The complications of obesity that are associated with cardiovascular disease include hypertension, dyslipidemia, insulin resistance, glucose intolerance, type 2 diabetes mellitus, left ventricular hypertrophy, and pulmonary hypertension resulting from obstructive sleep apnea.55 Many of these outcomes of obesity have traditionally been viewed as problems of adulthood. However, further study has revealed that many of these abnormalities may begin in childhood and adolescence.
Obesity in children has been associated with the development of early myocardial changes and coronary and carotid artery pathology. Kortelainen evaluated the autopsies of 210 children aged 5 to 15 years who had suffered a violent death.56 Ponderal index was a significant predictor of heart weight and the presence of coronary artery intimal fatty streaks. Similarly, Berenson et al57 demonstrated in the Bogalusa Heart Study that children and young adults who died primarily of trauma showed an association between BMI, systolic blood pressure, diastolic blood pressure, and the presence of fatty streaks and fibrous plaques in the aorta and coronary arteries at autopsy. Gidding et al58 studied by electron beam computed tomography 29 patients aged 11 to 23 years with familial hypercholesterolemia to evaluate the presence of coronary artery calcium. Coronary artery calcium deposits were found in 7 of 29 subjects and were associated with increased body mass index. Sorof et al59 measured carotid intimal-medial thickness by duplex vascular ultrasound in children and adolescents with essential hypertension to assess for evidence of early arterial changes. Carotid intimal-medial thickness was positively correlated with weight, BMI, and left ventricular mass index, but not with height or age.
Left ventricular hypertrophy has been shown to be an independent risk factor for cardiovascular disease morbidity and mortality.60 In children and adolescents, left ventricular mass is determined by body size, assessed both by growth (height) and weight (adiposity). Urbina et al61 reported that the major factor influencing left ventricular mass in the Bogalusa Heart Study was linear growth determined by height, but that measures of ponderosity were also significant determinants of LVM. Daniels et al21 reported that lean body mass was the strongest determinant of LVM, but that fat mass and systolic blood pressure were also significant predictors of LVM. In adolescents with essential hypertension, Daniels et al62 found severe LVH in 14% of subjects, with greater body mass index one of the major factors associated with increased LVM. A recent study of 115 children undergoing evaluation for hypertension found an overall prevalence of LVH of 38%.63 This shows that LVH can occur early in the course of hypertension in young individuals. Patients with LVH were heavier and had greater BMI than those without LVH, and LVMI was positively correlated with BMI. These findings suggest that the combination of obesity, hypertension, and other risk factors for cardiovascular disease presents a particularly adverse profile for ultimate cardiovascular outcomes.
Obesity early in life appears to increase the likelihood of clustering of cardiovascular risk factors. In a study of adolescent girls, Morrison et al64 found that almost 11% of overweight white girls and 65% of overweight black girls had three cardiovascular risk factors compared with an expected frequency of 0.8%. Similar findings were reported for boys.65 The distribution of fat may also be important. Daniels et al21 evaluated the effects of fat distribution on risk factors for cardiovascular disease in adolescents. A more central deposition of fat (android pattern) was associated with elevation of triglycerides, decreased HDL cholesterol, increased systolic blood pressure, and increased LV mass. These relationships persisted after controlling for other variables such as age, race, gender, and height. The most compelling evidence of cardiovascular risk factor clustering in youth comes from the Bogalusa autopsy study, in which subjects with 0, 1, 2, and 3 or 4 risk factors had, respectively, 19.1%, 30.3%, 37.9%, and 35.0% of the intimal surface covered with fatty streaks in the aorta.57
Most interventions for pediatric obesity have focused on behavioral approaches to diet and physical activity to address the main components of energy balance. Although these approaches have been shown to have both short- and long-term beneficial effects on BMI in selected patients,66 such success has not been uniform. This management approach is very labor intensive and is often not covered by medical insurance.67 Other dietary approaches which have been tried include the very low calorie diet68 and the protein-modified fast.69 Although these dietary approaches can be effective in selected patients, they have also been associated with important adverse effects. Surgical approaches have been used in morbidly obese adolescents but are clearly not appropriate for a large number of patients.
The role of pharmacological management in the management of pediatric obesity has been controversial. The history of pharmacological treatment of obesity in adults is replete with problems, and there have been few well-controlled studies to show that the available drugs are well tolerated and effective for use in obese children. Many of the drug treatments that have been tried in adults have resulted in complications such as with amphetamines and fenfluramine/dexfenfluramine. This history has reinforced the debate regarding whether medications should be used to treat obesity except under the most extreme circumstances. On the one hand, obesity is a chronic problem requiring long-term management and potentially long-term exposure to the adverse effects of medications, an issue of particular concern in growing and developing children. On the other hand, evidence for the benefits of weight loss on blood pressure in children may tilt the risk-benefit balance in favor of a more aggressive management approach for the prevention of future cardiovascular disease. One medication that is currently being evaluated for treatment of obesity in adolescents is sibutramine, an inhibitor of the reuptake of serotonin and norepinephrine. However, the safety and efficacy of sibutramine in patients under 16 years of age is still unknown. Furthermore, sibutramine may be associated with increased blood pressure in some patients and is not recommended for use in patients with a history of hypertension. Orlistat is a gastrointestinal lipase inhibitor that may hold promise for safe and effective pharmacological treatment for childhood obesity.
The benefits of weight loss on blood pressure reduction in children have been investigated in both observational and interventional studies. In a retrospective study based on a 10-year period of observation, Clarke et al70 reported that children whose ponderosity increased over that period had a relative increase in blood pressure by 18 percentiles compared with their peers, whereas children whose ponderosity decreased had a relative reduction in blood pressure by 13 percentiles. The positive effect of weight loss on blood pressure in children has also been demonstrated in several interventional studies. One of the first such studies by Brownell et al71 reported blood pressure reductions of up to 16/9 mm Hg in obese children who achieved significant weight reduction after 16 months of dietary counseling. Figueroa-Colon et al72 found that blood pressure was significantly reduced compared with baseline at all points of a study comparing 2 hypocaloric dietary modifications in obese children. Wabitsch et al42 reported a blood pressure reduction of 9/5 mm Hg associated with a weight reduction of 8.5 kg after a 6-week dietary intervention in obese adolescent girls. Similarly, Gallistl et al73 reported an 8/7 mm Hg blood pressure reduction associated with weight loss of 3.9 kg after a 3-week diet and exercise program in obese children.
Although these studies suggest that blood pressure reductions are induced by weight loss in obese children, each is limited by the absence of a matched control group to show that the blood pressure reduction was directly attributable to weight loss. The only controlled trial to date was performed by Rocchini et al54 who randomized overweight adolescents to 3 interventions over a 20-week period: diet alone, diet plus exercise, and control (no intervention). Changes in systolic blood pressure from baseline in the diet plus exercise group, diet alone group, and control group were −16 mm Hg, −10 mm Hg, and +4 mm Hg, respectively. This latter study provides the most definitive evidence that weight loss, particularly in conjunction with exercise, can be beneficial in the management of obesity hypertension in children. However, the long-term benefits of weight loss on blood pressure remain to be defined because it is unknown whether the decline of blood pressure observed during acute weight loss is maintained.
The prevalence and severity of obesity is increasing in children and adolescents. These observations suggest that the trend of decreasing cardiovascular disease in adults observed over the past 50 years may be reversed as the current population of overweight children and adolescents become adults.74 At present, treatment for all overweight children and adolescents can be recommended based on available data. However, the methods used to achieve weight management remain controversial. It seems appropriate to reserve pharmacological therapy for children most severely affected by obesity and its sequelae. It is also appropriate to reserve such therapy for those who have failed or have had only modest success with behavioral therapy directed at dietary modification and increased physical activity. The presence of ongoing obesity-related outcomes such as hypertension, diabetes mellitus or impaired glucose tolerance, and dyslipidemia may increase the rationale for more aggressive therapy. Ultimately, multiple therapeutic strategies may be necessary to achieve the desired goal.
Obesity in childhood should be considered a chronic medical condition and, thus, is likely to require long-term treatment. Public health initiatives to educate community leaders and health care providers may prove instrumental in stemming the evolving epidemic of pediatric obesity and its complications. In addition, the scope and acuity of the problem facing our youth suggests that substantial research is needed that is focused on the mechanisms of hypertension related to obesity in the pediatric population. Such research will serve as the basis for future guidelines for prevention and treatment of obesity hypertension.
By Jonathan Sorof and Stephen Daniels
- 55 Dietz WH. Health consequences of obesity in youth: childhood predictors of adult disease. Pediatrics. 1998; 101: 518–525.MedlineGoogle Scholar
- 56 Kortelainen ML. Adiposity, cardiac size and precursors of coronary atherosclerosis in 5- to 15-year-old children: a retrospective study of 210 violent deaths. Int J Obesity. 1997; 21: 691–697.CrossrefGoogle Scholar
- 57 Berenson GS, Srinivasan SR, Bao W, Newman WP, Tracy RE, Wattigney WA. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl J Med. 1998; 338: 1650–1656.CrossrefMedlineGoogle Scholar
- 58 Gidding SS, Bookstein LC, Chomka EV. Usefulness of electron beam tomography in adolescents and young adults with heterozygous familial hypercholesterolemia. Circulation. 1998; 98: 2580–2583.CrossrefMedlineGoogle Scholar
- 59Sorof JM, Alexandrov AV, Cardwell G, Portman RJ. Carotid artery intimal-medial thickness and left ventricular hypertrophy in children with elevated blood pressure. Pediatrics 2002; In press.Google Scholar
- 60 Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990; 322: 1561–1566.CrossrefMedlineGoogle Scholar
- 61 Urbina EM, Gidding SS, Bao W, Pickoff AS, Berdusis K, Berenson GS. Effect of body size, ponderosity, and blood pressure on left ventricular growth in children and young adults in the Bogalusa Heart Study. Circulation. 1995; 91: 2400–2406.CrossrefMedlineGoogle Scholar
- 62 Daniels SR, Loggie JM, Khoury P, Kimball TR. Left ventricular geometry and severe left ventricular hypertrophy in children and adolescents with essential hypertension (see comments). Circulation. 1998; 97: 1907–1911.CrossrefMedlineGoogle Scholar
- 63 Sorof JM, Hanevold C, Portman RJ, Daniels SR. Left ventricular hypertrophy in hypertensive children: a Report from the International Pediatric Hypertension Association. Am J Hypertens. 2002; 15: 31A–31A.Abstract.CrossrefMedlineGoogle Scholar
- 64 Morrison JA, Sprecher DL, Barton BA, Waclawiw MA, Daniels SR. Overweight, fat patterning, and cardiovascular disease risk factors in black and white girls: the National Heart, Lung, and Blood Institute Growth and Health Study. J Pediatr. 1999; 135: 458–464.CrossrefMedlineGoogle Scholar
- 65 Morrison JA, Barton BA, Biro FM, Daniels SR, Sprecher DL. Overweight, fat patterning, and cardiovascular disease risk factors in black and white boys. J Pediatr. 1999; 135: 451–457.CrossrefMedlineGoogle Scholar
- 66 Epstein LH, Valoski A, Wing RR, McCurley J. Ten-year follow-up of behavioral, family-based treatment for obese children. JAMA. 1990; 264: 2519–2523.CrossrefMedlineGoogle Scholar
- 67 Tershakovec AM, Watson MH, Wenner WJJ, Marx AL. Insurance reimbursement for the treatment of obesity in children. J Pediatr. 1999; 134: 573–578.CrossrefMedlineGoogle Scholar
- 68 Very low-calorie diets. National Task Force on the Prevention and Treatment of Obesity, National Institutes of Health. JAMA. 1993; 270: 967–974.CrossrefMedlineGoogle Scholar
- 69 Bistrian BR. Clinical use of a protein-sparing modified fast. JAMA. 1978; 240: 2299–2302.CrossrefMedlineGoogle Scholar
- 70 Clarke WR, Woolson RF, Lauer RM. Changes in ponderosity and blood pressure in childhood. The Muscatine Study. Am J Epidemiol. 1986; 124: 195–206.CrossrefMedlineGoogle Scholar
- 71 Brownell KD, Kelman JH, Stunkard AJ. Treatment of obese children with and without their mothers: changes in weight and blood pressure. Pediatrics. 1983; 71: 515–523.MedlineGoogle Scholar
- 72 Figueroa-Colon R, von Almen TK, Franklin FA, Schuftan C, Suskind RM. Comparison of two hypocaloric diets in obese children. Am J Dis Child. 1993; 147: 160–166.MedlineGoogle Scholar
- 73 Gallistl S, Sudi KM, Aigner R, Borkenstein M. Changes in serum interleukin-6 concentrations in obese children and adolescents during a weight reduction program. Int J Obes Relat Metab Disord. 2001; 25: 1640–1643.CrossrefMedlineGoogle Scholar
- 74 Daniels SR. Is there an epidemic of cardiovascular disease on the horizon? J Pediatr. 1999; 134: 665–666.CrossrefMedlineGoogle Scholar