A Clinical Guide to Pediatric Weight Management and Obesity, 1st Edition

7

Cardiovascular Complications

Overview

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:

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  • 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).

Etiology

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

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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).

Hypertension

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).

Definitions

  • 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).

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TABLE 7.1. Recommended dimensions for blood pressure cuff bladders

Age range

Width (cm)

Length (cm)

Maximum arm circumference, (cm)a

Newborn

4

8

10

Infant

6

12

15

Child

9

18

22

Small adult

10

24

26

Adult

13

30

34

Large adult

16

38

44

Thigh

20

42

52

a Calculated so that the bladder would still be able to encircle the largest arm by at least 80%.

Reprinted with permission from National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004;114:555–576.

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.

Etiology

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).

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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).

Evaluation

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.

Treatment

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

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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

 

 

Systolic blood pressure (mm Hg) Percentile of height

Diastolic blood pressure (mm Hg) Percentile of height

Age (y)

Blood pressure percentilea

5th

10th

25th

50th

75th

90th

95th

5th

10th

25th

50th

75th

90th

95th

1

50th

80

81

83

85

87

88

89

34

35

36

37

38

39

39

 

90th

94

95

97

99

100

102

103

49

50

51

52

53

53

54

 

95th

98

99

101

103

104

106

106

54

54

55

56

57

58

58

 

99th

105

106

108

110

112

113

114

61

62

63

64

65

66

66

2

50th

84

85

87

88

90

92

92

39

40

41

42

43

44

44

 

90th

97

99

100

102

104

105

106

54

55

56

57

58

58

59

 

95th

101

102

104

106

108

109

110

59

59

60

61

62

63

63

 

99th

109

110

111

113

115

117

117

66

67

68

69

70

71

71

3

50th

86

87

89

91

93

94

95

44

44

45

46

47

48

48

 

90th

100

101

103

105

107

108

109

59

59

60

61

62

63

63

 

95th

104

105

107

109

110

112

113

63

63

64

65

66

67

67

 

99th

111

112

114

116

118

119

120

71

71

72

73

74

75

75

4

50th

88

89

91

93

95

96

97

47

48

49

50

51

51

52

 

90th

102

103

105

107

109

110

111

62

63

64

65

66

66

67

 

95th

106

107

109

111

112

114

115

66

67

68

69

70

71

71

 

99th

113

114

116

118

120

121

122

74

75

76

77

78

78

79

5

50th

90

91

93

95

96

98

98

50

51

52

53

54

55

55

 

90th

104

105

106

108

1110

111

112

65

66

67

68

69

69

70

 

95th

108

109

110

112

114

115

116

69

70

71

72

73

74

74

 

99th

115

116

118

120

121

123

123

77

78

79

80

81

81

82

6

50th

91

92

94

96

98

99

100

53

53

54

55

56

57

57

 

90th

105

106

108

110

111

113

113

68

68

69

70

71

72

72

 

95th

109

110

112

114

115

117

117

72

72

73

74

75

76

76

 

99th

116

117

119

121

123

124

125

80

80

81

82

83

84

84

7

50th

92

94

95

97

99

100

101

55

55

56

57

58

59

59

 

90th

106

107

109

111

113

114

115

70

70

71

72

73

74

74

 

95th

110

111

113

115

117

118

119

74

74

75

76

77

78

78

 

99th

117

118

120

122

124

125

126

82

82

83

84

85

86

86

8

50th

94

95

97

99

100

102

102

56

57

58

59

60

60

61

 

90th

107

109

110

112

114

115

116

71

72

72

73

74

75

76

 

95th

111

112

114

116

118

119

120

75

76

77

78

79

79

80

 

99th

119

120

122

123

125

127

127

83

84

85

86

87

87

88

9

50th

95

96

98

100

102

103

104

57

58

59

60

61

61

62

 

90th

109

110

112

114

115

117

118

72

73

74

75

76

76

77

 

95th

113

114

116

118

119

121

121

76

77

78

79

80

81

81

 

99th

120

121

123

125

127

128

129

84

85

86

87

88

88

89

10

50th

97

98

100

102

103

105

106

58

59

60

61

61

62

63

 

90th

111

112

114

115

117

119

119

73

73

74

75

76

77

78

 

95th

115

116

117

119

121

122

123

77

78

79

80

81

81

82

 

99th

122

123

125

127

128

130

130

85

86

86

88

88

89

90

11

50th

99

100

102

104

105

107

107

59

59

60

61

62

63

63

 

90th

113

114

115

117

119

120

121

74

74

75

76

77

78

78

 

95th

117

118

119

121

123

124

125

78

78

79

80

81

82

82

 

00th

124

125

127

129

130

132

132

86

86

87

88

89

90

90

12

50th

101

102

104

106

108

109

110

59

60

61

62

63

63

64

 

90th

115

116

118

120

121

123

123

74

75

75

76

77

78

79

 

95th

119

120

122

123

125

127

127

78

79

80

81

82

82

83

 

99th

126

127

129

131

133

134

135

86

87

88

89

90

90

91

13

50th

104

105

106

108

110

111

112

60

60

61

62

63

64

64

 

90th

117

118

120

122

124

125

126

75

75

76

77

78

79

79

 

95th

121

122

124

126

128

129

130

79

79

80

81

82

83

83

 

99th

128

130

131

133

135

136

137

87

87

88

89

90

91

91

14

50th

106

107

109

111

113

114

115

60

61

62

63

64

65

65

 

90th

120

121

123

125

126

128

128

75

76

77

78

79

79

80

 

95th

124

125

127

128

130

132

132

80

80

81

82

83

84

84

 

99th

131

132

134

136

138

139

140

87

88

89

90

91

92

92

15

50th

109

110

112

113

115

117

117

61

62

63

64

65

66

66

 

90th

122

124

125

127

129

130

131

76

77

78

79

80

80

81

 

95th

126

127

129

131

133

134

135

81

81

82

83

84

85

85

 

99th

134

135

136

138

140

142

142

88

89

90

91

92

93

93

17

50th

114

115

116

118

120

121

122

65

66

66

67

68

69

70

 

90th

127

128

130

132

134

135

136

80

80

81

82

83

84

84

 

95th

131

132

134

136

138

139

140

84

85

86

87

87

88

89

 

99th

139

140

141

143

145

146

147

92

93

93

94

95

96

97

The 90th percentile is 1.28 SD, the 95th percentile is 1.645 SD, and the 99th percentile is 2.326 SD over the mean.

Reprinted with permission from National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004;114: 555–576.

TABLE 7.3. Blood pressure for girls by age and height percentile

 

 

Systolic blood pressure (mm Hg) Percentile of height

Diastolic blood pressure (mm Hg) Percentile of height

Age (y)

Blood pressure percentilea

5th

10th

25th

50th

75th

90th

95th

5th

10th

25th

50th

75th

90th

95th

1

50th

83

84

85

86

88

89

90

38

39

39

40

41

41

42

 

90th

97

97

98

100

101

102

103

52

53

53

54

55

55

56

 

95th

100

101

102

104

105

106

107

56

57

57

58

59

59

60

 

99th

108

108

109

111

112

113

114

64

64

65

65

66

67

67

2

50th

85

85

87

88

89

91

91

43

44

44

44

45

46

47

 

90th

98

99

100

101

103

104

105

57

58

58

59

60

61

61

 

95th

102

103

104

105

107

108

109

61

62

62

63

64

65

65

 

99th

109

110

111

112

114

115

116

69

69

70

70

71

72

72

3

50th

86

87

88

89

91

92

93

47

48

48

49

50

50

51

 

90th

100

100

102

103

104

106

106

61

62

62

63

64

64

65

 

95th

104

104

105

107

108

109

110

65

66

66

67

68

68

69

 

99th

111

111

113

114

115

116

117

73

73

74

74

75

76

76

4

50th

88

88

90

91

92

94

94

50

50

51

52

52

53

54

 

90th

101

102

103

104

106

107

108

64

64

65

66

67

67

68

 

95th

105

106

107

108

110

111

112

68

68

69

70

71

71

72

 

99th

112

113

114

115

117

118

119

76

76

76

77

78

79

79

5

50th

89

90

91

93

94

95

96

52

53

53

54

55

55

56

 

90th

103

103

105

106

107

109

109

66

67

67

68

69

69

70

 

95th

107

107

108

110

111

112

113

70

71

71

72

73

73

74

 

99th

114

114

116

117

118

120

120

78

78

79

79

80

81

81

6

50th

91

92

93

94

96

97

98

54

54

55

56

56

57

58

 

90th

104

105

106

108

109

110

111

68

68

69

70

70

71

72

 

95th

108

109

110

111

113

114

115

72

72

73

74

74

75

76

 

99th

115

116

117

119

120

121

122

80

80

80

81

82

83

83

7

50th

93

93

95

96

97

99

99

55

56

56

57

58

58

59

 

90th

106

107

108

109

111

112

113

69

70

70

71

72

72

73

 

95th

110

111

112

113

115

116

116

73

74

74

75

76

76

77

 

99th

117

118

119

120

122

123

124

81

81

82

82

83

84

84

8

50th

95

95

96

98

99

100

101

57

57

57

58

59

60

60

 

90th

108

109

110

111

113

114

114

71

71

71

72

73

74

74

 

95th

112

112

114

115

116

118

118

75

75

75

76

77

78

78

 

99th

119

120

121

122

123

125

125

82

82

83

83

84

85

86

9

50th

96

97

98

100

101

102

103

58

58

58

59

60

61

61

 

90th

110

110

112

113

114

116

116

72

72

72

73

74

75

75

 

95th

114

114

115

117

118

119

120

76

76

76

77

78

79

79

 

99th

121

121

123

124

125

127

127

83

83

84

84

85

86

87

10

50th

98

99

100

102

103

104

105

59

59

59

60

61

62

62

 

90th

112

112

114

115

116

118

118

73

73

73

74

75

76

76

 

95th

116

116

117

119

120

121

122

77

77

77

78

79

80

80

 

99th

123

123

125

126

127

129

129

84

84

85

86

86

87

88

11

50th

100

101

102

103

105

106

107

60

60

60

61

62

63

63

 

90th

114

114

116

117

118

119

120

74

74

74

75

76

77

77

 

95th

118

118

119

121

122

123

124

78

78

78

79

80

81

81

 

99th

125

125

126

128

129

130

131

85

85

86

87

87

88

89

12

50th

102

103

104

105

107

108

109

61

61

61

62

63

64

64

 

90th

116

116

117

119

120

121

122

75

75

75

76

77

78

78

 

95th

119

120

121

123

124

125

126

79

79

79

80

81

82

82

 

99th

127

127

128

130

131

132

133

86

86

87

88

88

89

90

13

50th

104

105

106

107

109

110

110

62

62

62

63

64

65

65

 

90th

117

118

119

121

122

123

124

76

76

76

77

78

79

79

 

95th

121

122

123

124

126

127

128

80

80

80

81

82

83

83

 

99th

128

129

130

132

133

134

135

87

87

88

89

89

90

91

14

50th

106

106

107

109

110

111

112

63

63

63

64

65

66

66

 

90th

119

120

121

122

124

125

125

77

77

77

78

79

80

80

 

95th

123

123

125

126

127

129

129

81

81

81

82

83

84

84

 

99th

130

131

132

133

135

136

136

88

88

89

90

90

91

92

15

50th

107

108

109

110

111

113

113

64

64

64

65

66

67

67

 

90th

120

121

122

123

125

126

127

78

78

78

79

80

81

81

 

95th

124

125

126

127

129

130

131

82

82

82

83

84

85

85

 

99th

131

132

133

134

136

137

138

89

89

90

91

91

92

93

16

50th

108

108

110

111

112

114

114

64

64

65

66

66

67

68

 

90th

121

122

123

124

126

127

128

78

78

79

80

81

81

82

 

95th

125

126

127

128

130

131

132

82

82

83

84

85

85

86

 

99th

132

133

134

135

137

138

139

90

90

90

91

92

93

93

17

50th

108

109

110

111

113

114

115

64

65

65

66

67

67

68

 

90th

122

122

123

125

126

127

128

78

79

79

80

81

81

82

 

95th

125

126

127

129

130

131

132

82

83

83

84

85

85

86

 

99th

133

133

134

136

137

138

139

90

90

91

91

92

93

93

a The 90th percentile is 1.28 SD, the 95th percentile is 1.645 SD, and the 99th percentile is 2.326 SD over the mean.

Reprinted with permission from National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004;114: 555–576.

TABLE 7.4. Indications for antihypertensive drug therapy in children

Symptomatic hypertension

Diabetes (types 1 and 2)

Secondary hypertension

Persistent hypertension despite nonpharmacologic measures

Hypertensive target-organ damage

 

Reprinted with permission from National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004; 114:555–576.

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).

Dyslipidemia

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

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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

 

SBPor DBP percentilea

Frequency of BP measurement

Therapeutic lifestyle changes

Pharmacologic therapy

Normal

<90th

Recheck at next scheduled physical examination

Encourage healthy diet, sleep, and physical activity

 

Prehypertension

90th to <95th or if BP exceeds 120/80 even if <90th percentile up to <95th percentileb

Recheck in 6 mo

Weight-management counseling if overweight; introduce physical activity and diet managementc

None unless compelling indications such as chronic kidney disease, diabetes mellitus, heart failure, or LVH exist

Stage 1 hypertension

95th–99th percentile plus 5 mm Hg

Recheck in 1–2 wk or sooner if the patient is symptomatic; if persistently elevated on 2 additional occasions, evaluate or refer to source of care within 1 mo

Weight-management counseling if overweight; introduce physical activity and diet management

Initiate therapy based on indications inTable 7.4 or if compelling indications (as shown above) exist

Stage 2 hypertension

>99th percentile plus 5 mm Hg

Evaluate or refer to source of care within 1 wk or immediately if the patient is symptomatic

Weight-management counseling if overweight; introduce physical activity and diet management

Initiate therapyd

BP, blood pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure; LVH, left ventricular hypertrophy.

a For gender, age, and height measured on at least three separate occasions; if systolic and diastolic categories are different, categorize by the higher value.

b This occurs typically at 12 years old for SBPand at 16 years old for DBP.

c Parents and children trying to modify the eating plan to the Dietary Approaches to Stop Hypertension Study eating plan could benefit from consultation with a registered or licensed nutritionist to get them started.

d More than one drug may be required.

Reprinted with permission from National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004; 114:555–576.

Coronary artery calcification correlates with increased BMI in childhood and with increased blood pressure and decreased HDL cholesterol levels. Coronary risk

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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

 

Low

Normal

High

Total cholesterol

<170 mg/dL

170–199 mg/dL

>200 mg/dL

HDL cholesterol

>40 mg/dL

 

<40 mg/dL

LDL cholesterol

<100 mg/dL

100–129 mg/dL

>130 mg/dL

Triglycerides

<200 mg/dL

 

>200 mg/dL

Reprinted with permission from Gidding SS, Dennison BA, Birch LL, Daniels SR, Gilman MW, Lichtenstein AH, Rattay KT, Steinberger J, Stettler N, Van Horn L; American Heart Association. American Heart Association Dietary Recommendations for Children and Adolescents: a guide for practitioners. Pediatrics. 2006;117:544–549.

Definitions

  • 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.

Treatment

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

Eat foods low in saturated fat (<10% of calories/day), cholesterol (<300 mg/dL), trans fatty acids.

Include a variety of fruits, vegetables, whole grains, dairy products, and lean protein sources in the daily nutrition plan.

Match energy intake with energy needs for normal growth and development.

Limit intake of salt and sugar.

Passive and active cigarette smoking should be discouraged.

Physical activity for children and adolescents should be fun.

Children and adolescents should have 60 minutes of physical activity daily.

Reprinted with permission from Mahoney LT, Burns TL, Stanford W, et al. Coronary risk factors measured in childhood and young adult life are associated with coronary artery calcification in young adults: the Muscatine Study. J Am Coll Cardiol. 1996;27:277–284.

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TABLE 7.8. Other risk factors that contribute to earlier onset of coronary heart disease

Family history of premature coronary heart disease, cerebrovascular disease, or occlusive peripheral vascular disease (definite onset before the age of 55 yin siblings, parent, or sibling of parent)

Cigarette smoking

Elevated blood pressure

Low HDL-cholesterol concentration (<35 mg/dL)

Obesity (≥95th BMI)

Diabetes mellitus

Physical inactivity

HDL, high-density lipoprotein; BMI, body mass index.

Reprinted with permission from Libby P. Vascular biology of atherosclerosis: overview and state of the art. Am J Cardiol. 2003;91(3A):3A–6A.

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

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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.

 

Etiology

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).

Evaluation

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).

Treatment

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.

 

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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).

Clinical Manifestations

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
  • Orthopnea
  • 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.

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Treatment

Treatment of cardiac failure is primary, with long-term treatment focused on weight loss.

Case

Initial Presentation

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.

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Second Visit

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.

Third Visit

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.

Fourth Visit

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.

Fifth Visit

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.

References

  1. World Health Organization. Cardiovascular Disease Facts. http://www.who.int/dietphysicalactivity/publications/facts/cvd/en/(accessed 5/1/06).
  2. Relationship of atherosclerosis in young men to serum lipoprotein cholesterol concentrations and smoking: a preliminary report from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. JAMA.1990;264:3018–3024.
  3. Berenson GS, Srinivasan SR, Bao W, Newman WP 3rd, 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.
  4. Daniels SR, Arnett DK, Eckel RH, Gidding SS, Hayman LL, Kumanyika S, Robinson TN, Scott BJ, St Jeor S, Williams CL. Overweight in children and adolescents: pathophysiology, consequences, prevention and treatment. Circulation.2005;111:1999–2012.

P.82

 

  1. Freedman DS, Serdula MK, Srinivassan SR, Berenson GS. The relation of circumference and skinfolds to levels of lipids and insulin: the Bogalusa Heart Study. Am J Clin Nutr.1999;69:308–317.
  2. Ford ES. Galuska DA, Gillespie C, Will JC, Giles WH, Dietz WH. C reactive protein and body mass index in children findings of the Third National Health and Nutrition Examination Survey 1988–1994. J Pediatr.2001;138:486–492.
  3. Pilz S, Horejsi R, Moller R, Almer G, Scharnagl H, Stojakovic T, Dimitrova R, Weihrauch G, Borkenstein M, Maerz W, Schauenstein K, Mangge H. Early atherosclerosis in obese juveniles is associated with low serum levels of adiponectin. J Clin Endocrinol Metab.2005;90:4792–4796.
  4. Estelles A, Dalmau J, Falco C, Berbel O, Castello R, Espana F, Aznar J. Plasma PA-1 levels in obese children: effect of weight loss and influence of PAI-1 promoter 4G/5G genotype. Thromb Haemost.2001;86:647–652.
  5. Gallistl S, Sudi K, Mangge H, Erwa W, Borkenstein M. Insulin is an independent correlate of plasma homocysteine levels in obese children and adolescents. Diabetes Care.2000;23:1348–1352.
  6. Freedman DS, Dietz WH, Srinivasan SR, Berenson GS. The relation of overweight to cardiovascular risk factors among children and adolescents: the Bogalusa Heart Study. Pediatrics.1999;103(6 Pt 1): 1175–1182.
  7. Janssen I, Katzmarzyk PT, Srinivasan SR, Chen W, Malina RM, Bouchard C, Berenson GS. Combined influence of body mass index and waist circumference on coronary artery disease risk factors among children and adolescents. Pediatrics.2005;115:1623–1630.
  8. Gidding SS, Nehgme R, Heise C, Muscar C, Linton A, Hassink S. Severe obesity associated with cardiovascular deconditioning, high prevalence of cardiovascular risk factors, diabetes mellitus/hyperinsulinemia, and respiratory compromise. J Pediatr.2004;144:766–769.
  9. Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB. Low grade systemic inflammation in overweight children. Pediatrics.2001;107(1):e 13.
  10. Isasi CR, Deckelbaum RJ, Tracy RP, Starc TJ, Berglund L, Shea S. Physical fitness and C reactive protein level in children and young adults: The Columbia University Bio Markers Study. Pediatrics.2003;111:332–338.
  11. Cohen MS. Fetal and childhood onset of adult cardiovascular disease. Pediatr Clin North Am.2004;51:1697–1719.
  12. Leeson CP, Whincup PH, Cook DG, Donald AE, Papacosta O, Lucas A, Deanfield JE. Flow mediated dilation in 9 to 11 year old children: the influence of intrauterine and childhood factors. Circulation.1997;96:2233–2238.
  13. Woo KS, Chook P, Yu CW, Sung RY, Qiao M, Leung SS, Lam CW, Metreweli C, Celermajer DS. Overweight in children is associated with arterial endothelial dysfunction and intima-media thickening. Int J Obes Relat Metab Disord.2004;28:1–6.
  14. Barker DJ. The intrauterine origins of cardiovascular disease. Acta Paediatr Suppl.1993;82(Suppl 391):93–99.
  15. Hales CN, Barker DJ, Clark PM, Cox LJ, Fall C, Osmond C, Winter PD. Fetal and infant growth and impaired glucose tolerance at age 64. BMJ.1991;303:1019–1022.
  16. Martyn CN, Barker DJ, Osmond C. Mothers pelvic size, fetal growth, and death from stroke and coronary heart disease in men in the UK. Lancet.1996;348:1264–1268.
  17. Barker DJ, Bull AR, Osmond C, Simmonds SJ. Fetal and placental size and risk of hypertension in adult life. BMJ.1990;301:259–262.
  18. Barker DJ, Hales CN, Fall CH, Osmond C, Phipps K, Clark PM. Type 2 (non insulin dependent) diabetes mellitus, hypertension and hyperlipidemia (syndrome X): relation to reduced fetal growth. Diabetologia.1993;36:62–67.
  19. Ong KK, Dunger DB. Perinatal growth failure: the road to obesity insulin resistance and cardiovascular disease in adults. Best Pract Res Clin Endocrinol Metab.2002;16:191–207.
  20. Forsen T, Eriksson J, Tuomilehto J, Reunanen A, Osmond C, Barker D. The fetal and childhood growth of person who develop type 2 diabetes. Ann Intern Med.2000;133:176–182.
  21. Phillips DI, Walker BR, Reynolds RM, Flanagan DE, Wood PJ, Osmond C, Barker DJ, Whorwood CB. Low birth weight predicts elevated plasma cortisol concentrations in adults from 3 populations. Hypertension.2000;35:1301–1306.
  22. Phillips DI, Barker DJ, Fall CH, Seckl JR, Whorwood CB, Wood PJ, Walker BR. Elevated plasma cortisol concentrations: a link between low birth weight and the insulin resistance syndrome? J Clin Endocrinol Metab.1998;83:757–760.
  23. World Health Report 2002. Reducing risks, promoting healthy life. http://www.who.int/whr/2002/en/p. 69 (accessed 5/2/06).

P.83

 

  1. Falkner B, Kushner H, Onesti G, Angelakos ET. Cardiovascular characteristics in adolescents who develop essential hypertension.Hypertension.198;13:521–527.
  2. Bao W, Threefoot SA, Srinivasan SR, Berenson GS. Essential hypertension predicted by tracking of elevated blood pressure from childhood to adulthood: the Bogalusa Heart Study. Am J Hypertens.1995;8:657–665.
  3. Sorof JM, Lai D, Turner J, Poffenbarger T, Portman RJ. Overweight, ethnicity, and the prevalence of hypertension in school-aged children. Pediatrics.2004;113(3 Pt 1):475–482.
  4. Falkner B, Gidding SS, Ramirez-Garnica G, Wiltrout SA, West D, Rappaport EB. The relationship of body mass index and blood pressure in primary care pediatric patients. J Pediatr.2006;148:195–200.
  5. Portman RJ, McNiece KL, Swinford RD, Braun MC, Samuels JA. Pediatric hypertension: diagnosis, evaluation, management and treatment for the primary care physician. Curr Probl Pediatr Adolesc Health Care.2005;35:262–294.
  6. Kaufmann MA, Pargger H, Drop LJ. Oscillometric blood pressure measurement by different devices are not interchangeable. Anesth Analg.1996;82:377–381.
  7. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT JR, Roccella EJ; National Heart, Lung and Blood Institute Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. National Heart, Lung and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Hypertension.2003;42:1206–1253.
  8. Freedman, DS, Khan LK, Dietz WH, Srinivasan SR, Berenson GS. Relationship of childhood obesity to coronary heart disease risk factors in adulthood: The Bogalusa Heart Study. Pediatrics.2001;108: 712–718.
  9. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation and treatment of high blood pressure in children and adolescents. Pediatrics.2004;114(2 Suppl):555–576.
  10. Davis PH, Dawson JD, Riley WA, Lauer RM. Carotid intimal medial thickness is related to cardiovascular risk factors measured from childhood through middle age: the Muscatine Study. Circulation.2001;104:2815–2819.
  11. Arnett DK, Glasser SP, McVeigh G, Prineas R, Finklestein S, Donahue R, Cohn JN, Sinaiko A. Blood pressure and arterial compliance in young adults: the Minnesota Children's Blood Pressure study. Am J Hypertens.2001;14:200–205.
  12. DeFronzo RA. The effect of insulin on renal sodium metabolism A review with clinical implications. Diabetologia.1981;21:165–171.
  13. Antic V, Dulloo A, Montani JP. Multiple mechanisms involved in obesity-induced hypertension. Heart Lung Circ.2003;12(2):84–93.
  14. Hall JE, Brands MW, Henegar JR. Mechanisms of hypertension and kidney disease in obesity. Ann NY Acad Sci.1999;892:91–107.
  15. Ribeiro MM, Silva AG, Santos NS, Guazzelle I, Matos LN, Trombetta IC, Halpern A, Negrao CE, Villares SM. Diet and exercise training restore blood pressure and vasodilatory responses during physiological maneuvers in obese children. Circulation.2005;111:1915–1923.
  16. Haynes WG. Role of leptin in obesity-related hypertension. Exp Physiol.2005;90:683–688.
  17. Watkins LL, Sherwood A, Feinglos M, Hinderliter A, Babyak M, Gullette E, Waugh R, Blumenthal JA. Effects of exercise and weight loss on cardiac risk factors associated with syndrome X. Arch Intern Med.2003;163:1889–1895.
  18. Stern JS, Hirsch J, Blair SN, Foreyt JP, Frank A, Kumanyika SK, Madans JH, Marlatt GA, St Jeor ST, Stunkard AJ. Weighing the options—criteria for evaluating weight management programs. The committee to develop criteria for evaluating the outcomes of approaches to prevent and treat obesity. Obes Res.1995;3:591–604.
  19. Reinehr T, Andler W. Changes in the atherogenic risk factor profile according to degree of weight loss. Arch Dis Child.2004;89:419–420.
  20. Sinaiko AR, Donahue RP, Jacobs DR, Prineas RJ. Relation of weight and rate of increase in weight during childhood and adolescence to body size, blood pressure, fasting insulin, and lipids in young adults. The Minneapolis Children's Blood Pressure Study. Circulation.1999;99:1471–1476.
  21. Owen CG, Whincup PH, Odoki K, Gilg JA, Cook DG. Birth weight and blood cholesterol level: a study in adolescents and systematic review. Pediatrics.2003;111(5 Pt 1):1081–1089.

P.84

 

  1. Gidding SS, Dennison BA, Birch LL, Daniels SR, Gilman MW, Lichtenstein AH, Rattay KT, Steinberger J, Stettler N, Van Horn L; American Heart Association. American Heart Association Dietary Recommendations for Children and Adolescents: a guide for practitioners. Pediatrics.2006;117: 544–549.
  2. Libby P. Vascular biology of atherosclerosis; overview and state of the art. Am J Cardiol.2003; 91(3A):3A–6A.
  3. Mahoney LT, Burns TL, Stanford W, Thompson BH, Witt JD, Rost CA, Lauer RM. Coronary risk factors measured in childhood and young adult life are associated with coronary artery calcification in young adults: the Muscatine Study. J Am Coll Cardiol.1996;27:277–284.
  4. Lowe GD. Circulating inflammatory markers and risks of cardiovascular and non-cardiovascular disease. J Thromb Haemost.2005;3:1618–1627.
  5. American Academy of Pediatrics. Cholesterol in Childhood Committee on Nutrition. Pediatrics.1998;101:141–147.
  6. Gidding SS. Cardiovascular risk factors in adolescents. Curr Treat Options Cardiovasc Med.2006;8.
  7. Medline plus. http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202137.html (accessed 5/3/06).
  8. Kavey RE, Daniels SR, Lauer RM, Atkins DL, Hayman LL, Taubert K; American Heart Association. American Heart Association guideline for primary prevention of atherosclerotic cardiovascular disease beginning childhood. Circulation.2003;107:1562–1566.
  9. Stein EA, Illingworth DR, Kwiterovich PO Jr, Liacouras CA Siimes MA, Jacobson MS, Brewster TG, Hopkins P, Davidson M, Graham K, Arensman F, Knopp RH, DuJovne C, Williams CL, Isaachsohn JL, Jacobsen CA, Laskarzewski PM. Ames S, Gormley GJ. Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia: a randomized controlled trial. JAMA.1999;281:137–144.
  10. Wiegman A, Hutten BA, deGroot E, Rodenburg J, Bakker HD, Buller HR, Sijbrands EJ, Kastelein JJ. Efficacy and safety of statin therapy in children with familial hypercholesterolemia a randomized controlled trial. JAMA.2004;292:331–337.
  11. deJongh S, Ose L, Szamosi T, Gagne C, Lambert M, Scott R, Perron P, Dobbelaere D, Saborio M, Tuohy MB, Stepanavage M, Sapre A, Gumbiner B, Mercuri M, van Trotsenburg AS, Bakker HD, Kastelein JJ; Simvastatin in Children Study Group. Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized, double blind, placebo controlled trial with Simvastatin. Circulation.2002;106:2231–2237.
  12. McCrindle BW, Ose L, Marais AD. Efficacy and safety of atorvastatin in children and adolescents with familial hypercholesterolemia or severe hyperlipidemia: a multicenter, randomized placebo-controlled trial. J Pediatr.2003;439:74–80.
  13. Clauss SB, Holmes KW, Hopkins P, Stein E, Cho M, Tate A, Johnson-Levonas AO, Kwiterovich PO. Efficacy and in safety of lovastatin therapy in adolescent girls with heterozygous familial hypercholesterolemia. Pediatrics.2005;116:682–688.
  14. de Simone G, Devereux RB, Daniels SR, Koren MJ, Meyer RA, Laragh JH. Effect of growth on variability of left ventricular mass: assessment of allometric signals in adults and children and their capacity to predict cardiovascular risk. J Am Coll Cardiol.1995;25:1056–1062.
  15. Daniels SR, Kimball TR, Morrison JA, Khoury P, Witt S, Meyer RA. Effect of lean body mass, fat mass, blood pressure, and sexual maturation on left ventricular mass in children and adolescents. Statistical, biological and clinical significance. Circulation.1995;92:3249–3254.
  16. Daniels SR, Loggie JM, Khoury P, Kimball TR. Left ventricular geometry and severe left ventricular hypertrophy in children and adolescents with essential hypertension. Circulation.1998;97: 1907–1911.
  17. de Simone G, Daniels SR, Devereux RB, Meyer RA, Roman MJ, de Divitiis O, Alderman MH. Left ventricular mass and heart size in normotensive children and adults: assessment of allometric relations and impact of overweight. J Am Coll Cardiol.1992;20:1251–1260.
  18. Rocchini AP, Katch V, Anderson J, Hinderliter J, Becque D, Martin M, Marks C. Blood pressure in obese adolescents: effect of weight loss. Pediatrics.1988;82:16–23.
  19. MacMahon SW, Wilcken DEL, Macdonald GJ. The effect of weight reduction on left ventricular mass: a randomized controlled trial in young overweight hypertensive patients. N Engl J Med.1986;314:334–339.
  20. Alpert MA. Obesity cardiomyopathy: pathophysiology and evolution of the clinical syndrome. Am J Med Sci.2001;321:225–236.
  21. Kraiczi H, Caidahl K, Samuelsson A, Peker Y, Hedner J. Impairment of vascular endothelial function and left ventricular filling association with the severity of apnea induced hypoxemia during sleep. Chest.2001;119:1085–1091.
  22. Alexander JK. Obesity and the heart. Curr Prob Cardiol.1980;5(3):6–41.
  23. Yoshinaga M, Yuasa Y, Hatano H, Kono Y, Nomura Y, Oku S, Nakamura M, Kanekura S, Otsubo K, Akiba S, et al. Effect of total adipose weight and systemic hypertension of left ventricular mass in children. Am J Cardiol.1995;76:785–787.