Hypertension

Hypertension Main page
Overview
Causes
Classification Primary Hypertension Secondary Hypertension Hypertensive Emergency Hypertensive Urgency
Screening

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Usama Talib, BSc, MD [2]

Overview

Hypertension is a major risk factor for cardiovascular disease and is a major public health problem. The prevalence of hypertension increased among the united states due to changing The previous cut-off 140/90 mmHg. Hypertension is a leading cause of mortality worldwide. More than half of hypertensive patients are not aware of the disorder and some diagnostic patients do not take the medication. The new guideline recommends considering the average of reading BP≥2 visits office. Home blood pressure monitoring (HBPM) and ambulatory blood pressure monitoring (ABPM) are helpful to determine masked hypertension or white coat hypertension out of the office.

Historical Perspective

• [Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
• In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
• In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].

Classification

Hypertension may be classified according to the underlying disorder into two groups:

• Primary hypertension or essential hypertension, (90-95%)

• Gradually rising in blood pressure
• History of environmental exposure (weight gain, high-sodium diet, decreased physical activity, job change leading increased travel, excessive consumption of alcohol
• Family history of hypertension

• Secondary hypertension, (5%), due to underlying disorder

• BP lability, suddenly rising BP with pallor and dizziness (pheochromocytoma)
• Snoring, hypersomnolence (obstructive sleep apnea)
• Prostatism (chronic kidney disease due to post-renal urinary tract obstruction)
• Muscle cramps, weakness (hypokalemia from primary aldosteronism or secondary aldosteronism due to renovascular disease)
• Weight loss, palpitations, heat intolerance (hyperthyroidism)
• Edema, fatigue, frequent urination (kidney disease or kidney failure)
• History of coarctation repair (residual hypertension associated with coarctation)
• Central obesity, facial rounding, easy bruisability (Cushing syndrome)
• Medication or substance use (alcohol, NSAIDS, cocaine, amphetamines)
• Absence of family history of hypertension

• Resistant hypertension is defined as a higher level of BP above the goal in spite of concurrent use of three antihypertensive drugs including a long-acting calcium channel blocker, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and a diuretic and requires ≥ medications.
• Refractory hypertension is explained as failing to control hypertension with at least five classes of antihypertensive drugs including long-acting thiazide-type diuretic, such as chlorthalidone, and a mineralocorticoid receptor antagonist, such as spironolactone

Comparison between two guidelines of hypertension

Hypertension Guidline	ACC/AHA	ESC/ESH
Definition of hypertension (mmHg)	≥130/80	≥140/90
Normal blood pressure range (mmHg)	Normal: <120/80 Elevated:120-129/<80	Optimal:<120/80 Normal:120-129/80-84 High normal:130-139/85-89
Hypertension stage (mmHg)	Stage1:130-139/80-89 Stage2: ≥140/90	Grade1:140-159/90-99 Grade2:160-179/100-109 Grade3: ≥180/110
Age specific blood pressure targets(9mmHg)	<65 years:<130/80 ≥65 years:<130/80	<65years:<120-129/70-79 >65 years:<130-139/70-79

2017/ACC/AHA Guideline of hypertension

• Hypertension can be classified based on the guideline into 2 stages:

Blood pressure category	Systolic blood pressure	Diastolic blood pressure
Normal	<120/80 mmHg	<80 mmHg
Elevated	120-129 mmHg	<80 mmHg
Stage 1 hypertension	130–139 mm Hg	80–89 mm Hg
Stage 2 hypertension	≥140 mm Hg	≥90 mm Hg

Pathophysiology

• The pathogenesis of hypertension is characterized by a malfunction in the renin-angiotensin-aldosterone system (RAAS), natriuretic peptides ,endothelium, sympathetic nervous system (SNS),immune system.
• Allelic variants of several genes have been associated with the development of primary hypertension.
• Endothelial dysfunction and increased TGF-B was shown in salt sensitivity patients lead to increased systolic blood pressure 10 mmHg following ingestion of 5 gr salt.

Causes

Common causes of hypertension include:

• Genetic susceptibility

• Hypertension is a Polygenic disorder
• Findings of 25 rare mutations,120 single-nucleotide polymorphisms in hypertensive patients
• Monogenic forms of hypertension: glucocorticoid-remediable aldosteronism, Liddle syndrome, Gordon’s syndrome
• Association between high blood pressure with age and increased defects in the gene

Environmental exposure

• Overweight, obesity

• Direct relationship between body mass index and BP
• Strong relationship between waist-to hip ratio, distribution of central fat and BP
• Relation between Obesity at a young age with further hypertension

• Sodium intake

• Association between sodium intake and BP in migrants
• Triat of salt sensitivity in blacks, older adults, patients with higher level of BP, CKD, DM, metabolic syndrome

• Potassium

• Inverse relation with BP
• Inverse relation with stroke
• Higher level of [[potassium] may reduce the effect of sodium on BP

• Physical fitness

• Inverse relation between physical fitness and physical activity with BP
• Modest exercise activity reduces the risk of BP

• Alcohol

Pharmacological causes of hypertension	Management:
Alcohol	Limiting alcohol to ≤1 drink daily for women and ≤2 drinks for men
Amphetamines ( amphetamine, methylphenidate, dextroamphetamine)	Discontinue or decrease dose Behavior therapy for ADHD
Antidepressants (MAOI, SNRI, TCA)	Using alternative agents such as SSRI Avoidance of taking tyramine-containing foods with MAOI
Atypical antipsychotics (clozapine, olanzapine)	Discontinue or decrease the dose Using alternative agents such as aripiprazole, ziprasidone with a lower risk of weight gain, diabetes mellitus, dyslipidemia
Caffeine	Limiting caffeine intake to <300 mg/day in uncontrolled hypertension cause of increasing blood pressure in hypertensive patients No relationship between longterm use of [[coffeine] and hypertension or cardiovascular disease
Decongestants (phenylephrine, pseudoephedrine)	Avoidance in severe uncontrolled hypertension Using shortest duration types Using alternative agents such as nasal saline, intranasal corticosteroids, antihistamines
Herbal supplements such as Ma Huang ephedra, St. John’s wort (with MAO inhibitors, yohimbine)	Avoid use
Immunosuppressants (cyclosporine)	Using alternative agent such as tacrolimus with less effect on blood pressure
Oral contraceptives	Avoidance in uncontrolled hypertension Using progestin only form Using low dose 20-30 mcg ethinyl estradiol agents Alternative agents (barrier, abstinence, IUD)
NSAIDs	Using alternative agents such as acetaminophen, tramadol, topical NSAIDs
Recreational drugs (bath salts MDPV, cocaine, methamphetamine	Avoide use
Systemic corticosteroids ( dexamethasone, fludrocortisone, methylprednisolone, prednisone, prednisolone)	Using alternative agents ( inhaled, topical)

Differentiating [disease name] from other Diseases

• [Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:

• [Differential dx1]
• [Differential dx2]
• [Differential dx3]

Epidemiology and Demographics

• The prevalence of hypertension is approximately 45,600 per 100,000 individuals worldwide.
• Between the years 2000-2002, the incidence of hypertension was estimated to be 5680 for whites, 8490 for African-Americans, 6570 for Hispanics, and 52.2 for Chinese cases per 100,000 individuals in United States.

Age

• Hypertension is more commonly observed among elderly patients

Gender

• Males are more commonly affected with hypertension than [[females].

Race

• Hypertension usually affects individuals of the black race, Asians and Hispanic Americans.

Risk Factors

• Common risk factors in the development of hypertension are:

• Diabetes mellitus
• Family history of hypertension
• Dyslipidemia
• Increased age
• Obesity
• Low socioeconomic state
• Physical inactivity/low fitness
• Male sex
• Unhealthy diet
• Obstructive sleep apnea
• Psychological stress

• Common risk factors associated with resistant hypertension include:

• older age
• obesity
• CKD
• black race
• DM

Modifiable risk factors	Fixed risk factors
Current smoker, secondhand smoking	Chronic kidney disease
Diabetes mellitus	Family history
Dyslipidemia/hypercholesterolemia	Increased age
Obesity	Low socioeconomic/educational status
Physical inactivity/low fitness	Male sex
Unhealthy diet	Obstructive sleep apnea Psychological stress

Natural History, Complications and Prognosis

• The patients with primary hypertension usually remain asymptomatic.
• The clinical features of secondary hypertension dependent on the characteristics of an underlying disorder.
• If hypertension left untreated, 33% of patients with hypertension may progress to develop heart attack and stroke.

• Common complications of resistant hypertension include MI, stroke, ESRD, and death that are 2-7 times higher compared with patients without resistant hypertension.
• Prognosis is generally poor without treatment, and the 10­ year mortality rate of patients with hypertension is approximately 11%.
• Ascending aorta dilation and increased cardiothoracic ratio may be associated with hypertension.

Echocardiography or Ultrasound

Echocardiography may be helpful in the diagnosis of complications of hypertension, which include left ventricular hypertrophy (LVH), left ventricular (LV) diastolic dysfunction and left atrial dilation.

CT scan

• CT scan may be helpful in the diagnosis of underlying causes of secondary hypertension such as hyperaldosteronism, pheochromocytoma, hyperparathyroidism, aortic coarctation.

• CT scan may also show the complication of hypertension including:

• Cardiovascular system: aortic aneurysm, acute aortic syndrome
• Central nervous system: stroke, subarachnoid hemorrhage, posterior reversible encephalopathy syndrome

MRI

• Cardiac MRI is a reliable tool in the diagnosis of hypertensive heart disease by evaluation of left ventricular hypertrophy, left ventricular mass, biventricular function, valvular disease, inflammation and stress myocardial perfusion-fibrosis.

Other Imaging Findings

There are no other imaging findings associated with hypertension.

Other Diagnostic Studies

There are no other diagnostic studies associated with hypertension.

Treatment

Medical Therapy

• The mainstay of therapy for resistant hypertension is:

• Improving medications adherence
• Diagnosis and treatment of the causes of secondary hypertension
• Adding spironolactone or hydralazine or minoxidil to first line therapy (CCBs, inhibitors of RAS, chlorthalidone.

• [Medical therapy 1] acts by [mechanism of action 1].
• Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

Treatment strategy

Nomal BP (BP<120/80 mmHg)

Elevated BP(BP120-129/<80mmHg

Stage1 hypertension(BP 130-139/80-89mmHg

Stage 2 hypertension (BP≥ 140/90

Life style modifications

Nonpharmocological therapy(class1)

10 years CVD risk≥ 10%

Non pharmacological therapy and BPlowering medication

Reevaulation in 1 year (class 2a)

Reevaulation in 3-6 months(class 1)

Nonpharmocological therapy(class1)

Non pharmacological therapy and BPlowering medication

Reevaulation in 3-6 months(class 1)

Reevaulation in 1 months(class 1)

BPgoal reached

NO, Evaluation and optimization the adherence to medical therapy

Yes,Reevaulation in 3-6 months(class 1)

Intensification of medical therapy

First line of treatment	Drug_ Dosage(mg/day)_ Frequency	Comments
Thiazide or thiazidetype diuretics	Chlorthalidone 12.5–25 1 Hydrochlorothiazide 25–50 1 Indapamide 1.25–2.5 1 Metolazone 2.5–5 1	Chlorthalidone is a prolonged half-life drug and reduces cardiovascular risk Hyponatremia, hypokalemia, uric acid and calcium levels should be monitored
ACE inhibitors	Benazepril 10–40 1-2 Captopril 12.2-150 2-3 Enalapril 5-40 1-2 Fosinopril 10–40 1 Lisinopril 10-40 1 Moexipril 7.5–30 1-2 Perindopril 4-16 1 Quinapril 10-80 1-2 Ramipril 2.5-20 1-2 Trandolapril 1-4 1	Avoidance of using in combination with ARB and direct renin inhibitor Using with caution in CKD or in patients are on K sparing agents due to the risk of hyperkalemia Avoidance in pregnancy Avoidance in patients with a history of angioedema with ACEI Avoidance in severe bilateral renal artery stenosis
ARB	Azilsartan 40-80 1 Candesartan 8–32 1 Eprosartan 600-800 1-2 Irbesartan 150-300 1 Losartan 50-100 1-2 Olmesartan 20-40 1 Telmisartan 20-80 1 Valsartan 80-320 1	Avoidance of using in combination with ACEI or direct renin inhibitor Using with caution in CKD or in patients are on K sparing drugs due to the risk of hyperkalemia Avoidance in pregnancy Avoidance in patients with a history of angioedema with ARB It can be used in patients with a history of angioedema with ACEI after 6 weeks of discontinuation of ACEI Avoidance in severe bilateral renal artery stenosis
CCB—dihydropyridines	Amlodipine 2.5–10 1 Felodipine 2.5–10 1 Isradipine 5–10 2 Nicardipine SR 60–120 2 Nifedipine LA 30–90 1 Nisoldipine 17–34 1	Avoidance of using in heart failure reduced EF except amlodipine,felodipine Pedal edema is dose associated, more common in women
CCB—nondihydropyridines	Diltiazem ER 120–360 1 Verapamil IR 120–360 3 Verapamil SR 120–360 1-2 Verapamil-delayed onset ER 100–300 1 (in the evening)	Avoidance of using in combination with betablocker due to the risk of bradycardia Avoidance of using in heart failure reduced EF Avoidance of using diltiazem with verapamil due to drug interaction via CYP3A4
Second line of treatment	Drug_ Dosage(mg/day)_ Frequency	Comments
Diuretics—loop	Bumetanide 0.5–2 2 Furosemide 20–80 2 Torsemide 5–10 1	Preferred diuretic in symptomatic heart failure Preffered diuretic in moderate to severe CKD (GFR<30 cc/min)
Diuretics—potassium sparing	Amiloride 5–10 1-2 Triamterene 50–100 1-2	Mild antihypertensive effect Useful for treatment of hypokalemia due to thiazide monotherapy Avoidance of using in patients with significant CKD (GFR <45 mL/min).
Diuretics—aldosterone antagonists	Eplerenone 50–100 1-2 Spironolactone 25–100 1	Preferred for primary aldostronism and resistant hypertension Add-on therapy in resistant hypertension Lesser risk of gyncomasty and impotence with eplerenone Avoidance of combination therapy with K sparing agents
Betablocker-cardioselective	Atenolol 25–100 2 Betaxolol 5–20 1 Bisoprolol 2.5–10 1 Metoprolol tartrate 100–200 2 Metoprolol succinate 50–200 1	Beta-blockers are not first-line therapy of hypertension unless in the presence of IHD orheart failure Preferredbeta-blockers in bronchospastic airway disease preferred Bisoprolol, metoprolol succinate in heart failure reduced EF
Betablocker-cardioselective and vasodilatory	Nebivolol 5–40 1	Induction of nitric oxide Vasodilarory effect
Beta blockers—noncardioselective	Nadolol 40–120 1 Propranolol IR 80–160 2 Propranolol LA 80–160 1	Not recommended, especially in IHD or heart failure
Beta blockers—intrinsic sympathomimetic activity	Acebutolol 200–800 2 Penbutolol 10–40 1 Pindolol 10–60 2	Not recommended , especially in IHD or heart failure
Beta blockers—combined alpha-beta receptor	Carvedilol 12.5–50 2 Carvedilol phosphate 20–80 1 Labetalol 200–800 2	Carvedilol is preferred in heart failure reduced EF
Direct renin inhibitor	Aliskiren 150–300 1	Avoidance of using in combination with ARB or ACEI Using with caution in CKD or patients are on K sparing agents due to the risk of hyperkalemia Avoidance in pregnancy Avoidance in severe bilateral renal artery stenosis
Alpha-1 blockers	Doxazosin 1–16 1 Prazosin 2–20 2-3 Terazosin 1–20 1-2	Side-effect is orthostasis hypotension, especially in old patients Seconde line of treatment, preferred in BPH and hypertension
Central alpha2-agonist and other centrally acting drugs	Clonidine oral 0.1–0.8 2 Clonidine patch 0.1–0.3 1 weekly Methyldopa 250–1000 2 Guanfacine 0.5–2 1	Last line of treatment due to CNS adverse effect on elderly patients Avoidance of abrupt discontinuation of clonidine because of rebound hypertension
Direct vasodilators	Hydralazine 100–200 2-3 Minoxidil 5–100 1-3	Recommended to use with betablocker and diuretic due to sodium and water retention and reflex tachycardia Side effect of hydralazine is drug-induced lupus-like syndrome at higher doses Side effect of [[minoxidil] is hirsotism,pericardial effusion

Class I, Level of evidence:A

In patients with atherosclerotic renal artery stenosis, medical therapy is recommended

Class IIb, Level of evidence:C

Revascularization (percutaneous renal artery angioplasty and/ or stent placement) indicates in patients with refractory hypertension, worsening renal function, intractable heart failure, nonatherosclerotic disease (fibromuscular dysplasia)

Class IIb, Level of evidence:B

The effectiveness of continuous positive airway pressure (CPAP) to decrease blood pressure in patients with obstructive sleep apnea and hypertension is not verified

Surgery

• [Surgical procedure] may be performed for patients with secondary hypertension such as coarctation of aorta, primary aldostronism.

Prevention

• There are no primary preventive measures available for [disease name].

• Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

• Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].

Recommendations for masked hypertension and white coated hypertension : (Class IIa, Level of Evidence B)

❑ Screening for white coat hypertension in patients with systolic blood pressure 130-160 mmHg and diastolic blood pressure 80=-110 mmHg by using ABPM or HBPM before diagnosis of hypertension

(Class IIa, Level of Evidence C)

❑ Periodic monitoring of blood pressure with ABPM or HBPM for detection of transient or sustained hypertension in white coat hypertension

(Class IIa, Level of Evidence C)

❑ Finding of white coat hypertension by HBPM and ABPM in high office blood pressure inspite of receiving treatment,is recommended

(Class IIa, Level of Evidence B)

❑ Finding of mask hypertension by HBPM or ABPM in office blood pressure 120-129 /75-79 mmHg

(Class IIb, Level of Evidence C)

❑ Finding of white coat hypertension by HBPM or ABPM if office blood pressure 10 mmHg higher than normal in spite of receiving multiple medications ❑ Finding of masked hypertension by HBPM in patients with end organ damage or high cardiovascular risk but office reading blood pressure at goal ❑ Finding of masked hypertension by ABPM in patients with high HBPM inspite of receiving medications

References

Screening

The age to begin screening for hypertension varies between 13-20 years of age, according to different authorities. Generally, hypertension is defined as SBP > 140 mmHg and/or DBP > 90 mmHg. In specific populations, however, routine follow-up target BP may be different; and initiation of treatment may be considered at even lower BP values than those considered for the normal population.