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Hypertension - Final Year Medical Student Guide

Definition & Classification (ACC/AHA 2017 + 2025)

Important note: The 2018 ESC/ESH guidelines retain 140/90 mmHg as the threshold for hypertension (not 130/80), so thresholds differ between European and American guidelines.

• Isolated systolic hypertension: SBP ≥ 140 + DBP < 90 - common in the elderly from reduced aortic compliance
• Malignant hypertension: BP > 200/120 with advanced bilateral retinopathy (grade III-IV)
• White coat hypertension: Elevated in clinic, normal out-of-office
• Masked hypertension: Normal in clinic, elevated out-of-office
• Resistant hypertension: BP ≥ 130/80 on ≥ 3 agents (one being a diuretic) at maximally tolerated doses, or controlled on ≥ 4 agents

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Epidemiology

• Hypertension is the leading cause of CV mortality and morbidity worldwide (stroke, ischemic heart disease, heart failure, CKD)
• Affects > 100 million US adults; lifetime risk of developing HTN is ~90%
• For every 20 mmHg rise in SBP (or 10 mmHg in DBP) in people aged 40-69 years, CV mortality doubles across the entire range from 115/75 to 185/115 mmHg
• Framingham data: hypertensive patients have a 4x increase in CVA and 6x increase in CHF vs normotensives
• 90% have primary (essential) hypertension; only 5-10% have secondary causes

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Pathophysiology

Primary (Essential) Hypertension - Multifactorial

1. RAAS activation - Angiotensin II causes direct vasoconstriction + aldosterone-driven sodium/water retention
2. Sympathetic nervous system overdrive - Increased catecholamines raise cardiac output and peripheral resistance
3. Endothelial dysfunction - Reduced nitric oxide (NO) bioavailability; NO is generated from L-arginine via nitric oxide synthase (NOS). Accumulation of asymmetric dimethylarginine (ADMA) inhibits NOS
4. Salt sensitivity & volume expansion - Impaired pressure-natriuresis; sodium retention elevates extracellular fluid volume
5. Vascular remodeling - Smooth muscle hypertrophy increases systemic vascular resistance (SVR)
6. Genetic polymorphisms + environmental factors (obesity, sodium intake, sedentary lifestyle, alcohol)

"It seems likely that essential hypertension is a multifactorial disorder resulting from the cumulative effects of multiple genetic polymorphisms and interacting environmental factors." - Robbins Pathologic Basis of Disease

Vascular Changes

• Hyaline arteriolosclerosis: Pink homogeneous wall thickening - associated with benign hypertension and diabetes
• Hyperplastic arteriolosclerosis ("onion-skin"): Concentric laminated thickening - associated with malignant hypertension; may cause fibrinoid necrosis

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Causes of Secondary Hypertension (~5-10% of cases)

• Onset before age 30 (especially no family history, no obesity)
• Resistant or difficult-to-control hypertension
• Hypokalemia (think primary aldosteronism)
• Paroxysmal symptoms - headache, palpitations, sweating (think phaeochromocytoma)
• Abdominal bruit (think renal artery stenosis)
• Truncal obesity, striae, moon face (think Cushing's)
• Elevated creatinine, abnormal urinalysis (think renal parenchymal)

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Clinical Evaluation

Three Key Questions (NKF Primer Framework)

1. Is this primary or secondary hypertension? - History, examination, initial investigations to screen for identifiable cause
2. What other CV risk factors are present? - Smoking, diabetes, dyslipidaemia, obesity, age, sex, family history
3. Is there end-organ damage?

End-Organ Damage to Assess

Measuring BP Correctly

• Rest for ≥5 minutes before measurement
• Appropriate cuff size (too small → falsely elevated)
• Two readings per visit, two visits minimum
• Both arms initially (significant difference > 15 mmHg suggests subclavian stenosis or aortic disease)
• Confirm with ambulatory BP monitoring (ABPM) or home BP if suspected white coat or masked HTN

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Non-Pharmacological Treatment (Lifestyle Modification)

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Pharmacological Treatment

When to Start

BP Treatment Target

First-Line Drug Classes

Chlorthalidone is preferred over HCTZ - longer half-life, greater BP reduction, superior outcomes data

Drug Combos

• Standard initial 3-drug combination: A + C + D (ACEi/ARB + CCB + Diuretic)
• Do NOT combine ACEi + ARB (dual RAAS blockade - increases adverse effects without added benefit)
• Beta-blockers are not first-line for uncomplicated HTN but are preferred when:
  • Post-MI or high coronary risk
  • Heart failure with reduced EF
  • Rate control in AF

Compelling Indications - Drug of Choice

Resistant Hypertension

• Add spironolactone (MRA) as 4th agent - most evidence; primary aldosteronism very common in resistant HTN
• Chlorthalidone > HCTZ in advanced CKD
• Second-generation catheter-based renal denervation modestly lowers BP but not yet FDA-approved

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Hypertensive Crisis

Hypertensive Urgency

• BP ≥ 180/110 mmHg without new/worsening end-organ damage
• Patient often asymptomatic or minimally symptomatic
• Management: Restart/adjust oral antihypertensives; no need for IV drugs or hospital admission in most cases; schedule prompt outpatient follow-up
• Do NOT lower BP too rapidly - risk of ischaemia

Hypertensive Emergency

• BP ≥ 180/110 mmHg with new acute end-organ damage
• Occurs in ~0.3% of all ED visits
• Common presentations:
  • Hypertensive encephalopathy (headache, obtundation, visual disturbance, seizures, absent focal signs, posterior leukoencephalopathy/PRES on MRI)
  • Acute pulmonary oedema/flash pulmonary oedema
  • Acute coronary syndrome
  • Acute ischaemic or haemorrhagic stroke
  • Acute aortic dissection
  • Hypertensive retinopathy with papilloedema

• Reduce MAP by 10-20% in the first hour, then a further 5-15% over the next 23 hours
• Exceptions (faster or more cautious lowering needed):
  • Aortic dissection - target SBP < 120 within minutes (IV labetalol/esmolol + nitroprusside)
  • Acute ischaemic stroke - DO NOT lower BP aggressively unless thrombolysis planned (target < 185/110 before tPA) or BP > 220/120
  • Intracerebral haemorrhage - Target SBP < 140

IV Drugs for Hypertensive Emergency

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Hypertension in Special Populations

CKD

• HTN is almost universal in advanced CKD (80-85% prevalence)
• Mechanism: volume expansion + salt sensitivity + sympathetic activation + endothelin + impaired NO generation + ADMA accumulation
• Treatment: ACEi or ARB (first-line; especially with proteinuria) + diuretic + dietary sodium restriction
• Thiazides effective until eGFR ~30; loop diuretics (furosemide) preferred when eGFR < 30
• Target: < 130/80 mmHg

Diabetes Mellitus

• Target: < 130/80 mmHg (those with ≥ 15% 10-yr ASCVD risk); some guidelines accept < 140/90 for lower-risk diabetics
• Preferred: ACEi/ARB (renoprotective); SGLT2i increasingly added for CV-renal protection

Pregnancy

• Chronic HTN in pregnancy: methyldopa, labetalol, nifedipine
• Avoid ACEi/ARB (teratogenic - fetopathy)
• Pre-eclampsia: HTN after 20 weeks + proteinuria (or end-organ dysfunction); IV labetalol or hydralazine in severe cases; MgSO4 for seizure prophylaxis
• HELLP syndrome: Haemolysis, Elevated Liver enzymes, Low Platelets - obstetric emergency

Elderly

• Isolated systolic hypertension common (aortic stiffening)
• CCB (amlodipine) and thiazides particularly effective
• Target < 130/80 mmHg if tolerated; avoid orthostatic hypotension

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Complications (End-Organ Damage)

Hypertensive Retinopathy Grading (Keith-Wagener-Barker)

• Grade I: Arteriolar narrowing/silver wiring
• Grade II: AV nipping (arteriovenous nicking)
• Grade III: Flame haemorrhages, cotton wool spots, hard exudates
• Grade IV: Grade III + papilloedema (= malignant hypertension)

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Key Exam Points

1. Threshold for treatment: 130/80 (ACC/AHA) vs 140/90 (ESC/ESH) - know both
2. First-line: ACEi/ARB + CCB + thiazide - the A+C+D combination
3. Avoid ACEi/ARB in: pregnancy, bilateral renal artery stenosis
4. Avoid ACEi + ARB combined (dual blockade)
5. Resistant HTN: add spironolactone 4th
6. Emergency vs urgency: end-organ damage is the differentiator
7. Aortic dissection: target SBP < 120 rapidly; use labetalol or esmolol + nitroprusside
8. Stroke: do NOT lower BP aggressively (except before thrombolysis)
9. Pheochromocytoma: alpha-blocker FIRST, then beta-blocker (never beta-blocker alone - paradoxical crisis)
10. Chlorthalidone > HCTZ (superior outcomes, longer half-life)
11. SPRINT trial: SBP < 120 reduced CV events vs < 140 in non-diabetics
12. ACCORD trial: intensive SBP reduction did not reduce primary CV endpoint in diabetes
13. Medication nonadherence is the most common cause of apparent resistant hypertension

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2025 AHA/ACC Guideline Update

• Designed as a "living document" with ongoing updates
• Reaffirms < 130/80 mmHg treatment target for most adults
• Emphasises lifestyle intervention and team-based care
• Note: An erratum was published (PMID: 42160500)

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Hypertension - High-Yield Exam Q&A

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DEFINITION & CLASSIFICATION

ESC/ESH (European) guidelines use ≥ 140/90 as the threshold - know both for exams.

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PATHOPHYSIOLOGY

1. RAAS activation - Angiotensin II → vasoconstriction + aldosterone → Na/water retention
2. Sympathetic overdrive - ↑ catecholamines → ↑ cardiac output + ↑ SVR
3. Endothelial dysfunction - ↓ nitric oxide (NO) production; ADMA accumulates and inhibits NOS
4. Salt sensitivity - Impaired pressure-natriuresis → volume expansion
5. Vascular remodelling - Smooth muscle hypertrophy → ↑ SVR
6. Genetic + environmental - Multiple polymorphisms + obesity, sedentary lifestyle, excess sodium/alcohol

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• Hyaline arteriolosclerosis - Pink, homogeneous wall thickening; benign/chronic hypertension + diabetes
• Hyperplastic ("onion-skin") arteriolosclerosis - Concentric laminated SMC thickening; malignant hypertension; may cause fibrinoid necrosis

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SECONDARY HYPERTENSION

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• Onset < 30 years, no family history, non-obese
• Resistant/difficult-to-control HTN
• Hypokalaemia → primary aldosteronism
• Paroxysmal headache, sweating, palpitations → phaeochromocytoma
• Abdominal bruit → renal artery stenosis
• Truncal obesity, striae, moon face → Cushing's
• Abnormal urine/creatinine → renal parenchymal disease
• Difference in BP between arms / delayed radial-femoral pulse → coarctation

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CLINICAL ASSESSMENT

1. Primary or secondary hypertension?
2. Presence of other CV risk factors?
3. Evidence of end-organ damage?

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NON-PHARMACOLOGICAL TREATMENT

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PHARMACOLOGICAL TREATMENT

• Stage 1, low risk (no ASCVD, 10-yr CVD risk < 10%): lifestyle first; add drug only if target not met after 3-6 months
• Stage 1 + ASCVD or 10-yr risk ≥ 10%: start drug immediately + lifestyle
• Stage 2 (≥ 140/90): drug + lifestyle from the outset; if BP > 20/10 above target, start 2-drug combination straight away
• Treatment target: < 130/80 mmHg in most patients

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Standard 3-drug combo: A + C + D (ACEi/ARB + CCB + thiazide diuretic)

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• Pregnancy (fetopathy - renal agenesis, oligohydramnios)
• Bilateral renal artery stenosis (efferent dilatation → acute renal failure)
• Hyperkalaemia (ACEi)
• Angioedema (ACEi - switch to ARB)
• Do NOT combine ACEi + ARB (dual RAAS blockade - no benefit, increased harm)

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HYPERTENSIVE EMERGENCY

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• Hypertensive encephalopathy - Headache, obtundation, seizures, visual disturbance, no focal signs; PRES (posterior reversible encephalopathy syndrome) on MRI
• Flash pulmonary oedema
• ACS/myocardial infarction
• Acute ischaemic or haemorrhagic stroke
• Aortic dissection
• Eclampsia
• Grade IV hypertensive retinopathy + papilloedema

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Nitroprusside risk: cyanide toxicity - avoid in liver/renal failure

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• Reduce MAP by 10-20% in the first hour
• Then a further 5-15% over the next 23 hours
• Exceptions (need faster or different strategy): aortic dissection, acute ischaemic stroke, intracerebral haemorrhage

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HIGH-YIELD TRIAL FACTS

• SPRINT - SBP target < 120 vs < 140 in non-diabetics; intensive group had fewer CV events and deaths; however, more adverse effects (AKI, hypotension)
• ACCORD - Same intensive target in diabetics; no reduction in primary CV composite endpoint (though stroke was reduced); result conflicts with SPRINT

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COMMON EXAM TRAPS

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