Hypertension

Etiology and Risk Factors

More than 90% of patients have primary hypertension, meaning that no single identifiable cause is found. Mechanisms continue to be identified for subsets of patients once placed in this category, so the share of cases classified as essential continues to decline (Mitrovic, 2019; Williams et al., 2026).

Risk factors for primary hypertension include (Norris, 2020; Williams et al., 2026):

• Increasing age
• Family history
• Black race, associated with earlier onset and more severe disease
• Excess dietary sodium
• Obesity, especially central obesity
• Physical inactivity
• Heavy alcohol use
• Insulin resistance and type 2 diabetes
• Dyslipidemia
• Obstructive sleep apnea
• Adverse social determinants of health, including limited access to care and to healthy, low-sodium food

Secondary causes include (Mitrovic, 2019; Norris, 2020; Williams et al., 2026):

• Chronic kidney disease
• Renovascular disease from atherosclerosis in older adults or fibromuscular dysplasia in younger women
• Primary aldosteronism
• Obstructive sleep apnea
• Cushing syndrome and glucocorticoid excess
• Pheochromocytoma
• Thyroid and parathyroid disease
• Coarctation of the aorta
• Medications and substances, including estrogen-containing contraceptives, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, decongestants and other sympathomimetics, cocaine, amphetamines, erythropoietin, and licorice

Epidemiology and Clinical Context

Hypertension is the leading modifiable risk factor for cardiovascular disease and affects nearly half of U.S. adults. Awareness is incomplete, and blood pressure is controlled in only about a quarter of patients (Williams et al., 2026). Prevalence rises with age, exceeding 80% in adults 75 years and older, and is highest in non-Hispanic Black adults. Before age 65, prevalence is lower in women than men; after 65, it is higher in women (Williams et al., 2026). Untreated hypertension reduces life expectancy by an average of 10 to 20 years (Mitrovic, 2019).

Pathophysiology

Mean arterial pressure is the product of cardiac output and peripheral vascular resistance, and every mechanism of hypertension acts on one or both. Because resistance varies inversely with the fourth power of the vessel radius, small degrees of arteriolar narrowing produce large increases in pressure (Mitrovic, 2019).

In established primary hypertension, increased peripheral vascular resistance is the dominant abnormality. Sodium and fluid loading first raise pressure by expanding volume and cardiac output, but autoregulation then increases resistance and returns cardiac output toward normal, so long-term hypertension is sustained by resistance (Williams et al., 2026).

Contributing mechanisms include:

• Renal sodium handling: Impaired renal sodium excretion combined with high dietary sodium is considered the most important cause of essential hypertension, and nearly all monogenic forms share reduced renal sodium excretion (Williams et al., 2026). Salt sensitivity varies among individuals and is more common in patients with hypertension and in Black patients (Mitrovic, 2019).
• Sympathetic overactivity: Increases heart rate, cardiac output, and vasoconstriction and is more prominent in younger adults (Williams et al., 2026).
• Renin-angiotensin-aldosterone system: Angiotensin II constricts arterioles, and aldosterone promotes sodium and water retention (Mitrovic, 2019; Williams et al., 2026).
• Endothelial dysfunction: Reduced nitric oxide availability impairs vasodilation (Mitrovic, 2019).
• Obesity: Visceral and perivascular fat produce leptin and inflammatory mediators that activate the sympathetic and renin-angiotensin systems and promote sodium retention (Mitrovic, 2019; Norris, 2020).
• Arterial aging: Collagen replaces elastin in large arteries, the stiffer aorta buffers systolic ejection poorly, and systolic pressure rises while diastolic pressure stays level or falls, widening the pulse pressure (Norris, 2020).

Sustained pressure injures target organs directly and by accelerating atherosclerosis. The left ventricle hypertrophies against increased afterload, setting up heart failure, arrhythmia, and ischemia. Glomerular injury produces nephrosclerosis and chronic kidney disease, cerebral small-vessel disease contributes to stroke and cognitive impairment, and retinal arterioles narrow and sclerose (Norris, 2020).

Clinical Manifestations

Hypertension itself does not cause symptoms. Headache, fatigue, and dizziness are no more common in people with hypertension than in normotensive controls, and the condition is usually found through screening or through its complications (Mitrovic, 2019).

Findings of long-standing or severe hypertension include (Mitrovic, 2019; Norris, 2020; Williams et al., 2026):

• Hypertensive retinopathy, including arteriolar narrowing, arteriovenous nicking, hemorrhages, exudates, and cotton-wool spots
• Left ventricular hypertrophy
• Albuminuria and rising creatinine
• Heart failure
• Angina or myocardial infarction
• Stroke or transient ischemic attack
• Cognitive impairment
• Peripheral artery disease

Clues to secondary hypertension include a continuous abdominal bruit in renal artery stenosis, higher pressure in the arms than the legs in coarctation of the aorta, and hypokalemia in hyperaldosteronism (Mitrovic, 2019; Williams et al., 2026).

Diagnostic Evaluation

Blood Pressure Classification

The 2025 American College of Cardiology/American Heart Association (ACC/AHA) multisociety hypertension guideline retains the blood pressure categories introduced in 2017 (Jones et al., 2025; Williams et al., 2026):

• Normal: Systolic below 120 mm Hg and diastolic below 80 mm Hg
• Elevated: Systolic 120 to 129 mm Hg and diastolic below 80 mm Hg
• Stage 1 hypertension: Systolic 130 to 139 mm Hg or diastolic 80 to 89 mm Hg
• Stage 2 hypertension: Systolic 140 mm Hg or higher or diastolic 90 mm Hg or higher

When systolic and diastolic values fall in different categories, the higher category applies (Williams et al., 2026). Hammer and McPhee describe the older Joint National Committee definition of hypertension as 140/90 mm Hg or higher (Mitrovic, 2019); that threshold now corresponds to stage 2.

Measurement

• Have the patient sit quietly for at least 5 minutes with the back supported, feet flat, and legs uncrossed.
• Support the arm at heart level.
• Use a cuff bladder that encircles at least 80% of the arm.
• Avoid caffeine, nicotine, alcohol, and exercise for 30 to 60 minutes beforehand.
• Take at least two readings 1 minute apart and average them.
• Use home or ambulatory monitoring to identify white coat hypertension and elevations missed in the office (Williams et al., 2026).

Baseline Testing

Baseline testing profiles cardiovascular risk and establishes values for monitoring therapy (Williams et al., 2026):

• Fasting lipid panel
• Hemoglobin A1c or fasting glucose
• Complete blood count
• Sodium, potassium, calcium, and creatinine with estimated glomerular filtration rate
• Thyroid-stimulating hormone
• Urinalysis

A urine albumin-to-creatinine ratio, electrocardiogram, and echocardiogram can identify target-organ damage (Williams et al., 2026).

Risk Estimation

The 2025 guideline uses the AHA PREVENT-CVD calculator to estimate 10-year total cardiovascular risk and help guide decisions about treatment (Jones et al., 2025; Williams et al., 2026).

Evaluation for Secondary Causes

Secondary causes should be considered in patients with (Williams et al., 2026):

• Onset before 35 years of age
• Rapid worsening or marked elevation at presentation
• Resistant hypertension
• Significant hypokalemia

Expected Findings

Sustained primary hypertension is supported by repeated office readings of at least 130/80 mm Hg confirmed by home or ambulatory monitoring, without features suggesting a secondary cause (Norris, 2020; Williams et al., 2026).

Differential Diagnosis

White Coat Hypertension

Blood pressure is elevated in the clinic but normal during daily activities. Home or ambulatory monitoring distinguishes it from sustained hypertension (Mitrovic, 2019; Williams et al., 2026).

Measurement Error and Transient Elevation

Poor technique, an undersized cuff, recent caffeine or nicotine, pain, anxiety, and short-term use of NSAIDs, corticosteroids, or decongestants can raise measured blood pressure (Williams et al., 2026).

Secondary Hypertension

Kidney disease, renovascular disease, primary aldosteronism, sleep apnea, endocrine disorders, coarctation of the aorta, and medications should be considered when the presentation is atypical or the response to treatment is poor (Norris, 2020; Williams et al., 2026).

Hypertensive Emergency

Severe elevation with acute target-organ damage requires immediate treatment and differs from severe elevation without target-organ damage, which can generally be managed by adjusting oral therapy (Norris, 2020; Williams et al., 2026).

Findings That Reduce Diagnostic Probability

Few findings exclude hypertension by themselves. The following findings should lower confidence in the diagnosis of sustained primary hypertension or prompt evaluation for an alternative:

• Normal home or ambulatory readings with elevated office readings suggest white coat hypertension (Williams et al., 2026).
• Elevated readings obtained with poor technique or after caffeine, nicotine, or exercise should be repeated under proper conditions (Williams et al., 2026).
• Young age, abrupt onset, severe or resistant hypertension, or hypokalemia makes primary hypertension less likely and warrants evaluation for a secondary cause (Williams et al., 2026).

Treatment and Management

Treatment Goals

The treatment goal for most adults is less than 130/80 mm Hg, and the 2025 guideline emphasizes that systolic values closer to 120 mm Hg may lower risk further (Jones et al., 2025; Williams et al., 2026).

Lifestyle Modification

Lifestyle measures include (Norris, 2020; Williams et al., 2026):

• Dietary sodium restriction, the central nonpharmacologic intervention
• Weight loss; a loss of as little as 4.5 kg (10 lb) can lower blood pressure in overweight patients
• Heart-healthy diet
• Regular physical activity
• Moderation of alcohol intake

Pharmacologic Therapy

Key principles of drug therapy include (Jones et al., 2025; Williams et al., 2026):

• Whether medication is started at stage 1 depends on cardiovascular risk and comorbid conditions such as clinical cardiovascular disease, diabetes, or chronic kidney disease. Lower-risk patients may begin with a trial of lifestyle therapy.
• First-line drug classes are thiazide or thiazide-like diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and dihydropyridine calcium channel blockers.
• β-Blockers are no longer considered first-line for uncomplicated hypertension but are used for compelling indications.
• Combination therapy is more effective than a single agent and is generally preferred when blood pressure is more than 20/10 mm Hg above target. Fixed-dose combinations reduce pill burden.
• ACE inhibitors or ARBs are recommended in chronic kidney disease to slow its progression.
• Black patients with diabetes and no chronic kidney disease may benefit from initial treatment with a thiazide-type diuretic or calcium channel blocker.
• Check electrolytes and renal function within 4 weeks after starting an ACE inhibitor, ARB, or diuretic.

Resistant and Secondary Hypertension

Resistant hypertension is uncontrolled blood pressure despite adherence to optimal doses of three agents of different classes, one of them a diuretic, or control that requires four or more agents. Evaluation includes secondary causes, nonadherence, white coat effect, and measurement error. A low-dose mineralocorticoid receptor antagonist such as spironolactone is an effective addition (Williams et al., 2026). When a secondary cause is identified, treating it can be curative (Mitrovic, 2019).

Severe Elevation

Hypertensive emergency requires immediate treatment to protect target organs (Jones et al., 2025; Norris, 2020). Severe elevation without target-organ damage can generally be managed by restarting or intensifying oral therapy and treating contributing factors such as pain or anxiety, with close follow-up rather than emergency department referral (Jones et al., 2025; Williams et al., 2026).

Complications and Red Flags

Urgent escalation is required for:

• Blood pressure above 180/120 mm Hg with headache, confusion, seizures, or visual change
• Chest pain or signs of heart failure
• New neurologic deficits
• Acute kidney injury
• Retinal hemorrhages, exudates, or papilledema
• Severe hypertension in pregnancy or the postpartum period

Complications include myocardial infarction, heart failure, stroke, hypertensive encephalopathy, chronic kidney disease, and malignant hypertension (Mitrovic, 2019; Norris, 2020).

Clinical Reasoning Priorities

Confirm sustained hypertension with proper technique and out-of-office readings, then use overall cardiovascular risk and features of secondary disease to guide treatment intensity (Jones et al., 2025; Williams et al., 2026).

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References

Jones, D. W., Ferdinand, K. C., Taler, S. J., Johnson, H. M., Shimbo, D., Abdalla, M., Altieri, M. M., Bansal, N., Bello, N. A., Bress, A. P., Carter, J., Cohen, J. B., Collins, K. J., Commodore-Mensah, Y., Davis, L. L., Egan, B., Khan, S. S., Lloyd-Jones, D. M., Melnyk, B. M., . . . Williamson, J. D. (2025). 2025 AHA/ACC/AANP/AAPA/ABC/ACCP/ACPM/AGS/AMA/ASPC/NMA/PCNA/SGIM 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 Joint Committee on Clinical Practice Guidelines. Circulation, 152(11), e114–e218. https://doi.org/10.1161/CIR.0000000000001356

Mitrovic, I. (2019). Cardiovascular disorders: Vascular disease. In G. D. Hammer & S. J. McPhee (Eds.), Pathophysiology of disease: An introduction to clinical medicine (8th ed.). McGraw-Hill Education.

Norris, T. L. (2020). Porth’s essentials of pathophysiology (5th ed.). Wolters Kluwer. Williams, C., Finks, S. W., & Chisholm-Burns, M. A. (2026). Hypertension. In M. A. Chisholm-Burns, P. M. Malone, J. M. Kolesar, K. C. Lee, P. B. Bookstaver, & K. R. Matthias (Eds.), Pharmacotherapy principles & practice (7th ed.). McGraw Hill.