Management of Hypertension: An Overview

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Management of HypertensionAn Overview Update

• 11/12/11
• Marcus Weiser, DO
• PGY3
• Chief Resident
• Via Christi Family Medicine

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Outline

• Classification
• Causes
• History, PE, initial testing
• Antihypertensive agents
• Monotherapy combination therapy

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Hypertension

• Sustained elevation of arterial systemic blood
  pressure
• Single most common diagnosis at US family
  physician office visits (coded at 11.1)
• Age 20-50 usually affected
• 29 of US adults
• Prevalence increases with age

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Hypertension

• Baseline high blood pressure at age 50 reduces
  life expectancy by about 5 years.1
• Associations
• Erectile dysfunction, ophthalmologic conditions,
  osteoporosis, anxiety, chronic kidney disease,
  obstructive sleep apnea, coronary artery disease,
  cerebrovascular disease, peripheral arterial
  disease, congestive heart failure, dementia

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Types

• Prehypertension (SBP 120-139 or DBP 80-89)
• Stage I (SBP 140-159 or DBP 90-99)
• Confirm within 2 months
• Stage II (SBP gt 159 or DBP gt 99)
• Evaluate within 1 month (within 1 week if gt
  180/110)
• Type I (vasoconstriction, high renin, high SBP)
• Treat with ACE, ARB, BB
• Type II (Na dependent, low renin, high DBP)
• Treat with diuretics, CCB

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ICD-10 codes

• I10 essential (primary) hypertension
• ICD-10-CA modification in Canada
• I10.0 benign hypertension
• I10.1 malignant hypertension
• I11 hypertensive heart disease
• I11.0 hypertensive heart disease with
  (congestive) heart failure
• I11.9 hypertensive heart disease without
  (congestive) heart failure
• ICD-10-CA modification in Canada - 4th character
  extensions were deleted to allow for use of dual
  classification for added specificity
• I12 hypertensive renal disease
• I12.0 hypertensive renal disease with renal
  failure
• I12.9 hypertensive renal disease without renal
  failure
• ICD-10-CA modification in Canada - 4th character
  extensions were deleted to allow for use of dual
  classification for added specificity
• I13 hypertensive heart and renal disease
• I13.0 hypertensive heart and renal disease with
  (congestive) heart failure
• I13.1 hypertensive heart and renal disease with
  renal failure
• I13.2 hypertensive heart and renal disease with
  both (congestive) heart failure and renal failure
  
• I13.9 hypertensive heart and renal disease,
  unspecified
• ICD-10-CA modification in Canada - 4th character
  extensions were deleted to allow for use of dual
  classification for added specificity
• I15 secondary hypertension

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Causes

• CKD (any cause)
• Renal Artery Stenosis
• Cushing Syndrome
• Primary Hyperaldosteronism
• Hyper/Hypothyroidism
• Hyperparathyroidism
• Pheochromocytoma
• Obstructive Sleep Apnea
• Coarctation of the Aorta
• Black Licorice

• Medications
• BP Cuff too small
• Arm position
• Caffeine
• Nicotine
• Substance Abuse/Intoxication
• Short sleep duration
• Alcohol Use
• Salt intake?
• Impatience, hostility

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History

• Symptoms
• Medications
• Corticosteroids, OCPs, NSAIDs, venlafaxine,
  buspirone, carbamazepine, clozapine,
  bromocriptine, cyclosporin, tacrolimus, EPO
• Past Medical History
• DM, CAD, CHF, DSLD, Thyroid/Renal Dz
• Social History
• Dietary sodium, stress, smoking, alcohol intake,
  activity level, St. Johns wort, ergot-containing
  herbal preparations, cocaine, anabolic steroids,
  narcotic withdrawal, meth, PCP

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Physical Exam

• Proper blood pressure measurement
• Seated in chair with back in calm, quiet, warm
  room for at least 5 minutes. Bare arm elevated
  so elbow is level with heart. No smoking or
  caffeine 1 hour prior
• Cuff width gt 2/3 arm diameter
• Cuff length gt 2/3 arm circumference
• Average of 2 measurements
• Carotid bruits
• Cardiac auscultation
• Abdomen
• Extremities

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Initial Testing

• Serum Potassium
• Serum Creatinine
• Fasting Blood Glucose
• Fasting Lipid Panel
• Urinalysis
• Electrocardiogram
• - Uniformly recommended by 4 expert panels (CHEP,
  ESH/ESC, ICSI, JNC7)

• Hematocrit
• Serum Calcium
• Serum Sodium
• Serum Uric Acid
• Urine Albumin/Creatinine Ratio
• - Recommended by some, not all 4 panels

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Additional Testing to Consider

• PTH
• TSH
• 24 hour urine metanephrine
• Plasma Aldosterone
• Plasma Renin
• Dexamethasone supression test
• Sleep study
• RAS imaging

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Agents

• Ace-inhibitors (ACEs)
• Angiotensin Receptor Blockers (ARBs)
• Calcium Channel Blockers (CCBs)
• Beta Blockers (BBs)
• Thiazide Diuretics (TZD)
• Loop Diuretics (Loops)
• Aldosterone Antagonists
• Alpha Blockers
• Other agents

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ACEs ARBs

• Special Indications
• ACE
• CHF (SOLVD, AIRE, TRACE)
• Post-MI (SAVE)
• Diabetes (UKPDS, HOPE)
• CKD (REIN, AASK, CAPTOPRIL)
• Recurrent Stroke Prevention (PROGRESS)
• High CAD Risk (ALLHAT, HOPE, ANBP2)
• ARB
• CHF (Val-HeFT)
• Diabetes
• CKD (RENAAL, IDNT, CAPTOPRIL)

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ACEs ARBs

• Contraindications
• Pregnancy, Angioedema, Renovascular Disease,
  Hyperkalemia, Acute Renal Failure
• Monitor
• Creatinine, Potassium
• Agents
• Benazepril or Lisinopril (20mg to 40mg PO daily)
• Enalapril, Ramipril
• Losartan, Olmesartan, Valsartan

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Calcium Channel Blockers

• Special Indications
• High CAD risk (ALLHAT, CONVINCE)
• Migraines
• Raynauds
• Angina (non-dihydropyridine)
• Atrial Fibrillation (non-dihydropyridine)
• Atrial Flutter (non-dihydropyridine)

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Calcium Channel Blockers

• Contraindications
• 2nd or 3rd degree heart block
• Agents
• Amlodipine (5mg to 10mg PO daily)
• Nifedipine, Nicardipine, Felodipine

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Beta Blockers

• Special Indications
• CHF (MERIT-HF, COPERNICUS, CIBIS)
• Post-MI (BHAT, CAPRICORN)
• Angina, Atrial Fibrillation, Atrial Flutter,
  Tremor, Migraine
• Contraindications
• Asthma, COPD, 2nd or 3rd degree heart block,
  Depression, Acute CHF
• Avoid abrupt cessation
• Agents
• Metoprolol (50mg to 200mg PO BID)
• Carvedilol (3.125mg to 25mg PO BID)
• Atenolol, Nebivolol, Labetalol, Esmolol,
  Propranolol, Timolol

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Beta BlockersInappropriate first-line treatment

• JNC8
• Worse BP control (LIFE)
• Worse CV outcome prevention (LIFE)
• Increased mortality (ASCOT)
• Higher risk of stroke 2
• More side effects 2
• Increased risk of type II diabetes 3

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Thiazide Diuretics

• Special Indications
• High CAD risk (ALLHAT)
• Recurrent stroke prevention (PROGRESS)
• DM without proteinuria (ALLHAT)
• Edema
• Osteoporosis

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Thiazide Diuretics

• Contraindications
• Stage IV CKD, Gout, Hyponatremia, Acute Renal
  Failure
• Monitor
• Creatinine, Potassium, Sodium
• Agents
• Chlorthalidone (12.5mg to 25mg PO daily)
• Hydrochlorothiazide, Indapamide, Metolazone

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Thiazide equivalence?

• Chlorthalidone vs HCTZ
• Chlorthalidone use has sharply declined over the
  last 20 years for reasons unknown 4

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ACCOMPLISH
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Chlorthalidone vs HCTZ

• Amlodipine appears superior to HCTZ

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ALLHAT

• Secondary Outcome

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Chlorthalidone vs HCTZ

• Amlodipine appears superior to HCTZ
• Chlorthalidone appears superior to Amlodipine

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ALLHAT

• Secondary Outcome
• Lower rate of combined CVD with
  Chlorthalidone

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Chlorthalidone vs HCTZ

• Amlodipine appears superior to HCTZ
• Chlorthalidone appears superior to Amlodipine
• Chlorthalidone appears superior to Lisinopril

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ACE-I Beats Diuretic (ANBP2)

• Rate of events per year

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Chlorthalidone vs HCTZ

• Amlodipine appears superior to HCTZ
• Chlorthalidone appears superior to Amlodipine
• Chlorthalidone appears superior to Lisinopril
• Enalapril appears superior to HCTZ

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Thiazide equivalence?

• Chlorthalidone vs HCTZ
• Chlorthalidone use has sharply declined over the
  last 20 years for reasons unknown 4
• No evidence that HCTZ improves cardiovascular
  outcomes
• Large body of evidence in major trials (ALLHAT)
  showing cardiovascular event reduction and
  outcome benefit with chlorthalidone
• Chlorthalidone has much longer half-life, is
  1.5-2.0 times more potent, and has slightly more
  hypokalemia (7-8 patients require treatment 5,6)

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Thiazide Diuretics

• Chlorthalidone superior reduction of nighttime
  BP, compared to HCTZ 7
• 13.5 mmHg vs 6.4 mmHg
• Chlorthalidone (12.5-25mg) vs HCTZ (25-50mg)
• Agents
• Chlorthalidone (12.5mg to 25mg PO daily)
• Hydrochlorothiazide, Indapamide, Metolazone

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Loop Diuretics

• Special Indications
• CHF, Edema
• Contraindications
• Gout, Acute Renal Failure
• Monitor
• Creatinine, Electrolytes
• Agents
• Torsemide (5mg to 10mg PO daily)
• Furosemide, Bumetanide

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Aldosterone Antagonists

• Special Indications
• CHF (RALES)
• Post-MI (EPHESUS)
• Contraindications
• Gout, Hyperkalemia, Acute Renal Failure
• Monitor
• Creatinine, Potassium
• Agents (ASCOT)
• Spironolactone (25mg to 50mg once daily)
• Amiloride, Triamterene

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ASCOT

• Patients with uncontrolled hypertension on 3
  antihypertensive agents
• Spironolactone 25mg once daily added as 4th agent
• Mean BP drop of 22/10 at one year follow-up

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Alpha Blockers

• Special Indications
• BPH
• Contraindications
• High CV risk (ALLHAT)
• Agents
• Doxazosin, Prazosin, Terazosin

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Other Agents

• Clonidine
• Methyldopa
• Hydralazine
• Tekturna
• Minoxidil
• Isosorbide dinitrate/mononitrate

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Low . . . but how low is too low?

• Treatment goal lt 140/90
• lt 130/80 in diabetics per JNC7 recommendation
• ACCORD, INVEST
• BP targets below 140/90 overall do not improve
  morbidity or mortality
• DBP lt 70 increases risk of death, MI, stroke

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Lifestyle ModificationsFirst-Line Treatment

• Sodium Restriction (2-8 mmHg)
• DASH (8-14 mmHg)
• Fruits, vegetables, low-fat dairy, reduced fat
• Aerobic physical activity (4-9 mmHg)
• Weight Reduction
• (5-20 mmHg per 10 kg lost)
• Moderate alcohol (2-4 mmHg)
• Smoking Cessation
• From JNC7 Express Report, 2003

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Monotherapy vs Multi-Drug Therapy

• Sequential treatment
• Avoid excessive dosing
• First-line agents

• Avoid similar agents
• Avoid excessive dosing
• Other agents

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Monotherapy 1st line agents

• 1. Thiazide
• Chlorthalidone 12.5mg daily, titrate to 25mg?
• 2. ACE/ARB
• Benazepril or Lisinopril 20mg daily
• Titrate up to 40mg, possibly beyond
• 3. Calcium Channel Blocker (dihydropyridine)
• Amlodipine 5mg daily
• Titrate up to 10mg once daily

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Monotherapy

• Sequential treatment
• Try one agent, titrate up
• If inadequate control, switch instead of add
• Each first-line agent will normalize BP in 30-50
  of patients 8,9
• 49.1 chance a different agent will control Stage
  I Hypertension following failure of initial agent
  10
• May prevent unnecessary multi-drug treatment
• JNC7 recommendation for uncontrolled stage I
  hypertension on monotherapy is to optimize dose
  or add 2nd medication
• Addition of a second drug from a different class
  should be initiated when use of a single drug in
  adequate doses fails to achieve the BP goal

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Combination Therapy

• Consider combination for Stage 2
• Add if sequential monotherapy fails
• Drugs for each compelling indication
• ACCOMPLISH
• Include a diuretic
• Consider Spironolactone as 4th agent (ASCOT)
• First-line agents

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ACCOMPLISH
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ACCOMPLISH
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ACCOMPLISH
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Combination Therapy

• Drugs for each compelling indication
• ACCOMPLISH
• Include a diuretic
• First-line agents
• Consider Spironolactone as 4th agent (ASCOT)

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Resistant Hypertension

• Uncontrolled on 3 medications
• Controlled on 4 or more medications
• Must include a diuretic

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Causes

• CKD (any cause)
• Renal Artery Stenosis
• Cushing Syndrome
• Primary Hyperaldosteronism
• Hyper/Hypothyroidism
• Hyperparathyroidism
• Pheochromocytoma
• Obstructive Sleep Apnea
• Coarctation of the Aorta
• Licorice

• Medications
• BP Cuff too small
• Arm position
• Caffeine
• Nicotine
• Substance Abuse/Intoxication
• Short sleep duration
• Alcohol Use
• Salt intake?
• Impatience, hostility

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Who do I screen for secondary causes of
hypertension?

• Resistant Hypertension
• Early or Late onset
• History Physical Exam
• Abnormal initial labs
• Low potassium
• High calcium
• Abnormal subsequent monitoring
• Increase Cr gt 20 after starting ACE/ARB

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Additional Testing to Consider

• PTH
• TSH
• 24 hour urine metanephrine
• Plasma Aldosterone
• Plasma Renin
• Dexamethasone supression test
• Sleep study
• RAS imaging

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Cases

• 31 yo healthy AAM, BMI 31, BP 132/99
• Benazepril
• Chlorthalidone
• Losartan
• Metoprolol

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Cases

• 77 yo 100 lb WF with hyperlipidemia
• BP 159/82
• Benazepril
• Metoprolol
• HCTZ
• Spironolactone

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Cases

• 58 yo M, GFR 48, proteinuria, BP 150/95
• Lisinopril
• HCTZ
• Torsemide
• Amlodipine

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Cases

• 47 yo M with depression/gout, BP 162/96
• Chlorthalidone
• Benazepril
• Amlodipine
• Metoprolol

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