Essential Hypertension

Definition

Pathophysiology

• Fluid volume expansion → increased cardiac output → peripheral vasoconstriction → elevated blood pressure
• A new steady state ("resetting of pressure natriuresis") is reached, but only at the cost of chronically elevated pressure. (Robbins & Cotran Pathologic Basis of Disease)

• Increased sympathetic nerve activity (especially renal) driven by leptin and other adipokines
• Activation of the renin-angiotensin-aldosterone system (RAAS) → raised angiotensin II and aldosterone
• Physical compression of the kidneys by perinephric fat
• Reduced arterial baroreceptor sensitivity (Guyton & Hall Textbook of Medical Physiology)

• Heritability is estimated at ~30%; concordance is higher in monozygotic than dizygotic twins

• 500 genetic variants from genome-wide association studies are linked to blood pressure

• Rare Mendelian forms (Liddle syndrome, Gordon syndrome, apparent mineralocorticoid excess) illustrate how sodium-channel mutations can cause hypertension — highlighting sodium metabolism's central role (Goldman-Cecil Medicine; Robbins & Cotran)

• High dietary sodium (hypertension is rare at < 50 mmol/day sodium intake)
• Physical inactivity
• Heavy alcohol consumption (≥3 drinks/day → sympathetic activation via withdrawal)
• Obstructive sleep apnea → nocturnal sympathetic surges
• Low dietary potassium intake

Clinical Features

• The vast majority of patients are asymptomatic — hypertension is often detected incidentally
• Some experience sleep disturbance or reduced exercise tolerance
• On physical examination, the earliest sign is typically hypertensive retinopathy
• Secondary hypertension should be excluded, especially in younger patients or those with resistant hypertension

Vascular Pathology

Hyaline arteriolosclerosis (left) and hyperplastic arteriolosclerosis — "onion-skinning" (right). From Robbins, Cotran & Kumar, Pathologic Basis of Disease.

Key Points Summary

Stepwise Drug Selection for Essential Hypertension

Before Any Drug: Lifestyle Modification (Foundation Step)

Step 1 — First-Line Monotherapy (or Low-Dose Dual Therapy)

Race consideration (JNC/AHA): In Black patients, thiazide diuretic or CCB is preferred over ACEi/ARB alone as monotherapy (ACEi/ARB less effective as monotherapy in this group).

Step 2 — Add a Second Drug (If Step 1 Fails After 4–8 Weeks)

• ACEi or ARB + CCB (e.g., Ramipril + Amlodipine) ← most commonly recommended by WHO/ESC
• ACEi or ARB + Thiazide diuretic (e.g., Lisinopril + Chlorthalidone)
• CCB + Thiazide diuretic (for Black patients or when RAAS not tolerated)

⚠️ Avoid: ACEi + ARB together — minimal added BP benefit, high risk of renal impairment and hyperkalemia.

β-blockers are not recommended for initial therapy in uncomplicated hypertension — they are less effective for stroke prevention than first-line drugs.

Step 3 — Triple Therapy (If Step 2 Fails)

ACEi/ARB + CCB + Thiazide-like diuretic

Step 4 — Resistant Hypertension (Fails Triple Therapy at Optimal Doses)

1. Confirm adherence and rule out pseudo-resistance (white coat effect)
2. Ensure long-acting thiazide-like diuretic (chlorthalidone or indapamide — not HCTZ alone)
3. Check for secondary causes

Summary Stepwise Algorithm

STEP 0:  Lifestyle modification (all patients)
          ↓
STEP 1:  One first-line drug (thiazide / ACEi / ARB / CCB)
         [Consider low-dose dual therapy if BP >20/10 above target]
          ↓
STEP 2:  ACEi or ARB  +  CCB  or  Thiazide
          ↓
STEP 3:  ACEi/ARB  +  CCB  +  Thiazide-like diuretic (triple pill)
          ↓
STEP 4:  Add spironolactone ± β-blocker ± α-blocker ± clonidine
         (Resistant HTN — investigate secondary causes)

Preferred Drug by Compelling Indication