Hypertension with Comorbidities Treatment of Metabolic Risk Factors in Children and Adolescents

Hypertension with Comorbidities Treatment of Metabolic Risk Factors in Children and Adolescents Stella Stabouli Ass. Professor Pediatrics 1 st Department of Pediatrics Hippocratio Hospital

Evaluation of a child or adolescent with hypertension Etiology of Hypertension Target organ damage Cardiometabolic risk factors

The Case : A 14-year old Caucasian boy referred for BP levels for age, sex and height on more than 3 different occasions OBESITY WITH CENTRAL DISTRIBUTION Born preterm, BW: 2.4 Kg Weight at age of 1 year >90 th percentile Weight at age of 3 years > 95 th percentile, height> 90 th percentile OBESITY, PHYSCICAL INACTIVITY, HIGH SALT-FAT The patient reported 2-3 attempts to lose weight with diet with temporary results DIET His regular physical activity is limited to gymnastics classes-30 min sessions/1-2 times per week His regular diet includes daily consumption of soft drinks and salted snacks and many fast food meals His mother is also obese and has HTN and type 2 diabetes FAMILY HISTORY OF HTN and OBESITY GLUCOSE INTOLERANCE ELEVATED TRIGLYCERIDES, LOW HDL CHOLESTEROL

Metabolic risk factors and hypertension Hypertension Insulin resistance, glucose intolerance Diabetes Obesity Hgh TG Low HDL

Metabolic risk factors and hypertension Obesity Hypertension Hgh TG Low HDL Insulin resistance, glucose intolerance Diabetes Increased prevalence of TOD At risk of future CV morbidity and mortality

LVH prevalence (%) LVH and in children with HTN and metabolic risk factors 90 80 70 60 50 40 30 LVMI<95th pc LVMI >95th pc 20 10 0 HTN 2 3 4 No of metabolic risk factors in addition to HTN Modified from Litwin et al, AJH 2007;20:875-882

Prevalence of CVD risk factors among US adolescents, NHANES 1999 2008 N = 3383 Ashleigh L. May et al. Pediatrics 2012;129:1035-1041

Obesity and Nocturnal Blood Pressure Elevation in Children The role of insulin resistance Lurbe et al, Hypertension 2008;51:635-641

Trends in High Blood Pressure among United States Adolescents across Body Weight Category between 1988 and 2012 Yang et al, J Pediatr. 2016 Feb;169:166-73

Prehypertension and Cardiovascular Risk Factors in Children and Adolescents Participating in the Community-Based Prevention Education Program Family Heart Study Haas et al, Int J Prev Med. 2014 Mar; 5(Suppl 1): S50 S56

Hypertension. 2014;63:1326-1332

Management of HTN in children and adolescents with metabolic risk factors Goals: Reduce the risk of future cardiovascular events Delay or prevent the progression of TOD Target: BP Target : Metabolic risk factors

Lifestyle modification is the cornerstone of treatment Blood pressure Insulin resistance, diabetes Lifestyle modification Dyslipidemia Obesity

Effectiveness of Lifestyle Interventions in Child Obesity: Systematic Review With Meta-analysis Ho et al, Pediatrics 2012;130:e1647 e1671

A. Differences in mean diastolic blood pressure B. Differences in mean systolic blood pressure Effectiveness of Lifestyle Interventions in Child Obesity: Systematic Review With Meta-analysis Ho et al, Pediatrics 2012;130:e1647 e1671

Differences in mean fasting insulin and HOMA-IR Effectiveness of Lifestyle Interventions in Child Obesity: Systematic Review With Meta-analysis Ho et al, Pediatrics 2012;130:e1647 e1671

A. Mean differences in triglycerides concentrations B. Mean differences in LDL cholesterol C. Mean differences in HDL concentrations Effectiveness of Lifestyle Interventions in Child Obesity: Systematic Review With Meta-analysis Ho et al, Pediatrics 2012;130:e1647 e1671

2016 ESH guidelines for the management of high blood pressure in children and adolescents

BMI 2016 ESH guidelines for the management of high blood pressure in children and adolescents

Changes in BMI SDS, SBP and DBP SDS during weight loss in boys and girls Holm et al, Journal of Hypertension 2012, 30:368 374

Holm et al, Journal of Hypertension 2012, 30:368 374 Changes in BMI SDS, SBP and DBP SDS during weight regain in boys and girls

Association of Parental Overweight and Cardiometabolic Diseases and Pediatric Adiposity and Lifestyle Factors with Cardiovascular Risk Factor Clustering in Adolescents Lee et al, Nutrients 2016, 8, 567

Physical activity 2016 ESH guidelines for the management of high blood pressure in children and adolescents

Exercise and BP control Physical activity reduces the risk for cardiovascular disease and prevents the development of HTN BP decreases and remains lower for the rest of 24h period after a 30min moderate exercise session The mechanisms involved in the BP lowering effect of physical activity are decreases in SNS, RAS activity, reduced production of inflammatory cytokines, improvement of insulin sensitivity and endothelial function Stabouli et al, Expert Rev. Cardiovasc. Ther. 2011;9(6): 753-61.

Cardiorespiratory Fitness and Clustered Cardiovascular Disease Risk in U.S. Adolescents 1,247 youths aged 12 19 years in the1999 2002 National Health and Nutrition Examination Surveys Lobelo et al, Journal of Adolescent Health 47 (2010) 352 359

Cardiorespiratory Fitness and Clustered Cardiovascular Disease Risk in U.S. Adolescents 1,247 youths aged 12 19 years in the1999 2002 National Health and Nutrition Examination Surveys The association remained significant in both overweight and normal weight males and in normal weight females (p <.05) Lobelo et al, Journal of Adolescent Health 47 (2010) 352 359

Improvement of early vascular changes and cardiovascular risk factors in obese children after a six-month exercise program Intervention: Sixty-seven obese subjects (age 14.7 ±2.2 years) were randomly assigned to 6 months exercise(1 h, 3 times/week) or nonexercise protocol Improved endothelial function Significant reduction in cardiovascular risk factors BMI, BMI SD scores, waist/hip ratio, Ambulatory SBP, Fasting insulin, Insulin resistance, Triglycerides, LDL, Low-degree inflammation(crp, fibrinogen) Meyers et al, J Am Coll Cardiol. 2006;7;48(9):1865-70.

Diet 2016 ESH guidelines for the management of high blood pressure in children and adolescents

He et al, Hypertension. 2006 Nov;48(5):861-9.

He et al, Hypertension. 2008;51:629-634

DASH diet The DASH diet emphasizes lower sodium consumption with plenty of fruits, vegetables, low-fat dairy, whole grains, and plant-based proteins The American Academy of Pediatrics has stated a DASH-style diet with sufficient protein and calories may also have potential health benefits for children Gidding SS, Dennison BA, Birch LL, et al. Dietary recommendations for children and adolescents: A guide for practitioners. Pediatrics. 2006;117(2):544-559.

Dietary Approaches to Stop Hypertension Diet, Weight Status, and Blood Pressure among Children and Adolescents: National Health and Nutrition Examination Surveys 2003-2012 9,793 individuals aged 8 to 18 years Accordance with the DASH diet was low across the age groups DASH score was inversely associated with SBP among 14- to 18-year-olds a 1-point increase in DASH score was associated with a 0.46 mm Hg decrease in SBP No significant differences were seen among the other age categories, and there no significant differences seen with DBP, weight status, or waist circumference Cohen et al, J Acad Nutr Diet. 2017;117:1437-1444

Change in DASH diet score and cardiovascular risk factors in youth with type 1 and type 2 diabetes mellitus: The SEARCH for Diabetes in Youth Study 797 participants in the SEARCH for Diabetes in Youth Study representing three time points: baseline, 12- and 60-month follow-up DASH-related adherence was poor and changed very little over time Increase in DASH diet score was significantly associated with: in HbA1c levels in youth with type 1 diabetes (β=-0.20, P=0.0063) in systolic blood pressure among youth with type 2 diabetes (β=-2.02, P=0.0406) Barnes et al, Nutrition & Diabetes (2013) 3, e91

The Efficacy of a Clinic-Based Behavioral Nutrition Intervention Emphasizing a DASH-Type Diet for Adolescents with Elevated BP Coucb et al, J Pediatr 2008;152:494-501

When to initiate antihypertensive treatment?

When to initiate antihypertensive treatment? High-normal BP Hypertension Hypertensive Emergency/urgency One or more of the following conditions: Symptomatic Secondary Organ damage Diabetes NO Nonpharmacological treatment YES Pharmacological treatment 2016 ESH guidelines for the management of high blood pressure in children and adolescents

Choosing an antihypertensive agent HTN with metabolic risk factors Targeting on mechanisms of obesity-induced hypertension Drugs acting to SNS and RAS system or promote natriuresis Effect on obesity and related metabolic abnormalities Drugs affecting insulin resistance Changes in glucose levels Changes in lipid profile Redon J, et al., Scientific Council of the European Society of Hypertension. The metabolic syndrome in hypertension: European society of hypertension position statement. J Hypertens 2008; 26:1891 1900 Lurbe et al. 2016 European Society of Hypertension guidelines for the management of high blood pressure in children and adolescents J Hypertens. 2016 ;34(10):1887-920

Impact of antihypertensive drugs on metabolic risk factors ACEIs and ARBs Inhibition of RAS may improve blood flow to muscles, decrease activity of SNS, improve insulin sensitivity May also have PPAR-γ effect on insulin sensitivity These agents are associated with lower risk of incidence of diabetes CCBs promote natriuresis and have vasolidating action β-blockers favor weight gain, adversely affect lipid and glucose metabolism and may increase the incidence of diabetes in patients with hyperinsulinemia Thiazide-like diuretics promote hypokaliemia, which worsens glucose intolerance Redon J, et al., Scientific Council of the European Society of Hypertension. The metabolic syndrome in hypertension: European society of hypertension position statement. J Hypertens 2008; 26:1891 1900

BP goals- General hypertensive population children <16 years <95 th pc for age, sex and height pc (Recommended) <90 th pc (should be considered) (office BP, 24-h ABP, home BP) Diabetes type 1 and 2 adolescents 16 years <140/90 mmhg (Recommended) <90 th pc (Recommended) <75 th pc in non-proteinuric CKD (Recommended) <50 th pc in proteinuric CKD (Recommended) < 130/80 mmhg (Recommended) <125/75 mmhg in proteinuric CKD (Recommended) 2016 ESH guidelines for the management of high blood pressure in children and adolescents

Pharmacological treatment of metabolic risk factors?

Pharmacological treatment of metabolic risk factors in hypertensive children and adolescents? Uncertain state of knowledge on long-term safety of pharmacological therapy

The SEARCH for Diabetes in Youth Study Hamman et al, Diabetes Care 2014;37:3336 3344

A Clinical Trial to Maintain Glycemic Control in Youth with Type 2 Diabetes 699 randomly assigned participants (mean duration of diagnosed type 2 diabetes, 7.8 months) over an average follow-up of 3.86 years N Engl J Med. 2012 June 14; 366(24): 2247 2256

Management of metabolic risk factors Obesity gradual weight loss to reduce BMI<85 th pc lifestyle and behavioral modification for healthier dietary habits: Total fat 25-35% of calories, saturated fat<7% trans fat<1%, chilesterol<200mg/day, consume fruits, vegetables, fiber, reduce salt and sugar intake Physical inactivity <2h screen time/day, 60min moderate aerobic activity/day Glucose intolerance gradual weight loss to reduce BMI<85 th pc decrease calorie intake, physical activity Dyslipidemia Decrease low saturated and trans fat, physical activity Steinberg et al, Circulation. 2009;119:628-647 AHA Scientific statement. Progress and Challenges in Metabolic Syndrome in Children and Adolescents Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: Summary Report. Pediatrics 2011;128;S213

Recommendations for pharmacological treatment may start at LDL-C >= 130 mg/dl if clustered CV risk factors If LDL >= 130 mg/dl and 2 high-level RF or 1 high-risk and 2 moderate level RF If LDL >= 160 mg/dl and 1 high-level RF or 2 moderate level RF If LDL >= 190 mg/dl Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: Summary Report. Pediatrics 2011;128;S213

Conclusions The hypertensive child with metabolic risk factors represents a challenging case Lifestyle changes remain the cornerstone of the initial management as they appear to have significantly beneficial effect on both BP and metabolic abnormalities Close follow up is important and detection of TOD may emerge the need for early pharmacological therapy

Thank you for attention