Essential Hypertension

Essential hypertension-QR

ACKNOWLEDGEMENTS:

Thanks to Dr. Andrew Steele, MD, FRCPC, Medical Director and Chief of Nephrology, Lakeridge Health, Associate Professor of Medicine (Adjunct) Queens University, ON Canada, and Dr. Sadie Sattan, RN, BScN, MN, School of Nursing, Faculty of Health Sciences, McMaster University/Mohawk College, Hamilton, ON Canada for their expertise with the initial review of this topic.

Definition

Elevation in blood pressure beyond normal parameters

  • Essential (Primary) – No identifiable cause
  • Secondary (~5-10%) – Identifiable underlying cause

Classification of blood pressure for adults

Etiology

Primary (essential hypertension)

  • No identifiable cause

Secondary

  • Endocrine (e.g. hyperaldosteronism, thyroid, parathyroid, pheochromocytoma)
  • Renal disorders (e.g. glomerulonephritis)
  • Obstructive sleep apnea
  • Metabolic syndrome
  • Coarctation of aorta
  • Drug induced
  • Genetic (rare)
  • Lifestyle
  • Others

Risk factors

  • Cigarette smoking
  • Age (men >55, women >65)
  • Obesity (body mass index ≥30 kg/m2)
  • Dyslipidemia
  • Diabetes mellitus and metabolic syndrome
  • Physical inactivity
  • Diet-high sodium intake
  • Family history of premature vascular disease

Epidemiology

  • Third leading cause of death worldwide
  • Increases with age
  • An estimated 1.13 billion people worldwide have hypertension
  • Nearly 108 million (45%) of adults in the United States have hypertension
  • About 1 in 5 adults or ~7.5 million people in Canada live with hypertension
  • Affects 25% of the adult Canadian population
  • Typical onset between 25 and 55 years

Pathophysiology

Though still poorly understood, various factors have been suggested including enhanced beta adrenergic response, increased angiotensin II activity, and excess mineralocorticoids, which ultimately lead to:

  • Increased peripheral vascular resistance
  • Increased cardiac output
  • Increased blood volume

Genetic factors account for 30% cases (patients with family history of one or both parents).

A structural and functional change in the heart and vessels includes:

Atherosclerosis: Affects the intima of large and medium size arteries, by depositing blood components, lipid, calcium, carbohydrates and fibrous tissue in the intimal layer and then penetrating the medial (smooth muscle) layer ultimately forming atheromas or plaques.

Arteriosclerosis (hardening of arteries): a diffuse process in which the muscle fiber and the endothelial lining of the walls of small arteries become thickened.

The pathology of arteriosclerosis and atherosclerosis differ, but they rarely occur without the other.

  • Increased collagen deposits
  • Fragmentation of arterial elastins
  • Impaired vasodilation

Large arteries are less accommodating with aging leading to increased arterial pressure; a common cause of isolated systolic hypertension in old age.

Clinical Manifestations:

1) Mild to moderate cases:

  • Often asymptomatic
  • May present with early morning pulsating headaches, which subsides during the day

2) Chronic cases:

– Usually asymptomatic

– May present with

Symptoms of target organ damage (TOD) including

Microvascular:

  • Chronic kidney disease (CKD)
    • Fatigue
    • Anemia
    • Signs and symptoms of uremia
    • Labs: Proteinuria, reduced GFR
  • Retinopathy
    • Blurred vision
    • Floating spots
    • Loss of vision

Macrovascular damage:

  • Cardiac manifestations
    • Chest pain
    • Edema
    • Dyspnea/ CHF
  • Cerebral manifestations
    • Headache
    • visual disturbance
    • Stroke
    • Confusion/ encephalopathy
  • Peripheral arterial damage
    • Claudication
    • Skin changes, dryness, scaling, hair loss
    • Cold extremities
    • Reduced peripheral pulses
    • Ulceration, gangrene

– Associated with underlying cause include

  • Edema due to chronic kidney disease
  • Hormonal symptoms such as weight changes, sweating, tachycardia, anxiety

3) Hypertensive Emergency and Urgency:

Emergency:

Characterized by a severe elevation in blood pressure with evidence of target organ damage (TOD). CHEP 2012 guidelines suggest a DBP of ≥130 with TOD, while JNC VII suggests BP of >180/120 mmHg complicated by evidence of impending or progressive target organ dysfunction.

  • Hypertensive encephalopathy: Accelerated hypertension associated with somnolence, confusion, visual disturbances, nausea and vomiting
  • Intracranial hemorrhage: Sudden severe headache followed by altered mentation, paralysis, stupor, and coma
  • Acute aortic dissection or MI: Sudden severe pain in the chest
  • Acute left ventricular failure or acute pulmonary edema: Dyspnea, edema
  • Acute renal failure: Oliguria, anuria, altered mentation

Urgency:

Characterized by severe elevation in BP (>180 systolic ± >120 diastolic) without any progressive target organ damage, i.e. patient may be symptomatic but no TOD)

  • Blurred vision, headache, dizziness, edema, nausea
  • Epistaxis
  • Shortness of breath

4) Pheochromocytoma:

Episodic hypertension mostly accompanied with anxiety attacks due to catecholamine release

  • Palpitation
  • Perspiration
  • Pallor
  • Tremor
  • Vomiting
  • Angina
  • Orthostatic hypotension

5) White coat hypertension, WCH (doctors office hypertension)

  • Is suspected when there is a significant increase in BP values within the medical environment compared to with outside usual activities (usually diagnosed with an ambulatory blood pressure monitor)
  • Once diagnosed, accurate home BP values may be the best guide for therapy

6) Uncontrolled hypertension:

Failure to achieve targeted pressure despite ≥3 antihypertensive drugs (whereby patient is adherent) may suggest an identifiable or secondary cause, such as obesity, renovascular hypertension (renal stenosis) or primary hyperaldosteronism.

7) Pregnancy:

  • Hypertension in pregnancy is defined as an SBP  140 mm Hg and/or a DBP  90 mm Hg (average of at least 2 measurements taken at least 15 minutes apart)
  • BP levels between 140/90 mm Hg and < 160/110 mm Hg are considered non-severe hypertension in pregnancy
  • A systolic BP ≥160 mmHg or a diastolic BP ≥110 mmHg is often a part of following hypertensive emergency presentation:
    • Eclampsia: Icteric, pruritus, headaches, seizures
    • Hypertensive encephalopathy: Restlessness, irritability, headaches, seizure, and coma

Workup and Diagnosis

HISTORY:

  • Episodes of headache, sweating, palpitations, weakness, muscle cramp, and vision disturbances
  • Previous episodes of high blood pressure
  • History of diabetes, CAD, peripheral artery disease and renal disease
  • History of coexisting diseases such as migraine, gout, asthma, heart failure, and BPH
  • Inquire about sedentary lifestyle, dietary habits, salt intake, cigarette smoking, and alcohol consumption
  • Family history of hypertension, diabetes, CAD, peripheral artery disease and renal disease
  • Medication history
    • Oral contraceptives
    • NSAIDs
    • Antidepressants
    • Nasal decongestants

PHYSICAL EXAM:

Look for evidence of target organ damage and clues to secondary causes of hypertension.

– Vitals:

  • Confirm BP and consider an automated BP cuff e.g. The BP Tru™

– General appearance:

  • Example: Cushingoid facies

– Weight:

  • Assess for obesity, metabolic syndrome

– Fundoscopy:

  • Papilledema
  • Hypertensive retinopathy

– Neck exam:

  • Carotid bruits
  • Distended veins
  • Enlarged thyroid gland

– Chest auscultation for

  • Abnormal heart sound
  • Pulmonary edema

– Abdominal exam:

  • Renal bruits
  • Palpable kidney
  • Masses
  • Abnormal aortic pulsations

– Examination of the extremities:

  • Diminished/ absent peripheral arterial pulsations
  • Bruits
  • Edema

LABS:

  • Complete blood count (CBC)
  • Serum electrolytes
  • Uric acid
  • Blood sugar: Fasting blood glucose and/or glycated hemoglobin (A1C)
  • Creatinine and eGFR
  • Lipid profile: Fasting or non-fasting
  • Urine analysis and albuminuria assessment with urine albumin/creatinine ratio (ACR)
  • Electrocardiogram (ECG)

Additional investigations for secondary causes:

  • Plasma renin level (renovascular hypertension)
  • Serum aldosterone or 24-hour urine aldosterone
  • 24-hour urinary free cortisol level
  • Thyroid-stimulating hormone (TSH) level
  • Urinary catecholamines and fractionated metanephrines
  • Adrenal venous sampling (AVS): In patients with primary hyperaldosteronism and a definite adrenal mass considering surgery

IMAGING

  • Chest X-ray
  • Renal ultrasound
  • Renal angiogram (usually with CT/CTA or MRI/MRA)
  • CT scan of abdomen
  • ECHO cardiography
RN/Medical Management:

Goal is to control and achieve target blood pressure (mmHg)

Goal To control Hypertension

NON-PHARMACOLOGICAL THERAPY

– Weight:

Aim for an ideal Body Mass Index, decrease as little as 4.5 kg in weight significantly reduces BP.

Target: BMI = 18.5 to 24.9 kg/m2

Formula: BMI = weight in kilograms / height in meter 2

– Waist circumference:

1-b-Image-HTN-Treatment-Waist circumference

– Salt intake:
To decrease BP, consider reducing sodium intake toward 2000 mg (5 g of salt or 87 mmol of sodium) per day

Low Sodium Age Recommended

1,500 mg sodium (Na) = 65 mmol sodium (Na) = 3.75 g of salt (NaCl) = 1/2 level teaspoon of table salt

– Alcohol: Restrict intake to a maximum of

  • Two standard drinks per day or 14 drinks per week for men and 9 drinks per week for women

One standard drink is equivalent to:

  • 5 oz./142 ml of wine (12% alcohol)
  • 1.5 oz./43 ml of spirits (40% alcohol)
  • 12 oz./341 ml regular strength beer (5% alcohol)

– Potassium intake:

In patients not at risk of hyperkalemia, increase dietary potassium intake to reduce BP

When appropriate, patients with hypertension should be encouraged to consume foods with higher potassium content (e.g. fresh fruits, vegetables, and legumes)

– Exercise:

Moderate intensity dynamic exercise, such as brisk walking for 30-60 minutes, 4-7 days per week in addition to the routine activities of daily living

– Diet:

A diet rich in fruits, vegetables, and dairy products with reduced saturated and total fat can substantially lower BP – consider the DASH diet.

– Smoking:

Cessation of smoking and smoke-free environment is important to reduce hypertension, stroke, and cardiovascular risk.

PHARMACOLOGICAL THERAPY

Indications:

  • Average SBP >160 or DBP >100 mm Hg without TOD or risk factors
  • Average  SBP ≥140 and/or DBP ≥90 mm Hg for patients with target organ damage e.g. left ventricular hypertrophy
  • Diabetes or chronic kidney disease with BP ≥130/80 mm Hg
  • Chronic kidney disease with BP ≥140/90 mm Hg
  • Presence of other risk factors (over 90% of Canadians with hypertension have other risk factors)

Treatment Gap Alert: Many younger hypertensive Canadians with multiple cardiovascular risks are currently not treated with pharmacotherapy. Health care professionals need to be aware of this important care gap and recommend pharmacotherapy.

Considerations in selection of therapy:

  • Race: Diuretics preferred over renin-angiotensin system (RAS) inhibitors for African-Americans
  • Age
  • Coexisting diseases and therapies
  • Quality of life (QOL)
  • Economic consideration
  • Dose per day (compliance factor)

– Diuretics:

  • Thiazides are used as 1st line agents because of effectiveness, compliance, and cost
  • Loop diuretics should be used in patients with decreased renal function, defined as CrCl <20-30 mL/min
  • Aldosterone antagonists: Prescribed in patients with primary hyperaldosteronism or those with resistant hypertension

– Βeta blockers:

  • May be used 1st line for patients with ischemic heart disease, CHF, those with migraine
  • Not indicated 1st line in patients over the age of 60 years

– ACE inhibitors:

  • Should be considered in patients with diabetes, chronic kidney disease, atrial fibrillation, CAD or CHF
  • Contraindicated in pregnancy

– Angiotensin receptor blocking agents:

  • Considered in patients with diabetes, renal insufficiency, chronic kidney disease, or CHF (when ACE intolerant)
  • Contraindicated in pregnancy

– Dihydropyridine calcium channel blockers:

  • Considered in patients with isolated systolic hypertension, angina, and those at high CV risk
  • Shown to be safe in pregnancy

– Non-dihydropyridine calcium channel blockers:

  • Considered in patients with atrial arrhythmia, tachycardia, stable angina, concomitant migraine

– Alpha-adrenoceptor antagonists:

  • Non-selective antagonists are usually reserved for use in hypertensive emergencies caused by a pheochromocytoma or as 4th line agents
  • Consider in hypertensive males with BPH

– Direct renin inhibitors:

  • Indicated for the treatment of mild to moderate essential hypertension and reduction of proteinuria in addition to ACEIs or ARBs
  • Contraindicated in pregnancy

– Drugs with central sympatholytic action (alpha

agonists, central):

  • Effective in hypertensive patients with renal disease because they do not compromise renal function; considered as 4th line agents
  • Methyldopa is traditionally considered as first-line therapy in pregnancy

– Vasodilators:

  • Usually prescribed as adjunct therapy with other BP drugs and rarely are used alone
  • Hydralazine also may be used to control high BP in pregnant women
  • Nitroglycerin/ nitroprusside can be used in hypertensive emergencies

– Combination drugs:

May be used to:

  • Simplify regimen and improve adherence
  • Avoid side effects that may occur from high doses of a single agent
  • If the BP is >20 mm Hg systolic ± >10 mm Hg diastolic above target – consideration should be given initially to start with 2 drugs from different classes, preferably as a combination product

-Note: Beta-blockers and non-DHP CCBs should not be used routinely in combination. ACEIs and ARBs are also not recommended to be used in combination; as the combination has not been shown to reduce CV events; when compared with ACEI alone

If hypertension is NOT adequately controlled with single-agent, patient should follow up monthly or more frequently if severe hypertension. Also, consider:

  • Patient non-adherence: Cost and adverse effects/allergy should be considered
  • Suboptimal dose: Increase dose if the patient is considered adherent, however combination therapy is usually preferred to maximal doses of single agents
  • Add in a second drug from another class; to improve control, and minimize adverse effects caused by the maximum dose of single agents
  • If no change in BP, and the patient is adherent, 1st choice option may be ineffective and a new agent should be substituted

Specific Paradigms for Treatment of Hypertension:

HYPERTENSIVE EMERGENCY AND URGENCY:

Emergency:

  • Initially reduce mean arterial BP by no more than 25% within minutes to an hour, once stable, further stabilization to 160/100-110 mm Hg within the next 2-6 hours to avoid further organ damage

Urgency:

  • Avoid precipitous drop in BP. Aggressive dosing with intravenous drugs or even oral agents, to rapidly lower BP is not without risk
  • Patients with stage II hypertension with associated symptoms such as severe headache, shortness of breath, epistaxis, or severe anxiety, should have their BP lowered up to 20% over several hours
  • Some hypertensive urgencies may benefit from treatment with oral, short-acting agents. Most importantly, patients should not leave the ER without a confirmed follow-up appointment within a few days

Management:

  • Monitor for end-organ injury:
    • Abnormal neurologic signs (stroke, seizures)
    • Severe headache
    • Pulmonary edema
    • Chest pain (MI, aortic dissection)
    • Vision difficulty (retinal edema, hemorrhage)
  • Hospitalization, IV treatment, and ICU monitoring usually required for hypertension emergency/urgency
  • Parenteral antihypertensive agents may include:
    • Vasodilators: e.g. Sodium nitroprusside, nitroglycerin, hydralazine
    • Adrenergic inhibitors: e.g. Labetalol, methyldopa, phentolamine
    • ACEIs: e.g. Enalaprilat
  • Diuretics may be used to induce diuresis if required
  • Ionotropic pressure support may be required for precipitous drop in BP

Special Considerations:

Hypertension and stroke

  • Avoid overzealous BP lowering in acute stroke. Treat extreme BP elevation (systolic >220 mmHg, diastolic >120 mm Hg) by 15-25% over the first 24 hours with gradual reduction thereafter
  • If eligible for thrombolytic therapy in acute stroke, treat very high BP (>185/110 mm Hg)
  • In secondary prevention, the benefits of BP lowering is seen in both normotensive and hypertensive patients
  • ACEI plus diuretic or ARB – based treatment should be considered

Aortic dissection

  • Emergent cases, often requiring surgical management, especially in ascending aortic dissection
  • Do not use sodium nitroprusside without beta blockers, (increases the chances of aortic rupture)

Pheochromocytoma

  • Alpha and beta-adrenergic receptors are stimulated by excess catecholamine in pheochromocytoma
  • Preferred treatment is surgical resection of tumour, following α-adrenergic blockade to avoid catecholamine surge
  • β-Adrenergic blockade alone may result in more severe hypertension owing to the unopposed α-adrenergic stimulation

Elderly hypertensive patient (age >60 years)

  • May also have coexisting medical conditions
  • Dosage should be increased gradually
  • Diuretics, CCBs and ACE inhibitors/ARBs are good choices
  • Avoid excess BP lowering especially if postural hypotension

Hypertension in patients of African descent

  • Beta blockers and ACE inhibitors are less effective
  • Calcium channel blockers, diuretics and possibly ARBs are good choice

Obese hypertensive patient

  • Weight reduction is the mainstay of non-pharmacological therapy
  • Treatment is similar to isolated hypertension. However, there may be associated risk of left ventricular hypertrophy, endothelial dysfunction, renal hyperfiltration, microalbuminuria, hence ACEI or ARB may be reasonable option

The diabetic patient

  • Usually require combination therapy to achieve desired levels ≤130/80 mm Hg
  • Should start with ACE inhibitors (or ARBs) and consider combination therapy if BP is >20 mm Hg systolic ± >10 mm Hg diastolic above target
  • Caution with blockers because of their masking hypoglycemic symptoms

Patient with chronic kidney disease

  • Most patients with hypertension require combination therapy to achieve optimal BP goals <130/80 mm Hg
  • Initially start with diuretics (especially loop diuretics if Clcr <20-30 mL/min) and ACEI or ARBs

Patient with left ventricular hypertrophy (LVH)

  • May start with ACEI or ARBs. Long-acting CCB or thiazide diuretics are other options

Patients with coronary artery disease (CAD)

  • Increased risk of unstable angina (UA) and myocardial infarction (MI)
  • May start with beta adrenergic antagonist, long-acting CCB or ACE inhibitors
  • Cautiously use non-dihydropyridine calcium channel blockers in MI and cardiac conduction system disease

Patients with heart failure (HF)

  • ACEI and Beta blocker (ARB if ACEI intolerant)
  • Titrate doses of beta-blockers and ACEI/ ARB to those used in clinical trials
  • Avoid calcium channel blockers because of negative inotropic effects
  • Add aldosterone antagonist in class 2, 3 or 4 HF

Pregnancy and hypertension

  • Treatment is recommended for average SBP 140 mm Hg or DBP 90 mm Hg in pregnant women with chronic hypertension, gestational hypertension, or preeclampsia
  • Pregnant women receiving antihypertensive therapy with chronic hypertension or gestational hypertension or preeclampsia, a DBP of 85 mm Hg should be targeted
  • Avoid non-pharmacologic therapy such as:
    • Weight reduction
    • Exercise
  • Oral alpha methyldopa has the largest amount of safety data and is still preferred
  • First-line monotherapy drugs to be considered are labetalol, long-acting oral nifedipine, or other oral b-blockers (acebutolol, metoprolol, pindolol, and propranolol)
  • Second-line drugs to be considered are clonidine, hydralazine, and thiazide diuretics
  • Alpha-methyldopa has the largest amount of safety data and is still preferred
  • ACEIs, ARBs, and nitroprusside are contraindicated in the pregnancy

Surgical/ Interventional

Treatment of renovascular hypertension

  • Percutaneous transluminal angioplasty
  • Stent placement (for fibromuscular hyperplasia and for discrete stenotic arteriosclerotic lesions not involving the renal artery ostium)
  • Rarely bypass graft
Medications:

Diuretics

  • Thiazide diuretics
  • Loop diuretics
  • Aldosterone receptor blockers
  • Inhibitors of renal epithelial Na+ channels

Thiazide diuretics

Mechanism:

  • Block Na/Cl transport in the proximal part of renal distal convoluted tubules

Dose:

Hydrochlorothiazide

  • Initial 12.5 mg PO daily. Usual dose 25 mg PO daily; minimal benefit for lowering BP beyond 25 mg, however, side effects (such as hypokalemia and hyponatremia) increase

Chlorthalidone

  • Initial 12.5 mg PO daily, increase to 25 mg/day if needed. Maximum dose is 50 mg/day, although there is minimal additional BP lowering effect beyond 25 mg/day

Indapamide

  • Initial 1.25 mg PO daily; usual 2.5 mg/day, can be used when renal function <30 mL/min
  • Titration: Increase by 1.25 mg PO every 4 weeks, according to blood pressure response; Max. 2.5 mg daily

Loop diuretics

Mechanism:

  • Loop Diuretics → Block Na/K/Cl transporter in the renal loop of Henle

Dose:

Furosemide

  • Initial 20 mg PO BID, it can be given 40 mg PO BID and then adjusted according to the response

Note: Will only consider if eGFR <30 mL/minute

Aldosterone receptor blockers

Mechanism:

  • Blocks aldosterone receptors in renal collecting tubule → results in increased excretion of sodium and water and decreased excretion of potassium

Dose:

Spironolactone

  • Initial 25-100 mg PO in single or divided doses, should be continued for 2 weeks then adjustments should be made according to the response

Eplerenone

  • Initial 50 mg PO Daily for should be continued for 4 weeks, can go up to 50 mg PO BID. No therapeutic benefits observed with >100 mg/day

Inhibitors of renal Epithelial Na+ Channels

Mechanism:

  • Disrupts sodium ↔ potassium exchange in the distal convoluted tubule and collecting ducts of the nephron
  • Inhibits Sodium-Potassium-ATPase
  • Decreases calcium excretion
  • Increases magnesium loss

Dose:

Amiloride

  • Initial 5 mg PO daily, usual 5-10 mg PO daily; Max. 20 mg/day (usually used in combination with another antihypertensive)

Triamterene

  • Initial 50 mg PO daily; usual 50-100 mg PO daily (usually used in combination with thiazide diuretic)

Beta-adrenergic blocking agents

Cardioselective:

  • Acebutolol
  • Atenolol
  • Bisoprolol
  • Metoprolol
  • Nebivolol

Non- Cardioselective:

  • Carvedilol
  • Nadolol
  • Propranolol
  • Timolol
  • Pindolol
  • Labetalol

Mechanism:

  • Block beta receptors
  • Decrease heart rate and cardiac output
  • Decrease renin release

Dose:

Cardioselective:

Acebutolol

  • Mild to moderate hypertension 200-400 mg PO daily in 2 divided doses
  • Patient with severe hypertension may respond to higher doses

Atenolol

  • Initial 25-50 mg PO daily, doses >100 mg/day show no additional benefit

Bisoprolol

  • In some case initial 2.5 mg PO daily is preferable (especially in renal and hepatic impairment), usual 5 mg PO daily; may increase up to 20 mg/day if required

Metoprolol

Conventional tablets:

  • Initial 25-50 mg/day PO BID; usual 100-200 mg/day in divided doses; Max. 400 mg/day in 2 divided doses

Extended-release tablets:

  • Initial 25-100 mg PO daily; usual 100-200 mg PO daily

IV Metoprolol:

May be used to control hypertension/ventricular rate control in patients NPO or nonfunctioning GI tract.

  • Initial low dose of 1.25-5 mg IV every 6-12 hrs

Nebivolol

  • Initial 5 mg PO once daily, usual 5 to 10 mg once daily; can be increased at two-week intervals up to 20 mg once daily

Non- Cardioselective:

Carvedilol

Extended-release capsules:

  • Initial 10 mg PO daily; Max. 80 mg/day

Immediate-release tablets (not indicated in Canada for HTN):

  • Initial 6.25 mg PO BID; usual 12.5-25 mg PO BID; Max. 25 mg PO BID

Labetalol

  • Initial 100 mg PO BID; usual 200-400 mg PO BID
  • In severe hypertension maximum dose 1200 mg/day
  • Titration: Increase dosage by 100 mg PO BID every 2-3 days

Hypertensive emergency

  • IV: Initial 10-20 mg IV over 2 min x 1
    • Additional doses of up to 40-80 mg at 10-minute intervals may be required to achieve desired BP. Total cumulative dose of 300 mg; Max. 300 mg/day IV
  • IV infusion: Initial 0.5-2 mg/minute continuous IV infusion (discontinue after 2.5 hrs of infusion)
  • Oral dose following IV: Initial 100 mg PO daily; maintenance dose 200-400 mg PO in 2 divided doses

Nadolol

  • Initial 40 mg PO daily; usual 40-80 mg PO daily; Max. 320 mg/day
  • Titration: Gradually increase by 40-80 mg/day every 3-7 days
  • In renal impairment depending on the CrCl dose interval is increased and doses are reduced

Propranolol

Conventional tablets:

  • Not indicated for hypertension

Long acting (extended- release) capsules:

  • Initial 80 mg PO; usual 160-320 mg PO daily; Max. 320 mg/day
  • Titration: Increase dose 120-160 mg/day every 3-7 days

Timolol

  • Initial 10 mg PO BID; usual 20-40 mg/day in 2 divided doses; Max. 60 mg/day
  • Titration: May increase dose gradually at 5 mg BID intervals every 14 days

Pindolol

  • Initial 5 mg PO twice daily; usual dose is 10-40 mg PO BID; Max. 60 mg/day
  • Titration: Increase gradually by 10 mg/day every 3-4 wks

ACE (angiotensin-converting enzyme) inhibitors

  • Benazepril
  • Captopril
  • Cilazapril
  • Enalapril
  • Fosinopril
  • Lisinopril
  • Perindopril
  • Ramipril
  • Quinapril
  • Trandolapril

Mechanisms:

  • Inhibition of the renin-angiotensin-aldosterone system
  • Inhibit bradykinin degradation
  • Stimulate vasodilating prostaglandin synthesis
  • Reduce sympathetic nervous system activity

Caveat: Inhibitors of the RAS (ACEI/ARB/DRI) might precipitate acute renal failure in the setting of conditions/illnesses that can be associated with dehydration.

Dose:

Benazepril

  • Initial: 1 mg once daily. Usual: 20 mg once daily; Maximum: 40 mg daily

Captopril

  • Initial 12.5-25 mg PO BID or TID; usual 50 mg PO BID or TID; Max. 450 mg/day
  • Titration: Increase by 12.5-25 mg/dose every 1-2 week; up to 50 mg 3 times/day
  • Usually after 50 mg PO TID, consider adding a diuretic (thiazide)

Cilazapril

  • Initial 2.5 mg PO once daily. Usual: 2.5 to 5 mg once daily; Maximum: 10 mg daily
  • Elderly: Initial 1.25 mg PO once dailyRenal Impairment: Creatinine Clearance
    • > 40 mL/min: 1 mg once daily; Max. 5 mg once daily
    • 10 – 40 mL/min: 0.5 mg once daily; Max. 2.5 mg once daily
    • < 10 mL/min: 0.25 – 0.5 mg once or twice a week

    Hepatic Impairment:

    Cirrhosis: Initial ≤ 0.5 mg PO once daily

Enalapril

  • Initial 2.5-5 mg PO daily; usual 2.5-40 mg/day in 1-2 divided doses; Max: 40 mg/day

Enalaprilat IV

  • Initial 1.25 mg IV over 5 minutes every 6 hrs; usual 0.625-1.25 mg IV over 5 minutes given every 6 hrs, up to 36 hrs
  • If concomitant diuretic use – begin with 0.625 mg IV over 5 minutes

Fosinopril

  • Initial: 10 mg PO once daily. Usual: 20 mg daily as a single dose; Maximum: 40 mg daily

Lisinopril

  • Start 10 mg PO daily; usual 10-40 mg PO daily; Max. 80 mg/day
  • If concomitant diuretic – use cautiously, begin with 5 mg PO daily
  • Moderate renal failure (CrCl 10-30): Begin with 5 mg PO daily; only if the decline/failure is not secondary to bilateral renal stenosis
  • Dialysis patients: Begin with 2.5 mg once daily (adjust according to BP response)

Perindopril

  • Initial 2-4 mg PO daily; usual 4-8 mg PO daily; Max. 16 mg/day

Ramipril

  • Initial 2.5 mg PO daily (Max. 20 mg/day). Adjust at 1-2 week intervals by doubling dose, or 5 mg increments

Quinapril

  • Initial: 10 mg once daily. Usual: 10 to 20 mg once daily; Maximum: 40 mg daily

Trandolapril

  • Initial 1 mg PO daily or 2 mg PO daily in black patients; usual 2-4 mg PO daily. Adjust dosage at weekly intervals

Angiotensin receptor blocking agents

  • Azilsartan
  • Candesartan
  • Eprosartan
  • Telmisartan
  • Irbesartan
  • Losartan
  • Olmesartan
  • Valsartan

Mechanisms:

  • Block AT1 angiotensin receptors
  • Blocks the vasoconstrictor and aldosterone secreting effects of angiotensin II
  • Reduce vasoconstriction

Caveat: Inhibitors of the RAS (ACEI/ARB/DRI) might precipitate acute renal failure in the setting of conditions/illnesses that can be associated with dehydration.

Dose:

Azilsartan

  • Initial 40 mg PO once daily. Max. 80 mg once daily

Candesartan

  • Initial 8-16 mg PO daily; Max. 32 mg/day

Eprosartan

  • Initial 400-600 mg PO daily. Total daily dose 400-800 mg/day in 1-2 divided doses; Max 800 mg daily

Irbesartan

  • Initial 150 mg PO daily; usual 150-300 mg PO daily; Max. 300 mg/day

Note: Starting dose in volume-depleted patients should be 75 mg.

Losartan

  • Initial 50 mg PO daily; usual 25-100 mg PO daily in 2 divided doses; Max. 100 mg

Telmisartan

  • Initial 40 mg PO daily; usual 20-80 mg PO daily; Max. 80 mg/day

Olmesartan

  • Initial: 20 mg once daily. Usual: 20 to 40 mg once daily; Maximum: 40 mg daily and 29 mg in mild to moderate renal impairment

Valsartan

  • Initial 80-160 mg PO daily, in non-volume depleted patients; Max. dose is 320 mg PO daily

Direct renin inhibitor

  • Aliskiren

Mechanism:

Decrease plasma renin activity → inhibits conversion of angiotensinogen to angiotensin I → result in decreased the formation of angiotensin II

Caveat: Inhibitors of the RAS (ACEI/ARB/DRI) might precipitate acute renal failure in the setting of conditions/illnesses that can be associated with dehydration.

Dose:

Aliskiren

  • Initial 150 mg PO daily; Max. 300 mg/day

Calcium channel blocking agents (CCBs)

Non- Dihydropyridines:

  • Diltiazem
  • Verapamil

Dihydropyridines:

  • Amlodipine
  • Felodipine
  • Nifedipine

Mechanisms:

  • Blocks the inward movement of calcium by binding to the L-type calcium channels in the heart and in smooth muscle of the peripheral vasculature
  • This decreases intracellular calcium leading to a reduction in muscle contraction
  • Significant reduction in afterload but not preload

Dose:

Non- Dihydropyridines:

Diltiazem

  • Initial 120-240 mg Po daily, usual 180-360 mg PO in 2 divided doses, Max. 360 mg/day
  • Titration: Over 7-14 days

Canadian extended-release formulations

  • XC or CD: Initial 120-240 mg PO daily; usual 240-360 mg PO daily

USA extended-release formulations-XR form and LA

  • XR: Initial 180-240 mg PO daily; usual 180-480 mg PO daily
  • LA: Initial 180-240 mg PO daily; usual 120-540 mg PO daily

Verapamil

Immediate-release form:

  • Initial 80 mg TID or, usual 80 mg PO TID; Max. 480 mg/day; Elderly: Initial 40 mg PO TID

Verapamil (SR):

  • Initial 180 mg every morning, usual 120-480 mg/day; Max. 480 mg/day; Elderly: Initial 120 mg every morning

Extended-release form (PM):

  • Initial 200 mg at night, usual 200 mg at bedtime; Max. 400 mg/day; Elderly: Initial 100 mg at bedtime

Verapamil (HS):

  • Initial 180 mg PO at bedtime; usual 240-480 mg PO at bedtime; Max. 480 mg PO at bedtime

Dihydropyridines:

Amlodipine

  • Initial 5 mg PO daily or 2.5 mg PO daily in elderly; usual 5-10 mg PO once daily; Max. 10 mg/day
  • Titration: Increase 2.5 mg over 1-2 wk (up to a maximum dose)

Felodipine

  • Initial 2.5-5 mg PO daily; usual 5-10 mg PO daily; Max. 20 mg/day

Nifedipine – DO NOT USE immediate release formulation

Extended-release:

  • Initial 30-60 mg PO daily; usual 30-90 mg PO daily; Max. 120 mg/day
  • Titration: Increase dose by every 7-14 days

Nicardipine

  • Oral: Initial 20 mg PO TID; usual 20-40 mg PO TID; Max. 120 mg/day

– Other Dihydropyridine NOT available in Canada:

Alpha-adrenoceptor antagonists

Selective alpha-adrenoceptor antagonists

  • Prazosin
  • Terazosin
  • Doxazosin

Non-selective alpha-adrenoceptor antagonists

  • Phentolamine

Mechanism:

  • Block postsynaptic alpha receptors
  • Relax smooth muscle
  • Lowers peripheral vascular resistance

Dose:

Prazosin

  • Initial 2-3 mg PO TID daily; maintenance 2-20 mg in 2-3 divided doses; Max. 20 mg/day

Terazosin

  • Initial 1 mg PO daily at bedtime; usual 1-10 mg daily at bedtime; Max. 20 mg/day

Doxazosin

  • Initial 1 mg PO daily at bedtime; may increase dose to 2 mg daily, make subsequent adjustments by doubling dose at intervals of 2-4 weeks until desired effect is achieved; Max. 16 mg/day
  • Note: Substantial risk of syncope/postural effects with dosages >4 mg/daily.

Phentolamine

Hypertensive crisis (especially secondary to catecholamine excess)

  • IV: Initial 5-15 mg bolus

Agents with central sympatholytic action (alpha agonists, central)

  • Clonidine
  • Methyldopa

Mechanisms:

  • Stimulates alpha-adrenergic receptors in the central nervous system → reduces efferent peripheral sympathetic outflow

Dose:

Clonidine

Oral:

  • Initial 0.05 mg PO BID. Usual 0.1 mg/day PO daily
  • Titration: May increase by 0.1 mg/day every week until desire response achieved, then taper dose gradually over 2-4 days

Transdermal (available in the US):

  • Initial 0.1 mg/week; usual 0.1-0.3 mg/week
  • Titration: May increase by 0.1 mg 1-2 week interval

Methyldopa

Oral:

  • Initial 250 mg BID or TID; usual 250 mg to 1 g daily in 2-3 divided doses. Max. 3 g/day (divided) in adults; 1 g/day in elderly
  • Titration: Adjust dosage every 2 days until an adequate response is achieved

Intravenous (IV):

  • 250 mg to 1 g every 6-8 hr, maximum: 1 g every 6 hrs

Vasodilators

  • Hydralazine
  • Minoxidil
  • Nitroglycerin
  • Nitroprusside

Mechanisms:

  • Relax vascular smooth muscle
  • Produce peripheral vasodilatation
  • Decrease pre and after-load
  • Reduces myocardial oxygen demand
  • Nitroglycerin dilates coronary arteries

Dose:

Hydralazine

Oral:

  • Initial 10 mg/day every 6 hrs for 2-4 days; usual 25 mg/day QID; Max. 300 mg/day
  • Titration: Dosage may increase by 10-25 mg/dose every 2-5 days; up to a maximum dosage

Intravenous (maximum rate: 5 mg/minute):

  • 10-20 mg every 4-6 hr
  • Titration: May increase to 40 mg/dose

Intramuscular (IM):

  • 10-50 mg every 4-6 hr
  • Titration: May increase to 40 mg/dose

Minoxidil

  • Oral: Initial 5-10 mg PO daily; usual 10-40 mg/day in 1-2 divided doses; Max. 100 mg/day

Nitroglycerin

In hypertensive emergency

  • IV: 5 mcg/min; usual range 5-100 mcg/min; Max. 200 mcg/min
  • Titration: Increase 5 mcg/minute every 3-5 min to 20 mcg/minute, if no response; increase 10-20 mcg/min every 3-5 min up to maximum dosage

Nitroprusside

In hypertensive emergency

  • IV: Initial 0.25-0.3 mcg/kg/min; usual 3-4 mcg/kg/min; Max. 10 mcg/kg/min for 10 min
  • Titration: Increase 0.5 mcg/kg/minute to maximum dosage till the desired effect achieved or adverse effect appears

COMBINATION DRUGS:

Examples of some commonly used agents

Diuretic combinations:

Hydrochlorothiazide 25 mg/Spironolactone 25 mg

  • Dosage: Initial 1/2 tab/day; Max. 4 tab/day

Hydrochlorothiazide 25 mg/Triamterene 37.5 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day

Hydrochlorothiazide 50 mg/Amiloride 5 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day

Ace inhibitors and Diuretics

Benazepril 10 mg/Hydrochlorothiazide 12.5 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day

Captopril 25 mg/Hydrochlorothiazide 15 mg

  • Dosage: Initial 1 tab/day; Max. 2 tabs/day

Lisinopril 10 mg/Hydrochlorothiazide 12.5 mg

  • Dosage: Initial 1 tab/day; Max. 2 tabs/day

Enalapril 5 mg/Hydrochlorothiazide 12.5 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day

Angiotensin receptor blockers and Diuretics

Losartan 50 mg/Hydrochlorothiazide 12.5 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day

Candesartan 16 mg/Hydrochlorothiazide 12.5 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day

Irbesartan 150 mg/ Hydrochlorothiazide 12.5 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day

Valsartan 80 mg/Hydrochlorothiazide 12.5 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day

Beta-adrenergic blockers and Diuretics

Atenolol 50 mg/Chlorthialidone 25 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day

Pindolol 10 mg/Hydrochlorothiazide 25 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day

Metoprolol 50 mg/Hydrochlorothiazide 25 mg

  • Dosage: 1 tab once or twice daily; Max. 2 tab

Propranolol 40 mg/Hydrochlorothiazide 25 mg

  • Dosage: 2 tab BID; Max. 3 tab

Central alpha/Adrenergic agonist and Diuretics

Methyldopa 250 mg/Hydrochlorothiazide 15 mg

  • Dosage: Initial 1 tab PO BID; Max. 4 tab

Calcium channel blockers and Ace inhibitors

Amlodipine 2.5 mg/Benazepril 10 mg

  • Dosage: Initial 1 cap daily; Max. 4 cap/day

Felodipine 5 mg/Enalapril 5 mg

  • Dosage: Initial 1 tab daily; Max. 3 tab/day

Verapamil extended-release 180 mg/Trandolapril 2 mg

  • Dosage: Initial 1 tabs daily; Max. 3 tab/day

Perindopril arginine and Amlodipine

  • Dosage: initiated at the recommended starting dose of 3.5 mg/2.5mg once daily; After four weeks of treatment, the dose may be increased to 7 mg/5 mg once daily in adult patients whose blood pressure is not at the appropriate target. If necessary, titration to 14 mg/10 mg once daily may be considered in adult patients insufficiently controlled after four weeks of treatment with 7 mg/5 mg
  • Not indicated for the initiation of treatment in elderly patients (> 65 years of age)

Calcium channel blockers and Angiotensin II receptor blocker

Amlodipine (mg)/Telmisartan (mg)

  • Dosage: 40/5, 40/10, 80/5 and 80/10 are all available

Direct renin inhibitor and Diuretics

Aliskiren 150/Hydrochlorothiazide 12.5

  • Dosage: Initial 1 tab daily; Max. 2 tab/day
Diagnosis and Goals:

Nursing diagnosis:

  • Incomplete information of treatment regimen, its effects, and control of disease process-ineffective health maintenance
  • Non-compliance due to side effects of therapy-ineffective therapeutic regimen management
  • Anxiety
  • Sexual dysfunction
  • Disturbed body image

Collaborative problems/Potential complications:

  • Cerebrovascular (TIA, stroke)
  • Cardiac (MI, LVH)
  • Renal (chronic renal failure)
  • Retinal (retinopathy)

Treatment Goals:

  • To understand the disease process and treatment, and participate in self care
  • To control and achieve targeted blood pressure
    • In general population: <140/90 mmHg
    • Diabetes mellitus: <130/80 mmHg
    • Chronic renal disease: <140/90 mmHg
  • To decrease the risk of morbid hypertensive complications as documented above
  • To understand and implement a therapeutic plan
  • Experience minimal side effects of therapy
Nursing Intervention:

Providing Basic Education

  • Hypertension can be controlled not cured, strategies are develop according to the concept of controlling the disease
  • Explain how lifestyle changes and medication can control the disease process
    • Arrange a dietician to help plan the diet
    • Advise DASH diet and tips documented in non-pharmacological management
    • Recommend support groups for cessation of smoking, weight control and stress reduction
    • Provide assistance and explain to family and friends of the total treatment plan
  • Emphasize on the consequences of uncontrolled hypertension
    • Cerebrovascular (TIA, stroke)
    • Cardiac (MI, left ventricular hypertrophy)
    • Renal (chronic renal failure)
    • Stress on the importance of lifelong adherence to the treatment , periodic evaluation and regular follow-ups
  • Each followup visit requires history and physical exam to assess disease control and progression
  • Explain all diagnostic and therapeutic activities to the patient
  • Educate and explain the pharmacologic control of hypertension
  • Drugs used for control, will likely produce adverse effects
    • Warn for orthostatic hypotension, instruct to get up slowly from chair or bed
    • Patient should sit or lie down if he feels dizzy
    • Light headedness, fatigue, and anorexia, should be expected by the patients
    • Patient should be aware of all the symptoms and adverse effects which are to be reported immediately
    • Inform the doses are individualized so need to be adjusted accordingly
    • Patient should know abrupt discontinuation will result in rebound hypertension
    • Patient should be warned of certain activities, when on vasodilators
      • – Long hot baths, hot weather
      • – Fever and alcohol consumption
    • Patients should be monitored very closely in dehydration, or diarrhea

Gerontologic Alert

Combination therapy, cognitive changes, and sensory deficit in elderly make dose adjustments and control of BP very challenging.

  • Devise simple method for compliance
  • Patients are sensitive to therapeutic levels so start with lower doses
  • Monitor closely for safety and efficacy

Encouraging Self-Management

  • Teach proper method of taking BP at home and at work if required
  • Automatic or semiautomatic devise should be advised for home use
  • Encourage regular maintenance of home measurement decive
  • Inform patient of desired range and the readings that are to be reported
  • Develop a plan of instruction for medication self-management
    • Simple and convenient time for medication
    • Checklist should be provided on which patient can record, blood pressure and medications used
    • Be sure the patient knows the generic and brand names of all medications
    • Patient should be aware of all the generic and brand names of the medications
    • Provide information on the response of antihypertensive therapy
  • Determine recommended dietary plans and provide dietary education as appropriate
    • Most patients have a basic knowledge of nutrients and minerals, such as fats and sodium, and can be taught to read labels

Evaluation: Expected patient outcomes

  • Demonstrates increased knowledge about high BP, medication effects, and prescribed therapeutic activities-active involvement in therapeutic plan
  • Maintain adequate tissue perfusion by
    • Controlling blood pressure as desired
    • Having no signs of angina or vision changes
    • Have no renal impairment
    • Has palpable peripheral pulses
  • Takes medications, keeps follow-up appointments
  • No unpleasant side effects of drug therapy
Nursing Alerts:
  • BP should be reduced gradually except in (emergency with end organ damage) because lowered BP → decrease perfusion of vital organs
  • Monitor for adverse effects of medications
  • Identify and report side effects-headache, tachycardia, orthostatic hypotension, dry mouth, sexual dysfunction, frequent urination
  • Observe for hyperkalemia, especially if patient is placed on potassium-sparing diuretic therapy, watch for arrhythmias
  • Note signs of confusion, irritability, lethargy, and disorientation
  • Listen for complaints of headache, difficulty with vision
  • Check for evidence of nausea or vomiting
  • Measure urine output accurately
  • Monitor ECG continuously
  • Observe for CNS complications
    • Be alert for signs of seizure activity. Provide a safe environment-padded side rails. Keep bed in lowest position
  • Reduce activity and provide quiet environment
  • Maintain constant vigilance until BP is decreased and stable and then begin a hypertension teaching program

References

Core Resources:

  • Butalia S, Audibert F, Côté AM, et al. Hypertension Canada’s 2018 Guidelines for the Management of Hypertension in Pregnancy. Can J Cardiol. 2018;34:526-531. doi: 10.1016/j.cjca.2018.02.021. Epub 2018 Mar 1
  • Canadian Hypertension Education Program 2013 guidelines; www.hypertension.ca
  • Compendium of Pharmaceuticals and Specialties (CPS). Canadian Pharmacist Association. Toronto: Webcom Inc. 2012
  • Day RA, Paul P, Williams B, et al (eds). Brunner & Suddarth’s Textbook of Canadian Medical-Surgical Nursing. 2nd ed. Philadelphia: Lippincott Williams and Wilkins; 2010
  • Foster C, Mistry NF, Peddi PF, Sharma S, eds. The Washington Manual of Medical Therapeutics. 33rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010
  • Gray J, ed. Therapeutic Choices. Canadian Pharmacists Association. 6th ed. Toronto: Webcom Inc. 2011
  • Grundy SM, Cleeman JI, Bairey Merz CN, et al, for the Coordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004; 110:227-239
  • Hurst’s the Heart Manual of Cardiology, 12th Edition
  • Katzung BG, Masters SB, Trevor AJ, eds. Basic and Clinical Pharmacology. 11th ed. New York: McGraw-Hill; 2009
  • Leiter LA, Fitchett DH, Gilbert RE, Gupta M, et al. Cardiometabolic Risk in Canada: A Detailed Analysis and Position Paper. Canadian Journal of Cardiology 27 (2011) e1-e33
  • Longo D, Fauci A, Kasper D, et al (eds). Harrison’s Principles of Internal Medicine. 18thed. New York: McGraw-Hill; 2011
  • McPhee SJ, Papadakis MA, eds. Current Medical Diagnosis & Treatment. 49th ed. New York: McGraw-Hill; 2010
  • Nerenberg KA, Zarnke KB, Leung AA, at al. Hypertension Canada’s 2018 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults and Children. Can J Cardiol. 2018;34:506-525  DOI:https://doi.org/10.1016/j.cjca.2018.02.022
  • Pagana KD, Pagana TJ eds. Mosby’s Diagnostic and Laboratory Test Reference. 9th ed. St. Louis: Elsevier-Mosby; 2009
  • Skidmore-Roth L. ed. Mosby’s drug guide for nurses. 9th ed. St. Louis: Elsevier-Mosby; 2011
  • Skidmore-Roth L, ed. Mosby’s nursing drug reference. 24th ed. St. Louis: Elsevier-Mosby; 2011
  • Stergiou G, Palatini P, Asmar R, et al. Blood Pressure Measurement and Hypertension Diagnosis in the 2017 US Guidelines. Hypertension 2018;71: 963-965. https://doi.org/10.1161/HYPERTENSIONAHA.118.10853
  • Whelton PK, Carey RM, Aronow WS, et al.. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018; 71: e13-e113. https://doi.org/10.1161/HYP.0000000000000065

Online Pharmacological Resources:

  • e-Therapeutics
  • Lexicomp
  • RxList
  • Epocrates

Journals/Clinical Trials:

  • Al-Balas M, Bozzo P, Einarson A. Use of diuretics during pregnancy Can Fam Physician. 2009; 55(1): 44-45
  • Beckett NS et al. Treatment of hypertension in patients 80 years of age or older (HYVET) NEJM 2008; 358:1887-98
  • 2012 CHEP Recommendations for the Management of Hypertension
  • Canadian Hypertension Education Program, 2013, www.hypertension.ca
  • Canadian Hypertension Education Program. 2011 guideline details: assessment of overall cardiovascular risk. Available at: www.hypertension.ca/assessment-of-overall-cardiovascular-risk. Accessed October 17, 2011
  • Cushman WC, Evans GW, Byington RP et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus.N Engl J Med 2010; 362:1575-1585
  • Dahlof B, Devereux RB, Kjeldsen SE et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomized trial against Atenolol. Lancet. 2002;359:995-1003
  • Genest J, McPherson R, Frohlich J, et al. 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult – 2009 recommendations. Can J Cardiol 2009; 25;567-579
  • The 7th Report of the Joint National Committee (JNC-7) on Prevention, detection, evaluation and treatment of high blood pressure. JAMA 2003: 289; 2560-71
  • Kenneth J, et al. Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) N Engl J Med 2008; 359:2417-2428
  • Okin PM, Wachtell K, Kjeldsen SE, et al. Incidence of atrial fibrillation in relation to changing heart rate over time in hypertensive patients: the LIFE study. Circ Arrhythm Electrophysiol. 2008 ;1:337-43
  • Olsen MH, Wachtell K, Beevers G, et al. Effects of losartan compared with atenolol on lipids in patients with hypertension and left ventricular hypertrophy: the Losartan Intervention For Endpoint reduction in hypertension study. J Hypertens. 2009; 27:567-74
  • Olsen MH, Wachtell K, Beevers G, et al. Prognostic importance of hemoglobin in hypertensive patients with electrocardiographic left ventricular hypertrophy: the Losartan Intervention For End point reduction in hypertension (LIFE) study. Am Heart J. 2009; 157:177-84
  • Sharma AM. Is There a Rationale for Angiotensin Blockade in the Management of Obesity Hypertension? Hypertension. 2004; 44: 12-19
  • The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. NIH Publication No. 04-5230; August 2004