A chronic cardiovascular condition defined by persistently elevated systemic arterial blood pressure (≥130/80 mmHg), increasing the risk of end-organ damage to the heart, brain, kidneys, and vasculature.

Exam domain	One-glance essentials
Definition / diagnosis	Hypertension = sustained elevated arterial BP; local/ESC-style office threshold is generally ≥ 140/90 mmHg ^[1] It is usually asymptomatic and treated to prevent hypertension-mediated organ damage ^[1]
Epidemiology / risks	Essential HTN accounts for about 95%; obesity, high sodium, inactivity, alcohol, diabetes and family history contribute ^[2] Suspect secondary HTN with young onset, resistant disease, sudden worsening, hypokalaemia or specific clues ^[2]
Core mechanism	BP = cardiac output × total peripheral resistance; renal sodium handling, SNS and RAAS sustain chronic elevation ^[3] Pressure injury → LVH, endothelial dysfunction, arteriosclerosis and progressive target-organ ischaemia ^[2]
Clinical picture	Usually silent; symptoms reflect crisis, complications or a secondary cause ^[2] Examine bilateral/standing BP, BMI, fundoscopy, peripheral pulses/bruits, heart and kidneys ^[2]
Investigations	Confirm moderate office elevation with HBPM/ABPM; 24-hour ABPM hypertension is ≥ 130/80 mmHg ^[2] Baseline: urinalysis/ACR, RFT, K/Ca, glucose/HbA1c, lipids, TSH, ECG and fundoscopy ^[1]^[2] Targeted tests: ARR, ONDST, metanephrines, renal Doppler/CTA, PSG or aortic imaging as indicated ^[2]
Management	*Lifestyle measures for all: DASH-style diet, sodium restriction, exercise, weight/alcohol control and smoking cessation* ^[1] Stepwise: A or C or D → A+C/A+D → A+C+D → add spironolactone for resistant HTN ^[3] Match therapy to comorbidity and treat secondary causes ^[2]
Complications	Heart: LVH → HFpEF/HFrEF, IHD and AF; brain: ischaemic/haemorrhagic stroke and encephalopathy ^[1] Kidney: nephrosclerosis/CKD; eyes: retinopathy; vessels: PAD, aneurysm and dissection ^[1]
Prevention / follow-up	Monitor home BP, adherence, renal function/electrolytes and annual cardiovascular risk/organ damage ^[2] Use single-pill combinations where appropriate and address diabetes, lipids, obesity and OSA ^[3]
Exam traps	*Emergency vs urgency depends on acute target-organ damage, not the BP number alone* ^[1] Emergency: lower BP by no more than ~25% in the first hour, then gradually ^[2] Bilateral renal artery stenosis/pregnancy → avoid ACEI/ARB; phaeochromocytoma needs alpha before beta blockade ^[2]

References

^[1] Lecture slides: GC 058. High Blood Pressure.pdf ^[2] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf ^[3] Senior notes: Block A - Clinical Pharmacology of anti-HT and anti-HF medications.pdf

Hypertension — Definition, Epidemiology, Risk Factors, Anatomy & Function, Etiology, Pathophysiology, Classification, and Clinical Features

Hypertension (HTN) literally breaks down as: "hyper" = excessive, "tension" = pressure. It refers to a sustained elevation of systemic arterial blood pressure above a defined threshold associated with increased cardiovascular risk.

Key Principle — Why We Treat HTN

Hypertension itself is often asymptomatic. It is only treated because of its associated risks of target organ damage (TOD) and adverse cardiovascular events ^[1]^[2]. The entire rationale for diagnosis and management revolves around preventing end-organ injury — not treating a number.

Defining Thresholds

Different guidelines use slightly different cut-offs. For HKUMed exams, be familiar with both:

Category	ACC/AHA 2017 (mmHg)	ESC/ESH 2023 (mmHg)
Normal	< 120/80	< 120/80 (optimal)
Elevated / High-Normal	120–129/ < 80	130–139/85–89
Stage 1 HTN	130–139/80–89	140–159/90–99 (Grade 1)
Stage 2 HTN	≥ 140/90	160–179/100–109 (Grade 2)
Stage 3 / Severe	—	≥ 180/110 (Grade 3)
Isolated systolic HTN	SBP ≥ 140 and DBP < 90	Same

The GC 058 lecture slide framework aligns with ESC-style grading (Grade 1/2/3) and emphasises that the diagnosis must integrate concomitant CVS risk factors and target organ damage alongside the BP number ^[1].

Clinical Pearl

In Hong Kong clinical practice, the treatment threshold for most patients remains ≥ 140/90 mmHg (or ≥ 130/80 mmHg for high-risk groups such as diabetics, CKD, or established CVD) per the Hong Kong Reference Framework. The ACC/AHA 2017 threshold of 130/80 is referenced but not universally adopted locally.

2. Epidemiology

Affects approximately 1.28 billion adults worldwide (WHO 2023 estimate); a leading modifiable risk factor for global mortality.
Responsible for ~10.8 million deaths/year (predominantly through stroke and ischaemic heart disease).
Prevalence increases sharply with age: < 10% in the 20s → > 60% in those ≥ 60 years.

Population Survey on CVD Risk Factors 2020–22 (CHP): prevalence of hypertension in adults aged 15–84 is approximately 27–29%.
Among those with HTN, roughly half are unaware of their diagnosis ("the rule of halves": half undiagnosed, half of diagnosed untreated, half of treated uncontrolled — although control rates have improved to ~40–50% in Hong Kong).
Leading cause of CKD progression and stroke in Hong Kong.
Ethnic considerations: Chinese populations tend to have higher stroke-to-MI ratios compared to Western populations for the same degree of BP elevation, making BP control even more critical locally.

3. Risk Factors

Understanding risk factors requires separating them into non-modifiable and modifiable, because this directly informs clinical history-taking and management.

Factor	Explanation
Advanced age	Arterial stiffness increases with age (loss of elastin, ↑ collagen cross-linking, medial calcification) → isolated systolic hypertension in the elderly
Sex (Male > Female pre-menopause)	Oestrogen has vasodilatory and anti-atherogenic effects; after menopause, female risk equals or exceeds male risk
Race	Black race is a risk factor for adverse prognosis ^[1]; East Asians have high salt-sensitivity
Family history / Genetics	Polygenic; heritability ~30–50%; family history of HTN points towards essential HTN ^[2]^[3]

Factor	Mechanism
Obesity	Central adiposity → insulin resistance → sympathetic activation + Na⁺ retention + endothelial dysfunction; adipokine dysregulation
High-sodium diet	Na⁺ retention → ↑ intravascular volume → ↑ BP; particularly relevant in salt-sensitive populations (East Asian)
Physical inactivity	↓ NO bioavailability, ↑ sympathetic tone, ↑ arterial stiffness
Excessive alcohol intake	Dose-dependent ↑ BP; activates RAAS and sympathetic nervous system
Smoking	Acute ↑ BP (sympathomimetic); chronic endothelial damage accelerates atherosclerosis
Diabetes mellitus	Insulin resistance + endothelial dysfunction + accelerated arterial stiffness
Hypercholesterolaemia / Dyslipidaemia	Endothelial dysfunction; accelerated atherosclerosis
Stress / Depression	Sustained sympathetic activation
Excess caffeine / stimulant use	Acute ↑ sympathetic tone

The GC 058 slide "Risk Factors for an Adverse Prognosis in Hypertension" lists: Black race, youth (young age at diagnosis implies more severe disease), male sex, persistent DBP > 115 mmHg, smoking, diabetes mellitus, hypercholesterolaemia, obesity, excess alcohol intake, plus evidence of end-organ damage (cardiac enlargement, ECG LV strain/ischaemia, MI, CHF, retinal exudates/haemorrhages/papilloedema, impaired renal function, CVA) ^[1].

High Yield — Adverse Prognostic Factors (Harrison's per GC Slide)

Concomitant CVS risk factors + target organ damage = worse prognosis. The GC slide explicitly frames prognosis as a function of three pillars: (1) HTN grade, (2) concomitant CVS risk factors, (3) target organ damage ^[1].

4. Anatomy & Physiology of Blood Pressure Regulation

To understand hypertension from first principles, you need to understand the equation that governs blood pressure and every physiological system that feeds into it.

\text{Blood Pressure} = \text{Cardiac Output} \times \text{Total Peripheral Resistance (TPR)}

\text{CO} = \text{Heart Rate} \times \text{Stroke Volume}

BP = CO × TPR — "So basically all drugs are just manipulating this equation" ^[4]. There are 6 parameters you can modify, and also reducing body sodium and volume ^[4].

Therefore, any cause of hypertension must work through one or both of:

↑ Cardiac Output (↑ HR or ↑ SV, usually via ↑ preload/volume)
↑ Total Peripheral Resistance (arteriolar vasoconstriction, arterial stiffness, endothelial dysfunction)

4.2 Physiological Regulators of Blood Pressure

Short-term regulation (seconds to minutes).
Baroreceptors in the carotid sinus and aortic arch detect ↓ BP → ↑ sympathetic outflow from the vasomotor centre (medulla) → ↑ HR (β₁), ↑ contractility (β₁), arteriolar vasoconstriction (α₁) → ↑ BP.
In chronic HTN, the baroreceptor set-point resets upward, meaning the body "accepts" a higher BP as normal — this is why patients with longstanding HTN can be asymptomatic.

Intermediate to long-term regulation.
Juxtaglomerular (JG) cells in the afferent arteriole sense ↓ renal perfusion pressure, ↓ NaCl delivery to macula densa, or ↑ sympathetic stimulation → release renin.
Renin cleaves angiotensinogen (from liver) → angiotensin I → angiotensin-converting enzyme (ACE, mainly in pulmonary endothelium) → angiotensin II (AngII).
AngII effects:
- Vasoconstriction (↑ TPR) — directly on vascular smooth muscle
- Aldosterone secretion (zona glomerulosa of adrenal cortex) → Na⁺ and water reabsorption in the collecting duct → ↑ intravascular volume
- ADH release from posterior pituitary → water reabsorption
- Sympathetic potentiation (central and peripheral)
- Cardiac and vascular remodelling (hypertrophy, fibrosis) — this is why RAAS blockade is "cardio- and reno-protective"
- Efferent arteriolar vasoconstriction → maintains GFR when perfusion is low (important for understanding ACEI/ARB in renal artery stenosis — see below)

The dominant long-term determinant of BP.
In health, when BP rises → kidney excretes more Na⁺ and water (pressure-natriuresis) → blood volume falls → BP returns to normal.
In hypertension, this curve is shifted to the right — the kidney requires a higher perfusion pressure to excrete the same amount of Na⁺. This is why every form of sustained hypertension must involve some degree of renal dysfunction in sodium handling (Guyton's hypothesis).

Nitric oxide (NO): potent vasodilator; produced by endothelial NO synthase (eNOS). ↓ NO bioavailability (due to oxidative stress, endothelial damage) → ↑ TPR.
Endothelin-1 (ET-1): potent vasoconstrictor; ↑ in essential HTN.
Prostacyclin (PGI₂): vasodilator; counterbalances thromboxane A₂.

ANP (atrial) and BNP (ventricular): released in response to volume overload → promote natriuresis + vasodilation → counter-regulatory to RAAS.

Released from posterior pituitary in response to ↑ osmolality or ↓ blood volume → water reabsorption in collecting ducts + vasoconstriction (V1 receptors).

5. Etiology

Category	Prevalence	Key Point
Essential (Primary) HTN	~95%	No single identifiable cause; reflects a combination of genetic and environmental factors ^[2]^[3]
Secondary HTN	~5%	Important to identify because these are potentially curable/treatable and won't respond well to traditional antihypertensives ^[2]

"As a GP, 95% of the patients you see with HT will be of the essential type. Your job is to find the 'one in many', i.e. the secondary HT cases such as renal HT or endocrine HT — since these secondary HT are treatable, won't respond well to traditional antihypertensives, and are associated with more comorbidities." ^[2]

"By definition there's no underlying cause — however, can be attributed to 2 factors: Environmental (diet, obesity, sedentary life) and Genetic." ^[2]

Pathophysiology — multifactorial, involving interplay of:

Genetic susceptibility (polygenic; > 1,000 GWAS loci identified, each contributing small effect)
- Genes affecting: RAAS components, Na⁺ channels (ENaC), adrenergic receptors, endothelial function, renal Na⁺ transporters
- Heritability ~30–50%
Sympathetic overactivity
- ↑ Resting sympathetic tone (measurable by muscle sympathetic nerve activity)
- ↑ HR, ↑ CO, ↑ TPR
- Potentiated by obesity, stress, and physical inactivity
RAAS dysregulation
- Inappropriate renin secretion for the volume status
- ↑ AngII → vasoconstriction + Na⁺ retention + vascular remodelling
Impaired pressure-natriuresis
- The kidney's set point for Na⁺ excretion shifts rightward → needs higher BP to maintain Na⁺ balance
- May be due to subtle renal microvascular disease, intrarenal RAAS activation, or genetic defects in tubular Na⁺ handling
Endothelial dysfunction
- ↓ NO bioavailability, ↑ ET-1, ↑ oxidative stress
- Results in ↑ TPR and vascular stiffness
Arterial stiffness
- Age-related loss of elastin + ↑ collagen → ↑ pulse wave velocity → ↑ systolic BP, ↓ diastolic BP → isolated systolic HTN in the elderly
- Also accelerated by DM, CKD, dyslipidaemia
Insulin resistance / Metabolic syndrome
- Central obesity → ↑ FFA + adipokines → insulin resistance → ↑ sympathetic tone, ↑ renal Na⁺ reabsorption, endothelial dysfunction
- Metabolic syndrome: cluster of metabolic disorders linked by insulin resistance & associated with accelerated atherosclerosis — requires ≥ 3 of: glucose intolerance/T2DM, HTN, hypertriglyceridaemia, low HDL, central obesity ^[5]
Dietary sodium excess
- High Na⁺ intake → volume expansion → ↑ CO
- In salt-sensitive individuals, the kidney cannot adequately excrete the Na⁺ load without a higher perfusion pressure
Low potassium intake
- K⁺ promotes natriuresis and vasodilation; ↓ K⁺ → relative Na⁺ retention
Fetal programming (Barker hypothesis)
- Low birth weight → fewer nephrons → impaired pressure-natriuresis → ↑ BP in adulthood

5.3 Secondary Hypertension

When to Suspect Secondary HTN

Suspect secondary hypertension when: onset < 35 or > 55 years, resistant HTN (uncontrolled on ≥ 3 drugs including a diuretic), sudden worsening of previously controlled HTN, malignant/accelerated HTN, or specific clinical clues pointing to an underlying cause ^[1]^[2]^[3].

The GC 058 and GC 066 lecture slides emphasise a systematic approach to screening for secondary causes: renal artery stenosis (ultrasound Doppler), Conn syndrome, Cushing syndrome, phaeochromocytoma, obesity, and OSA ^[1]^[6]^[4].

5.3.1 Renal Causes (Most Common Secondary Cause)

Glomerulonephritis, chronic pyelonephritis, diabetic nephropathy, polycystic kidney disease, connective tissue disease, gouty nephritis, renal amyloidosis, radiation nephritis, TB, hypernephroma, other renal tumours, perinephritis, renal haematoma ^[2]
Mechanism: damaged nephrons → impaired Na⁺ excretion → volume expansion; intrarenal RAAS activation; ↓ renal vasodilators (PGE₂, NO)
This is the most common cause of secondary HTN

Atherosclerotic obstruction of renal artery (older patients, ♂ > ♀, diffuse atherosclerosis elsewhere), fibromuscular dysplasia (young women, beading appearance on angiography), thrombotic/embolic obstruction ^[2]
Mechanism: ↓ renal perfusion → JG cells sense ↓ pressure → ↑ renin → ↑ AngII → vasoconstriction + Na⁺ retention → HTN (this is the classic Goldblatt hypertension model)
"Not uncommon; renal artery stenosis is often found in patients with other stenosis of either the carotids or coronary arteries" ^[7]
CT renal artery can confirm presence/absence of renal artery stenosis → cause of secondary HTN ^[7]

Critical Warning — ACEI/ARB in Bilateral Renal Artery Stenosis

If bilateral renal artery stenosis, ACEI/ARB can be life-threatening ^[8]. When both kidneys are poorly perfused, GFR is maintained by AngII-mediated efferent arteriolar vasoconstriction. Blocking AngII → loss of this protective mechanism → precipitous drop in GFR → acute kidney injury. "Not an uncommon situation, so THINK before you prescribe (feel peripheral pulses, listen for bruit, echo with Doppler to visualise)" ^[8].

5.3.2 Endocrine Causes

Most common endocrine cause of secondary HTN (~5–10% of all HTN if actively screened)
Autonomous aldosterone secretion from adrenal adenoma (Conn's) or bilateral adrenal hyperplasia
Mechanism: ↑ aldosterone → ↑ ENaC-mediated Na⁺ reabsorption in collecting duct → volume expansion + K⁺ wasting + metabolic alkalosis
Clinical clue: hypokalaemia (but may be normokalaemic), resistant HTN, no specific symptoms/signs ^[3]
Screening: aldosterone-to-renin ratio (ARR) ^[1]^[6]

↑ Cortisol (exogenous steroids most common cause; endogenous: pituitary adenoma/adrenal tumour/ectopic ACTH)
Mechanism: cortisol at high concentrations overwhelms 11β-HSD2 → acts on mineralocorticoid receptors → Na⁺ retention; also ↑ angiotensinogen synthesis, ↑ vascular reactivity to catecholamines
Clinical clues: steroid use, proximal muscle weakness, moon facies, central obesity, striae, buffalo hump ^[3]
Screening: overnight dexamethasone suppression test (ONDST) ^[1]^[3]

Catecholamine-secreting tumour of chromaffin cells (adrenal medulla 90%, extra-adrenal paraganglioma 10%)
Mechanism: episodic release of adrenaline/noradrenaline → ↑ HR, ↑ contractility, ↑ TPR → paroxysmal or sustained HTN
Clinical clues: paroxysmal headache, palpitations, sweating ("the classic triad"), pallor (vasoconstriction), anxiety, weight loss ^[3]
"Phaeochromocytoma" → "phaeo" = dusky/dark (refers to chromaffin staining), "chromo" = colour, "cytoma" = cell tumour
Screening: 24-hour urine catecholamines / metanephrines, or plasma metanephrines ^[1]^[3]

Mechanism: ↑ T₃/T₄ → ↑ β₁-adrenergic receptor expression → ↑ HR, ↑ contractility → ↑ CO → predominantly systolic HTN with widened pulse pressure; also ↓ TPR (peripheral vasodilation)
Clinical clues: heat intolerance, weight loss despite good appetite, tremor, lid lag ^[3]
Screening: TFT ^[2]

↑ GH → ↑ IGF-1 → Na⁺ retention, ↑ vascular smooth muscle proliferation
Clinical clues: headache, visual field disturbance (bitemporal hemianopia from pituitary macroadenoma), ↑ glove & shoe size, coarsened facial features ^[3]
Screening: IGF-1 ^[3]

↑ PTH → hypercalcaemia → vasoconstriction + ↑ RAAS activity
Screening: serum calcium ^[2]

One of the most common and underdiagnosed causes of secondary HTN ^[1]^[6]
Mechanism: recurrent apnoeas → intermittent hypoxia → ↑ sympathetic surges → ↑ BP (particularly nocturnal/morning HTN); chronic oxidative stress + endothelial dysfunction + RAAS activation
Clinical clues: heavy snoring, morning headache, excessive daytime sleepiness (EDS), obesity ^[3]
Characteristic finding: non-dipping or reverse-dipping pattern on 24-hour ABPM

Congenital narrowing of the aorta, usually just distal to the left subclavian artery origin (juxtaductal)
Mechanism: ↑ afterload proximal to the coarctation → HTN in upper limbs; ↓ perfusion to kidneys → ↑ renin → further ↑ BP
Clinical clues: upper limb HTN with radio-femoral delay, weak/absent femoral pulses, BP differential > 20 mmHg between upper and lower limbs, rib notching on CXR (from collateral intercostal arteries)
"Coarctation" → from Latin "coarctare" = to press together / constrict

Immunosuppressants (ciclosporin, tacrolimus), sympathomimetics (nasal decongestants e.g. pseudoephedrine), corticosteroids, NSAIDs (↓ renal PG → Na⁺ retention), combined oral contraceptives (↑ angiotensinogen), erythropoietin, liquorice (inhibits 11β-HSD2), MAOIs + tyramine ^[3]

Neurogenic: brain tumour, ↑ ICP (Cushing reflex — HTN + bradycardia + irregular respirations) ^[2]
Pregnancy-related: pre-eclampsia, eclampsia (covered separately in GC 224)
Aortic stiffness (pseudohypertension in elderly)

Cause	Screening Test	Clinical Clue
Renal parenchymal disease	RFT, urinalysis, renal US	Proteinuria, haematuria, ↑ Cr
Renal artery stenosis	Renal Doppler US / CT renal angiography	Abdominal bruit, flash pulmonary oedema, ↑ Cr on ACEI
Primary hyperaldosteronism	Aldosterone-to-renin ratio (ARR)	Hypokalaemia, resistant HTN
Cushing syndrome	Overnight dexamethasone suppression test (ONDST)	Cushingoid features
Phaeochromocytoma	24h urine catecholamines/metanephrines	Paroxysmal triad
Hyperthyroidism	TFT (TSH)	Thyrotoxic symptoms
Acromegaly	IGF-1	Acral enlargement
OSA	Polysomnography (AHI)	Snoring, EDS, obesity
Coarctation of aorta	Echo, CT/MR aorta	Radio-femoral delay

GC 066 and GC 153 slides reinforce this systematic screening approach, particularly the biochemical investigation of hypertension including ARR, ONDST, 24h urine catecholamines, IGF-1, and TFT ^[6]^[9].

6. Classification

Primary (Essential) — 95%
Secondary — 5% (as detailed above)

Category	SBP (mmHg)		DBP (mmHg)
Optimal	< 120	and	< 80
Normal	120–129	and/or	80–84
High Normal	130–139	and/or	85–89
Grade 1 HTN	140–159	and/or	90–99
Grade 2 HTN	160–179	and/or	100–109
Grade 3 HTN	≥ 180	and/or	≥ 110
Isolated Systolic HTN	≥ 140	and	< 90

Office/Clinic BP: measured in clinical setting; susceptible to white-coat effect
Home BP Monitoring (HBPM): "Better since this ambulatory monitoring allows for a more continuous assessment of the genuine hypertension trends" ^[4]
Ambulatory BP Monitoring (ABPM): 24-hour recording; gold standard for diagnosing white-coat and masked HTN

Phenomenon	Office BP	Out-of-office BP	Significance
White-coat HTN	↑	Normal	Lower CV risk than sustained HTN; may not need drugs
Masked HTN	Normal	↑	Higher CV risk; often missed
Sustained HTN	↑	↑	Highest risk

The GC 058 slide emphasises correct BP measurement technique — "Correct technique to prevent over or underestimation" ^[1]^[4]. Key points: patient seated, rested ≥ 5 min, arm supported at heart level, appropriate cuff size (bladder encircling ≥ 80% of the arm), no caffeine/smoking 30 min prior, average of ≥ 2 readings.

	Hypertensive Emergency	Hypertensive Urgency
BP	> 180/120 mmHg	> 180/120 mmHg
Target Organ Damage	Present (new or worsening)	Absent
Examples	Hypertensive encephalopathy, acute MI, APO, aortic dissection, AKI, eclampsia, intracranial haemorrhage ^[3]^[10]	Severely elevated BP + headache, epistaxis, or anxiety without acute TOD ^[10]
BP Reduction Goal	Reduce by 20–25% of baseline within 1 hour, then gradually to target over 24–48h ^[10]	Reduce to target within 24–48 hours (oral agents) ^[10]

Exam Trap — Emergency vs Urgency

The distinction is NOT the BP number — it is the presence or absence of acute target organ damage. A BP of 200/120 with headache only (no papilloedema, no encephalopathy, no AKI) is urgency. The same BP with flash pulmonary oedema is an emergency ^[10].

"Need to balance between target-organ damage due to hypertension as well as risk of organ hypoperfusion due to rapid BP drop" ^[10] — autoregulation in chronic HTN is shifted rightward; too-rapid BP lowering → watershed ischaemia (stroke, MI, AKI).

7. Clinical Features

The clinical features of hypertension can be divided into:

Features of elevated BP itself (often none)
Features of target organ damage (TOD) / hypertensive end-organ damage (HMOD)
Features suggesting a secondary cause
Features of concomitant CVD risk factors

7.1 Symptoms

Most patients are asymptomatic — this is why HTN is called the "silent killer"
When symptomatic:
- Headache — classically occipital, early morning, throbbing; mechanism: ↑ intracranial pressure from ↑ cerebral perfusion pressure; or related to sleep apnoea
- Dizziness / light-headedness — altered cerebral autoregulation
- Palpitations — ↑ sympathetic drive, LVH-related arrhythmias
- Easy fatigability — ↓ cardiac reserve from chronically elevated afterload
- Epistaxis — ↑ pressure on nasal mucosal vessels; though NOT a reliable indicator
- Visual disturbance — hypertensive retinopathy (see below)
- Impotence — endothelial dysfunction, atherosclerosis of pudendal arteries; also drug side-effect

Target Organ	Symptoms	Pathophysiological Basis
Brain	Headache, confusion, seizures, focal neurological deficits (sudden hemiplegia, dysphasia)	Hypertensive encephalopathy: ↑ BP exceeds upper limit of cerebral autoregulation → forced vasodilation → cerebral oedema. Stroke: ↑ BP → accelerated atherosclerosis (ischaemic) or rupture of Charcot-Bouchard microaneurysms in perforating arteries (haemorrhagic — basal ganglia, thalamus, pons)
Heart	Exertional dyspnoea, orthopnoea, PND, chest pain (angina), palpitations	Chronically ↑ afterload → LV concentric hypertrophy (↑ wall thickness to normalise wall stress, Laplace's law: wall stress = P×r / 2h) → diastolic dysfunction → HFpEF → eventually systolic dysfunction → HFrEF. Also accelerates coronary atherosclerosis → IHD
Kidney	Nocturia, haematuria, oliguria, frothy urine	↑ BP → hypertensive nephrosclerosis (arteriolar hyalinosis → ischaemic glomerular damage) → ↓ GFR → CKD. Also ↑ intraglomerular pressure → proteinuria. "Benign" nephrosclerosis (gradual) vs "malignant" nephrosclerosis (accelerated, fibrinoid necrosis)
Eyes	Blurred vision, visual field loss, sudden visual loss	Hypertensive retinopathy — see grading below
Peripheral Vasculature	Claudication, cold extremities	Accelerated atherosclerosis → PAD
Aorta	Sudden tearing chest/back pain	Accelerated medial degeneration → ↑ risk of aortic dissection

Cause	Key Symptoms	Why
OSA	Heavy snoring, witnessed apnoeas, morning headache, EDS	Intermittent hypoxia → sympathetic surges
Renal disease	Oliguria, haematuria, frothy urine, oedema	Renal parenchymal damage / nephritic-nephrotic features
Primary hyperaldosteronism	Muscle weakness, cramps, polyuria (hypokalaemia-related)	K⁺ wasting → hypokalaemic myopathy, nephrogenic DI
Cushing syndrome	Proximal weakness, easy bruising, weight gain, mood changes, steroid use	Cortisol excess → catabolic effects
Phaeochromocytoma	Paroxysmal headache, palpitations, sweating, anxiety, pallor	Episodic catecholamine release
Hyperthyroidism	Heat intolerance, weight loss, tremor, diarrhoea	↑ metabolic rate, ↑ adrenergic sensitivity
Acromegaly	Headache, visual disturbance, ↑ glove/shoe size	GH-secreting pituitary adenoma compressing chiasm
Coarctation	Exertional leg fatigue, headache, epistaxis	↓ Lower limb perfusion, ↑ upper body pressure

7.2 Signs

Measure in BOTH upper extremities — a difference > 20 mmHg suggests aortic coarctation, subclavian stenosis, or aortic dissection ^[2]
Measure supine AND standing — orthostatic drop suggests autonomic dysfunction (common in DM, elderly, drug-induced) ^[2]
Radio-femoral delay — coarctation of aorta

GC 058 and CFB physical examination slides: "BP and pulses in the two upper extremities (supine and standing)" ^[1]^[2].

BMI and waist circumference — obesity / metabolic syndrome ^[2]
Cushingoid habitus — moon facies, central obesity, striae, buffalo hump
Acromegalic features — prognathism, frontal bossing, spade-like hands
Thyroid signs — goitre, lid lag, tremor, tachycardia

This is extremely high yield. Fundoscopy is part of the routine initial evaluation.

Modified Scheie Classification / "SAFE" mnemonic ^[3]:

Grade	Findings	Pathophysiology
Grade 1	Arteriolar narrowing (↑ arteriolar light reflex, "silver wiring" early)	Chronic ↑ BP → arteriolar vasoconstriction → wall thickening (hyaline arteriosclerosis)
Grade 2	AV nicking (arteriole compresses the venule at crossings, causing "nipping" with venule bulging on either side)	Thickened arteriolar wall compresses adjacent venule sharing a common adventitial sheath
Grade 3	Silver wiring, cotton-wool spots, hard exudates, flame haemorrhages	Silver wiring: severe arteriolar sclerosis. Cotton-wool spots: retinal nerve fibre layer infarcts (ischaemia). Hard exudates: lipid/protein leakage from damaged capillaries (chronic leakage). Flame haemorrhages: rupture of superficial retinal capillaries
Grade 4	Papilloedema (blurred disc margin)	Malignant HTN → severe ↑ in intracranial pressure OR optic nerve head ischaemia + ↑ capillary permeability → disc swelling

The GC 058 slide lists under "Evidence of end organ damage — Eyes: Retinal exudates and hemorrhages, Papilledema" ^[1].

High Yield — Keith-Wagener-Barker vs Modified Scheie

Both classification systems exist. The Keith-Wagener-Barker system was the original (Grades I–IV). The Modified Scheie classification is used in some HKU materials ^[3]. For exams, know that Grade 3 = flame haemorrhages + cotton-wool spots + hard exudates, and Grade 4 = papilloedema (implies malignant/accelerated HTN) ^[1]^[3].

Sign	Significance	Why
Loud A₂ (aortic component of S2)	↑ aortic pressure at time of valve closure	Higher back-pressure against which the aortic valve snaps shut
S4 gallop	LVH with ↓ compliance → forceful atrial contraction into stiff ventricle	Diastolic dysfunction from concentric hypertrophy
Sustained, heaving, displaced apex beat	LVH (heaving = pressure overload); displacement suggests dilatation (later)	Chronically ↑ afterload → compensatory hypertrophy
Aortic regurgitation murmur	Aortic root dilatation from chronic HTN	↑ Pressure stretches aortic root → incomplete valve coaptation
S3 gallop, bibasal crackles, elevated JVP, peripheral oedema	Heart failure (late)	Decompensated LV → ↑ LVEDP → pulmonary congestion; ± RV failure

Sign	Significance
Carotid bruits	Carotid atherosclerosis (↑ stroke risk)
Renal artery bruit	Renal artery stenosis (listen 2 cm above and lateral to umbilicus)
Absent/reduced femoral pulses	Coarctation of aorta or aortoiliac disease
Peripheral arterial disease signs	Absent pedal pulses, hair loss, trophic skin changes

Palpable kidneys bilaterally → polycystic kidney disease
Renal bruit (as above)

Focal neurological deficits → stroke
↓ Consciousness, confusion → hypertensive encephalopathy
Papilloedema on fundoscopy → ↑ ICP / malignant HTN

This is the crux of why we care about hypertension. The GC 058 lecture slide frames prognosis as: HTN + CVS Risk Factors + Target Organ Damage → Prognosis ^[1].

"Evidence of end organ damage — Cardiac: cardiac enlargement, ECG signs of ischaemia or LV strain, MI, CHF. Eyes: retinal exudates and haemorrhages, papilloedema. Renal: impaired renal function. Nervous system: cerebrovascular accident." ^[1]

Summary of HMOD with Pathophysiological Basis

Organ	Damage	Mechanism
Heart	LVH, diastolic dysfunction → HFpEF → HFrEF; coronary atherosclerosis → IHD/MI; atrial fibrillation	↑ Afterload → Laplace's law compensation (↑ wall thickness) → myocyte hypertrophy + fibrosis → stiff ventricle → diastolic dysfunction. LA pressure rises → LA dilatation → AF. Coronary demand-supply mismatch (↑ O₂ demand from hypertrophied muscle, ↓ supply from ↑ LVEDP compressing subendocardial vessels + coronary atherosclerosis)
Brain	Ischaemic stroke, haemorrhagic stroke (ICH), TIA, hypertensive encephalopathy, vascular dementia, lacunar infarcts	Atherosclerosis of large cerebral vessels → ischaemic stroke. Lipohyalinosis of small perforating arteries + Charcot-Bouchard microaneurysm formation → rupture → ICH (classically basal ganglia). Chronic small vessel disease → lacunar infarcts → vascular dementia
Kidney	Hypertensive nephrosclerosis, CKD, proteinuria, ESRD	Arteriolar hyalinosis → ischaemic nephron loss → ↓ GFR. Intraglomerular HTN → glomerulosclerosis → proteinuria. "Mild CKD and albuminuria has been shown to increase the risk of cardiovascular death" ^[7]
Eyes	Hypertensive retinopathy (Grades 1–4, as above)	As detailed in fundoscopy section
Large Arteries	Atherosclerosis, aortic aneurysm/dissection, PAD	↑ Shear stress + endothelial dysfunction → accelerated atherosclerosis; medial degeneration → aneurysm/dissection

"Markers of HMOD" — the GC 058 slide references a "traffic light table" for screening HMOD ^[1]^[4]. In practice, this means systematically checking: ECG (LVH, ischaemia), echo (LVH, LVEF), fundoscopy, RFT + urinalysis (eGFR, albuminuria), carotid US (IMT), and ABI.

9. Approach to History-Taking in Hypertension

Based on GC 058 and the senior notes, the structured approach is ^[1]^[2]^[3]:

Duration and previous BP levels
How was it measured? (office vs home vs ABPM)
Any previous treatment? Compliance?

Headache, dizziness, visual disturbance, epistaxis, palpitations

Heart: chest pain, dyspnoea, orthopnoea, PND, ankle swelling
Brain: headache, weakness, speech difficulty, visual loss
Kidney: nocturia, haematuria, frothy urine
Eyes: visual disturbance
Peripheral vasculature: claudication

OSA: heavy snoring, morning headache, EDS ^[3]
Renal: oliguria, haematuria, frothy urine ^[3]
Endocrine ^[3]:
- Primary hyperaldosteronism: no specific S/S (but ask about muscle cramps/weakness)
- Cushing syndrome: steroid use, proximal muscle weakness
- Phaeochromocytoma: paroxysmal headache, palpitation, sweating
- Acromegaly: headache, visual field disturbance, glove & shoe size
- Hyperthyroidism: heat intolerance, weight loss despite good appetite
Drug history: NSAIDs, steroids, OCP, decongestants, immunosuppressants

Smoking, DM, lipid disorders, family history of early CVD deaths ^[2]
Lifestyle: diet (salt intake), physical activity, alcohol, family status, work, educational level ^[2]

Family history of HTN → essential HTN ^[2]
Family history of premature CVD

"When asked to physically examine a patient with hypertension" ^[2]:

General appearance — body habitus, Cushingoid features, acromegalic features, thyroid signs
BP and pulses in BOTH upper extremities (supine and standing) ^[2]
Height and weight → BMI, waist circumference ^[2]
Fundoscopy ^[2] — grade retinopathy
Palpation and auscultation of ALL peripheral arteries ^[2] — carotids (bruits), radials, femorals (delay?), pedal pulses; renal bruit
CVS examination ^[2] — apex beat character, heart sounds (S4? S3? murmurs), lung bases (crackles), JVP, peripheral oedema
Abdominal examination — palpable kidneys (PKD), renal bruit, aortic pulsation (aneurysm)
Neurological examination — if any suspicion of stroke or encephalopathy

11. Investigations — Initial Evaluation

GC 058 and GC 153 slides outline the initial workup ^[1]^[2]^[9]:

Urinalysis — haematuria, proteinuria → rule out renal disease ^[2]
Spot urine albumin-to-creatinine ratio (ACR) — early nephropathy

Test	Rationale
Serum creatinine, urea	Baseline kidney function; rule out kidney failure ^[2]
Serum K⁺ and Ca²⁺	Secondary causes: ↓ K⁺ → hyperaldosteronism; ↑ Ca²⁺ → hyperparathyroidism ^[2]
Serum glucose / HbA1c	Rule out diabetes ^[2]
Total cholesterol, HDL, LDL, TG	Assess CVS risk factors ^[2]
Serum uric acid	Baseline + gout association (HTN is one of the most common comorbidities of gout) ^[2]
TSH	Rule out thyroid disorders ^[2]
FBC	Anaemia (CKD?), polycythaemia

Test	What to Look For
ECG	LVH (Sokolow-Lyon: S in V1 + R in V5/V6 ≥ 35mm; Cornell: R in aVL + S in V3 > 28mm ♂ / > 20mm ♀), MI, ischaemia, heart block, AF ^[2]
CXR	Cardiomegaly (CTR > 0.5), signs of cardiac failure (upper lobe diversion, Kerley B lines, pleural effusion) ^[2]
Echocardiography	LV wall thickness, LVEF, diastolic function, valvular disease
Renal US	Kidney size asymmetry (RAS), cysts (PKD), chronic changes (small, echogenic kidneys)

Suspected Cause	Investigation
Primary hyperaldosteronism	ARR (aldosterone-to-renin ratio)
Cushing syndrome	ONDST (overnight dexamethasone suppression test)
Phaeochromocytoma	24h urine catecholamines / metanephrines
Acromegaly	IGF-1
Hyperthyroidism	TFT
Renal artery stenosis	Doppler US / CT renal angiography / MRA
OSA	Polysomnography
Coarctation	Echocardiography, CT/MR aorta

GC 153 (Biochemical Investigation of Hypertension) details these investigations systematically ^[9].

High Yield Summary

HTN = BP ≥ 140/90 mmHg (office) in most guidelines; treatment threshold may be lower (≥ 130/80) for high-risk patients
BP = CO × TPR — all causes and treatments work through this equation
95% essential, 5% secondary — the secondary causes (renal, endocrine, OSA, CoA, drugs) are treatable/curable and must be actively sought
Secondary HTN clues: onset < 35 or > 55, resistant HTN, sudden worsening, specific symptoms (paroxysmal triad for phaeochromocytoma, snoring for OSA, Cushingoid features, radio-femoral delay for CoA)
Target organ damage determines prognosis — Heart (LVH → HF), Brain (stroke), Kidney (nephrosclerosis → CKD), Eyes (retinopathy), Arteries (atherosclerosis, dissection)
Hypertensive retinopathy grading (Scheie/KWB): Grade 1 = narrowing, Grade 2 = AV nicking, Grade 3 = haemorrhages + exudates + cotton-wool spots, Grade 4 = papilloedema
Hypertensive emergency vs urgency: NOT about the number — it's about the presence of acute target organ damage. Emergency → IV drugs, reduce BP 20–25% in 1 hour. Urgency → oral drugs, reduce over 24–48h.
ACEI/ARB contraindicated in bilateral renal artery stenosis — blocks the AngII-mediated efferent arteriolar vasoconstriction that maintains GFR
Initial workup: urinalysis, RFT, electrolytes (K⁺, Ca²⁺), glucose, lipids, uric acid, TSH, ECG, CXR, fundoscopy
Adverse prognostic factors (Harrison's per GC slide): Black race, youth, male, DBP > 115, smoking, DM, hypercholesterolaemia, obesity, excess alcohol, + evidence of TOD

Active Recall - Hypertension (Definition, Epidemiology, Etiology, Clinical Features)

^[1] Lecture slides: GC 058. High Blood Pressure.pdf (slides on CVS risk factors, target organ damage, prognosis, secondary causes, BP measurement) ^[2] Senior notes: Block A - High blood pressure_ hypertension.pdf (history, physical examination, investigations, etiology of secondary HTN, essential HTN contributors) ^[3] Senior notes: Maksim Medicine Notes.pdf (p.78 — clinical approach to hypertension, differential diagnosis, hypertensive crisis) ^[4] Senior notes: Block A - Clinical Pharmacology of anti-HT and anti-HF medications.pdf (BP = CO × TPR, home BP monitoring, HMOD markers, secondary HTN screening) ^[5] Senior notes: Block A - Polyuria and polydipsia_ glucose metabolism; diabetes mellitus; diabetic ketoacidosis.pdf (metabolic syndrome definition) ^[6] Lecture slides: GC 066. I have fluctuating BP.pdf (secondary HTN screening approach) ^[7] Senior notes: Block A - Chronic Kidney Disease and its Complications.pdf (CT renal artery, mild CKD and CV death risk) ^[8] Senior notes: Block A - Drugs and the Kidney.pdf (RAAS blockade and GFR, bilateral RAS contraindication) ^[9] Lecture slides: GC 153. Biochemical Investigation of Hypertension.pdf (biochemical workup for secondary HTN) ^[10] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.321–323 — hypertensive emergency vs urgency definitions and management principles, etiology of primary HTN)

Differential Diagnosis of Hypertension

The differential diagnosis of hypertension is not a list of conditions that mimic hypertension — hypertension itself is the finding. The real clinical question when you encounter an elevated BP is: "Why does this patient have high blood pressure?" You are differentiating between the causes of the elevated BP, ranging from the overwhelmingly common essential HTN to the uncommon-but-curable secondary causes. A second, equally important layer is distinguishing true sustained hypertension from measurement artefacts and transient elevations.

Think of the DDx in two tiers:

Before committing to a diagnosis of hypertension, you must exclude situations where the measured BP does not represent the patient's true resting arterial pressure.

Condition	Explanation	How to Identify
White-coat hypertension	BP elevated in clinical setting due to anxiety/sympathetic response, but normal on home or ambulatory monitoring. "Prevalence especially in elderly and pregnant … requires close follow-up and monitoring, as it is potentially a precursor to hypertension" ^[2]	HBPM or ABPM shows normal out-of-office readings ^[10]
Pseudohypertension	Falsely elevated cuff BP due to heavily calcified, non-compressible arteries (Mönckeberg's medial sclerosis, advanced CKD, elderly). The cuff must generate extra pressure to compress a rigid artery, over-reading the true intra-arterial pressure	Osler's manoeuvre: if the radial artery is still palpable after the cuff is inflated above systolic pressure, the artery is non-compressible → pseudohypertension likely. Gold standard: intra-arterial BP measurement
Incorrect measurement technique	Wrong cuff size (too small → over-reads), unsupported arm, patient talking, recent caffeine/smoking, no rest period	"Correct technique to prevent over or underestimation" ^[4] — repeat measurement with proper protocol
Masked hypertension	BP appears normal in clinic but is elevated on HBPM/ABPM — the opposite of white-coat HTN. Higher CV risk than white-coat HTN	ABPM/HBPM reveals elevated out-of-office readings; suspect in patients with unexplained TOD despite "normal" office BP
Transient BP elevation	Acute pain, anxiety, full bladder, acute illness, post-exercise	Repeat after addressing the precipitant; will normalise

Clinical Pearl

The GC 058 lecture and the ABCDE mnemonic both start with "A — Accuracy of diagnosis: Is it genuine HT?" ^[2]. Before launching into an expensive secondary HTN workup, always confirm the reading first. A single elevated office reading is insufficient for diagnosis — unless there is evidence of target organ damage or hypertensive crisis.

3. Tier 2 — Causes of True Sustained Hypertension

"Essential hypertension (95%)" ^[3]

No single identifiable cause; reflects a combination of genetic (family history) and environmental factors (overweight, excess salt, alcoholism, lack of exercise) ^[10]
This is a diagnosis of exclusion — you diagnose it after reasonably ruling out secondary causes
Pathophysiology reviewed in the previous section (SNS overactivity, RAAS dysregulation, impaired pressure-natriuresis, endothelial dysfunction, arterial stiffness, insulin resistance, genetic susceptibility)

When to confidently attribute HTN to essential/primary:

Age 35–55 years
Family history of HTN
Presence of metabolic syndrome features (obesity, dyslipidaemia, impaired glucose tolerance)
No red flags for secondary causes (see below)
Responds to standard antihypertensive therapy

3.2 Secondary Hypertension (~5%)

"Secondary hypertension (5%) — important!" ^[3]. The GC 058 and GC 066 lecture slides both dedicate sections to systematic screening for secondary causes ^[1]^[6].

When to Suspect Secondary HTN — Red Flags

Age of onset < 35 or > 55 years ^[2]
Resistant hypertension (uncontrolled on ≥ 3 drugs at optimal doses, including a diuretic) ^[11]
Sudden worsening of previously well-controlled HTN
Malignant / accelerated HTN (Grade 3–4 retinopathy)
Specific clinical clues pointing to a secondary cause (see below)
Hypokalaemia (spontaneous or diuretic-induced beyond expectation) ^[12]
Acute rise in creatinine on starting ACEI/ARB → renal artery stenosis ^[8]

Cause	Mechanism	Clinical Clues	Screening
Renal parenchymal disease: CKD, GN, chronic pyelonephritis, diabetic nephropathy, PCKD ^[3]^[10]	Impaired Na⁺ excretion → volume overload; intrarenal RAAS activation; ↓ renal vasodilators	Haematuria, proteinuria (frothy urine), oliguria, oedema, nocturia ^[3]; palpable kidneys (PKD); "a patient presenting with HT — good practice to get a urine dipstick" ^[13]	RFT (Cr, urea), urinalysis (dipstick for blood/protein), urine ACR, renal USS
Renovascular disease (Renal Artery Stenosis — RAS) ^[3]^[10]	"Blockage of renal artery reduces blood flow to kidneys → kidneys interpret as low BP and over-stimulate the RAAS → ↑ renin, ↑ aldosterone, ↑ plasma Na⁺" ^[10] — classic Goldblatt mechanism	Abdominal/renal bruit, flash pulmonary oedema, early onset HTN esp. in women (fibromuscular dysplasia), reduced renal function with ACEI/ARB, generalised atherosclerosis (coronary/carotid/peripheral) ^[2]^[11]	Renal duplex USG, CT renal angiography, MRA ^[4]^[11]

The senior notes list the renovascular patient demographic: "Elderly, smoking, diabetes, generalised atherosclerosis, reduced renal function with ACE-I/ARB" ^[2]. "Everything links back to generalised atherosclerosis: bilateral RAS, abdominal bruits, coronary artery disease, LVH, impaired renal function, secondary hyperaldosteronism, peripheral vascular disease" ^[2].

Two subtypes of RAS — know the difference:

Feature	Atherosclerotic RAS	Fibromuscular Dysplasia
Demographics	Elderly, male, smokers, diabetics	Young women (15–50 years)
Location	Ostial/proximal renal artery	Mid-to-distal renal artery
Angiographic appearance	Eccentric plaque	"String of beads" (alternating stenosis and microaneurysms in the media)
Associated findings	Atherosclerosis elsewhere (CAD, PAD, carotid stenosis)	May be isolated; can also affect carotid/vertebral arteries

Cause	Prevalence among HTN	Mechanism	Clinical Clues	Screening
Primary hyperaldosteronism (Conn syndrome) (8–20%) ^[11]	Most common endocrine cause	Autonomous aldosterone → ↑ ENaC Na⁺ reabsorption → volume expansion + K⁺ wasting + metabolic alkalosis	Resistant HTN, hypokalaemia, muscle cramps, LL weakness, arrhythmias (esp AF) with hypoK, adrenal incidentaloma ^[11]; "no specific S/S" ^[3]	Plasma aldosterone-to-renin ratio (ARR) → confirmatory: salt loading test ^[3]^[11]
Cushing syndrome ( < 0.1%) ^[11]	Rare but important	Cortisol overwhelms 11β-HSD2 → mineralocorticoid effect → Na⁺ retention; ↑ angiotensinogen; ↑ vascular reactivity	Steroid use (most common cause is iatrogenic!), proximal muscle weakness, moon facies, central obesity, striae, easy bruising, facial plethora, hyperglycaemia ^[3]^[10]; "rapid weight gain esp central obesity and other Cushingoid features" ^[11]	ONDST (overnight 1 mg dexamethasone suppression test) ^[3]^[11]^[14]
Phaeochromocytoma (0.1–0.6%) ^[11]	Rare	"Tumour of adrenal medulla produces large amount of adrenaline and noradrenaline → ↑ peripheral resistance by vasoconstriction, ↑ contractility, ↑ renin release" ^[10]	Classic triad: paroxysmal headache, palpitations, sweating ^[3]^[10]; pallor, anxiety, paroxysmal or sustained HTN + postural hypotension (adrenaline at lower doses causes β₂-mediated vasodilation in skeletal muscle); skin stigmata of neurofibromatosis ^[2]; "10% rule: 10% familial, 10% bilateral, 10% extra-adrenal, 10% malignant…" ^[15]	24h urine fractionated metanephrines (more sensitive: continuous release) / plasma metanephrines ^[3]^[11]^[15]
Hyperthyroidism ^[3]	Uncommon	↑ T₃/T₄ → ↑ β₁-adrenergic receptor expression → ↑ HR, ↑ CO → predominantly systolic HTN with wide pulse pressure	Heat intolerance, weight loss despite good appetite, tremor, tachycardia, lid lag, goitre ^[3]	TFT (TSH, fT4) ^[3]
Acromegaly ^[3]	Rare	↑ GH → ↑ IGF-1 → Na⁺ retention, vascular smooth muscle proliferation; also causes OSA (macroglossia)	Headache, visual field disturbance (bitemporal hemianopia), ↑ glove & shoe size, coarsened facial features, prognathism, interdental spacing ^[3]^[16]	IGF-1 ^[3]^[12]
Hyperparathyroidism ^[10]	Uncommon	↑ PTH → hypercalcaemia → vasoconstriction, ↑ RAAS	Hypercalcaemia symptoms: "bones, stones, groans, moans"	Serum Ca²⁺, PTH
Congenital adrenal hyperplasia ^[10]	Rare	11β-hydroxylase deficiency (CYP11B1) or 17α-hydroxylase (CYP17) → ↑ deoxycorticosterone (mineralocorticoid effect) ^[10]	Virilisation (11β-OH def), sexual infantilism (17α-OH def), hypokalaemia	Steroid profile, genetic testing
Apparent mineralocorticoid excess / Liquorice ingestion ^[10]	Rare	"11β-HSD2 deficiency → cortisol activates mineralocorticoid receptor (as plasma cortisol is 100× > aldosterone)" ^[10]; liquorice contains glycyrrhizinic acid which inhibits 11β-HSD2	Hypokalaemia, metabolic alkalosis; dietary history (liquorice/herbal remedies common in HK/Chinese medicine)	Low renin, low aldosterone, urine cortisol/cortisone ratio

Pathophysiology Deep-Dive — Why 11β-HSD2 Matters

The mineralocorticoid receptor in the kidney binds both aldosterone AND cortisol with equal affinity. Since plasma cortisol concentration is ~100× that of aldosterone ^[10], cortisol would overwhelm the receptor — except that the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) converts cortisol → cortisone (inactive) at the receptor site. When this enzyme is deficient (genetic = apparent mineralocorticoid excess) or inhibited (liquorice, Cushing syndrome), cortisol acts as a potent mineralocorticoid → Na⁺ retention, K⁺ wasting, HTN. This elegantly explains why Cushing syndrome causes hypertension even though cortisol is not a "mineralocorticoid."

"OSA (25–50%)" prevalence among patients with resistant HTN ^[11] — this is an enormous number and makes OSA arguably the most common treatable secondary cause in practice.

Mechanism: recurrent upper airway obstruction during sleep → intermittent hypoxia and hypercapnia → chemoreceptor-mediated sympathetic surges → ↑ HR, ↑ TPR → ↑ BP. Chronic effects: RAAS activation, endothelial dysfunction, oxidative stress, systemic inflammation → sustained daytime HTN
Clinical clues: heavy snoring, witnessed apnoeic episodes, daytime somnolence, morning headache, fatigue, obesity ^[3]^[10]^[11]
Characteristic ABPM pattern: non-dipping or reverse-dipping (BP does not fall the expected 10–20% during sleep; may even rise)
Screening: clinical evaluation (Epworth Sleepiness Scale, STOP-BANG questionnaire) → polysomnography ^[12]

"Obesity → most common [cause of secondary HTN]. OSA → daytime sleepiness, occupation" ^[12]. The overlap between obesity and OSA is extensive — central obesity → fatty infiltration of pharyngeal tissues → ↑ collapsibility → OSA.

"CoA (0.1%)" ^[11]

Mechanism: congenital narrowing of the aorta (usually juxtaductal, distal to left subclavian artery) → ↑ afterload to proximal aorta → upper limb HTN; ↓ renal perfusion → RAAS activation → further ↑ BP
Clinical clues: young hypertension < 30 years, upper limb > lower limb BP, radio-femoral delay, continuous murmur at back/chest/abdominal ^[11]; "diminished and delayed femoral pulses and reduced femoral BP" ^[2]
CXR: rib notching (from dilated intercostal collateral arteries), "3 sign" or "reverse E sign" of the aortic knuckle
Screening: echocardiogram, CTA/MRA thorax ^[11]

"Drug-induced: immunosuppressant, sympathomimetic (nasal decongestant), steroid" ^[3]

Drug Class	Mechanism	Examples
NSAIDs	Inhibit COX → ↓ renal PGE₂/PGI₂ → Na⁺ retention + ↓ renal blood flow	Ibuprofen, naproxen, diclofenac
Glucocorticoids / steroids	Mineralocorticoid effect (overwhelm 11β-HSD2) + ↑ angiotensinogen + ↑ vascular reactivity	Prednisolone, dexamethasone
Sympathomimetics	Direct α₁-agonist → vasoconstriction; or ↑ catecholamine release	Nasal decongestants (pseudoephedrine), amphetamines
Combined OCP	↑ Hepatic angiotensinogen synthesis → ↑ AngII	Ethinylestradiol-containing pills
Immunosuppressants	Calcineurin inhibitors → renal vasoconstriction, Na⁺ retention, ↓ NO	Ciclosporin, tacrolimus
Erythropoiesis-stimulating agents (ESA)	↑ RBC mass → ↑ viscosity; direct vasoconstriction (↑ ET-1)	Epoetin alfa
Cocaine	Blocks catecholamine reuptake → intense sympathetic stimulation	—
Liquorice / Chinese herbal medicines	Glycyrrhizinic acid inhibits 11β-HSD2 → pseudo-hyperaldosteronism	—
MAOIs + tyramine	↓ Monoamine oxidase → inability to degrade dietary tyramine → massive catecholamine release ("cheese reaction")	Phenelzine + aged cheese/wine

Always take a thorough drug history — "Important to exclude for any patient who presents with hypertension → many drugs can cause hypertension as a side effect" ^[2].

Cause	Mechanism	Notes
Neurogenic: brain tumour, ↑ ICP ^[2]	Cushing reflex: ↑ ICP → brainstem compression → sympathetic surge → HTN + reflex bradycardia + irregular respirations	Rare; acute presentation
Pregnancy-related: pre-eclampsia, eclampsia	Placental ischaemia → anti-angiogenic factors (sFlt-1) → endothelial dysfunction → HTN + proteinuria	Covered in GC 224
Renal vein thrombosis ^[3]	↓ Renal venous drainage → renal congestion → ↑ renin	Nephrotic syndrome, hypercoagulable states
Aortic stiffness (isolated systolic HTN in elderly)	Loss of elastin, ↑ collagen cross-linking → ↑ pulse wave velocity → ↑ SBP, ↓ DBP	Very common; technically not "secondary" but age-related

This mnemonic is from the GC lecture and senior notes — "keep in your mind during history, physical, as well as investigations" ^[2]:

Letter	Differential
A	Accuracy of diagnosis (is it genuine HT?) + Apnoea (OSA)
B	Bruit (renal artery stenosis) + Bad kidney (renal failure, polycystic kidney)
C	Catecholamine (phaeochromocytoma) + Cushing's + Coarctation of aorta
D	Drug-induced + Diet (salt, liquorice, alcohol)
E	Endocrine (primary hyperaldosteronism, thyroid disease, acromegaly, hyperparathyroidism) + Erythropoietin

High Yield Mnemonic — ABCDE for Secondary HTN

ABCDE: Accuracy/Apnoea, Bruit/Bad kidney, Catecholamine/Cushing's/Coarctation, Drug-induced/Diet, Endocrine/Erythropoietin ^[2]. This is an HKU in-house teaching mnemonic — very likely to appear in SAQs.

The table below summarises the key distinguishing clinical features and screening tests for the major secondary causes, consolidating the GC slide content with the Ryan Ho Cardiology secondary HTN table ^[11]:

Cause	Prevalence	Key Clinical Clue	When to Screen	Screening Test
Primary hyperaldosteronism	8–20% of HTN	Resistant HTN, hypokalaemia, muscle weakness	Resistant HTN, unexplained hypoK, adrenal incidentaloma, FHx early-onset HTN/stroke < 40y	Plasma ARR → salt loading test
Renal artery stenosis	5–34% of resistant HTN	Abrupt onset/worsening, flash APO, renal bruit, ↑ Cr on ACEI/ARB	When clinically indicated	Renal duplex USG → MRA/CTA
Renal parenchymal disease	1–2%	Haematuria, proteinuria, recurrent UTI, FHx PKD	When clinically indicated	Renal USG, urinalysis → renal biopsy
OSA	25–50% of resistant HTN	Snoring, restless sleep, daytime sleepiness, obesity	When clinically indicated	Clinical evaluation → polysomnography
Coarctation	0.1%	Young HTN < 30y, UL > LL BP, radio-femoral delay	When clinically indicated	Echo → CTA/MRA thorax
Phaeochromocytoma	0.1–0.6%	Paroxysmal HTN, headache/sweating/palpitations triad, adrenal incidentaloma, NF1 stigmata	When clinically indicated	24h urine fractionated metanephrines / plasma metanephrines
Cushing syndrome	< 0.1%	Cushingoid features, proximal myopathy, hyperglycaemia	When clinically indicated	Overnight 1 mg DST

Diabetes → most common cause of CKD in HK (51%) → CKD is a major cause of secondary HTN ^[13]. Always check renal function and urine in any hypertensive patient.
Chinese herbal medicine use is common and may contain liquorice (甘草, gān cǎo) or aristolochic acid (causing Chinese herb nephropathy → CKD → HTN). Ask about TCM use.
High dietary sodium intake in the local diet (preserved foods, soy sauce, congee with salted egg) contributes to both essential HTN and salt-sensitive HTN.
OSA is under-diagnosed in Hong Kong — high prevalence of obesity-related and craniofacial-predisposed OSA in the Chinese population.
NPC (nasopharyngeal carcinoma) — common in southern Chinese; post-radiotherapy hypopituitarism can paradoxically cause secondary HTN if there is isolated GH deficiency leading to metabolic syndrome, though more commonly causes hypotension. However, radiotherapy for NPC is classically associated with iatrogenic hypopituitarism ^[17].

High Yield Summary — Differential Diagnosis of Hypertension

Always confirm genuine HTN first — exclude white-coat HTN (HBPM/ABPM), pseudohypertension (Osler's manoeuvre), measurement error, and transient causes.
Essential HTN accounts for ~95% — a diagnosis of exclusion; polygenic + environmental.
Secondary HTN (~5%) is critical to identify because it is potentially curable — the ABCDE mnemonic (Accuracy/Apnoea, Bruit/Bad kidney, Catecholamine/Cushing's/Coarctation, Drug-induced/Diet, Endocrine/Erythropoietin) covers the key causes.
Most common secondary causes: renal parenchymal disease (overall), primary hyperaldosteronism (endocrine), OSA (in resistant HTN).
Red flags: onset < 35 or > 55, resistant HTN, sudden worsening, malignant HTN, hypoK, ↑ Cr on ACEI/ARB, specific clinical clues.
Know the mechanism for each secondary cause — they all work through ↑ CO, ↑ TPR, or both (volume expansion via Na⁺ retention, RAAS activation, sympathetic overactivity, or vasoconstriction).
Drug-induced HTN is common and under-recognised — NSAIDs, steroids, OCP, sympathomimetics, immunosuppressants, liquorice, cocaine.

Active Recall - Differential Diagnosis of Hypertension

References

^[1] Lecture slides: GC 058. High Blood Pressure.pdf (CVS risk factors, target organ damage, secondary causes) ^[2] Senior notes: Block A - High blood pressure_ hypertension.pdf (ABCDE mnemonic, history/PE, secondary HTN etiologies, white-coat HTN, renovascular HTN features, screening tests, medications and HTN) ^[3] Senior notes: Maksim Medicine Notes.pdf (p.78 — DDx of HTN, SAQ format, secondary causes, investigations) ^[4] Senior notes: Block A - Clinical Pharmacology of anti-HT and anti-HF medications.pdf (BP measurement technique, home BP monitoring, HMOD markers, secondary HTN screening) ^[6] Lecture slides: GC 066. I have fluctuating BP.pdf (secondary HTN screening approach) ^[8] Senior notes: Block A - Drugs and the Kidney.pdf (RAAS blockade in RAS, ACEI/ARB contraindication) ^[10] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.320–324 — HTN classification, white-coat HTN, malignant HTN, secondary HTN table, drug-induced HTN, 11-beta-HSD2 mechanism) ^[11] Senior notes: Ryan Ho Cardiology.pdf (p.178 — secondary HTN table with prevalence, clinical features, screening) ^[12] Senior notes: Block A - Endocrine Data Interpretation.pdf (youth HTN approach, investigations for secondary causes) ^[13] Senior notes: Block A - Chronic Kidney Disease and its Complications.pdf (diabetes as #1 cause of CKD in HK, CKD clinical features including HTN) ^[14] Senior notes: Ryan Ho Chemical Path.pdf (p.29 — diagnosis of Cushing syndrome, DST) ^[15] Senior notes: Maksim Surgery Notes.pdf (p.205 — phaeochromocytoma, 10% rule, investigations) ^[16] Senior notes: Block A - Introduction to Endocrine investigations.pdf (acromegaly facial features, OSA from macroglossia) ^[17] Senior notes: Block A - I keep on bumping into people on my side_ pituitary tumours; hypopituitarism.pdf (radiotherapy for NPC causing hypopituitarism)

Diagnostic Criteria, Diagnostic Algorithm, and Investigation Modalities for Hypertension

1. Diagnostic Criteria — What Counts as "Hypertension"?

Hypertension is defined by blood pressure thresholds, but the actual diagnostic process involves confirming reproducibility, ruling out measurement artefacts, and placing the BP in context with cardiovascular risk and target organ damage. There is no single blood test or biopsy — the "gold standard" is repeated, properly performed BP measurement.

WHO / ESC-ESH definition: repeated resting levels of systolic > 140 mmHg OR diastolic > 90 mmHg ^[10].

2017 ACC/AHA Guidelines ^[10]:

Category	Systolic (mmHg)		Diastolic (mmHg)
Normal	< 120	AND	< 80
Elevated	120–129	AND	< 80
Stage 1 HTN	130–139	OR	80–89
Stage 2 HTN	≥ 140	OR	≥ 90
Hypertensive crisis	≥ 180	OR	≥ 120

"In case of disparity in category between systolic and diastolic pressure then the higher value determines the severity of hypertension" ^[10].

Exam Note — Which Guideline to Use?

For HKUMed in-house exams, the ESC/ESH framework (HTN defined at ≥ 140/90) is most commonly used for treatment thresholds, while the ACC/AHA 2017 table is frequently shown for classification. The key GC 058 slide uses a Grade 1/2/3 system consistent with ESC/ESH ^[1]. Know both, but default to ≥ 140/90 as the threshold for diagnosing HTN unless the question specifies ACC/AHA.

Why do we need these? Because office BP can be falsely elevated (white-coat effect) or falsely normal (masked HTN). Out-of-office measurements provide a more representative picture of the patient's true haemodynamic burden.

Ambulatory (ABPM) and Home (HBPM) BP diagnostic thresholds ^[10]:

Setting	Systolic (mmHg)	Diastolic (mmHg)
24-hour ABPM average	≥ 130	≥ 80
Daytime (awake) ABPM average	≥ 135	≥ 85
Night-time (asleep) ABPM average	≥ 120	≥ 70
HBPM average	≥ 135	≥ 85

Notice how out-of-office thresholds are lower than office thresholds by roughly 5–10 mmHg. Why? Because the alerting response of being in a clinic inherently raises BP; out-of-office readings strip away this artefact, so a lower number carries the same risk.

	Office BP ↑	Office BP Normal
Out-of-office BP ↑	Sustained HTN (highest CV risk)	Masked HTN (often missed; significant CV risk)
Out-of-office BP Normal	White-coat HTN (lower CV risk; monitor) ^[2]^[10]	Normotension

"White-coat hypertension: defined as blood pressure that is consistently elevated by office reading but does not meet diagnostic criteria for hypertension based upon out-of-office readings. Common in elderly and pregnant woman. Diagnosis is usually made by HBPM or ABPM." ^[10]

The Ryan Ho Cardiology notes synthesise the diagnostic rules neatly ^[11]:

Diagnosis is made when:

Hypertensive crisis, i.e. > 180/120 (immediate diagnosis, no need for repeat) OR

Evidence of target organ damage + elevated BP ≥ 160/100 (immediate diagnosis) OR

Otherwise, high office BP ≥ 130/80 should be confirmed by HBPM/ABPM ^[11]

The logic: if the BP is dangerously high or there's already evidence of damage, you don't waste time confirming — you diagnose and act. For moderate elevations, you confirm to avoid labelling someone who just has white-coat effect.

High Yield Diagnostic Rule

Three pathways to diagnosis ^[11]:

Crisis (> 180/120) → diagnose immediately
TOD + BP ≥ 160/100 → diagnose immediately
Office BP ≥ 130/80 without crisis or overt TOD → confirm with HBPM or ABPM

This is the foundation of everything. A badly measured BP leads to misdiagnosis and inappropriate treatment.

"Blood pressure measurement — correct technique to prevent over or underestimation" ^[4]^[1].

Standard Protocol (ESC/ESH 2023):

Step	Detail	Why
Patient preparation	Seated, back supported, legs uncrossed, feet flat on floor	Crossed legs ↑ SBP by ~2–8 mmHg (squeezes venous return → ↑ CO)
Rest period	≥ 5 minutes quiet rest before measurement	Allows sympathetic tone to settle
Avoid stimulants	No caffeine, smoking, exercise for 30 min prior	All acutely ↑ sympathetic tone
Empty bladder	Full bladder ↑ SBP by ~10–15 mmHg	Sympathetic reflex from bladder distension
Arm position	Supported at heart level (mid-sternum)	Arm below heart → overestimates; above heart → underestimates (hydrostatic effect)
Cuff size	Bladder encircling ≥ 80% of arm circumference	Too small → overestimates ("cuff hypertension"); too large → underestimates
Number of readings	≥ 2 readings, 1–2 min apart; average the last 2	Reduces variability
Both arms	Measure in both arms at first visit	Difference > 15–20 mmHg → aortic coarctation, subclavian stenosis, aortic dissection
Supine AND standing	Measure standing after 1 and 3 min	Detect orthostatic hypotension (especially elderly, diabetic, on antihypertensives)

"BP and pulses in the two upper extremities (supine and standing)" ^[2].

The following algorithm integrates the initial encounter through to confirmation, initial workup, and decision on secondary HTN investigation. This is the clinical pathway you should have in your head on ward rounds.

4. Investigation Modalities — Detailed Interpretation

The investigations for hypertension serve three purposes, and you should mentally categorise every test you order into one of these buckets:

"Aims: (1) Screen for CVD risk factors, (2) Rule out secondary hypertension, (3) Evaluate target organ damage" ^[11].

4.1 Baseline / Routine Investigations (All Hypertensive Patients)

Test	What to Look For	Interpretation
Urine dipstick	Protein, blood	Proteinuria → renal parenchymal disease (GN, diabetic nephropathy); haematuria → GN, stones, malignancy ^[2]. "Finish off with urine dipstick" ^[12] — always do this as part of the hypertension workup
Urine albumin-to-creatinine ratio (ACR)	Microalbuminuria (3–30 mg/mmol) or macroalbuminuria ( > 30 mg/mmol)	Early marker of hypertensive nephropathy or diabetic nephropathy; also an independent marker of CV risk. "UACR — especially for diabetic patients or CKD patients" ^[18]. Done on first morning void for best accuracy
Urine protein-to-creatinine ratio (uPCR)	uPCR > 15 mg/mmol = abnormal; > 300 mg/mmol ≈ nephrotic range	Alternative to 24h urine collection. "In QMH use uPCR instead of UACR" ^[18]
Urine microscopy	Red cell casts → glomerulonephritis; WBCs → infection or tubulointerstitial nephritis	Casts confirm glomerular origin of haematuria (dysmorphic RBCs/RBC casts) vs lower tract bleeding

"Urine examination — to rule out renal disease" ^[2]. This seemingly simple test is one of the highest-yield investigations in hypertension. A positive dipstick for protein and blood in a young hypertensive patient completely changes the management trajectory.

Test	Rationale	Key Findings & Interpretation
Serum creatinine, urea	"Baseline kidney function; to rule out kidney failure" ^[2]	↑ Cr → CKD (if chronic) or AKI. Used to calculate eGFR (CKD-EPI formula most accurate ^[13]). eGFR < 60 mL/min/1.73m² on 2 readings ≥ 3 months apart = CKD
Serum K⁺	"Secondary causes of hypertension — hyperaldosteronism" ^[2]	↓ K⁺ → suspect primary hyperaldosteronism (especially if spontaneous, i.e. not on diuretics). Also drug effect: ACEI/ARB → ↑ K⁺; thiazides → ↓ K⁺
Serum Ca²⁺	"Secondary causes — hyperparathyroidism" ^[2]	↑ Ca²⁺ → primary hyperparathyroidism → HTN via vasoconstriction + RAAS activation
Serum glucose / HbA1c	"To rule out diabetes" ^[2]	DM is both a cause of secondary HTN (via nephropathy, metabolic syndrome) and a major CV risk factor. Fasting glucose ≥ 7.0 mmol/L or HbA1c ≥ 48 mmol/mol (6.5%) = DM
Fasting lipid profile (TC, HDL, LDL, TG)	"Look for associated CVS risk factors" ^[2]	↑ LDL, ↑ TG, ↓ HDL → dyslipidaemia → ↑ CV risk. Guides need for statin therapy and overall risk stratification
Serum uric acid	"Baseline + any gout (hypertension is one of the most common comorbidities of gout)" ^[2]	↑ Uric acid associated with ↑ CV risk; also baseline before starting thiazides (which ↑ uric acid)
TSH	"To rule out thyroid disorders" ^[2]	↓ TSH → hyperthyroidism (↑ CO → systolic HTN); ↑ TSH → hypothyroidism (↑ TPR → diastolic HTN)
FBC	Baseline; detect anaemia or polycythaemia	Normochromic normocytic anaemia → CKD (↓ EPO). Polycythaemia → ↑ viscosity → ↑ BP

Maksim Medicine Notes summarise the investigation approach: "CV risk: fasting glucose/HbA1c, lipids. Underlying cause: ARR, ONDST, 24h urine catecholamines, IGF-1, TFT" ^[3]. This neatly divides investigations into CV risk assessment vs secondary cause workup.

"ECG — LVH, MI, cardiac failure, heart block" ^[2]

Finding	Criteria / Description	What It Tells You
LVH voltage criteria	Sokolow-Lyon: S in V1 + R in V5 or V6 ≥ 35 mm. Cornell: R in aVL + S in V3 > 28 mm (♂) or > 20 mm (♀)	Chronic pressure overload → concentric hypertrophy. Most important ECG finding in HTN workup — indicates established HMOD
LV strain pattern	ST depression + T-wave inversion in lateral leads (I, aVL, V5–V6) with asymmetric T-wave morphology	Suggests significant LVH with subendocardial ischaemia — adverse prognostic marker
Left atrial enlargement	P mitrale (bifid P wave in lead II, > 120 ms)	↑ LA pressure from diastolic dysfunction
Ischaemic changes	ST depression, T-wave inversion, pathological Q waves	Concurrent IHD; previous MI
Atrial fibrillation	Irregularly irregular rhythm, absence of P waves, fibrillatory baseline	LA dilatation from chronic HTN → AF. AF itself then ↑ stroke risk
Heart block	Prolonged PR, dropped beats	Drug effect (beta-blockers, non-DHP CCB) or conduction disease

"CXR — cardiomegaly, cardiac failure" ^[2]

Finding	Interpretation
Cardiomegaly (cardiothoracic ratio > 0.5 on PA film)	LV dilatation from decompensated HTN; but does not specify which chamber ^[19] — need echo for that
Upper lobe venous diversion	↑ LVEDP → pulmonary venous congestion → blood redistribution to upper lobes ^[19]
Kerley B lines	Interstitial pulmonary oedema — fluid in interlobular septa
Pleural effusions	Transudative effusion from heart failure
Rib notching	Coarctation of aorta — dilated intercostal collateral arteries erode inferior rib margins
"3 sign" / "reverse E sign"	Aortic knuckle deformity in coarctation
Widened mediastinum	Aortic dissection or aortic aneurysm

Already covered in the clinical features section but is formally an investigation — performed at the initial evaluation.

"Fundoscopy for HT retinopathy: modified Scheie classification / SAFE" ^[3]:

Grade 1: arteriolar narrowing

Grade 2: AV nicking

Grade 3: silver wiring, cotton-wool spots, hard exudates, flame haemorrhages

Grade 4: papilloedema (blurred disc margin) ^[3]

Beyond the baseline tests above, further investigations may be ordered to quantify HMOD more precisely:

Organ	Investigation	Key Findings
Heart	Echocardiography	LV wall thickness (interventricular septum, posterior wall > 11 mm = LVH), LV mass index, LVEF (systolic function), E/A ratio and E/e' (diastolic function), LA size, valvular disease. More sensitive and specific for LVH than ECG
Kidney	eGFR + urine ACR (already in baseline)	eGFR < 60 or ACR > 3 mg/mmol = renal HMOD
Brain	CT brain (if neurological symptoms)	Lacunar infarcts, white matter disease, haemorrhagic stroke
Large arteries	Carotid intima-media thickness (CIMT) / carotid plaque by USS	CIMT > 0.9 mm or presence of plaque = subclinical atherosclerosis
Large arteries	Pulse wave velocity (PWV)	Carotid-femoral PWV > 10 m/s = arterial stiffness (independent CV risk factor)
Large arteries	Ankle-brachial index (ABI)	ABI < 0.9 = peripheral arterial disease
Eyes	Fundoscopy (as above)	Grades 1–4 retinopathy

The GC 058 slide emphasises that prognosis is determined by: HTN grade + concomitant CVS risk factors + target organ damage ^[1]. The investigation panel above is designed to capture all three dimensions.

4.3 Secondary Hypertension Workup

"Endocrine is unique in that you need biochemistry before imaging — resolution is too high with our imaging nowadays — so we might find benign lesions which are not related to the condition" ^[20]. This is the principle of biochemistry first, imaging second in endocrine workup.

The sequence is: "(1) History and PE → (2) Baseline bloods → (3) Screening biochemistry → (4) Confirmatory tests (sometimes dynamic suppression/stimulation) → (5) Imaging with MRI/CT → (6) Invasive tests (venous sampling)" ^[20].

Step	Test	Interpretation
Screening	Plasma aldosterone-to-renin ratio (ARR)	Primary hyperaldosteronism: ↓ basal PRA ( < 1), ↑ basal aldosterone (≥ 10 ng/dL), ARR > 30 (90% sensitivity, 90% specificity) ^[21]. Compare: secondary hyperaldosteronism → ↑ PRA, ↑ Ald, ARR < 10
Pre-test preparation	Stop interfering drugs ≥ 2 weeks before (MRA ≥ 6 weeks)	"Stop diuretics, β-blockers, and ACEI for at least 2 weeks before dynamic biochemical tests → since these drugs will mess up potassium metabolism" ^[22]. Diuretics ↑ renin; BB/clonidine/methyldopa ↓ renin; ACEI ↓ Ald; MRA ↓ Ald action → ↑ renin ^[21]
Confirmatory	Salt-loading test / saline infusion test	IV NS over 4h → measure Ald post-loading. Normal: suppression of aldosterone. Primary hyperAld: failure to suppress (Ald still > 10) ^[21]. Exception: spontaneous hypoK with Ald ≥ 20 → practically diagnostic ^[21]
Subtype differentiation	Postural (balance) test	Adenoma (ACTH-dependent) → Ald ↓ from morning to noon. Hyperplasia (RAAS-dependent) → Ald ↑ from morning to noon ^[21]
Imaging	CT adrenals (with contrast + washout)	Unilateral adenoma vs bilateral enlargement. But CT can miss small adenomas and find non-functioning incidentalomas, hence biochemistry must come first
Gold standard localisation	Adrenal venous sampling (AVS)	If postural test + CT cannot confirm lateralisation → AVS measures aldosterone gradient to confirm unilateral source (adenoma) vs bilateral (hyperplasia) ^[21]^[22]

Exam Pearl — ARR Interpretation

An ARR > 30 with suppressed PRA and elevated aldosterone is the screening cut-off. But remember: many antihypertensives interfere with the ARR. The only drug that does NOT significantly affect ARR is α-blockers (e.g. doxazosin) and verapamil (slow-release) — these can be used to control BP while other drugs are washed out ^[21].

Step	Test	Interpretation
First: exclude iatrogenic	Drug history	"Iatrogenic Cushing's syndrome due to excessive exogenous glucocorticoid exposure must be ruled out first" ^[14] — this is by far the most common cause
Screening	Overnight 1 mg dexamethasone suppression test (ONDST)	Give 1 mg dex at 11 pm → measure 9 am cortisol. Normal: cortisol suppressed to < 50 nmol/L. Cushing: failure to suppress ^[14]. Alternative screens: 24h urinary free cortisol (UFC) ×2, late-night salivary cortisol ×2 ^[14]
Confirmatory	Low-dose dexamethasone suppression test (LDDST)	0.5 mg dex q6h × 48h → measure cortisol. Confirms autonomous cortisol production
Localisation	ACTH level	ACTH-dependent (high ACTH): pituitary adenoma (Cushing disease) or ectopic ACTH (SCLC, carcinoid). ACTH-independent (low/suppressed ACTH): adrenal adenoma or carcinoma ^[22]
Further localisation	High-dose DST, CRH stimulation, MRI pituitary, CT adrenals	Pituitary Cushing disease → partial suppression with high-dose dex; ectopic → no suppression
Invasive	Inferior petrosal sinus sampling (IPSS)	Gold standard to differentiate pituitary vs ectopic ACTH

"9 am morning cortisol → followed up by suppression tests" ^[12].

Step	Test	Interpretation
Screening	24h urine fractionated metanephrines (most commonly used) or plasma free metanephrines (most sensitive)	Metanephrines are continuously produced from catecholamines by COMT, making them more sensitive than catecholamines themselves (which are episodically released) ^[3]^[11]. Elevated metanephrines > 2× upper limit of normal is highly diagnostic
Why metanephrines > catecholamines?	—	Catecholamines have a very short half-life and are released in bursts → a spot sample may miss the peak. Metanephrines are produced continuously from catecholamine metabolism within the tumour cells, so their levels are more consistently elevated
Localisation	CT or MRI abdomen/pelvis (adrenals first)	90% adrenal; 10% extra-adrenal (paraganglioma). MRI preferred if radiation concern or paraganglioma suspected
Functional imaging	MIBG scan (¹²³I-metaiodobenzylguanidine) or ⁶⁸Ga-DOTATATE PET	For extra-adrenal localisation or metastatic disease
Genetic testing	RET, VHL, SDHB/C/D, NF1	"10% familial" ^[15] — MEN2, VHL, NF1, SDH mutations

Critical Rule

"Biopsy is NOT required: high risk of hypertensive crisis and haematoma" ^[15]. Never biopsy a suspected phaeochromocytoma — catecholamine release during needle manipulation can trigger a lethal hypertensive crisis.

Step	Test	Interpretation
Screening	Renal duplex ultrasonography (Doppler)	Measures renal artery peak systolic velocity and resistive index. PSV > 200 cm/s or renal-to-aortic ratio > 3.5 suggests > 60% stenosis ^[4]^[11]. Non-invasive, no contrast, no radiation — first-line
Confirmatory	CT renal angiography (CTA)	"CT of renal arteries can help you confirm the presence or absence of any renal artery stenosis" ^[13]. Excellent anatomical detail; shows atherosclerotic plaque, fibromuscular dysplasia ("string of beads"), and kidney size asymmetry
Alternative	MR angiography (MRA)	Avoids radiation and iodinated contrast (useful if CKD); but may overestimate stenosis degree
Gold standard	Conventional catheter angiography	Most accurate but invasive; reserved for when intervention (angioplasty ± stenting) is planned
Clue on routine labs	↑ Creatinine after starting ACEI/ARB	"Reduced renal function with ACE-I/ARB" ^[2] — a > 30% rise in Cr after starting ACEI/ARB strongly suggests bilateral RAS or RAS in a solitary kidney

Step	Test	Interpretation
Clinical screening	STOP-BANG questionnaire, Epworth Sleepiness Scale	STOP-BANG ≥ 5 = high risk for moderate-to-severe OSA
Diagnostic	Polysomnography (PSG)	Gold standard. Measures AHI (apnoea-hypopnoea index). Normal < 5; Mild OSA = 5–15; Moderate = 15–30; Severe > 30
Home sleep apnoea testing	Portable sleep study	Acceptable alternative for uncomplicated patients; may underestimate AHI

"OSA → polysomnography" ^[12].

Step	Test	Interpretation
Clinical	BP in all 4 limbs, radio-femoral delay	Upper limb BP > lower limb BP by > 20 mmHg; delayed/weak femoral pulses
Imaging	Echocardiography (transthoracic)	May visualise the coarctation segment and associated bicuspid aortic valve (present in ~50% of CoA); Doppler shows diastolic "tail" flow pattern across the narrowing
Definitive	CTA or MRA thorax	Precise anatomy for surgical/interventional planning
CXR	Rib notching, "3 sign"	Classic but late findings

Cause	Screening	Confirmatory
Hyperthyroidism	TSH (suppressed), fT4 (elevated)	TRAb (Graves'), thyroid scan (uptake pattern)
Hypothyroidism	TSH (elevated), fT4 (low)	—
Acromegaly	IGF-1 (elevated) ^[3]	Oral glucose tolerance test (OGTT) — failure to suppress GH to < 1 μg/L after 75g glucose load. MRI pituitary for adenoma

Once HTN is confirmed, formal CV risk assessment guides treatment intensity:

Tool	Population	Variables
Framingham Risk Score	Western populations	Age, sex, TC, HDL, SBP, smoking, DM
ACC/AHA ASCVD Risk Calculator	General	Age, sex, race, TC, HDL, SBP, BP Rx, DM, smoking
SCORE2 / SCORE2-OP (ESC 2021)	European	Age, sex, SBP, TC, HDL, smoking
Chinese Multiprovincial Cohort Study (CMCS)	Chinese	Age, sex, SBP, TC, smoking, DM

"Formal assessment if ≥ 40y + ≥ 1 ASCVD risk factor (HK consensus 2016)" ^[23]. Not needed if patient already has overt ASCVD, DM, or severe HTN → automatically meets threshold for treatment.

Purpose	Investigation	Key Findings
Confirm diagnosis	Office BP (×2–3 visits), HBPM, ABPM	Sustained ↑ BP
CV risk factors	Glucose/HbA1c, lipids, uric acid, BMI	Metabolic syndrome components
TOD — Heart	ECG, Echo	LVH, diastolic dysfunction, LVEF
TOD — Kidney	RFT, eGFR, urine ACR/uPCR	↑ Cr, ↓ GFR, albuminuria
TOD — Eyes	Fundoscopy	Retinopathy grading
TOD — Vessels	ABI, carotid USS, PWV	PAD, carotid plaque, arterial stiffness
TOD — Brain	CT brain (if symptomatic)	Lacunar infarcts, haemorrhage
2° HTN — Renal	RFT, urinalysis, renal USS, Doppler/CTA	Parenchymal disease, RAS
2° HTN — Aldo	K⁺, ARR, salt loading, CT adrenals, AVS	↓ K⁺, ↑ ARR, non-suppressible Ald
2° HTN — Cushing	ONDST, 24h UFC, ACTH, MRI pit/CT adrenals	Non-suppressible cortisol
2° HTN — Phaeo	24h urine metanephrines / plasma metanephrines, CT/MRI	↑ Metanephrines
2° HTN — Thyroid	TSH, fT4	↓ TSH (hyper), ↑ TSH (hypo)
2° HTN — Acromegaly	IGF-1, OGTT for GH, MRI pituitary	↑ IGF-1, non-suppressible GH
2° HTN — OSA	Polysomnography	AHI ≥ 5
2° HTN — CoA	4-limb BP, Echo, CTA/MRA	Upper > lower limb BP, narrowing
2° HTN — Drugs	Drug history	Offending agent identified

High Yield Summary — Diagnosis of Hypertension

HTN diagnosis requires repeated elevated BP readings — office BP ≥ 140/90 (ESC) or ≥ 130/80 (ACC/AHA); confirm with HBPM/ABPM unless crisis or overt TOD
Out-of-office thresholds are lower (ABPM 24h ≥ 130/80, daytime ≥ 135/85, night ≥ 120/70; HBPM ≥ 135/85) because the white-coat effect is removed
Three immediate diagnosis pathways: crisis ( > 180/120), TOD + BP ≥ 160/100, or confirmed by HBPM/ABPM
Correct measurement technique is essential — wrong cuff, unsupported arm, uncrossed legs, recent caffeine all introduce error
Baseline investigations for ALL hypertensives: urinalysis, RFT, K⁺, Ca²⁺, glucose/HbA1c, lipids, uric acid, TSH, FBC, ECG, CXR, fundoscopy
Secondary HTN workup: biochemistry BEFORE imaging (endocrine principle); ARR for hyperaldosteronism, ONDST for Cushing, 24h urine metanephrines for phaeo, Doppler/CTA for RAS, PSG for OSA
Stop interfering drugs ≥ 2 weeks (MRA ≥ 6 weeks) before ARR testing — α-blockers and slow-release verapamil are safe alternatives for BP control during washout
Never biopsy a phaeochromocytoma — risk of catecholamine storm

Active Recall - Diagnostic Criteria, Algorithm & Investigations for Hypertension

References

^[1] Lecture slides: GC 058. High Blood Pressure.pdf (BP grading, CVS risk factors, target organ damage, prognosis framework) ^[2] Senior notes: Block A - High blood pressure_ hypertension.pdf (history, PE, investigations for initial evaluation, secondary HTN screening, renovascular HTN demographics) ^[3] Senior notes: Maksim Medicine Notes.pdf (p.78 — investigations, fundoscopy grading, secondary cause workup: ARR, ONDST, 24h urine catecholamines, IGF-1, TFT) ^[4] Senior notes: Block A - Clinical Pharmacology of anti-HT and anti-HF medications.pdf (BP measurement technique, home BP monitoring, secondary HTN screening including renal Doppler) ^[10] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.320–322 — ACC/AHA and WHO criteria, ABPM/HBPM thresholds, white-coat HTN, malignant HTN) ^[11] Senior notes: Ryan Ho Cardiology.pdf (p.176–178 — diagnostic rules, secondary HTN table with prevalence/clinical features/screening, TOD assessment) ^[12] Senior notes: Block A - Endocrine Data Interpretation.pdf (youth HTN workup, investigations targeting differentials: cortisol, IGF-1, PSG, Doppler) ^[13] Senior notes: Block A - Chronic Kidney Disease and its Complications.pdf (eGFR formulas, CT renal artery for RAS, causes of CKD, albuminuria causes) ^[14] Senior notes: Ryan Ho Chemical Path.pdf (p.29 — diagnosis of Cushing syndrome, ONDST, 24h UFC, late-night salivary cortisol) ^[15] Senior notes: Maksim Surgery Notes.pdf (p.205 — phaeochromocytoma investigations, 10% rule, biopsy contraindication) ^[18] Senior notes: Block A - Introduction to Renal Investigations (RFT, urine tests and US kidneys).pdf (uPCR vs UACR, urine microscopy, renal imaging) ^[19] Senior notes: Block A - Introduction to CVS investigations (including ECG).pdf (CXR interpretation in CVS disease, CT ratio, Kerley B lines) ^[20] Senior notes: Block A - Introduction to Endocrine investigations.pdf (principle: biochemistry before imaging, sequence of endocrine investigations, ARR reference) ^[21] Senior notes: Ryan Ho Endocrine.pdf (p.58–59 — primary hyperaldosteronism approach: ARR, salt-loading, postural test, AVS, drug interference) ^[22] Senior notes: Block A - I have fluctuating BP_ cushing syndrome; adrenal diseases and tumours; other endocrine tumours.pdf (Conn's investigation principles, Cushing ACTH-dependent vs independent, differential diagnosis) ^[23] Senior notes: Ryan Ho Endocrine.pdf (p.125 — ASCVD risk assessment tools, HK consensus 2016)

Management Algorithm and Treatment Modalities for Hypertension

Before prescribing a single pill, understand what you are trying to achieve. Hypertension management has three simultaneous objectives:

Reduce blood pressure to target — to prevent target organ damage
Reduce overall cardiovascular risk — HTN rarely exists in isolation; address all modifiable risk factors
Identify and treat secondary causes — curable HTN should be cured, not masked with lifelong drugs

"The BP goal is more important [than the specific drug choice]" ^[4]. "Just make sure your choice is personalised to the patient" ^[4].

Targets vary by patient population. The general principle: lower is generally better, but there is a floor below which hypoperfusion risks outweigh benefits, especially in the elderly.

Population	Target	Source / Rationale
General population	< 140/90 mmHg (ESC 2023); < 130/80 (ACC/AHA 2017 for most)	Standard threshold supported by large RCTs (SPRINT, STEP)
High-risk patients (DM, CKD, established CVD)	< 130/80 mmHg	Greater absolute risk reduction from tighter control
CKD patients	< 120/80 mmHg (KDIGO 2021) ^[13]	Slows progression to ESRD; but must monitor for AKI and hyperkalaemia
Elderly (≥ 65 years)	SBP 130–139 mmHg if tolerated; < 150/90 if frail	"Guidelines are becoming age-related, more lenient for older individuals — big trials show super stringent HT guidelines for elderly cause more mortality, increase chance of severe hypotension" ^[4]
Acute stroke	Do NOT acutely lower BP (unless > 220/120 or thrombolysis planned at < 185/110)	"Acute stroke — contraindicated, since the rapid reduction in BP will cause loss of cerebral autoregulation, less perfusion, consequent risk of cerebral infarction" ^[2]
Aortic dissection	SBP < 120 mmHg within first hour	"Anything increasing heart rate and cardiac output increases the dissection of the aorta" ^[4] — need both HR < 60 and SBP < 120

High Yield — Target in CKD

KDIGO 2021: target < 120/80 for CKD patients ^[13]. This is more aggressive than general population targets. Rationale: SPRINT CKD subgroup showed significant reduction in cardiovascular events and all-cause mortality with intensive BP control. However, must monitor RFT and electrolytes closely — risk of AKI and hyperkalaemia with RAAS blockade ^[13].

Lifestyle measures should be initiated for ALL hypertensive patients, regardless of whether drugs are prescribed. They also serve "as initial therapy before starting medications" and "as adjunct to or facilitate step-down of medications" ^[11].

Modification	Expected SBP Reduction	Mechanism
Weight reduction (if overweight/obese)	~5–20 mmHg per 10 kg lost	↓ Insulin resistance → ↓ sympathetic tone, ↓ RAAS activation; ↓ blood volume. "Weight loss of 5–10% of total body weight is already associated with health benefit" ^[24]
DASH diet (↑ fruits/vegetables, ↓ saturated fat)	~8–14 mmHg	↑ K⁺ and fibre → natriuresis, vasodilation
Dietary sodium restriction (< 5 g NaCl/day or < 2 g Na⁺/day)	~2–8 mmHg	↓ Intravascular volume; ↓ arterial stiffness
Potassium supplementation (aim 3.5–5 g/day)	~2–4 mmHg	K⁺ promotes natriuresis via Na⁺/K⁺-ATPase; direct vasodilator
Regular aerobic exercise (30 min/day, most days) ^[11]	~4–9 mmHg	↓ Sympathetic tone, ↑ NO bioavailability, ↑ insulin sensitivity
Alcohol moderation (≤ 2 drinks/day for men, ≤ 1 for women) ^[11]	~2–4 mmHg	↓ RAAS activation, ↓ sympathetic tone
Smoking cessation	Minimal direct BP effect, but massive CV risk reduction	Smoking ↑ acute BP transiently; chronic endothelial damage → atherosclerosis
Stress management	Variable	↓ Sustained sympathetic activation

"Diet: ↓ Na/fat, ↑ fruit/vegetables, ↑ K, DASH diet" ^[11]. DASH = Dietary Approaches to Stop Hypertension.

5. Pharmacological Management

The four first-line drug classes for hypertension are remembered as ABCD:

Letter	Drug Class	Example	Primary Mechanism
A	ACEI / ARB	Ramipril, perindopril / Losartan, valsartan	Block RAAS → ↓ AngII → ↓ vasoconstriction + ↓ aldosterone → ↓ Na⁺ retention
B	Beta-blockers	Bisoprolol, atenolol, metoprolol, carvedilol	↓ HR + ↓ contractility → ↓ CO; ↓ renin secretion
C	Calcium channel blockers	Amlodipine, nifedipine (DHP); verapamil, diltiazem (non-DHP)	Block L-type Ca²⁺ channels → arteriolar smooth muscle relaxation → ↓ TPR
D	Diuretics (thiazide/thiazide-like)	Hydrochlorothiazide, indapamide, chlorthalidone	↓ Blood volume (short-term); ↓ TPR (long-term via mechanism not fully understood)

"ABCD treatment for blood pressure control" ^[4]. "Newer guidelines suggest combination therapy at any stage of treatment" ^[4] — "Dual combo is the choice" ^[4].

Key Point — Beta-Blockers Are Second-Line

"β-blockers (B) are LESS effective in treatment of hypertension" ^[10] compared to ACE/ARB, CCB, and thiazides for primary uncomplicated HTN. They are however first-line when there is a compelling indication (HF, post-MI, rate control for AF, aortic dissection). The stepwise approach is A + C or A + D → A + C + D → then add spironolactone or BB ^[11]^[10].

Based on ESC 2023 and the GC 058 / Clinical Pharmacology lecture frameworks ^[1]^[4]^[10]^[11]:

Step	Regimen	Notes
Step 1	Monotherapy: A or C or D	Any single first-line agent achieves ~10–15 mmHg ↓ SBP ^[11]. Choice guided by comorbidities. Consider upfront dual therapy if > 20/10 mmHg above goal ^[11]
Step 2	Dual combination: A + C or A + D	"A + C combination demonstrated to be superior in cardiovascular outcome to A + D in ACCOMPLISH trial" ^[11]. Do NOT combine ACEI + ARB (no benefit, ↑ adverse effects — "Never prescribe ACEI and ARB together" ^[25])
Step 3	Triple combination: A + C + D	If still uncontrolled on dual therapy
Step 4 (Resistant HTN)	Add spironolactone (25–50 mg)	PATHWAY-2 trial showed spironolactone superior to other add-on agents for resistant HTN (↓ aldosterone-mediated volume retention). Alternatives: alpha-blocker, Ald antagonist, or vasodilator ^[11]
Beyond	Re-evaluate adherence, timing, home BP, secondary causes, refer to specialist	"AT-Home-GOAL: Adherence → Timing → Home BP → Greater dose → Other classes → Alternative Rx → Look for contributing factors" ^[11]

"Resistant hypertension requires initial assessment of eGFR" ^[4] — must check kidney function before escalating, especially before adding MRA or increasing RAAS blockade.

5.3 Individual Drug Classes — Detailed Pharmacology, Indications, and Contraindications

Name breakdown: "ACE" = angiotensin-converting enzyme; "inhibitor" = blocks. Prevents conversion of AngI → AngII.
Also blocks the degradation of bradykinin (ACE = kininase II) → ↑ bradykinin → vasodilation + but also dry cough (accumulation of bradykinin in bronchial mucosa) and angioedema (rare but potentially fatal)

	Detail
Examples	Ramipril, perindopril, enalapril, lisinopril, captopril
Mechanism	↓ AngII → ↓ vasoconstriction + ↓ aldosterone → ↓ Na⁺/H₂O retention; ↑ bradykinin → vasodilation; ↓ cardiac remodelling
Compelling Indications	Diabetes (renoprotective), CKD/proteinuria (↓ intraglomerular pressure), heart failure with reduced EF (HFrEF), post-MI with LV dysfunction (EF < 40%), IHD with HTN, LVH regression ^[2]^[10]^[26]
Contraindications	Pregnancy (teratogenic — renal agenesis), bilateral renal artery stenosis (precipitates AKI), hyperkalaemia (K⁺ > 5.5), angioedema history ^[10]^[26]
Relative contraindications	Women of childbearing potential ^[10]
Key side effects	Dry cough (10–15%, more common in East Asians — due to bradykinin accumulation), hyperkalaemia, hypotension (especially first-dose in volume-depleted patients), angioedema, ↑ creatinine (up to 30% rise acceptable on initiation — reflects ↓ intraglomerular pressure, actually renoprotective)

Why ACEI/ARB Are Renoprotective

AngII preferentially vasoconstricts the efferent arteriole → ↑ intraglomerular pressure → glomerular hyperfiltration → progressive glomerular damage. By blocking AngII, ACEI/ARB dilate the efferent arteriole → ↓ intraglomerular pressure → ↓ proteinuria → ↓ glomerulosclerosis. This is why they are first-line in diabetic nephropathy and CKD with proteinuria. The trade-off: GFR may initially drop (acceptable up to 30%) as you remove the hyperfiltration.

Name breakdown: blocks the AT₁ receptor for angiotensin II directly.
Does NOT affect bradykinin metabolism → no cough (key advantage over ACEI)

	Detail
Examples	Losartan, valsartan, candesartan, irbesartan, telmisartan
Mechanism	Blocks AT₁ receptor → same downstream effects as ACEI but without bradykinin accumulation
Compelling Indications	Same as ACEI; used when ACEI not tolerated (usually due to cough) ^[26]. "ARBs are recommended for patients who have indications for, but are intolerant of, ACE inhibitors" ^[26]
Contraindications	Same as ACEI: pregnancy, bilateral RAS, hyperkalaemia ^[10]^[26]
Key side effects	Hyperkalaemia, hypotension, angioedema (very rare, but still possible)

Two subtypes — understand the difference:

	Dihydropyridines (DHP)	Non-Dihydropyridines (Non-DHP)
Examples	Amlodipine, nifedipine, felodipine	Verapamil, diltiazem
Primary action	Peripheral arteriolar vasodilation (↓ TPR)	Both vasodilation AND cardiac effects (↓ HR, ↓ contractility, ↓ AV conduction)
Selectivity	Vascular smooth muscle >> cardiac	Cardiac ≈ vascular
Key side effects	Peripheral oedema (especially amlodipine — due to precapillary arteriolar dilation → ↑ capillary hydrostatic pressure; NOT fluid retention), flushing, headache, reflex tachycardia (less with amlodipine)	Bradycardia, constipation (verapamil), heart block, negative inotropy

	Detail
Compelling Indications	Isolated systolic HTN (elderly), angina (anti-anginal), atherosclerosis ^[10], Raynaud's; non-DHP for rate control of AF
Contraindications	DHP: tachyarrhythmia ^[10]; Non-DHP: heart failure (negative inotrope → worsens HF), 2nd/3rd degree heart block, combination with beta-blocker (risk of severe bradycardia/asystole)

"Amlodipine → seems to have less effect of rebound phenomenon" ^[4]. This is why amlodipine is the most commonly used CCB — long half-life (~35 hours), smooth BP control, minimal rebound.

For CKD patients: "Generally these are good, since they don't affect kidney and potassium — specifically talking about amlodipine" ^[13]. CCBs are safe when you are worried about hyperkalaemia.

Name breakdown: "thiazide" refers to the benzothiadiazine chemical structure; "diuretic" = promotes urination.
Act on the Na⁺-Cl⁻ co-transporter (NCC) in the distal convoluted tubule → ↓ Na⁺ reabsorption → ↓ blood volume (acute effect) → and chronically ↓ TPR (mechanism unclear, possibly via ↓ Na⁺ in vascular smooth muscle → ↓ Ca²⁺ entry → vasodilation)

	Detail
Examples	Hydrochlorothiazide (HCTZ), indapamide, chlorthalidone (longer-acting, preferred in trials)
Compelling Indications	Isolated systolic HTN (especially elderly), heart failure (volume overload), blacks (respond well to diuretics and CCBs) ^[10], recurrent calcium kidney stones (thiazides ↓ urinary Ca²⁺ excretion)
Contraindications	Gout (↑ uric acid by competing for urate secretion in proximal tubule) ^[10]; hyponatraemia
Relative contraindications	Metabolic syndrome, glucose intolerance (thiazides ↓ insulin secretion via hypoK → worsen glucose control) ^[10], pregnancy ^[10]
Key side effects	Hyponatraemia, hypokalaemia (↑ Na⁺ delivery to collecting duct → ↑ Na⁺/K⁺ exchange), hyperuricaemia/gout, hyperglycaemia, hypercalcaemia (↑ Ca²⁺ reabsorption in DCT), dyslipidaemia

Metabolic mnemonic for thiazides: "HyperGLUC": Hyperglycaemia, Gout (hyperuricaemia), Lipids (↑), Uric acid (↑), Calcium (↑) — plus hypoNa, hypoK, hypoMg.

	Detail
Examples	Bisoprolol (most cardioselective), atenolol, metoprolol, propranolol (non-selective), carvedilol (α + β), labetalol (α + β), nebivolol (β₁ + NO release)
Mechanism	β₁ blockade → ↓ HR, ↓ contractility → ↓ CO; ↓ renin release (β₁ on JG cells); central sympatholytic effect
Compelling Indications	Heart failure (HFrEF — bisoprolol, carvedilol, metoprolol succinate, nebivolol), post-MI, angina pectoris, aortic dissection (↓ dP/dt), AF rate control, aortic aneurysm ^[10]
Contraindications	Asthma (β₂ blockade → bronchospasm — but bisoprolol more cardioselective, can still try in asthma patients ^[4]), 2nd/3rd degree heart block ^[10]
Relative contraindications	COPD (except vasodilator β-blockers like carvedilol/nebivolol) ^[10], metabolic syndrome, glucose intolerance (mask hypoglycaemia symptoms, ↓ insulin sensitivity), athletes/physically active patients (limit exercise tolerance) ^[10], peripheral arterial disease (β₂ blockade → unopposed α vasoconstriction → worsens claudication — but evidence weak)
Key side effects	Fatigue, cold extremities, bradycardia, erectile dysfunction, depression, bronchospasm, rebound tachycardia on abrupt withdrawal

"Bisoprolol more cardioselective, as opposed to metoprolol. So even in patients with asthma, can still try bisoprolol, won't affect airway" ^[4].

Metoprolol formulations: "Metoprolol tartrate is short-acting and is usually taken at least twice a day. No clinical outcome benefit" ^[4]. Use metoprolol succinate (extended-release) for HF — this is the formulation with trial evidence (MERIT-HF).

Drug	Mechanism	Indication	Contraindications / Cautions
Spironolactone / Eplerenone (MRA)	Aldosterone receptor antagonist → ↓ Na⁺ reabsorption, ↓ K⁺ secretion in collecting duct	Resistant HTN (4th-line), primary hyperaldosteronism (medical Rx for bilateral hyperplasia), HFrEF	Renal failure (eGFR < 30), hyperkalaemia ^[10]. Spironolactone → gynecomastia (anti-androgen); eplerenone → more selective, less gynaecomastia but more expensive ^[22]
Alpha-blockers (doxazosin, prazosin)	α₁ blockade → arteriolar and venous dilation → ↓ TPR	HTN + BPH ("Patient has concomitant HT and BPH — alpha blockers" ^[13]), resistant HTN	Postural hypotension (especially first-dose), reflex tachycardia
Hydralazine	Direct arteriolar vasodilator	Pregnancy (safe), HF combination (with isosorbide dinitrate, especially in Black patients)	Reflex tachycardia, fluid retention, SLE-like syndrome (slow acetylators)
Methyldopa	Central α₂ agonist → ↓ sympathetic outflow	Pregnancy (safest, most evidence) ^[10]	Sedation, depression, hepatotoxicity, haemolytic anaemia, rebound HTN on withdrawal
Finerenone (non-steroidal MRA)	Selective MRA → ↓ kidney fibrosis	DM + CKD (FIDELIO-DKD, FIGARO-DKD trials)	"Molecular structure permits finerenone to be much more targeted → hyperkalemia side effect much lower than conventional MRAs" ^[27]

This is extremely high-yield for exams. You must match the antihypertensive to the patient's comorbidities.

"Choice of drug dependent on whether there are compelling indications, contraindications" ^[2].

Comorbidity	Preferred Drug	Why
Diabetes	ACEI or ARB ^[2]	Renoprotective (↓ intraglomerular pressure, ↓ proteinuria); also add SGLT2i for cardiorenal protection
CKD / Proteinuria	ACEI or ARB ^[2]^[10]	Same renoprotective mechanism; ↓ albuminuria
Heart failure (HFrEF)	ACEI/ARB (or ARNI), BB (bisoprolol/carvedilol/metoprolol/nebivolol), MRA, SGLT2i — the 4 pillars ^[4]^[10]	"4 pillars of heart failure" ^[4]: each independently ↓ mortality. ACEI ↓ remodelling; BB ↓ HR/arrhythmia; MRA ↓ fibrosis; SGLT2i ↓ preload/natriuresis
Heart failure (HFpEF)	BP control (any agent), diuretics (cautious), SGLT2i	"Treat underlying causes e.g. BP control; cautious use of diuretic; regression of LVH" ^[28]
Post-MI	BB + ACEI ^[10]	BB ↓ oxygen demand, ↓ arrhythmia; ACEI ↓ remodelling
Angina pectoris	BB + CCB ^[10]	BB ↓ HR → ↑ diastolic filling time → ↑ coronary perfusion; CCB → coronary vasodilation
Aortic aneurysm	BB ^[10]	↓ dP/dt (rate of rise of aortic pressure) → ↓ shear stress on aortic wall
Aortic dissection	IV BB first (labetalol or esmolol), then IV nitroprusside	"Reduce SBP to 100–120 and ↓ cardiac contractility" ^[29]. BB first to prevent reflex tachycardia from vasodilator
AF (prevention)	ACEI/ARB ^[10]	↓ LA pressure → ↓ LA remodelling
AF (rate control)	BB or non-DHP CCB (verapamil/diltiazem) ^[10]	↓ AV nodal conduction → ↓ ventricular rate
LVH	ACEI/ARB + CCB ^[10]	ACEI/ARB most effective at LVH regression (↓ AngII-mediated hypertrophy)
Isolated systolic HTN (elderly)	CCB or thiazide ^[10]	Target arterial stiffness; both well-tolerated in elderly
Metabolic syndrome	ACEI/ARB + CCB ^[10]	BB and thiazides worsen glucose intolerance
Pregnancy	Labetalol, methyldopa, nifedipine ^[10]^[29]	Safe in pregnancy. ACEI/ARB absolutely contraindicated (teratogenic). Hydralazine IV for pre-eclampsia ^[29]
Blacks	CCB + thiazide ^[10]	Lower renin states → better response to volume-reducing agents than RAAS blockers
BPH	Alpha-blocker ^[13]	Dual benefit: ↓ BP + relaxes prostatic smooth muscle
OSA	Treat OSA with CPAP + standard antihypertensives	nCPAP is the most consistently effective treatment for OSA ^[30]; BP often improves once OSA is treated

From MBBS Final MB (Medicine) Felix PY Lai notes ^[10]:

Drug	Absolute Contraindications	Relative Contraindications
ACEI / ARB	Pregnancy, bilateral RAS, hyperkalaemia	Women of childbearing potential
Beta-blockers	Asthma, 2nd/3rd degree heart block	COPD (except vasodilator BB), metabolic syndrome, glucose intolerance, athletes
CCB (DHP)	Tachyarrhythmia	Heart failure
CCB (non-DHP)	Heart failure (negative inotrope), severe bradycardia/heart block	Use with beta-blocker (risk of asystole)
Thiazide diuretics	Gout	Pregnancy, metabolic syndrome, glucose intolerance, hypercalcaemia, hypokalaemia
MRA (spironolactone/eplerenone)	Renal failure (eGFR < 30), hyperkalaemia	—

"Severe aortic stenosis, drug contraindications: Beta-blockers → negative inotropes; Non-DHP CCB → negative inotropes; Nitrates → compromises preload" ^[4]. This is a classic exam scenario — patient with aortic stenosis and HTN. Use ACEI/ARB cautiously (monitor for hypotension) or DHP-CCB.

6. Management of Hypertensive Crises

	Hypertensive Emergency	Hypertensive Urgency
Definition	BP > 180/120 + new/worsening TOD	BP > 180/120, no acute TOD
Timeline	Immediate Rx within 1 hour ^[1]^[2]	Early Rx within 24 hours ^[1]^[2]
Route	IV medications, ICU/CCU with intra-arterial BP monitoring ^[3]	Oral medications, observe
BP target	≤ 25% reduction in first hour, then to 160/110 in next 2–6h, then gradually to normal over 24–48h ^[11]	Gradual reduction to target over 24–48h

GC 058 slide: "Hypertensive emergency (immediate Rx within 1 hr): Malignant HT, HT encephalopathy, acute heart failure, unstable angina/MI, dissecting aortic aneurysm, cerebral haemorrhage, renal failure, severe pre-eclampsia, adrenergic crisis" ^[1].

GC 058 slide: "Hypertensive urgency (early Rx within 24 hrs): HT with grade III or IV retinal changes, severe preoperative or perioperative HT" ^[1].

Drug	Mechanism	Best Indication	Cautions
Labetalol	Combined α₁ + β blockade → ↓ HR, ↓ TPR	Most versatile; aortic dissection, adrenergic crisis, pregnancy	Contraindicated in asthma, decompensated HF, severe bradycardia
Sodium nitroprusside	NO donor → arteriolar + venous dilation	Hypertensive encephalopathy, general emergency	"Vasodilation specifically for the arteries" ^[4]. Cyanide toxicity with prolonged use (> 48h); contraindicated in pregnancy
Nitroglycerin (GTN)	Predominantly venodilation → ↓ preload	ACS + HTN, acute pulmonary oedema	"Vasodilation of venous system" ^[4]. Headache, tolerance. Contraindicated in severe aortic stenosis ^[4]
Esmolol	Ultra-short-acting β₁-blocker (t½ ~9 min)	Aortic dissection, perioperative HTN	Easily titrated; safe to "test" BB in borderline patients
Hydralazine IV	Direct arteriolar vasodilator	Pre-eclampsia / eclampsia ^[29]	Reflex tachycardia; contraindicated in ACS and aortic dissection (↑ cardiac work) ^[29]
Phentolamine	Non-selective α-blocker	Phaeochromocytoma crisis	Short-acting; used during tumour manipulation/surgery
Nicardipine	IV DHP-CCB	General emergency, pregnancy	Smooth onset, easy to titrate
Fenoldopam	Dopamine D₁ agonist → renal vasodilation	HTN emergency with AKI (improves renal perfusion)	Expensive, limited availability in HK

Specific scenarios ^[29]:

APO: nitroprusside/GTN + loop diuretic; avoid diazoxide/hydralazine (increase cardiac work) or labetalol/BB in LV dysfunction

ACS: GTN, nitroprusside, labetalol, CCB; diazoxide/hydralazine contraindicated

Aortic dissection: nitroprusside + labetalol/propranolol IV; target SBP 100–120

Phaeochromocytoma/sympathetic excess: phentolamine, labetalol, nitroprusside; BB alone contraindicated (unopposed α → further ↑ BP) ^[29]

Pregnancy: IV hydralazine, nicardipine, labetalol; no nitroprusside (cyanide toxicity), no ACEI ^[29]

Critical Concept — Why BB Before Vasodilator in Aortic Dissection

If you give a vasodilator (e.g. nitroprusside) first → reflex tachycardia → ↑ dP/dt (rate of aortic pressure rise) → propagates the dissection flap. Always establish β-blockade first (↓ HR to < 60, ↓ contractility) to abolish the reflex tachycardia, THEN add a vasodilator to bring SBP down further. "Anything increasing heart rate and cardiac output increases the dissection of the aorta" ^[4].

Critical Concept — Phaeochromocytoma: Alpha Before Beta

"Important to initiate an alpha-blockade first with phenoxybenzamine, then beta-blockade with propranolol. If you give beta-blocker first, vasoconstriction due to unopposed alpha-adrenoceptor activity may occur → exacerbate hypertension" ^[22]. This is the opposite order to aortic dissection management — know both scenarios.

Cause	Treatment
Primary hyperaldosteronism — adenoma	Unilateral laparoscopic adrenalectomy (pre-op spironolactone to optimise K⁺) ^[22]. "HTN can remain in 40–65% due to ?irreversible damage to systemic microcirculation (hypertensive nephrosclerosis)" ^[21]
Primary hyperaldosteronism — bilateral hyperplasia	Medical: spironolactone/eplerenone (1st line) or amiloride/triamterene (2nd line) ^[22]. "Bilateral adrenalectomy would lead to adrenal crisis" ^[15]
Phaeochromocytoma	Surgery after full alpha-blockade (phenoxybenzamine ≥ 10–14 days) → then add beta-blockade ^[22]
Cushing syndrome	Treat underlying cause (stop exogenous steroids if iatrogenic; transsphenoidal surgery for pituitary adenoma; adrenalectomy for adrenal tumour)
Renal artery stenosis	Renal artery revascularisation (angioplasty ± stent) for: flash pulmonary oedema, resistant HTN, ischaemic nephropathy with CKD ^[2]. Medical Rx with antihypertensives for stable disease (CORAL/ASTRAL trials showed no benefit of routine revascularisation over medical Rx for stable atherosclerotic RAS)
OSA	nCPAP (most effective), weight loss, mandibular advancement device, surgery in selected cases ^[30]
Coarctation	Surgical repair or balloon angioplasty ± stenting
Drug-induced	Stop the offending drug

Aspect	Frequency / Detail
BP monitoring	Every 1–3 months until at target; then every 3–6 months once stable. HBPM encouraged
RFT and electrolytes	2 weeks after starting or uptitrating ACEI/ARB/diuretic ^[13]; then every 6–12 months
CV risk reassessment	Annually: glucose/HbA1c, lipids, uric acid
TOD reassessment	Annually: ECG, urine ACR, fundoscopy
Drug compliance	Inquire at every visit — commonest reason for poor control; consider single-pill combinations
Secondary cause review	If resistant HTN develops, re-screen

High Yield Summary — Management of Hypertension

Lifestyle modifications for ALL — DASH diet, ↓ Na⁺, exercise, weight loss, alcohol moderation, smoking cessation
Step-wise pharmacotherapy: Step 1: A or C or D → Step 2: A+C or A+D → Step 3: A+C+D → Step 4: add spironolactone (resistant HTN)
Beta-blockers are second-line for uncomplicated HTN but first-line when compelling indication exists (HF, post-MI, aortic dissection, AF)
Match drug to comorbidity — DM/CKD → ACEI/ARB; HFrEF → 4 pillars; elderly/ISH → CCB or thiazide; pregnancy → labetalol/methyldopa/nifedipine
Never combine ACEI + ARB; ACEI/ARB contraindicated in pregnancy and bilateral RAS
Hypertensive emergency: IV drugs in ICU, ↓ BP by ≤ 25% in first hour, then gradually. Key IV agents: labetalol, nitroprusside, GTN, esmolol, hydralazine (pregnancy)
Aortic dissection: BB FIRST (↓ dP/dt), then vasodilator; target SBP < 120. Phaeochromocytoma: alpha-blocker FIRST, then BB — opposite order!
Acute stroke: do NOT acutely lower BP (unless extremely high or thrombolysis planned) — risk of watershed infarction from loss of autoregulation
Secondary HTN Rx: surgery for adenoma (Conn's, phaeo); medical for bilateral hyperplasia; CPAP for OSA; stop offending drugs

Active Recall - Management of Hypertension

References

^[1] Lecture slides: GC 058. High Blood Pressure.pdf (indications for immediate/early treatment, hypertensive emergency vs urgency, malignant HTN definition) ^[2] Senior notes: Block A - High blood pressure_ hypertension.pdf (compelling indications, drug choices, renovascular HTN management, hypertensive emergency indications, acute stroke contraindication) ^[3] Senior notes: Maksim Medicine Notes.pdf (p.78 — hypertensive emergency definition and management) ^[4] Senior notes: Block A - Clinical Pharmacology of anti-HT and anti-HF medications.pdf (ABCD framework, combination therapy, BB cardioselectivity, CCB rebound, nitroprusside vs nitrates, aortic dissection, aortic stenosis contraindications, BP targets in elderly, 4 pillars HF, resistant HTN, SGLT2i) ^[10] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.332–334 — treatment regimen A+C or A+D, recommended medications by condition table, contraindications table, pregnancy drugs) ^[11] Senior notes: Ryan Ho Cardiology.pdf (p.180–182 — lifestyle measures, medical therapy steps, combination therapy rationale, ACCOMPLISH trial, resistant HTN approach AT-Home-GOAL, malignant HTN, hypertensive emergency/urgency definitions and management) ^[13] Senior notes: Block A - Chronic Kidney Disease and its Complications.pdf (KDIGO 2021 target, ACEI/ARB monitoring in CKD, CCB safety, alpha-blocker for BPH+HTN, diuretic caution) ^[15] Senior notes: Maksim Surgery Notes.pdf (Conn's syndrome management — adenoma vs hyperplasia, bilateral adrenalectomy risk) ^[21] Senior notes: Ryan Ho Endocrine.pdf (p.58–59 — primary hyperaldosteronism management, post-op persistent HTN, aldosterone antagonist choice) ^[22] Senior notes: Block A - I have fluctuating BP_ cushing syndrome; adrenal diseases and tumours; other endocrine tumours.pdf (aldosteronism management — surgery vs medical, phaeochromocytoma alpha-before-beta principle) ^[24] Senior notes: Block A - I am overweight, doctor_ obesity; Hyperlipidaemia.pdf (weight loss targets) ^[25] Senior notes: Block A – Nephrology Data Interpretation.pdf (never combine ACEI + ARB, ACEI/ARB contraindicated in bilateral RAS) ^[26] Senior notes: Block A - WCS32 Chest pain on exertion_ ischaemic heart disease; angina pectoris.pdf (ACEI/ARB indications in IHD, side effects, contraindications) ^[27] Senior notes: Block A - Nephrology Interactive Tutorial.pdf (finerenone advantages over conventional MRA) ^[28] Senior notes: Block A - Shortness of breath on exertion_ heart failure.pdf (HFpEF management principles, CRT/ICD indications) ^[29] Senior notes: Handbook of Internal Medicine 2024.pdf (p.36 — specific IV agents by clinical scenario: APO, ACS, aortic dissection, pregnancy, phaeochromocytoma) ^[30] Senior notes: Ryan Ho Respiratory.pdf (p.160–161 — OSA consequences including secondary HTN, CPAP as treatment, other modalities)

Complications of Hypertension

Hypertension does not kill by itself — it kills through its complications, which are collectively termed hypertension-mediated organ damage (HMOD) or target organ damage (TOD). Every complication traces back to the same fundamental process: chronically elevated intravascular pressure damages blood vessels, and since blood vessels supply every organ, the damage is systemic.

GC 058 slide: "Hypertension → CVS Risk Factors → Target Organ Damage → Prognosis → Secondary Causes" — this progression map shows that prognosis is ultimately determined by the degree of TOD ^[1].

"Evidence of end organ damage — Cardiac: cardiac enlargement, ECG signs of ischaemia or left ventricular strain, myocardial infarction, congestive heart failure. Eyes: retinal exudates and haemorrhages, papilloedema. Renal: impaired renal function. Nervous system: cerebrovascular accident." ^[1]

The two fundamental pathological processes that drive all HTN complications are:

Accelerated atherosclerosis of large vessels — HTN ↑ shear stress on endothelium → endothelial injury → lipid deposition, smooth muscle proliferation, plaque formation → luminal narrowing or plaque rupture → ischaemic events (MI, ischaemic stroke, PAD)
Hyaline arteriosclerosis and fibrinoid necrosis of small vessels — chronic ↑ pressure → plasma proteins forced into arteriolar walls → hyaline thickening → luminal narrowing → ischaemic damage to downstream parenchyma (kidney, retina, brain); in malignant HTN, acute severe ↑ pressure → fibrinoid necrosis → microangiopathic haemolytic anaemia

1. Cardiovascular Complications

Pathological change: LVH ^[10]
Mechanism from first principles: Chronically ↑ afterload (↑ aortic pressure against which the LV must eject) → ↑ LV wall stress. By Laplace's law: wall stress = (P × r) / (2h), where P = intracavitary pressure, r = radius, h = wall thickness. To normalise wall stress, the LV compensates by increasing h — myocyte hypertrophy with parallel addition of sarcomeres → concentric hypertrophy (thick walls, normal or reduced cavity size).
Why it matters: LVH is not benign — it is an independent risk factor for sudden cardiac death, heart failure, and arrhythmias. The hypertrophied myocardium is:
- Stiffer → diastolic dysfunction (impaired relaxation and filling)
- More oxygen-demanding (greater muscle mass) but relatively underperfused (capillary density does not increase proportionally) → subendocardial ischaemia
- Electrically unstable → substrate for ventricular arrhythmias
Detection: ECG (Sokolow-Lyon, Cornell criteria), echocardiography (LV mass index — more sensitive)

"Congestive heart failure" ^[1]^[10]

Progression: LVH → diastolic dysfunction → HFpEF (heart failure with preserved ejection fraction) → eventually myocyte loss and fibrosis → systolic dysfunction → HFrEF (heart failure with reduced ejection fraction)
"So when having DM and HT at the same time, you triple the risk of heart diseases" ^[2]
HFpEF is more common than HFrEF in Hong Kong (> 50% of HF cases) ^[28] and HTN is its most common cause
Symptoms: exertional dyspnoea → orthopnoea → PND → resting dyspnoea; ankle oedema, fatigue
HTN can also cause acute heart failure / acute pulmonary oedema (APO) during a hypertensive crisis — severely ↑ afterload → acute LV decompensation → fluid floods into alveoli

"Myocardial infarction" ^[1]; "Ischaemic heart disease" ^[10]

Mechanism: HTN is a major risk factor for coronary atherosclerosis (↑ shear stress → endothelial injury → plaque formation). Additionally, LVH ↑ myocardial oxygen demand while coronary reserve is diminished → supply-demand mismatch
Manifestations: stable angina, unstable angina, NSTEMI, STEMI
HTN is also a risk factor for arterial thrombosis — alongside hypercholesterolaemia, DM, chronic renal impairment, and male gender ^[31]

Mechanism: chronic HTN → LVH + diastolic dysfunction → ↑ LA pressure → LA dilatation and structural remodelling → electrical substrate for AF. Additionally, pulmonary vein micro-electrical circuits provide the trigger for re-entry ^[32]
AF then dramatically ↑ stroke risk (stasis in dilated LA → thrombus formation, particularly in the LA appendage → cardioembolic stroke)

"Atherosclerosis, aneurysm formation" ^[10]
Aortic aneurysm: chronic HTN → medial degeneration (smooth muscle apoptosis, elastin fragmentation, mucoid deposition) → weakening of aortic wall → progressive dilatation → aneurysm (abdominal or thoracic)
Aortic dissection: "HT is the most important risk factor" for aortic dissection ^[33]. Tear in the aortic intima → blood enters the media → creates a false lumen separating intima from adventitia ^[33]. Consequences depend on type:
- Type A (ascending) → aortic regurgitation, cardiac tamponade (dissection into pericardium), MI (coronary ostia compromise), stroke (carotid involvement)
- Type B (descending) → renal/mesenteric/limb ischaemia, spinal cord ischaemia (paraplegia) ^[33]
- "False lumen dilation depends on BP" ^[33] — this is why acute management targets SBP < 120

2. Cerebrovascular Complications

"Cerebral infarction" ^[10]; "Cerebrovascular accident" ^[1]

Mechanism: HTN accelerates atherosclerosis of the carotid arteries and large intracranial arteries → plaque rupture or in-situ thrombosis → territory infarction. Also, chronic small vessel disease (lipohyalinosis of perforating arteries) → lacunar infarcts (small, deep infarcts in basal ganglia, thalamus, pons, internal capsule)
HTN is the single most important modifiable risk factor for stroke — both ischaemic and haemorrhagic
"When having DM and HT at the same time, you double the risk of stroke" ^[2]

"Cerebral hemorrhage" ^[10]; "Mostly related to hypertension. Common sites: basal ganglia, cerebellum, brainstem" ^[34]

Mechanism from first principles: Chronic HTN → lipohyalinosis of small perforating arteries (lenticulostriate arteries off the MCA) → weakening of the vessel wall → formation of Charcot-Bouchard microaneurysms → rupture under high pressure → haemorrhage into brain parenchyma
Classic locations: basal ganglia (putamen — most common), thalamus, pons, cerebellum, lobar (lobar haemorrhage more often due to amyloid angiopathy or AVM in non-hypertensive patients ^[34])
Presentation: sudden severe headache, focal neurological deficit, ↓ consciousness

"HT encephalopathy — cerebral oedema → insidious onset of headache, N/V followed by non-localising neurological symptoms (confusion, restlessness), visual disturbances, transient paralysis, seizure, coma" ^[11]

Mechanism: when BP exceeds the upper limit of cerebral autoregulation (normally ~150–180 mmHg MAP, but higher in chronic HTN patients because the curve shifts rightward), the cerebral arterioles can no longer vasoconstrict sufficiently → forced dilation → breakdown of the blood-brain barrier → vasogenic cerebral oedema
This is a hypertensive emergency — requires immediate IV treatment
Reversible if treated promptly; fatal if not

Chronic HTN → cumulative small vessel disease → multiple lacunar infarcts + white matter ischaemia (leukoaraiosis) → progressive cognitive decline
Stepwise deterioration (unlike the gradual decline of Alzheimer's)
HTN in midlife is one of the strongest modifiable risk factors for dementia in later life

3. Renal Complications

"Nephrosclerosis — damage to the kidneys" ^[10]; "Impaired renal function" ^[1]

Mechanism: two forms exist:
- Benign nephrosclerosis (chronic, gradual): ↑ BP → hyaline arteriosclerosis of the afferent arteriole → narrowing of the lumen → ischaemic injury to downstream glomeruli and tubules → glomerulosclerosis → progressive nephron loss → ↓ GFR → CKD
- Malignant nephrosclerosis (acute, rapid): markedly ↑ BP → fibrinoid necrosis of arterioles → intravascular thrombosis → rapid renal failure with oliguria and proteinuria
Hypertension is the 2nd most common cause of CKD in Hong Kong (after diabetes) ^[13]
"So when having DM and HT at the same time, you sextuple the risk of CKD" ^[2]
"Mild CKD and albuminuria has been shown to increase the risk of cardiovascular death" ^[13] — this creates a vicious cycle: HTN → CKD → further ↑ BP (impaired natriuresis) → accelerated CKD

HTN damages the kidney → CKD → fluid retention, RAAS activation, sympathetic overactivity, anaemia, uraemic toxins → all worsen cardiac function → heart failure → further ↓ renal perfusion → worsening CKD
This bidirectional injury is why CKD is classified as a "coronary heart disease risk equivalent"

4. Ophthalmological Complications

CFB (OPHTH02) slide: "Hypertensive Retinopathy (A Grading System Rather Than a Disease)" ^[35]

Keith-Wagener-Barker (KWB) grading ^[10]:

Grade	Findings	Pathophysiology
Grade 1	Silver wiring (arteriolar sclerosis) — sclerosis of vessel wall reduces its transparency, central light reflex becomes broader and shinier; arteriolar constriction/thickening/tortuosity	Chronic ↑ BP → arteriolar smooth muscle hypertrophy and fibrosis → thickened wall
Grade 2	As Grade 1 + AV nicking/nipping — indentation or deflection of veins when crossed by arteries	Thickened arteriole shares a common adventitial sheath with the venule; the rigid arteriole compresses the venule at crossing points → bulging of the venule on either side
Grade 3	As Grade 2 + flame-shaped haemorrhages, soft exudates (cotton-wool spots) caused by ischaemia, hard exudates (lipid residues from leaking vessels)	Severe arteriolar damage → rupture of superficial retinal capillaries (flame haemorrhages); ischaemic infarction of nerve fibre layer (cotton-wool spots); chronic capillary leakage with lipid/protein deposition (hard exudates)
Grade 4	As Grade 3 + swelling of the optic disc (papilloedema)	Severe ↑ intracranial pressure OR optic nerve head ischaemia + ↑ capillary permeability → disc swelling. "Papilloedema was the hallmark of a more advanced condition associated with higher mortality (akin to having a malignancy)" — hence the historical term "malignant hypertension" ^[10]

High Yield — 'Malignant HTN' is an Outdated Term

"Moderate to severe hypertensive retinopathy was formerly called 'malignant hypertension', a term which clinicians should AVOID. Effective antihypertensive drug therapy has improved the prognosis." ^[10] However, Grade 3–4 retinopathy still indicates severe, accelerated HTN requiring urgent treatment.

CFB (OPHTH02): "Retinal Complications of Hypertension — Retinal Vein Occlusion" ^[35]

Retinal vein occlusion (CRVO / BRVO): the most common retinal vascular complication of HTN ^[36]
- Mechanism: at AV crossing points, the thickened hypertensive arteriole compresses the venule → turbulent flow → endothelial damage → thrombus formation → venous occlusion → retinal haemorrhages, oedema, and ischaemia
- "CRVO: acute sudden onset painless blurring of vision" ^[11]
- Branch RVO (BRVO) is commoner and less severe than central RVO (CRVO)
Retinal artery occlusion (CRAO / BRAO): embolic or thrombotic occlusion of retinal arteries → sudden painless monocular visual loss with "cherry-red spot" (fovea stands out against pale, ischaemic retina)
Retinal arterial macroaneurysms: fusiform dilatation of retinal arterioles due to chronic HTN → risk of rupture → vitreous haemorrhage
Chronic papilloedema → optic nerve atrophy ^[36]

5. Vascular Complications

Mechanism: accelerated atherosclerosis of lower limb arteries (aortoiliac, femoropopliteal) → intermittent claudication, rest pain, critical limb ischaemia, gangrene
Detected by ABI (ankle-brachial index) < 0.9

Atherosclerosis of carotid bifurcation → TIA / ischaemic stroke via artery-to-artery embolism or haemodynamic compromise
Detected by carotid duplex USS; carotid bruit on auscultation

When HTN becomes acutely severe (typically > 180/120), organ damage occurs rapidly and constitutes a hypertensive emergency ^[1]^[2]:

Complication	Mechanism	Clinical Features
Hypertensive encephalopathy	Exceeds cerebral autoregulatory limit → forced vasodilation → vasogenic oedema	Headache → confusion → seizures → coma
Acute pulmonary oedema (APO)	Acutely ↑ afterload → LV cannot cope → ↑ LVEDP → pulmonary capillary pressure exceeds oncotic pressure → transudation into alveoli	Acute dyspnoea, orthopnoea, pink frothy sputum, bilateral crackles
Acute MI / unstable angina	↑ Afterload + ↑ myocardial O₂ demand → supply-demand mismatch; plaque rupture	Chest pain, ECG changes, ↑ troponin
Aortic dissection	As above (section 1.5)	Tearing chest/back pain, pulse deficit, murmur of AR
Acute kidney injury	Fibrinoid necrosis of renal arterioles → acute ischaemic damage; "malignant nephrosclerosis"	Oliguria, ↑ creatinine, proteinuria ^[2]
Eclampsia	Endothelial dysfunction + vasospasm in pregnancy → seizures	Seizures in a pregnant woman with HTN + proteinuria
Microangiopathic haemolytic anaemia (MAHA)	Fibrinoid necrosis creates damaged endothelial surface → RBCs sheared as they pass through → fragmented RBCs (schistocytes)	"Malignant HT: elevated BP with encephalopathy or nephropathy or papilloedema ± microangiopathic haemolytic anaemia" ^[1]
Intracranial haemorrhage	Acute ↑ BP → rupture of Charcot-Bouchard aneurysms or vascular malformations	Sudden severe headache, focal deficit, ↓ GCS

Complications do not only arise from uncontrolled HTN — overzealous or inappropriate treatment also has consequences:

Complication	Mechanism	How to Avoid
Hypotension / syncope	Excessive BP lowering, especially with first-dose alpha-blockers or in volume-depleted patients	"First-dose phenomenon — ask patient to take it before sleeping" ^[4]. Start low, go slow
Rebound hypertension	Abrupt withdrawal of beta-blockers or clonidine → sudden sympathetic surge → severe HTN	"If you stop, patient may rebound to severe hypertension — hemodynamic crash, watershed infarct, stroke" ^[4]. Always taper, never stop abruptly
ACEI-induced cough	Accumulation of bradykinin → irritation of bronchial mucosa	Switch to ARB
Angioedema	Bradykinin-mediated swelling of deep subcutaneous tissues (ACEI)	Stop ACEI immediately; ARB with caution or use alternative class
Hyperkalaemia	ACEI/ARB/MRA → ↓ aldosterone → ↓ K⁺ excretion	Monitor K⁺; avoid combination of ACEI + ARB + MRA; dietary counselling
AKI from ACEI/ARB	Efferent arteriolar dilation → ↓ GFR, especially in bilateral RAS or hypovolaemia	Check RFT 1–2 weeks after initiation ^[13]; > 30% Cr rise → stop and investigate for RAS
Metabolic disturbance from thiazides	HypoK, hypoNa, hyperuricaemia, hyperglycaemia, hypercalcaemia	Monitor electrolytes; avoid in gout; caution in metabolic syndrome
Watershed ischaemia from rapid BP lowering	In chronic HTN, autoregulatory curves are shifted right → organs require higher perfusion pressure. If BP dropped too fast → ischaemia of watershed territories (brain, gut, kidney)	In emergencies: reduce BP by only 25% in first hour, then gradually to 160/110 over next 2–6h, then to normal over 24–48h ^[11]. "Acute stroke — contraindicated, since the rapid reduction in BP will cause loss of cerebral autoregulation" ^[2]

Clinical Pearl — The Danger of Too-Rapid BP Reduction

In a patient with longstanding uncontrolled HTN (e.g. SBP 220 for months), the cerebral autoregulatory curve has shifted rightward — the brain needs an MAP of perhaps 120–140 mmHg to maintain adequate perfusion. If you drop their BP to "normal" (MAP ~90) within minutes, you will create watershed cerebral infarction. This is why the 25% rule exists — reduce gradually.

Many complications of hypertension feed back to worsen the hypertension itself, creating self-perpetuating cycles:

HTN → CKD → ↓ Na⁺ excretion → volume expansion → worse HTN (the renal cycle)
HTN → LVH → diastolic dysfunction → ↑ LA pressure → AF → ↑ stroke risk + ↑ HF (the cardiac cycle)
HTN → atherosclerosis → renal artery stenosis → ↑ renin → worse HTN (the vascular cycle)
HTN → arterial stiffness → ↑ pulse pressure → endothelial damage → more atherosclerosis → worse HTN (the stiffness cycle)

This is why early identification and treatment of HTN is critical — breaking these cycles before they become self-sustaining.

"Risk factors for poor prognosis: young males of black race, persistent diastolic pressure > 115 mmHg, DM, obesity, hypercholesterolaemia, smoking, alcoholism" ^[10]

"Prognosis mainly dependent on: concomitant CVS risk factors (esp DM — several × risk of CVD and CKD in HTN+DM patient), target organ damage" ^[11]

The three most common comorbidities of hypertension are: obesity, diabetes, and hyperlipidaemia — "they come like a bundle deal" ^[2]. This cluster (metabolic syndrome) dramatically amplifies CV risk beyond what any single condition would produce alone.

Malignant HTN: historically had "25–50% 5-year mortality" when untreated ^[11], comparable to many cancers (hence the name "malignant"). With modern treatment, outcomes have improved dramatically, but it remains a medical emergency.

High Yield Summary — Complications of Hypertension

Cardiovascular: LVH → diastolic dysfunction → HFpEF → HFrEF; IHD (coronary atherosclerosis); AF (from LA dilatation); aortic aneurysm/dissection
Cerebrovascular: ischaemic stroke (atherosclerosis, lacunar infarcts); ICH (Charcot-Bouchard microaneurysm rupture — basal ganglia, pons, cerebellum); hypertensive encephalopathy (forced vasodilation → cerebral oedema); vascular dementia
Renal: hypertensive nephrosclerosis (benign = hyaline arteriosclerosis; malignant = fibrinoid necrosis); CKD → ESRD; HTN is the 2nd most common cause of CKD in HK
Ophthalmological: hypertensive retinopathy (KWB Grades 1–4); retinal vein/artery occlusion; retinal arterial macroaneurysm; optic nerve atrophy
Vascular: PAD, carotid artery disease; aortic aneurysm/dissection
Crisis complications: encephalopathy, APO, ACS, aortic dissection, AKI, MAHA, eclampsia, ICH
Treatment complications: rebound HTN (abrupt BB/clonidine withdrawal), ACEI cough/angioedema, hyperkalaemia (ACEI/ARB/MRA), watershed infarction from rapid BP lowering
Vicious cycles amplify damage: HTN → CKD → worse HTN; HTN → LVH → AF → stroke; HTN → atherosclerosis → RAS → worse HTN

Active Recall - Complications of Hypertension

References

^[1] Lecture slides: GC 058. High Blood Pressure.pdf (end organ damage list, risk factors for adverse prognosis, malignant HTN definition with MAHA) ^[2] Senior notes: Block A - High blood pressure_ hypertension.pdf (comorbidities of HTN, DM+HTN risk multiplication, hypertensive crisis indications, acute stroke BP contraindication, malignant HTN complications) ^[4] Senior notes: Block A - Clinical Pharmacology of anti-HT and anti-HF medications.pdf (rebound hypertension, first-dose phenomenon, HMOD markers) ^[10] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.335–337 — pathological changes: LVH, vessel damage, stroke, nephrosclerosis; complications list; KWB retinopathy grading; prognosis risk factors; malignant HTN definition) ^[11] Senior notes: Ryan Ho Cardiology.pdf (p.179, 182 — hypertensive encephalopathy mechanism and features, TOD pathology table including CRVO, malignant HTN definition and mortality, BP reduction targets in emergency) ^[13] Senior notes: Block A - Chronic Kidney Disease and its Complications.pdf (HTN as 2nd most common cause of CKD in HK, mild CKD and CV death risk, CKD complications including HTN, monitoring of ACEI/ARB) ^[28] Senior notes: Block A - Shortness of breath on exertion_ heart failure.pdf (HFpEF prevalence in HK, HFpEF management principles) ^[31] Senior notes: Block A - Leg swelling and chest pain_ deep vein thrombosis; pulmonary embolism; Thrombophilia.pdf (HTN as risk factor for arterial thrombosis) ^[32] Senior notes: Block A - Three Cases of Dyspnea.pdf (AF from pulmonary vein micro-electrical re-entry in mitral disease and LA dilatation) ^[33] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (p.903–907 — aortic dissection etiology with HTN as most important RF, pathogenesis, Type A/B complications) ^[34] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p.41 — haemorrhagic stroke mostly related to HTN, common sites) ^[35] Lecture slides: CFB (OPHTH02) Ocular Manifestations of Systemic Disease.pdf (hypertensive retinopathy as grading system, retinal vein occlusion) ^[36] Senior notes: Ryan Ho Opthalmology.pdf (p.73 — Modified Scheie and KWB classification, retinal vascular complications: CRAO/BRVO, macroaneurysms, optic nerve atrophy)

High Yield Summary

HTN = BP ≥ 140/90 mmHg (office) in most guidelines; treatment threshold may be lower (≥ 130/80) for high-risk patients
BP = CO × TPR — all causes and treatments work through this equation
95% essential, 5% secondary — the secondary causes (renal, endocrine, OSA, CoA, drugs) are treatable/curable and must be actively sought
Secondary HTN clues: onset < 35 or > 55, resistant HTN, sudden worsening, specific symptoms (paroxysmal triad for phaeochromocytoma, snoring for OSA, Cushingoid features, radio-femoral delay for CoA)
Target organ damage determines prognosis — Heart (LVH → HF), Brain (stroke), Kidney (nephrosclerosis → CKD), Eyes (retinopathy), Arteries (atherosclerosis, dissection)
Hypertensive retinopathy grading (Scheie/KWB): Grade 1 = narrowing, Grade 2 = AV nicking, Grade 3 = haemorrhages + exudates + cotton-wool spots, Grade 4 = papilloedema
Hypertensive emergency vs urgency: NOT about the number — it's about the presence of acute target organ damage. Emergency → IV drugs, reduce BP 20–25% in 1 hour. Urgency → oral drugs, reduce over 24–48h.
ACEI/ARB contraindicated in bilateral renal artery stenosis — blocks the AngII-mediated efferent arteriolar vasoconstriction that maintains GFR
Initial workup: urinalysis, RFT, electrolytes (K⁺, Ca²⁺), glucose, lipids, uric acid, TSH, ECG, CXR, fundoscopy
Adverse prognostic factors (Harrison's per GC slide): Black race, youth, male, DBP > 115, smoking, DM, hypercholesterolaemia, obesity, excess alcohol, + evidence of TOD

High Yield Summary — Differential Diagnosis of Hypertension

Always confirm genuine HTN first — exclude white-coat HTN (HBPM/ABPM), pseudohypertension (Osler's manoeuvre), measurement error, and transient causes.
Essential HTN accounts for ~95% — a diagnosis of exclusion; polygenic + environmental.
Secondary HTN (~5%) is critical to identify because it is potentially curable — the ABCDE mnemonic (Accuracy/Apnoea, Bruit/Bad kidney, Catecholamine/Cushing's/Coarctation, Drug-induced/Diet, Endocrine/Erythropoietin) covers the key causes.
Most common secondary causes: renal parenchymal disease (overall), primary hyperaldosteronism (endocrine), OSA (in resistant HTN).
Red flags: onset < 35 or > 55, resistant HTN, sudden worsening, malignant HTN, hypoK, ↑ Cr on ACEI/ARB, specific clinical clues.
Know the mechanism for each secondary cause — they all work through ↑ CO, ↑ TPR, or both (volume expansion via Na⁺ retention, RAAS activation, sympathetic overactivity, or vasoconstriction).
Drug-induced HTN is common and under-recognised — NSAIDs, steroids, OCP, sympathomimetics, immunosuppressants, liquorice, cocaine.

High Yield Summary — Diagnosis of Hypertension

HTN diagnosis requires repeated elevated BP readings — office BP ≥ 140/90 (ESC) or ≥ 130/80 (ACC/AHA); confirm with HBPM/ABPM unless crisis or overt TOD
Out-of-office thresholds are lower (ABPM 24h ≥ 130/80, daytime ≥ 135/85, night ≥ 120/70; HBPM ≥ 135/85) because the white-coat effect is removed
Three immediate diagnosis pathways: crisis ( > 180/120), TOD + BP ≥ 160/100, or confirmed by HBPM/ABPM
Correct measurement technique is essential — wrong cuff, unsupported arm, uncrossed legs, recent caffeine all introduce error
Baseline investigations for ALL hypertensives: urinalysis, RFT, K⁺, Ca²⁺, glucose/HbA1c, lipids, uric acid, TSH, FBC, ECG, CXR, fundoscopy
Secondary HTN workup: biochemistry BEFORE imaging (endocrine principle); ARR for hyperaldosteronism, ONDST for Cushing, 24h urine metanephrines for phaeo, Doppler/CTA for RAS, PSG for OSA
Stop interfering drugs ≥ 2 weeks (MRA ≥ 6 weeks) before ARR testing — α-blockers and slow-release verapamil are safe alternatives for BP control during washout
Never biopsy a phaeochromocytoma — risk of catecholamine storm

High Yield Summary — Management of Hypertension

Lifestyle modifications for ALL — DASH diet, ↓ Na⁺, exercise, weight loss, alcohol moderation, smoking cessation
Step-wise pharmacotherapy: Step 1: A or C or D → Step 2: A+C or A+D → Step 3: A+C+D → Step 4: add spironolactone (resistant HTN)
Beta-blockers are second-line for uncomplicated HTN but first-line when compelling indication exists (HF, post-MI, aortic dissection, AF)
Match drug to comorbidity — DM/CKD → ACEI/ARB; HFrEF → 4 pillars; elderly/ISH → CCB or thiazide; pregnancy → labetalol/methyldopa/nifedipine
Never combine ACEI + ARB; ACEI/ARB contraindicated in pregnancy and bilateral RAS
Hypertensive emergency: IV drugs in ICU, ↓ BP by ≤ 25% in first hour, then gradually. Key IV agents: labetalol, nitroprusside, GTN, esmolol, hydralazine (pregnancy)
Aortic dissection: BB FIRST (↓ dP/dt), then vasodilator; target SBP < 120. Phaeochromocytoma: alpha-blocker FIRST, then BB — opposite order!
Acute stroke: do NOT acutely lower BP (unless extremely high or thrombolysis planned) — risk of watershed infarction from loss of autoregulation
Secondary HTN Rx: surgery for adenoma (Conn's, phaeo); medical for bilateral hyperplasia; CPAP for OSA; stop offending drugs

High Yield Summary — Complications of Hypertension

Cardiovascular: LVH → diastolic dysfunction → HFpEF → HFrEF; IHD (coronary atherosclerosis); AF (from LA dilatation); aortic aneurysm/dissection
Cerebrovascular: ischaemic stroke (atherosclerosis, lacunar infarcts); ICH (Charcot-Bouchard microaneurysm rupture — basal ganglia, pons, cerebellum); hypertensive encephalopathy (forced vasodilation → cerebral oedema); vascular dementia
Renal: hypertensive nephrosclerosis (benign = hyaline arteriosclerosis; malignant = fibrinoid necrosis); CKD → ESRD; HTN is the 2nd most common cause of CKD in HK
Ophthalmological: hypertensive retinopathy (KWB Grades 1–4); retinal vein/artery occlusion; retinal arterial macroaneurysm; optic nerve atrophy
Vascular: PAD, carotid artery disease; aortic aneurysm/dissection
Crisis complications: encephalopathy, APO, ACS, aortic dissection, AKI, MAHA, eclampsia, ICH
Treatment complications: rebound HTN (abrupt BB/clonidine withdrawal), ACEI cough/angioedema, hyperkalaemia (ACEI/ARB/MRA), watershed infarction from rapid BP lowering
Vicious cycles amplify damage: HTN → CKD → worse HTN; HTN → LVH → AF → stroke; HTN → atherosclerosis → RAS → worse HTN

Hypertension

1. Definition

2. Epidemiology

Global

Hong Kong–Specific Data

3. Risk Factors

3.1 Non-Modifiable Risk Factors

3.2 Modifiable Risk Factors

4. Anatomy & Physiology of Blood Pressure Regulation

4.1 The Fundamental Equation

4.2 Physiological Regulators of Blood Pressure

4.2.1 Sympathetic Nervous System (SNS)

4.2.2 Renin–Angiotensin–Aldosterone System (RAAS)

4.2.3 Renal Sodium Handling (Guyton's Pressure-Natriuresis)

4.2.4 Endothelial Factors

4.2.5 Natriuretic Peptides

4.2.6 Vasopressin (ADH)

5. Etiology

5.1 Overview

5.2 Essential (Primary) Hypertension

5.3 Secondary Hypertension

5.3.1 Renal Causes (Most Common Secondary Cause)

A. Renal Parenchymal Disease

B. Renovascular Disease (Renal Artery Stenosis)

5.3.2 Endocrine Causes

A. Primary Hyperaldosteronism (Conn Syndrome)

B. Cushing Syndrome

C. Phaeochromocytoma

D. Hyperthyroidism

E. Acromegaly

F. Hyperparathyroidism

5.3.3 Obstructive Sleep Apnoea (OSA)

5.3.4 Coarctation of the Aorta (CoA)

5.3.5 Drug-Induced HTN

5.3.6 Other Causes

5.4 Summary Table: Secondary HTN Causes with Screening

6. Classification

6.1 By Etiology

6.2 By BP Category (ESC/ESH 2023, preferred for GC exams)

6.3 By Measurement Setting

6.4 Hypertensive Crises

7. Clinical Features

7.1 Symptoms

A. Symptoms of Elevated BP

B. Symptoms of Target Organ Damage

C. Symptoms Suggesting Secondary Cause

7.2 Signs

A. Blood Pressure Measurement Findings

B. General Examination Signs

C. Fundoscopy — Hypertensive Retinopathy

D. Cardiovascular Signs

E. Vascular Signs

F. Renal Signs

G. Neurological Signs (if TOD present)

8. Hypertension-Mediated Organ Damage (HMOD) — Target Organ Damage

9. Approach to History-Taking in Hypertension

A. Confirm the Diagnosis

B. Assess for Symptoms of Elevated BP

C. Assess for Target Organ Damage

D. Screen for Secondary Causes

E. Assess CVD Risk Factors

F. Family History

10. Approach to Physical Examination in Hypertension

11. Investigations — Initial Evaluation

A. Urine

B. Bloods

C. Imaging and ECG

D. Further Investigations for Secondary Causes (if suspected)

Active Recall - Hypertension (Definition, Epidemiology, Etiology, Clinical Features)

References

1. Framework for the Differential Diagnosis

2. Tier 1 — Is the Elevated BP Genuine?

3. Tier 2 — Causes of True Sustained Hypertension

3.1 Essential (Primary) Hypertension (~95%)

3.2 Secondary Hypertension (~5%)

A. Renal Causes (Most Common Category of Secondary HTN)

B. Endocrine Causes

C. Respiratory — Obstructive Sleep Apnoea (OSA)

D. Vascular — Coarctation of the Aorta (CoA)

E. Drug-Induced Hypertension