Pediatric Hypertension

Preface to the Fifth Edition
Preface to the Fourth Edition
Preface to the Third Edition
Preface to the Second Edition
Preface to the First Edition
Contents
About the Editors
Contributors
Part I: Regulation of Blood Pressure and Pathophysiological Mechanisms of Hypertension
	1 Neurohumoral and Autonomic Regulation of Blood Pressure
		Introduction
		Neural Components of BP Regulation
			Central Nervous System
				Sympathetic Activity
				Vasopressin
				Melanocortin
		Autonomic Nervous System
			Sympathetic Activity
			Parasympathetic Activity
		Baro- and Chemoreflexes
		Humoral Components of BP Regulation
			Renin-Angiotensin-Aldosterone System
			Atrial Natriuretic Peptides
			The Apelin System
		The Kidney, Fluid Volume, and Salt Intake
		The Vasculature and Nitric Oxide
		Circadian Variation of Blood Pressure
		Conclusion
		Cross-References
		References
	2 Cardiovascular Influences on Blood Pressure
		Introduction
		Relevance of BP Level During Childhood
		Hemodynamic Phenotypes of Primary Hypertension and Their Clinical Relevance
		Components of Blood Pressure: Static and Pulsatile
		Pulsatile Components of Blood Pressure
		Physiological Changes in CO, SVR, and HR During Childhood
		Evidence for a ``Hyperdynamic State´´ in Hypertension
		Evidence of a Vascular Change in the Early Phase of Hypertension
		Conclusion
		Cross-References
		References
	3 Vasoactive Factors and Blood Pressure in Children
		Introduction
		Renin-Angiotensin-Aldosterone System
		Angiotensinogen
		Prorenin, Renin, and (Pro)renin Receptor
		Angiotensin-Converting Enzyme
		Angiotensin II Receptors
		Angiotensin-Converting Enzyme 2
		Developmental Aspects of the RAAS
		Aldosterone
		Glucocorticoids
		Kallikrein-Kinin System
		Arginine Vasopressin
		Endothelium-Derived Vasoactive Factors
			Nitric Oxide
				Asymmetrical Dimethylarginine
			Endothelin
			Natriuretic Peptides
			Vasoactive Factors and Developmental Programming of Hypertension
			Urotensin II
			Renalase
		Conclusion
		Cross-References
		References
	4 Ions and Fluid Dynamics in Hypertension
		Introduction
		Sodium Channels
			NHE Transporters
			NKCC Transporters
			The NCCT
			ENaC
			Na+/K+ ATPase
		Calcium Flux
		Regulation of Ion Flux: The Role of α-Adducin
		Sodium Distribution and Blood Pressure
		Conclusions
		Cross-References
		References
	5 Uric Acid in the Pathogenesis of Hypertension
		Introduction
		The History of Uric Acid and Hypertension
		Animal Models of Hyperuricemic Hypertension
		Epidemiology
		Uric Acid Metabolism
			Proximal Tubular Urate Transport
			Genetic Associations
			Pediatric Clinical Trials
		Clinical Trials in Adults
		Clinical Summary
		Implications
		Cross-References
		References
6 Insulin Resistance and Other Mechanisms of Obesity Hypertension
	Introduction
	Postulated Mechanisms for Insulin Resistance Leading to Hypertension
	Measurement of Insulin Resistance
	Insulin Resistance in Obesity-Associated Hypertension
		Metabolic Syndrome
		Mechanism for Obesity-Associated Hypertension
	Insulin Resistance in Chronic Kidney Disease (CKD)
	Diabetes, Insulin Resistance, and Hypertension
	Low Birth Weight and Subsequent Insulin Resistance
	Genetic Influences on Insulin Resistance
	Treatment of Insulin Resistance
	Conclusion and Future Directions
	Cross-References
	References
7 Monogenic and Polygenic Contributions to Hypertension
	Introduction
	Monogenic Forms of Human Hypertension
	Familial Hyperaldosteronism
		Glucocorticoid-Remediable Aldosteronism or Familial Hyperaldosteronism Type 1 [OMIM #103900]
		Familial Hyperaldosteronism Type 2 OMIM #605635
		Familial Hyperaldosteronism  Type 3 [OMIM# 613677]
		Familial Hyperaldosteronism Type 4 [OMIM # 617027]
		Apparent Mineralocorticoid Excess [AME] [OMIM # 218030]
		Mineralocorticoid Receptor Gain-of-Function Mutation (OMIM # 605115)
		Steroidogenic Enzyme Defects Leading to Hypertension
	Steroid 11β-Hydroxylase Deficiency
	Steroid 17α-Hydroxylase Deficiency
	Mutations in Renal Transporters Causing Low-Renin Hypertension
		Pseudohypoaldosteronism Type II - Gordon Syndrome [OMIM#145260]
	Liddle Syndrome [OMIM # 177200]
		Pheochromocytoma-Predisposing Syndromes
		Hypertension with Brachydactyly [OMIM #112410]
		Other Forms of Mendelian Hypertension
	When to Suspect Monogenic Hypertension
	Non-Mendelian, Polygenic Hypertension
		Experimental Hypertension as a Tool to Investigate Polygenic Hypertension
		Human Hypertension
	Mendelian Randomization Studies
		Candidate Genes
		Candidate Susceptibility Genes
	Variants or Subphenotypes
	Conclusions and Implications for Pediatric Hypertension
	Cross-References
	References
8 Antenatal Programming of Blood Pressure
	Introduction
	Overview of Clinical and Epidemiological Evidence
	Select Blood Pressure-Programming Mechanisms
		Kidney-Altered Structure and Function
		Kidney-Altered Sodium Transport
		Kidney-Altered Hormonal Pathways
		Kidney-Altered Neural Tone
	Brain
	Vasculature
	Heart
	Potential Sex Differences
	Conclusion
	Cross-References
	References
9 Familial Aggregation of Blood Pressure and the Heritability of Hypertension
	Introduction
	Evidence of Familial Aggregation of Blood Pressure
	Age Dependency of Genetic Effects on BP
	Findings of GWAS Studies
	Familial Aggregation of BP and Its Associations
	Future Research Opportunities
	Conclusion
	Cross-References
	References
10 The Role of Dietary Electrolytes and Childhood Blood Pressure Regulation
	Introduction
	Dietary Sodium and Blood Pressure in Youth
	Dietary Potassium and Blood Pressure in Youth
	Nutritional Interventions and Blood Pressure in Youth
	Nutrition and Dietary Adherence in Youth
	Conclusions and Implications for Future Research
	Cross-References
	References
11 Endothelial Dysfunction and Vascular Remodeling in Hypertension
	Introduction
	Role of the Endothelium in Blood Pressure Homeostasis
	Etiologies  of Endothelial Dysfunction and Resultant Blood Pressure Derangements
		Chronic Kidney Disease
		Acute Kidney Injury
		Obesity
	Vascular Remodeling
		Hemodynamic Forces
		Reactive Oxygen Species
		Renin-Angiotensin-Aldosterone System
		Adiponectin
		MicroRNAs
	Conclusions
	Cross-References
	References
12 Adverse Childhood Experiences and Their Relevance to Hypertension in Children and Youth
	Introduction
	ACEs as Compared to Other Adverse Events
	Clinical Studies
		Examples of Studies in Children and Youth
		Examples of Studies in Adults
	What Are the Mechanisms by Which ACEs Effect Changes?
	Limitations in Studies of ACEs
	Conclusion
	References
13 Salt Sensitivity in Childhood Hypertension
	Introduction
	Definitions and Methodologies
	Pathogenesis of Salt Sensitivity
	Phenotype of Salt-Sensitive Hypertension
	Obesity
	Diabetes Type 2 and Insulin Resistance
	Low Birth Weight
	Race and Ethnicity
	Chronic Kidney Disease
	Stress and Adverse Childhood Events
	Interventions for Salt Sensitivity
	Surrogate Markers for Salt Sensitivity
	Clinical Implications
	Conclusion
	Cross-References
	References
14 Early Vascular Aging in Pediatric Hypertension Patients
	Introduction
	The Concept of Early Vascular Aging
	Features of EVA in Hypertensive Children
	Biological Determinants of Blood Pressure in Childhood and Adolescence.
	Determinants of EVA in Children with Primary Hypertension
	Altered Body Composition
	Metabolic Abnormalities, Metabolic Syndrome, and Oxidative Stress in Adolescents with PH
	Immune Abnormalities and Inflammatory Activation in Children with PH
	Accelerated Biological Maturation and Childhood Hypertension
	Hemodynamic Determinants of EVA in Hypertensive Children
	Reversibility of Features of EVA in Children with PH
	Conclusions
	Cross-References
	References
Part II: Assessment of Blood Pressure in Children: Measurement, Normative Data, and Epidemiology
15 Methodology of Office Blood Pressure Measurement
	Introduction
	Blood Pressure Measurement Steps
	Patient Preparation
		Before the Measurement
		Positioning
	Cuff Selection
	Cuff Placement
	Measurement Procedure
		Automated Blood Pressure Measurement
		Manual Auscultation
		Leg Blood Pressure
	Blood Pressure Measurement in Special Populations
	Importance of Training and Retraining
	Device Selection and Maintenance
	Conclusion
	Cross-References
	References
16 Value of Routine Screening for Hypertension in Childhood
	Introduction
	Recognizing Pediatric Hypertension Can Be Challenging
	Different Points of View
	The Evidence Advocating Pediatric Hypertension As a Pathologic Condition
		Blood Pressure Tracking
		Left Ventricular Hypertrophy
		Carotid Intima-Media Thickness
		Arterial Pulse Wave Velocity
		Microalbuminuria
		Metabolic Syndrome
	Benefits and Risks of Screening
	Future Directions
	Conclusions
	Cross-References
	References
17 Development of Blood Pressure Norms and Definition of Hypertension in Children
	Introduction
	Outcome of Childhood Hypertension
	Prevelance of Hypertension in Childhood
	Definition of Hypertension in Childhood
	Normative Blood Pressure Distribution in Children and Adolescents
	Application of Blood Pressure Normative Data
	Conclusion
	Cross-References
	References
18 Ambulatory Blood Pressure Monitoring Methodology and Norms in Children
	Introduction
	Advantages of Ambulatory Blood Pressure Monitoring
		Role of Ambulatory Blood Pressure Monitoring in the Diagnosis of Specific Conditions
		Indications for Ambulatory Blood Pressure Monitoring
	Methods for Ambulatory Blood Pressure Monitoring
		Ambulatory Blood Pressure Monitors
		Editing Ambulatory Blood Pressure Monitoring Data
		Applying the Device
	Normative Ambulatory Blood Pressure Monitoring Data
	Ambulatory Blood Pressure Monitoring Report and Interpretation
	Ambulatory Blood Pressure Monitoring Classification
	Role of Mean Arterial Pressure in the Evaluation of Ambulatory Blood Pressure Monitoring
	Calculation of Ambulatory Blood Pressure Monitoring Z-Scores or Percentile Data
	Blood Pressure Variability
	When to Repeat Ambulatory Blood Pressure Monitoring?
	Tolerability of Ambulatory Blood Pressure Monitoring
	Reproducibility of Ambulatory Blood Pressure Monitoring
	Limitations of Ambulatory Blood Pressure Monitoring
	Cost Effectiveness of Ambulatory Blood Pressure Monitoring
	Conclusion
	Cross-References
	References
19 Methodology and Applicability of Home Blood Pressure Monitoring in Children and Adolescents
	Introduction
	Advantages and Disadvantages of Home Blood Pressure Monitoring in Children
		Advantages
		Disadvantages
	Methodology
		Comparison of BP Measurement Methods
			Home Versus Office BP
			Home Versus Ambulatory BP
		Impact of Age on Differences Between BP Measurement Methods
		Reproducibility of Home BP
		Diagnostic Value of Home BP
	Relationship with Preclinical Target-Organ Damage
	Home BP in Clinical Research
	Clinical Application of Home BP Monitoring
		Feasibility of Home BP Monitoring
		Home BP Monitoring Schedule
		Normal Range of Home BP
		Devices for Home BP Monitoring
		Nighttime BP Monitoring Using Home Monitors
	Clinical Indications of Home BP Monitoring
	Conclusions
	Cross-References
	References
20 Epidemiology of Hypertension and Cardiovascular Disease in Children and Adolescents
	Introduction
	Definitions of Hypertension and Evolving Guidelines
	Periodicity of Blood Pressure Measurements and Impact on Hypertension Epidemiology
	Reproducibility of Blood Pressure Measurements and Impact on Hypertension Epidemiology
	Prevalence of Isolated Hypertensive Level Blood in Children and Adolescents
	Prevalence of Elevated Blood Pressure in Children and Adolescent
	Incidence and Prevalence of Hypertension in Children and Adolescents
	Primary Versus Secondary Hypertension
	Stability of Elevated Blood Pressure or Hypertension Over Time
	Trends in Elevated Blood Pressure and Hypertension Prevalence Over Time
	Risk Factors for Elevated Blood Pressure and Primary Hypertension
		Overweight and Obesity
		Race/Ethnicity
		Age/Pubertal Status
		Sodium Intake
		Adverse Childhood Exposures
	Consequences of Elevated Blood Pressure and Hypertension in Children and Adolescents
	Conclusion
	Cross-References
	References
Part III: Hypertension in Children: Etiologies and Special Populations
21 Ethnic Differences in Childhood Blood Pressure
	Introduction
	Adults
	Do Racial Differences in Blood Pressure Begin in Childhood?
	Hispanics and Ethnic Differences in BP
	Origins of Ethnic and Racial Differences
	Ambulatory Blood Pressure Monitoring
	Ethnic Differences in BP-Related Target Organ Damage in Children
	Response to Therapy
	Systemic Racism and Blood Pressure Differences
	Conclusion
	Cross-References
	References
22 Obesity Hypertension: Clinical Aspects
	Introduction
	Childhood Obesity: Prevalence and Demographics
	Association of Obesity with Hypertension
	Other Cardiovascular Sequelae of Obesity
	Pathophysiology
	Workup and Diagnosis
	Management
		Lifestyle Modification and Weight Loss
		Bariatric Surgery
		Pharmacologic Therapy: Antihypertensive Medications
		Pharmacologic Therapy: Anti-Obesity Medications
	Impact of the Coronavirus Pandemic
	Conclusion
	Cross-References
	References
23 Hypertension in Children with Type 2 Diabetes or the Metabolic Syndrome
	Introduction
	Classification of Blood Pressure in the Young
	Hypertension in Persons with Metabolic Syndrome
	Hypertension in Persons with Type 2 Diabetes
	Pathophysiology
	Therapy
		Role of Non-Pharmacologic Therapy
		Cardiovascular Effects of Oral Hypoglycemic Agents
		Antihypertensive Drug Therapy
			Indications for Antihypertensive Drug Therapy
			Choice of Antihypertensive Medication
			Therapeutic Goals
			Role of Bariatric Surgery
	Conclusions
	Cross-References
	References
24 Primary Hypertension in Children
	Introduction
	Definitions and Techniques
	Primary Versus Secondary Hypertension
	Incidence and Prevalence
	Predictors of Primary Hypertension
	BP Homeostasis and Pathophysiology of Hypertension
	Risk Factors for Primary Hypertension
		Non-Modifiable Risk Factors
			Age and Sex
			Race and Ethnicity
			Genetics and Family History
		Modifiable Risk Factors
			Obesity
			Dietary Sodium Intake
			Obstructive Sleep Apnea
			Exercise
			Lipids
			Tobacco Smoking
			Childhood Adversity
	Long-Term Effects of Hypertension in Children
	Conclusions
	Cross-References
	References
25 White Coat and Masked Hypertension
	Introduction
	Definition of White Coat Hypertension and Masked Hypertension
		White Coat Hypertension
		Masked Hypertension
	White Coat Hypertension
		Prevalence
		Pathogenesis
		Clinical Implications
	Masked Hypertension
		Prevalence
		Pathogenesis
		Clinical Implications
	Conclusion
	Cross-References
	References
26 Hypertension in Chronic Kidney Disease
	Introduction
	Definition of Hypertension in Children with CKD
	Prevalence of Hypertension Among Children with CKD
	Pathophysiology
		Sodium
		Renin-Angiotensin-Aldosterone System (RAAS)
		The Sympathetic Nervous System
		Autoregulatory Systems
		Pharmacologic Factors
		Mineral Bone Disease
		Uric Acid
	Risk Factors for Hypertension Among Children with CKD
	Diagnosis
		Measurement Methods
		Ambulatory Blood Pressure Monitoring (ABPM)
		Home BP Monitoring
		Normative Values
		Additional Testing
	Treatment
		Goals of Therapy
		Non-Pharmacologic Measures
		Medication Selection
		Medication Dosing
	Sequelae of Hypertension in Pediatric CKD
		CKD Progression
		Left Ventricular Hypertrophy (LVH)
		Carotid Intima-Media Thickness (cIMT)
		Other Markers of Cardiovascular Dysfunction
		Neurocognitive Function
	Conclusion
	Cross-References
	References
27 Hypertension in End-Stage Kidney Disease: Dialysis
	Introduction
	Epidemiology
		Hypertension
		Left Ventricular Hypertrophy
	Etiology and Pathogenesis
	Diagnostic Evaluation
		Peridialytic Blood Pressure Monitoring
		Interdialytic Blood Pressure Monitoring
		Assessment of Volume Status
	Nonpharmacological Management
	Pharmacological Management
	The ``Patient Factor´´
	Conclusions
	Cross-References
	References
28 Hypertension in End-Stage Kidney Disease: Transplantation
	Introduction
	Measurement of Blood Pressure in Transplanted Children
	Definition and Prevalence of Hypertension in Transplanted Children
	Clinical Presentation of Posttransplant Hypertension
	Etiology and Pathogenesis of Hypertension in Transplanted Children
	Complications of Hypertension in Transplanted Children
	Evaluation of Hypertensive Children After Kidney Transplantation
	Treatment of Hypertensive Children After Kidney Transplantation
		Causal Treatment
		Pharmacological Therapy
		Timing of Antihypertensive Drug Administration
		Non-pharmacological Treatment
	Target Blood Pressure for Transplanted Patients
		Control of Hypertension
	Conclusion
	Cross-References
	References
29 Renovascular Hypertension, Vasculitis, and Aortic Coarctation
	Introduction
	Renovascular Disease
		Etiology
			Fibromuscular Dysplasia
			Takayasu Arteritis
		Genetic Considerations in Renovascular Hypertension
		Presentation
		Aneurysmal Disease
		Diagnostic Imaging
		Renal Vein Renin Sampling
		Treatment
			Angioplasty
			Surgery
		Coarctation of the Aorta
	Conclusion
	Cross-References
	References
30 Endocrine Hypertension
	Pheochromocytoma
	Diseases of the Adrenal Cortex Causing Hypertension
		Hypertensive Forms of Congenital Adrenal Hyperplasia
		Primary Aldosteronism
		Cushing Syndrome
		Generalized Glucocorticoid Resistance
	Hyperthyroidism
	Conclusion
	Cross-References
	References
31 Neonatal and Infant Hypertension
	Introduction
	Measurement of Blood Pressure
	Factors Influencing Neonatal Blood Pressure
		Maternal Factors Influencing Neonatal Blood Pressure
		Perinatal Factors Influencing Neonatal Blood Pressure
		Infant Factors Influencing Neonatal Blood Pressure
	Normative Blood Pressure
		First Days of Life
		First Weeks of Life
		First Year of Life
	Definition of Hypertension
	Incidence of Hypertension
	Risk Factors for Hypertension
	Causes of Hypertension
		Renovascular Causes
		Renal Parenchymal Causes
		Cardiovascular Causes
		Other Causes
	Evaluation
	Management
		Hypertensive Crises
			Non-emergent Hypertension
	Long-Term Outcome
	Neonatal Risk Factors for Later Kidney and Cardiovascular Disease
	Conclusions
	Cross-References
	References
32 Obstructive Sleep Apnea and Hypertension in Children
	Introduction
	Normal Cardiovascular Function During Sleep
	Clinical Presentation of Obstructive Sleep Apnea
	Evaluation of Obstructive Sleep Apnea in Children
	Insufficient Sleep Time and Blood Pressure
	Autonomic Nervous System and Obstructive Sleep Apnea
	Blood Pressure and Obstructive Sleep Apnea
		Hypertension and Obstructive Sleep Apnea
		Obstructive Sleep Apnea, Hypertension, and Obesity
		Nocturnal Dipping and Obstructive Sleep Apnea
	Cardiac Evaluation in Patients with Obstructive Sleep Apnea
	Treatment
	Long-Term Follow Up
	Conclusion
	Cross-References
	References
33 Hypertension in the Pregnant Teenager
	Introduction
	Case
	The Pregnant Adolescent: General Considerations
	Definitions of Hypertensive Disorders of Pregnancy
	BP Patterns Through the Course of Pregnancy
	Ambulatory Blood Pressure (ABP) During Pregnancy
	Mechanisms of Preeclampsia and Gestational Hypertension
		Vascular Remodeling of the Terminal Branches of the Placental Arterial System (Spiral Arteries)
		Immune Factors in the Process of Placental Vascular Remodeling
		Endothelial Mediator Imbalance
		Increased Sensitivity to Angiotensin Type 1 Receptor
		Complement Dysregulation
	Risk Factors for Preeclampsia
	Features Unique to the Pregnant Teenager
	Impact of Chronic Hypertension on Pregnancy Outcome
	Treatment of Hypertension During Pregnancy
	Risk of Future Cardiovascular Disease and Chronic Kidney Disease
	Conclusion
	Cross-References
	References
34 Neurocognition in Childhood Hypertension
	Introduction
	Studies of Cognition in Hypertensive Adults: Implications for Children
	Studies in Children with Primary Hypertension
	Studies in Children with Chronic Kidney Disease
	Potential Mechanisms of Altered Neurocognition Studies in Adults
		Cerebrovascular Structure  and Function
		White Matter Integrity and Small Vessel Disease
		Autoregulation, Endothelial Function, and Neurovascular Coupling
		Blood-Brain Barrier
		Hypertension and the Cerebral Vasculature: Evidence in Youth
		Cerebrovascular Reactivity
		Cognition and Blood Pressure Variability
		Cognition and Metabolic Syndrome
		Cognition and Uric Acid and Metabolism
	Potential Mechanisms: Studies in CKD
	Implications and Conclusions
	Cross-References
	References
35 Stroke and Childhood Hypertension
	Introduction
	Definitions and Epidemiology
		Pediatric Stroke
		Perinatal Stroke
		Childhood Stroke
		Childhood Hypertension
	Barriers and Limitations
	Hypertension and Brain End-Organ Damage
	Stroke and Childhood Hypertension
	Ischemic Stroke and Hypertension
	Transient Ischemic Attack and Hypertension
	Mortality in Ischemic Stroke and Hypertension
	Stroke Recurrence and Hypertension
	Hemorrhagic Stroke and Hypertension
	Risk of Stroke and Stroke Mortality in Midlife
	Sickle Cell Disease
	Cerebral Arteriopathies and Renovascular Disease
	Cognition, Hypertension, and Potential Implications for Neurovascular Health
	Management of Hypertension in Childhood Stroke
	Conclusion
	Cross-References
	References
36 Medication and Substance-Induced Hypertension: Mechanisms and Management
	Introduction
	Medication-Induced Hypertension
	Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
	Glucocorticoids
	Oral Contraceptives
	OTC Sympathomimetic Medications
	Weight Loss Agents
	Calcineurin Inhibitors
	Herbal Supplements
	Antidepressants
	VEGF Signaling Pathway (VSP) Inhibitors
	Attention Deficit Hyperactivity Disorder (ADHD) Medications
	Environmental Exposure (Heavy Metals)
		Mercury
		Lead
	Substance-Induced Hypertension
	Stimulants
	Cocaine
	Amphetamines (Including Methamphetamine)
	Caffeine: Energy Drinks
	Club Drugs
	Methylenedioxymethamphetamine (MDMA)
	Ketamine and PCP (Dissociatives)
	Lysergic Acid Diethylamide (LSD) and Mescaline (Hallucinogens)
	New Psychoactive Substances (NPS)
		Synthetic Stimulants
		Synthetic Cannabinoids
	Miscellaneous
	Conclusion
	Cross-References
	References
37 Hypertension in Oncology and Stem Cell Transplant Patients
	Introduction
	Definitions
	Evaluation of High Blood Pressure
		Measurement
		Clinical History
		Physical Examination
		Laboratory Evaluation
		Imaging
	Hypertension Associated with Specific Cancer Diagnoses
	Syndromes of Acute Hypertension in the Pediatric Oncology Patient
		Posterior Reversible Encephalopathy Syndrome (PRES)
		Thrombotic Microangiopathy
	High Blood Pressure in Children Treated for Cancer Outside the Acute Setting
		Overview of Incidence and Prevalence
		Long-Term Hypertension in Pediatric Cancer Survivors
	Consensus Recommendations
	Treatment
	Conclusions
	Cross-References
	References
38 Hypertension in Older Adolescents and Young Adults
	Introduction
	Epidemiology and Outcomes of Hypertension in Older Adolescents and Young Adults
	Definition of Hypertension in Older Adolescents and Young Adults
		Elevated BP
		Resistant Hypertension
		Hypertension in Young Adults with Chronic Kidney Disease
	Etiology of Hypertension Among Young Adults
	Diagnosis
		BP Measurement
		Evaluation of Hypertension Among Older Adolescents and Young Adults
			History
			Physical Examination
			Laboratory and Imaging Evaluation
	Therapy
		Treatment Targets
		Non-pharmacologic Interventions
		Pharmacologic Treatment
		Transition of Adolescents with Hypertension to Adult Care
	Conclusion
	Cross-References
	References
39 Hypertension in the Developing World
	Introduction
	Hypertension and CVD in the Developing World
	The Fetal Origins Hypothesis and DOHAD: Developmental Origin of Health and Adult Disease
	Evidence of Epigenetic Mechanisms in Animals and Its Importance as a Cause of Adult Nephropathy and Arterial Hypertension
	Evidence of Epigenetic Mechanisms in Humans and Its Importance as a Cause of Adult Nephropathy and Arterial Hypertension: A Po...
	The Future of Hypertension and Cardiovascular Disease in Middle- and Low-Income Countries
	Conclusion
	Cross-References
	References
Part IV: Evaluation and Management of Pediatric Hypertension
40 Diagnostic Evaluation of Pediatric Hypertension
	Introduction
	Confirming the Diagnosis and Establishing the Phenotype
	Summary of Recommended Diagnostic Evaluation
	First-Line Investigations
	Further Investigations
		Plasma Renin Activity and Aldosterone Level
		Genetic Testing
		Diagnostic Imaging to Detect Kidney and Vascular Disease
		Investigations for Pheochromocytoma and Paraganglioma
		Endocrine Investigations
		Additional Considerations Among Children with Cancer
		Other Diagnostic Tests
	End-Organ Damage and Cardiovascular Disease Risk Stratification
	Conclusion
	Cross-References
	References
41 Sequelae of Hypertension in Children and Adolescents
	Introduction
	Cardiac Structure
		Atrial Structure
		Left Ventricular Structure and Function
	Vascular Structure and Function
		Carotid Intimal Medial Thickness
		Pulse Wave Velocity
		Atherosclerotic Changes in Autopsy Studies
		Endothelial Function
	The Kidneys
	The Retina
	Cognition
	Sequelae of Acute Hypertensive Crisis
		Central Nervous System
		Cardiovascular System
		The Kidneys
	Conclusion
	Cross-References
	References
42 Cardiovascular Assessment of Childhood Hypertension
	Introduction
	Rationale for Measuring CV Function in Youth
	Measures of CV Structure and Function and Their Relationship to BP Levels in Children
	Relationships Between Vascular and Cardiac Dysfunction
	Strategies for Improving Vascular and Cardiac Function
	Conclusion
	Cross-References
	References
43 The Role of ABPM in Evaluation of Hypertensive Target-Organ Damage
	Introduction
	Ambulatory Blood Pressure Monitoring
	Assessment of Target Organ Damage
	Ambulatory Blood Pressure Parameters and Target Organ Damage
		Heart
			Left Ventricular Hypertrophy
			Myocardial Function Indices
		Arteries
			Carotid Intima-Media Thickness
			Flow-Mediated Dilatation
		Kidneys
		Brain
		Eyes
	Hypertensive TOD in BP Phenotypes
		White Coat Hypertension
		Masked Hypertension
		Nocturnal Hypertension
	Predictive Value of ABPM Parameters
	Conclusions
	Cross-References
	References
44 Exercise Testing in Hypertension and Hypertension in Athletes
	Introduction
	The Basics: Measurements and Interpretation of the Exercise Stress Test
	Indications and Contraindications for Exercise Testing
	Normal Blood Pressure Response to Exercise
	Blood Pressure Response to Exercise in Pediatric Subpopulations
	Children with Obesity
	Elevated Blood Pressure and Hypertensive Children
	Children with Dyslipidemia
	Children with Impaired Glucose Tolerance/Type 2 Diabetes
	Children of Parents Who Smoke
	Congenital Heart Disease: Resting Blood Pressure and Blood Pressure Response During Exercise
	Coarctation of the Aorta
	Exercise Recommendations in Hypertensive Athletes
	Hypertensive Athlete and Athletic Performance
	Conclusions
	Cross-References
	References
45 Nonpharmacologic Treatment of Pediatric Hypertension
	Introduction
	Sodium
	Dietary Patterns
	Physical Activity
	Weight Reduction
	Other Nonpharmacological Approaches
	Conclusions
	Cross-References
	References
46 Pharmacologic Treatment of Pediatric Hypertension
	Introduction
	General Approach to the Hypertensive Child
	Angiotensin-Converting Enzyme Inhibitors
	Angiotensin Receptor Blockers
	Aldosterone Receptor Antagonists
	Beta-Adrenergic Antagonists
	Calcium Channel Blockers
	Direct Renin Inhibitor
	Diuretics
	Direct Vasodilators
	Other Antihypertensive Agents
	Future Directions in Drug Studies
	Targeted Approach to Therapy
		Renovascular Hypertension
		Coarctation of the Aorta
		Chronic Kidney Disease
		Primary Hypertension/Obesity-Related Hypertension
		The Hypertensive Athlete
		Monogenic Forms of Hypertension
	Conclusion
	Cross-References
	References
47 Management of Hypertensive Emergencies
	Introduction
	Definitions of Hypertensive Crises, Emergencies, and Urgencies
	Organ Systems Susceptible to Hypertensive Injury
	Pathophysiology
	Etiologies of Severe Hypertension
	Clinical Presentation
	Evaluation of Children with Hypertensive Crises
	Treatment of Severe Hypertension
	Conclusion
	Cross-References
	References
48 Hypertension Care During Emergencies and Pandemics
	Introduction
	Barriers to Hypertension Care
	Emergence of Telehealth as a Pandemic Solution
	Practicalities in Out-of-Office Blood Pressure Measurement
	Health Trends During Pandemics and Its Impact on Hypertension
	Resources to Help Support Heart Healthy Lifestyle
	Medication Availability
	Conclusion
	Cross-References
	References
Part V: Hypertension Research in Pediatrics
49 Hypertensive Models and Their Relevance to Pediatric Hypertension
	Introduction
	Nongenetic Models of Hypertension
		Induction of Hypertension with Substances and Drugs
	Surgically-Induced Models of Hypertension
		Renovascular Hypertension
		Hypertension from Perinephric Compression
		Subtotal Nephrectomy and Renoprival Hypertension
		Neurogenic Hypertension
	Dietary Models of Hypertension
	Models of Stress-Related Hypertension
	Genetic Forms of Hypertension
		Inbred Strains and the Development of Hypertension
	Sexual Dimorphic Models
	Murine Models of Mendelian Hypertension
		Transgenic, Knock Out, and Knock In Models
		Developmental Origins Models
	Tissue and Organ Manipulation
	In Vitro Models of Hypertension
	Conclusions
	Cross-References
	References
50 Cohort Studies, Meta-analyses, and Clinical Trials in Childhood Hypertension
	Introduction
	Cross-Sectional Studies
		Strengths and Weaknesses of Cross-Sectional Studies
		How to Read a Cross-Sectional Study
		The Perils of P-values
		Notable Cross-Sectional Studies
	Diagnostic Test Accuracy Studies
		How to Read a Study for Quality
		Notable Test Accuracy Studies
	Cohort Studies
		Strengths and Weaknesses of Cohort Studies
		How to Read a Cohort Study
		Notable Cohort Studies
	Randomized Controlled Trials
		Strengths and Weaknesses of Randomized Controlled Trials
		How to Read Randomized Controlled Trials
		Notable Randomized Controlled Studies
	Systematic Reviews and Meta-analyses
		Strengths and Weaknesses of Systematic Reviews and Meta-analyses
		How to Read Systematic Reviews and Meta-analyses
		Notable Systematic Reviews and Meta-analyses
	Data Sharing
	Qualitative Research and Consumer Engagement
	Conclusion
	Cross-References
	References
51 Changes in Drug Development Regulations and Their Impact on Clinical Trials
	Introduction and Review of Recent Regulatory Initiatives
	Pediatric Antihypertensive Clinical Trial Design
	Written Request Criteria
	Clinical Efficacy Studies
	Conclusion
	Cross-References
	References
Index