Hypertension

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 patients^r1, 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

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 pressure^r5
  • 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 microangiopathy^r9
  • 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

Clinical Presentation

Causes and Risk Factors

Diagnostic Procedures

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

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

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 nitroglycerin^r28 and β-blockers^r4r8
  • A fast-acting drug is preferable;^r4esmolol is suggested as an agent of choice^r1
  • 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

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

• 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

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