A Clinical Guide to Pediatric Weight Management and Obesity, 1st Edition
Heart disease has become a major cause of morbidity and mortality worldwide. Cardiovascular disease accounted for 29.2% of deaths (16.7 million individuals) across the globe in 2003. Once thought to be a disease of developed countries, it is expected to become the leading cause of death in developing countries by 2010. Approximately 80% of cardiovascular disease deaths occur in low- and middle-income countries: “This rise in cardiovascular disease reflects a shift in dietary habits, physical activity levels and tobacco consumption as a result of industrialization, urbanization, economic development and food market globalization” (1). The major biologic risk factors for cardiovascular disease are hypertension, elevated cholesterol, type 2 diabetes, and obesity. The epidemiologic and biologic risk for cardiovascular disease begins in childhood, and the full effect of risk exposure in the population has yet to occur (1). The increasing obesity epidemic points to the alarming future of cardiovascular disease in the young adult and adult population.
Cardiovascular disease risk is increased when children become obese.
Obesity was among the risk factors, which included increased low-density lipoprotein (LDL) and cholesterol, hypertension, and smoking, that were linked to arterial plaque formation in boys as young as 15 years (2). Specific risk factors for cardiovascular disease, high blood pressure, dyslipidemia, and elevated body mass index (BMI) in childhood, are associated with coronary artery lesions (3). Obesity-related comorbidities of obstructive sleep apnea, left ventricular hypertrophy, and insulin resistance also contribute to risk of cardiovascular morbidity in obese children and adolescents (4).
State of the Problem
Risk factors for cardiovascular disease cluster in obese individuals. In an analysis of coronary heart disease risk factors among obese children, excess adiposity was associated with the following:
- Increased triglycerides
- Increased LDL cholesterol
- Decreased high-density lipoprotein (HDL) cholesterol
- Increased insulin (5)
- Increased C-reactive protein (CRP) (6,7)
- Increased plasminogen activator inhibitor type I (8)
- Increased homocysteine levels (7,9)
- Decreased adiponectin (7)
In the Bogalusa Heart Study (10), clusters of cardiovascular risk factors (LDL cholesterol >130 mg/dL, triglyceride >130 mg/dL, HDL cholesterol <35 mg/dL, elevated insulin level, systolic or diastolic blood pressure >95th percentile) were more common in children with BMI greater than the 95th percentile. Specific risk clusters may exist within the population of overweight and obese children and adolescents.
Visceral adiposity is reflected in increased waist circumference. Obese children with increased waist circumference have higher mean triglyceride level, mean LDL cholesterol level, glucose level, insulin level, and blood pressure than obese children with lower waist circumference (11).
Adding to the overall risk of cardiovascular disease in obese children is a significant level of physical deconditioning, which has been found in children and adolescents with BMI greater than 40 (12). In an analysis of data from the National Health and Nutrition Examination Survey III (NHANES III), CRP was elevated in children with a BMI greater than the 95th percentile (20.6% of boys and 18.7% of girls) (13) and has been inversely related to levels of physical fitness in boys (14).
Vascular endothelial dysfunction, a precursor of atherosclerosis, may be the earliest manifestation of cardiovascular risk in children (15). Children with a history of low birth weight had diminished vascular reactivity compared with normal weight peers, indicating that this may be another effect of the intrauterine environment (16). Childhood obesity is also associated with peripheral vascular dysfunction, the severity of the dysfunction increasing with BMI. Obese children also have a greater carotid intimal medial thickness compared with normal weight children (17). Cardiovascular risk factors can increase along the entire trajectory of childhood.
Population studies have shown that a connection exists between low birth weight and cardiovascular disease (18), diabetes (19), stroke (20), and hypertension (21). Low birth weight has also been linked to risk factors for cardiovascular disease, including obesity, insulin resistance, and impaired glucose tolerance, and is independent of gestational length, smoking, alcohol consumption, and socioeconomic status (22).
Individuals born small for gestational age have been found to have a number of metabolic differences from their normal weight counterparts, which may begin to explain their increased risk for cardiovascular morbidity. Undernutrition in the intrauterine environment may “program” the fetus to respond differently to
extrauterine life, particularly if there is an overabundance of available calories, and rapid catch-up growth occurs (23). The highest rate of development of type 2 diabetes occurred in individuals who had low birth weight and increased postnatal growth (24). Early morning fasting cortisol levels in adults increased with lower birth weights, independent of age, BMI, or changes in cortisol binding globulin (25). Fasting cortisol also correlated with current blood pressure, fasting and 2-hour plasma glucose concentration after a glucose tolerance test, plasma triglyceride levels, and insulin resistance (26).
State of the Problem
Worldwide, high blood pressure is estimated to cause 7.1 million deaths, about 13% of total mortality. Blood pressure usually increases steadily with age. Factors associated with hypertension include excess salt intake, lack of exercise, and obesity (27). Children and adolescents with hypertension have an increased risk of hypertension as adults (28,29). In a population study of school-aged children, in whom hypertension was defined as blood pressure greater than the 95th percentile for age and gender, the strongest determinant of essential hypertension in all ethnic groups was BMI percentile (30).
In a study of primary care pediatric patients between the ages of 2 and 19 years, there was a significant correlation between increasing BMI and both systolic and diastolic blood pressure in all age groups (31).
- Childhood/adolescent hypertension—Systolic and/or diastolic blood pressure greater than the 95th percentile on repeated measurement.
- Prehypertension—Systolic and/or diastolic hypertension between the 90th and 95th percentiles. Ambulatory blood pressure monitoring may be useful in situations of “white coat hypertension” (32).
Measuring Blood Pressure
The inflatable bladder of a blood pressure cuff should cover 80% to 100% of the circumference of the arm, with a width-to-length ratio of 1:2. Blood pressure will be overestimated with a cuff that is too small and underestimated with one too large (32) (Table 7.1). Oscillometric blood pressure equipment measures mean arterial pressure, then calculates systolic and diastolic pressures. The algorithms used in these calculations differ for different devices, and measurement can vary widely (33).
The relationship between blood pressure and cardiovascular disease is continuous. Postmortem studies of children and adolescents have demonstrated significant correlations between the level of blood pressure and the presence of atherosclerotic lesions in the aorta and coronary arteries (32).
TABLE 7.1. Recommended dimensions for blood pressure cuff bladders
In adults, mortality from cardiovascular disease doubles for every 20 mm Hg systolic or 10 mm Hg diastolic blood pressure increase above normal (34). In a study of school-aged children, those with a BMI less than 85% had a prevalence of hypertension of only 2.6% compared with 10.7% in those with a BMI greater than the 95th percentile. The rise in blood pressure with BMI was continuous (30). Systolic blood pressure showed a progressive increase with BMI percentile, whereas no such association was found between diastolic blood pressure and BMI (30). In a longitudinal population study, the effect of childhood BMI on cardiovascular risk factors in adulthood was mediated through the association of childhood BMI with later adult BMI (35). Significant correlations among plasma insulin and systolic blood pressure, diastolic blood pressure, and triglyceride levels have been found in obese children and adolescents (36). In addition, childhood levels of blood pressure have been linked with carotid intimal medial thickness (37) and large artery compliance (38) in young adults.
Several basic mechanisms have been proposed to explain obesity-related hypertension. Insulin has an antinatriuretic effect on the kidney via a direct influence on the renal tubule (39). Increased sympathetic stimulation and/or increased activity of the renin-angiotensin system may also contribute to greater sodium resorption as well as increased vasoconstriction (40). Compression of tubules and vasa recta in the renal medulla may also result in greater sodium resorption in obesity (41). Moreover, obese children have increased aldosterone levels (41). Similar to findings in adults, forearm blood flow and forearm vascular resistance have been noted to increase in obese compared with normal weight children (42). A recent study showed that mean blood pressure rose in obese children during exercise and mental stress while forearm blood flow decreased (42). These changes were reversed by an intervention of diet plus exercise training (42).
Leptin may also be involved in the development of obesity-induced hypertension by mediating increased sympathoactivation. In addition, leptin adversely shifts the renal pressure-natriuresis curve, leading to relative sodium retention (43).
The “Fourth Report on the Diagnosis, Evaluation and Treatment of High Blood Pressure in Children and Adolescents” has recommended obtaining a fasting lipid panel for all overweight children with a blood pressure at the 90th percentile or greater, given that both elevated blood pressure and dyslipidemia dramatically increase the risk for cardiovascular disease (36).
Auscultation is the recommended method of blood pressure measurement in children. Elevated blood pressure must be confirmed on repeat visits before diagnosing hypertension in a child (36) (Tables 7.2, 7.3, and 7.4).
Obesity does not rule out other reasons for hypertension, and evaluation for other possible causes should be undertaken as indicated.
Control of hypertension in adults reduces morbidity and mortality (32). Weight loss has been shown to reduce blood pressure in adults (44), and weight loss of at least 1 BMI unit over a year has been shown to reduce morbidity (45). Weight loss in children was associated with an improvement in systolic and diastolic blood pressure, LDL cholesterol, triglycerides, and insulin resistance with increased HDL cholesterol, if the body mass index standard deviation score (SDS-BMI) decreased by at least 0.5 over 1 year (46).
The National High Blood Pressure Education Program Working Group on High Blood Pressure has recommended that childhood/adolescent hypertension be treated with weight loss secondary to lifestyle intervention and by pharmacologic therapy as needed (36). Increased physical activity and increased fruit, vegetable, and dairy intake are also recommended. If pharmacologic therapy is indicated, treatment should be initiated with a single drug. Recommended acceptable drug classes for children include angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, and diuretics (36).
The panel recommends that “the goal for antihypertensive treatment in children should be reduction of BP to <95th percentile unless concurrent conditions are present, in which case BP should be lowered to <90th percentile. A definite indication for initiating pharmacologic therapy should be ascertained before a drug is prescribed” (36).
Table 7.4 lists the indications for use of antihypertensive drugs in children as recommended by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. Additional details regarding pharmacologic therapy are outlined in the group's report (36).
Ongoing monitoring of target organ damage and drug side effects should be part of the care plan for children with hypertension. Periodic monitoring of electrolytes
in children treated with ACE inhibitor or diuretics should be performed. Specific attention to contraindications (e.g., ACE inhibitors are contraindicated for use during pregnancy) and continued counseling regarding lifestyle change are critical (36). Screening for additional comorbidities of obesity should be included in the treatment and care plan. Counseling regarding other cardiovascular risk factors, such as smoking and alcohol use, is important and should begin early. If blood pressure responds to changes in lifestyle, that is, weight loss and increased physical activity, pharmacologic therapy could be tapered (36).
TABLE 7.2. Blood pressure levels for boys by age and height percentile
TABLE 7.3. Blood pressure for girls by age and height percentile
TABLE 7.4. Indications for antihypertensive drug therapy in children
A complete discussion and recommendations for treatment of hypertension in children and adolescents are found in “The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents” (36) (Table 7.5).
Abnormalities in lipid profiles are part of the increased atherogenic risk in obese children. The metabolic syndrome, common in obese children, is associated with the dyslipidemia triad (triglycerides >150 mg/dL, HDL cholesterol <40 mg/dL, LDL >130 mg/dL) (47).
In obese children 4 to 15 years of age, 45% had blood pressure above the 95th percentile for age and gender, 36% had increased insulin resistance defined as homeostasis model assessment (HOMA) greater than 4, 32% had hypertriglyceridemia, 13% had LDL higher than 150 mg/dL, and 5% had HDL cholesterol lower than 35 mg/dL (46). In a study of 13- to 16-year-olds, total cholesterol was correlated with BMI (48).
LDL cholesterol levels below 100 mg/dL are considered optimal. In children and adolescents, the criteria in Table 7.6 are used to determine elevated lipid levels (49).
State of the Problem
Excess LDL cholesterol can collect in the intima of the arterial wall. As LDL accumulates, the lipids undergo oxidation. Endothelial cells react to these changes by secreting cytokines, which attract monocytes to the intima. Monocytes then mature to active macrophages, which ingest the LDL particles. T cells also respond and, together with the LDL-containing macrophages, form a fatty streak (50).
As the inflammatory process progresses, smooth muscle cells of the media migrate to the top of the intima, producing a fibrous covering over the plaque. As
inflammation continues or flares, the plaque can weaken and break open, causing a clot to form over the break and resulting in a heart attack or stroke (50).
TABLE 7.5. Classification of hypertension in children and adolescents, with measurement frequency and therapy recommendations
Coronary artery calcification correlates with increased BMI in childhood and with increased blood pressure and decreased HDL cholesterol levels. Coronary risk
factors in childhood and adolescence are associated with development of coronary artery calcification in young adult life (51).
TABLE 7.6. Criteria for determining elevated lipid levels
- C-reactive protein (CRP)—An acute phase protein and marker for systemic inflammation that has been associated with risk of coronary heart disease in adults (52).
- Interleukin-6—A proinflammatory cytokine expressed by adipose tissue that stimulates the production of CRP in the liver.
Lifestyle changes aimed at improvement in nutrition, activity, and weight loss are the first steps in treating an obese child or adolescent with borderline or abnormal lipid levels (Table 7.7).
Weight loss is effective; a decrease in SDS-BMI of 0.5 or more over a year was associated with a significant lowering of systolic and diastolic blood pressure, LDL serum cholesterol, triglycerides, and insulin resistance and an increase in HDL cholesterol. LDL cholesterol decreased by a mean of 28 mg/dL, and triglycerides decreased by a mean of 82 mg/dL; HDL increased by a mean of 9 mg/dL and HOMA of insulin resistance decreased by a mean of 0.6 (46).
TABLE 7.7. American Heart Association recommended pattern of nutrition and activity for cardiovascular health in all children and adolescents older than 2 years of age
TABLE 7.8. Other risk factors that contribute to earlier onset of coronary heart disease
The American Academy of Pediatrics statement “Cholesterol in Childhood” recommends that drug therapy be considered in children older than 10 years whose LDL cholesterol remains higher than 190 mg/dL after an adequate trial of dietary therapy (6–12 months). Pharmacologic treatment can also be considered if a child has an LDL cholesterol level that remains higher than 160 mg/dL, with two additional major risk factors (53) (Table 7.8).
The decision to initiate pharmacologic therapy should include careful consideration of both risk and protective factors, the latter including negative family history, female gender, and high HDL cholesterol (54). Cholestyramine, a bile acid binding resin, is approved for use in children. Absorption of medications may be affected, some of which include anticoagulants, digitalis, diuretics, penicillin G, phenylbutazone, propranolol, tetracycline, thyroid hormone, and vancomycin. Medical conditions that can be worsened by the use of cholestyramine include bleeding problems, constipation, gallstones, hemorrhoids, ulcers, hypothyroidism, renal disease, and phenylketonuria (55). Gastrointestinal side effects, including constipation, flatulence, and bloating, are common; fat-soluble vitamin malabsorption is a concern. Cholestyramine is contraindicated when triglyceride levels are higher than 400 mg/dL (54).
Triglyceride elevations are common in obese children, often associated with insulin resistance. A dietary plan should be the first course of treatment, focusing on decreasing the intake of simple sugars. If fasting levels of triglycerides are persistently elevated, evaluation for diabetes, thyroid disease, renal disease, and alcohol abuse is warranted (56). Fish oil (omega-3 fatty acids) can be used to treat hypertriglyceridemia (>500–700 mg/dL), usually at a dose of 2 g/day. Contact sports may be restricted because of an increased risk of bleeding (54). Specific pharmacologic treatment may be initiated at triglyceride levels higher than 400 mg/dL to protect against postprandial triglyceridemia of 1,000 mg/dL or greater, which may be associated with pancreatitis (54). Lovastatin (57), pravastatin (58), simvastatin (59), and atorvastatin (60), 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase) inhibitors, have been studied in randomized trials of up to 48 weeks in the pediatric population. No long-term studies have been completed and these drugs are not approved in pregnancy. In one study of postmenarchal girls with familial hypercholesterolemia enrolled for 24 weeks, lovastatin treatment reduced LDL cholesterol by
23% to 25%, depending on dose (61). (Further discussion of pharmacotherapy for hyperlipidemia is found in Chapter 8, pp. 96–97.)
Left Ventricular Hypertrophy
State of the Problem
Left ventricular hypertrophy is the most prominent evidence of target end- organ damage from hypertension.
Left ventricular hypertrophy is caused by hypertension in children and adolescents and has been reported in up to one third of children with mild, untreated hypertension (36).
Increased left ventricular mass is an independent predictor of coronary artery disease, stroke, and sudden death in adults. A left ventricular mass index of greater than 51 g/m2.7has been associated with a more than 3 times greater than normal risk of cardiovascular disease in adults (62). Left ventricular hypertrophy has been related to overweight in children. Lean body mass, fat mass, and systolic blood pressure have been shown to be independently associated with left ventricular mass in children and adolescents (63). In a study of 130 patients (6–23 years old) followed up in a hypertension clinic for at least 2 years, 8% had a left ventricular mass index greater than 51 g/m2.7 (64).
Children and adolescents with hypertension should have an echocardiogram to determine if they have left ventricular hypertrophy. Left ventricular mass is calculated from measurements of intraventricular septal thickness, left ventricular end-diastolic dimension, and left ventricular posterior wall thickness (65).
Weight loss has been shown to decrease left ventricular mass and blood pressure in children (66,67).
Cardiomyopathy of Obesity
State of the Problem
Cardiomyopathy of obesity is end-organ failure due to interacting effects of obesity on the heart.
Excessive obesity leads to an increase in blood volume and cardiac output caused by greater stroke volume. This increase in cardiac output leads to left ventricular dilation with increasing wall stress and resultant hypertrophy. When hypertrophy does not keep pace with ventricular dilation, wall stress becomes greater and systolic dysfunction may occur, resulting in left ventricular failure. Left ventricular failure can progress to pulmonary hypertension. If sleep apnea is also present, right ventricular failure may occur (68). In morbidly obese adults, increased blood flow and volume and impaired left ventricular compliance caused by left ventricular hypertrophy can predispose to diastolic dysfunction. The degree of dysfunction is affected by the duration of obesity (68). Obstructive sleep apnea has also been associated with left ventricular hypertrophy, diastolic dysfunction, and decrease in the nitric oxide–dependent dilatory capacity of the arterial wall (69).
In adults, signs and symptoms of obesity-related cardiomyopathy have been found in about 10% of patients whose BMI is greater than 40 kg/m2, most of whom have been obese for more than 10 years (70). Clinical signs include the following (68):
- Progressive dyspnea on exertion
- Paroxysmal nocturnal dyspnea
- Lower extremity edema (68)
Cardiomegaly can be seen on chest radiograph (Fig. 7.1). In a study of obese children, mean left ventricular size, posterior wall thickness, and left ventricular mass were significantly greater than in normal weight children (71).
FIG. 7.1. Cardiomyopathy of obesity in a morbidly obese 17-year-old.
Treatment of cardiac failure is primary, with long-term treatment focused on weight loss.
BJ is a 17-year-old African American young man who comes to your office complaining of fatigue and worrying about his physical endurance. His weight is 146.6 kg (>95th percentile) and his height is 167.4 cm (10th percentile), with a BMI of 52.3 (>95th percentile). He says that he never really feels hungry, but his mother, who is with him, says that his portions are large. He has tried cutting back on eating and increasing his exercise but “nothing has worked.” He is living with his mother and younger brother, neither of whom have a problem with weight. His father is not obese.
His dietary pattern is random, with frequent snacking, high consumption of sugar-containing beverages, and eating in his room. He has about 6 to 8 hours of combined computer and television time per day. He has recently tried a summer intramural basketball league, and his performance prompted his concerns about endurance. He is a senior, and his grades are good.
His family history is positive for hypertension, high cholesterol, and cardiovascular disease in his first- and second-degree relatives and for diabetes in the extended family.
His review of systems is positive for inhaler use for exercise asthma, snoring, orthopnea, and daytime tiredness.
On physical examination, his blood pressure is 138/72 mm Hg (systolic >95th percentile). He has acanthosis nigricans and a waist circumference of 132 cm.
His laboratory values show a combined hyperlipidemia, with total cholesterol of 191 mg/dL, triglycerides of 190 mg/dL, LDL cholesterol of 122 mg/dL, and HDL of 31 mg/dL. His fasting insulin is mildly elevated at 30 U/mL. Fasting blood glucose and liver function studies are normal. His metabolic panel is also normal.
You outline the medical problems, which include possible sleep apnea, metabolic syndrome, elevated blood pressure, and morbid obesity with probable significant deconditioning.
You link these comorbidities with his weight and assess BJ's and the family's interest in beginning to make lifestyle change. His mother is supportive of change to help him, and BJ wants to lose weight.
The first step you take with the family is to suggest eliminating the sugared beverages. Both the mother and BJ agree. You also work with them on a structured eating plan, so BJ can have meals on time and dinner with his mom and brother. You give them information about healthy snack and meal choices.
You arrange for BJ to see the pulmonologist for a sleep study and plan for ongoing monitoring of his blood pressure and insulin. BJ and his mother are scheduled to return in 4 weeks.
BJ and his mother are in your office. His weight is 143.6 kg, his height is 167.4 cm, and his BMI is 50.88. His blood pressure is 142/88 mm Hg. He has switched to diet drinks, started eating breakfast, and decreased his intake of cheese. BJ reports he is feeling slightly less hungry and a little more energetic. He is on the schedule for a sleep study. You reinforce his progress, set a goal of daily walking, and ask him to return in 1 month.
On the third visit, BJ's weight is 142.5 kg, down 4.1 kg from his initial visit. His blood pressure is 128/78 mm Hg; you put him on Vasotec 5 mg/day to start treatment and order an echocardiogram. He has been doing “a little walking.” His sleep study was completed and showed significant sleep apnea. Bilevel airway pressure (BiPAP) was recommended, and so far he refuses to use it. You discuss the implications of sleep apnea with him, including the effect on blood pressure, and he says he will “try.” You reschedule an appointment for 2 months because of the mother's concern that BJ will miss school.
BJ returns after 2 months. His weight is 137.1 kg, which makes a total weight loss of 9.5 kg. His blood pressure is 126/72 mm Hg. He has tried his BiPAP a few nights and reports that he feels better after using it but is still having trouble with consistent use. He has begun to play flag football with his friends and is feeling more optimistic about his performance. You encourage continued diet and activity changes.
Two months later, BJ returns with a weight of 132.8 kg, down 13.8 kg total. Laboratory studies show a total cholesterol of 172 mg/dL, triglycerides of 111 mg/dL, and insulin of 6.8 µU/mL. He is happier with himself, is doing well in school, and has begun to wear his BiPAP almost all the time.
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