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    Apr.30.2024

    Hypertension

    Synopsis

    Key Points

    • Hypertension is defined as systolic blood pressure 130 mm Hg or higher and diastolic blood pressure 80 mm Hg or higher in adults r1
    • Most patients with hypertension have essential hypertension, for which there is no identifiable cause. In 10% of patientsr1, hypertension has an identifiable secondary cause, most commonly renal artery stenosis, renal parenchymal disease, endocrine abnormalities, adverse effect of a drug, or coarctation of the aorta r2
    • Initial office evaluation is focused on identification of hypertensive end-organ damage (eg, eyes, heart, kidneys) and identification of other cardiovascular risk factors. Focus search for secondary causes by clinical suspicion
    • 2017 American College of Cardiology/American Heart Association guidelines for prevention, detection, evaluation, and management of high blood pressure in adults and 2019 American College of Cardiology/American Heart Association guidelines on primary prevention of cardiovascular disease recommend a blood pressure target of lower than 130/80 mm Hg for most patients r1r3
    • For Black patients, ACE inhibitors and angiotensin receptor blockers are less effective than thiazide diuretics and calcium channel blockers for lowering blood pressure. For patients of other ethnic groups, initial drug treatment should include a thiazide diuretic, a calcium channel blocker, an ACE inhibitor, or an angiotensin receptor blocker
    • Strategies for managing blood pressure inadequately controlled on initial medication include dose titration before addition of another drug or adding another drug without maximizing dosage of the first. Frequently readdress lifestyle factors that may affect blood pressure

    Urgent Action

    • Hypertensive emergency is an acutely elevated blood pressure, usually more than 120 mm Hg diastolic, accompanied by symptoms or objective signs of acute end-organ dysfunction or damage (eg, hypertensive encephalopathy, stroke, acute coronary syndromes, pulmonary edema, aortic dissection, acute kidney injury) r4
      • Quickly manage hypertensive emergencies with IV administration of carefully selected antihypertensive drugs to reduce blood pressure by no more than 25% over the first hour in most cases
      • Sodium nitroprusside, nicardipine (IV), and/or labetalol (IV) are appropriate for most hypertensive emergencies

    Pitfalls c1

    • To be considered a hypertensive emergency, there must be evidence of end-organ damage; mild headache, epistaxis, and vague, non-anatomically suggestive symptoms are not diagnostic of a hypertensive emergency
    • Treatment of hypertensive emergency may be complex and must be guided by careful, individualized consideration of the type of acute end-organ dysfunction or damage. Goal blood pressure reduction may need to be modified for stroke, especially if thrombolytics are administered
    • If there is no evidence of acute end-organ damage with a severely elevated blood pressure, the patient is considered to have hypertensive urgency (also known as severe asymptomatic hypertension). Acute reduction of blood pressure is not advised owing to potential adverse effects and lack of clinical benefit r5
    • Confirm isolated high blood pressure measurements on more than 1 encounter before treatment is started unless the initial blood pressure is very high
    • White coat hypertension may cause diagnostic confusion; ambulatory 24-hour monitoring can clarify the issue
    • Medication nonadherence is the most common cause of uncontrolled blood pressure

    Terminology

    Clinical Clarification

    • Hypertension is defined as systolic blood pressure 130 mm Hg or higher and diastolic blood pressure 80 mm Hg or higher in adults r1
      • Blood pressure reference range: systolic lower than 120 mm Hg and diastolic lower than 80 mm Hg
      • Elevated blood pressure: systolic 120 to 129 mm Hg and diastolic lower than 80 mm Hg
    • Isolated diastolic hypertension: systolic lower than 130 mm Hg and diastolic 80 mm Hg or higher r6

    Classification

    • Etiology
      • Essential hypertension: not attributed to underlying, identifiable cause
      • Secondary hypertension: attributed to underlying, identifiable cause (10% of patients)
    • Stages r1
      • Stage 1 hypertension: systolic 130 to 139 mm Hg or diastolic 80 to 89 mm Hg
      • Stage 2 hypertension: systolic 140 mm Hg or higher or diastolic 90 mm Hg or higher
    • Other terminology
      • Resistant hypertension r2r7
        • Blood pressure above goal despite adherence to a combination of at least 3 optimally dosed antihypertensive medications with different mechanisms of action
        • Blood pressure that achieves target values on 4 or more antihypertensive medications
      • Hypertensive urgency: acute rise in blood pressure (diastolic higher than 120 mm Hg) without evidence of acute end-organ dysfunction r8r9
        • American College of Emergency Physicians uses the synonymous term asymptomatic markedly elevated blood pressurer5
      • Hypertensive emergency: acute rise in blood pressure (diastolic higher than 120 mm Hg) accompanied by objective findings of acute end-organ dysfunction (usually of the heart, kidneys, or brain). The blood pressure threshold at which dysfunction occurs may be markedly different in individual patients r4
        • Terms hypertensive crisis and malignant hypertension are no longer recommended r8
        • Malignant hypertension describes a hypertensive emergency characterized by severe hypertension and systemic microcirculatory damage as evidenced by advanced hypertensive retinopathy; an alternative term for this is acute hypertensive microangiopathyr9
      • White coat hypertension: blood pressure that is significantly higher when measured in the medical office than when measured at home or via ambulatory blood pressure monitor in patient’s usual environment r10
        • Risk factor for development of sustained essential hypertension
        • Some evidence that white coat hypertension contributes to cardiovascular mortality (to a lesser extent than essential hypertension) r10
          • Exception: if office reading is high but both home blood pressure measurement and ambulatory 24-hour measurement are within reference range, then cardiovascular risk is not higher than that of a normotensive person r11
      • Masked hypertension: blood pressure is in hypertensive range out of office but not when measured in office r12
        • Present in 15% to 30% of the general population who are normotensive during office blood pressure measurement
        • Nocturnal hypertension is a form particularly prevalent in Black patients
        • Associated with an increased risk for cardiovascular disease similar to that for sustained hypertension present in office environment
      • Isolated diastolic hypertension r6
        • May be more common in younger people
        • Not associated with increased risk of atherosclerotic cardiovascular disease or cardiovascular mortality

    Diagnosis

    Clinical Presentation

    History

    • Usually asymptomatic c2
    • Mild headache, dizziness, or epistaxis is sometimes reported with elevated blood pressure, but they do not suggest end-organ dysfunction if physical examination findings are normal c3c4c5c6
    • Symptoms that suggest acute end-organ dysfunction caused by hypertensive emergency include:
      • Dyspnea c7
      • Chest pain c8
      • Severe headache c9
      • Blurry vision c10
      • Nausea c11c12
      • Vomiting
      • Confusion c13
      • Seizures c14
      • Somnolence c15
      • Focal neurologic symptoms c16
    • Symptoms that raise suspicion of secondary hypertension include:
      • Fatigue (suggests kidney disease, hypercortisolism, thyroid disorders, or obstructive sleep apnea) c17
      • Polyuria, oliguria, edema, dysuria, and flank pain (suggest kidney disease) c18c19c20c21c22
      • Dyspnea caused by pulmonary edema (suggests renal artery stenosis) c23
      • Headache, flushing, palpitations, syncope or near syncope, visual disturbances, and excessive perspiration (suggest pheochromocytoma) c24c25c26c27c28c29c30c31
      • Changes in body habitus such as weight gain with truncal obesity, buffalo hump, moon facies, or purple striae (suggest hypercortisolism) c32c33c34c35
      • Cold extremities and lower extremity claudication (suggest coarctation of the aorta) c36c37
    • Patient may report use of drugs that can elevate blood pressure, including:
      • Oral contraceptives c38
      • NSAIDs and cyclooxygenase-2 inhibitors c39c40
      • Antidepressants c41
      • Steroids c42
      • Decongestants c43c44
      • Cyclosporine c45
      • Tacrolimus c46
      • Antiretrovirals c47
      • Therapeutic stimulants c48
      • Intoxicants with stimulant properties c49c50
    • Sudden discontinuation of a centrally acting α₂-adrenergic agonist drug (eg, clonidine, methyldopa) may result in abrupt rise in blood pressure c51c52
    • Antihypertensive medication nonadherence is a common cause of acutely increased blood pressures above baseline c53

    Physical examination

    • Examination findings may be normal except for blood pressure c54
    • Measure blood pressure with patient at rest; repeat later during same encounter if elevated
    • Increased body weight and obesity are common r13
    • Examine for signs of hypertensive end-organ disease
      • Hypertensive retinopathy classically categorized by fundal examination findingsr15 but not necessarily clinically useful r14
        • Grade 0: normal examination findings c55
        • Grade 1: minimal arterial narrowing c56
        • Grade 2: obvious arterial narrowing with focal irregularities c57
        • Grade 3: arterial narrowing with retinal hemorrhages, exudate, or both c58c59c60
        • Grade 4: grade 3 findings plus disk swelling c61c62c63c64
        • Hard exudates are a common late finding c65
      • Signs of acute retinal injury (a hypertensive emergency)
        • Focal intraretinal periarteriolar transudates c66
        • Focal retinal pigment epithelial lesions c67
        • Macular and optic disk edema c68c69
        • Cotton-wool spots c70
      • Carotid artery bruits c71
      • If chest or back pain is present, pulse deficits and discrepancies in blood pressure between limbs (suggest aortic dissection) r16c72c73
      • Rales or decreased breath sounds (suggest congestive heart failure with pulmonary edema) c74c75
      • Cardiac gallops or murmurs (suggest atherosclerotic heart disease or congestive heart failure) c76c77
      • Diastolic decrescendo murmur of aortic regurgitation (suggests type A aortic dissection but is present in only 44% of patients) r16c78
      • Dependent edema (suggests pulmonary edema or renal dysfunction) c79
      • Altered mental status with nonfocal neurologic findings (suggests hypertensive encephalopathy) c80
      • Anatomically suggestive focal deficits on neurologic examination (suggest ischemic or hemorrhagic stroke) c81
    • Signs of possible secondary cause of hypertension
      • If there is any suspicion of coarctation of the aorta as the cause of secondary hypertension, measure blood pressure in both arms and 1 thigh to look for systolic pressure differential
        • Brachial pressure differential between right and left arms of more than 30 mm Hg (suggests that compromised blood flow occurs before the left subclavian artery) r17c82
        • Upper extremity systolic blood pressure 20 mm Hg higher than that of the lower extremity (suggests significant coarctation) r18
      • Abdominal bruit that is usually high pitched and holosystolic (suggests renal artery stenosis) c83
      • Truncal obesity, buffalo hump, moon facies, or purple striae (suggests hypercortisolism) c84c85c86c87

    Causes and Risk Factors

    Causes

    • Essential hypertension is considered idiopathic c88
    • Secondary hypertension occurs as a result of the following: r19
      • Hormonal and organ system abnormalities
        • Chronic kidney disease c89
        • Renovascular disease (renal artery stenosis) c90
        • Hyperaldosteronism c91
        • Obstructive sleep apnea c92
        • Renal parenchymal disease c93
        • Cushing disease and Cushing syndrome c94c95
        • Hyperthyroidism and untreated hypothyroidism c96c97
        • Coarctation of the aorta c98
        • Pheochromocytoma c99
      • Drug-induced hypertension
        • Oral contraceptives c100
        • Decongestants c101
        • Antidepressants (ie, tricyclics, selective serotonin reuptake inhibitors) c102c103c104
        • Steroids c105
        • NSAIDs c106
        • Cyclosporine c107
        • Tacrolimus c108
        • Antiretrovirals r20c109
        • Tyramine reaction with use of MAOIs c110
        • Serotonin syndrome c111
        • Anti-cancer drugs r21
          • VEGF signaling pathway inhibitors
          • MAPK inhibitors
          • BTK inhibitors
          • RET-kinase inhibitors
          • Certain PARP inhibitors
          • mTOR inhibitors
      • Intoxicant-induced hypertension
        • Cocaine c112
        • Amphetamines c113
        • Methamphetamines c114
        • Other drugs with sympathomimetic effects c115
        • Phencyclidine c116
      • Abrupt discontinuation of sympatholytic drug (eg, clonidine) may precipitate hypertension c117

    Risk factors and/or associations

    Age
    • Prevalence of essential hypertension increases with age c118c119c120c121c122
    • In the United States, 4.9% of children and adolescents aged 8 to 17 years had hypertension as defined by 2017 guidelines from the American Academy of Pediatrics (data from National Health and Nutrition Examination Survey 2015-2016) r22
    • In the United States, prevalence of hypertension was 28.2% among those aged 20 to 44 years, 60.1% among those aged 45 to 64 years, and 77.0% among those aged 65 years or older (data from National Health and Nutrition Examination Survey 2015-2018) r22c123c124
    Sex r23
    • Hypertension is more common in males than females up to age 64 years; after age 65 years, the percentage of females with hypertension is higher than that for males r22c125c126
    • In the United States, lifetime risk of hypertension (as defined by the 2017 guidelines) for those between ages 20 and 85 years was 83.8% for White male patients and 69.3% for White female patients; rates did not significantly differ among Black male patients and Black female patients r22c127
    Genetics
    • Increased risk of essential hypertension with family history c128
    Ethnicity/race
    • Highest prevalence of essential hypertension is in non-Hispanic Black population r22c129c130c131c132
    Other risk factors/associations
    • Risk factors for essential hypertension
      • Overweight and obesity r13c133
        • Increase in body fat is the most common cause of hypertension r24
          • Contributing mechanisms include unhealthful nutrition, physical inactivity, insulin resistance, increased sympathetic nervous system activity, renal dysfunction, cardiovascular dysfunction, increased pancreatic insulin secretion, sleep apnea, and psychosocial stress
        • More than 70% of patients with hypertension have overweight or obesity r24
      • Chronic kidney disease c134
      • High-sodium diet c135
      • Smoking c136
      • Excess alcohol intake r19r25c137
      • White coat hypertension r11c138
      • Psychosocial stress c139
      • Sedentary lifestyle c140
      • Poor sleep patterns (self-reported short sleep duration, difficulty sleeping, excessive daytime sleepiness, and sleep apnea symptoms) r26
    • Exposure to ambient air pollution is associated with elevated blood pressure in children and adolescents r27c141c142

    Diagnostic Procedures

    Primary diagnostic tools

    • Confirm hypertension; document elevated blood pressure on at least 2 encounters using sphygmomanometry or automated blood pressure measurement r28c143
      • Proper technique when taking blood pressure is important; proper cuff size must be used, because a cuff that is too small can cause a spuriously high reading
        • Seat patient with feet flat on floor, legs uncrossed, and back supported; allow patient to sit for 3 to 5 minutes without talking or moving around before recording blood pressure r12
      • Do not use blood pressure readings taken when patients are in pain or acutely ill as support for a diagnosis, because they may be spuriously high
      • Home blood pressure self-monitoring or ambulatory blood pressure monitoring add additional data when white coat hypertension or masked hypertension is a consideration or office measurements are not consistent r12r29r30
      • US Preventive Services Task Forcer31 and guidelines from Canada,r32 the United Kingdom,r15 and Europer33r30 recommend routine ambulatory blood pressure monitoring to confirm hypertension diagnosis after elevated office readings
    • History, physical examination (including ophthalmoscopy), ECG, and laboratory testing r28c144
      • Outpatient evaluation of hypertension: examination, ECG, and routine laboratory tests to assess for chronic end-organ damage and to identify modifiable cardiovascular risk factors c145
      • With acute elevation in blood pressure suggesting hypertensive urgency or emergency
        • Assess for symptoms of acute end-organ damage (eg, brain, heart, kidneys, eyes)
          • For asymptomatic patients with acute rise in blood pressure (ie, hypertensive urgency)
            • Obtain creatinine level, but there is no evidence to guide other testing recommendations in hypertensive urgency r5c146
          • For symptomatic patients with acute rise in blood pressure (ie, hypertensive emergency)
            • Obtain broader laboratory testing, imaging, and ECG based on apparent end-organ damage r4
      • Evaluate for secondary causes of hypertension (with early specialist consultation to direct appropriate workup) in the following settings:
        • Any symptoms or signs suggestive of a secondary cause
        • Abrupt onset of hypertension
        • Blood pressure resistant to appropriate treatment

    Laboratory

    • Routine tests at the time of hypertension diagnosis to assess for chronic end-organ damage and modifiable cardiovascular risk factors r28
      • Fasting blood glucose level and hemoglobin A1Cr15c147c148
      • Serum sodium, potassium, and calcium levels c149c150c151
      • Serum BUN and creatinine levels (with estimated or measured GFR) c152c153
      • Fasting lipid profile c154
      • Hematocrit level c155
      • Urinalysis c156
      • Measurement of urinary albumin excretion level or albumin to creatinine ratio is considered an optional baseline test unless diabetes or kidney disease is present c157c158
    • During hypertensive urgency (ie, asymptomatic patient)
      • Serum creatinine level may be useful to identify patients with occult renal dysfunction but cannot differentiate acute from chronic abnormality r5c159
    • During hypertensive emergency, evaluate for acute end-organ dysfunction r4
      • CBC c160
        • Schistocytes on manual differential suggest microangiopathic hemolytic anemia caused by renal arteriolar damage c161
      • Serum BUN and creatinine levels c162c163
        • Increased levels suggest hypertensive nephropathy
      • Urinalysis (if renal dysfunction is suspected) c164
        • Proteinuria and casts suggest hypertensive nephropathy
      • Cardiac troponin level (if chest pain or dyspnea is present) c165

    Imaging

    • Imaging is not routinely recommended for adult patients with newly diagnosed hypertension unless there is clinical suspicion of secondary hypertension r28r34
      • Targeted imaging studies for suspected underlying causes are best selected with specialist consultation
    • Obtain appropriate imaging in a hypertensive emergency based on suspected end-organ dysfunction r4r9
      • Head CT or MRI scan if hypertensive encephalopathy or stroke is present c166c167
      • Chest radiography if dyspnea is present or there is concern for acute coronary syndrome c168
      • Chest radiography and CT angiography if aortic dissection is suspected c169c170
      • Renal ultrasonography to assess for postrenal obstruction and kidney size r9

    Functional testing

    • ECG
      • Recommended for adults at baseline; may identify, with low sensitivity, evidence of chronic cardiac end-organ dysfunction (eg, left ventricular hypertrophy) r15r28c171
      • Indicated with complaints of dyspnea or chest pain in the setting of hypertensive emergency c172
    • Echocardiography r32
      • Not routinely recommended c173
      • May be useful in selected cases for assessment of left ventricular hypertrophy to help define future risk of cardiovascular events c174
      • Echocardiographic assessment of left ventricular mass, as well as of systolic and diastolic left ventricular function, is recommended for patients with hypertension who are suspected of having left ventricular dysfunction or coronary artery disease
      • Can be used in patients with hypertension and evidence of heart failure for assessment of left ventricular ejection fraction c175

    Differential Diagnosis

    • Secondary hypertension occurs as a result of specific hormone and organ system abnormalities or drug use (therapeutic or recreational); suspect based on suggestive symptoms, signs, and results of baseline screening tests r19
      • Renal causes
        • Chronic kidney disease c176c177d1
          • Structural or functional kidney damage that is present for more than 3 months, with implications for health, irrespective of cause
          • Most common in middle-aged and geriatric populations and in patients with diabetes c178c179
          • Symptoms of fatigue and edema are suggestive
          • Baseline laboratory tests show elevated BUN and/or creatinine levels
          • Obtain renal ultrasonography; may show small, hypoechoic kidneys
        • Renal parenchymal disease c180c181
          • Common cause of secondary hypertension in preadolescent children but less common in adults c182c183c184
          • Usually caused by congenital abnormalities, glomerulonephritis, or reflux nephropathy
          • Baseline laboratory testing may show elevated BUN and creatinine levels; urinalysis results are typically positive for proteinuria, hematuria, and RBC casts
          • Renal ultrasonography is usually first imaging test
          • Biopsy is often required unless there is good evidence of prior bacterial infection and postinfectious glomerulonephritis is suspected
      • Renovascular disease (renal artery stenosis) r19c185c186
        • Characterized by reduced arterial blood flow to 1 or both kidneys usually secondary to atherosclerosis or fibromuscular dysplasia of the renal arteries
          • Less common causes include renal artery aneurysm, systemic vasculitis, arteriovenous fistula, aortic coarctation, and extrinsic compression of the renal artery
        • Occurs in about 5% of patients diagnosed with hypertension
        • More prevalent among those aged 65 years or older
        • Atherosclerotic renovascular disease (90%)
          • Most common in patients aged 50 years or older
          • Suspect in patients with widespread atherosclerosis (especially peripheral arterial disease), diabetes, smoking history, recurrent pulmonary edema, and an abdominal bruit
        • Fibromuscular dysplasia (9%)
          • Most commonly in females younger than 50 years
          • Consider in patients with onset of hypertension at younger than 30 years, accelerated and/or malignant hypertension, drug resistant hypertension, unilateral small kidney without causative urologic abnormality, an abdominal bruit in the absence of atherosclerotic risk factors, renal artery dissection, or fibromuscular dysplasia in another artery
        • If suspected, confirm with imaging studies
          • Renal artery Doppler ultrasonography, catheter-based angiographic imaging, CT angiography, or magnetic resonance angiography is diagnostic, but the preferred imaging modality is controversial and should be selected in consultation with a nephrologist
            • Gold standard for diagnosis is renal angiogram
      • Endocrine causes
        • Hyperaldosteronism c187c188
          • Primary hyperaldosteronism (Conn Syndrome) is caused by oversecretion of aldosterone by adrenal glands c189
            • Most common cause of secondary hypertension r19
            • Present in up to 20% of patients with hypertension; more commonly those with more severe hypertension r19
            • Usually caused by bilateral adrenal hyperplasia
            • Sometimes caused by aldosterone-secreting adenoma or abnormal aldosterone-producing cell clusters present within morphologically normal adrenal glands r19
            • It is suggested that there is a spectrum of renin-independent autonomous hyperaldosteronism, ranging from subclinical to overt hyperaldosteronism, that occurs in all stages of hypertension and even in normotensive patients r35
          • Secondary hyperaldosteronism is caused by decreased renal perfusion, leading to increased renin and aldosterone secretion c190
            • Unexplained hypokalemia is a common feature
          • Diagnose by measuring plasma aldosterone concentration and renin activity; follow with adrenal imaging, usually with CT scan
        • Cushing disease and Cushing syndrome c191c192c193
          • Caused by increased pituitary secretion of corticotropin (Cushing disease), increased adrenal secretion of cortisol without stimulation by corticotropin, or ectopic production of corticotropin
          • Found in less than 0.1% of patients with hypertension r19
          • Most common in middle-aged adults c194c195
          • Central weight gain, striae, buffalo hump, and moon facies are common features
          • Glucose intolerance may be present
          • Diagnose in consultation with an endocrinologist
            • Determine if hypercortisolism is present with 24-hour urine collection or salivary cortisol measurement
            • Measure corticotropin levels to determine if the hypercortisolism is corticotropin dependent or corticotropin independent
            • Obtain imaging of adrenal glands, brain, or both, depending on results of laboratory testing and suspected source of hypercortisolism
        • Pheochromocytoma c196c197
          • Rare catecholamine-secreting tumor of the adrenal gland
          • Identified in 0.01% to 0.2% of patients with hypertension with higher prevalence in those with resistant hypertension r19
          • Most common in middle-aged adults c198
          • Presentation may include labile blood pressure, palpitations, flushing, sweating, headaches, syncope, and near syncope
          • May result in acute sympathetic crisis with severe hypertension owing to sudden rise in serum catecholamine levels
          • Diagnose with 24-hour urine collection for metanephrines or blood specimen for plasma-free metanephrines
          • If there is biochemical confirmation of catecholamine excess, perform MRI (preferred) or CT scan of abdomen and pelvis; scintigraphy may be necessary to locate extra-adrenal pheochromocytoma
        • Hypothyroidism or hyperthyroidism c199c200c201c202d2
          • Excess triiodothyronine raises systolic pressure in hyperthyroidism; decreased cardiac output eventually leads to increased blood pressure in untreated hypothyroidism d3
          • Found in less than 1% of patients with hypertension r19
          • Temperature intolerance, weight gain or loss, and tachycardia may be present
          • Diagnose with thyroid function laboratory testing
      • Obstructive sleep apnea c203c204
        • Strongly associated with hypertension
        • Found in more than 80% of patients with resistant hypertension r19
        • Most common in middle-aged adults with obesity or overweight c205c206
        • Presentation may include daytime somnolence, snoring, or apneic episodes while sleeping
        • Diagnose with polysomnography
      • Coarctation of the aorta c207c208c209
        • Found in less than 1% of patients with hypertension r19
        • Most commonly diagnosed in children and young adults c210c211
        • Presentation may include delayed or decreased femoral pulses, blood pressure or pulse difference between arms depending on anatomic location, significant systolic blood pressure differential between arms and legs, and systolic or continuous cardiac murmur
        • Diagnose with echocardiography
      • Acute sympathetic crisis caused by intoxicant c212
        • Paroxysmal hypertension caused by stimulants such as cocaine, amphetamines, methamphetamines, other drugs with sympathomimetic effects, and phencyclidine c213c214
        • In addition to hypertension, other prominent symptoms include tachycardia, fever, diaphoresis, dysrhythmias, chest pain, and agitation
        • If cause of intoxication is unknown, order toxicology screening of blood, urine, or gastric contents for suspected intoxicants

    Treatment

    Goals

    • For hypertensive emergency, rapidly lower blood pressure to minimize end-organ damage without compromising cerebral blood flow
      • For adults with a compelling condition (eg, aortic dissection, severe preeclampsia or eclampsia, pheochromocytoma crisis), reduce systolic blood pressure to lower than 140 mm Hg during the first hour and to lower than 120 mm Hg in aortic dissection r1
      • For adults without a compelling condition, reduce systolic blood pressure by no more than 25% within the first hour; then, if stable, to 160/100 mm Hg within the next 2 to 6 hours; and then cautiously to within reference range during the 24 to 48 hours that follow r1
      • In aortic dissection, rapid lowering of systolic blood pressure is required r1r8
        • Aim to achieve goal systolic blood pressure of 120 mm Hg or lower within 20 minutes r1r9
      • In acute ischemic stroke, blood pressure goal depends on planned treatment (thrombolysis versus no thrombolysis) r1r8r36
        • In patients with very high blood pressure (higher than 220/120 mm Hg) who are not receiving thrombolytic therapy, it is reasonable to lower blood pressure by 15% during the first 24 hours after symptom onset r37
        • In patients who have high blood pressure and who are eligible for thrombolytic therapy, lower blood pressure to lower than 185/110 mm Hg before therapy and maintain at lower than 180/105 mm Hg for 24 hours after therapy r37
        • No specific minimum systolic blood pressure is recommended, but systolic pressures between 141 and 150 mm Hg have been associated with optimal mortality and functional outcomes r38
      • In intracerebral hemorrhage r1r36
        • For adults with intracerebral hemorrhage who present with systolic blood pressure higher than 220 mm Hg, it is reasonable to use continuous IV drug infusion and close blood pressure monitoring to lower systolic blood pressure
        • Immediate lowering of systolic blood pressure to lower than 140 mm Hg in adults with spontaneous intracerebral hemorrhage who present within 6 hours of the acute event and have systolic blood pressure between 150 and 220 mm Hg is not helpful in reducing death or severe disability and is potentially harmful
    • For hypertensive urgency with no evidence of acute end-organ damage, there is no specific threshold of blood pressure that must be urgently treated or specific blood pressure level that must be reached before discharge r5
      • There is no indication for referral to the emergency department, immediate reduction in blood pressure in the emergency department, or hospitalization r1
        • Acute reduction of blood pressure in the emergency department is not advised owing to potential adverse effects and lack of clinical benefit r5
      • Goal for most patients is outpatient initiation of oral antihypertensive medication by the patient's personal physician with gradual reduction of blood pressure (over a period of days) r4r5
      • Emergency department physician may start treatment with an oral antihypertensive if warranted by social or clinical situation (eg, patient lacks transportation, other factor that limits access to outpatient follow-up) r5
    • For newly diagnosed or chronic hypertension (nonhypertensive emergency)
      • Blood pressure targets are generally based on degree of cardiovascular risk; more stringent blood pressure goals are recommended for patients at high risk of future cardiovascular events r1
        • High-risk factors include:
          • Established atherosclerotic cardiovascular disease (eg, coronary artery disease, ischemic stroke, peripheral vascular disease)
          • Heart failure
          • Diabetes
          • Chronic kidney disease
          • Multiple risk factors and a 10-year atherosclerotic cardiovascular disease risk of 10% or more
          • Aged older than 65 years
      • Blood pressure goals for specific risk groups
        • Patients with coronary artery disease
          • 2017 American College of Cardiology/American Heart Association Task Force on clinical practice guidelines recommend blood pressure target of lower than 130/80 mm Hg for adults with confirmed hypertension and known cardiovascular disease or 10-year atherosclerotic cardiovascular disease event risk of 10% or higher r1
          • UK guidelines recommend the same blood pressure targets as for people without cardiovascular disease r15
        • Patients with transient ischemic attack or ischemic stroke
          • American Heart Association/American Stroke Association guidelines r39
            • A goal of office blood pressure lower than 130/80 mm Hg is recommended for most patients r39
          • American College of Physicians and American Academy of Family Physicians guidelines recommend the following: r40
            • Consider starting or intensifying pharmacologic treatment in adults aged 60 years or older with a history of stroke or transient ischemic attack to achieve a target systolic blood pressure of lower than 140 mm Hg to reduce the risk for recurrent stroke
        • Patients with diabetes
          • 2017 American College of Cardiology/American Heart Association Task Force on clinical practice guidelines recommend a target of lower than 130/80 mm Hg in adults r1
          • American Diabetes Association recommends blood pressure target of lower than 130/80 mm Hg for most patients with diabetes if it can be achieved safely r41
          • American Association of Clinical Endocrinologists recommend blood pressure target of lower than 130/80 mm Hg for most patients r42
            • May opt for higher goal in patients with autonomic neuropathy, orthostatic hypotension, acute coronary syndrome, or frailty
            • May consider blood pressure goal of lower than 120/70 mm Hg in patients with micro- or macroalbuminuria, coronary artery disease, peripheral vascular disease, or retinopathy
        • Patients with chronic kidney disease (all ages)
          • Reduce blood pressure to lower than 130/80 mm Hg r1r43
      • For patients at low risk (none of the above comorbidities)
        • Clinical trial evidence is strongest for blood pressure target of lower than 140/90 mm Hg; however, a target of lower than 130/80 mm Hg may also be reasonable r1r3
        • 2019 American College of Cardiology/American Heart Association guidelines on primary prevention of cardiovascular disease recommend target blood pressure of lower than 130/80 mm Hg in most cases r3
        • American Academy of Family Physicians recommends treating to a blood pressure target of lower than 140/90 mm Hg to reduce the risk of all-cause and cardiovascular mortality r15r44
          • Treating to a target of less than 135/85 mm Hg may further reduce the risk of myocardial infarction but does not provide additional mortality benefit
        • When using ambulatory blood pressure monitoring or home blood pressure monitoring to monitor adults with hypertension, use the average blood pressure level taken during the person's usual waking hours; UK guidelines recommending aiming for below 135/85 mm Hg for adults younger than 80 years r15
      • Older adults
        • Recommendations vary across guidelines, especially for adults aged 80 years or older
          • Many advocate for higher target of systolic blood pressure for octogenarians in comparison with the general population (ie, systolic blood pressure lower than 150 mm Hg) r45
          • Benefit of intensive treatment in frail older adults is unclear, because they are at higher risk for both cardiovascular events and severe adverse effects of antihypertensive drug therapy
          • Evidence supports an individualized approach of less aggressive blood pressure lowering in very old patients with few risk factors and stricter blood pressure control in patients with multiple risk factors r46
            • Benefit of blood pressure reduction appears to be greater in patients at higher risk even among those with advanced age
        • 2017 American College of Cardiology/American Heart Association Task Force on clinical practice guidelines recommend a systolic blood pressure treatment goal of lower than 130 mm Hg for noninstitutionalized ambulatory community-dwelling adults aged 65 years or older r1
          • In patients aged 60 to 80 years, intensive treatment with a systolic blood pressure target of 110 to 130 mm Hg resulted in a lower risk of cardiovascular events than treatment with a target of 130 to 150 mm Hg r47
          • Goals need not differ even for community-dwelling patients older than 80 years
            • Treatment of hypertension significantly reduced cardiovascular mortality and morbidity in patients aged 80 years or older; relative risk reduction similar to that in patients aged 60 to 79 years r48r49
          • However, blood pressure targets can be individualized in patients with significant comorbidities and a limited life expectancy; less aggressive blood pressure lowering may be considered
        • Earlier American College of Physicians and American Academy of Family Physicians joint guidelines for patients aged 60 years or older recommended higher targets, which are not consistent with those of other professional organizations; they recommended the following: r40
          • Reducing systolic blood pressure to lower than 150 mm Hg (for patients without history of stroke or transient ischemic attack and without high individual cardiovascular risk)
          • Considering starting or intensifying pharmacologic treatment in some adults aged 60 years or older at high cardiovascular risk (based on individualized assessment) to achieve a target systolic blood pressure of lower than 140 mm Hg, reducing the risk for stroke or cardiac events
        • UK guidelines recommend in-clinic blood pressure goal of lower than 150/90 mm Hg for patients aged 80 years or older; use clinical judgement for patients who are frail or who have multiple comorbidities r15
          • When using ambulatory blood pressure monitoring or home blood pressure monitoring to monitor adults with hypertension, use the average blood pressure level taken during the person's usual waking hours; aim for below 145/85 mm Hg for adults aged 80 years or older

    Disposition

    Admission criteria

    Hypertensive urgency (severe asymptomatic hypertension) does not typically require acute blood pressure lowering in the emergency department or inpatient admission r1r5

    Criteria for ICU admission
    • In adults with a hypertensive emergency, admission to an intensive care unit is recommended for continuous monitoring of blood pressure and target organ damage, and for parenteral administration of an appropriate agent r1r9

    Recommendations for specialist referral

    • Refer to primary care physician for follow-up within 1 week for patients discharged from the emergency department with hypertensive urgency (severe asymptomatic hypertension) r4
    • Refer to hypertension specialist (usually cardiologist; nephrologist for patients with kidney disease) when goal blood pressure is not reached with multiple drugs r7

    Treatment Options

    Hypertensive emergency

    • 2017 American College of Cardiology/American Heart Association Task Force on clinical practice guidelines provide recommendations for management of hypertensive emergencies r1
      • For adults with a compelling condition (eg, aortic dissection, severe preeclampsia or eclampsia, or pheochromocytoma crisis), reduce systolic blood pressure to lower than 140 mm Hg during the first hour and to lower than 120 mm Hg in aortic dissection
      • For adults without a compelling condition, reduce systolic blood pressure by no more than 25% within the first hour; then, if stable, to 160/100 mm Hg within the next 2 to 6 hours; and then cautiously to within reference range during the following 24 to 48 hours
      • For patients with ischemic stroke, lower blood pressure to a lesser degree, within the following parameters:
        • In patients with very high blood pressure (higher than 220/120 mm Hg) who are not receiving thrombolytic therapy, it is reasonable to lower blood pressure by 15% during the first 24 hours after symptom onset r37
        • In patients who have high blood pressure and are eligible for thrombolytic therapy, lower their blood pressure to lower than 185/110 mm Hg before therapy and maintain at lower than 180/105 mm Hg for 24 hours after therapy r37
        • No specific minimum systolic blood pressure is recommended, but systolic pressures between 141 and 150 mm Hg have been associated with optimal mortality and functional outcomes r38
      • For adults with intracerebral hemorrhage who present with systolic blood pressure higher than 220 mm Hg, it is reasonable to use continuous IV drug infusion and close blood pressure monitoring to lower systolic blood pressure
      • For patients with aortic dissection, rapid lowering of systolic blood pressure is required r1r8
        • Aim for goal systolic blood pressure of 120 mm Hg or lower to be achieved within 20 minutes r1
      • Otherwise, avoid rapid, extreme pressure reductions to prevent organ hypoperfusion r28
    • Parenteral drugs are preferred (given as titrated IV boluses or by infusion) r28
    • Sodium nitroprusside, nicardipine (IV), and/or labetalol (IV) are appropriate for most hypertensive emergencies, but initial drug of choice is based on the acute end-organ dysfunction at presentation; recommendations are consensus based r9r28
      • Sublingual or immediate-acting nifedipine is contraindicated
      • Begin oral antihypertensives before discontinuing IV drugs
    • If acute coronary syndrome is present and there is evidence of heart failure, give nitroglycerinr28 and β-blockersr4r8
      • A fast-acting drug is preferable;r4esmolol is suggested as an agent of choicer1
      • Nitroprusside may result in coronary steal syndrome r4
    • If pulmonary edema is present, preferred drugs include sodium nitroprusside, nitroglycerin, and clevidipine r1r4r8
      • Use loop diuretics cautiously, because patients are often normovolemic or hypovolemic r4
      • β-Blockers are contraindicated r1
    • If acute kidney injury is present, give calcium channel blocker (nicardipine or clevidipine) or fenoldopam r1r4r8
      • Calcium channel blockers do not affect renal perfusion; fenoldopam promotes renal excretion and is as effective as nitroprusside r4
    • If hypertensive encephalopathy (without stroke) is present, switch to nitroprusside, labetalol, nicardipine, and/or enalapril r5
      • Benzodiazepines, phenytoin, and barbiturates (given for seizure control and delirium) also result in blood pressure decrease r4
    • If ischemic stroke is present, give IV nicardipine, labetalol, or clevidipine; switch to IV nitroprusside if blood pressure is not controlled or diastolic pressure is higher than 140 mm Hg r37
    • If aortic dissection is present, give β-blocker to reduce shearing forces (esmolol is ideal) followed by nitroprusside or nicardipine (to provide arteriodilation) r1r4
    • If sympathetic crisis is caused by pheochromocytoma, give phentolamine, nicardipine, or clevidipine r1r8
    • If sympathetic crisis is caused by cocaine, benzodiazepines are indicated and may be sufficient to decrease blood pressure r4
      • Phentolamine or nitroprusside may be administered if benzodiazepines not successful r50
      • Do not give β-blockers owing to reflex tachycardia risk r50
    • If sympathetic crisis is caused by phencyclidine, amphetamine, tyramine reaction with use of MAOIs, or abrupt withdrawal from sympatholytic medications, give phentolamine, nitroprusside, or labetalol r4
      • Avoid β-blocker use as sole treatment owing to risk of reflex tachycardia

    Hypertensive urgency

    • No evidence for a specific threshold blood pressure that must be urgently treated or a specific blood pressure level that must be reached before discharge r5
    • There is no indication for referral to the emergency department, immediate reduction in blood pressure in the emergency department, or hospitalization for such patients r1
      • No evidence that acute treatment in the emergency department results in short-term cardiovascular risk reduction r4
    • For most patients, outpatient follow-up with beginning of oral antihypertensive medications at that time is recommended unless medical follow-up is not ensured r5
    • If medical follow-up is not ensured, emergency physicians may treat markedly elevated blood pressure in the emergency department and/or begin therapy for long-term control r5

    Essential hypertension r1

    • Start lifestyle interventions in all patients to reduce both blood pressure and cardiovascular disease risk
      • Consists of weight loss, dietary sodium reduction, potassium supplementation, healthy dietary pattern, increased physical activity, and limited alcohol consumption
    • Patients with stage 1 hypertension (systolic 130-139 mm Hg or diastolic 80-89 mm Hg) and an estimated 10-year atherosclerotic cardiovascular disease risk lower than 10% can be treated initially with lifestyle modifications alone with repeat blood pressure evaluation within 3 to 6 months r51
      • Continue lifestyle therapy and start pharmacologic therapy if blood pressure remains elevated after 3 to 6 months of lifestyle interventions r51r52
    • For patients with stage 1 hypertension and either history of cardiovascular disease or who are at increased risk for atherosclerotic cardiovascular disease, a combination of lifestyle modification and pharmacologic therapy with a single agent is recommended from the outset r53
    • For patients with stage 2 hypertension (systolic 140 mm Hg or higher or diastolic 90 mm Hg or higher), antihypertensive drug therapy using 2 drugs of different classes is recommended r53
    • First line pharmacologic therapy options include thiazide diuretics, calcium channel blockers, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers or available 2-drug combinations r1
      • Consider patient-specific factors (eg, age, concurrent medications, drug adherence, drug interactions, overall treatment regimen, out-of-pocket costs, comorbidities) when selecting agent
        • Begin treatment with a thiazide diuretic or a calcium channel blocker in Black patients without heart failure or chronic kidney disease, including those with diabetes r1
        • Therapy should include angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with chronic kidney disease r1
        • In general, β-blockers are not recommended for initial treatment except in patients with angina pectoris, arrhythmias, heart failure, or a recent myocardial infarction; effect on cardiovascular morbidity and mortality is lower than other agents r54r55
      • Use of fixed-dose, single-pill combinations is recommended to improve adherence to antihypertensive therapy
      • Initial therapy with low-dose fixed combinations may be as effective as standard-dose monotherapy r53
      • Simultaneous use of an ACE inhibitor, angiotensin receptor blocker, and/or renin inhibitor is potentially harmful and is not recommended to treat adults with hypertension
      • Patients can take once-daily antihypertensive medication at the time of day that they find most convenient
        • Previous studies found that bedtime dosing lowered nocturnal blood pressure and improved cardiovascular outcomes; however, the largest and most rigorous trial to date found no difference in major cardiovascular outcomes and adverse events between evening dosing and morning dosing r56r57
    • 2 or more antihypertensive medications are usually necessary to achieve a blood pressure target of lower than 130/80 mm Hg in most adults with hypertension, especially in Black adults with hypertension
    • Additional medications are added in a stepwise manner until blood pressure goals are met (after optimizing adherence and maximizing dosage)
      • In patients who do not respond to or do not tolerate treatment with 2 to 3 medications or medication combinations, team-based care may be effective, encouraging both nonpharmacologic and pharmacologic treatments
    • If blood pressure control remains inadequate with treatment with 3 antihypertensive agents of different classes at optimal doses and dosing intervals and with good adherence (resistant hypertension), screen for secondary hypertension, assess for end-organ damage, then manage as follows: r7r53
      • Optimize lifestyle interventions r7
      • Switch to a long-acting thiazide or thiazidelike diuretic (chlorthalidone or indapamide) in place of a shorter-acting thiazide
      • Add a mineralocorticoid receptor antagonist (spironolactone or eplerenone) if a fourth agent is necessary
      • Add other agents with complementary mechanisms of action in a stepwise manner
      • Consider referral to a hypertension specialist
    • Renal denervation using radiofrequency or ultrasound is a possible treatment option in adult patients with uncontrolled resistant hypertension confirmed by ambulatory blood pressure measurements r58
    • Comparative efficacy of specific antihypertensive agents
      • Cochrane reviews comparing efficacy of recommended first line drugs found that all-cause mortality is similar when ACE inhibitors or angiotensin receptor blockers are compared with other first line antihypertensive agents r59r60
        • First line calcium channel blockers reduce risk of stroke compared with ACE inhibitors and reduce risk of myocardial infarction compared with angiotensin receptor blockers, but they increase risk of congestive heart failure compared with both ACE inhibitors and angiotensin receptor blockers r59
        • ACE inhibitors and angiotensin receptor blockers are associated with an increased risk of heart failure and stroke compared with thiazide diuretics
        • Calcium channel blockers reduce major cardiovascular events, stroke, and cardiovascular mortality more than β-blockers r59
        • First line thiazides and thiazidelike drugs likely do not effect mortality but reduce cardiovascular events and adverse effects–associated withdrawal compared to beta-blockers, calcium channel blockers, ACE inhibitors, and alpha-blockers r61
      • Another Cochrane review reported that first line low-dose thiazides reduced all morbidity and mortality outcomes in adult patients with moderate to severe primary hypertension r62
        • First line high-dose thiazides and first line β-blockers were inferior to first line low-dose thiazides
      • A Cochrane review compared dose-related blood pressure–lowering effect of thiazide diuretics r63
        • Hydrochlorothiazide has a dose-related blood pressure–lowering effect, but no dose effect was seen with other thiazide drugs (the lowest doses studied reduced blood pressure maximally) c215

    Treatment of secondary hypertension is specific to the underlying cause

    • Renovascular disease (renal artery stenosis)
      • Initial treatment is medical control of hypertension, management of hyperlipidemia, and antiplatelet therapy r64
        • Drugs that block the renin-angiotensin-aldosterone system (ACE inhibitors and angiotensin receptor blockers) improve cardiovascular outcomes based on observational studies, but they must be used with caution owing to risk of worsened renal function
      • Renal angioplasty with or without stenting is an accepted treatment for fibromuscular dysplasia, but benefit in atherosclerotic renal artery stenosis is unclear but is accepted in FMD r19
        • A Cochrane review determined there was insufficient data to conclude that balloon angioplasty, with or without stenting, is superior to medical therapy for the treatment of atherosclerotic renal artery stenosis in patients with hypertension. Balloon angioplasty resulted in a small improvement in diastolic blood pressure and a small reduction in antihypertensive drug requirements r65
      • Surgical revascularization or bypass may be considered in patients with anatomically complex disease refractory to medical management or those undergoing vascular repair for other reasons r19r64
    • Coarctation of the aorta r18
      • Requires surgical or interventional (transcatheter) catheter treatment in most cases
      • Peak-to-peak gradient of 20 mm Hg or more by cardiac catheterization is an indication for intervention
    • Endocrine conditions
      • Hypercortisolism caused by Cushing disease (pituitary cause) or Cushing syndrome (adrenal cause)
        • Transsphenoidal surgery is the treatment of choice for Cushing disease r66
        • Surgery is usually the treatment of choice for Cushing syndrome except when the tumor cannot be located r67
        • Medical management is necessary before surgery and when surgery is contraindicated r67
          • Dopamine or somatostatin agonists to modulate corticotropin release
          • Steroidogenesis inhibitors (metyrapone, ketoconazole, mitotane)
          • Glucocorticoid receptor antagonist (mifepristone)
      • Pheochromocytoma r68
        • Requires surgical resection of the tumor
        • Hypertension must be medically managed preoperatively and intraoperatively and for inoperable disease
        • α-Blocker (phenoxybenzamine) recommended for 10 to 14 days before surgery
        • Labetalol or nitroprusside is commonly used intraoperatively
      • Hyperaldosteronism r69
        • Unilateral adrenalectomy, usually laparoscopic, is indicated in patients with an aldosterone-producing adrenal adenoma
        • Hypertension resolves within 6 months of surgery in up to 50% of patients; remainder of patients are usually less hypertensive
        • Treatment is medical with mineralocorticoid antagonists for patients with bilateral disease or for those with unilateral disease who are not surgical candidates
          • Spironolactone is the first line medical therapy; eplerenone is an alternative with fewer antiandrogenic effects
          • Amiloride may also be effective
        • An aldosterone synthase inhibitor (lorundrostat) may have the same antihypertensive benefit as mineralocorticoid receptor antagonists and is being studied as a possible treatment option for resistant hypertension secondary to hyperaldosteronism r70
      • Thyroid disorders
        • Treat hypothyroidism with thyroid hormone replacement
        • Hyperthyroidism may be treated medically (antithyroid drugs), with radioactive iodine, or with surgical resection r71
          • β-Blockers and calcium channel blockers (verapamil, diltiazem) may be used to reduce adrenergic manifestations of hyperthyroidism
    • Kidney disease
      • Treatment of renal parenchymal disease caused by glomerulonephritis depends on specific underlying cause r72
      • Manage chronic kidney disease according to published guidelines r43r73
        • Include an ACE inhibitor or angiotensin receptor blocker for blood pressure management r43
          • Requires careful monitoring of serum creatinine and potassium levels
        • Include diuretics in the antihypertensive regimen for most patients
    • Obstructive sleep apnea
      • Treated with nocturnal continuous positive airway pressure mask; in milder cases, a dental appliance may be effective r74
    • Drug-related causes are managed with discontinuation of the offending agent

    Drug therapy

    • Oral administration (for initial and add-on therapy)
      • Thiazide diuretics c216
        • Chlorthalidone c217c218
          • Chlorthalidone Oral tablet; Adults: 12.5 to 25 mg PO once daily, initially. May increase dose to 50 mg PO once daily if response is insufficient and to 100 mg PO once daily if further control is needed.
        • Hydrochlorothiazide c219c220
          • Hydrochlorothiazide Oral tablet; Adults: 25 mg PO once daily, initially. May increase dose to 50 mg/day in 1 to 2 divided doses.
        • Metolazone c221c222
          • Metolazone Oral tablet; Adults: 2.5 to 5 mg PO once daily.
      • Thiazidelike diuretic
        • Indapamide
          • Indapamide Oral tablet; Adults: 1.25 mg PO once daily, initially. May double dose every 4 weeks if further control is needed. Max: 5 mg/day.
      • Calcium channel blockers
        • Amlodipine c223c224
          • Amlodipine Besylate Oral tablet; Adults: 5 mg PO once daily, initially. May increase dose after 7 to 14 days if further control is needed. Max: 10 mg/day.
          • Amlodipine Besylate Oral tablet; Older Adults: 2.5 mg PO once daily, initially. May increase dose after 7 to 14 days if further control is needed. Max: 10 mg/day.
        • Diltiazem (extended-release forms are the only form recommended for hypertension) c225c226
          • Once-daily dosage form
            • Diltiazem Hydrochloride Oral tablet, extended-release; Adults: 180 to 240 mg PO once daily, initially. May increase dose after 14 days if further control is needed. Usual dose range: 120 to 360 mg/day. Max: 540 mg/day.
          • Twice-daily dosage form
            • Diltiazem Hydrochloride Oral capsule, sustained release 12 hour; Adults: 60 to 120 mg PO twice daily, initially. May increase dose after 14 days if further control is needed. Usual dose range: 120 to 360 mg/day. Max: 360 mg/day.
        • Nifedipine (extended-release forms are the only form recommended for hypertension) c227c228
          • Nifedipine Oral tablet, extended-release; Adults: 30 or 60 mg PO once daily, initially. May increase dose over 7 to 14 days if further control is needed. Usual dose range: 30 to 90 mg/day. Max: 120 mg/day.
      • ACE inhibitors
        • Benazepril c229c230
          • Benazepril Hydrochloride Oral tablet; Adults: 10 mg PO once daily, initially. May increase dose if further control is needed. Usual dose range: 10 to 40 mg/day PO in 1 to 2 divided doses. Max: 80 mg/day.
        • Enalapril c231c232
          • Enalapril Maleate Oral tablet; Adults: 5 mg PO once daily, initially. May increase dose if further control is needed. Usual dose range: 5 to 40 mg/day PO in 1 to 2 divided doses.
        • Lisinopril c233c234
          • Lisinopril Oral tablet; Adults: 10 mg PO once daily, initially. May increase dose if further control is needed. Usual dose range: 10 to 40 mg/day. Max: 80 mg/day.
      • Angiotensin receptor blockers
        • Irbesartan c235c236
          • Irbesartan Oral tablet; Adults: 150 mg PO once daily, initially. May increase dose to 300 mg PO once daily if further control is needed.
        • Losartan c237c238
          • Losartan Potassium Oral tablet; Adults: 50 mg PO once daily, initially. May increase dose to 100 mg/day in 1 to 2 divided doses if further control is needed.
        • Valsartan c239c240
          • Valsartan Oral tablet; Adults: 80 or 160 mg PO once daily, initially. May increase dose if further control is needed. Usual dose range: 80 to 320 mg/day. Max: 320 mg/day.
    • Oral administration (for treatment of resistant hypertension [goal not reached with 3-drug regimen])
      • Aldosterone antagonists (mineralocorticoid antagonists)
        • Spironolactone r75c241
          • Spironolactone Oral tablet; Adults: 25 to 100 mg PO once daily or in divided doses.
        • Eplerenone r76c242
          • Eplerenone Oral tablet; Adults: 50 mg PO once daily, initially. May increase dose to 50 mg PO twice daily after 4 weeks. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
      • α-Blockers
        • Doxazosin c243
          • Doxazosin Mesylate Oral tablet; Adults: 1 mg PO once daily, initially. May double daily dose as needed if further control is needed. Max: 16 mg/day.
        • Prazosin c244
          • Prazosin Hydrochloride Oral capsule; Adults: 1 mg PO 2 to 3 times daily, initially. May increase dose if further control is needed. Usual dose range: 2 to 20 mg/day. Max: 40 mg/day.
        • Terazosin c245
          • Terazosin Hydrochloride Oral tablet; Adults: 1 mg PO once daily at bedtime, initially. Usual dose range: 1 to 20 mg/day in 1 or 2 divided doses. Max: 20 mg/day.
      • β-Blockers
        • Atenolol c246
          • Atenolol Oral tablet; Adults: 50 mg PO once daily, initially. May increase dose to 100 mg PO once daily after 7 to 14 days if further control is needed. Usual dose range: 25 to 100 mg/day in 1 or 2 divided doses.
        • Carvedilol c247
          • Immediate-release
            • Carvedilol Oral tablet; Adults: 6.25 mg PO twice daily, initially. May double dose every 7 to 14 days if further control is needed. Max: 25 mg PO twice daily.
          • Extended-release
            • Carvedilol Oral capsule, extended-release; Adults: 20 mg PO once daily, initially. May double dose every 7 to 14 days if further control is needed. Max: 80 mg PO once daily.
        • Metoprolol c248
          • Immediate-release
            • Metoprolol Tartrate Oral tablet; Adults: 100 mg PO once daily or in divided doses. May increase dose after at least 7 days if further control is needed. Usual dose range: 100 to 200 mg/day in 2 divided doses. Max: 450 mg/day.
          • Extended-release
            • Metoprolol Succinate Oral tablet, extended-release; Adults: 25 to 100 mg PO once daily, initially. May increase dose after at least 7 days if further control is needed. Usual dose range: 50 to 200 mg/day. Max: 400 mg/day.
      • Centrally acting adrenergic agents
        • Clonidine c249
          • Oral
            • Clonidine Hydrochloride Oral tablet; Adults: 0.1 mg PO twice daily, initially. May increase dose by 0.1 mg/day every 7 days if further control is needed. Usual dosage range: 0.1 to 0.8 mg/day. Max: 2.4 mg/day.
          • Transdermal c250
            • Clonidine Transdermal patch - weekly; Adults: 0.1 mg/24 hours transdermally every 7 days. May increase dose by 0.1 mg/24 hours after 7 to 14 days if further control is needed. Usual dosage range: 0.1 to 0.3 mg/24 hours every 7 days. Max: 0.6 mg/24 hours every 7 days.
        • Guanfacine c251
          • Guanfacine Hydrochloride Oral tablet; Adults: 1 mg PO once daily at bedtime, initially. May increase dose by 1 mg/day after 3 to 4 weeks if further control is needed. Usual dosage range: 0.5 to 2 mg/day. Max: 3 mg/day.
        • Methyldopa c252
          • Methyldopa Oral tablet; Adults: 250 mg PO 2 to 3 times daily, initially. May increase dose every 2 days if further control is needed. Usual dosage: 250 to 2,000 mg/day in 2 to 4 divided doses. Max: 3,000 mg/day.
      • Loop diuretics
        • Furosemide c253
          • Furosemide Oral tablet; Adults: 40 mg PO twice daily, initially. May increase dose if further control is needed. Usual dose range: 20 to 80 mg/day. Max: 600 mg/day.
        • Torsemide c254
          • Torsemide Oral tablet; Adults: 5 mg PO once daily, initially. May increase dose to 10 mg PO once daily after 4 to 6 weeks if further control is needed. Max: 10 mg/day.
      • Renin inhibitors
        • Aliskiren c255
          • Aliskiren Hemifumarate Oral tablet; Adults: 150 mg PO once daily, initially. May increase dose to 300 mg PO once daily if further control is needed.
      • Vasodilators
        • Hydralazine c256
          • Hydralazine Hydrochloride Oral tablet; Adults: 10 mg PO 4 times daily for 2 to 4 days, then 25 mg PO 4 times daily for the balance of the first week, initially. May increase dose to 50 mg PO 4 times daily if further control is needed. Usual dose range: 100 to 200 mg/day in 2 to 4 doses. Max: 300 mg/day.
        • Minoxidil c257
          • Minoxidil Oral tablet; Adults: 5 mg PO once daily, initially. May increase dose to 10, 20, and then 40 mg/day in single or divided doses every 3 days if further control is needed. Usual dose range: 5 to 100 mg/day in 1 to 3 divided doses. Max: 100 mg/day.
    • IV administration
      • Calcium channel blockers
        • Nicardipine c258
          • For short-term treatment of hypertension when oral therapy is not feasible or desirable (substituting for oral nicardipine therapy)
            • Nicardipine Hydrochloride Solution for injection; Adults: 0.5 mg/hour continuous IV infusion for 20 mg PO every 8 hours, 1.2 mg/hour continuous IV infusion for 30 mg PO every 8 hours, or 2.2 mg/hour continuous IV infusion for 40 mg PO every 8 hours.
          • For the treatment of acute hypertension, including perioperative hypertension, hypertensive urgency, and hypertensive emergency
            • Nicardipine Hydrochloride Solution for injection; Adults: 5 mg/hour continuous IV infusion, initially. Titrate by 2.5 mg/hour every 5 to 15 minutes until goal blood pressure is attained. Max: 15 mg/hour. Reduce to 3 mg/hour after response achieved.
        • Clevidipine c259
          • Clevidipine Emulsion for injection; Adults: 1 to 2 mg/hour continuous IV infusion, initially. Double dose every 90 seconds until the blood pressure approaches goal, then increase by less than double every 5 to 10 minutes as needed. Max: 32 mg/hour or 1,000 mL/24 hours due to lipid load restrictions. Max duration: 72 hours.
      • β-Blockers
        • Esmolol c260c261
          • For hypertensive emergency or hypertensive urgency
          • Esmolol Hydrochloride Solution for injection; Adults: 500 to 1,000 mcg/kg IV over 1 minute, then 50 mcg/kg/minute continuous IV infusion, initially. Repeat bolus and titrate by 50 mcg/kg/minute until goal blood pressure is attained. Max: 200 mcg/kg/minute.
        • Labetalol c262
          • Bolus dosing
            • Labetalol Hydrochloride Solution for injection; Adults: 10 to 20 mg IV, then 20 to 80 mg IV every 10 to 30 minutes until goal blood pressure is attained. Max cumulative dose: 300 mg.
          • Continuous infusion
            • Labetalol Hydrochloride Solution for injection; Adults: 1 to 8 mg/minute continuous IV infusion until goal blood pressure is attained then transition to oral labetalol. Usual total dose: 50 to 200 mg. Max cumulative dose: 300 mg.
      • Nitrates
        • Nitroglycerin c263
          • Nitroglycerin Solution for injection; Adults: 5 mcg/minute continuous IV infusion, initially. Titrate by 5 mcg/minute every 3 to 5 minutes to clinical response, or a dose of 20 mcg/minute. May further titrate by 10 mcg/minute, and if the desired effect is still not achieved, by 20 mcg/minute. Max titration: 20 mcg/minute every 3 to 5 minutes. Usual dose range: 5 to 100 mcg/minute. Max: 200 mcg/minute.
      • Vasodilators
        • Fenoldopam c264
          • Fenoldopam Mesylate Solution for injection; Adults: 0.01 to 0.3 mcg/kg/minute continuous IV infusion, initially. Titrate by 0.05 to 0.1 mcg/kg/minute every 15 minutes until goal blood pressure is attained. Max: 1.6 mcg/kg/minute. Max duration: 48 hours.
        • Nitroprusside c265
          • Sodium Nitroprusside Solution for injection; Adults: 0.3 to 0.5 mcg/kg/minute continuous IV infusion, initially. Titrate by 0.5 mcg/kg/minute every 5 minutes until desired effect or blood pressure cannot be further reduced without compromising organ perfusion. Max: 10 mcg/kg/minute for 10 minutes.
          • Cyanide ions, a by-product of nitroprusside metabolism, can build up to toxic levels during nitroprusside therapy. To maintain the steady-state thiocyanate concentration below 1 mmol/L, the rate of a prolonged infusion (ie, longer than 72 hours) should not exceed 3 mcg/kg/minute in patients with normal renal function and 1 mcg/kg/minute in anuric patients
      • α-Blocker
        • Phentolamine c266
          • Phentolamine Mesylate Solution for injection; Adults: 5 mg IV every 10 minutes as needed. Dose range: 5 to 15 mg.
      • ACE inhibitor
        • Enalaprilat c267
          • Enalaprilat Solution for injection; Adults: 1.25 mg IV every 6 hours. Up to 5 mg IV every 6 hours has been used. Max: 20 mg/day.

    Nondrug and supportive care

    • Lifestyle modifications are recommended for patients with elevated blood pressure and hypertension r3r32r77c268
      • Weight loss
        • Target weight loss based on BMI goal of ideal body weight; aim for at least a 1-kg reduction in body weight r1c269c270
        • Emphasize reduction of caloric intake and increased physical activity r13
        • Pharmacotherapy can be considered for weight loss in patients who fail to respond to lifestyle modifications alone and have a BMI 30 kg/m² or higher (for males) or 27 kg/m² or higher (for females) r13
          • Anti-obesity medications such as glucagon-like peptide-1 receptor agonists (e.g., semaglutide and liraglutide), glucagon-like peptide-1, and glucose-dependent insulinotropic polypeptide receptor agonist (e.g., tirzepatide) reduce blood pressure, particularly when use results in significant weight loss r24
        • Bariatric surgery can be considered for males with a BMI 40 kg/m² or higher and females with a BMI 35 kg/m² or higher who are psychologically stable and have no active substance misuse; can result in reduction in both blood pressure and body weighr24t r13
      • Physical activity
        • Participate in aerobic activity at least 90 to 150 minutes per week (eg, exercise for 40-60 minutes at least 3 times per week) r1r53c271
        • Reduce sedentariness (eg, by interrupting sitting time with walking or standing breaks) r13
        • Blood pressure–lowering effects have been documented for aerobic exercise (eg, brisk walking, swimming, running) and dynamic resistance exercise (eg, hand grip or yoga) r53
      • Sodium restriction c272
        • Optimal goal is less than 1500 mg/day; aim for at least a 1000-mg/day reduction in most adults; however, any decrease in sodium intake is helpful r1r53
        • Evidence confirms significant reduction in systolic blood pressure with salt restriction r78
        • Because salt sensitivity is on an individual continuum (30%-50% of patients are considered salt sensitive), individual effect of salt reduction may vary r79
          • Salt sensitivity is common in Black people; older adults; and people with low-renin hypertension, comorbid obesity, or metabolic syndrome
          • Low intake of potassium increases the salt sensitivity of blood pressure, particularly in Black people r80
        • Low sodium intake may increase the risk of cardiovascular events in some patients, for example, those with congestive heart failure treated with high doses of diuretics, diabetes
      • Potassium supplementation r53
        • Randomized clinical trials have shown that potassium supplementation (approximately 60 mmol/day) significantly lowers blood pressure
          • Effects on blood pressure are greatest in patients with a higher initial blood pressure, Black patients, and those consuming more than 2500 mg/day of sodium
        • Use of salt substitutes with reduced sodium levels and increased potassium levels has been shown to lower blood pressure and lower the rates of stroke, major cardiovascular events, and death in older patients with hypertension r81
        • Increased intake of foods high in potassium (fruits and vegetables) is preferred owing to general health benefits
      • Healthy dietary pattern
        • Follow an established healthy dietary patterns such as the Mediterranean diet or DASH (Dietary Approaches to Stop Hypertension); both emphasize fruits, vegetables, legumes, nuts, and seeds, with moderate intake of fish, seafood, poultry, and dairy and limited red meat, processed meat, and sweets r1r13r82r83c273
        • Reduce consumption of foods with saturated fat, cholesterol, salt, and refined grains, and ultra-processed foods
        • Evidence for beneficial effects of specific dietary components on blood pressure is often conflicting or poor quality; however, calcium supplementation and magnesium supplementation may be associated with a slight reduction in BP r83r84r85
      • Limit alcohol intake
        • There is a direct dose-response relationship between alcohol consumption and level of blood pressure and incidence of hypertension r53
        • Limit alcohol intake to 2 drinks per day or fewer for males (total 30 mL ethanol) and 1 drink per day or fewer for females (total 15 mL ethanol) r1r32c274
          • 1 drink is equal to 355 mL (12 oz) of beer, 148 mL (5 oz) of wine, and 44 mL (1.5 oz) of 80-proof liquor r28
      • Smoking cessation
        • Decreases overall cardiovascular risk r1d4

    Comorbidities

    • Diabetes c275
      • Approximately 80% of patients with diabetes have systolic blood pressure of 130 mmHg or higher or diastolic blood pressure of 80 mmHg or higher or are taking prescription medication for their high blood pressure r86
      • Hypertension is a modifiable risk factor for cardiovascular complications and progression of diabetic kidney disease r87
      • Blood pressure targets in patients with diabetes differ according to type of diabetes and degree of impairment in kidney function r87
      • ACE inhibitors are generally the first line agent for treating hypertension in patients with diabetes and chronic kidney disease; angiotensin receptor blockers are an alternative if ACE inhibitor therapy is contraindicated or not tolerated r87
      • Thiazide diuretics may cause hyperglycemia; consider increased monitoring of glucose levels
    • Chronic kidney disease c276d1
      • Hypertension is the most common cause of chronic kidney disease; conversely, chronic kidney disease can lead to or exacerbate hypertension r43
      • Target systolic blood pressure of lower than 120 mm Hg is recommended r43
      • ACE inhibitor or angiotensin receptor blocker is recommended for patients with high blood pressure, chronic kidney disease, or moderate or severely increased albuminuria, with or without diabetes r43
      • Treat adult kidney transplant recipients with a dihydropyridine calcium channel blocker or angiotensin receptor blocker to a target blood pressure of lower than 130 mm Hg r43
      • Sodium intake should be less than 2 g/day (equivalent to 5 g of sodium chloride) for most patients r43
      • Progressive azotemia and hyperkalemia are possible; periodic laboratory monitoring is recommended

    Special populations

    • Non-Hispanic Black patients
      • Risk of hypertension-related kidney failure is markedly elevated; ACE inhibitors or angiotensin receptor blockers are renoprotective but are less effective than thiazide diuretics and calcium channel blockers for lowering blood pressure r2
    • Children
      • Primary hypertension occurs mainly in children older than 13 years and is associated with family history and obesity; secondary hypertension is more common in younger children and may be caused by genetic conditions or renal, endocrine, or cardiovascular disorders r88
      • Hypertension in childhood and adolescence is associated with hypertension and cardiovascular disease in adulthood r89r90r91
      • Diagnose based on blood pressure compared with blood pressure percentile norms for age, sex, and height r32
      • Hypertension is diagnosed if systolic or diastolic blood pressure is at the 95th percentile or greater for age, sex, and height on at least 3 separate occasions, or if systolic or diastolic blood pressure is higher than 120/80 mm Hg in children aged 6 to 11 years, or higher than 130/85 mm Hg in children aged 12 to 17 years r32
        • Blood pressure is defined as "high normal" if systolic or diastolic blood pressure is in 90th to 95th percentile for age, sex, and height or 120/80 to 139/89 mm Hg in adolescents aged 13 years or older confirmed on 3 separate visits r92
      • Evaluate children with hypertension with serum biochemistry, lipids, glucose, urinalysis, renal ultrasonography, echocardiogram, and retinal examination r32
      • Initial treatment of high normal blood pressure is aimed at lifestyle modifications of altering diet, increasing exercise, and controlling weight
      • Commence pharmacologic therapy in cases of symptomatic hypertension; hypertension with end-organ damage; blood pressure greater than 95th percentile plus 12 mm Hg; blood pressure in the 90th percentile or greater associated with diabetes, chronic kidney disease, or heart failure; or persistent hypertension despite a 6-month or longer trial of nonpharmacologic therapy r32
      • Goal blood pressure levels are those that are consistently below 90th percentile for age, sex, and height or below 120/80 mm Hg in adolescents aged 13 years or older r92
      • Initial pharmacologic treatment consists of monotherapy with either an ACE inhibitor, angiotensin receptor blocker, or calcium channel blocker; refer to a pediatric hypertension specialist if not controlled with monotherapy r32
    • Pregnant patients
      • Hypertension in pregnancy includes the following: r52
        • Chronic (preexisting) hypertension
          • Blood pressure higher than 140/90 mm Hg that predates the pregnancy or begins before the 20th week of gestation r93
        • Gestational hypertension
          • Blood pressure higher than 140/90 mm Hg with onset after 20 weeks of gestation in a previously normotensive female: lasts less than 6 weeks postpartum
          • Not accompanied by proteinuria or severe features of preeclampsia (thrombocytopenia, renal insufficiency, elevated liver transaminase levels, pulmonary edema, cerebral or visual symptoms)
        • Preexisting hypertension with superimposed preeclampsia (gestational hypertension plus proteinuria)
        • Preeclampsia and eclampsia d5
          • Preeclampsia is defined by the presence of hypertension with proteinuria and/or new onset of signs of end-organ damage (known as severe features of preeclampsia) with onset after the 20th week of pregnancy r93
            • Severe features of preeclampsia include thrombocytopenia, renal insufficiency, elevated liver transaminase levels, pulmonary edema, cerebral or visual symptoms
          • Eclampsia presents as generalized, tonic-clonic seizures in patient with preeclampsia
        • Hemolysis, elevated liver enzyme levels, and low platelet count (HELLP syndrome) may be accompanied by severe hypertension d6
      • Maternal risks of hypertension in pregnancy include placental abruption, stroke, multiple organ failure, and disseminated vascular coagulation r52
      • Fetal risks include intrauterine growth restriction, preterm birth, and intrauterine death r52
        • Increased risk of congenital defects is seen in both treated and untreated hypertension, but risk is greater for babies of treated mothers r94
      • Thresholds for pharmacologic treatment vary
        • American College of Obstetricians and Gynecologists recommends pharmacologic therapy for chronic hypertension in pregnancy (ie, blood pressure higher than 140/90 mm Hg) r95r96
          • Treatment threshold of 140/90 mm Hg is associated with improved outcomes compared with the previously recommended threshold of 160/105 mm Hg r95r96
          • Patients already taking antihypertensive medications at the start of pregnancy can be maintained on these medications, providing they are safe for use in pregnancy, rather than discontinuing and resuming treatment if blood pressure reaches threshold
            • ACE inhibitors and angiotensin receptor blockers are contraindicated during pregnancy; labetalol, long-acting nifedipine, or methyldopa are preferred (see below). Medication adjustment, if indicated, should be a part of preconception planning
        • International Society of Hypertension recommends pharmacologic treatment at blood pressure higher than 150/95 mm Hg in all pregnant patients and at blood pressure higher than 140/90 mm Hg in patients with gestational hypertension, preexisting hypertension with superimposed gestational hypertension, and hypertension with subclinical hypertension-mediated organ damage any time during pregnancy r52
        • Hypertension Canada guidelines recommend starting antihypertensive therapy at average systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher in pregnant patients with chronic hypertension, gestational hypertension, or preeclampsia r32
      • Initial therapy consists of monotherapy with either oral labetalol, methyldopa, long-acting nifedipine, or other β-blockers r52
        • Second line agents include clonidine, hydralazine, and thiazide diuretics
        • ACE inhibitors and angiotensin receptor blockers are contraindicated during pregnancy owing to teratogenicity and neonatal renal agenesis r32
      • Treatment with antihypertensives decreases risk of progression to severe hypertension, thrombocytopenia, and elevated liver enzyme levels but does not decrease risk of preeclampsia or other serious maternal complications or fetal or neonatal death or morbidity r97r98
      • US Preventive Services Task Force and American College of Obstetricians and Gynecologists recommend the use of low-dose aspirin (81 mg/day) for prevention of preeclampsia for patients at high risk after 12 weeks of gestation r95r99r100
        • Begin between 12 and 28 weeks of gestation (ideally before 16 weeks) and continue daily until delivery
      • Patients with severe hypertension (systolic at least 160-170 mm Hg and/or diastolic higher than 105-110 mm Hg) require immediate hospitalization and urgent antihypertensive therapy; considered an obstetric emergency
        • IV labetalol and hydralazine are first line medications for the management of acute-onset, severe hypertension in pregnant patients; immediate-release oral nifedipine is an alternative if IV access is not established r93
        • Magnesium sulfate is indicated for seizure prophylaxis in females with acute-onset severe hypertension during pregnancy (regardless of whether it is gestational hypertension or preeclampsia with severe features or eclampsia) r101
        • Delivery, after maternal stabilization, is recommended for patients who have a diagnosis of gestational hypertension or preeclampsia with severe features at or beyond 34 weeks of gestation r101
        • Delivery at or beyond 37 weeks of gestation is recommended in patients with gestational hypertension or preeclampsia without severe features r101

    Monitoring

    • Treat adults with an elevated blood pressure or stage 1 hypertension who have an estimated 10-year atherosclerotic cardiovascular disease risk lower than 10% with nonpharmacologic therapy, and evaluate blood pressure again within 3 to 6 months r1c277
    • Initially treat adults with stage 1 hypertension who have an estimated 10-year atherosclerotic cardiovascular disease risk of 10% or higher with a combination of nonpharmacologic and antihypertensive drug therapy, and evaluate blood pressure again in 1 month r1c278
    • Adults with stage 2 hypertension should be evaluated by or referred to a primary care practitioner within 1 month of the initial diagnosis, have a combination of nonpharmacologic and antihypertensive drug therapy (with 2 agents of different classes) started, and have blood pressure evaluated again in 1 month r1c279c280
    • For adults with a very high average blood pressure (eg, systolic 180 mm Hg or higher, diastolic 110 mm Hg or higher), evaluation followed by prompt antihypertensive drug treatment is recommended r1c281
    • Adults starting a new or adjusted drug regimen for hypertension should have a follow-up evaluation of adherence and response to treatment at monthly intervals until control is achieved r1c282c283
    • For adults with blood pressure within reference range, repeating evaluation every year is reasonable r1c284
    • Self-measured blood pressure monitoring is a validated approach for out-of-office blood pressure measurement and may be associated with improved blood pressure control r102
    • Laboratory monitoring
      • For all patients, monitor serum potassium and creatinine levels at least once or twice yearly r28c285c286
      • For patients taking angiotensin receptor blockers or ACE inhibitors r103
        • Measure creatinine and potassium levels within 1 to 2 weeks of beginning therapy and 1 to 2 weeks after each dose increase; measure within 7 days if patient is at higher risk for hyperkalemia or acute kidney injury c287c288
        • If creatinine level increases by 30% over baseline after starting, discontinue drug and recheck levels in 3 days
          • If cause is temporary (eg, dehydration), patient may resume drug once resolved
          • If no cause is identified, consider renal artery stenosis or drug-induced kidney injury
        • Potassium level higher than 5.6 mEq/L generally necessitates dose reduction or discontinuation
      • For patients taking aldosterone antagonists r104r105
        • Monitor serum potassium before beginning of therapy, within the first week, and 1 month after the start of treatment or dose adjustment. Periodically assess serum potassium thereafter.
        • Potassium level higher than 5.5 mEq/L generally necessitates dose reduction or discontinuation
        • Advise patients to avoid taking potassium supplements or using dietary salt substitutes that contain potassium

    Complications and Prognosis

    Complications

    • Cardiovascular disease
      • Chronic hypertension is a major risk factor for cardiovascular disease and mortality, with no evidence of a threshold effect down to 115/75 mm Hg r106
      • Coronary artery disease c289
        • Diastolic blood pressure elevation is the primary predictor of risk in persons younger than 50 years r106
        • Systolic blood pressure is a more important predictor in persons older than 60 years r106
        • In adults aged 40 to 69 years, each 20-mm Hg increase in systolic blood pressure (or each 10-mm Hg increase in diastolic pressure) doubles the risk of a fatal coronary event r107
      • Stroke (including ischemic and hemorrhagic stroke) c290c291c292
        • In adults aged 40 to 69 years, each 20-mm Hg increase in systolic blood pressure (or each 10-mm Hg increase in diastolic pressure) more than doubles the risk of stroke r107
        • Similar hazard ratios for mortality for cerebral hemorrhage and ischemic stroke r106
      • Left ventricular hypertrophy and heart failure c293c294
        • In the long term, treatment of hypertension reduces the risk of heart failure by approximately 50% and reduces heart failure mortality r108
      • Increased risk of atrial fibrillation c295
    • Hypertension is the most common cause of chronic kidney disease; conversely, chronic kidney disease can lead to or exacerbate hypertension r43c296
    • Chronic hypertensive retinopathy may cause significant vision loss over time c297
    • End-organ damage or dysfunction may also occur acutely (during hypertensive emergency), including:
      • Hypertensive encephalopathy with cerebral hyperperfusion and cerebral edema c298c299
      • Stroke, either ischemic or hemorrhagic c300c301
      • Acute coronary syndrome c302
      • Pulmonary edema caused by diastolic dysfunction or acute mitral regurgitation with left ventricular failure c303
      • Aortic dissection c304
      • Acute kidney injury c305
        • HELLP syndrome may occur with very high blood pressure and microangiopathic hemolytic anemia associated with kidney injury c306c307c308
      • Acute hypertensive retinopathy with disk edema, choroidal infarction, and retinopathy c309

    Prognosis

    • Essential hypertension persists for life; blood pressure tends to increase with age
    • Nearly all patients will need to continue medication throughout life
    • Untreated hypertension, especially with other cardiovascular risk factors, may lead to stroke, coronary artery disease, and heart failure

    Screening and Prevention

    Screening

    At-risk populations

    • US Preventive Services Task Force recommends screening for high blood pressure in all adults aged 18 years or older r109c310c311
      • Adults aged 40 years or older and persons at increased risk for high blood pressure: screen annually
      • Adults aged 18 to 39 years with no increased risk for hypertension and with prior blood pressure readings within reference range: screen every 3 to 5 years
    • US Preventive Services Task Force does not recommend screening for high blood pressure in asymptomatic children and adolescents aged 3 to 18 years r88
      • However, American Academy of Pediatrics, European Society of Hypertension, and Canadian hypertension guidelines do recommend regular screening blood pressure measurement in children and adolescents r32r92r110

    Screening tests

    • Office measurement of blood pressure with a manual or automated sphygmomanometer r109c312
      • Use the mean of 2 measurements taken while the patient is seated
      • Multiple measurements over time have better positive predictive value than measurement on a single day
      • Ambulatory and self-measured home blood pressure monitoring can be used to confirm a diagnosis of hypertension after initial screening r102
      • Other indications for self-measured blood pressure monitoring include the diagnosing of white coat hypertension and masked hypertension and detection of morning hypertension; validated blood pressure monitoring devices that use the oscillometric method are preferred r102

    Prevention

    • Risk of developing essential hypertension may be decreased by the following:
      • Maintenance of body weight within reference range r13c313
      • Regular exercise c314
      • Low-sodium diet c315
    • Calcium intake more than 1000 mg/day slightly reduces both systolic and diastolic blood pressure in normotensive people, but this finding requires confirmation r84c316
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