Hypertension
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Hypertension
Definition
Hypertension (HTN) is defined as a sustained elevation of blood pressure (BP) to ≥140 mm Hg systolic and/or ≥90 mm Hg diastolic, based on the average of two or more readings taken on two or more separate occasions in stable conditions, in adults not taking antihypertensive drugs and not acutely ill.
The ACC/AHA 2017 guideline lowered the threshold to ≥130/80 mm Hg for stage 1 hypertension, particularly in patients with chronic kidney disease (CKD), where all individuals with BP >130/80 mm Hg require both lifestyle intervention and at least one antihypertensive medication.
- Brenner and Rector's The Kidney, 2-Volume Set (JNC 7 / ACC-AHA classification)
- Park's Textbook of Preventive and Social Medicine
Classification
JNC 7 / ESH Classification
| Category | Systolic (mm Hg) | Diastolic (mm Hg) |
|---|---|---|
| Normal | < 120 | and < 80 |
| Prehypertension | 120-139 | or 80-89 |
| Stage 1 Hypertension | 140-159 | or 90-99 |
| Stage 2 Hypertension | ≥ 160 | or ≥ 100 |
ESH / WHO Grade Classification (Park's Preventive Medicine)
| Category | Systolic (mm Hg) | Diastolic (mm Hg) |
|---|---|---|
| Optimal | < 120 | and < 80 |
| Normal | 120-129 | and/or 80-84 |
| High Normal | 130-139 | and/or 85-89 |
| Grade 1 Hypertension | 140-159 | and/or 90-99 |
| Grade 2 Hypertension | 160-179 | and/or 100-109 |
| Grade 3 Hypertension | ≥ 180 | and/or > 110 |
| Isolated Systolic HTN | ≥ 140 | and < 90 |
When systolic and diastolic values fall into different categories, use the higher category to classify. - Park's Textbook of Preventive and Social Medicine
ESH Stage 3 = SBP ≥ 180 or DBP ≥ 110 mm Hg.
Epidemiology
- HTN affects approximately one-third of the adult population.
- Only ~50% of people achieve BP goals in the United States - undertreatment is common.
- It is one of the leading modifiable risk factors for stroke, MI, heart failure, and CKD.
- It confers a 2.5-fold (men) to 3.9-fold (women) age-adjusted risk for peripheral arterial disease (PAD).
- Textbook of Family Medicine, 9e
Pathophysiology
HTN results from increased cardiac output, increased peripheral vascular resistance, or both. Key mechanisms:
- Renin-Angiotensin-Aldosterone System (RAAS) activation - intrarenal RAAS activation increases angiotensin II, promoting vasoconstriction, sodium retention, and volume expansion.
- Sympathetic nervous system overactivity - increases heart rate, cardiac output, and peripheral resistance.
- Sodium and volume retention - impaired pressure natriuresis leads to chronic volume expansion.
- Endothelial dysfunction - impaired nitric oxide (NO)-mediated vasodilation; endothelin-1 elevation promotes vasoconstriction.
- Insulin resistance - contributes to sympathetic activation and impaired NO production.
In secondary hypertension (e.g., renovascular HTN), renal artery stenosis activates the RAAS via the Goldblatt mechanism, leading to elevated circulating and intrarenal angiotensin II.
- Brenner and Rector's The Kidney, 2-Volume Set
Diagnosis and Assessment
BP Measurement Technique (Box 46.1)
- Patient seated quietly for 3-5 minutes before measurement; legs uncrossed, back and arm supported
- Arm at heart level (fourth intercostal space)
- Use a correctly sized cuff (bladder length = 80% arm circumference; width = 40%)
- Take at least two readings, average them
- Measure both arms (~20% of individuals have an interarm difference)
- Neither patient nor examiner should talk during measurement
- Use Korotkoff phase V (disappearance of sounds) for diastolic
"White Coat" Effect
BPs measured by physicians are systematically higher. Validated automated oscillometric office devices (measured while clinician is absent) reduce this effect and are better predictors of CV morbidity.
Additional BP Monitoring Methods
- Home BP monitoring goal: < 135/85 mm Hg (average)
- 24-hour ambulatory BP monitoring (ABPM) goal: < 130/80 mm Hg
- ABPM in children/young adults often reveals nocturnal BP elevations and attenuated dipping before clinical HTN develops.
Target Organ Status (TOS) Assessment
Evaluate for:
- Funduscopic changes (Keith-Wagener retinopathy)
- Cardiac: LVH on ECG/echo, heart failure
- Vascular: carotid stenosis, abdominal aortic aneurysm, PAD
- Neurological: stroke, TIA
- Renal: proteinuria, elevated creatinine/eGFR
Secondary Causes (Must Exclude)
| Cause | Clue |
|---|---|
| Primary aldosteronism | Hypokalemia, adrenal adenoma |
| Renovascular HTN | Young woman + renal bruit, flash pulmonary edema |
| Pheochromocytoma | Episodic HTN, headache, palpitations, sweating |
| Obstructive sleep apnea | Resistant HTN, obesity, snoring |
| CKD | Elevated creatinine, proteinuria |
| Coarctation of aorta | Young patient, differential BP arms vs. legs |
| Cushing's syndrome | Central obesity, striae, steroid use |
| Hypothyroidism/Hyperthyroidism | TSH abnormality |
Organ Damage
The degree of end-organ damage does not always correlate linearly with BP level. The presence of any organ damage markedly increases CV risk at any BP level. Target organs include:
-
Heart: LVH, coronary artery disease, heart failure
-
Brain: stroke, TIA, hypertensive encephalopathy
-
Kidneys: proteinuria, CKD, ESKD
-
Eyes: hypertensive retinopathy (AV nicking, flame hemorrhages, papilledema in grade 4)
-
Vessels: aortic aneurysm, PAD
-
Park's Textbook of Preventive and Social Medicine
Management
Goals
- General: < 140/90 mm Hg
- CKD (with or without proteinuria): < 130/80 mm Hg
- Patients age > 60 (JNC 8): < 150/90 mm Hg
1. Lifestyle Modifications (All Patients)
| Intervention | Expected SBP Reduction |
|---|---|
| DASH diet (rich in fruits, vegetables, low-fat dairy) | 8-14 mm Hg |
| Weight reduction (per 10 kg loss) | 5-20 mm Hg |
| Aerobic exercise (30 min most days) | 4-9 mm Hg |
| Sodium restriction (< 2.4 g/day) | 2-8 mm Hg |
| Moderation of alcohol | 2-4 mm Hg |
| Smoking cessation (CV risk, not BP per se) | - |
2. Pharmacological Treatment
Key principles:
- If BP is > 20/10 mm Hg above target, start two antihypertensives (consider a combination pill).
- Most patients (~75%) require two or more drugs to reach goal.
- Avoid monotherapy with a beta-blocker or alpha-blocker in uncomplicated HTN (inferior clinical trial evidence).
- NEVER combine two RAAS blockers (e.g., ACE inhibitor + ARB, or ARB + renin inhibitor) - almost always contraindicated (hyperkalemia, AKI risk).
First-line drug classes:
| Class | Example Drugs | Notes |
|---|---|---|
| Thiazide diuretics | Chlorthalidone, HCTZ, indapamide | Preferred first-line; chlorthalidone superior to HCTZ |
| ACE inhibitors | Lisinopril, ramipril, enalapril | First-line in CKD, DM, HF, post-MI; cough/angioedema side effects |
| ARBs | Losartan, valsartan, irbesartan | Alternative to ACEI if cough |
| Calcium channel blockers (CCBs) | Amlodipine (DHP), diltiazem/verapamil | Amlodipine preferred in combination therapy |
| Beta-blockers | Metoprolol, atenolol, bisoprolol, carvedilol | Preferred in CAD, HFrEF, post-MI |
Best two-drug combination (based on ACCOMPLISH trial):
ACE inhibitor + CCB (amlodipine) - superior to ACE inhibitor + thiazide for CV outcomes.
Compelling Indications (JNC 7 approach):
| Condition | Preferred Drug Class |
|---|---|
| Heart failure (HFrEF) | ACE inhibitor/ARB + beta-blocker + aldosterone antagonist |
| Post-MI | Beta-blocker + ACE inhibitor |
| Diabetic nephropathy | ACE inhibitor or ARB |
| CKD with proteinuria | ACE inhibitor or ARB |
| Isolated systolic HTN (elderly) | Thiazide or CCB |
| Pregnancy | Methyldopa, labetalol, nifedipine (NOT ACE/ARB) |
Resistant Hypertension (BP uncontrolled on 3+ drugs including a diuretic):
- Affects ~10% of hypertensive population
- Add spironolactone 12.5-50 mg/day (aldosterone blockade is empirically effective)
- Check for medication non-adherence and secondary causes
- CPAP for OSA has been shown to reduce BP in resistant HTN (HIPARCO trial)
Drug Dosage Table (Selected)
| Drug Class | Agent | Usual Dose |
|---|---|---|
| Loop diuretics | Furosemide | 20-80 mg/day (twice daily) |
| Loop diuretics | Torsemide | 5-10 mg/day |
| K-sparing | Spironolactone | 12.5-100 mg/day |
| K-sparing | Amiloride | 5-10 mg/day |
| Central alpha-agonist | Clonidine | 0.1-0.8 mg/day (2-3x/day) |
| Central alpha-agonist | Methyldopa | 250-500 mg (twice daily) |
| Alpha-blockers | Doxazosin | 2-16 mg/day |
| Alpha-blockers | Prazosin | 1-10 mg/day (twice daily) |
- Textbook of Family Medicine, 9e
Special Populations
| Population | Key Considerations |
|---|---|
| Pregnancy | Avoid ACE inhibitors and ARBs (teratogenic); use methyldopa, labetalol, or nifedipine; pre-eclampsia defined as BP ≥ 140/90 + proteinuria after 20 weeks |
| CKD | Target < 130/80; ACE inhibitor or ARB first-line; watch potassium and eGFR |
| Elderly | Lower targets may increase falls; JNC 8 suggests < 150/90 for age > 60 |
| Diabetes | Target < 130/80; RAAS blockade preferred |
| ADPKD | HTN affects ~50% of young adults with ADPKD and normal renal function; ~100% with ESKD; RAAS is key mediator |
Hypertensive Emergencies vs. Urgencies
| Emergency | Urgency | |
|---|---|---|
| Definition | Severe HTN with acute end-organ damage | Severe HTN without end-organ damage |
| BP threshold | Usually > 180/120 | > 180/120 |
| Treatment | IV antihypertensives (labetalol, nicardipine, sodium nitroprusside); reduce MAP by ≤25% in first hour | Oral antihypertensives; gradual reduction over hours-days |
| Examples | Hypertensive encephalopathy, aortic dissection, eclampsia, acute stroke, STEMI | Severe asymptomatic HTN |
Recent Evidence (2024-2026)
- A 2025 Lancet systematic review (PMID: 40885583) evaluated the blood pressure-lowering efficacy of antihypertensive drugs and their combinations across randomised placebo-controlled trials, providing updated comparative efficacy data.
- A 2024 Circulation systematic review/meta-analysis (PMID: 39355923) assessed catheter-based renal denervation as a non-pharmacological option for resistant HTN, showing consistent BP reductions.
- A 2025 American Journal of Obstetrics and Gynecology network meta-analysis (PMID: 40216176) compared oral antihypertensive agents specifically during pregnancy.
Sources: Textbook of Family Medicine 9e | Brenner and Rector's The Kidney, 2-Volume Set | Park's Textbook of Preventive and Social Medicine | Comprehensive Clinical Nephrology, 7th Edition | PubMed 2024-2025
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