HIGH BLOOD PRESSURE
| RESISTANT HYPERTENSION —Richard J. Solomon, MD, Professor of Medicine, University of Vermont College of
Medicine, and Chief, Section of Nephrology, Fletcher Allen Health Care, Burlington, VT
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| Definition: documented hypertension (HTN); patient on pharmacologic therapy that includes 3 medications, one of
which diuretic in appropriate dose; must be adherent to medications; in-office blood pressure (BP) not at target appropriate
for therapy (<140/90 mm Hg for majority of people with HTN); target even lower in patients with diabetes or
primary kidney disease (<130/80 mm Hg); most failure to achieve target due to systolic pressure
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| Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT): largest antihypertensive
study; different classes of agents had same outcomes; 44,000 individuals followed for 6 to 7 yr; at 5 yr,
34% uncontrolled on 2 agents and 23% uncontrolled on 3 agents (National Health and Nutrition Examination Survey
[NHANES] data showed 8% uncontrolled on 4 agents)
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| Lack of adherence: not resistant HTN if patient not taking medication; contributors—multiple drug regimens; complex
dosing; expense; side effects and interactions
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| White coat effect: definition—elevated BP in office but normal or substantially lower out of clinic; occurs in 25% to
33% of patients; suspect when self-reported BP at home much lower and patient has no evidence of complications
from HTN; only reimbursable reason for performing 24-hr ambulatory BP monitoring (ABPM); affects therapeutic
decisions; if diagnosis confirmed, use out-of-office BP to monitor therapy; target BP changes (if using home BP,
lower target by 5 mm Hg)
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| Associated conditions: frequently associated with volume overload; occurs more frequently in overweight patients
due to increase in extracellular volume and enhanced activity of sympathetic nervous system (SNS) and renin-angiotensin
system (RAS), which contributes to kidneys retaining excess salt and water; excess dietary salt often hidden in
packaged foods
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| Renal insufficiency: associated with increased retention of salt and water; at stage 3 (glomerular filtration rate [GFR]
<60 mL/min), prevalence of HTN starts to increase; at stage 4, 70% to 80% of patients with chronic kidney disease hypertensive;
factors associated with HTN—sodium retention; activation of RAS; when kidney ischemic, it signals brain
(through sympathetic afferent nerves) to enhance sympathetic nerve activity; all mechanisms supporting BP (volume,
sympathetic angiotensin II, and catecholamines) upregulated in patients with chronic kidney disease; clue as to why single
medication unable to lower BP
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| Exogenous substances: nonsteroidal anti-inflammatory drugs (NSAIDs)—interfere with kidney’s ability to excrete
sodium; enhance any tendency of kidney to retain sodium due to, eg, activation of SNS, loss of nephrons, activation of
RAS, enhanced salt intake; stimulants—ephedrine, amphetamine, dexadrine, cold remedies, and ephedra raise BP; oral
contraceptives (OCs)—about one third of young women taking OCs have significant increase in BP; specific drugs—
erythropoietin; immunosuppressive agents; some antidepressants; some evidence that alcohol contributes to HTN, but
mechanism unclear (adherence problem?)
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| Secondary HTN: certain forms of secondary HTN prevalent in individuals resistant to antihypertensive therapy;
pathophysiologic process identified, and if corrected, BP corrected or substantially improved; obstructive sleep apnea
(OSA)—most significant pathophysiologic process found in people with resistant HTN; reflects increasing obesity in
population and increasing sympathetic activity in individuals chronically hypoxemic; if diagnosed and appropriately
treated, BP lowered; in prospective study, 83% of resistant hypertensives found to have OSA on polysomnography;
continuous positive airway pressure (CPAP) shown to lower BP; consider in obese patient with resistant HTN; renal
disease—next most common; all patients with resistant HTN should have estimated GFR calculated; if <60 mL/min,
resistant HTN attributable to kidney disease (not loss of renal function with aging); hyperaldosteronism—found in
20% of resistant hypertensives; renal artery disease—prevalence on imaging high; controversy whether any intervention
has impact on BP; other conditions include hypercalcemia, pheochromocytoma, Cushing’s disease, and coarctation
of aorta
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| Evaluation: ask patient whether he or she missed any doses of medicine in last week; if patient admits to missing one
dose, assume that he or she missed >1 and adherence possible problem; more objectively, can look for expected
consequences of medications patient using (eg, if patient on diuretics, and edema not responsive [either wrong dose
or consuming excess salt]); create dosing program that makes sense to patient; ensure that BP measured accurately
and appropriately; recommendations from Joint National Committee on Prevention, Detection, Evaluation, and
Treatment of High BP (JNC)—seat patient with feet on floor; 5 min of quiet rest before measurement; 2 measurements
1 min apart; appropriate cuff size; inflate and deflate cuff 2 mm Hg per second; white coat effect—home BP
monitoring
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 | Laboratory evaluation: calculate estimated GFR; look for sleep apnea; if concerned about patient’s salt intake, obtain
24-hr urinalysis for sodium excretion; if concerned about possibility of hyperaldosteronism, not necessary to stop
antihypertensive medications, except spironolactone (Aldactone); measure plasma aldosterone and renin; ratio >80
consistent with aldosteronism; plasma renin level low in primary aldosteronism; not necessarily adenoma, usually
hyperplasia; for most part, not surgical disease and treated pharmacologically
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| Treatment: lifestyle modification—weight loss; sodium restriction; cessation of alcohol use; combination
pharmacotherapy—any antihypertensive agent with diuretic; 2-in-1 combination pill; limiting sodium intake makes
antihypertensive drugs of all classes work better; diuretics—for pure essential HTN without renal disease, use thiazide
diuretic (25 mg maximum); start patient at 12.5 mg and if not achieving BP goal, increase to 25 mg; once patient has renal
disease (GFR <60 mL/min), thiazide diuretics tend to lose natriuretic ability; switch to loop diuretics (eg, lasix, furosemide);
furosemide—more potent natriuretic agent at peak effect; peak effect short in duration, compared to thiazide
diuretic; antihypertensive effect (over 24 hr) weaker than thiazide diuretic; necessary to give multiple times during day if
using as antihypertensive agent; if patient not experiencing increased frequency of urination, keep doubling dose until
response obtained; absorption dramatically affected by food; can avoid by giving branded loop diuretic (eg, torsemide
[Demadex], bumetanide [Bumex]) but costs more; other strategies—furosemide combined with hydrochlorothiazide
or metalozone (thiazide-like diuretic) in patients with massive edema; with longer-acting agents (eg, torsemide), once-
daily dosing may be sufficient; adding antialdosterone drug (eg, spironolactone, eplerenone, amiloride) may be effective
in resistant HTN; inexpensive; effect not predicted by plasma aldosterone (not necessary to measure renin and aldosterone);
summary— controlling BP enhances quality and duration of life and reduces mortality by 50%
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| HYPERTENSION IN CHILDREN AND ADOLESCENTS —Lauren M. Simon, MD, MPH, Associate Professor of
Family Medicine, and Director, Primary Care Sports Medicine, Loma Linda University, Loma Linda, CA
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| Hypertension: well established risk factor for cardiovascular disease; want to find it if present in children and adolescents;
antecedents for HTN occur in children and adolescents; however, not enough good data on HTN and its progression
(ie, whether cardiovascular disease ultimately preventable); prevalence—4.5% in school-age children
(average age, 13.5 yr), according to study of ≈5100 children
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| Definition: based on NHANES data (1999-2000) and Centers for Disease Control and Prevention (CDC) growth charts
(updated); body size important determinant of BP in children; height percentile needed to determine if BP normal;
percentiles based on age, sex, and height; revised childhood BP tables include 50th, 90th, 95th, and 99th percentiles;
normal BP—systolic BP <90th percentile; if diastolic and systolic percentiles different, categorize by higher value;
prehypertension—average systolic or diastolic BP ≥90th percentile, but <95th percentile for age, sex, and height;
HTN—average systolic or diastolic BP ≥95th percentile for age, sex, and height, measured on ≥3 separate occasions; adolescent
with BP >120/80 mm Hg considered prehypertensive (assess for risk factors); stage 1 HTN—from 95th percentile
to 5 mm Hg above 99th percentile; stage 2 HTN—>5 mm Hg above 99th percentile; aggressively look for
symptoms and obtain control of underlying disorder to prevent risk for end-organ damage; white coat HTN—systolic
BP and/or diastolic BP 95th percentile when measured in physician’s office or clinic, but average outside clinical setting
<90th percentile
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| BP measurement: seated patient after 5 min of rest; avoid stimulant food, beverages, or drugs; seated with back supported,
feet on floor, with right arm supported; cubital fossa at heart level; auscultation preferred measurement method;
mercury sphygmomanometer ideal (most accurate); cuff size—bladder length 80% to 100% of arm circumference;
bladder width ≈40% of arm circumference at point midway between olecranon and acromion; cuff width has to cover at
least two thirds of arm length from shoulder to elbow; oversized cuff can underestimate BP; undersized cuff can overestimate
BP; by convention, right arm used (tables based on right arm); may have decreased BP in left arm if aortic coarctation
present; if BP >90th percentile, repeat measurement twice at same office visit to check validity; check both arms
and one leg; whether left arm BP lower depends on where coarctation located; ambulatory BP monitoring—useful for
white coat HTN; used for 24 hr; also used in chronic renal disease to measure response to therapy; need to measure BP
on 3 visits before classifying level of HTN; deflate cuff 2 to 3 mm Hg per heartbeat; check BP routinely in every child
≥3 yr of age (based on consensus guidelines of National High Blood Pressure Education Program [NHBPEP]); United
States Preventive Services Task Force (USPSTF) decided not enough evidence that checking BP at 3 yr of age will prevent
future cardiovascular disease; if child had umbilical catheterization at birth, admitted to neonatal intensive care
unit (NICU), or had neonatal shock or hypovolemic episode, monitor BP at <3 yr of age (at higher risk for early HTN
and vascular complications)
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| Coarctation of aorta: difference in BP between both arms, especially if >10 mm Hg, raises suspicion; BP in leg normally
higher, but if lower, also raises suspicion; usually found in younger children and occasionally, depending on location
and severity, in teens; HTN in upper extremities with diminished femoral pulses; location of coarctation and
site of origin of left subclavian artery determinants
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| Etiology of HTN: in children, HTN usually secondary to underlying disorder; renal parenchymal disease accounts for
60% to 70% of cases; in adolescents, primary or essential HTN accounts for 85% to 95% of cases; risk factors include
family history, elevated body mass index (BMI), and metabolic syndrome; primary HTN rare in children <10 yr of age
(diagnosis of exclusion); secondary HTN—renal (renal parenchymal disease, scarring, and glomerulonephritis); endocrine
(thyroid disorders [particularly hyperthyroidism], Cushing’s syndrome, and pheochromocytoma); cardiovascular;
medications (sympathomimetic agents [cold preparations], anabolic steroids, OCs, glucocorticoids, and some
dietary supplements); note—stimulant beverages cause transient rise in BP
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| Etiology of childhood HTN: age 1 to 6 yr—renal parenchymal disease and renal vascular disease major causes, particularly
in stage 2 HTN; ≈50% of cases of renal vascular disease from fibromuscular dysplasia; other causes include
endocrine, cardiovascular, and primary HTN (rare); age 6 to 12 yr—renal parenchymal disease number one cause;
primary HTN due to increased BMI second; other causes include renal vascular disease, endocrine disorders, cardiovascular
disorders, and iatrogenic illness
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| Etiology of adolescent HTN: age 12 to 18 yr—primary HTN number one cause (due to obesity epidemic); other causes
include iatrogenic illness, renal parenchymal disease, renal vascular disease, endocrine disorders, and cardiovascular disease
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| Evaluation of HTN: history and physical examination most important; check for family history of HTN; urinalysis and
urine culture (look for infection, proteinuria, and hematuria); blood urea nitrogen (BUN) and creatinine (renal disease);
complete blood count with differential (anemia of chronic renal disease); renal ultrasonography (US; structural abnormalities
and scarring); echocardiography in patient with HTN to look for end-organ damage; screening tests necessary
on all children with confirmed diagnosis of HTN; additional tests and imaging based on risk factors, results of screening
tests, and family history
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| Family history: HTN, cardiovascular disease, OSA, and dyslipidemia in family may indicate risk for primary HTN; presence
of renal disorders or deafness (possible renal disease association) may indicate risk for secondary HTN
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| Child’s history: hematuria, enuresis, neonatal hypovolemia, neonatal umbilical artery catheterization, and/or urinary tract
infections (UTIs) may indicate renovascular disease or scarring etiology; change in weight, excess sweating, growth
abnormalities, and temperature intolerance (endocrine disorder etiology); chest pain, dyspnea, edema, and palpitations
(cardiovascular etiology); rashes, arthralgias, and myalgias (rheumatologic etiology, particularly systemic lupus
erythematosus [SLE]); medications, over-the-counter medicines, cough remedies, decongestants, illicit substances, and
performance-enhancing agents
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| Physical examination: check BP, height, BMI, and pulse; take BP readings in both arms and one leg (to rule out aortic
coarctation); categorize BP; skin—acne (especially if distributed across body, may indicate anabolic steroid use),
striae, hirsutism (Cushing’s syndrome), malar rash (SLE); flushing (pheochromocytoma); head, eyes, ears, nose, and
throat—enlarged tonsils (OSA), moon facies (Cushing’s syndrome), enlarged thyroid (hyperthyroidism); cardiovascular
system—tachycardia (hyperthyroidism, pheochromocytoma), murmurs; abdomen—bruits (renal artery disease),
tumor, hydronephrosis, polycystic kidney disease, and obesity (metabolic syndrome); extremities—edema
(renal or cardiovascular etiology), diminished lower extremity pulses or perfusion (aortic coarctation); lungs—
crackles (fluid overload); evaluate for end organ damage in all patients with HTN; look for retinopathy, microalbuminuria,
and left ventricular hypertrophy
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| Pharmacotherapy for children and adolescents with HTN: use one medication, increasing dose until therapeutic
effect achieved, side effects preclude use, or maximum dose reached; per seventh report of JNC (JNC 7), diuretics and
β-blockers first-line agents; add second medication if further reduction of BP needed after above criteria met; long-
acting preparation may improve compliance; be alert for sports restrictions or prohibitions; consider environmental effects
on medications (eg, diuretic may not be appropriate for athlete in hot climate); β-blockers and diuretics known to
impair sports performance
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Suggested Readings
Antes LM et al: Principles of diuretic therapy. Dis Mon 44:254, 1998; Calhoun DA: Use of aldosterone antagonists in
resistant hypertension. Prog Cardiovasc Dis 48:387, 2006; Chandran P: Resistant or difficult-to-control hypertension.
N Engl J Med 355:1934, 2006; Chesney RW et al: Is there a role for beta-adrenergic blockers in treating hypertension in
children? J Pediatr 150:121, 2007; Falkner B et al: The relationship of body mass index and blood pressure in primary
care pediatric patients. J Pediatr 148:195, 2006; Flynn JT et al: Pharmacologic treatment of hypertension in children
and adolescents. J Pediatr 149:746, 2006; Gandhi S et al: Resistant hypertension. Suggestions for dealing with the problem.
Postgrad Med 100:97, 1996; Ingelfinger JR: Pediatric antecedents of adult cardiovascular disease--awareness and
intervention. N Engl J Med 350:2123, 2004; Kaplan NM: Resistant hypertension: what to do after trying 'the usual'. Geriatrics
50:24, 1995; Luma GB et al: Hypertension in children and adolescents. Am Fam Physician 73:1558, 2006;
Mitsnefes MM: Hypertension in children and adolescents. Pediatr Clin North Am 53:493, 2006; Moser M et al: Clinical
practice. Resistant or difficult-to-control hypertension. N Engl J Med 355:385, 2006; Moser M: Why are physicians
not prescribing diuretics more frequently in the management of hypertension? JAMA 279:1813, 1998; Osterberg L et al:
Adherence to medication. N Engl J Med 353:487, 2005; Park MK: Blood pressure tables. Pediatrics 115:826, 2005;
Pratt-Ubunama MN et al: Plasma aldosterone is related to severity of obstructive sleep apnea in subjects with resistant
hypertension. Chest 131:453, 2007; Sorof JM et al: Overweight, ethnicity, and the prevalence of hypertension in school-
aged children. Pediatrics 113:475, 2004; Vidt DG: Contributing factors in resistant hypertension. Truly refractory disease
is rarely found in a properly conducted workup. Postgrad Med 107:57, 2000
Educational Objectives
| The goal of this program is to increase awareness and improve management of resistant hypertension (HTN) and HTN
in children and adolescents. After hearing and assimilating this program, the clinician will be better able to:
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| 1. Define and identify resistant and white-coat HTN.
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| 2. Discuss secondary HTN and its associated conditions.
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| 3. Prescribe appropriate treatment for resistant HTN.
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| 4. More accurately measure blood pressure in children and adolescents.
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| 5. Recognize HTN early in children and adolescents and treat appropriately.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose relevant
financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified
conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business
or commercial interest. For this program, the faculty reported nothing to disclose.
Acknowledgements
Dr. Solomon was recorded at the 32nd Annual Vermont Family Medicine Review Course, held June 13-16, 2006, in
Burlington, VT, and sponsored by the University of Vermont College of Medicine. Dr. Simon was recorded at Family
Medicine: Pearls, Perils, Practice Guidelines held June 25, 2006, in Loma Linda, CA, and sponsored by the Loma
Linda University School of Medicine. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation
in the production of this program.
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