Hypertension and the Metabolic Syndrome in Children and Adolescents – What Should We Be Doing About It?

1. Hypertension and the Metabolic Syndrome in Children and Adolescents – What Should We Be Doing About It? Bonita Falkner, MD Thomas Jefferson University Nothing to disclose

2. Metabolic Syndrome in Childhood • Definition of the Metabolic Syndrome in Childhood • Prevalence of the Metabolic Syndrome: Child vs Adult • Relationship of the Metabolic Syndrome to Cardiovascular Disease • Causal Factors in the Metabolic Syndrome: Who gets it and why?

3. Metabolic Syndrome(Syndrome X) • Resistance to insulin-stimulated glucose uptake • Hyperinsulinemia • Hypertension • Glucose intolerance • Increased VLDL triglyceride • Decreased HDL cholesterol Reaven G. Clinician. 1989;7:10–14.

4. Metabolic Syndrome(dysmetabolic syndrome) Diagnosis (ICD-9 code 277.7) requires 3 or more of the following: Obesity (BMI >95th %) Elevated BP (systolic and/or diastolic >90th %) Abnormal blood lipids (HDL-C < 40 mg/dl, and/or Triglycerides > 150mg/dl) Impaired glucose tolerance (fasting glucose >100 mg/dl, 2 hr glucose >140, or any glucose > 200 mg/dl) (*source: modified for youth from JAMA 2002;287:356-359)

5. Prevalence(%) of Obesity in US Adults From NHANES 1999-2000 data.

6. Prevalence (%) of Metabolic Syndrome in US Adult Women From NHANES 1999-2000 data.

7. Prevalence (%) of Metabolic Syndrome in US Adult Men From NHANES 1999-2000 data.

8. Type 2 Diabetes Mellitus Stage III Macroangiopathy Microangiopathy Stage IIImpairedglucosetolerance Postprandialplasma glucose  Glucose production  Glucose transport  Insulin secretory deficiency Stage INormalglucosetolerance Atherogenesis Hyperinsulinemia Insulin resistance TG HDL Lipogenesis Obesity Waist/hip ratio HTN Diabetes Genes Type 2 DM is the Tip of the Iceberg Beck-Nielsen H, Groop LC. J Clin Invest. 1994;94:1714–1721.

9. Body Mass Index vs systolic BP among males & females (n=284) Body Mass Index (Kg/m2) Systolic BP (mmHg)

10. Insulin Sensitivity vs systolic BP among males & females (n=284) M/I (mg/Kg-min/uU/ml) Systolic BP (mmHg)

11. Urinary Albumin Excretion in African Americans Campbell KL, Kushner H, Falkner B. Obesity and high blood pressure: a clinical phenotype for the insulin resistance syndrome in African Americans. J of Clinical Hypertension 6:364-372, 2004

12. A New Endocrine Organ:(Visceral) Adipose Tissue • Secretes proteins with metabolic effects in distant cells and tissues • These proteins are responsible for some of the adverse metabolic consequences of overweight/obesity • Adipose tissue excess and deficiency both produce adverse metabolic effects Kershaw E et al J Clin Endocrinol Metab 89: 2548-2556, 2004

13. Adipocytokines • Leptin • Indicator of energy sufficiency • Regulates neuroendocrine function • Affects puberty and reproductive function • TNFα • Associated with insulin resistance • Affects glucose and fat metabolism

14. Adipocytokines • IL-6 • Correlated with obesity, impaired glucose tolerance, & insulin resistance • Levels decrease with weight loss • Plasma concentration predicts type 2 DM and cardiovascular disease

15. Adipocytokines • PAI-1 (plasminogen activator inhibitor) • Expressed in visceral fat • Correlated with metabolic syndrome • Causal link between obesity and CV disease • MCP-1 (macrophage, monocyte chemoattrancant protein) • Pro-inflammatory • Implicated in development of atherosclerosis

16. Adipocytokines • Adiponectin • The “protective” cytokine • Inverse relationship with insulin resistance and inflammation • Increases with weight loss • Anti-inflammatory, antidiabetic, and anti-atherogenic

17. Body Mass Index Obese NBP (A) vs Obese HBP (B)

18. Plasma adiponectin concentration Obese-NBP (A) vs Obese-HBP (BP)

19. Urinary Albumin Excretion mg/Gm creatinineObese NBP (A) vs Obese HBP (B)

23. Mean Systolic Blood Pressure by Age and BMIMales BP-mmHg Age - Years

24. Sorof J, Daniels S. Obesity hypertension in children. Hypertension 40:441-55, 2004

25. Left Ventricular Hypertrophy in Children with Primary Hypertension N = 130 children with BP > 90% LVH = LVMI > 51 gm/m2.7 Daniels et al. Circulation 97:1907, 1998

26. Abnormal Glucose Tolerance in Obese Children and Adolescents Sinha et al, N Engl J Med, 2002

27. Prevalence of Atherosclerosis by HbA1c Concentration in Youth: PDAY Autopsy analyses in 15 to 34 y.o. subjects dead from external causes (n=1300) Prevalence (%) >5% RaisedLesions(Thoracic Aorta) >5% RaisedLesions(Abdominal Aorta) >5% FattyStreaks >5% RaisedLesions (Right Coronary Artery) McGill HC Jr et al. Arterioscler Thromb Vasc Biol. 1995;15:431–440.

28. Association of Risk Factors with Vessel Pathology Berenson et al, N Engl J Med 1998

30. Metabolic Syndrome(dysmetabolic syndrome) Diagnosis (ICD-9 code 277.7) requires 3 or more of the following: Obesity (BMI >95th %) Elevated BP (systolic and/or diastolic >90th %) Abnormal blood lipids (HDL-C < 40 mg/dl, and/or Triglycerides > 150mg/dl) Impaired glucose tolerance (fasting glucose >100 mg/dl, 2 hr glucose >140, or any glucose > 200 mg/dl) (*source: modified for youth from JAMA 2002;287:356-359)

31. Metabolic Syndrome in the Young: How Can it be Managed? • Detection: A condition of multiple CV risk factors • Treatment: Therapeutic Lifestyle Change (TLC) Medical management of Co- morbidity

32. BMI definition for obesity in children is linked with age (and height).

33. Definition of Obesity in Children: Obesity: BMI> 95th Overweight: BMI> 85th

34. Classification of HTN in Children & Adolescents, With Measurement Frequency and Therapy Recommendations SBP or DBP Percentile Normal <90th Prehypertension 90th to <95th or if BP exceeds 120/80 even if below 90th percentile up to <95th percentile Stage 1 hypertension 95th percentile to the 99th percentile plus 5 mmHg Stage 2 hypertension >99th percentile plus 5 mmHg

35. Blood Pressure Levels for Boys by Age and Height Percentile Systolic BP (mmHg) Diastolic BP (mmHg) Age BP Percentile of Height Percentile of Height (Year) Percentile 5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th 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

36. Clinical Evaluation of Confirmed Hypertension

37. Treatment to Improve Insulin Sensitivity • Decrease insulin resistant tissue (fat mass) with reduction in caloric intake. • Increase insulin sensitive tissue (muscle mass) with physical exercise. • Decrease stimulated insulin secretion by reducing free sugar intake. • Manage the co-morbid components of the syndrome of insulin resistance. • Control Blood Pressure • Control Lipids • Screen for Diabetes/Prediabetes.

38. Diet Change to Improve Insulin Sensitivity (and weight control) • Eliminate sugar containing drinks (soda, juice, other sugar sweetened drinks) • Decrease White Foods (pasta, rice, potatos) • Increase Bright Color Foods (vegetables, fruits) (Dash style diet for kids)

39. Physical Activity Change • Decrease Screen time: Television, Video Games, Computer • Increase Physical Activity: Sports or other activities.

40. Extent of Potential Premature Cardiovascular Disease in the Young Overweight (obese) children: 15% = 10,500,000 Hypertension: 1-3% = 700,000- 2,100,000 Metabolic Syndrome: about 30% = 3,150,000 of overweight children Prediabetes: about 25% = 2,625,000 of overweight children (Yale)