 weeks of treatment with lovastatin or placebo to determine the effect of lovastatin on the human lens. Patients were given a biomicroscopic (slit-lamp) examination of the lens, and a previously validated, standardized classification system was used to describe the findings. A total of 8,245 patients were randomly assigned in equal numbers to treatment with placebo or lovastatin 20 or 40 mg once or twice daily in this double-blind, parallel-group study. Statistical analyses of the distribution of cortical, nuclear and subcapsular opacities at 48 weeks, adjusted for age and presence of an opacity at baseline, showed no significant differences (p less than 0.01) between the placebo and lovastatin-treated groups. Visual acuity assessments at week 48 were also not found to have significantly different distributions among treatment groups. Moreover, no significant differences were found among the groups in the frequencies of greater than or equal to 2-line worsening in visual acuity with concurrent progression in lenticular opacity, cataract extraction, or any spontaneously reported adverse ophthalmologic experience. No evidence was found for an effect of lovastatin on the human lens after 48 weeks of treatment.

Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia.

In the Expanded Clinical Evaluation of Lovastatin (EXCEL) Study, a multicenter, double-blind, diet- and placebo-controlled trial, we evaluated the efficacy and safety of lovastatin in 8245 patients with moderate hypercholesterolemia. Patients were randomly assigned to receive placebo or lovastatin at a dosage of 20 mg once daily, 40 mg once daily, 20 mg twice daily, or 40 mg twice daily for 48 weeks. Lovastatin produced sustained, dose-related (P less than .001) changes as follows (for dosages of 20 to 80 mg/d): decreased low-density lipoprotein-cholesterol level (24% to 40%), increased high-density lipoprotein-cholesterol level (6.6% to 9.5%), decreased total cholesterol level (17% to 29%), and decreased triglyceride level (10% to 19%). The National Cholesterol Education Program's low-density lipoprotein-cholesterol level goal of less than 4.14 mmol/L (160 mg/dL) was achieved by 80% to 96% of patients, while the less than 3.36 mmol/L (130 mg/dL) goal was achieved by 38% to 83% of patients. The difference between lovastatin and placebo in the incidence of clinical adverse experiences requiring discontinuation was small, ranging from 1.2% at 20 mg twice daily to 1.9% at 80 mg/d. Successive transaminase level elevations greater than three times the upper limit of normal were observed in 0.1% of patients receiving placebo and 20 mg/d of lovastatin, increasing to 0.9% in those receiving 40 mg/d and 1.5% in those receiving 80 mg/d of lovastatin (P less than .001 for trend). Myopathy, defined as muscle symptoms with a creatine kinase elevation greater than 10 times the upper limit of normal, was found in only one patient (0.1%) receiving 40 mg once daily and four patients (0.2%) receiving 80 mg/d of lovastatin. Thus, lovastatin, when added after an adequate trial of a prudent diet, is a highly effective and generally well-tolerated treatment for patients with moderate hypercholesterolemia.

Expanded clinical evaluation of lovastatin (EXCEL) study: design and patient characteristics of a double-blind, placebo-controlled study in patients with moderate hypercholesterolemia.

The randomized, double-blind, placebo-controlled trial described in this report was undertaken to clarify the dose-response relation of lovastatin therapy to lipid-modifying efficacy (lipid/lipoprotein modification) and drug-related adverse events in a population with moderately elevated fasting plasma total cholesterol (240 to 300 mg/dl) and low-density lipoprotein cholesterol (greater than or equal to 160 mg/dl). Men or women (postmenopausal or surgically sterile), aged 18 to 70 years, were entered into the trial with minimal exclusion criteria. After 4 to 6 weeks of an American Heart Association phase I diet or a more stringent diet, 8,245 patients from 362 sites were randomized to 1 of 5 parallel diet and drug treatment groups: placebo (n = 1,663) or lovastatin, 20 mg (n = 1,642) and 40 mg (n = 1,645) with the evening meal, and 20 mg (n = 1,646) or 40 mg twice daily (n = 1,649). The regimen of diet and lovastatin (or placebo) was followed for 48 weeks. The 5 treatment groups were similar at baseline. The total cohort had the following characteristics: 59% were men (mean age 56 years); 92% were white; 59% had completed at least 1 year of education beyond high school; 57% had a history of cardiovascular and associated disease; 40% had a history of hypertension; and 29% had coronary artery disease. Health habits were similar among groups, with 18% of patients reporting cigarette smoking, 14% reporting that they consume greater than 1 alcoholic beverage daily and 67% reporting no strenous exercise. Mean lipid/lipoprotein levels were also similar among groups, with the following average levels: total cholesterol (258 mg/dl), low-density lipoprotein cholesterol (180 mg/dl), high-density lipoprotein cholesterol (45 mg/dl) and triglycerides (median = 155 mg/dl). The large size of this trial, its placebo-controlled, double-blind design and the similarity of treatment groups at baseline should allow clear documentation of the long-term effects of lovastatin treatment and generalization of the results to a substantial portion of patients who may be candidates for lipid-modifying therapy.

Clinical experience with lovastatin.

New information on the tolerability of lovastatin has emerged from an ongoing study of long-term therapy; preliminary results from a large, 48-week clinical trial; and spontaneous reports of adverse events observed during prescription use of the drug in the United States. As of June 1989, 744 patients had received lovastatin for an average duration of 3.6 years in the long-term study. Drug-attributable adverse events necessitated withdrawal of 17 patients (2.3%) from the study. These adverse effects were asymptomatic elevations of transaminases (10), skin rash (3), gastrointestinal symptoms (2), myopathy (1) and insomnia (1). No effect of lovastatin on the human lens was observed. In the 48-week study, 8,245 patients were randomized into 5 equal groups to receive placebo or lovastatin 20 or 40 mg once or twice daily on a double-blind basis. Only 3 cases of myopathy were observed, all in patients taking lovastatin 40 mg twice daily. The incidence of withdrawal from the study because of raised transaminases was approximately 0.1% in the placebo group vs 0.1, 0.7, 0.6 and 1.5% in patients taking lovastatin in doses of 20 mg once daily, 40 mg once daily, 20 mg twice daily and 40 mg twice daily, respectively. Lovastatin has been available in the United States since September 1987. By June 1989, the drug had been prescribed for approximately 1 million patients. Drug-attributable adverse events not observed in clinical trials (such as hypersensitivity reactions and symptomatic hepatitis) have been reported, but the incidence of each appears to be extremely low.

Combined low-dose medication and primary intervention over a 30-month period for sustained high blood pressure in childhood.

Studies of the pathobiologic consequences of high blood pressure in childhood, as well as those following blood pressure levels into young adulthood, indicate that early intervention in the natural history of essential hypertension is warranted. In an exploratory study of the concept, 95 children out of 1604 (aged 8 to 18 years), who persistently scored higher than the 90th percentile for blood pressure over a 4-month period, considering the race, sex, and height of the children, were studied. Five series of replicate measurements with 30 total observations were obtained. Children with evidence of secondary hypertension were excluded. The study children were randomly divided into treatment (n = 48) and high-comparison (n = 47) groups. Treatment consisted of low-dose combined drug therapy (propranolol and chlorthalidone) with an educational program directed towards hypertension and dietary and exercise modification. Monthly follow-up was continued for 30 months. Significant systolic (-3.59 mm Hg) and diastolic (-1.73 mm Hg) changes were noted up to 30 months (p less than 0.05) with minimal side effects. Furthermore, analyses suggested that the blood pressure change, at least in the first month, was mostly attributable to drug therapy. Moreover, the mechanism of blood pressure change appeared to be race-specific, with whites having pulse rate changes and blacks having significant weight changes, which were associated with blood pressure change. This trial shows further research is warranted to determine optimum approaches for early treatment of essential hypertension to prevent future hypertensive disease.

Risk factors in early life as predictors of adult heart disease: the Bogalusa Heart Study.

The adult heart diseases, coronary artery disease and essential hypertension, are now clearly recognized to begin in childhood. The evidence comes from autopsy studies of cardiovascular-renal changes in the first two decades of life. Cardiovascular risk factors can be identified in children just as in adults and these have a high correlation with the anatomic disease. This relationship underscores the importance of risk factor screening of children. Of interest is that clinical risk factors tend to persist within a rank (track) so that studies in childhood can be predictive of future levels. Behavior and lifestyle of eating, cigarette smoking, alcohol intake, and use of oral contraceptive pills influence risk factors in children. Familial aggregation of risk factors are also noted. Studies of apolipoproteins, B and A-I, have identified subsets of children that have a greater frequency of paternal myocardial infarction. The findings from the Bogalusa Heart Study and other epidemiological studies of children show the need to begin prevention of adult heart disease in early life. Approaches to prevention should include high risk families and children and a public health or population approach. Cardiovascular health education for elementary school children should be directed to children in the general population in an effort to encourage them to adopt healthy life styles.

Secular trends of obesity in early life: the Bogalusa Heart Study.

Secular changes in height and weight measurements were examined in five- to 14-year-olds from 1973 to 1984. The age-sex specific 85th percentile was used to classify persons as overweight (based on ponderal index; kg/m3). Secular increases in weight (2.5 kg), and ponderosity (0.5-0.7 kg/m3) were found. Gains in ponderosity over the 11-year period were greater at the 75th percentile than at the 25th percentile, and the prevalence of overweight increased from 15 per cent to 24 per cent.

Cardiovascular risk factors from birth to 7 years of age: the Bogalusa Heart Study. Blood pressure.

BP was measured in 440 children followed longitudinally from birth to 7 years of age in Bogalusa, LA. Levels, trends, and determinants of BP were evaluated in this newborn cohort. Both systolic and diastolic BP levels remained relatively constant between the ages of 6 months and 7 years. BP levels varied between the different instruments, and differences were also noted between measures obtained using the same instrument before and after venipuncture. White children were noted to have slightly higher levels of systolic and diastolic BP pressure at 6 months and 1 year of age, even after adjustment for body size. Significant prediction of year 7 BP rank occurred as early as 6 months of age for systolic and at 1 year of age for diastolic BP levels. Body size was inconsistently related to BP levels from ages 6 months through 4 years, but the relationship was stronger and more consistent with changes in body size. Of interest is the relatively constant levels of indirect BP during this period of rapid growth, as measured by currently available instruments. These data emphasize the importance of cardiovascular risk factor measurement during early life and of the need to improve methods of indirect BP measurement in infancy.

Relation of body fat distribution to hyperinsulinemia in children and adolescents: the Bogalusa Heart Study.

The relation of body fat distribution to plasma levels of glucose and insulin during an oral glucose tolerance test was examined in 355 Black and White school-age children. Both central and peripheral fat were similarly related to fasting, 30-min, and 1-h glucose. Unlike peripheral fat, central body fat was more strongly related to the 1-h insulin response (r = 0.35 vs 0.26); this association remained significant for central fat independent of peripheral fat (r = 0.18). The strong relation of central fat to insulin response was noted in both races and sexes but not in either sexually immature or relatively thin children. These findings indicate that, even in early life, a central body fat pattern relates positively to insulin response to glucose load. Thus, knowledge of body fat localization may help identify persons most susceptible to hyperinsulinemia in early life.

Correlates of high density lipoprotein cholesterol and apolipoprotein A-I levels in children. The Bogalusa Heart Study.

Levels of high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apo A-I) may provide independent information concerning cardiovascular disease risk. Therefore, possible correlates of HDL-C and apo A-I levels were studied in 2827 5- to 17-year-olds from a biracial community, and the possible differences in these relationships were assessed. The characteristics examined included sexual maturation, plasma levels of glucose and insulin, obesity, reported oral contraceptive use, alcohol consumption, and cigarette smoking. In addition, levels of endogenous sex hormones (testosterone, estrogen, and progesterone) were measured in 515 adolescent males. HDL-C and apo A-I levels showed different (p less than 0.001) relationships with both obesity and oral contraceptive use. Increases in subscapular skinfold thickness corresponded more closely to decreases in HDL-C, rather than apo A-I, levels; the relationship with HDL-C was probably mediated by triglyceride levels. In contrast, oral contraceptive use was associated with increases in mean levels of apo A-I (8 mg/dl, whites; 16 mg/dl, blacks), but with only very small changes in HDL-C. (High-estrogen oral contraceptives were related most closely to increases in levels of both HDL-C and apo A-I). Levels of both HDL-C and apo A-I were similarly related to sexual maturation and levels of testosterone (negatively in boys), cigarette smoking (negatively), and alcohol intake (positively). Since levels of apo A-I independently of HDL-C may indicate an increased risk of cardiovascular disease, characteristics related to apo A-I levels should be further examined.