---

Hypertension - Comprehensive Review

---

1. DEFINITION

• Diagnosis requires two or more readings on two or more separate occasions
• When SBP and DBP fall in different categories, the higher classification is used
• In children <13 years: defined as SBP or DBP ≥95th percentile for age/sex/height, or ≥130/80 mmHg

• White-coat hypertension: elevated office BP but normal out-of-office readings (prevalence 15-25%)
• Masked hypertension: normal office BP but elevated out-of-office readings (prevalence 15-25%; CVD risk similar to sustained hypertension)

---

2. PREVALENCE & EPIDEMIOLOGY

• Affects >103 million U.S. adults; ~46% overall prevalence in adults
• Prevalence: 20-30% in adults aged 20-44, rising to 80-85% in those ≥75 years
• Non-Hispanic Black adults: highest prevalence (59%), with earlier onset and more target-organ damage
• Global burden: ~31.5% (1.04 billion) in low/middle-income countries using SBP ≥140 as threshold
• Prevalence is slightly declining in high-income countries but rising in low/middle-income countries

---

3. CAUSES / ETIOLOGY

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

• Genetic factors: polygenic inheritance, family history
• Dietary sodium excess: direct relationship with BP; urinary sodium excretion >200 mmol/d strongly associated
• Obesity/Overweight: adipocyte-derived cytokines (IL-6, TNF-α), insulin resistance, RAAS activation
• Physical inactivity
• Alcohol consumption: roughly linear dose-response; each standard drink raises SBP ~1.5 mmHg
• Aging: progressive vascular stiffness
• Socioeconomic/environmental factors

B. Secondary Hypertension (~5-10%)

---

4. PATHOPHYSIOLOGY

Hemodynamic Framework

• Increased CO (early in obesity-related hypertension, high-output states)
• Increased TPR (most established hypertension)
• Or both

Key Mechanisms

• Angiotensin II causes potent vasoconstriction, aldosterone-mediated sodium retention, and direct vascular remodeling
• RAAS overactivation is central to renovascular and many forms of secondary hypertension

• Increased catecholamines raise heart rate, contractility, and vascular tone
• Prominent in younger hypertensives and those with obesity/sleep apnea

• Impaired pressure natriuresis - kidneys require higher BP to excrete a sodium load
• Dietary sodium excess leads to volume expansion and raised cardiac output

• Chronic hypertension causes inward eutrophic remodeling (smaller lumen, same wall mass), media hypertrophy, and reduced vascular compliance
• Arterial stiffness elevates systolic pressure and pulse pressure, especially in the elderly

• Reduced nitric oxide (NO) bioavailability, increased oxidative stress, impaired vasodilation
• Creates a self-perpetuating cycle with further vascular injury

• Causes sodium retention, potassium excretion, and direct cardiac/vascular fibrosis (independent of BP)

---

5. PATHOLOGICAL CHANGES (Target Organ Damage)

Heart

• Left Ventricular Hypertrophy (LVH): concentric LVH initially; diastolic dysfunction progressing to systolic failure
• Coronary artery disease: accelerated atherosclerosis
• Heart failure (both HFpEF and HFrEF)
• Arrhythmias: atrial fibrillation

Brain

• Lacunar infarcts: small vessel disease in penetrating arteries
• Cerebral hemorrhage: particularly in hypertensive urgency/emergency
• Hypertensive encephalopathy: raised ICP, cerebral edema
• Vascular dementia

Kidneys

• Hypertensive nephrosclerosis: arteriolar sclerosis of afferent arterioles, glomerulosclerosis, tubular atrophy
• Microalbuminuria → overt proteinuria → progressive CKD
• End-stage renal disease (ESRD)

Blood Vessels

• Aortic aneurysm and dissection
• Peripheral arterial disease: aortoiliac and femoropopliteal occlusion
• Arteriosclerosis of medium and small vessels

Eyes (Hypertensive Retinopathy)

---

6. CLINICAL FEATURES

Symptoms

• Hypertension is classically "the silent killer" - most patients are asymptomatic
• Symptoms (when present) are usually due to target organ damage or very high BP levels

Signs

• Elevated BP (the defining finding)
• Fundoscopy: AV nipping, haemorrhages, papilloedema
• Displaced apex beat / S4 gallop: LVH, diastolic dysfunction
• Renal bruits: renal artery stenosis
• Radiofemoral delay: coarctation of the aorta
• Cushingoid features: Cushing's syndrome
• Thyroid enlargement / tremor: thyroid disease

Hypertensive Emergency vs. Urgency

---

7. INVESTIGATIONS

Baseline Investigations (All Newly Diagnosed Patients)

Additional Investigations (As Clinically Indicated)

---

8. MANAGEMENT

A. Goals of Treatment

• Primary goal: reduce BP to <130/80 mmHg in most adults (ACC/AHA 2017)
• Prevent target organ damage and major adverse cardiovascular events (MACE): stroke, MI, heart failure, CKD, death

B. Non-Pharmacological (Lifestyle) Interventions

C. Pharmacological Therapy

• Stage 1 HT (130-139/80-89): if 10-year ASCVD risk ≥10%, or with known CVD/diabetes/CKD
• Stage 2 HT (≥140/90): initiate drug therapy in all patients
• Hypertensive emergency: IV therapy immediately

• Aldosterone antagonists: Spironolactone, Eplerenone (resistant HT, primary aldosteronism)
• Alpha-1 blockers: Prazosin, Doxazosin (BPH, pheochromocytoma)
• Central alpha-2 agonists: Methyldopa (pregnancy), Clonidine
• Direct vasodilators: Hydralazine (pregnancy, heart failure)
• Renin inhibitors: Aliskiren

• For Stage 2 HT or BP >20/10 mmHg above goal: start with 2-drug combination
• Preferred combination: ACEi/ARB + CCB or ACEi/ARB + Thiazide diuretic
• Avoid: ACEi + ARB combination (increased risk of AKI, hyperkalaemia)
• Resistant hypertension (BP uncontrolled on 3 drugs including a diuretic): add spironolactone

D. Specific Populations

E. Hypertensive Emergency Management

• Target: reduce MAP by no more than 25% in the first hour, then to 160/100 over 2-6 hours
• Do NOT rapidly lower BP to normal (risks cerebral/coronary ischaemia)
• IV agents used:
  • Labetalol (IV infusion) - most conditions
  • Sodium nitroprusside - most emergencies; caution (cyanide toxicity)
  • Nicardipine (IV) - stroke, post-operative HT
  • Nitroglycerin - acute pulmonary oedema, ACS
  • Hydralazine - eclampsia
  • Esmolol - aortic dissection (with nitroprusside)

---

Summary Table