Hypertension
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Hypertension - Clinical Overview
1. Definition & Classification
Blood pressure (BP) is a continuous variable with no threshold below which risk disappears. Current ACC/AHA classification (adopted 2017, reaffirmed in the 2025 AHA/ACC Guideline [PMID 40811516]):
| Category | SBP (mmHg) | DBP (mmHg) |
|---|---|---|
| Normal | < 120 | and < 80 |
| Elevated | 120-129 | and < 80 |
| Stage 1 Hypertension | 130-139 | or 80-89 |
| Stage 2 Hypertension | ≥ 140 | or ≥ 90 |
Note: The older JNC 7 threshold of ≥140/90 for "hypertension" is no longer current in US guidelines. The 2017 ACC/AHA criteria lowered the diagnostic threshold to ≥130/80, which increased estimated US prevalence from ~32% to ~46% of adults. European guidelines (ESC/ESH 2023) retain ≥140/90 as the treatment threshold in most patients.
Diagnosis requires an average of ≥2 readings on ≥2 separate occasions. Out-of-office confirmation (home BP monitoring or ambulatory BP monitoring) is recommended before initiating pharmacotherapy to exclude white-coat hypertension. - Fuster and Hurst's The Heart, 15th Edition, p. 217-218
2. Epidemiology & CVD Risk
- Hypertension has a worldwide prevalence ~31-46% of adults and is rising with aging populations and obesity.
- US control rates are <50%; in low/middle-income countries, 8-14%.
- Hypertension carries the largest population-attributable fraction for CVD events among all modifiable risk factors (22% in the PURE study of 155,722 participants across 21 countries) - Fuster and Hurst's The Heart, 15th Edition, p. 224.
- For every 20/10 mmHg increase in SBP/DBP, mortality from coronary heart disease doubles, with risk rising log-linearly above 115/75 mmHg.
- Hypertension is a 2.5-3.9-fold risk factor for peripheral arterial disease and contributes substantially to stroke, heart failure, CKD, atrial fibrillation, and dementia. - Textbook of Family Medicine 9e, p. 701
3. Pathophysiology
BP = Cardiac Output × Total Peripheral Resistance. Both components are dysregulated in hypertension through interacting mechanisms:
Renin-Angiotensin-Aldosterone System (RAAS)
Increased renin secretion (from reduced renal perfusion, increased sympathetic tone, or low sodium delivery) generates angiotensin II - a potent vasoconstrictor that also stimulates aldosterone secretion, promoting sodium and water retention, thereby increasing both CO and TPR.
Sympathetic Nervous System Overactivation
Increased adrenergic tone raises CO (via increased heart rate and contractility), promotes renal sodium retention, and stimulates renin release. This is a central mechanism in younger patients with hypertension and in those with obesity or sleep apnea.
Renal Sodium Handling
Impaired pressure natriuresis (the kidney's ability to excrete sodium at a given BP) is a fundamental defect. High dietary sodium, reduced nephron number (from low birth weight, aging, or prior CKD), and RAAS overactivation all contribute.
Endothelial Dysfunction
Reduced nitric oxide bioavailability impairs vasodilation. Oxidative stress and chronic low-grade inflammation promote vascular stiffening (loss of aortic compliance), which becomes the dominant mechanism of isolated systolic hypertension in older adults.
Genetic Factors
~30-50% of BP variance is heritable. Rare single-gene causes include Liddle syndrome (ENaC gain of function), glucocorticoid-remediable aldosteronism, and apparent mineralocorticoid excess. Common variants each have small individual effect sizes (polygenic).
4. Evaluation & Diagnosis
History
- Duration and severity of elevated BP
- Prior treatment and adherence
- Risk factors: smoking, dyslipidemia, diabetes, obesity, family history of CVD or early death
- Symptoms of secondary causes (headaches/palpitations/sweating for pheo; muscle weakness/polyuria for primary aldosteronism)
- Drug causes: NSAIDs, oral contraceptives, decongestants, stimulants, liquorice, cocaine, cyclosporine, erythropoietin
Physical Exam
- Accurate BP measurement: 2+ readings, 5 min seated, averaged; measure both arms initially
- Fundoscopy: grade the retinopathy (AV nicking, flame hemorrhages, papilledema)
- Cardiac: LVH by palpation/auscultation
- Abdominal bruit (renovascular HTN), radio-femoral delay (coarctation)
- Signs of Cushing's, acromegaly, or thyroid disease
Initial Workup (Routine)
All newly diagnosed hypertensive patients require:
- Fasting metabolic panel (serum Na, K, creatinine/eGFR, glucose)
- Lipid panel
- Urine albumin-creatinine ratio + urinalysis
- 12-lead ECG (LVH criteria, arrhythmia)
- Thyroid-stimulating hormone
- Optional: echocardiography for LVH assessment
Screening for Secondary Hypertension
| Suspected Cause | Key Clinical Clues | Preferred Test |
|---|---|---|
| Primary aldosteronism | Resistant HTN, hypokalemia, adrenal adenoma | Plasma renin + aldosterone ratio |
| Renovascular disease | Azotemia with ACEI/ARB, abdominal bruit, flash pulmonary edema | Renal duplex US, CTA/MRA |
| Pheochromocytoma | Paroxysmal HTN, palpitations, diaphoresis, pallor | Plasma metanephrines; 24-h urinary metanephrines |
| Cushing syndrome | Central obesity, striae, easy bruising, buffalo hump | Overnight dexamethasone suppression test |
| CKD | eGFR <60, urine albumin:Cr >200 mg/g | Serum Cr, urine ACR |
| Coarctation of aorta | Arm BP > leg BP, chest/back bruits, rib notching | MR angiography |
- Goldman-Cecil Medicine, p. 759
5. Management
BP Targets
- General population: <130/80 mmHg (ACC/AHA 2017/2025)
- High CVD risk, CKD, diabetes: <130/80 mmHg
- Frail elderly: individualize; more conservative reduction to avoid orthostatic hypotension and falls
- The J-curve concern (risk of low DBP in coronary disease) remains controversial; most evidence does not support a threshold effect at lower BPs in the population without pre-existing severe CAD.
Lifestyle Modification (Foundation for All Stages)
Even with drug therapy, lifestyle measures reduce BP by 4-11 mmHg and reduce CV risk independently:
| Intervention | Expected SBP Reduction |
|---|---|
| Dietary sodium restriction (<2.3 g/day) | 2-8 mmHg |
| DASH diet | 8-14 mmHg |
| Weight loss (per 10 kg) | 5-20 mmHg |
| Aerobic exercise (30 min/day, most days) | 4-9 mmHg |
| Limit alcohol (men ≤2 drinks/day; women ≤1) | 2-4 mmHg |
| Smoking cessation | Indirect CVD benefit |
When to Start Drug Therapy
| BP Category | Condition | Action |
|---|---|---|
| Elevated (120-129) | Any | Lifestyle only |
| Stage 1 (130-139/80-89) | Low CV risk (<10% 10-year ASCVD risk) | Lifestyle x 3-6 months, then reassess |
| Stage 1 (130-139/80-89) | High CV risk (≥10% ASCVD risk, CVD, diabetes, CKD) | Lifestyle + drug therapy |
| Stage 2 (≥140/90) | Any | Lifestyle + drug therapy |
| Very high (≥160/100) | Any | Initiate 2-drug combination |
First-Line Drug Classes
Four drug classes have robust outcome data and form the backbone of antihypertensive therapy. Selection is guided by comorbidities:
| Class | Key Indications | Key Cautions |
|---|---|---|
| Thiazide/thiazide-like diuretics (chlorthalidone preferred over HCTZ for outcome data; also indapamide) | Isolated systolic HTN, elderly, Black patients | Hypokalemia, hyperuricemia, glucose intolerance |
| ACE inhibitors (ramipril, lisinopril, enalapril) | CKD with proteinuria, heart failure with reduced EF, post-MI, diabetes | Bilateral renal artery stenosis, pregnancy (teratogenic), hyperkalemia, cough |
| Angiotensin Receptor Blockers (ARBs) (losartan, valsartan, olmesartan) | Same as ACEi; use if ACEi cough intolerable | Bilateral RAS, pregnancy - same as ACEi; no angioedema |
| Calcium Channel Blockers (CCBs) - dihydropyridines (amlodipine, nifedipine) | Elderly, ISH, Black patients, angina, Raynaud's | Peripheral edema; avoid in heart failure with reduced EF |
| Beta-blockers (not first-line for uncomplicated HTN) | Post-MI, heart failure with reduced EF, angina, rate control in AF | Bronchospasm, peripheral arterial disease, metabolic side effects |
ACEi and ARB should not be combined (dual RAAS blockade increases risk of hyperkalemia and acute kidney injury without added BP benefit - based on ONTARGET trial).
Initial Combination Therapy
For Stage 2 HTN (BP >20/10 mmHg above goal) or high-risk patients, initiation with two-drug combination is recommended. Rationale: single-drug therapy often limited by compensatory counter-regulatory mechanisms (e.g., diuretics activate RAAS, CCBs activate RAAS), while combination therapy doubles the BP-lowering effect, reduces response heterogeneity, and allows lower doses of each component - Comprehensive Clinical Nephrology, 7th Edition, p. 532.
Preferred combinations:
- ACEI/ARB + CCB (most evidence; both vasodilatory and nephroprotective)
- ACEI/ARB + thiazide diuretic
- CCB + thiazide diuretic
Single-pill combinations improve adherence; number of pills prescribed is inversely related to adherence rate.
Resistant Hypertension
Defined as BP above goal despite ≥3 antihypertensive agents at optimal doses (including a diuretic), or controlled on ≥4 agents. Evaluate for:
- Non-adherence (urinary drug testing if needed)
- White-coat effect (ABPM/HBPM)
- Secondary causes (especially primary aldosteronism and obstructive sleep apnea)
- Interfering medications (NSAIDs, stimulants, OCP)
Spironolactone (aldosterone antagonist) is the most effective add-on agent in resistant hypertension regardless of aldosterone levels, supported by the PATHWAY-2 trial. Other options: amiloride, beta-blocker, alpha-blocker, direct vasodilators (hydralazine, minoxidil). Renal denervation remains investigational.
6. Hypertensive Urgency vs. Emergency
| Feature | Urgency | Emergency |
|---|---|---|
| BP | ≥180/110 mmHg | Usually ≥180/110 mmHg (can be lower) |
| End-organ damage | Absent | Present (new or worsening) |
| Symptoms | Often asymptomatic or vague | ACS, acute pulmonary edema, encephalopathy, stroke, aortic dissection, eclampsia |
| Setting | Often outpatient | ICU/ED |
| BP lowering | Oral; gradual over 24-48h | Parenteral; rate depends on specific emergency |
- Goldman-Cecil Medicine, p. 759
Hypertensive Emergencies - Treatment by Presentation
| Emergency | Target | Preferred Agent |
|---|---|---|
| Hypertensive encephalopathy / malignant HTN | MAP -20-25% over several hours | Labetalol IV or nicardipine IV |
| Acute ischemic stroke (BP >220 mmHg, no thrombolysis) | MAP -15% over 1 hour | Labetalol IV or nicardipine IV |
| Acute ischemic stroke (eligible for tPA, BP >185/110) | <185/110 before lytic | Labetalol IV or nicardipine IV |
| Hemorrhagic stroke (SBP >180) | Systolic 130-180 mmHg, immediate | Labetalol IV or nicardipine IV |
| Acute coronary syndrome | Systolic <140 mmHg, immediate | Nitroglycerin IV or labetalol IV |
| Acute cardiogenic pulmonary edema | Systolic <140 mmHg, immediate | Nitroprusside or nitroglycerin + loop diuretic |
| Acute aortic dissection | Systolic <120 mmHg + HR <60, immediate | Esmolol IV + nicardipine or nitroprusside |
| Eclampsia | Acute: labetalol/hydralazine | Magnesium sulfate (seizure prophylaxis) |
Key principle: Do NOT rapidly normalize BP in most emergencies (except aortic dissection, pulmonary edema, ACS). In acute ischemic stroke, avoid aggressive lowering - cerebral autoregulation is disrupted and the ischemic penumbra depends on systemic pressure for perfusion. - Goldman-Cecil Medicine, p. 760
7. Special Populations
| Population | Key Considerations |
|---|---|
| Elderly (>65) | Isolated systolic HTN is common; CCBs and thiazides are particularly effective; risk of orthostatic hypotension; frail patients may benefit from less aggressive targets |
| CKD | ACEI or ARB to reduce proteinuria progression; monitor K+ and creatinine; thiazides less effective if eGFR <30 (use loop diuretics) |
| Diabetes | Target <130/80; ACEI/ARB first-line if microalbuminuria present; SGLT2 inhibitors and GLP-1 agonists have ancillary BP-lowering effects |
| Pregnancy | Methyldopa, labetalol, and nifedipine are safe; ACEi/ARBs are contraindicated (teratogenic); treat if BP ≥160/110 (severe HTN of pregnancy) |
| Heart failure with reduced EF | ACEI/ARB (or ARNI), beta-blocker, aldosterone antagonist, SGLT2i are guideline-directed; CCBs generally avoided |
| Post-MI | Beta-blocker + ACEI/ARB |
| African American patients | CCBs and thiazides tend to be more effective as monotherapy; RAAS blockade is less effective as monotherapy; combination therapy important |
| Resistant/obese HTN | Consider secondary HTN workup; CPAP for OSA |
8. Target-Organ Damage
| Organ | Manifestations |
|---|---|
| Heart | LVH, diastolic dysfunction, HFpEF, HFrEF, CAD, AF |
| Brain | Ischemic stroke, hemorrhagic stroke, lacunar infarcts, vascular dementia, hypertensive encephalopathy |
| Kidney | CKD, hypertensive nephrosclerosis, ESKD |
| Eye | Hypertensive retinopathy (AV nicking, flame hemorrhages, cotton-wool spots, papilledema) |
| Vasculature | Aortic aneurysm, aortic dissection, peripheral arterial disease |
Key Clinical Takeaways
- Measure BP properly - at least 2 readings on 2 separate occasions, confirm with out-of-office monitoring before starting treatment.
- Treat to <130/80 mmHg in most adults with hypertension (US guidelines), guided by ASCVD risk.
- Lifestyle + pharmacotherapy together, not sequentially in high-risk patients.
- Start with 2 drugs for Stage 2 HTN or >20/10 mmHg above goal; use single-pill combinations to maximize adherence.
- Screen for secondary causes in resistant HTN, early-onset HTN, or clinical clues pointing to a specific etiology.
- Hypertensive emergency requires diagnosis-specific IV therapy with careful, measured BP lowering - not normalization. Urgency does not require emergency treatment.
- The 2025 AHA/ACC guideline (PMID 40811516) is the most current US reference, replacing the 2017 guideline.
*Sources: Fuster and Hurst's The Heart 15e; Goldman-Cecil Medicine; Comprehensive Clinical Nephrology 7e; Harrison's Principles of Internal Medicine 22e; Textbook of Family Medicine 9e; 2025 AHA/ACC Hypertension Guideline [PMID 40811516]*That's a full clinical overview of hypertension across all major domains. Let me know if you'd like me to go deeper on any specific area - resistant hypertension workup, specific drug comparisons, hypertension in CKD, the SPRINT trial implications, or anything else.
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