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Hypertension

Updated : June 11, 2024





Background

Hypertension is a condition with consistently high force of blood against arteries. It is also called High blood pressure. 

Blood pressure measured in mmHg, which consists of two numbers:  

Systolic i.e., During heartbeat over Diastolic i.e., Between heartbeats pressure. 

Normal blood pressure is generally noted as 120/80 mmHg. 

Primary and secondary these are two types of hypertensions, and the risk factors include genetics, age and lifestyle. 

High blood pressure key risk factor for heart issues, stroke, kidney disease, peripheral vascular problems.  

Primary hypertension is the most common type, without a clear cause it affects 90% to95% of adults with hypertension while secondary hypertension shows 5% to 10% cases. 

Hypertensive emergencies show target organ dysfunction, while hypertensive urgencies are situations without target organ dysfunction. 

Epidemiology

Hypertension is a global epidemic condition. In the US national health and nutrition examination survey data from 2011 to 2014 shows 86 million adults more than 20 years observed hypertension, which represents a 34% prevalence rate in the population.  

Hypertension rates decreased in the early 2000s then again rises in 2014, with a noticeable increase among men in recent years. 

Around 972 million people worldwide shows hypertension cases, with prevalence expected to increase up to 29% by 2025 in developing countries. 

Black adults in the US and worldwide have high rates of hypertension. White adults may develop high BP later in their life and have lower average as compared to Black adults. 

Anatomy

Pathophysiology

Primary hypertension has complex pathogenesis with multiple factors which affects blood pressure includes vascular reactivity, blood volume, and neural stimulation.  

Primary hypertension progresses from occasional to established to complicated, that causes end-organ damage in the aorta, small arteries, heart, kidneys, and central nervous system as time passes.

Vascular changes cause increased systemic vascular resistance and cardiac output stays slightly reduced with normal blood volume. 

Etiology

Hypertension caused due to environmental factors and complex gene inheritance along with genetic components. 

DNA methylation and histone modification are linked with hypertension. High salt diets may cause nephron development due to methylation.
Mental stress initiates DNA methylase, increase autonomic response and methylation pattern predicts preeclampsia risk in pregnancy. 

Rare genetic causes of hypertension include Liddle syndrome, glucocorticoid-remediable hyperaldosteronism, and deficiencies in alpha-hydroxylase enzymes. 

Genetics

Prognostic Factors

Untreated hypertension worsens with age and increases mortality risk thus called as silent killer because it increases blood pressure.
Patients with resistant hypertension and comorbidities have higher risk for poor outcomes. Lower blood pressure may reduce risk for cardiovascular events. 

Mortality from ischemic heart disease and stroke rises with higher blood pressure.
Outcome in hypertensive emergencies is influenced by initial organ damage and subsequent blood pressure control.  

Hypertension increases risk of end-stage renal disease in Black patients even diabetic nephropathy patients with hypertension also at risk. 

Clinical History

Hypertension occurs more in youth till age of 20 due to rising obesity and sedentary behaviors. 

Hypertension increases significantly in individuals between 30 to 60 years old. 

Physical Examination

Blood Pressure Measurement 

Respiratory Examination 

Cardiovascular Examination 

Age group

Associated comorbidity

Associated activity

Acuity of presentation

High blood pressure develops slowly over the years, sometimes without any noticeable symptoms. 

Severe high blood pressure causes organ damage in hypertensive emergencies. 

Differential Diagnoses

Primary Hypertension 

Secondary Hypertension 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Middle-aged to elderly individuals with a family history of hypertension are affected and slight reduction can lower blood pressure. 

First-line medications for hypertension includes ACE inhibitors/ARBs, calcium channel blockers, and thiazide diuretics. 

Hypertension common in diabetic cases, it raises risk by 2.5 times in 5 years. Both conditions also increased risk of cardiovascular disease, stroke, and renal disease. 

Physician aims to identify acute hypertension patients with end-organ damage symptoms needing urgent antihypertensive therapy. Initial therapy for acutely ill infants with severe hypertension is continuous IV infusions.  

Therapy for renovascular hypertension aims to maintain normal blood pressure and prevent end-stage renal disease through various treatments. 

Pseudo-hypertension may occur when high blood pressure is observed without actual organ damage, hypotensive symptoms from medications. 

Surgical resection is preferred for pheochromocytoma as it cures hypertension. Preoperative alpha-adrenergic blockade with phenoxybenzamine is followed by beta-adrenergic blockade for tachycardia. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Use of a non-pharmacological approach for Hypertension

Patients should start walking, swimming, and cycling to improve heart condition under physician guidance. 

Include healthy diet such as fruits, vegetables, whole grains, and avoid unhealthy food. 

Psychological support is essential for managing stress, anxiety, and depression in heart patients. Use blood pressure measuring device and record blood pressure levels regularly. 

Breathing exercises is effective to control blood pressure also yoga exercises help in hypertension. Lifestyle modification like intake of healthy nutritional supplements and proper hydration should be followed by patients. 

Appointments with a cardiologist and preventing recurrence of disorder is an ongoing life-long effort. 

Use of Thiazide Diuretics

Hydrochlorothiazide: 

It is approved to manage hypertension alone or with other agents. It can be used in patients on ACE inhibitors. 

Use of Potassium-Sparing Diuretics

Triamterene: 

It raises potassium levels and use caution when combining with drugs that increase potassium. 

Amiloride: 

It is a potassium-conserving drug with mild effects compared to thiazide diuretics, that are used in hypertension and heart failure treatment. 

Use of loop Diuretics

Furosemide: 

Inadequately controlled hypertensive patients with thiazides may not respond to furosemide. 

Torsemide: 

It can be used alone or with other antihypertensives. Take a dose of 5 mg daily, then increase up to 10 mg. 

Use of Angiotensin converting enzyme inhibitors (ACEIs)

Captopril: 

It inhibits angiotensin conversion, activates bradykinin, which regulates blood pressure effectively. 

Ramipril: 

It relaxes blood vessels has widen easier blood flow. This reduces strain on the heart and improves circulation efficiency. 

Use of angiotensin receptor blockers (ARBs)

Losartan 

It relaxes blood vessels and lowers blood pressure, which increases blood and oxygen to the heart. 

Valsartan: 

It blocks the RAAS system, which inhibits neprilysin causing angiotensin II accumulation from breakdown prevention. 

Use of Beta-Blockers (Beta-1 Selective)

Atenolol: 

It treats angina, which improves survival post-heart attack, relaxes blood vessels, slows heart rate and reduces blood pressure. 

Propranolol: 

It competes with sympathomimetic neurotransmitters for non-selective beta receptor binding without preference for β1 or β2. 

Use of Vasodilators

Hydralazine: 

It reduces blood pressure through direct relaxation of vascular smooth muscle. 

Minoxidil: 

It is used for severe symptomatic hypertension with end-organ damage unresponsive to diuretic and antihypertensives. 

Use of Calcium channel blockers

Amlodipine: 

It inhibits calcium ions during depolarization in smooth muscle and myocardium. 

Verapamil: 

It is a non-dihydropyridine antihypertensive that works on both vascular and cardiac systems, which acts as a vasodilator. 

Eplerenone: 

It blocks aldosterone at receptors, which lowers BP and sodium reabsorption. 

Use of Renin Inhibitors

Aliskiren 

It lowers plasma renin, that inhibits angiotensinogen conversion, and disrupts renin-angiotensin-aldosterone system feedback loop. 

Use of Alpha-Blockers in Antihypertensives

Prazosin 

It blocks alpha1-receptors, that leads to peripheral vasodilation through vascular inhibition. 

Doxazosin: 

It inhibits alpha-adrenergic receptors, which causes vasodilation, decreased peripheral resistance, and lowered blood pressure. 

Use of Antihypertensives

Reserpine: 

It depletes biogenic amines, that causes sympathetic dysfunction and reduced peripheral vascular resistance and lowers blood pressure. 

Use of Endothelin Antagonists

Aprocitentan: 

It is used to treat hypertension in adults not controlled on other antihypertensive drugs which lowers blood pressure. 

Use of Intervention with a Procedure in treating Hypertension

Revascularization for renovascular hypertension with aortorenal bypass using saphenous vein graft or hypogastric artery. 

Surgery is preferred for pheochromocytoma and aldosterone-producing adenoma to cure hypertension through tumor removal. 

Angioplasty in fibromuscular dysplasia of renal artery has 60% to 80% hypertension resolution success. 

Use of phases in managing Hypertension

In the diagnosis phase, evaluation includes detailed patient history of cardiovascular disorders, elevated blood pressure and associated symptoms. 

In supportive care and management phase, patients should receive all the required attention in the form of postoperative care, monitoring, and rehabilitation. 

Track blood pressure on daily basis and note medication side effects if occurs also start follow up with physician in every 1 to 2 months until blood pressure is controlled. 

Pharmacologic therapy is very effective in the treatment as it includes first-line medications and combination therapy. 

The regular follow-up visits with the cardiologist are schedule to check the improvement of patients along with treatment response. 

Medication

 

metoprolol

IR tablets
Initial dose:

100

mg

Orally

once a day

Maintenance dose: 100-450 mg orally once a day
ER tablets:
Initial dose: 25-100 mg orally once a day
Maintenance dose: 100-400 mg orally once a day



prazosin

Initial:

1

mg

Orally

8 - 12

hrs

Maintenance: 6-15 mg once a day or divided 2 to 3 times a day alternatively



doxazosin

1

mg

Orally

once a day

; the dose can be titrated to double the dose up to 16 mg qDay based on blood pressure response
ER: not recommended for HTN



timolol

10 - 20

mg

Orally

every 12 hrs

Maintenance: 20-40 mg once a day
Do not exceed 60 mg per day



nadolol

40 - 320

mg

Tablet

Orally

once a day



terazosin

Initial:

1

mg

Orally

once a day


Maintenance: 1-5 mg per day for every 12hrsand can increase upto less than 20 mg per day



Dose Adjustments

Dosing considerations
To prevent syncope first dose and subsequent dose preferred at bedtime and can be taken with food

labetalol

100

mg

Orally

every 12 hrs

initially; increased up to100 mg for 12hrs every 2-3 days Usual dosage range: 200-400 mg orally every 12hrs Do not exceed 2400 mg per day



trandolapril 

Nonblack patients:

1

mg

orally

every day


black patients: 2 mg orally every day
Maintenance dose
2-4 mg orally every day or divided in every 12 hours



mecamylamine 

2.5

mg

Orally 

twice a day

; increase to 2.5 mg for at least 2 days



diltiazem 

Extended-release capsules:

Initial dose: 120-240mg orally once a day, increasing the dose as needed
Maintenance dose: 120 to 540mg orally once every day
Maximum dose:540mg/day

Extended-release coated capsules
Initial dose: 120-180mg orally once a day; increase the dose as needed
Maintenance dose: 240 to 360mg orally every day
Maximum dose: 480mg/day

Extended-release tablets
Initial dose: 180 to 240mg orally once a day; increase the dose as needed
Maintenance dose: 540mg orally every day



acebutolol 

400 - 1200

mg/day

Capsule

Orally 

every 12 hours



bumetanide 

off-label:

1

mg

Intravenous (IV)

loading dose, followed by 0.5-2 mg/day oral divided every 12 hours.



amlodipine/telmisartan 

Initial dose: Initiate with 40mg/5mg or 80mg/5mg orally every day. Do not exceed 80mg/10mg every day
Maximum dose: Telmisartan 80mg-amlodipine 10mg orally every day



Dose Adjustments

Hepatic impairment
Start with a lower dose of 2.5 mg amlodipine and increase the amount gradually

Renal impairment
Dosage adjustment is not required

hydrochlorothiazide/aliskiren 

Initial dose-12.5mg/150mg or 25mg/150mg orally every day; can increase the dose if needed after 2-4 weeks. Do not exceed 300mg/25mg
Maintenance dose-25mg/300mg orally every day



Dose Adjustments

Renal impairment
CrCl<30ml/min: caution is needed for the use. When CrCl is below 30 mL/min, hydrochlorothiazide is typically ineffective and contraindicated in anuric individuals; aliskiren has the potential to cause hyperkalemia and progressive renal failure
CrCl>30ml/min: No dosage adjustment is needed

Hepatic impairment
No dosage adjustment needed

amlodipine/olmesartan 

Initial dose:5mg/20mg orally once a day, can increase the dose after 1-2 weeks
Maintenance dose-10mg/40mg orally once a day



lisinopril/hydrochlorothiazide 

Initial dose-10 to 80mg/6.25 to 50mg orally once a day. May increase the dose after 2 to 3 weeks. Do not exceed 80mg/50mg per day



eprosartan/hydrochlorothiazide 

600mg/12.5mg to 600mg/25mg orally everyday



valsartan/hydrochlorothiazide 

Initial dose: 1 tablet (80-160mg valsartan/12.5-25mg hydrochlorothiazide) per day orally
Maintenance dose: May increase the dose after 1-2 weeks to a maximum dose of 320mg valsartan/25mg hydrochlorothiazide daily



Dose Adjustments

Renal impairment
CrCl less than 30 mL/min: Because hydrochlorothiazide is not anticipated to be filtered into the renal tubule, which is where it acts when the glomerular filtration rate is less than 30 mL/min, hydrochlorothiazide-valsartan is not advised

methyldopa/hydrochlorothiazide 

methyldopa 500mg/hydrochlorothiazide 30 to 50mg orally every day
methyldopa 250mg/hydrochlorothiazide 25mg orally twice a day or methyldopa 250mg/hydrochlorothiazide 15mg orally twice or thrice a day
Do not exceed 50mg of hydrochlorothiazide every day



Dose Adjustments

Renal impairment
In patients with creatinine clearance (CrCl) of less than 30 mL/min, valsartan/hydrochlorothiazide should be avoided due to the potential for azotemia (elevated blood urea nitrogen and creatinine levels)

moexipril/hydrochlorothiazide 

moexipril 7.5mg to 15mg/hydrochlorothiazide 12.5 to 25mg orally before a meal once a day
If hydrochlorothiazide 25 mg once a day monotherapy is effective in controlling blood pressure, but considerable potassium loss still occurs, hydrochlorothiazide 6.25 mg-moexipril 3.75 mg may be used to manage blood pressure without causing electrolyte disturbances (one-half of a hydrochlorothiazide 12.5-moexipril 7.5 mg tablet)



captopril/hydrochlorothiazide 

25 - 15

mg-- captopril/hydrochlorothiazide

Orally 

every day


Do not exceed 150 mg/50 mg captopril/hydrochlorothiazide



clonidine/chlorthalidone 

0.1 - 0.3

mg/15 mg

Orally 

every day or divided into 2 times a day



Do not exceed 0.6 mg/30 mg per day



nifedipine 

30 - 60

mg

Tablets (extended release)

Orally 

once a day

7 - 14

days

when required<
should not exceed more than 120 mg/day (Procardia XL) or 90 mg/day (Adalat CC)



quinapril/hydrochlorothiazide 

(10 mg/12.5 mg) or (20 mg/12.5 mg) orally each day Increase the dose from either of the drug components based on the clinical response Do not increase the hydrochlorothiazide part more than every 2-3 weeks



Dose Adjustments

Renal impairment- When CrCl ≥30 mL/min; no dose modification is required When CrCl <30 mL/min/1.73 m² or the serum creatinine ≥3 mg/dL, the drug is not recommended

metoprolol/hydrochlorothiazide 

Renal impairment-
In case of renal impairment, use the medication with caution
Thiazides may develop a cumulative effect if given in the impaired renal function :

Lopressor HCT: 50-100 mg metoprolol tartrate and 25-50 mg hydrochlorothiazide orally each day as single or divided doses
Dutoprol: 25-100mg metoprolol succinate and 12.5 mg hydrochlorothiazide orally each day as a single dose
The drug is not indicated for initial therapy