Essential Hypertension

Chapter: Essential Hypertension
McMaster Section Editor(s): Christine M. Ribic, Karen C.Y. To
Section Editor(s) in Interna Szczeklika: Andrzej Budaj, Wiktoria Leśniak
McMaster Author(s): K. Scott Brimble, Gordon Guyatt
Author(s) in Interna Szczeklika: Andrzej Januszewicz, Aleksander Prejbisz
Additional Information

Etiology and PathogenesisTop

Essential (or primary) hypertension is caused by a variety of genetic and environmental factors that interfere with the functioning of one or more of the systems involved in the regulation of blood pressure (BP) and thus lead to increased BP. The following factors play an important role in the development of hypertension: the renin-angiotensin-aldosterone (RAA) system, sympathetic nervous system, natriuretic peptides, and substances produced by the vascular endothelium (prostacyclin, nitric oxide, endothelins). Family history increases one’s risk of developing essential hypertension; it is likely that genetic contributions to hypertension risk are mediated through many or all of the factors enumerated above. The lifetime risk of developing hypertension approaches 80% in those aged 80 years or older.Evidence 1 High Quality of Evidence (high confidence that we know true effects of the intervention). Robitaille C, Dai S, Waters C, et al. Diagnosed hypertension in Canada: incidence, prevalence and associated mortality. CMAJ. 2012 Jan 10;184(1):E49-56. doi: 10.1503/cmaj.101863. Epub 2011 Nov 21. PubMed PMID: 22105752; PubMed Central PMCID: PMC3255225. Dannenberg AL, Garrison RJ, Kannel WB. Incidence of hypertension in the Framingham Study. Am J Public Health. 1988 Jun;78(6):676-9. PubMed PMID: 3259405; PubMed Central PMCID: PMC1350281. The risk and/or severity of hypertension are increased by excessive sodium intake, physical inactivity, obesity (especially abdominal), and stress (increased sympathetic activation).

Clinical Features and Natural HistoryTop

Clinical classification (grading) based on BP values: see Table 3.9-1.

Hypertension is usually asymptomatic. Headache, sleep disturbances, and easy fatigability may occur. Other signs and symptoms appear with the development of target organ complications of hypertension. In the majority of patients with uncomplicated essential hypertension, physical examination reveals no significant abnormalities aside from an increase in BP. Over time, ranging from months to decades, hypertension may lead to pathophysiologic changes, including the accelerated development of atherosclerosis, arterial stiffness, and left ventricular (LV) hypertrophy. The clinical manifestations of these changes lead to an increased risk of:

1) Coronary artery disease, including myocardial infarction and angina.

2) Stroke (ischemic and hemorrhagic).

3) Congestive heart failure.

4) Peripheral vascular disease.

5) Premature death from cardiovascular causes.

6) Persistent kidney injury (a urinary albumin-to-creatinine ratio [ACR] elevated ≥3 mg/mmol [30 mg/g] and/or decline in estimated glomerular filtration rate [eGFR] usually develops slowly; in mild to moderate hypertension the development of end-stage renal disease is rare and usually appears after many years of hypertension).

7) Aortic dissection.

8) Visual impairment.

DiagnosisTop

Diagnostic workup includes:

1) Confirmation of the diagnosis of hypertension.

2) If appropriate, search for causes of secondary hypertension.

3) Assessment of cardiovascular risk factors, target organ complications, and comorbidities.

Diagnostic Tests

1. BP measurements: To determine the BP, perform traditional measurements (office measurements using either the manual auscultatory method or automated oscillometric blood pressure; the latter allows a sufficient rest period with the health-care provider out of the room, is typically 5-10 mm Hg [or more] lower, and is preferred), and make use of the self-measurements performed by the patient (see below) as well as, in some cases, also of the results of ambulatory BP monitoring (ABPM).

2. Laboratory tests that are suggested include:

1) Serum levels of sodium, potassium, glucose (fasting) and/or serum glycated hemoglobin (HbA1c), creatinine (with calculation of eGFR using the CKD-EPI formula; see Chronic Kidney Disease), uric acid, total cholesterol, high-density (HDL-C) and low-density (LDL-C) lipoprotein cholesterols, and triglycerides.

2) Urinalysis: Urine dipstick test for blood and protein.

3. 12-lead electrocardiography (ECG) is suggested in all patients.

4. Additional studies are suggested as guided by the clinical assessment and routine laboratory tests:

1) Quantitative assessment of urinary albumin and urine microscopy (in patients with positive results of the dipstick test).

2) Measurements of daily urinary sodium excretion to evaluate sodium intake.

3) ABPM and/or home BP measurements.

4) Echocardiography with the assessment of LV hypertrophy and cardiovascular risk in patients where it is unclear if pharmacologic therapy should be initiated or in those with suspected LV dysfunction.

5) Screening for obstructive sleep apnea if clinically suspected (consider using the Epworth Sleepiness Scale [see Obstructive Sleep Apnea] or the STOP-Bang questionnaire [stopbang.ca]).

5. Suggested studies based on suspected etiology of secondary hypertension (frequently performed in referred/specialized care):

1) Renal parenchymal etiology if suggested by history (urinary tract infection or obstruction, hematuria, analgesic abuse; family history of polycystic kidney disease [PKD]), laboratory tests (protein and red blood cells in urine, decreased eGFR), or physical examination showing renal masses (PKD): Consider renal ultrasonography as a first-line additional test. If needed, follow with referral and more specialized tests (see Chronic Kidney Disease).

2) Renal vascular etiology if suggested by history (difficult to control hypertension, especially with early onset [fibromuscular dysplasia] or rapid onset [atherosclerosis]), physical examination (abdominal bruit) or tests (difference in kidney size on ultrasonography, rapid worsening of eGFR either spontaneously or after exposure to RAA system inhibitors (angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers [ARBs]): Investigations: see Renovascular Hypertension.

3) Primary hyperaldosteronism if suggested by history (early onset, cardiovascular events at an age <40 years), physical examination (arrhythmia secondary to low potassium), or laboratory tests (hypokalemia, either spontaneous or diuretic-induced): Investigations: see Primary Aldosteronism.

4) Cushing syndrome if suggested by history (rapid weight gain, polyuria and polydipsia), physical examination showing typical body habitus, and laboratory tests showing hyperglycemia: Investigations: see Cushing Syndrome.

5) Pheochromocytoma may be suggested by history (paroxysmal hypertension or crisis in the course of sustained hypertension; headache, sweating, palpitations, and pallor; family history of pheochromocytoma), physical examination (cutaneous neurofibromatosis (café au lait spots or neurofibromas), and laboratory tests (adrenal mass), with further investigations for the presence of excessive urinary catecholamines or their metabolites (metanephrines).

6. BP self-measurement may be indicated:

1) As part of diagnostic workup.

2) When starting or intensifying antihypertensive treatment.

3) As part of long-term monitoring of patients.

Diagnostic Criteria

The diagnosis is made on the basis of BP values obtained from ≥2 measurements performed on ≥2 visits. Essential hypertension (common) is considered probable if the history and/or initial testing do not suggest underlying secondary hypertension (rare).

Perform screening BP measurement in all adults periodically (frequency is based on underlying risk factors, including age and previous BP patterns).

Differential Diagnosis

1. Secondary hypertension: Clinical indications and diagnostics of secondary hypertension: see above.

2. White coat hypertension: Increase in BP in some patients during measurement performed by a physician or nurse; in such patients use ABPM. If the office BP levels are consistent with hypertension while the results of repeated home measurements or ABPM are normal, the diagnosis of white coat hypertension is made.

3. Masked hypertension: Conversely, if the patient has normal office BP levels and elevated results of home and ABPM measurements, the diagnosis of masked hypertension is established. This may be due to smoking, exercise-induced hypertension, anxiety, job stress, or other factors and is not only difficult to detect but also associated with an increased cardiovascular risk.

4. Pseudohypertension: In the elderly the results of BP measurements using auscultation may be significantly elevated due to increased arterial stiffness (sclerosis), which causes the early appearance and disappearance of pulse. This may be observed if the pulse remains palpable even after filling the cuff above the systolic blood pressure (SBP) level (the stiffened artery cannot be sufficiently compressed by the cuff). Another feature suggestive of pseudohypertension is the absence of target organ damage caused by hypertension. In patients with suspected pseudohypertension, measure the BP using oscillometric devices and not auscultation.

TreatmentTop

Acute and Urgent Treatment

The management procedure is determined by the BP values, type of target organ complications, patient’s age, and comorbidities (Table 3.9-2). In emergencies, such as pulmonary edema, hypertensive encephalopathy, or aortic dissection, immediately lower the BP using parenteral antihypertensive drugs (Table 3.9-3), preferably in a continuous IV infusion. We suggest that in such cases the mean arterial pressure should be reduced by <25% of BP reduction during the first hours and cautiously thereafter. In the case of acute stroke, BP should be reduced more gradually, if at all.

Long-Term Treatment

General Considerations

Comprehensive lifestyle optimization strategies have been shown to lower SBP and diastolic blood pressure (DBP) among patients with hypertension by 14.2 mm Hg and 7.4 mm Hg on average, respectively.Evidence 2 Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision and lack of a no-intervention group. Appel LJ, Champagne CM, Harsha DW, et al; Writing Group of the PREMIER Collaborative Research Group. Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial. JAMA. 2003 Apr 23-30;289(16):2083-93. PubMed PMID: 12709466. The evidence to date indicates that although some patients may not have hypertension as currently defined (ie, BP >140/90 mm Hg), they may nevertheless benefit from BP-lowering therapy, particularly if they have a higher baseline cardiovascular risk. One must therefore consider the current BP (and not just whether the patient has hypertension), the BP target based on the patient’s characteristics as outlined below, past tolerability of treatment, and personal preferences. With increasing evidence that targets vary among different patient groups, the utility of grading hypertension may ultimately be limited to guiding the rapidity at which to initiate pharmacologic therapy, the number of pharmacologic agents that will likely be required, and consideration of secondary causes. We have recommended a target BP in each case as a range of 10 mm Hg and suggested that treatment be initiated when the measured BP is persistently at or above the upper limit of that range.

1. Long-term treatment of hypertension includes:

1) Lifestyle optimization.

2) Treatment with antihypertensive drugs (Figure 3.9-1).

3) Optimization of other cardiovascular risk factors.

2. Decisions on the choice of treatment modalities depend on the patient’s BP levels and overall cardiovascular risk:

1) In patients with grade 3 hypertension (SBP ≥180 mm Hg and/or DBP ≥110 mm Hg), promptly start pharmacotherapy combined with lifestyle optimization regardless of the cardiovascular risk.

2) In patients with grade 2 hypertension (SBP 160-179 mm Hg and/or DBP 100-109 mm Hg), start treatment simultaneously with lifestyle modifications, especially in those with >2 cardiovascular risk factors or any one of the following: target organ damage, diabetes mellitus, cardiovascular disease, or chronic kidney disease. In patients not fulfilling these criteria it may be acceptable to delay treatment for a few weeks to observe the effects of lifestyle modifications.

3) In patients with grade 1 hypertension (SBP 140-159 mm Hg and/or DBP 90-99 mm Hg), start pharmacotherapy if the response to lifestyle optimization is inadequate.

3. Target BP levels: Note that these targets are guides and that in many cases the achieved BP will be higher due to treatment and patient factors, including undue adverse effects. The BP target may be 5 to 10 mm Hg higher if measured using methods different than automated oscillometric BP measurements, as described above. It is also worth noticing that different expert bodies, using similar data, have reached different conclusions regarding exact targetsEvidence 3High Quality of Evidence (high confidence that we know true effects of the intervention). Antza C, Doundoulakis I, Stabouli S, Kotsis V. Comparison Among Recommendations for the Management of Arterial Hypertension Issued by Last US, Canadian, British and European Guidelines. High Blood Press Cardiovasc Prev. 2018 Mar;25(1):9-16. doi: 10.1007/s40292-017-0236-x. Epub 2017 Nov 1. PubMed PMID: 29094260.:

1) SBP <140 mm Hg in all patients with hypertension, with the following exceptions:

a) In noninstitutionalized patients without dementia, diabetes mellitus, symptomatic heart failure, or prior stroke and (i) who are aged >50 years and have either clinically evident cardiovascular disease, an eGFR <60 mL/min/1.73m2, or a 10-year risk score >15% (which corresponds to ≥13 points for men and ≥16 points for women; see Table 3.15-1), or (ii) who are ≥75 years of age, the target SBP is <120 mm Hg (if measured using automated oscillometric BP measurement). Patients with ≥1 of these indications should participate in discussion about benefits and risks of more intensive therapy and give their consent.Evidence 4 Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to some heterogeneity in other populations. SPRINT Research Group, Wright JT Jr, Williamson JD, Whelton PK, et al. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med. 2015 Nov 26;373(22):2103-16. doi: 10.1056/NEJMoa1511939. Epub 2015 Nov 9. Erratum in: N Engl J Med. 2017 Dec 21;377(25):2506. PubMed PMID: 26551272; PubMed Central PMCID: PMC4689591. Lonn EM, Bosch J, López-Jaramillo P, et al; HOPE-3 Investigators. Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N Engl J Med. 2016 May 26;374(21):2009-20. doi: 10.1056/NEJMoa1600175. Epub 2016 Apr 2. PubMed PMID: 27041480. Yusuf S, Bosch J, Dagenais G, et al; HOPE-3 Investigators. Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N Engl J Med. 2016 May 26;374(21):2021-31. doi: 10.1056/NEJMoa1600176. Epub 2016 Apr 2. PubMed PMID: 27040132. Yusuf S, Lonn E, Pais P, et al; HOPE-3 Investigators. Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease. N Engl J Med. 2016 May 26;374(21):2032-43. doi: 10.1056/NEJMoa1600177. Epub 2016 Apr 2. PubMed PMID: 27039945. ACCORD Study Group, Cushman WC, Evans GW, Byington RP, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010 Apr 29;362(17):1575-85. doi: 10.1056/NEJMoa1001286. Epub 2010 Mar 14. PubMed PMID: 20228401; PubMed Central PMCID: PMC4123215. Brunström M, Carlberg B. Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses. BMJ. 2016 Feb 24;352:i717. doi: 10.1136/bmj.i717. Review. PubMed PMID: 26920333; PubMed Central PMCID: PMC4770818. Examples of risk calculators: Framingham Coronary Heart Disease Risk Score at mdcalc.com; ACC/AHA 2013 Cardiovascular Risk Assessment at medscape.com.

b) Patients with diabetes mellitus: see Special Considerations, below.

2) DBP <90 mm Hg in all patients.

Lifestyle Modifications

1. Reduction of weight in overweight patients and maintenance of a normal body weight (waist circumference ≤88 cm in women, ≤102 cm in men; body mass index <25 kg/m2).

2. A diet that emphasizes fruits and vegetables, low-fat dairy products, whole grains, and protein from plant sources that is reduced in saturated fat and cholesterol, including nuts, seeds, and legumes (the DASH [Dietary Approaches to Stop Hypertension] diet).

3. Reduction of sodium intake to ≤5 to 6 g of salt.

4. Limitation of daily alcohol consumption to a maximum of 20 to 30 g of ethanol in men and 10 to 20 g in women and individuals with a low body weight.

5. Appropriate physical activity: Regular aerobic exercise, such as brisk walking for 30 to 45 minutes daily.

6. Smoking cessation.

Antihypertensive Treatment

1. The major classes of antihypertensive agents are diuretics (mainly thiazide and thiazide-like diuretics), beta-blockers, calcium channel blockers, ACEIs, and ARBs. Their BP-lowering efficacy is similar. Beta-blockers have been shown to be inferior to the other agents in their efficacy to reduce cardiovascular eventsEvidence 5 High Quality of Evidence (high confidence that we know true effects of the intervention). Ettehad D, Emdin CA, Kiran A, et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016 Mar 5;387(10022):957-967. doi: 10.1016/S0140-6736(15)01225-8. Epub 2015 Dec 24. Review. PubMed PMID: 26724178. and are generally not recommended as first-line therapy in North American guidelines anymore. Specific indications and contraindications: Table 3.9-4. Agents and dosage: Table 3.9-5.

2. Additional antihypertensive drugs: Renin inhibitors (aliskiren), angiotensin receptor blocker/neprilysin inhibitor combinations, alpha1-blockers (doxazosin, terazosin, prazosin), centrally acting sympathetic inhibitors (methyldopa, clonidine), direct vasodilators (hydralazine, minoxidil), nonthiazide or thiazide-like diuretics. These agents are used in combination treatment and in special situations. Agents, dosage, specific indications and contraindications: Table 3.9-6.

3. Principles of pharmacotherapy: Depending on the cardiovascular risk as well as the baseline and target BP levels, start with 1 drug at a low dose (any agent of the main antihypertensive classes may be used, unless specific indications for or contraindications to any particular class exist), or 2 drugs at low doses (in patients with BP elevated by >20/10 mm Hg [ie, grade 2 or 3 hypertension] or at high cardiovascular risk). Most agents produce the full antihypertensive effect after a few weeks of treatment, so their effectiveness should be assessed after 2 to 4 weeks.

In patients in whom treatment with 1 drug at a low dose does not provide BP control (in a significant majority of patients treatment with ≥2 antihypertensive agents is necessary), you may:

1) Add a second drug (the preferred strategy).

2) Change to another drug (only if no hypotensive effects have been achieved or if adverse reactions occurred).

3) Increase the dose of the currently used drug (this increases the risk of adverse effects).

In patients in whom treatment with 2 drugs at low doses (either from the beginning or at a subsequent phase of treatment) is not effective, you may:

1) Increase the doses of the currently used drugs; or

2) Add a third drug at a low dose.

Usually 2 or 3 antihypertensive agents are used; less commonly more drugs are necessary. The main benefits of a combination therapy are higher efficacy and fewer adverse effects (drug doses used in combinations are lower than those used in monotherapy). Preferred combinations include:

1) A thiazide/thiazide-like diuretic + an ACEI.

2) A thiazide/thiazide-like diuretic + an ARB.

3) A thiazide/thiazide-like diuretic + a calcium channel blocker.

4) A calcium channel blocker + an ACEI.

5) A calcium channel blocker + an ARB.

The most rational triple-drug combination includes a drug acting on the RAA system (an ACEI or an ARB) + a calcium channel blocker + a thiazide/thiazide-like diuretic.

Follow-UpTop

The frequency of follow-up visits depends on the overall cardiovascular risk, BP level, and patient’s compliance (eg, regarding BP self-measurements at home). Once the target BP has been achieved and other risk factors have been adequately controlled, the frequency of visits can be significantly reduced. It may be of value to ask patients to record their resting BP, when possible, on several occasions prior to their follow-up visit.

Suggested schedule of follow-up visits in patients with hypertension:

1) After 2 to 4 weeks of starting antihypertensive treatment.

2) After 4 weeks of introducing a change in the treatment regimen.

3) Every 3 months after achieving the target BP.

Special ConsiderationsTop

Elderly Patients

1. In elderly patients (>65 years of age) the most common form of hypertension is isolated systolic hypertension. Additionally, orthostatic hypotension is frequent (BP must also be measured in the upright position).

2. General principles of antihypertensive treatment in the elderly:

1) Lower BP gradually, initially using low doses of drugs.

2) Note that interactions with other drugs may occur.

3) For many, a target SBP <140 mm Hg will be reasonable. In those who have been identified as potentially benefiting from an SBP target <120 mm Hg (see above), consider cautiously lowering SBP further while monitoring for adverse effects including orthostatic hypotension.

3. You can start treatment with a drug from any major antihypertensive class; however, in patients with isolated systolic hypertension start with a diuretic (thiazide or thiazide-like) or a calcium channel blocker. As comorbidities are frequent in patients with hypertension, these should be taken into consideration when choosing antihypertensive agents.

4. In a significant proportion of patients, it is necessary to use ≥2 antihypertensive drugs to achieve the target BP levels.

Patients With Diabetes Mellitus

1. There is currently some uncertainty as to the BP target, as demonstrated by differences in the most key clinical practice guidelines. SBP targets range between 130 and 140 mm Hg and DBP between 80 and 90 mm Hg. We suggest a BP target <130/80 mm Hg, particularly in those with diabetic nephropathy, if it can be achieved without undue treatment burden (see Diabetes Mellitus).

2. All the major classes of antihypertensive drugs have beneficial effects in this group of patients.

3. ACEIs and ARBs have renal protective effects, significantly reduce proteinuria, and are the preferred option in patients with albuminuria.

4. In a significant proportion of patients, the target BP values can only be achieved with ≥3 appropriately selected antihypertensive drugs.

5. BP should also be measured in the upright position due to the increased risk of orthostatic hypotension.

6. Intensive lifestyle modifications are of particular importance (see Lifestyle Modifications, above).

White Coat Hypertension

In patients with no additional cardiovascular risk factors, consider limiting the intervention to lifestyle changes, as long as careful follow-up is continued. In patients with a higher cardiovascular risk due to metabolic disturbances or asymptomatic target organ damage, you may consider adding antihypertensive pharmacotherapy.

Masked Hypertension

Consider introducing both lifestyle changes and antihypertensive drugs, as this category of hypertension is associated with a cardiovascular risk similar to that of hypertension observed in both office and home measurements.

Resistant Hypertension

Hypertension is defined as resistant if target BP values cannot be achieved despite the use of ≥3 antihypertensive drugs (including a diuretic) at optimal doses and in appropriate combinations.

Causes:

1) Noncompliance with the antihypertensive drug regimen and with lifestyle modifications (alcohol abuse, tobacco smoking, excessive sodium intake, persistent obesity).

2) Inappropriate drug combinations (failure to include a diuretic in treatment, using a diuretic at inadequate doses, or failure to adapt the type of the diuretic to the patient’s renal function).

3) Pseudoresistance to treatment (BP measurement errors, white coat hypertension [see above]).

4) Pseudohypertension (see Differential Diagnosis, above).

5) Obstructive sleep apnea.

6) Drug interactions reducing the efficacy of antihypertensive drugs (nonsteroidal anti-inflammatory drugs [NSAIDs]).

7) Treatment with drugs that increase BP.

8) Metabolic syndrome (insulin resistance).

9) Chronic kidney disease.

10) Unrecognized secondary hypertension.

Management:

1) Resistance to treatment is confirmed in patients in whom target office BP levels are not achieved despite treatment with ≥3 antihypertensive drugs at optimal doses, including a diuretic.

2) Exclude pseudoresistance: Determine whether the patient is compliant with the recommended treatment and exclude white coat hypertension (if the patient has abnormal office BP levels with normal BP levels in self-measurement or ABPM, pseudoresistance to treatment is confirmed).

3) Identify and attempt to modify adverse lifestyle factors, such as obesity, excessive alcohol consumption, or high sodium intake.

4) Eliminate or minimize the effect of substances that increase blood pressure, such as NSAIDs, sympathomimetic agents (appetite suppressants, decongestants), stimulants, and oral contraceptives.

5) Search for causes of secondary hypertension.

6) Modify pharmacotherapy: Maximize diuretic treatment (consider adding an aldosterone antagonist or amiloride, use loop diuretics in patients with renal failure), use drugs with different mechanisms of action.

7) Refer the patient to a specialist in the case of a confirmed or suspected secondary hypertension, or if hypertension remains uncontrolled despite a sufficient duration of treatment.

Accelerated Hypertension

The most severe form of hypertension, characterized by a DBP >120 to 140 mm Hg, rapid progression of target organ complications, and particularly by the development of heart failure, renal failure, and severe lesions in the retinal vessels (transudates, ecchymoses, papilledema). This type of hypertension may develop in the course of hypertension of various etiologies, both essential and secondary, and is most common in patients with renal artery stenosis or glomerulonephritis. The term “malignant hypertension” was used in the past to indicate the very poor prognosis in such patients.

Symptoms are often present and can include weakness, headache, dizziness, dyspnea, chest pain, and less commonly abdominal pain (caused by abnormalities of intestinal vessels). Symptoms of rapidly progressive renal failure as well as central nervous system symptoms of varying severity, up to severe encephalopathy, may predominate. The patients are at increased risk of stroke and heart failure, often in the form of pulmonary edema.

Diagnosis is based on the clinical and laboratory manifestations.

Tables and FiguresTop

Table 3.9-2. Treatment of hypertensive emergencies

Clinical presentation

Target BP

Recommended drugs

Accelerated (malignant) hypertension

MAP reduced by 20%-25%

– First choice: Labetalol or nicardipinea

– Second choice: Nitroprusside or urapidila

Hypertensive encephalopathy

MAP reduced by 20%-25%

– First choice: Labetalol or nicardipinea

– Second choice: Nitroprusside

Acute coronary event

SBP <140 mm Hg

 

– First choice: Nitroglycerine or labetalol

– Second choice: Urapidila

Acute cardiogenic pulmonary edema

SBP <140 mm Hg

– First choice: Nitroglycerine or nitroprusside (with loop diuretic)

– Second choice: Urapidila (with loop diuretic)

Acute aortic dissection

SBP <120, HR <60 beats/min

– First choice: Beta-blocker (esmolol, propranolol); add nitroglycerine, nitroprusside, or nicardipinea if needed

– Second choice: Labetalol or metoprolol

Eclampsia and severe preeclampsia/HELLP

SBP <160 mm Hg, DBP <105 mm Hg

– Magnesium sulfate plus one or more of labetalol, nicardipine,a or oral nifedipine

– Consider immediate delivery

Notes:

1) Treatment in the ICU or an equivalent setting is mandatory.

2) Drugs are usually delivered IV.

3) BP reduction should occur immediately (or within several hours in case of accelerated/malignant hypertension).

a Not available in Canada.

Adapted from Eur Heart J. 2018;39(33):3021-3104.

BP, blood pressure; DBP, diastolic blood pressure; HELLP, hemolysis, elevated liver enzymes, and low platelets; IV, intravenous; MAP, mean arterial pressure; SBP, systolic blood pressure.

Table 3.9-3. Parenteral drugs for treatment of hypertensive emergencies

Drug

Dose

Onset/duration of action

Contraindications

Adverse effectsa

Special indications

Vasodilators

Enalaprilat

0.625-1.25 mg IV bolus

5-15 min/4-6 h

History of angioedema

 

Acute LV failure; avoid in acute MI

Fenoldopam

0.1-0.3 microg/kg/min as IV infusion

<5 min/30 min

 

Tachycardia, headache, nausea, flushing

In most hypertensive emergencies; use with caution in patients with glaucoma

Hydralazine

10-20 mg IV

10-20 min/1-4 h

 

Tachycardia, flushing, headache, vomiting, worsening of angina pectoris

Eclampsia

Nicardipine

5-15 mg/h IV infusion, starting dose 5 mg/h, increase every 15-30 min by 2.5 mg until target BP is achieved, then decrease to 3 mg/h

5-15 min/30-40 min

Liver failure

Headache, reflex tachycardia

In most hypertensive emergencies except for acute heart failure; use with caution in patients with coronary ischemia

Nitroglycerin

5-100 microg/min as IV infusion

2-5 min/5-10 min

 

Headache, vomiting, methemoglobinemia, development of tolerance with prolonged use

Myocardial ischemia, heart failure

Sodium nitroprusside

0.25-10 microg/kg/min as IV infusion (max dose may be administered only for 10 min)

Immediate/1-2 min

Liver/kidney failure (relative)

Nausea, vomiting, muscle cramps, sweating, cyanide and thiocyanate poisoning

In most hypertensive emergencies; use with caution in patients with high intracranial pressure or CKD

Adrenergic inhibitors

Esmolol

250-500 microg/kg/min IV bolus followed by 50-100 microg/kg/min as IV infusion; bolus may be repeated after 5 min or infusion rate increased to 300 microg/min

1-2 min/10-30 min

Second- or third-degree AV block, systolic heart failure, asthma, bradycardia

Nausea, AV block

Aortic dissection, perioperative emergencies

Labetalol

20-80 mg IV bolus every 10 min or 0.5-2 mg/min as IV infusion

5-10 min/3-6 h

Second- or third-degree AV block, systolic heart failure, asthma, bradycardia

Vomiting, scalp tingling, burning sensation in throat, dizziness, AV block

In most hypertensive emergencies except for acute heart failure

Phentolamine

5-15 mg IV

1-2 min/10-30 min

 

Tachycardia, headache, flushing

Catecholamine excess (eg, pheochromocytoma)

Urapidil (not available in Canada)

10-50 mg IV bolus then repeat once; or as IV infusion starting with 2 mg/min, then continued at average rate of 9 mg/h

1-5 min/1-2 h

 

Dizziness, headache, nausea, vomiting, dyspnea, palpitations, tachycardia or bradycardia, chest discomfort, arrhythmia

In most hypertensive emergencies

a Each of these drugs may cause hypotension.

Based on JAMA. 2014;311(5):507-20 and Eur Heart J. 2018;39(33):3021-3104.

AV, atrioventricular; CKD, chronic kidney disease; IV, intravenous; LV, left ventricle; MI, myocardial infarction.

Table 3.9-4. Preferred indications and contraindications for the use of key classes of antihypertensive drugs

Drug class

Preferred indications

Contraindications

Diuretics

 

Thiazide and thiazide-like diuretics

Isolated systolic hypertension (in the elderly), HF, hypertension in black patients

Gout, pregnancy,a hypercalcemia,a hyponatremia, hypokalemiaa

Aldosterone antagonists

HF, prior MI, prevention of AF (may be considered)

Hyperkalemia

Beta‑blockers

Angina pectoris, prior MI, HF, aortic aneurysm, pregnancy, prevention of AF (may be considered), ventricular rate control in AF

Asthma, second-degree/third-degree AV block, peripheral artery disease,a metabolic syndrome,a IGT,a COPD (except for beta-blockers with vasodilation effects),a athletes or physically active patients

Calcium channel blockers

 

Dihydropyridines

LV hypertrophy, asymptomatic atherosclerosis, angina pectoris, peripheral artery disease, isolated systolic hypertension (in the elderly), pregnancy, hypertension in black patients

Tachyarrhythmia,a HFa

Verapamil and diltiazem

Ventricular rate control in AF, LV hypertrophy, asymptomatic atherosclerosis, angina pectoris, peripheral artery disease, isolated systolic hypertension (in the elderly), metabolic syndrome, pregnancy, hypertension in black patients

Second-degree/third-degree AV block, severe LV dysfunction, HF

ACEIs

LV hypertrophy, asymptomatic atherosclerosis, microalbuminuria, renal dysfunction, prior MI, HF, prevention of AF (may be considered), end-stage renal failure/proteinuria, peripheral artery disease, metabolic syndrome, DM

Pregnancy, angioedema, hyperkalemia, bilateral renal artery stenosis, renal artery stenosis of a solitary functioning kidney

ARBs

LV hypertrophy, microalbuminuria, renal dysfunction, previous MI, HF, prevention of AF (may be considered), end-stage renal failure/proteinuria, metabolic syndrome, DM

Pregnancy, hyperkalemia, bilateral renal artery stenosis, renal artery stenosis of a solitary functioning kidney

a Relative contraindications.

Adapted from Can J Cardiol. 2018;34(5):506-525, Eur Heart J. 2018; 29(33):3021-3104, and Eur Heart J. 2013;34(28):2159-219.

ACEI, angiotensin-converting enzyme inhibitor; AF, atrial fibrillation; ARB, angiotensin receptor blocker; AV, atrioventricular; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus; HF, heart failure; IGT, impaired glucose tolerance; LV, left ventricle; MI, myocardial infarction.

Table 3.9-5. Typical dosage of oral antihypertensive agents

Agents and formulations

Dosage

Beta-blockers

Acebutolol

400 mg once daily or 200 mg bid

Atenolol

25-100 mg once daily

Betaxolol

5-20 mg once daily

Bisoprolol

2.5-10 mg once daily (max 20 mg/d)

Celiprolola

100-400 mg once daily

Carvedilol

6.25-25 mg once daily or bid

Metoprolol
 

Standard release

Controlled release

25-100 mg bid

50-100 mg once daily (up to 200 mg once daily)

Nebivolol

5 mg once daily

Pindolol

5-10 mg/d bid (doses up to 20 mg/d may be administered once daily; max 60 mg/d)

Propranolol

40-80 mg bid to qid

Calcium channel blockers

Amlodipine

2.5-10 mg once daily

Diltiazem
 

Standard release

Controlled release

30-60 mg tid

90-480 mg once daily or 90-240 mg bid

Felodipine

5-10 mg once daily

Isradipinea

2.5-10 mg once daily or 5 mg bid

Lacidipinea

4-6 mg once daily

Lercanidipinea

10-20 mg once daily

Nitrendipinea

10-20 mg once daily (max 20 mg bid)

Verapamil
 

Standard release

Extended release

40-120 mg tid to qid

120-240 mg once daily to bid

Diuretics    

Amiloride in a fixed-dose combination with hydrochlorothiazide

2.5-5 mg once daily to bid

Chlorthalidone (INN chlortalidone)

12.5-50 mg once daily or 50 mg every other day

Furosemide

20-40 mg daily to bid (typically bid when used as an antihypertensive)

Hydrochlorothiazide

12.5-50 mg once daily

Indapamide
 

Standard release

Extended release

1.25-2.5 mg once daily

1.5 mg once daily

Clopamidea

5-20 mg once daily

Spironolactone

25-50 mg once daily to bid

Torasemidea

2.5-10 mg once daily

Angiotensin-converting enzyme inhibitors

Benazepril

5-20 mg once daily to bid

Quinapril

5-40 mg once daily to bid

Cilazapril

2.5-5 mg once daily

Enalapril

2.5-20 mg once daily to bid (bid preferred)

Imidaprila

5-20 mg once daily

Captopril

25-50 mg bid to tid

Fosinopril

10-40 mg daily

Lisinopril

10-40 mg once daily

Perindopril

4(5)-8(10) mg once daily

Ramipril

2.5-5 mg once daily (max 10 mg)

Trandolapril

2-4 mg once daily

Zofenoprila

30 mg once daily (max 60 mg once daily or in 2 divided doses)

Angiotensin receptor blockers

Eprosartan

600 mg once daily

Irbesartan

150-300 mg once daily

Candesartan

8-32 mg once daily

Losartan

25-100 mg once daily or in 2 divided doses

Telmisartan

20-80 mg once daily

Valsartan

80-320 mg once daily

a Not available in Canada.

bid, 2 times a day; INN, international nonproprietary name; qid, 4 times a day; tid, 3 times a day.

Table 3.9-6. Additional antihypertensive drugs

Drugs

Dosage

Specific indications

Contraindications

Aliskiren

150-300 mg once daily

 

As in ARBs (see Table 3.9-4)

Sacubitril/valsartan

24/26-97/103 mg bid

Congestive heart failure

As in ARBs (see Table 3.9-4)

Doxazosin

1-16 mg once daily

Prostatic hypertrophy

Orthostatic hypotension, heart failure

Terazosin

1-20 mg once daily

Methyldopa

0.25-1 g bid

Hypertension in pregnancy; use in combination with a diuretic

Liver failure, pheochromocytoma, hemolytic anemia, depression, sexual dysfunction

Clonidine

0.05-0.2 mg bid to tid

Use in combination with a diuretic

Renal or liver failure, depression, sick sinus syndrome, bradyarrhythmia

Moxonidinea

0.2-0.6 mg/d

Mild and moderate hypertension, especially in young patients with symptoms of sympathetic activation

Severe depression, severe renal failure

Rilmenidinea

1 mg once daily to bid

Hydralazine

75-200 mg/d in 3-4 divided doses

Use in exceptional cases in combination with a diuretic and a beta-blocker

Tachycardia, cerebrovascular disease, mitral stenosis, aortic aneurysm, hypertrophic cardiomyopathy, ischemic heart disease, liver and kidney dysfunction, porphyria

a Not available in Canada.

ARB, angiotensin receptor blocker; bid, 2 times a day; tid, 3 times a day.

Figure 3.9-1. Decision algorithm for monotherapy vs combination treatment strategies in hypertension. Treatment should be intensified whenever target BP values are not achieved. Adapted from guidelines by the European Society of Hypertension, European Society of Cardiology, and Hypertension Canada.

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