Hypertension

Hypertension is a common condition that affects one in every three adults in the United States. It is defined by the JNC 8 criteria as a blood pressure of ≥ 140/90 mm Hg and by the AHA/ACC guideline as ≥ 130/80 mm Hg. Hypertension can be classified as either primary (essential) or secondary. Primary hypertension accounts for approx. 95% of cases of hypertension and has no detectable cause, whereas secondary hypertension is due to a specific underlying condition. Typical underlying conditions include renal, endocrine, or vascular diseases (e.g., renal failure, primary hyperaldosteronism, or coarctation of the aorta). Clinically, hypertension is usually asymptomatic until organ damage occurs, which then commonly affects the brain, heart, kidneys, or eyes (e.g., retinopathy, myocardial infarction, stroke). Common early symptoms of hypertension include headache, dizziness, tinnitus, and chest discomfort. Hypertension is diagnosed if blood pressure is persistently elevated on two or more separate measurements. Further diagnostic measures include evaluation of possible organ damage (e.g., kidney function tests) and additional tests if an underlying disease is suspected. Treatment of primary hypertension includes lifestyle changes (e.g., diet, weight loss, exercise) and pharmacotherapy. Commonly prescribed antihypertensive medications includes ACE inhibitors, angiotensin receptor blockers, thiazide diuretics, and calcium channel blockers. To treat secondary hypertension, the underlying cause needs to be addressed. In cases of hypertensive emergency, a condition with a sudden and severe increase in blood pressure and impending end-organ damage, immediate treatment with intravenously administered antihypertensives is required to prevent serious consequences such as cerebral hemorrhage.

Primary (essential) hypertension

• Accounts for 85–95% of cases of hypertension in adults
• No specific cause; multifactorial etiology including epigenetic/genetic and environmental factors
• Non-modifiable risk factors
  • Positive family history
  • Ethnicity
  • Advanced age
• Modifiable risk factors
  • Obesity
  • Diabetes
  • Smoking; , excessive alcohol or caffeine intake
  • Diet high in sodium, low in potassium
  • Physical inactivity
  • Psychological stress

Secondary hypertension

• Accounts for 5–15% of cases of hypertension in adults.
• Caused by a specific organic condition
  • Endocrine hypertension
    • Primary hyperaldosteronism; (Conn syndrome)
    • Primary hyperparathyroidism
    • Pheochromocytoma
    • Hypercortisolism (Cushing syndrome)
    • Hyperthyroidism
    • Acromegaly
    • Congenital adrenal hyperplasia
  • Renal hypertension
    • Renovascular hypertension; (e.g., due to renal artery stenosis)
    • Polycystic kidney disease (ADPKD)
    • Renal failure (renal parenchymal hypertension)
    • Glomerulonephritis
    • Systemic lupus erythematodes
    • Renal tumors
    • Atrophic kidney
• Others
  • Coarctation of the aorta
  • Obstructive sleep apnea
  • Medication: sympathomimetic drugs, corticosteroids, NSAIDs, oral contraceptives
  • Recreational drug use: amphetamines; , cocaine; , phencyclidine
  • Isolated systolic hypertension: See “subtypes and variants” below for details.

References:^{[11][11][12][1][13][14][15][16][17]}

Hypertension is usually asymptomatic until complications of end-organ damage arise or an acute increase in blood pressure occurs (see hypertensive urgency below). Possible symptoms include:

• Headaches, esp. early morning or waking headache
• Dizziness; , tinnitus, blurred vision
• Flushed appearance
• Epistaxis
• Chest discomfort, palpitations; strong, bounding pulse on palpation
• Nervousness
• Fatigue, sleep disturbances
• Additional symptoms of an underlying disease in secondary hypertension (see “Etiology” above)
• Symptoms of end-organ damage (see “Complications” below)

Since hypertension is often asymptomatic, regular screening is necessary to prevent end-organ damage!

References:^[5][17]

White coat hypertension (white coat effect)

• Definition: arterial hypertension detected only in clinical settings or during blood pressure measurement at a physician's practice
• Etiology: anxiety experienced by the patient
• Clinical features: consistently normal blood pressure measurements and normalization of elevated blood pressure outside of a clinical setting
• Diagnostics: 24-hour blood pressure monitoring

Isolated systolic hypertension (ISH)

• Definition: increase in systolic blood pressure (≥ 140 mm Hg) with diastolic BP within normal limits (≤ 90 mm Hg)
• Etiology
  • ISH in elderly: decreased arterial elasticity and increased stiffness → decreased arterial compliance
  • ISH secondary to increased cardiac output
    • Anemia
    • Hyperthyroidism
    • Chronic aortic regurgitation
    • AV fistula
• Clinical features:
  • Often asymptomatic
  • Signs of increased pulse pressure: e.g., head pounding; , rhythmic nodding, or bobbing of the head in synchrony with heartbeats
  • Symptoms of hypertension (see “clinical features” above)
• Diagnostics: See “diagnosis of hypertension” below.
• Treatment: thiazide diuretics or dihydropyridine calcium antagonists
• Prognosis: high risk of cardiovascular events (MI, stroke, renal dysfunction)

References:^{[4][11][12][18][19][20][21][22][23][24][25][26][27][28][29][30][3][31][32]}

General approach

• Blood pressure monitoring
  • Repeated measurements on both arms → Hypertension is diagnosed if the average blood pressure of ≥ 2 readings obtained on ≥ 2 separate visits is elevated
  • Long-term measurement of blood pressure (24 hours)
  • Basic measurement approach: See “Blood pressure measurement” for details.
• Initial evaluation of newly diagnosed hypertensive patients:
  • Stratification of cardiovascular risk: fasting blood glucose, lipid profile (HDL, LDL, and triglycerides levels)
  • Evaluation of end-organ damage and underlying causes
    • Complete blood count
    • Renal function tests: serum creatinine and eGFR
    • Serum Na⁺, K⁺, and Ca²⁺
    • Urinalysis
    • TSH
    • Electrocardiogram (ECG)
• Evaluation of secondary hypertension if an underlying condition is suspected (see below)

Approach to diagnosing secondary hypertension

• General indicators of secondary hypertension
  • Young age (< 30 years) at onset of hypertension or onset of diastolic hypertension at an older age (> 55 years)
  • Abrupt onset of hypertension
  • End-organ damage that is disproportionate to the degree of hypertension
  • Recurrent hypertensive crises
  • Resistant hypertension: hypertension that is resistant to treatment with ≥ 3 antihypertensives of different classes
• Specific indicators (for details on individual diagnostic procedures, see the individual learning cards.)

Diagnostic findings		Underlying condition
Hypokalemia		Conn syndrome Renal artery stenosis
Metabolic alkalosis and ↑ aldosterone-to-renin ratio		Conn syndrome
Difference in blood pressure	In both arms	Takayasu's arteritis Aortic dissection Aortic arch syndrome Subclavian steal syndrome
	Of upper and lower limbs	Coarctation of the aorta distal to the left subclavian artery
Day time sleepiness (Epworth scale, Berlin questionnaire) Nondipping in 24-hour blood pressure monitoring		Obstructive sleep apnea
Increased 24-hour urinary metanephrines		Pheochromocytoma
↑ Serum calcium, ↑ PTH level, ↓ serum phosphates		Hyperparathyroidism
↑ Serum cortisol		Excess of glucocorticoids (e.g., Cushing syndrome)
↓TSH, ↑ free T4		Hyperthyroidism

References:^{[33][12][18][1][17][34][3][35][36][37][38]}

Nonpharmacologic measures (lifestyle changes)

Intervention		Target	Approximate systolic BP reduction in hypertensive patients
Decrease dietary sodium		Daily sodium intake < 1500 mg/day	5-6 mm Hg
Increase dietary potassium		Daily potassium intake < 3.5–5 g	4-5 mm Hg
DASH diet		Diet rich in fruits, vegetables, whole grains and low in staturated and trans fats	11 mm Hg
Weight loss		Ideal body weight	1 mm Hg per kg reduction in body weight in overweight individuals
Exercise	Aerobic	90–150 minutes per week 65–75% of maximum heart rate (e.g., brisk walk)	5–8 mm Hg
	Dynamic resistance (e.g., weight training)	50–80% of maximum strength 6 exercises with 3 sets per exercise and 10 repetitions per set 90–150 minutes per week	4 mm Hg
	Isometric resistance (e.g., hand grip exercise)	30–40% of maximum strength 4 repetitions/session, 3 sessions/week for 8–10 weeks	5 mm Hg
Decreased alcohol intake		♂: ≤ 2 drink daily ♀: ≤ 1 drink daily	4 mm Hg
Smoking cessation		Completely quit smoking	3–5 mm Hg after 1 year; 6–7 mm Hg after 3 years [39]

Non-pharmcological measures should be implemented in any patient with a systolic BP > 120 mm Hg or a diastolic BP > 80 mm Hg!

Pharmacologic treatment

Guideline	JNC 8	AHA/ACC 2017
Indication for pharmacological therapy	Adults without diabetes mellitus or chronic kidney disease Age ≥ 60 years: BP ≥ 150/90 mm Hg Age < 60 years: BP ≥ 140/90 mm Hg Adults with diabetes mellitus and/or chronic kidney disease: ≥ 140/90 mm Hg	BP ≥ 140/90 mm Hg BP ≥ 130/80 mm Hg with a 10-year-risk of cardiovascular death ≥ 10% (e.g., patients with age ≥ 65 years, diabetes mellitus, chronic kidney disease, heart failure, stable ischemic heart disease, peripheral artery disease, and/or previous stroke)
Treatment goal	BP less than threshold for initiating pharmacological therapy	Age < 65: BP < 130/80 mm Hg Age ≥ 65: systolic BP < 130 mm Hg

• Specific recommendations
  • Non-black population (including those with diabetes): initial treatment should include a thiazide-type diuretic, calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACE-I), or angiotensin receptor blocker (ARB)
  • General African American population (including those with diabetes): initial treatment should be a thiazide-type diuretic or CCB
  • In adults with chronic kidney disease, initial (or add-on) treatment should include an ACE inhibitor or ARB to improve kidney outcome.
• Initiation of treatment and follow-up
  1. Number of antihypertensives
     • Newly diagnosed hypertension with BP < 150/90 mm Hg: begin therapy with one primary antihypertensive
     • Newly diagnosed hypertension with BP > 150/90 mm Hg: begin therapy with two primary antihypertensives
  2. Reassess within one month of initiating or changing pharmacological therapy.
     • If treatment goal is not reached with one drug: Increase the dose of the initial drug or add a second drug
     • If treatment goal cannot be reached with two drugs
       • Add a third drug.
       • Evaluate for secondary causes of hypertension
     • If blood pressure is controlled: reassess after 3–6 months and annually thereafter

Overview of antihypertensive drugs

Drug class		Comments	Side effects
Primary drugs
ACE inhibitors (e.g., lisinopril, captopril, enalapril)		Preferred as a first-line drug among patients with diabetes mellitus, renal disease (nephroprotective), ischemic heart disease, and heart failure ACEi and ARBs should not be used in combination	Dry cough, angioedema ↑ K+ Teratogenic
Angiotensin-receptor blockers (ARB) (e.g., losartan, valsartan)			↑ K+ Teratogenic
Thiazide diuretics (e.g., hydrochlorothiazide, chlorthalidone)		Preferred as a first-line drug among African Americans, salt-sensitive patients, and patients with isolated systolic hypertension	↓ K+, ↓ Na ↑ Glucose and cholesterol
Calcium channel blockers	Dihydropyridines (e.g., nifedipine, amlodipine)	Preferred as a first-line drug among African Americans and patients with isolated systolic hypertension Non-dihydropyridines are not commonly used Non-dihydropyridines are contraindicated in patients with reduced ejection fraction Dihydropyridines should be avoided in patients with HFrEF	Headache Constipation Gastroesophageal reflux Pedal edema Bradycardia (non-dihydropyridines)
	Non-dihydropyridines (e.g., diltiazem, verapamil)
Secondary drugs
Beta blockers (e.g., propranolol, metoprolol, labetalol)		Should be avoided in hypertension due to aortic regurgitation Often used as a primary drug in patients with any of the following co-morbidities: Ischemic heart disease Heart failure Atrial fibrillation Thoracic aortic disease (e.g., dissection, aneurysm) Thyrotoxicosis Migraine Essential tremor Beta blockers with intrinsic sympathomimetic activity (e.g., acebutolol) should not be used as antihypertensives	Bronchoconstriction with non-cardioselective beta blockers Increased triglycerides
Aldosterone antagonists (e.g., eplerenone, spironolactone)		Used in hypertension due to primary aldosteronism Can be used as add-on therapy in resistant hypertension	↑ K+ Gynecomastia (spironolactone)
Direct renin inhibitors (e.g., aliskiren)		Should not be used in combination with ACEi or ARBs	↑ K+
Alpha-1 blockers (e.g., prazosin, doxazosin)		Used in hypertension due to pheochromocytoma May be used as an adjunct in patients with benign prostatic hypertrophy	Postural hypotension Headache
Alpha-2 agonists (e.g., clonidine)		Rarely used	CNS depression Bradycardia Rebound hypertension
Direct arteriolar vasodilators (e.g., hydralazine)		Hydralazine is a first-line treatment in pregnancy Sodium nitroprusside is used only in hypertensive emergencies	Reflex tachycardia Sodium and water retention Cyanide toxicity with long-term use of sodium nitroprusside

Pharmacologic treatment in pregnancy

• First-line treatment: methyldopa; , labetalol, hydralazine (vasodilator), and nifedipine (CCB)
• Second-line treatment: thiazides, clonidine (a2-agonist)
• Contraindicated: furosemide, ACE-I, ARB, renin inhibitors (aliskiren)

References:^{[33][11][12][1][34][40][41][42][3]}

Arterial hypertension leads to changes in the vascular endothelium, particularly of the small vessels, and can therefore affect any organ system.

Cardiovascular system

• Congestive heart failure; , dilated cardiomyopathy, hypertrophic cardiomyopathy
• Coronary artery disease and myocardial infarction
• Atrial fibrillation
• Aortic aneurysm
• Aortic dissection
• Carotid artery stenosis
• Peripheral artery disease

Brain

• Stroke , TIA
• Subcortical arteriosclerotic encephalopathy (Binswanger's disease)
• Cognitive changes such as memory loss

Kidneys

• Hypertensive nephrosclerosis
  • Pathophysiology: chronic hypertension → narrowing of afferent and efferent arterioles → reduction of glomerular blood flow → glomerular and tubular ischemia → arteriolonephrosclerosis and fibrosis (focal segmental glomerulosclerosis) → end-stage renal disease
  • Typical findings
    • Initially microalbuminuria and microhematuria
    • With disease progression, nephrosclerosis with macroalbuminuria (usually < 1 g/day) and progressive renal failure occur
    • Biopsy: sclerosis in capillary tufts, arterial hyalinosis

Eyes

• Hypertensive retinopathy
  • Arteriosclerotic and hypertension-related changes of the retinal vessels
  • Fundoscopic examination: cotton-wool spots, retinal hemorrhages (i.e., flame-shaped hemorrhages), arteriovenous nicking; , marked swelling and prominence of the optic disk with indistinct borders due to papilledema and optic atrophy (end-stage disease)

Local treatment of the eye is not possible; therefore, systemic reduction of blood pressure is critical!

Classification system according to Keith-Wagener-Barker	Findings	Symptoms
Grade I	Vessel diameter variation: arteriolar constriction and tortuosity	Usually asymptomatic
Grade II	Gunn's sign and marked constriction of vessels and sclerosis of arterioles
Grade III	Cotton-wool exudates, hard exudates, retinal hemorrhage, retinal edema, macular star formation	Decreased and/or blurred vision, headaches
Grade IV	Papilledema, optic atrophy

Hypertensive crisis (acute severe hypertension)

• Definition: acute increase in blood pressure > 180/120 mm Hg

Classification

• Hypertensive urgency: acute increase in blood pressure without symptoms and with no signs of organ damage
• Hypertensive emergency: severely increased BP with signs of end-organ damage (mainly in the cardiovascular, central nervous, and renal system)
  • Cardiac presentation (chest pain, dyspnea)
    • Pulmonary edema
    • Myocardial infarction
    • Congestive heart failure and dilated cardiomyopathy
    • Aortic dissection
  • Neurologic presentation (headache, confusion, blurry vision)
    • Hypertensive encephalopathy
    • Ischemic or hemorrhagic stroke
    • Malignant hypertension: severe hypertension that occurs with retinopathy (flame hemorrhages, papilledema)
  • Renal presentation: azotemia and/or oliguria due to acute renal failure

Diagnostics ^[43]

• Evaluation for end-organ damage
  • CBC
  • Serum electrolytes, BUN, creatinine
  • Cardiac markers (e.g., troponin)
  • Urinalysis
  • ECG
  • Fundoscopy
• Additional evaluation
  • Women of child-bearing age: perform a pregnancy test
  • Patients with suspected drug overdose: toxicology screen
  • Patients with chest pain and/or dyspnea: perform a chest x-ray to screen for aortic dissection
    • If chest pain is highly suggestive of aortic dissection (e.g., abrupt onset with severe intensity and ripping/tearing quality): directly perform a CT (see also “Diagnostics” in aortic dissection)
  • If clinical features suggest pulmonary edema: perform echocardiography (see also “Diagnostics” in congestive heart failure)
  • If neurological symptoms are present: perform a cranial CT

Treatment

Hypertensive urgency

• Reinstitute or increase dosage of oral antihypertensive therapy

Hypertensive emergency

• ICU admission and immediate initiation of intravenous antihypertensive therapy (see table below)

Rate of blood pressure reduction

• General goal
  • Reduce BP by max. 25% within the first hour; to prevent coronary insufficiency and to ensure adequate cerebral perfusion!
  • Reduce BP to 160/100–110 mm Hg over next 2–6 hours
  • Reduce BP to normal over 24–48 hours
• Special cases
  • Severe pre-eclampsia/eclampsia or pheochromocytoma: systolic BP < 140 mm Hg within the first hour
  • Aortic dissection: systolic BP < 120 mm Hg within 20 minutes
  • Acute intracerebral hemorrhage:
  • Acute ischemic stroke
    • If the patient qualifies for thrombolytic therapy
      • Systolic BP < 185 mm Hg and diastolic BP < 110 mm Hg before thrombolysis
      • BP < 180/105 mm Hg for the first 24 hours after thrombolysis
    • If the patient does not qualify for thrombolytic therapy
      • BP ≤ 220/110 mm Hg: DO NOT lower BP during the first 48–72 hours
      • BP > 220/110 mm Hg: lower BP by 15% in the first 24 hours

Choice of intravenous antihypertensive drug

• The selection of an intravenous antihypertensive and its dosing is based on the desired rate of BP decrease, the presence or absence of certain co-morbidities, and the drug's pharmacodynamic properties

Associated co-morbidity	Preferred intravenous antihypertensive	Comments
Aortic dissection	First-line: esmolol or labetalol Second-line (as an adjunct): nitroprusside or nicardipine	Beta blockers should precede administration of vasodilators (e.g., nicardipine, nitroprusside)
Pulmonary edema	Clevidipine Nitroprusside Nitroglycerin	Nitroglycerin is contraindicated if the patient had received a phosphodiesterase inhibitor (e.g., sildenafil, tadafil) within the past 48 hours Beta blockers are contraindicated if the patient has pulmonary edema, bradycardia, 2nd/3rd degree heart block, or cardiogenic shock Enaliprat is contraindicated in acute coronary syndrome
Acute coronary syndrome	Nitroglycerin Esmolol Labetalol Nicardipine
Acute renal failure	Clevidipine Nicardipine Fenoldopam	Nitroprusside and esmolol should be avoided
Catecholamine excess	Clevidipine Nicardipine Phentolamine (off-label)	Beta blockers should be avoided
Acute ischemic stroke	Labetalol Clevidipine Nicardipine	Fenoldopam, nitroprusside, and nitroglycerin should be avoided
Acute intracerebral hemorrhage
Eclampsia/severe pre-eclampsia	Hydralazine (off-label) Labetalol Nicardipine	Nitroprusside and enaliprat is contraindicated
Intravenous antihypertensives
Calcium channel blocker: nicardipine, clevidipine Nitric-oxide dependent vasodilators: sodium nitroprusside, nitroglycerin Direct arterial vasodilators: hydralazine Anti-adrenergic drugs Selective beta-1 blocker: esmolol Non-selective beta blocker with alpha-1 antagonism: labetalol Non-selective alpha blocker: phentolamine D1 agonist: fenoldopam ACE inhibitor: enaliprat

The most commonly used drugs to treat hypertensive emergency are nitroprusside, labetalol, and nicardipine.

Prognosis

• If left untreated, hypertensive emergencies are associated with a 1-year death rate > 80% and a median survival of 10–11 months ^[3]

References:^{[19][20][21][22][23][24][25][26][27][28][29][30][3][31][32]}

References:^{[11][12][1][17][44][45][46][47]}

We list the most important complications. The selection is not exhaustive.