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Pediatric Hypertension Matthew Grinsell, MD, PhD Disclosure I have no financial disclosures. Outline Focus will be outpatient HTN in children and adolescents. Definition of HTN in children and adolescents. Blood pressure measurement. Epidemiology. Etiology. Diagnosis. Evaluation. Therapy. Monitoring. Definition of Hypertension HTN-Adult vs. Pediatrics HTN is defined as the BP above which there is increased risk of morbidity and mortality. In adults, HTN is relatively clearly defined by outcome data such as: Mortality. CVD. Stroke. This is why 120/80 is considered pre-HTN. 140/90 is HTN. Hypertension-Adult vs. Pediatrics In children and teens, there are very limited outcomes data, so we use a statistical standard defined by BP tables. Use of blood pressure tables available from: (www.nhlbi.nih.gov/ guidelines/hypertension/childtbl. pdf Easy way is to type in “pediatric blood pressure tables” in Google. Pediatric BP Tables We will come back to BP tables shortly (www.nhlbi.nih.gov/ guidelines/hypertension/childtbl. pdf Pediatric HTN Approximately 3-5% of children HTN and that number is likely increasing. Hypertension is an average SBP and/or diastolic BP (DBP) that is above the 95th percentile for gender, age, and height on three separate occasions. Systolic and diastolic are of equal importance. Regardless of the charted 95% BP for age, gender and height, any pediatric patient with BP above 120/80 mm Hg should be considered prehypertensive and evaluated. Pediatrics 2004;114;555 HTN Classification in Children and Adolescents Pediatrics 2004;114;555 HTN as a Global Health Issue HTN was the leading attributable cause of death worldwide in 2004 according to the WHO. In the United States: 33% of adults 20 years and older had HTN. HTN in 2007 was the 13th leading cause of death in the US but is a known risk factor or complication of: #1 Heart disease #4 Cerebrovascular diseases/Stroke #7 Diabetes Mellitus #9 Kidney disease http://www.who.int/healthinfo/global_burden_disease/global_health_risks/en/index.html http://www.cdc.gov/nchs/fastats/lcod.htm HTN as a Pediatric Health Issue Patients 10-17 years with elevated SBP on admission to hospital in Reykjavik, Iceland, 1950 to 1967. 126 individuals (54 men) invited for a follow-up in 2008. Median BP was 125/80 mmHg 1950-1967 Median BP 133/75 mmHg 2008 49/126 had been diagnosed with HTN (23 men) 12/126 with coronary artery disease (10 men). Significant correlation (P = 0.03) between the diagnosis of coronary artery disease in adulthood and elevated childhood systolic BP. Pediatr Nephrol. 2010 Feb;25(2):323-8 HTN and Early Atherosclerosis Pathobiological Determinants of Atherosclerosis in Youth (PDAY). Autopsies of 629 males age 15-34 who died of trauma. Normal cholesterol (< 160) and HDL (> 35). Hypertensive males had more raised aortic plaque lesions than normotensive males. Obese males had more extensive fatty streaks in the abdominal aorta and the left anterior descending coronary artery. HTN may impact the extent and severity of coronary artery disease and aortic atherosclerosis in adolescents and young adults. JAMA. 1990 Dec 19;264(23):3018-24 Circulation. 2001 Mar 20;103(11):1546-50. Measurement of Blood Pressure BP Measurement Who should have BP measured? Selection of correct cuff size. Oscillometry vs. auscultation. Confirmation of elevated blood pressures. Who Should Have BP Measured? AAP recommends: Children 3 years and older who are seen in a medical setting should have their BP measured at least once during that visit. Children under 3 years should have BP measured if they have certain risk factors. Pediatrics 2004;114;555 When to Measure BP in Children < 3 yrs • History of NICU stay, Prematurity, or VLBW. •Congenital Heart Disease •Recurrent urinary tract infections, hematuria, proteinuria •Known renal disease or urologic malformations •Family history of congenital renal disease •Solid organ transplant •Malignancy or bone marrow transplant •Treatment with drugs known to raise BP •Systemic illness with high blood pressure such as TS or NF •Evidence of elevated intracranial pressure When to Measure BP in Children < 3 yrs • History of NICU stay, Prematurity, or VLBW. •Congenital Heart Disease •Recurrent urinary tract infections, hematuria, proteinuria •Known renal disease or urologic malformations •Family history of congenital renal disease •Solid organ transplant •Malignancy or bone marrow transplant •Treatment with drugs known to raise BP •Systemic illness with high blood pressure such as TS or NF •Evidence of elevated intracranial pressure When to Measure BP in Children < 3 yrs • History of NICU stay, Prematurity, or VLBW. •Congenital Heart Disease •Recurrent urinary tract infections, hematuria, proteinuria •Known renal disease or urologic malformations •Family history of congenital renal disease •Solid organ transplant •Malignancy or bone marrow transplant •Treatment with drugs known to raise BP •Systemic illness with high blood pressure such as TS or NF •Evidence of elevated intracranial pressure When to Measure BP in Children < 3 yrs • History of NICU stay, Prematurity, or VLBW. •Congenital Heart Disease •Recurrent urinary tract infections, hematuria, proteinuria •Known renal disease or urologic malformations •Family history of congenital renal disease •Solid organ transplant •Malignancy or bone marrow transplant •Treatment with drugs known to raise BP •Systemic illness with high blood pressure such as TS or NF •Evidence of elevated intracranial pressure BP-Measurement Obtain patient’s height percentile. Select cuff appropriate for child’s size. Appropriate size cuff : bladder width = 40% upper arm circumference. Or, bladder length should encircle 80-100% upper arm circumference. A cuff too small may lead to high BP values. When in doubt use a larger cuff. Pediatric Nephrology Clinic Cuffs BP-Measurement No stimulant drugs or foods for 24 hours. Sitting quietly for 5 minutes with back supported, and feet on the floor. Right arm supported with cuff placed at the level of the heart. Right arm is preferred because standardized measurements are based on right arm BP. Stethoscope placed over the brachial artery below the bottom edge of the cuff. Inflate cuff to 99% + 20 initially (in kids 140-150 works). SBP = 1st Korotkoff sound “opening snap”. DBP = 5th Korotkoff sound or disappearance of sounds. BP-Measurement BP-Measurement Once BP is obtained, plot on BP charts as a function of: Gender. Age. Height percentile. For example: A 7y/o female who is 125 cm tall (75%). Measured BP is 105/65. Use of Pediatric Tables A 7y/o female who is 125 cm tall. Measured BP is 105/65. (www.nhlbi.nih.gov/ guidelines/hypertension/childtbl. pdf Use of Pediatric Tables A 7y/o female who is 125 cm tall. Measured BP is 105/65. (www.nhlbi.nih.gov/ guidelines/hypertension/childtbl. pdf Use of Pediatric Tables A 7y/o female who is 125 cm tall. Measured BP is 105/65. (www.nhlbi.nih.gov/ guidelines/hypertension/childtbl. pdf Use of Pediatric Tables A 7y/o female who is 125 cm tall. Measured BP is 105/65. (www.nhlbi.nih.gov/ guidelines/hypertension/childtbl. pdf Questions About BP Measurement Is there a significant difference between auscultation and oscillometric (Automated) measurements? Do stimulants used for ADD/ADHD significantly affect BP in children? Auscultation vs Oscillometry Ausculatation is the preferred method of BP measurement as tables are based on auscultation. Oscillometric measurement Reduces inter-observer variability. Highly reproducible. Oscillometric devices work by measuring MAP and using an algorithm to calculate SBP/DBP. Proprietary information. Makes standardization impossible. Auscultation vs Oscillometry 2001: Auscultation and oscillometric BP measurements on 7,208 school children age 5-17 years in San Antonio, TX. Dinamap 8100 Cross-over design: Children randomized to either auscultation or Dinamap as first measurement technique, then measured with alternate technique. On average, Oscillometry had a 10 mmHg higher SBP and 4.7 mmHg DBP. The difference was more pronounced in younger children. Arch Pediatr Adolesc Med/Vol 155,Jan 2001. Stimulants and BP Placebo controlled studies have found small but statistically significant increases in BP with stimulants. Generally 2-4 mmHg for SBP. 1-3 mmHg for DBP. The clinical significance of these findings remains unclear. One study did find a sustained BP > 95% in 2.5% of subjects following discontinuation of stimulants. On a population level, modest BP effect, but certain individuals may be sensitive. If needed, continue stimulants. Child Adolesc Psychiatr Clin N Am. 2009 April 1 Biol Psychiatry 2007;61:706–712 Epidemiology of Hypertension HTN-Epidemiology Pre-HTN and HTN have been increasing in children and adolescents over last 2-3 decades. How much? % Children with Pre-HTN (BP 90%-95%) Pre-HTN Increase 8-17 y/o Between the 2 time periods, Pre-HTN increased in all groups. Adapted from Circulation 2007, 116:1488-1496 HTN-Increase Over Time The prevalence HTN in 8-17 year olds in the US has increased over the last 20-25 years. 5 % Children with HTN (BP > 95%) 4.5 4 3.5 3 2.5 1988-1994 2 1999-2002 1.5 1 2012? 0.5 0 Non-Hispanic blacks Non-Hispanic whites Mexican Americans Adapted from Circulation 2007, 116:1488-1496 HTN in the Pediatric Age Group Between 1988-1994 and 1999-2002 in 8-17 y/o patinets: Pre-HTN and HTN increased significantly in Hispanics, Caucasians and African-Americans of both genders. So what has caused the increase in adolescent HTN? Likely mulitfactorial. However, I would like to go on a brief tangent…… Obesity-BMI and HTN in Children As BMI increases, so does HTN. So has pediatric BMI been increasing over time? Hypertension 2002, 40:441-447 Yes, Obesity and BMI are Rising There are some interesting if not outright causative chronologic associations with rising childhood BMI and obesity. Adapted from: http://www.cdc.gov/obesity/childhood/prevalence.html. Yes, Obesity and BMI are Rising 1971: Legislation signed allowing use of high fructose corn syrup in lieu of cane sugar. Adapted from: http://www.cdc.gov/obesity/childhood/prevalence.html. Yes, Obesity and BMI are Rising 1971: Legislation signed allowing use of high fructose corn syrup in lieu of cane sugar. 1976: High Fructose corn syrup enters widespread use. Adapted from: http://www.cdc.gov/obesity/childhood/prevalence.html. High Fructose Corn Syrup Use of High Fructose Corn Syrup Yes, Obesity and BMI are Rising 1980’s: Anything else? 1971: Legislation signed allowing use of high fructose corn syrup in lieu of cane sugar. 1976: High Fructose corn syrup enters widespread use. Adapted from: http://www.cdc.gov/obesity/childhood/prevalence.html. 1985 and the Link to Obesity Boris Becker becomes the youngest Wimbledon champion at 17 years old. Television series The Dukes of Hazzard goes off the air. Microsoft Corporation releases the first version of Windows, Windows 1.0. These are all exciting, but likely did not contribute to obesity. Had to be something else……… Obesity and Nintendo Not the only cause, but certainly a part of the bigger picture. Obesity and HTN Obesity and Hypertension are linked. These health problems do track into adulthood. Bogalusa Heart Study: Overweight children were 4.5 times and 2.4 times as likely to have elevated SBP and DBP, respectively. Possibility related to: Sympathetic overactivity. Insulin resistance. Altered vascular structure. Increased salt sensitivity. Etiology of HTN Etiology of HTN in Pediatrics Primary (essential) - no identifiable underlying cause. This has increased with obesity epidemic. Diagnosis of exclusion. Thought to be a complex interplay of environmental and genetic factors. Etiology of HTN in Pediatrics Secondary - Identifiable cause, potentially curable. Can be placed in a few broad categories. Renal parenchymal diseases. (most common) Aortic coarctation. Renovascular: FMD. Single Gene Disorders: Liddles, Gordons. Endocrine disorders. Malignancies: pheo. neuroblastoma Miscellaneous disorders: Ingestions, Williams syndrome. Secondary HTN-Etiology University of Texas Southwestern MC, 1994. 132 children 0-18 years with sustained HTN. 89 (67%) had secondary HTN due to kidney or renovascular disease. Most common causes of secondary HTN were: Glomerulonephritis. Reflux nephropathy. Renal Vein Thrombosis most common in neonatal period. Pediatr Nephrol 1994; 8:186. Secondary HTN-Etiology Children’s Hospital, Warsaw, Poland. 1,025 patients 1 month to 18 years old referred for HTN. 636 diagnosed with sustained HTN. 351 (55%) patients with secondary HTN. Age Group (years) 0-5 6-14 Total Patients with Patients Kidney/Renovascular disease. 105 83 (79%) 153 129 (84%) 15-18 93 66 (71%) Secondary HTN-Big DDx Pediatr Nephrol (2009) 24:2137–2146 White Coat HTN HTN in medical setting likely due to nerves/anxiety. Actually is a risk factor for sustained HTN with 30-40% of individuals with WCH developing sustained HTN after 10 years. Possibly related to increased sympathetic activity. Diagnosis of HTN HTN-Diagnosis Unlike adults, no outcomes data to identify a single cutoff value like 140/90. Diagnosis of HTN is made when there are 3 readings above the 95% or if patient is symptomatic. Stage 2 or symptomatic HTN does not need 3 readings for diagnosis. For example a 6 y/o with 170/110. Symptoms of HTN Headache. Blurry vision. Epistaxis. Nausea/vomiting. Poor feeding. Flushing. Cough. Abdominal pain. Shortness of breath. Heart palpitations. Slurred speech. Confusion. Seizures. Evaluation of HTN HTN-Evaluation If elevated BP is noted during medical visit: Prehypertension - Recheck in six months. Stage 1 HTN - Recheck within 1-2 weeks/ABPM. Stage 2 HTN - Evaluation for HTN should proceed within 5-7 days or immediately if the patient is symptomatic. In conjunction with drug therapy. Goal of evaluation is to differentiate primary from secondary HTN to identify potentially curable cause. HTN Evaluation-Historical Clues Primary (essential) Adolescent. Usually Stage 1 HTN. Strong family history. HTN. Cardiovascular disease. Obesity. Diabetes. History of sleep disorders/apnea/snoring. Secondary Prepubertal. Thin. Usually severe HTN (defined as stage 2 HTN) Acute rise from normal baseline. History of UTI. Edema (swole), rash, gross hematuria. C/O headache, sweating, tachycardia, feeling hot, and nausea. HTN-Other History Family history-ADPKD, transplantation, early CVD or HTN. Diet: Soda intake, fast food, processed foods. Medical history: Prematurity +/- UAC, urinary tract infections, other medical issues. Alcohol and tobacco exposure. Review of medications, illicit drugs, herbal or dietary supplements. Physical activity history. Screen time HTN-Medications HTN-Physical Exam Confirm HTN manual BP measurement. BMI – Obesity. 4 extremity BP - aortic coarctation, LE BP generally 1020 mm Hg higher than arms. Edema-Fluid overload, renal disease. Abdominal: Bruit. Rash-SLE, HSP, vasculitis. Fundoscopy – operator dependent. Tachycardia-catecholamine excess. Skin: Stigmata of NF1 or TSC. Lab Workup-Stage 1 HTN BMP/RFP- Kidney function. CBC-CKD. UA and culture (if indicated)-proteinuria, hematuria. Microscopy of urine sediment for casts, dysmorphic RBC’s. Urine protein/creatinine ratio-GN. TSH, Free T4. Lipid panel, fasting glucose, HgbA1c. Drug Screen if index of suspicion. Lab Workup-Stage 2 HTN CMP/RFP. CBC. UA, Urine culture, urine protein/creatinine ratio. Renin and Aldosterone. Complement components 3 & 4. Lab Workup-Other Studies Renal vein Renin sampling. ANA, anti-dsDNA. ANCA, MPO + PR3 titers. Anti-GBM. Plasma fractionated metanephrines/24 hour urine metanephrines, HVA & VMA. Imaging Renal US-Renal size and anatomy, cystic disease/dysplasia, hydronephrosis, blood flow. Echocardiogram - to assess for LVH which is by far the most common end organ damage. Also picks up Coarctation. Some reports show LVH in up to 35% of children with even mild HTN. Percentage of children with LVH increases with severity of HTN. Imaging Other studies: MAG3 scan to assess renal perfusion, obstruction and differential function. DMSA to assess for renal scarring due to recurrent pyelonephritis. VCUG to assess for reflux and posterior urethral valves. CT angiogram to assess for renal artery stenosis and can also assess for coarctation. These imaging studies can be done after therapy is initiated. MAG3 Left Right Renal Damage-DMSA VCUG CT Angiogram of RAS www.learningradiology.com/caseofweek Other Evaluation Options Sleep Study Ophthalmology assessment for retinal damage. Ambulatory Blood Pressure Monitoring. Helpful in identifying individuals with white-coat HTN. Pediatr Nephrol 2009; 24:707–719. Therapy of HTN HTN-Therapy Therapy for HTN in adults has proven benefits in reducing cardiovascular morbidity and mortality. Data in children only evaluate ability of therapies to lower BP, no data on long term clinical outcomes. Unique research opportunity in Utah with a large population that tends to stay local. Growing body of evidence that preventing/treating pediatric HTN will have long term benefits into adulthood. HTN-Non Pharmacologic Therapy DASH (Dietary Approaches to Stop Hypertension) Salt Restriction-1200-2000 mg/day High intake of fruits, vegetables, low fat or nonfat dairy, whole grains, lean meats, fish and poultry; nuts and beans. Small amounts of red meats, saturated fats, sweets, and sugar-containing beverages. DASH diet has been shown to reduce SBP 10-13 points and DBP 4-7 points. Exercise-Aerobic +/- resistance training. Limiting screen time to < 2 hrs per day (less Nintendo). http://www.kidney.org/professionals/kdoqi/guidelines_bp/guide_6.htm Weight Loss and HTN In adults, weight loss = 1-2 mm Hg per pound lost. 72 obese children and adolescents, 10-17 years old. Pre-randomization BP’s averaged 127/78. Group A: Diet and behavior change x 8 weeks Group B: Diet, behavior change and 1 hour exercise thrice weekly x 8 weeks. Group C: No intervention x 8 weeks. Group A: wt - 2 kg, BP from 127/80 to 117/68 Group B: wt - 3 kg, BP from 129/79 to 113/66 Group C: wt + 4 kg, BP from 126/78 to 130/77 Weight loss reduces BP in obese adolescents. Long term benefit? PEDIATRICS Vol. 82 No.1 July 1988 HTN-Non Pharmacologic Therapy We routinely encourage: Salt restriction with a no-added-salt diet. Restriction of sugar-sweetened beverages. Including Sports Drinks. Exercise. More fruits and veggies. Compliance is a definite struggle with individuals and families. Pharmacologic Therapy-Who Gets Treated? Stage 2 HTN. Symptomatic HTN. Insufficient response to non-pharmacologic interventions. Usually try a 3-6 month trial. Pre-HTN or Stage 1 HTN in patients with diabetes mellitus, CKD, or proteinuria. Evidence of end-organ damage, most importantly LVH. Stage 1 HTN with dyslipidemia. Pharmacologic Therapy-Goals Reduce BP to <95%. < 90% with other comorbid conditions. LVH, or diabetes. < 50% in children with CKD. Start lowest possible dose with single med and titrate up to desired effect or side-effects. Then start second med. As nearly all classes of anti-HTN medications have shown efficacy in lowering pediatric BP, choice of initial medication is at discretion of treating physician. N Engl J Med 2009;361:1639-50. Anti-Hypertensive Medications Due to patent protection provided by 1997 Food and Drug Administration Modernization Act (FDAMA) and the 2002 Best Pharmaceuticals for Children Act, more medications studied and approved for children. Commonly Used: Dihydropyridine Calcium Channel Blockers. ACE inhibitors/Angiotensin Receptor Blockers. Beta-Blockers. Diuretics. Less commonly used Clonidine, Doxasin, Prazosin, Hydralazine, Minoxidil. Calcium Channel BlockersDihydropyridine Class Amlodipine, Nifedipine, Nicardipine Extensive history of safety and efficacy in children. Relax smooth muscle. Low side effect profile, may cause peripheral edema and orthostatic symptoms. ACE inhibitors/Angiotensin Receptor Blockers Safe and effective in children/adolescents. Long term use may protect from chronic kidney disease. Possible side effects include increased creatinine, hyperkalemia, and chronic cough due to bradykinin excess. Teratogenic. Counseling required regarding use of ACEI/ARB with NSAIDS or dehydration. Preferred antihypertensive medication for athletes. Beta Blockers Among earliest and widely used anti-HTN medications in pediatrics. Well tolerated with few side effects. Contraindicated in asthma and heart block. Should be avoided in athletes. Diuretics Thiazides-HCTZ, Metolazone, Chlorthalidone Complications include hypokalemia, hyperglycemia. May elevate cholesterol and triglycerides. Loop diuretics – furosemide, bumetanide Also cause hypokalemia. Potassium sparing-Spironolactone, Eplerenone, Triamterene, Amiloride. Block action of Aldosterone. Other Medications Clonidine, central alpha-blocker. May cause sedation, rebound HTN. Doxazosin, Prazosin Used for treatment of pre-op HTN with pheochromocytoma. Hydralazine - Direct vasodilator. Minoxidil - Very potent direct vasodilator, promotes hair growth. Not a good long term option. Therapy Monitoring Once pharmaceutical therapy is initiated, check labs in 1-2 weeks. Assess for renal function, potassium. Particularly patients on ACEI/ARB and/or diuretics. Clinical follow-up frequent following initiation of meds. Every 2-4 weeks until stable, then space visits out. Maintenance visits every 3-6 months Continue to encourage lifestyle changes. Ongoing vigilance for medication side effects, end organ damage. ABPM to assess response to therapy every 6-12 months. Questions About BP Is sports participation safe in children and adolescents with HTN? HTN and Sports AAP Policy Statement, 2010 The presence of pre-HTN should not limit eligibility for competitive athletics. Encourage lifestyle modifications: Weight management. Daily physical activity. Well-balanced diet. BP should be measured every 6 months. Pediatrics 2010;125;1287 HTN and Sports Stage 1 HTN in the absence of end organ damage should not limit eligibility for competitive athletics. Recheck BP in 1-2 weeks or sooner if symptomatic. Appropriate referrals to pediatric medical subspecialists if patients have persistent HTN, are symptomatic, have LVH or concomitant heart disease. Require evaluation for lifestyle modification or drug therapy. Pediatrics 2010;125;1287 HTN and Sports Stage 2 HTN in the absence of end organ damage should be restricted from high-static sports (classes IIIA to IIIC) until their blood pressure is in normal range after lifestyle modification and/or drug therapy. These athletes should be promptly referred and evaluated by a qualified pediatric medical subspecialist within 1 week if they are asymptomatic or immediately if they are symptomatic. 801-662-1000 Ask for Pediatric Nephrologist on call. Pediatrics 2010;125;1287 High Static Sports Pediatrics 2010;125;1287 Summary Pre-HTN and HTN are increasing in pediatric population. SBP and DBP are equally important in diagnosis of HTN If you have a patient with HTN, check for kidney disease. If you suspect kidney disease, check for HTN. Regardless of the charted 95% BP for age, gender and height, any adolescents with BP above 120/80 mm Hg should be considered prehypertensive and evaluated. Summary Stage 2 or symptomatic HTN requires immediate therapy and evaluation. Initiate dietary counseling early. Avoid the potato chip aisle, chef Boyardee aisle and buildings with drive through windows. Consider referral to subspecialty care for pre-HTN. Recommend referral for stage 1 and 2 HTN. Thank you