Hypertension

Hypertension is a common condition that affects one in every three adults in the United States. The AHA/ACC guidelines define it as a blood pressure of ≥ 130/80 mm Hg and by JNC 8 criteria as ≥ 140/90 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 include ACE inhibitors, angiotensin receptor blockers, thiazide diuretics, and calcium channel blockers. Management of pediatric patients and pregnant women differs from that of nonpregnant adults because some of these drugs are contraindicated in these patient groups. To treat secondary hypertension, the underlying cause needs to be addressed. In cases of hypertensive emergency, a condition in which there is a sudden and severe increase in blood pressure and impending end-organ damage, immediate treatment with intravenous antihypertensives is required to prevent serious consequences such as cerebral hemorrhage.

• AHA/ACC 2017 definition: persistent systolic blood pressure of ≥ 130 mm Hg and/or diastolic blood pressure ≥ 80 mm Hg
• JNC 8 definition: persistent systolic blood pressure of ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg
• Definition of hypertension in children < 13 years: blood pressure ≥ 95^th percentile to < 95^th percentile + 12 mm Hg OR systolic blood pressure ≥ 130 mm Hg and/or diastolic blood pressure ≥ 80 mm Hg (whichever is lower) ^[1][2]

References:^[3][4][5]

• Prevalence
  • One in three adults in the US is affected.
  • Prevalence increases with age (∼ 65% among those ≥ 60 years of age).
  • African Americans are more commonly affected than Asian American or white individuals.
  • 60–75% of obese and overweight patients are affected.
• Sex: ♂ > ♀ below age of 45; ; the sex ratio is almost balanced at > 45 years of age (i.e., after menopause)
• Most common risk factor for cardiovascular disease

References:^{[6][7][3][8][9][10][11][12]}

Epidemiological data refers to the US, unless otherwise specified.

Primary (essential) hypertension

• No specific cause; multifactorial etiology including epigenetic/genetic and environmental factors
• Accounts for 85–95% of cases of hypertension in adults
• Accounts for 15–20% of cases of hypertension in children < 12 years of age
• Age at onset: 25–55 years (prevalence is increasing in adolescents)

Risk factors

• Nonmodifiable 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

• Caused by an identifiable underlying condition
• Accounts for 5–15% of cases of hypertension in adults
• Accounts for 70–85% of cases of hypertension in children < 12 years of age
• Age at onset < 25 years or > 55 years

Causes

• Endocrine hypertension
  • Primary hyperaldosteronism (Conn syndrome): most common cause of secondary hypertension in adults
  • Hypercortisolism (Cushing syndrome)
  • Hyperthyroidism
  • Pheochromocytoma
  • Primary hyperparathyroidism
  • 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 erythematosus
  • Renal tumors
• 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.

RECENT can help you remember the causes of secondary hypertension: R = Renal (e.g., renal artery stenosis, glomerulonephritis), E = Endocrine (e.g., Cushing syndrome, hyperthyroidism, Conn syndrome), C = Coarctation of aorta, E = Estrogen (oral contraceptives), N = Neurologic (raised intracranial pressure, psychostimulants use), T = Treatment (e.g., glucocorticoids, NSAIDs).

References:^{[13][13][14][3][15][16][17][18][19]}

• Hypertension is usually asymptomatic until:
  • Complications of end-organ damage arise (see “Complications” below)
  • Or an acute increase in blood pressure occurs (see hypertensive crisis below)
• Secondary hypertension usually manifests with symptoms of the underlying disease (e.g., abdominal bruit in renovascular disease, edema in CKD, daytime sleepiness in obstructive sleep apnea).
• Nonspecific symptoms of hypertension
  • 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

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

References:^[7][19]

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:^{[6][13][14][20][21][22][23][24][25][26][27][28][29][30][31][32][5][33][34][1][35]}

General approach

Blood pressure monitoring

• Repeated measurements on both arms; : Hypertension is diagnosed if the average blood pressure on at least two readings obtained on at least two separate visits is elevated.
• Long-term measurement of blood pressure (24 hours)
• See “Blood pressure measurement” for the basic approach to measurement.

AHA/ACC 2017 BP categories
BP category	Systolic blood pressure (mm Hg)		Diastolic blood pressure (mm Hg)
Normal blood pressure	< 120	and	< 80
Elevated	120–129	and	< 80
Stage 1 hypertension	130–139	or	80–89
Stage 2 hypertension	≥ 140	or	≥ 90

JNC 8 BP categories
BP category	Systolic blood pressure (mm Hg)		Diastolic blood pressure (mm Hg)
Normal blood pressure	< 120	and	< 80
Prehypertension	120–139	or	80–89
Stage 1 hypertension	140–159	or	90–99
Stage 2 hypertension	≥ 160	or	≥ 100

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)

Approach to diagnosing secondary hypertension

• General indicators of secondary hypertension
  • Young age (< 30 years) at onset of hypertension
    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 at least three antihypertensives of different classes including a diuretic
• Specific indicators (For details regarding 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 arteritis Aortic dissection Aortic arch syndrome Subclavian steal syndrome
	Of upper and lower limbs	Coarctation of the aorta distal to the left subclavian artery
Daytime 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

Screening for hypertension (USPSTF recommendations) ^[36]

• Individuals 18–39 years of age with normal blood pressure (< 130/85 mm Hg) and without other risk factors: Screen every 3–5 years.
• Individuals > 40 years of age or who are at increased risk for high blood pressure : Screen every year.

References:^{[37][14][20][3][19][38][5][39][40][41][42]}

Nonpharmacological measures (lifestyle changes for managing hypertension)

Intervention (in order of effectiveness)		Target	Approximate systolic BP reduction in hypertensive patients
Weight loss		Ideal body weight	1 mm Hg per kg reduction in body weight in overweight individuals
DASH diet		Diet rich in fruits, vegetables, and whole grains; low in saturated and trans fats	11 mm Hg
Decrease dietary sodium		Daily sodium intake < 1500 mg/day	5–6 mm Hg
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
Increase dietary potassium		Daily potassium intake 3.5–5 g	4–5 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 [43]

Nonpharmacological measures should be pursued in any patient with a systolic BP > 120 mm Hg or a diastolic BP > 80 mm Hg!
Patients should be taught to measure their own blood pressure to allow for long-term monitoring and assessment of treatment efficiency!

Pharmacologic treatment

Guideline	Indication for pharmacological therapy	Treatment goal
AHA/ACC 2017	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)	Age < 65: BP < 130/80 mm Hg Age ≥ 65: systolic BP < 130 mm Hg For patients with significant comorbidities or limited life expectancy, the BP goal is determined based on clinical judgment and the patient's preference.
JNC 8	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 less than threshold for initiating pharmacological therapy

• Initiation of treatment
  • 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.
  • Choice of antihypertensive drug
    • Non-African American patients (including individuals with diabetes): thiazide-type diuretic, calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACE-I), or angiotensin receptor blocker (ARB)
    • African American patients (including individuals with diabetes): 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.
• Follow-up
  • Reassess within one month of initiating or changing pharmacological therapy.
    • If the treatment goal is not reached with one drug, increase the dose of the initial drug or add a second drug.
    • If the 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
First-line drugs
ACE inhibitors (e.g., lisinopril, captopril, enalapril)		Preferred as a first-line drug in 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 in 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 Nondihydropyridines are not commonly used. Nondihydropyridines are contraindicated in patients with reduced ejection fraction.	Headache Constipation Gastroesophageal reflux Pedal edema Bradycardia (nondihydropyridines)
	Nondihydropyridines (e.g., diltiazem, verapamil)
Second-line 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 comorbidities: Ischemic heart disease Heart failure Atrial fibrillation Thoracic aortic disease (e.g., dissection, aneurysm) Thyrotoxicosis Migraine Essential tremor	Bronchoconstriction with noncardioselective beta blockers Increased triglycerides
Loop diuretics (e.g. furosemide, torsemide)		Used in symptomatic heart failure and CKD (if GFR < 30 mL/min)	↓ K+, ↓ Na ↑ Glucose ↑ Cholesterol
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

Treatment of hypertension in pregnancy

• First-line treatment: methyldopa; , labetalol, hydralazine (vasodilator), and nifedipine (CCB)
• Second-line treatment: thiazides, clonidine (alpha-2 agonist)
• Contraindicated: furosemide, ACE-I, ARB, renin inhibitors (aliskiren)
• For details, see treatment of gestational hypertension.

Treatment of hypertension in children

• Treat the underlying cause (e.g., surgical correction of coarctation of the aorta)
• Lifestyle changes in children with elevated BP (see nonpharmacologic measures in the treatment section below)
• Pharmacologic management is indicated for symptomatic hypertension, diabetes mellitus, CKD, and end-organ damage, as well as if there is an insufficient response or no response to lifestyle changes.
  • Goal: BP < 90^th percentile (BP < 50^th percentile in children with DM or CKD)
  • Drugs: ACE inhibitor, ARB, or calcium channel blocker
    • In children with CKD or diabetes mellitus, ACE inhibitors or ARBs are preferable.
• Hypertensive emergency: labetalol, nicardipine, or sodium nitroprusside

Beta blockers are not recommended for initial treatment of hypertension in children due to their metabolic side effects (e.g., impaired glucose tolerance) and the fact that they exacerbate asthma!

References:^{[37][13][14][3][15][38][44][45][46][5][1][2][47]}

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
• Cognitive changes such as memory loss

Kidneys

• Hypertensive nephrosclerosis
  • Pathophysiology: chronic hypertension → narrowing of afferent arterioles 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 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 systems)
  • 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: symptom complex of severe hypertension, headache, vomiting, confusion, seizure, blurry vision, and papilledema
    • 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

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 ^[48]
    • Systolic BP > 150 mm Hg and ≤ 220 mm Hg and no contraindications for acute BP treatment: systolic BP < 140 mm Hg
    • Systolic BP > 220 mm Hg: Consider aggressive lowering of systolic BP with IV infusion under frequent monitoring (every 5 minutes).
  • Acute ischemic stroke ^[49]
    • 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 ≤ 220/120 mm Hg: DO NOT lower BP during the first 48–72 hours
      • BP > 220/120 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 comorbidities, and the drug's pharmacodynamic properties.

Associated comorbidity	Preferred intravenous antihypertensive	Comments
Aortic dissection	First-line: esmolol or labetalol Second-line (as an adjunct): nitroprusside or nicardipine	Beta blockers should be administered before 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.
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 Labetalol Nicardipine	Nitroprusside 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 D1 agonist: fenoldopam

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

References:^{[13][14][21][22][3][19][23][24][25][26][27][28][29][30][50][51][52][48][31][32][5][33][34][53][49]}

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