Hypertension

Gary L. Schwartz, M.D.
Mayo Clinic

Sheldon G. Sheps, M.D.
Mayo Medical School

September 2004

Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy
Best References

Definition/Key Clinical Features

Prehypertension

• SBP: 120–139 mm Hg
• DBP: 80–89 mm Hg

Essential Hypertension

• Stage 1
• SBP: 140–159 mm Hg
• DBP: 90–99 mm Hg
• Stage 2
• SBP: ≥ 160 mm Hg
• DBP: ≥ 100 mm Hg
• Age at onset: 40–60 yr
• Family history of hypertension
• BP at diagnosis: < 180/< 110 mm Hg
• Asymptomatic
• Normal history, physical exam, and routine laboratory studies (no target-organ damage) at time of diagnosis
• BP control achieved with lifestyle changes and 1 or 2 drugs
• BP control maintained once achieved in a compliant patient

Secondary Hypertension

• Age at onset: < 30 yr or > 50 yr
• BP: > 180/110 mm Hg at diagnosis
• Significant target-organ damage at diagnosis
• Hemorrhages and exudates on retinal examination
• Renal insufficiency
• Left ventricular hypertrophy
• Poor response to appropriate 3-drug therapy (which includes a diuretic)
• Accelerated or malignant hypertension
• Sudden worsening of hypertension at any age

Differential Diagnosis

• Isolated clinic ("white-coat") hypertension
• Secondary hypertension

Best Tests

Essential Hypertension

BP Measurement

• At least 2 clinic visits 1–2 mo apart (shorter period if initial BP is severely elevated) with 2 standardized readings at each visit averaging ≥ 140/90 mm Hg
• Patient self-measured BP ≥ 135/85 mm Hg
• Elevated office BP with self-measured BP < 130/80 mm Hg identifies isolated clinic (white-coat) hypertension
• Ambulatory BP monitoring to distinguish sustained hypertension from isolated clinic (white-coat) hypertension and to assess the following:
• Hypotension
• Episodic hypertension
• Masked hypertension
• Suspected autonomic dysfunction in patients with postural hypotension

Lab Tests

• Identify CV risk factors
  • Cholesterol (total and HDL)
  • Triglycerides
  • Fasting blood glucose
• Identify target-organ injury
  • Chest x-ray
  • ECG
  • Urinalysis
  • Serum creatinine or BUN
  • Uric acid
• Serum creatinine
• Potassium
• Calcium
• Urinalysis
• If initial assessment suggests renal dysfunction, evaluate for chronic kidney disease by measuring 24-hour urinary protein excretion and estimating glomerular filtration rate (GFR):
• GFR = (140 – age in yr) Χ (weight in kg) Χ 0.85 (if patient is female)/72 Χ serum creatinine (mg/dl)

Screening Tests for Secondary Hypertension (Sensitivity/Specificity)

Renovascular Hypertension

• Captopril radionuclide renal scan (75% sens./85% spec.)
• Advantage: no contrast exposure
• Disadvantages: renal dysfunction impairs interpretation; may miss bilateral, accessory-, or branch-vessel disease
• Duplex ultrasound (80%–90% sens./90% spec.)
• Advantages: no contrast or radiation exposure; renal dysfunction does not impair interpretation; calculation of resistive index identifies subset of patients with renal dysfunction likely to benefit from intervention (RI < 0.80)
• Disadvantages: failure to visualize both renal arteries (15%–20% of cases); may miss accessory- or branch-vessel disease
• Spiral CT angiography
• Advantages: excellent images of renal arteries; can identify dissection, accessory vessels, and fibromuscular disease
• Disadvantages: considerable contrast load precludes use in presence of renal dysfunction; expensive
• Magnetic resonance angiography (85%–100% sens./79%–98% spec.)
• Advantages: no contrast or radiation exposure; renal dysfunction does not impair interpretation
• Disadvantages: cost; may overstate degree of stenosis; claustrophobic patients may not tolerate test
• Renal angiography: gold standard
• Advantages: identifies accessory- and branch-vessel disease; percutaneous interventions can be performed as part of study
• Disadvantages: cost; contrast exposure; invasive (atheroemboli)

Primary Aldosteronism

• Measurement of serum sodium, potassium, plasma renin activity (PRA), and plasma aldosterone concentration (PAC)
• 24-hr urinary aldosterone, sodium, and PRA after 3 days of a 200 mEq–sodium diet
• Screening: ratio of PAC/PRA > 20
  • Diagnosis confirmed if U_Na > 200 mEq, U_aldo > 12, and PRA < 1.0 after 3 days of high-sodium diet
  • Advantage: 30% of patients with primary aldosteronism are normokalemic at presentation; ratio is easy to obtain
  • Disadvantages: many antihypertensive drugs can influence values of PRA and PAC; sensitivity and specificity of ratio not established

• Plasma-free metanephrines (99% sens./89% spec.)
  • 24-hr fractionated urinary metanephrines (77% sens./93% spec.)
  • Use plasma test if degree of suspicion is high or familial syndrome is suspected

• 24-hr urinary free cortisol (95%–100% sens./97%–100% spec.)
  • Diagnosis certain if 24-hr urinary free cortisol level > 3 times normal
  • Diagnosis excluded if level normal
  • Use low-dose dexamethasone suppression test if elevation < 3 times normal

• Chest x-ray; transesophageal echocardiogram
• CT or MRI of the aorta
• Diagnostic findings on chest x-ray
  • "3" sign from dilation of aorta above and below the coarctation
  • Rib notching from collateral vessels

Best Therapy

Prehypertension

• Monitor BP annually
• Lifestyle adjustments to lower BP and CV risk and prevent progression to hypertension
• In patients with diabetes or renal disease, treat with lifestyle adjustments and antihypertensive drugs if systolic BP > 130 mm Hg or diastolic BP > 80 mm Hg

Essential Hypertension: Risk Stratification and Initial Treatment in Hypertensive Patients by Blood Pressure Stage (mm Hg)

• Prehypertension (120–139/80–89): lifestyle modification
• Stage 1 (140–159/90–99): lifestyle modification (up to 12 mo)
• Stage 2: (≥ 160/≥ 100): lifestyle modification + drug therapy

Risk Group B (≥ 1 CV Risk Factor, Not Including Diabetes; No Target-Organ Disease or Clinical Cardiovascular Disease)

• Prehypertension (120–139/80–89): lifestyle modification
• Stage 1 (140–159/90–99): lifestyle modification (up to 6 mo); consider adding drugs initially
• Stage 2: (≥ 160/≥ 100): lifestyle modification + drug therapy

Risk Group C (Target-Organ Disease or Clinical Cardiovascular Disease and/or Diabetes ± Other CV Risk Factors)

• Prehypertension (120–139/80–89)
  • Lifestyle modification
  • Drug therapy: use drugs if SBP > 130 or if DBP > 80 and patient has heart failure, chronic kidney disease, or diabetes
• Stage 1 (140–159/90–99): lifestyle modification + drug therapy
• Stage 2: (≥ 160/≥ 100): lifestyle modification + drug therapy
• Treatment goals
  • Reduce risk of cardiovascular morbidity and mortality
  • Lower BP to < 140/90; lower to < 130/80 in patients with heart failure, diabetes, renal disease; lower to < 140 mm Hg in older patients with isolated systolic hypertension
• Coexisting CVD risk factors should be addressed
• Consider low-dose aspirin once BP is controlled
• Encourage self-measurement of BP

Treatment for Patients with Essential Hypertension

• Continue lifestyle modifications
• Start with lowest recommended dose of a once-daily drug
  • Combination drug therapy is appropriate if BP > 20/10 above goal
  • Thiazide diuretic + one of the following as second agent: beta blocker; ACE inhibitor; angiotensin receptor blocker; calcium antagonist
  • If no response or significant side effects at 2–4 wk, substitute another drug from a different class
  • If partial response at 2–4 wk and drug is well tolerated, increase dose of initial drug or add agent from a different class (diuretic if not chosen initially)
  • If not at goal BP in 2–4 more wk, continue titrating doses and adding agents from other classes at regular follow-up visits
  • If patient on three drugs and goal BP not reached, review considerations for resistant hypertension; consider referral to hypertension specialist

Lifestyle Modification

• Weight reduction if overweight
• Reduce sodium intake to ≤ 100 mmol/day: 2.4 g sodium, 6 g salt
• Increase aerobic exercise: 30–45 min/day
• Limit alcohol intake to ≤ 1 oz/day
• Maintain adequate intake of potassium: 90 mmol/day
• Eat a diet rich in fruits, vegetables, and low-fat dairy products but reduced in saturated and total fat
• Discontinue tobacco use (reduce CVD risk)

Pharmacologic Therapy

• Thiazide diuretics are initial drugs of choice for most patients with uncomplicated hypertension
• Common comorbid conditions may dictate choice
• Long-acting agents preferable because compliance and consistency of BP control are superior with once-a-day dosing
• When monotherapy is unsuccessful, add second agent of a different class
• Initiate treatment with combination therapy (two drugs) if BP > 20/10 above goal
• Include a diuretic appropriate for level of renal function
• Refractory/resistant hypertension: consider the following: noncompliance, interfering substances, inappropriate regimens, office hypertension, secondary hypertension

Diuretics

• General side effects of diuretics: hyponatremia; hypokalemia; hypomagnesemia; hyperglycemia; hypercalcemia (decrease in urinary calcium excretion); hyperuricemia; increase triglycerides and cholesterol; decrease lithium secretion
• Contraindications: diuretics should be avoided in pregnancy and in patients with gout
• Hydrochlorothiazide (HCTZ)
  • First choice in uncomplicated hypertension and isolated systolic hypertension
  • Initial dose: 12.5 mg/day; range: 12.5–50 mg/day; cost/mo: $9
• Chlorthalidone
  • First choice in uncomplicated hypertension and isolated systolic hypertension
  • Initial dose: 12.5 mg/day; range: 12.5–25 mg/day; cost/mo: $9
• Indapamide
  • Use in presence of renal insufficiency
  • Initial dose: 1.25 mg/day; range: 1.25–5.0 mg/day; cost/mo: $16
• Metolazone
  • Use in presence of renal insufficiency
  • Initial dose: 1.25 mg/day; range: 1.25–5.0 mg/day; cost/mo: $66
• Furosemide
  • Alternate diuretic in renal insufficiency
  • Side effects: same as other diuretics but increases urinary calcium excretion
  • Initial dose: 20 mg/day; range: 20–320 mg/day; cost/mo: $11
• Bumetanide
  • Alternate diuretic in renal insufficiency
  • Side effects: same as other diuretics but increases urinary calcium excretion
  • Initial dose: 0.5 mg/day; range: 0.5–5.0 mg/day; cost/mo: $37
• Ethacrynic acid
  • Alternate diuretic in renal insufficiency or sulfa-based diuretic allergy
  • Only non–sulfa-based diuretic
  • Side effects: same as other diuretics but increases urinary calcium excretion
  • Initial dose: 25 mg/day; range: 25–100 mg/day
• Torsemide
  • Alternate diuretic in renal insufficiency
  • Long-acting loop diuretic
  • Side effects: same as other diuretics but increases urinary calcium excretion
  • Initial dose: 5 mg/day; range: 5–20 mg/day; cost/mo: $23
• Spironolactone (available combined with HCTZ)
  • Potassium sparing
  • Aldosterone antagonist
  • Avoid in renal insufficiency
  • Specific side effects: hyperkalemia, hyponatremia, painful gynecomastia, menstrual irregularities
  • Initial dose: 25 mg/day; range 25–100 mg/day; cost/mo: $40
• Eplerenone
  • Potassium sparing
  • Aldosterone antagonist
  • Fewer antiandrogen side effects than spironolactone
  • Avoid in renal insufficiency
  • Specific side effects: hyperkalemia, hyponatremia
  • Reduce dose by half if patient is on verapamil
  • Initial dose: 50 mg/day; range: 50–100 mg/day
• Triamterene (available combined with HCTZ)
  • Potassium sparing
  • Usually used for prevention of diuretic-induced hypokalemia
  • Specific side effects: hyperkalemia, nephrolithiasis
  • Initial dose: 50 mg/day; range: 50–150 mg/day; cost/mo: $18
• Amiloride (av

Best References

Chobanian A, et al: Hypertension 42:1206, 2003

European Society of Hypertension – European Society of Cardiology Guidelines Committee: J Hypertens 21:1011, 2003

Williams B, et al: J Hum Hypertens 18:139, 2004

September 2004

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