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Hypertension - Comprehensive 20-Mark Answer

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1. Definition and Classification

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2. Epidemiology

• Hypertension affects approximately 1.28 billion adults worldwide and is the leading modifiable risk factor for cardiovascular disease (CVD), stroke, renal failure, and premature death.
• It carries a 2.5-fold (men) to 3.9-fold (women) age-adjusted increased risk for peripheral arterial disease.
• Prevalence increases sharply with age, obesity, dietary sodium excess, and physical inactivity.
• African Americans tend to have more severe hypertension and higher rates of target organ damage than other populations.

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3. Etiology and Classification

A. Primary (Essential) Hypertension (~90-95%)

• Genetic factors: Polygenic inheritance; multiple modest-effect alleles
• Environmental/Lifestyle factors (the six key modifiable exposures):
  1. Poor diet quality (low adherence to DASH-style eating)
  2. Excess body weight / obesity (BMI ≥30)
  3. Excessive dietary sodium intake
  4. Insufficient dietary potassium intake
  5. Physical inactivity (<150 min aerobic exercise/week)
  6. Alcohol consumption (especially binge drinking)
• Other associations: Heavy metal exposure (lead, mercury, cadmium, arsenic), air pollution (PM2.5 increases SBP by ~3-5 mmHg), high altitudes, cold climate

B. Secondary Hypertension (~5-10%)

1. Treatment-resistant hypertension (BP >130/80 on 3+ drugs)
2. Abrupt worsening of previously controlled hypertension
3. Disproportionate target organ damage for BP level
4. Lab abnormalities: unprovoked hypokalemia, proteinuria, left ventricular hypertrophy

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4. Pathophysiology

Renin-Angiotensin-Aldosterone System (RAAS)

• Increased renin secretion → angiotensin I → angiotensin II (ACE) → vasoconstriction + aldosterone release → sodium/water retention → increased BP.

Sympathetic Nervous System Overactivity

• Enhanced adrenergic tone increases heart rate, CO, and causes arteriolar constriction.

Sodium and Volume Retention

• Impaired renal pressure-natriuresis curve: kidneys maintain sodium retention at inappropriately high BPs.

Endothelial Dysfunction

• Reduced nitric oxide (NO) production, increased endothelin, oxidative stress → decreased vasodilation.

Arterial Stiffness

• Loss of vascular compliance with aging amplifies pulse pressure; stiffened arteries contribute to isolated systolic hypertension and target organ damage.

Insulin Resistance / Metabolic Syndrome

• Associated with elevated angiotensin II, aldosterone, and sympathetic activation.

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5. Target Organ Damage (Complications)

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6. Clinical Features and Evaluation

• Headache (typically occipital, worse in the morning)
• Dizziness, tinnitus, epistaxis (less specific)
• Hypertensive urgency/emergency: severe headache, visual disturbance, confusion, chest pain, dyspnea

1. Confirm diagnosis (BP measured correctly; two readings at two visits)
2. Identify secondary causes
3. Assess cardiovascular risk profile and comorbidities
4. Identify target organ damage

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7. Investigations

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8. Treatment

A. Non-Pharmacologic (Lifestyle Modifications) - First-line for ALL patients

1. DASH diet (high fruits, vegetables, low saturated fat) - reduces SBP by 8-14 mmHg
2. Weight loss (each kg lost lowers SBP by ~1 mmHg)
3. Dietary sodium reduction to <2.3 g/day (SBP ↓ 2-8 mmHg)
4. Potassium supplementation (3500-5000 mg/day through diet)
5. Physical activity ≥150 min/week of moderate aerobic exercise (SBP ↓ 4-9 mmHg)
6. Alcohol reduction to ≤2 drinks/day in men, ≤1 in women

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B. Pharmacologic Therapy

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i. Thiazide Diuretics (e.g., hydrochlorothiazide, chlorthalidone)

• Mechanism: Inhibit NaCl reabsorption in the distal convoluted tubule → ↓ intravascular volume initially → long-term ↓ peripheral vascular resistance
• Use: First-line; useful in combination with most other agents
• Adverse effects: Hypokalemia, hyperuricemia, hyperglycemia, hypercalcemia, hyponatremia
• Caution: Not effective when eGFR <30 mL/min (use loop diuretics instead)

ii. ACE Inhibitors (e.g., enalapril, lisinopril, ramipril)

• Mechanism: Block conversion of angiotensin I → angiotensin II → ↓ vasoconstriction, ↓ aldosterone, ↓ sodium retention
• Compelling indications: CKD with proteinuria, heart failure with reduced EF (HFrEF), post-MI, diabetes with nephropathy
• Adverse effects: Dry cough (most common; 10-15%), angioedema (rare but serious), hyperkalemia, teratogenic (class D/X in pregnancy)
• Contraindications: Pregnancy, bilateral renal artery stenosis, history of angioedema

iii. Angiotensin Receptor Blockers - ARBs (e.g., losartan, valsartan, telmisartan)

• Mechanism: Block AT1 receptors → same effect as ACEi without cough (no bradykinin accumulation)
• Use: Alternative when ACEi not tolerated; same compelling indications
• Adverse effects: Hyperkalemia, angioedema (rare), teratogenic

iv. Calcium Channel Blockers - CCBs

• Dihydropyridines (amlodipine, nifedipine): Selective vascular smooth muscle → vasodilation → ↓ TPR; minimal cardiac effects; long half-life of amlodipine (30-50 hours) allows once-daily dosing
• Non-dihydropyridines - Verapamil and Diltiazem: Both vascular and cardiac effects (negative chronotropy, dromotropy, inotropy); used in AF rate control; avoid in HFrEF
• Adverse effects (DHPs): Peripheral edema, reflex tachycardia, flushing
• Adverse effects (non-DHPs): AV block, constipation (verapamil), bradycardia
• Useful in: Asthma, diabetes, peripheral vascular disease (where beta-blockers are problematic)

v. Beta-Blockers (e.g., metoprolol, atenolol, carvedilol, nebivolol)

• Mechanism: ↓ CO via reduced heart rate and contractility; ↓ renin release → ↓ angiotensin II; ↓ central sympathetic outflow
• Compelling indications: Post-MI, HFrEF (carvedilol, metoprolol succinate, bisoprolol), stable angina
• 3rd generation (nebivolol, carvedilol): Vasodilatory properties (via NO and alpha-blockade respectively)
• Adverse effects: Fatigue, sexual dysfunction, masking of hypoglycemia, bradycardia
• Contraindications: High-degree AV block, non-selective beta-blockers in asthma; caution in diabetes

vi. Mineralocorticoid Receptor Antagonists (e.g., spironolactone, eplerenone)

• Mechanism: Antagonize aldosterone at collecting duct → natriuresis + potassium retention
• Use: Resistant hypertension (evidence-based add-on); also in primary hyperaldosteronism, HFrEF
• Adverse effects: Hyperkalemia, gynecomastia (spironolactone), menstrual irregularities

vii. Alpha-1 Blockers (e.g., doxazosin, prazosin)

• Mechanism: Block alpha-1 receptors → vasodilation
• Additional benefit: Improve benign prostatic hyperplasia (BPH) symptoms
• Caution: First-dose orthostatic hypotension; less recommended as monotherapy

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C. Special Situations and Compelling Indications

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D. Hypertensive Emergency Management

• Goal: Reduce MAP by no more than 25% within the first hour, then to 160/100 mmHg over the next 2-6 hours, then normalize over 24-48 hours (too-rapid reduction risks ischemia due to impaired cerebral autoregulation)
• IV agents:
  • Sodium nitroprusside: Arterial and venous dilator; instant onset/offset; use in most emergencies (risk: cyanide toxicity with prolonged infusion)
  • Labetalol IV: Alpha + beta blockade; avoid in decompensated HF, asthma
  • Nicardipine IV: DHP-CCB; useful in perioperative or stroke hypertension
  • Hydralazine IV/IM: Used in hypertensive emergencies in pregnancy
  • Clevidipine IV: Ultrashort-acting DHP-CCB
  • Esmolol IV: Ultrashort beta-blocker; aortic dissection, perioperative HTN
  • Phentolamine: Alpha-blocker; drug of choice in pheochromocytoma crisis

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9. Resistant Hypertension

• Exclude pseudo-resistance: poor medication adherence, white coat effect, incorrect BP measurement, suboptimal regimen
• Evidence-based add-on: spironolactone (mineralocorticoid receptor antagonist)
• Consider secondary causes in all resistant hypertension cases

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10. Hypertension in Special Populations

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Summary Points for Exam

1. Hypertension = "silent killer"; defined as SBP/DBP ≥130/80 mmHg (ACC/AHA 2017)
2. Primary (essential) in 90-95%; secondary in 5-10% - always screen for secondary causes in resistant/refractory cases
3. Pathophysiology: abnormal CO and/or TPR, RAAS activation, SNS overactivity, sodium retention, endothelial dysfunction
4. Complications: cardiac (LVH, HF, IHD), neurological (stroke, encephalopathy), renal (nephrosclerosis, CKD), retinopathy, aortic dissection
5. Treatment: lifestyle first; pharmacologically use thiazide, CCB, ACEi, or ARB as first-line; combination preferred over high-dose monotherapy
6. Match drug to comorbidity (compelling indications)
7. Hypertensive emergency: reduce MAP by max 25% in 1st hour with IV agents
8. Resistant hypertension: add spironolactone; rule out secondary causes

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