Search

This article describes the validity and utility of screening tests for total cholesterol levels in school-age children to predict those who, when adults, will have cholesterol levels that the National Cholesterol Education Program suggests need continuing surveillance and intervention. Two thousand three hundred sixty-seven children aged 8 to 18 years were examined on several occasions and were followed up to ages 20 to 30 years. Of children with cholesterol concentrations exceeding the 75th percentile on two occasions, 75% of girls and 56% of boys would not qualify for intervention as adults by the National Cholesterol Education Program criteria. Of children with cholesterol levels exceeding the 90th percentile on two occasions, 57% of girls and 30% of boys would not qualify for intervention as adults. Because the efficacy, safety, acceptability, and cost of treatment for high cholesterol concentrations in childhood is evolving, the need for universal screening of childhood cholesterol levels must be considered carefully in view of the number of children with high levels of cholesterol who, as adults, do not meet the criteria for intervention suggested by the National Cholesterol Education Program. [ABSTRACT FROM AUTHOR]

The value of a coronary artery disease prediction algorithm, the Framingham risk score (score), for detecting coronary artery calcium (CAC) was examined in 385 men and 472 women, aged 29 to 43 years. Scores were compared in subjects with and without CAC and were also used to predict presence of CAC. Receiver-operating characteristic curves were computed to compare different prediction models. The score model was compared with age only, natural logarithm of body mass index (lnBMI) only, and score plus lnBMI models. CAC was detected in 30% of men and 16% of women. The mean score was significantly higher in men and women with CAC. For every 2-point increase in the score, the odds of CAC increased by 30% in women and 20% in men. Significant associations between CAC status and risk factors were observed for age in women, and high- density lipoprotein cholesterol and blood pressure in men and women. The area under the receiver-operating characteristic curve for the score was 0.67 and 0.57 for women and men, respectively. When lnBMI was added to the score model, the area increased to 0.76 in women (lnBMI p <0.0001, score p <0.005). For men, the area increased from 0.57 to 0.67, and the score was no longer significant (p >0.60) in the model with lnBMI (p <0.0001). Score predicts CAC in asymptomatic young adults. Inclusion of lnBMI in the score model adds significantly to the prediction of CAC in women and men. The lnBMI model has a greater predictive value than the score in this young population. [ABSTRACT FROM AUTHOR]

Petroleum resource development has generated a global legacy of millions of active and decommissioned energy wells. Associated with this legacy are concerns about wellbore integrity failure and leakage of fugitive gas into groundwater and atmosphere. The fate of fugitive gas in the shallow subsurface is controlled by sediment heterogeneity, hydrostratigraphy and hydraulic connectivity. We characterized the shallow subsurface at a site in northeastern British Columbia, Canada; a region of extensive petroleum resource development. We collected 13 core profiles, 9 cone-penetrometer profiles, 58 sediment samples and 4 electrical resistivity profiles. At the site, a ~ 12 m thick layer of low-permeability diamict (10 -8  m/s) overlays a more permeable (10 -6 - 10 -4  m/s) but highly heterogeneous sequence of glacigenic sand, clay and silt. We develop a conceptual hydrostratigraphic model for fluid flow in this system in the context of fugitive-gas migration. Driven by buoyancy forces, free-phase gas will move upward through discontinuous permeable zones within the Quaternary sediments, until it encounters lower permeability interbeds where it will pool, flow laterally or become trapped and dissolve into flowing groundwater. The vertical extent of gas migration will be significantly limited by the relatively continuous overlying diamict, a feature common across the Western Canadian Sedimentary Basin. However, intra-till lenses observed embedded within the diamict may provide pathways for gas to move vertically towards ground surface and into the atmosphere. This study provides one of the few investigations examining geological and hydrogeological heterogeneity in the shallow subsurface at scales relevant to gas migration. For glaciated regions with similar surficial geology, such as Western Canada Sedimentary Basin, gas that is released into the subsurface from an energy wellbore, below a surface diamict, will likely migrate laterally away from the wellbore, and be inhibited from reaching ground surface and emitting to atmosphere., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: A majority of the recognized risk factors for atherosclerosis and the development of cardiovascular disease have been derived from the study of older populations who have already manifested clinical symptoms. If risk factors can be identified earlier in life, such as genetic variation, preventive measures may be taken before overt symptoms of pathology have manifested, and when treatments may be most effective., Methods and Results: In an effort to identify individuals at increased risk for cardiovascular disease, we genotyped 732 members of the Muscatine Study Longitudinal Adult Cohort for candidate genetic markers associated with several pathogenetic processes. We identified age-adjusted increased risks for coronary artery calcium (OR 4.29; 95% CI 1.78, 10.31) and increased mean carotid artery intimal-medial thickness associated with the (-444)A>C promoter polymorphism of Leukotriene C4 Synthase (LTC4S) in women. There were no similar associations in men., Conclusions: LTC4S plays a key role in the process of inflammation as the rate limiting enzyme in the conversion of arachidonic acid to cysteinyl-leukotrienes, important mediators of inflammatory responses. The (-444)C variant upregulates LTC4S mRNA expression, increasing the synthesis of proinflammatory leukotrienes. Our results support genetic variation modifying inflammatory pathways as an important mechanism in the development of atherosclerosis.

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.

Purpose: To determine whether differences in body mass index (BMI) and image section levels representing the proximal through the distal sections of the heart are associated with attenuation differences in images of calcium phantoms scanned during computed tomographic (CT) imaging of study subjects., Materials and Methods: Mean attenuation values for three calcium phantoms (each with a different calcium hydroxyapatite concentration), as measured at each of four different image section levels, were obtained for 691 participants in the Muscatine CT Vascular Calcium Study. The subjects were grouped according to sex-specific BMI quartiles, and the degree of attenuation in each phantom was investigated as a function of image section level and BMI quartile. Spearman rank order correlation coefficients and one-, two-, and three-factor repeated-measures analysis of variance were used to examine the association between section level and BMI and the mean phantom attenuations., Results: Attenuation was, for the most part, significantly associated with both section level (P <.005) and BMI quartile (P <.0025-.05). The degree of attenuation tended to decrease in images obtained at the more distal cardiac levels and to increase with increasing BMI quartile., Conclusion: Differences in attenuation related to BMI and image section level appear to have a significant effect on current calcium scoring methods., (Copyright RSNA, 2004)

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.)

Background: Results of several studies have suggested that diet during adolescence may influence the risk of breast cancer in adulthood. We evaluated whether an intervention to lower fat intake among adolescent girls altered their serum concentrations of sex hormones that, in adults, are related to breast cancer development., Methods: We conducted an ancillary hormone study among 286 of the 301 girls who participated between 1988 and 1997 in the Dietary Intervention Study in Children, in which healthy, prepubertal, 8- to 10-year-olds with elevated low-density lipoprotein cholesterol were randomly assigned to usual care or to a behavioral intervention that promoted a low-fat diet. Median time on the intervention was 7 years. Blood samples collected before randomization and at the year 1, year 3, year 5, and last visits were assayed to determine the girls' serum levels of sex hormones. All P values are two-sided., Results: At the year 5 visit, girls in the intervention group had 29.8% (95% confidence interval [CI] = 5.4% to 47.9%; P =.02) lower estradiol, 30.2% (95% CI = 7.0% to 47.7%; P =.02) lower non-sex hormone binding globulin-bound estradiol, 20.7% (95% CI = 4.7% to 34.0%; P =.02) lower estrone, and 28.7% (95% CI = 5.1% to 46.5%; P =.02) lower estrone sulfate levels during the follicular phase of the menstrual cycle and 27.2% (95% CI = 5.7% to 53.1%; P =.01) higher testosterone levels during the luteal phase of the menstrual cycle than did girls in the usual care group. At the last visit, the luteal phase progesterone level was 52.9% (95% CI = 20.0% to 72.3%) lower for girls in the intervention group than for girls in the usual care group (P =.007)., Conclusion: Modest reductions in fat intake during puberty are associated with changes in sex hormone concentrations that are consistent with alterations in the function of the hypothalamic-pituitary-ovarian axis. Whether these changes influence breast cancer risk is currently unknown.

We have examined the transmission frequencies of the methylenetetrahydrofolate reductase (MTHFR) 677 T and C alleles from heterozygous parents to children with Down syndrome (trisomy 21) in 202 Caucasian families. Our results indicated that the MTHFR 677T allele was transmitted to children with Down syndrome at a significantly higher rate than would be expected based on Mendelian inheritance patterns, and the C allele was transmitted at a significantly lower rate (P < 0.009). Transmission frequencies were also examined independently for maternally and paternally transmitted alleles to assess potential parent-of-origin effects. Because the vast majority of conceptions with trisomy 21 end in pregnancy loss, we questioned whether the observed preferential transmission of the T allele to this population of liveborn infants with Down syndrome could reflect a survival advantage. A plausible biochemical interpretation of these results is presented based on a maternal-fetal MTHFR 677T allele interaction in the context of the constitutive overexpression of three copies of the cystathionine beta synthase gene in the trisomy 21 fetus. Published 2002 Wiley-Liss, Inc.

Early detection of cardiovascular disease would allow timely institution of preventive measures. Arterial endothelium play a primary role in processes leading to the development of atherosclerotic plaque and cardiovascular disease in general. Determination of flow-mediated dilatation (FMD) of brachial arteries from B-mode ultrasound image sequences offers a noninvasive surrogate index of endothelial function. A highly automated method for analysis of brachial ultrasound image sequences is reported and its performance assessed. The method overcomes the variability of brachial ultrasound images across subjects by incorporating machine learning and quality control steps. The automated method outperformed conventional manual analysis by providing a decreased analysis bias, increased reproducibility, and improved measurement accuracy. Consequently, it decreases inter- and intraobserver as well interinstitution variability. The method has been employed in a number of population studies with thousands of subjects analyzed.

Trisomy 21 (Down syndrome) is a common genetic condition with a high incidence of congenital heart defects (CHD), particularly those involving abnormal development of the embryonic atrioventricular (AV) canal. Type VI collagen (Col VI) is expressed in the developing AV canal extracellular matrix, and has been associated with trisomy 21 AV canal defects in human genetic studies. Although the molecular mechanisms linking Col VI and trisomy 21 AV canal defects are not well understood, a computer model predicts increased cell adhesiveness is responsible for these CHD. We compared integrin-mediated cell adhesive properties for skin fibroblasts isolated from trisomy 21 and non-trisomic individuals on Col VI, fibronectin (FN) and type I collagen (Col I). Cell lines demonstrate similar adhesion profiles to FN and Col I, but all trisomy 21 cells display increased adhesive capacity for Col VI compared to non-trisomic fibroblasts. Cell adhesion to type VI collagen was shown to be GRGDS independent, but beta(1) integrin family dependent. Function-blocking antibodies identified alpha(3)beta(1) as the predominant integrin mediating trisomy 21 and non-trisomic skin fibroblast adhesion on Col VI. Trisomy 21 and non-trisomic fibroblasts display similar expression levels for each of the integrin receptors examined. A beta(1) integrin-activating antibody augments non-trisomic cell adhesion on Col VI, but has no effect upon trisomy 21 fibroblasts. These results demonstrate that beta(1) integrin family members mediate trisomy 21 and non-trisomic skin fibroblast adhesion for Col VI. Altered activation state of the beta(1) integrin is a mechanism responsible for increased trisomy 21 cell adhesion on Col VI., (Copyright 2002 Wiley-Liss, Inc.)

Background: Higher carotid intimal-medial thickness (IMT) is associated with cardiovascular risk factors and is predictive of coronary artery disease and stroke in older adults. Carotid IMT was measured in young and middle-aged adults to determine its relationship with risk factors measured (1) in childhood, (2) currently, and (3) as a "load" from childhood to adulthood., Methods and Results: Carotid ultrasound studies were performed in 346 men and 379 women aged 33 to 42 years who were representative of a cohort followed since childhood and who live in Muscatine, Iowa. The mean of the measurements of maximal carotid IMT at 12 locations was determined for each subject. A medical questionnaire was completed, and measurements of anthropometric characteristics and risk factors were obtained. The mean maximum carotid IMT was 0.79+/-0.12 mm for men and 0.72+/-0.10 mm for women. On the basis of multivariable analysis, the significant current predictors of IMT were age and LDL cholesterol in both sexes and diastolic blood pressure in women. Total cholesterol was a significant childhood predictor in both sexes, while childhood body mass index was significant only in women. For men, LDL cholesterol, HDL cholesterol, and diastolic blood pressure were predictive of carotid IMT in a risk factor load model, whereas in women, LDL cholesterol, body mass index, and triglycerides were predictive., Conclusions: Higher carotid IMT in young and middle-aged adults is associated with childhood and current cardiovascular risk factors, as well as risk factor load.

Background: Few studies have shown the efficacy and safety of lower-fat diets in children., Objective: Our objective was to assess the efficacy and safety of lowering dietary intake of total fat, saturated fat, and cholesterol to decrease LDL-cholesterol concentrations in children., Design: A 6-center, randomized controlled clinical trial was carried out in 663 children aged 8-10 y with LDL-cholesterol concentrations greater than the 80th and less than the 98th percentiles for age and sex. The children were randomly assigned to either an intervention group or a usual care group. Behavioral intervention promoted adherence to a diet providing 28% of energy from total fat, <8% from saturated fat,

Background: Increased carotid intimal-medial thickness (IMT) and coronary artery calcification (CAC) are used as 2 markers of early atherosclerosis. Our objectives were to assess whether increased IMT and CAC are related and to determine the relationship between cardiovascular risk factors and carotid IMT in young adults., Methods and Results: A sample of 182 men and 136 women aged 33 to 42 years living in Muscatine, Iowa, underwent B-mode carotid ultrasound to determine the mean of 12 measurements of maximal carotid IMT. CAC was defined as calcification in the proximal coronary arteries in >/=3 contiguous pixels with a density of >/=130 HU. The mean IMT was 0.788 mm (SD 0.127) for men and 0.720 mm (SD 0.105) for women. CAC was present in 27% of men and 14% of women and was significantly associated with IMT in men (P<0.025) and women (P<0.005). With multivariate analysis, after adjustment for age, significant risk factors for carotid IMT were LDL cholesterol (P<0.001) and pack-years of smoking (P<0.05) in men and LDL cholesterol (P<0.001) and systolic blood pressure (P<0.01) in women. These risk factors remained significant after CAC was included in the multivariate model., Conclusions: There is an association between increased carotid IMT and CAC and between cardiovascular risk factors and increased IMT in young adults. Carotid IMT may provide information in addition to CAC that can be used to identify young adults with premature atherosclerosis.

Beginning in 1971 children in grades kindergarten through the 12th grade were examined on alternate years until 1992 in Muscatine, Iowa, in these examinations the following variables were assessed: height, weight, skinfold thickness, lipids, lipoproteins, smoking behaviors, as well other variables. In order to lend relevance to risk factors in childhood a number strategies have been used. These include: 1) Examination of familial aggregation and mortality; 2) Segregation analysis of genetic mechanisms; 3) Relationship of obesity in childhood to other established risk factors; 4) Examination of the relationship of childhood obesity to the development of coronary artery calcification as assessed by electron beam computed tomography. In these studies we have shown that obese children's siblings, mothers, fathers, aunts and uncles have significant greater body mass indices than leaner children. Children who are obese have significantly higher systolic and diastolic blood pressure, higher plasma triglycerides and lower HDL-cholesterol levels. The first and second degree relatives of obese hypertensive children have a higher mortality rate from cardiovascular disease than leaner children's relatives. From complex segregation analyses about 35% of the population of Muscatine appear to carry a gene for obesity and 6% appear homozygous. Over the past decade we have observed that the children in Muscatine, Iowa have become more obese than previously. Our longitudinal observations indicate that obesity acquired in childhood is predictive of adult obesity and is also predictive of the development of coronary artery calcification. Thus obesity in childhood is not only an important risk factor in children but also a growing public health problem for children and adolescents.

The identification of genetic loci involved in most forms of congenital heart disease has been hampered by the complex inheritance patterns of these disorders. Atrioventricular canal defects (AVCDs) are most commonly associated with Down syndrome, although non-syndromic cases also occur. Non-syndromic AVCDs have been attributed to multifactorial inheritance. However, the occurrence of a few kindreds with multiple affected individuals has suggested that a major genetic locus can account for the disorder in some families. We have used a combination of DNA pooling and shared segment analysis to perform a high density screen of the entire autosomal human genome in an extended kindred. In so doing, we have identified a genetic locus on chromosome 1 shared by all affected individuals. Our data demonstrate the existence of a congenital heart defect susceptibility gene, inherited as an autosomal dominant with incomplete penetrance, involved in AVCD. Furthermore, our data demonstrate the power of using key isolated kindreds in combination with high density genomic screens to identify loci involved in complex disorders such as congenital heart defects.

Objectives: This study was designed to estimate the prevalence of coronary artery calcification in young adult men and women and to examine the association between the presence of coronary artery calcification and coronary risk factors measured in childhood and young adult life., Background: Electron beam computed tomography is a sensitive, noninvasive method for detecting coronary artery calcification, a marker of the atherosclerotic process. Coronary artery calcification is associated with coronary risk factors in older adults., Methods: Subjects (197 men, 187 women) had coronary risk factors measured in childhood (mean age 15 years) and twice during young adult life (mean ages 27 and 33 years). Each underwent an electron beam computed tomographic study at their second young adult examination., Results: The prevalence of coronary artery calcification was 31% in men and 10% in women. Increased body size, increased blood pressure and decreased high density lipoprotein (HDL) cholesterol levels were the coronary risk factors that showed the strongest association with coronary artery calcification. Significant odds ratios for coronary artery calcification, using standardized risk factor measurements at a mean age of 33 years in men and women, respectively, were 6.4 and 13.6 for the highest decile of body mass index, 6.4 and 6.4 for the highest decile of systolic blood pressure and 4.3 and 4.7 for the lowest decile of HDL cholesterol., Conclusions: Coronary artery calcification is more prevalent in men in this young adult population. Coronary risk factors measured in children and young adults are associated with the early development of coronary artery calcification. Increased body mass index measured during childhood and young adult life and increased blood pressure and decreased HDL cholesterol levels measured during young adult life are associated with the presence of coronary artery calcification in young adults.

Background: Congenital heart disease is common in Down syndrome patients, with atrioventricular septal defects accounting for a majority of the abnormalities. The molecular mechanisms of meiotic nondisjunction resulting in Down syndrome were studied for associations with the presence of atrioventricular septal defects., Methods and Results: Twenty highly polymorphic chromosome 21 microsatellite markers were used to genotype two groups of patients (group 1: Down syndrome with atrioventricular septal defects, n = 43; and group 2: Down syndrome without cardiac defects, n = 51) to determine (1) the parental origin of the extra chromosome, (2) the stage of meiotic nondisjunction resulting in the trisomy, (3) the presence or absence of disomic homozygosity or heterozygosity, and (4) the degree of recombination in the nondisjoined chromosomes. The parental origin of the nondisjoined chromosome was maternal in 86.2% of the families, with no significant differences between groups. The most centromeric marker was nonreduced, indicating a meiosis I nondisjunction in 76.5% of maternally derived trisomies, and reduced, indicating a meiosis II nondisjunction in 76.9% of paternally derived trisomies, with no significant differences between groups. There were no significant differences in the proportion of reduced markers at any locus between groups. The distribution of the number of crossovers was significantly different between groups (chi 2 = 14.12, P < .001), with less recombination observed in group 1., Conclusions: In Down syndrome patients, no association was found between the presence of an atrioventricular septal defect and the parent of origin, stage of meiotic nondisjunction, or disomic homozygosity or heterozygosity. A significant association was found between the presence of an atrioventricular septal defect and reduced frequency of recombination.

The association between trisomy 21 and a high incidence of atrioventricular canal defects (AVCDs) indicates that a locus on chromosome 21 is involved in this congenital heart defect. We have investigated whether a genetic locus on chromosome 21 is also involved in familial nonsyndromic AVCDs. Short tandem repeat polymorphisms (STRPs) from chromosome 21 were used for linkage analysis of a family having multiple members affected with AVCDs. In this family, the gene for AVCDs is transmitted as an autosomal dominant with incomplete penetrance. The affected family members are nonsyndromic and have normal karyotypes. Two-point and multipoint linkage analyses produced significantly negative LOD scores for all informative markers. A comparison of the overlapping exclusion distances obtained for each marker at LOD equal -2.0 with the 1000:1 consensus genetic map of the markers, excludes chromosome 21 as the genetic location for AVCDs in this family. The exclusion of chromosome 21 indicates that another gene, not located on chromosome 21, is involved in atrioventricular canal defect formation.

More than 600,000 children in the United States have a congenital or acquired cardiac abnormality, and millions more are at risk of developing atherosclerotic disease in adulthood, a risk made particularly evident by the prevalence of cardiovascular risk factors in the young. There are barriers to optimum prevention and treatment of these conditions in children and youth. The AHA's Task Force on Children and Youth has described these barriers and outlined a series of recommendations and strategies to meet the challenges they impose. More research is needed, and research initiatives will be developed at scientific conferences designed to review critical areas of cardiac development and etiology of disease in children. Financial support for such research initiatives must be increased. Educational programs on cardiovascular risk factors will be extended to children and their families. When these programs are coordinated with efforts in the community and in schools, they will reduce the prevalence of cardiovascular risk factors. The task force recommends that various departments and committees of the AHA use their resources for the benefit of children: for example, by developing more research initiatives for funding by the AHA or NHLBI and increasing legislative and regulatory efforts in the areas such as mandatory school health programs and tobacco advertising. It is hoped that in the next decade, through research and educational efforts, many advances in the prevention and treatment of cardiovascular diseases in the young will be realized.

In adult populations, elevated blood pressure is related to the development of stroke, renal disease, and occlusive atherosclerosis. The significance of blood pressure levels in childhood, unless extremely elevated, has not been related to disease outcomes. In a study carried out in Muscatine, Iowa, the risk of high blood pressure in young adult life was evaluated based on the observations of blood pressure and other factors made during the school-aged years. Subjects, 2445 in number, were first observed at ages 7 through 18 years and again between 20 and 30 years. During childhood, measurements of blood pressure, height, and weight were made on alternate years. At adult ages, the same measurements were again made and a health questionnaire was administered. Adult blood pressure was correlated with childhood blood pressure, body size, and change in ponderosity from childhood to adult life. Adult ponderosity was related to childhood ponderosity, and those who were most obese as adults showed the greatest increase in weight from their childhood years. These observations suggest that strategies to prevent the acquisition of excess ponderosity during childhood may be useful in preventing adult hypertension.

Between 1971 and 1981 the Muscatine Coronary Risk Factor Project measured, in six biennial school surveys, 2631 schoolchildren 9 to 18 years of age. Beginning in 1981, these individuals were measured near their 23rd, 28th, and 33rd birthday. This article examines the tracking from childhood into young adult years of the heights, weights, body mass indices (BMI), and triceps skinfold thicknesses (TSF) of these individuals. Depending on age and gender, tracking correlations for height ranged from 0.41 to 0.97; for weight they ranged from 0.51 to 0.88; for BMI they ranged from 0.58 to 0.91; and for TSF they ranged from 0.26 to 0.58. From 49 to 70% of children in the upper quintile of weight were found in the upper quintile of weight as adults, from 48 to 75% of children in the upper quintile of BMI were again in the upper quintile as adults, and from 25 to 56% of children in the upper quintile of TSF were again in the upper quintile as adults. These measures track from childhood into young adult life, and the majority of obese children become obese adults. However, about 31% of children from the upper quintile of BMI became adults with substantially lower levels, while a similar number of lean children become obese adults. Why some obese children become obese adults and others do not remains an unanswered question. The data presented herein indicate that obesity is often acquired during childhood and adolescence when preventive measures could be applied.

Childhood obesity is predictive of obesity as an adult, and individual differences in body weight relative to height (body mass index) in adults are important predictors of morbidity as well as mortality from atherosclerotic cardiovascular disease. The observation of strong familial correlations does not ensure that genes are involved in the determination of body mass index, because individuals in families share environments as well as genes. However, several recent studies have found evidence for both additive (polygene) and nonadditive (major gene) components. A question that results from these analyses is--what gene(s) has been inherited that carries an associated risk, most likely mediated by environmental exposures, for obesity? Studies to identify genetic loci linked to familial obesity should add to our understanding of the genetic factors involved in the determination of obesity and may lead to early identification of individuals and families at high risk for the chronic disorders that are associated with obesity.

Total and cause-specific mortality was investigated in 387 first- and second-degree deceased adult relatives of three groups of children selected from those who participated in three biennial school surveys in Muscatine, Iowa: the lean group (students in the first quintile of relative weight on all three surveys); the random group (a random sample of all eligible students); and the heavy group (students in the fifth quintile of relative weight on all three surveys). A greater proportion of death certificates for heavy group relatives listed a cardiovascular cause of death (60%) compared with lean (48%) and random (43%) group relatives. The relative risk of dying of cardiovascular disease for heavy group vs random group relatives was 1.41 (95% confidence interval 1.01, 1.98). In a subset of heavy group families identified by children with elevated systolic blood pressure, the proportion of death certificates listing a cardiovascular cause was even higher (76%) and the estimate of relative risk vs random group relatives was 2.20 (95% confidence interval 1.43, 3.37). These results indicate that persistent obesity in children, particularly when accompanied by persistent blood pressure elevation, identifies families whose members are at increased risk of dying of cardiovascular disease.

The role of genetic and environmental factors in determining the variability in body mass index (BMI; kg/m2) was investigated in 1,302 relatives identified through 284 schoolchildren from Muscatine, IA. BMI levels were first adjusted for variability in age, by gender and by relative type. There was significant familial aggregation of adjusted BMI in the pedigrees, as indicated by inter- and intraclass correlation coefficients significantly different from zero. A mixture of two normal distributions fit the adjusted BMI data better than did a single normal distribution. Genetic and environmental models that could explain both the familial aggregation and the mixture of normal distributions were investigated using complex segregation analysis. There was strong support for a single recessive locus with a major effect that accounted for almost 35% of the adjusted variation in BMI. Polygenic loci accounted for an additional 42% of the variation. Approximately 23% of the adjusted variation was not explained by genetic factors. For spouses living in the same household, their shared environment accounted for 12% of their variation. For siblings living in the same household, their shared environment accounted for 10% of their variation. While shared environments contributed to variation in adjusted BMI, more than 75% of the variation was explained by genetic factors that include a single recessive locus. Approximately 6% of the individuals in the population from which these pedigrees were sampled are predicted to have two copies of the recessive gene, while 37% of the individuals are predicted to have one copy of the gene.

The prevention of cardiovascular disease beginning in childhood may be affected with two strategies. The first is a population approach to lower the cholesterol levels in all American children. The second is an individualized strategy to identify and treat children at particularly high risk in the health care system.

Longitudinal studies in children have tracked blood pressure through childhood and from childhood into adult life. However, many children do not maintain their rank during these periods of observation. Several of the factors contributing to maintenance of rank order are reviewed, such as initial level of blood pressure, body size, sexual maturation, and family history of high blood pressure. Children with initially high level of blood pressure are more likely to become adults with high blood pressure, particularly if they are obese as children or become obese as young adults, and if they have a positive family history for hypertension.

Blood pressure in infants and children is much lower than that in adults. It is suspected that children whose blood pressures are greatest for their age or body size may be destined for future hypertension. However, it is apparent that some children with lower blood pressures are also destined for hypertension as adults. Children with a family history of hypertension demonstrate greater blood pressure and heart rate responses to mental challenge. These responses are enhanced when a high salt diet is consumed. Increased maximal exercise systolic blood pressure and increased left ventricular wall mass in childhood add significantly to the prediction of future high blood pressure. In addition, the acquisition of excess weight for height from childhood to young adult life adds to the prediction of future blood pressure elevations. Both children and adults who are obese have significantly higher blood pressures than those who are lean. Approximately 34% of the variability in body mass index is explained by genotype differences at a single recessive locus, 41% by genotype differences at polygenic loci, and 25% by nongenetic factors. Thus, the genetic influence of obesity may be an important factor responsible for elevated blood pressure in both children and adults.

The public health implications of reducing or preventing the excess increase in blood pressure and the acquisition of obesity during childhood years are important. Many children with high blood pressure, particularly those who are initially obese or become obese as young adults and those with excess left ventricular mass for body size, become adults with high blood pressure. Although blood pressure and cholesterol have been shown to track during childhood and from childhood into the adult years, the use of repeated determinations along with measures of obesity and information concerning family history of diabetes and coronary heart disease can significantly add to the prediction of future elevated levels.

Smoking among adolescents is a developmental phenomenon with several factors exerting an influence on cigarette use at different times. We examined the longitudinal influences of several behavioral and social variables on the smoking status of 443 students followed from early to late adolescence. Of the factors examined, association with friends who smoke and previous smoking status were consistently associated with an adolescent's future smoking status. Other factors, such as attachment to father or to mother, parental supervision, extracurricular activity, perceived negative and positive effects of smoking, and academic involvement, were all related to late adolescent smoking status. These observations suggest that strategies that influence smoking behavior need to be directed not only to the individual child but also to influences within the child's home and school environment.