Hypertension
Hypertension is a chronic elevation of systemic arterial blood pressure (≥130/80 mmHg) that increases the risk of cardiovascular, cerebrovascular, and renal complications.
Hypertension — Definition, Epidemiology, Risk Factors, Anatomy & Function, Etiology, Pathophysiology, Classification, and Clinical Features
Hypertension (HTN) literally breaks down as "hyper" (Greek: excessive) + "tension" (Latin: pressure/stretching) — it is the presence of abnormally elevated arterial blood pressure [1][2].
Why does it matter? HTN itself is often asymptomatic. It is only treated because of its associated risks of target organ damage (TOD) and clinical events [2]. Think of HTN as a silent, cumulative mechanical and biochemical insult to the vasculature — over years, the excessive force against arterial walls causes endothelial injury, smooth muscle hypertrophy, atherosclerosis, and end-organ ischaemia.
Core Concept
Hypertension is not a disease in itself — it is a risk factor and a haemodynamic state that, left unchecked, drives cardiovascular, cerebrovascular, and renal morbidity and mortality. The entire rationale for treatment is reducing downstream complications.
Haemodynamic Basis
Blood pressure is governed by a simple relationship:
Therefore, any process that raises CO (e.g., volume overload, sympathetic drive) or SVR (e.g., arteriolar vasoconstriction, arterial stiffness) — or both — will raise BP. Every single cause and mechanism of hypertension can be traced back to this equation.
2. Epidemiology
- ~1 billion people worldwide have hypertension [2].
- HTN is the single largest contributor to global mortality, responsible for ~10.4 million deaths/year (mostly via ischaemic heart disease and stroke) [3].
- Prevalence has been rising in low- and middle-income countries due to urbanisation, dietary shifts (processed food, high salt), and ageing populations.
- Prevalence ~20% in Hong Kong [2], though community surveys suggest up to 27–30% of adults ≥ 15 years when including undiagnosed cases [1].
- Among those with HTN in HK, roughly half are unaware of their diagnosis — reinforcing the "silent killer" concept.
- HK's ageing population, high dietary sodium intake (average ~9–10 g salt/day, well above WHO recommendation of < 5 g/day), and increasing obesity rates are driving the epidemic.
- Leading cause of cardiovascular events (stroke, MI) in HK, with stroke being the 4th leading cause of death and IHD the 3rd.
- Prevalence increases steeply with age: ~10% in 20–30 year olds, > 60% in those ≥ 60 years.
- Age: ≥45 years (male) or ≥55 years (female) is considered a CVD risk factor [1][2].
- Before menopause, women have lower prevalence than men (oestrogen has a mild vasodilatory and anti-atherogenic effect). After menopause, prevalence equalises or exceeds males.
- Isolated systolic hypertension (ISH) is the dominant pattern in the elderly (due to large artery stiffness), while younger hypertensives more often have combined systolic and diastolic elevation.
- Black race is a risk factor for adverse prognosis in hypertension [3] — higher prevalence, earlier onset, more severe TOD, and higher rates of salt-sensitive HTN.
- In the HK/Chinese population, stroke (both ischaemic and haemorrhagic) is the predominant HTN-related complication, more so than coronary artery disease (compared with Western populations).
3. Risk Factors
| Factor | Explanation |
|---|---|
| Age | Arterial wall collagen increases, elastin degrades → large artery stiffness → ↑SVR → ISH. Progressive nephron loss → impaired sodium excretion |
| Sex | Males > females before menopause (oestrogen-mediated vasodilation via NO). Post-menopausal risk equalises |
| Family history | Polygenic inheritance. Family history of HT → essential HT [1]. First-degree relative with premature CVD (men < 55 y, women < 65 y) [2] |
| Ethnicity | Black race associated with worse prognosis [3] |
These are essentially the CVD risk factors and overlap heavily with the metabolic syndrome:
| Factor | Mechanism | Notes |
|---|---|---|
| High-sodium diet | Na⁺ retention → ↑intravascular volume → ↑CO; also activates local RAAS and causes endothelial dysfunction [1] | Average HK intake ~9-10 g salt/day |
| High-calorie diet / Obesity (BMI > 30) | Visceral adipose tissue → ↑sympathetic nervous system (SNS) activity, ↑RAAS, hyperinsulinaemia → Na⁺ retention, endothelial dysfunction [1][2] | Component of metabolic syndrome [1] |
| Physical inactivity | ↓Endothelium-dependent vasodilation (↓NO), ↑sympathetic tone, ↑insulin resistance [1] | CVD risk factor [1] |
| Cigarette smoking | Acute sympathetic activation → ↑HR, ↑SVR; chronic endothelial damage → accelerated atherosclerosis [1] | Major independent CVD risk factor |
| Excess alcohol intake | Dose-dependent ↑BP via ↑SNS, ↑cortisol, direct vascular toxicity; also ↑caloric intake → obesity [3] | > 2 standard drinks/day in men |
| Dyslipidaemia | ↑LDL → endothelial dysfunction → arterial stiffness; component of metabolic syndrome [1] | |
| Diabetes mellitus | Insulin resistance → ↑SNS, ↑RAAS, ↑Na⁺ retention; hyperglycaemia → advanced glycation end-products (AGEs) → arterial stiffness [1] | Component of metabolic syndrome [1] |
| Microalbuminuria or eGFR < 60 mL/min | Indicates subclinical renal damage — both a consequence and a perpetuator of HTN [1] | |
| IUGR (intrauterine growth restriction) | "Barker hypothesis" — foetal programming leads to fewer nephrons → impaired sodium handling in adulthood [2] |
CVD Risk Factors (Lecture Slide)
CVD Risk Factors [1]:
- Hypertension
- Cigarette smoking
- Obesity (BMI > 30 kg/m²)
- Physical inactivity
- Dyslipidaemia
- Diabetes mellitus
- Microalbuminuria or estimated GFR < 60 mL/min
- Age (older than 55 for men, 65 for women)
- Family history of premature CVD (men under age 55 or women under age 65)
Components marked with * are components of the metabolic syndrome [1].
Once HTN is established, certain factors predict worse outcomes [3]:
Risk Factors for an Adverse Prognosis in Hypertension [3]:
- Black race
- Youth (younger onset → longer exposure → more cumulative TOD)
- Male sex
- Persistent diastolic pressure > 115 mmHg
- Smoking
- Diabetes mellitus
- Hypercholesterolaemia
- Obesity
- Excess alcohol intake
- Evidence of end-organ damage (cardiac enlargement, ECG ischaemia/LV strain, MI, CCF, retinal exudates/haemorrhages, papilloedema, impaired renal function, cerebrovascular accident) [3]
4. Relevant Anatomy and Physiology
To understand hypertension from first principles, you need to understand the systems that regulate BP.
- Large conduit arteries (aorta, carotids, iliacs): contain a high proportion of elastin in the tunica media → "Windkessel function" — they expand during systole to absorb kinetic energy, then recoil during diastole to maintain flow. This is why diastolic pressure exists at all.
- With ageing: large conduit arteries become less compliant [1] — elastin fragments, collagen is deposited, medial calcification occurs → ↑pulse wave velocity → ↑systolic BP, ↓diastolic BP → widened pulse pressure → isolated systolic hypertension.
- Small resistance arterioles: the major determinant of SVR. Their tone is regulated by:
- Sympathetic nervous system (α₁ receptors → vasoconstriction)
- RAAS (angiotensin II → vasoconstriction)
- Endothelium-derived factors (NO → vasodilation; endothelin-1 → vasoconstriction)
- Local metabolites (adenosine, K⁺, CO₂)
The kidney is the long-term regulator of BP via control of sodium and water balance — this is the "pressure natriuresis" concept:
- When BP rises → renal perfusion pressure rises → kidney excretes more Na⁺ and water → blood volume decreases → BP normalises.
- Abnormal pressure natriuresis and sodium retention is a central defect in essential HTN [1] — the curve is "reset" rightward, so a higher BP is needed to achieve the same level of sodium excretion.
- Intrinsic renal factors (genetic and prenatal) regulate sodium excretion [1].
- Baroreceptors (carotid sinus and aortic arch) sense arterial stretch → signal via CN IX and X to the nucleus tractus solitarius in the medulla → modulate sympathetic outflow.
- Increased sympathetic nervous system activity is a key early feature in essential HTN [1] — this drives ↑HR, ↑contractility (↑CO), renal Na⁺ retention, and arteriolar vasoconstriction (↑SVR).
- The SNS also stimulates renin release from the juxtaglomerular apparatus (via β₁ receptors).
This is the dominant neurohormonal axis in BP regulation:
- Renin released from juxtaglomerular cells (stimulated by ↓renal perfusion, ↓Na⁺ at macula densa, ↑sympathetic β₁ stimulation) [4]
- Renin cleaves angiotensinogen (from liver) → Angiotensin I
- ACE (in pulmonary endothelium) converts Ang I → Angiotensin II
- Angiotensin II effects:
- Potent arteriolar vasoconstriction (↑SVR)
- Stimulates aldosterone secretion from zona glomerulosa → Na⁺/K⁺ ATPase at distal tubule → Na⁺ retention, K⁺ secretion, H⁺ secretion [4]
- Stimulates ADH release → water retention
- Stimulates thirst
- Promotes vascular smooth muscle hypertrophy and fibrosis
- High sodium level activates local angiotensin II in heart and arteries [1] — this is the tissue RAAS, which contributes to cardiac and vascular remodelling independent of circulating levels.
- Healthy endothelium produces nitric oxide (NO) via endothelial NO synthase (eNOS) → vasodilation, anti-platelet, anti-inflammatory, anti-proliferative.
- Endothelial-cell dysfunction in small resistance vessels is both a cause and a consequence of HTN [1] — ↓NO bioavailability, ↑endothelin-1, ↑reactive oxygen species → sustained vasoconstriction and vascular remodelling.
- Natriuretic peptides (ANP from atria, BNP from ventricles): released in response to myocardial stretch → vasodilation, natriuresis, inhibit RAAS → serve as a counter-regulatory "brake" on BP.
- Prostaglandins (PGI₂, PGE₂): vasodilatory prostaglandins in the kidney promote natriuresis — this is why NSAIDs (which inhibit COX) can raise BP.
- Dopamine: low-dose dopamine promotes renal vasodilation and natriuresis.
5. Etiology (with Focus on Hong Kong)
5.1 Essential (Primary) Hypertension — 95%
Essential hypertension accounts for ~95% of cases [2]. "Essential" is a historical misnomer (once thought to be "essential" for organ perfusion); it really means idiopathic/primary — no single identifiable cause, but rather a complex interplay of genetic susceptibility and environmental factors.
- Polygenic inheritance — genome-wide association studies have identified > 1000 loci, each with small effect sizes.
- Monogenic forms are rare but instructive (e.g., Liddle syndrome — gain-of-function ENaC mutation → constitutive Na⁺ reabsorption; glucocorticoid-remediable aldosteronism).
- Genetics plays a significant role [1][2] — family history of HTN is one of the strongest risk factors.
The lecture slide [1] provides an excellent integrated diagram of the pathogenesis. Let me walk through it systematically:
Pathogenesis of Essential Hypertension (from NEJM 2010, Sacks FM et al.) [1]:
- Increased sympathetic nervous system activity → ↑CO and ↑SVR
- Intrinsic renal factors (genetic and prenatal) regulate sodium excretion → abnormal pressure natriuresis → Na⁺ retention
- High sodium level activates local angiotensin II in heart and arteries → cardiac and vascular remodelling
- Increased tissue angiotensin II in kidneys and adrenal glands → Na⁺ retention, vasoconstriction
- Large conduit arteries become less compliant → ↑systolic BP, widened pulse pressure
- Smooth-muscle cell proliferation and rearrangement → arteriolar wall thickening → ↑SVR
- Endothelial-cell dysfunction in small resistance vessels → impaired vasodilation → ↑peripheral resistance
- Abnormal pressure natriuresis and sodium retention — the kidney cannot excrete Na⁺ adequately at normal BP
- Abdominal fat further increases conduit artery stiffness, sympathetic nervous system activity, and angiotensin II levels [1] — this is why obesity is such a potent driver
- Result: Increased cardiac output + Increased peripheral resistance → Increased blood pressure [1]
The key conceptual framework:
Age-dependent mechanism [2]:
- Young patients: predominantly ↑SNS and ↑RAAS activities → ↑SVR, ↑CO
- Elderly patients: predominantly arterial degeneration → ↑SVR
This is why younger hypertensives often have a hyperdynamic circulation (↑HR, ↑CO) and respond well to beta-blockers, whereas elderly patients have stiff arteries with wide pulse pressures and respond better to CCBs and diuretics.
Secondary hypertension: distinct, identifiable cause [2]. The mnemonic from the senior notes is DANCER [2]:
| Letter | Category | Specific Causes | Mechanism |
|---|---|---|---|
| D | Drugs | SNS-related: caffeine, amphetamines, levodopa, MAOI, antidepressants, decongestants [2] | ↑Sympathetic tone → ↑CO, ↑SVR |
| Fluid retention: OCP, anabolic steroids, mineralocorticoids, corticosteroids [2] | Na⁺/H₂O retention → ↑volume | ||
| Immunosuppressants (cyclosporine) [2] | Renal vasoconstriction, ↑endothelin | ||
| NSAIDs, COX-2 inhibitors [2] | Inhibit renal vasodilatory prostaglandins → Na⁺ retention + renal vasoconstriction | ||
| Alcohol, nicotine [2] | ↑SNS, direct vasotoxicity | ||
| Anti-cancer: chemotherapy, angiogenesis inhibitors, TKIs [2] | ↓VEGF → ↓NO → endothelial dysfunction | ||
| A | Apnoea | Obstructive sleep apnoea (OSA) | Intermittent hypoxia → ↑SNS, ↑endothelin, ↑oxidative stress → sustained ↑SVR even during daytime |
| N | Neurological | ↑ICP, stress, others [2] | Cushing reflex (↑ICP → ↑SNS → ↑BP to maintain CPP); chronic stress → sustained ↑SNS |
| C | Coarctation of aorta | Congenital narrowing of aorta (usually just distal to left subclavian) | Mechanical obstruction → ↑BP proximal to coarctation, ↓BP distal; also ↑RAAS (renal hypoperfusion) |
| E | Endocrine | Thyroid: hyperthyroidism, hypothyroidism [2] | Hyperthyroid → ↑CO (↑HR, ↑contractility) → systolic HTN. Hypothyroid → ↑SVR → diastolic HTN [2] |
| Adrenals: Cushing's, Conn's, phaeochromocytoma [2] | Cushing's: cortisol excess → mineralocorticoid activity + ↑SNS. Conn's: aldosterone → Na⁺ retention. Phaeochromocytoma: catecholamine excess | ||
| Parathyroid: hyperparathyroidism [2] | Hypercalcaemia → vasoconstriction, ↑vascular reactivity | ||
| Others: pre-eclampsia, acromegaly [2] | Pre-eclampsia: placental ischaemia → anti-angiogenic factors → endothelial dysfunction. Acromegaly: GH excess → ↑Na⁺ retention, ↑SVR | ||
| R | Renal | Renal vascular: renal artery stenosis (RAS) [2] | ↓Renal perfusion → ↑renin → ↑RAAS |
| Renal parenchymal: GN, polycystic kidney, kidney failure [2] | ↓Nephron mass → impaired Na⁺ excretion → volume overload; also ↑RAAS |
Indications to Look for Secondary HTN
Indications to look for causes of secondary HTN (ACC/AHA 2017) [2]:
General:
- Age of onset: < 30 y or diastolic HTN for ≥ 65 y
- Severity: accelerated or malignant HTN, disproportionate TOD for degree of HTN
- Course: abrupt onset, drug-resistant or exacerbation of previously controlled HTN
Specific:
- Unprovoked or excessive hypokalaemia (but note thiazide use!)
- Renal HTN: palpable kidney, renal bruit, abnormal urinalysis
- Endocrine: S/S of phaeochromocytoma, unexplained hypokalaemia, signs of Cushing's syndrome
- Coarctation: radiofemoral delay
Key Secondary Causes — Elaboration on Pathophysiology
Phaeochromocytoma (from senior notes [5]):
- Catecholamine-secreting tumour from chromaffin cells of adrenal medulla.
- 5 P's: Pressure (HT), Pain (headache/chest), Palpitation, Perspiration, Pallor (vasoconstriction) [5]
- Classic triad: paroxysmal headache, sweating, palpitations [5]
- 10% rule: 10% familial, 10% bilateral, 10% extra-adrenal, 10% malignant, 10% secrete adrenaline/dopamine (c.f. 90% noradrenaline), 10% children, 10% not associated with HT, 10% recurrence [5]
- Young-onset paroxysmal HT + postural hypotension (because adrenaline at moderate levels causes β₂-mediated vasodilation → orthostatic drop) [5]
Conn's Syndrome (Primary Hyperaldosteronism) [4][5]:
- ↓Renin, ↑aldosterone (negative feedback on renin from volume expansion)
- Aldosterone-producing adenoma (30-40%) vs. bilateral idiopathic adrenal hyperplasia (60-70%) [4]
- Clinical: HTN + hypokalaemia + metabolic alkalosis (aldosterone → ↑Na⁺ reabsorption, ↑K⁺ secretion → ↑H⁺ secretion via K⁺/H⁺ exchanger) [4]
Renal Artery Stenosis:
- Causes: atherosclerosis (older males, ostial lesion) vs. fibromuscular dysplasia (young females, mid-vessel "string of beads")
- ↓Renal perfusion → JG cells sense ↓pressure → ↑renin → ↑Ang II → ↑aldosterone → ↑BP
- Clue: flash pulmonary oedema, ↑creatinine with ACEI/ARB initiation, renal bruit
6. Classification
Definition of HTN (ACC/AHA 2017) [2]:
| Category | SBP (mmHg) | DBP (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 | and/or | > 120 |
Note: The ACC/AHA 2017 guidelines lowered the threshold for Stage 1 HTN to 130/80, which is more aggressive than the previous JNC 8 (140/90) or the ESC/ESH 2018 guidelines (which still define HTN as ≥ 140/90 but acknowledge 130/80 as "high-normal"). In HK clinical practice, many clinicians still use 140/90 as the treatment threshold for uncomplicated patients, and 130/80 for high-risk groups (DM, CKD, established CVD). Know both for exams.
The thresholds differ depending on how BP is measured [2]:
| Measurement | HTN Threshold |
|---|---|
| Office BP | ≥ 140/90 (or ≥ 130/80 by ACC/AHA) |
| HBPM (Home) | ≥ 135/85 |
| ABPM — Daytime mean | ≥ 135/85 |
| ABPM — Night-time mean | ≥ 120/70 |
| ABPM — 24-hour mean | ≥ 130/80 |
Why are out-of-office thresholds lower? Because office BP is subject to the alerting response and tends to be higher than "true" resting BP.
White-coat hypertension [2]:
- ↑Office BP but normal ABPM/HBPM
- Prevalence: 15–30%, especially elderly and pregnant
- ↑Risk < that of sustained HTN → reassurance
- ?Precursor to HTN → offer follow-up and monitoring
Masked hypertension [2]:
- Normal office BP but ↑ABPM/HBPM
- ↑Risk > patients with known but uncontrolled HTN — this is particularly dangerous because it goes undetected. Common in smokers, heavy alcohol users, high workplace stress, and OSA.
| Category | Definition |
|---|---|
| Malignant hypertension | BP ≥ 220/120 + Grade 3–4 fundal changes (flame haemorrhages, cotton-wool spots, papilloedema) [2] |
| Hypertensive emergency | BP > 180/120 + worsening/new TOD (e.g., ICH, APO, HTN encephalopathy, aortic dissection) [2] |
| Hypertensive urgency | Severe ↑BP without new/worsening TOD [2] |
- SBP ≥ 140 with DBP < 90
- Predominant form in elderly (> 60 years) — due to large artery stiffness [1]
- Associated with widened pulse pressure — an independent predictor of cardiovascular events
7. Clinical Features
Hypertensive patients may present with [2]:
- Asymptomatic (incidental finding) — most common presentation
- Symptoms of ↑BP itself
- Symptoms of HTN vascular disease (target organ damage)
- Symptoms/signs of a secondary cause
7.1 Symptoms
Most patients are asymptomatic. When symptoms do occur:
| Symptom | Pathophysiological Basis |
|---|---|
| Headache | Severe ↑BP → ↑intracranial pressure from impaired cerebral autoregulation; also ↑pulsatile stretch of meningeal vessels activating nociceptors. Classically occipital, worse in the morning (BP tends to peak in early morning), improves as the day goes on |
| Dizziness | ↑BP → impaired cerebrovascular autoregulation → cerebral hyperperfusion or relative ischaemia in watershed zones |
| Palpitations | ↑Sympathetic drive (in early/essential HTN) → ↑HR; also LVH → arrhythmias (esp. AF) |
| Easy fatigability | ↑Afterload → ↑myocardial O₂ demand → reduced exercise tolerance; also impaired peripheral perfusion from ↑SVR |
| Impotence / Erectile dysfunction | Endothelial dysfunction in penile vasculature → impaired NO-mediated vasodilation → poor corpus cavernosum filling |
| Symptom | Target Organ | Pathophysiological Basis |
|---|---|---|
| Epistaxis | Vascular | ↑Pressure in nasal mucosal arterioles (Kiesselbach's plexus) → vessel rupture. Often an early presenting feature in HK |
| Haematuria | Renal | Hypertensive nephrosclerosis → glomerular capillary damage → RBC leak into urine |
| Blurring of vision | Retina | Hypertensive retinopathy → arteriolar narrowing, cotton-wool spots (retinal ischaemia), macular oedema, papilloedema |
| Episodes of weakness/dizziness | CNS | TIA/stroke from hypertensive vascular disease — lipohyalinosis of perforating arteries → lacunar infarcts; or ↑risk of atherothrombotic/embolic stroke |
| Angina / Chest pain | Heart | LVH → ↑myocardial O₂ demand + coronary microvascular disease → supply-demand mismatch. Also accelerated coronary atherosclerosis |
| Dyspnoea | Heart | LVH → diastolic dysfunction (stiff, non-compliant LV) → ↑LV filling pressures → pulmonary congestion → dyspnoea. If progresses → systolic dysfunction (HFrEF) → overt heart failure |
| Nocturia | Renal | Impaired renal concentrating ability from chronic hypertensive nephropathy; also at night, recumbent position → ↑venous return → ↑renal perfusion → ↑urine output |
| Symptom | Suspected Cause |
|---|---|
| Paroxysmal headache, sweating, palpitations, pallor | Phaeochromocytoma [5] |
| Muscle weakness, polyuria, polydipsia | Conn's syndrome (hypokalaemia) |
| Weight gain, striae, easy bruising | Cushing's syndrome |
| Loud snoring, daytime somnolence, morning headache | OSA |
| Heat intolerance, tremor, weight loss, diarrhoea | Hyperthyroidism |
7.2 Signs
Physical examination [2]:
- BP/Pulse: bilateral arms, supine and standing
- Why bilateral? To detect coarctation of aorta (inter-arm difference > 20/10 mmHg) or subclavian stenosis.
- Why supine and standing? To detect orthostatic hypotension (common in elderly, diabetics, and autonomic neuropathy; also suggests phaeochromocytoma if paroxysmal HTN + postural drop).
| Sign | What It Tells You | Mechanism |
|---|---|---|
| BMI and waist circumference [2] | Obesity — major modifiable risk factor; central obesity particularly correlates with metabolic syndrome | Visceral fat → ↑SNS, ↑RAAS, ↑insulin resistance |
| Cushingoid features (moon face, truncal obesity, striae, buffalo hump) | Cushing's syndrome | Cortisol excess → glucocorticoid + mineralocorticoid effects |
| Café-au-lait spots, neurofibromas | NF1 — associated with phaeochromocytoma | Familial phaeochromocytoma syndromes |
| Sign | Significance | Mechanism |
|---|---|---|
| Palpation/auscultation of all peripheral arteries [2] | Screen for PVD (absent pulses, bruits); renal bruit (renal artery stenosis) | Atherosclerosis accelerated by chronic HTN |
| Displaced, sustained, heaving apex beat | Left ventricular hypertrophy (LVH) — the heart hypertrophies concentrically to normalise wall stress (Laplace's law: Wall stress = Pressure × Radius / 2 × Wall thickness) | Chronic pressure overload → concentric hypertrophy |
| Loud A₂ (aortic component of S2) | ↑Aortic diastolic pressure → forceful aortic valve closure | ↑Afterload |
| S4 gallop (atrial gallop) | Stiff, non-compliant LV from hypertrophy → atrial contraction into a stiff ventricle produces audible S4 | Diastolic dysfunction |
| Radiofemoral delay | Coarctation of aorta [2] | Blood reaches femoral arteries via collaterals → delayed pulse |
| Abdominal bruit (epigastric, renal angles) | Renal artery stenosis | Turbulent flow through stenosed renal artery |
| Radio-radial delay or inter-arm BP difference | Coarctation, subclavian stenosis | Unilateral obstruction to upper limb flow |
Fundoscopy is a critical bedside examination — the retina is the only place you can directly visualise arterioles:
| Grade | Finding | Pathophysiology |
|---|---|---|
| Grade 1 | Arteriolar narrowing (silver/copper wiring) | Chronic ↑intraluminal pressure → arteriolar smooth muscle hypertrophy → narrowed lumen. "Silver wiring" = fibrotic wall reflecting more light |
| Grade 2 | AV nipping (arteriovenous crossing changes) | Thickened arteriole compresses the underlying venule at crossing points |
| Grade 3 | Retinal haemorrhages and exudates [3] | Flame haemorrhages: rupture of retinal arterioles. Hard exudates: lipid and protein leakage from damaged capillaries. Cotton-wool spots: retinal nerve fibre layer micro-infarcts (ischaemia) |
| Grade 4 | Papilloedema [3] | Severe ↑BP → impaired optic nerve head perfusion + ↑intracranial pressure → optic disc swelling. Defines malignant hypertension |
Malignant hypertension is defined as BP ≥ 220/120 + Grade 3–4 fundal changes [2]. This represents a vicious cycle: severe HTN → fibrinoid necrosis of arterioles → renal ischaemia → ↑renin → further ↑BP → more vascular damage.
| Sign | Organ | Significance |
|---|---|---|
| Pulmonary crepitations, elevated JVP, peripheral oedema | Heart | Hypertensive heart failure (initially diastolic, then systolic dysfunction) |
| Palpable kidney [2] | Renal | Polycystic kidney disease → renal cause of HTN |
| Enlarged thyroid, tremor, lid lag, tachycardia | Endocrine | Hyperthyroidism → ↑CO → systolic HTN |
Evidence of end-organ damage [3]:
| Target Organ | Manifestation | Why? |
|---|---|---|
| Heart | Cardiac enlargement (LVH), ECG ischaemia/LV strain, MI, CHF [3] | Pressure overload → LVH → diastolic dysfunction → heart failure. Accelerated atherosclerosis → coronary events |
| Eyes | Retinal exudates, haemorrhages, papilloedema [3] | Arteriolar damage → leakage and ischaemia; severe: optic nerve head oedema |
| Kidneys | Impaired renal function [3], proteinuria, ↑creatinine | Hypertensive nephrosclerosis: afferent arteriolar hyalinosis → glomerular ischaemia → nephron loss → CKD |
| Brain/CNS | Cerebrovascular accident [3] | Haemorrhagic stroke (rupture of Charcot-Bouchard microaneurysms in perforating arteries); ischaemic stroke (accelerated atherosclerosis, lacunar infarcts) |
| Peripheral arteries | PAD, aortic aneurysm/dissection | Atherosclerosis + medial degeneration → aneurysm formation |
Target Organ Damage — What to Assess
Cardiac: ECG (LVH, ischaemia), Echocardiography (LV mass, EF, diastolic function)
Eyes: Fundoscopy (Keith-Wagener-Barker grading)
Renal: RFT (creatinine, eGFR), urinalysis (haematuria, UACR for albuminuria) [2]
Cerebrovascular: Clinical history (TIA/stroke), CT/MRI brain if indicated
Peripheral vascular: Peripheral pulse examination, ABI
8. Investigations at Initial Evaluation
Routine initial evaluation [2]:
- Age: consider secondary HTN < 35 y or > 55 y [1][2]
- Duration of HTN and previous BP levels [1]
- Family history of HT: essential HT [1]
- Other risk factors: cigarette smoking, diabetes mellitus, lipid disorders, family history of early CVD deaths [1]
- Lifestyle: diet, physical activity, family status, work [1]
- Blood [2]:
- RFT and electrolytes: baseline renal function, r/o renal parenchymal disease, hyperaldosteronism and hyperparathyroidism. Why? Hypercalcaemia can be a secondary cause of hypertension [2]
- Lipid profile for dyslipidaemia
- Serum fasting glucose: r/o DM
- ± Serum urate: baseline and look for hyperuricaemia (associated with CVD risk; also relevant if considering thiazide diuretics)
- ± Urinalysis: haematuria (r/o renal disease), UACR (albuminuria) [2]
- ECG: LVH, MI, cardiac failure, heart block [2]
- ± Echocardiogram: for LVH (more sensitive than ECG) [2]
- Calculation of 10-year CVD risk [2]
Consequences: leads to target organ damage (TOD) → clinical events → death [2]
The natural history of untreated hypertension:
Malignant hypertension [2]: rare but lethal — < 1% of HTN population, 25–50% 5-year mortality without treatment.
- Mechanism: accelerated microvascular damage including fibrinoid necrosis in small vessel walls and intravascular thrombosis [2].
- Clinical presentation: ↑BP + rapidly progressive TOD [2]:
- Retina: papilloedema, retinal haemorrhages and exudates
- HTN encephalopathy: severe headache, vomiting, visual disturbances, transient paralyses, convulsions, stupor and coma
- Heart: acute LV failure
- Kidneys: acute RF with oliguria, proteinuria
Many HTN patients do not exist in isolation — they cluster with other metabolic derangements. This is the metabolic syndrome:
Metabolic syndrome [4][6]: a cluster of metabolic disorders driven by insulin resistance (often from central obesity):
- Hypertension
- Dyslipidaemia (↑LDL-C, ↑TG, ↓HDL-C)
- Type 2 DM
- PCOS
- NAFLD
Why does insulin resistance cause HTN?
- Hyperinsulinaemia → ↑renal Na⁺ reabsorption (insulin stimulates ENaC and Na⁺/K⁺-ATPase in collecting duct)
- Hyperinsulinaemia → ↑SNS activity
- Insulin normally causes vasodilation via NO → insulin resistance → ↓NO → endothelial dysfunction
- Adipocytes release large amounts of FFA → insulin resistance; adipocytes release adipokines → insulin resistance [6]
- Abdominal fat further increases conduit artery stiffness, sympathetic nervous system activity, and angiotensin II levels [1]
High Yield Summary
Definition: HTN = abnormally ↑BP. Treated because of TOD risk, not symptoms.
Epidemiology: ~1 billion worldwide; ~20% prevalence in HK. Most common cause of CVD globally. Stroke is the predominant complication in Chinese populations.
BP = CO × SVR — every cause of HTN acts through one or both.
Essential HTN (95%): Polygenic + environmental (salt, obesity, alcohol, sedentary). Pathogenesis: ↑SNS + abnormal renal Na⁺ handling + ↑RAAS + endothelial dysfunction + arterial stiffness. Young = ↑SNS/RAAS; Elderly = arterial degeneration.
Secondary HTN (5%): DANCER — Drugs, Apnoea, Neurological, Coarctation, Endocrine, Renal. Suspect if < 30 y onset, resistant HTN, abrupt onset, hypokalaemia, or specific clinical clues.
Classification: ACC/AHA 2017: Stage 1 ≥ 130/80, Stage 2 ≥ 140/90, Crisis > 180/120. White-coat HTN: ↑office, normal ABPM. Masked HTN: normal office, ↑ABPM (higher risk!).
Clinical Features: Usually asymptomatic. Symptoms when present: headache (occipital, morning), dizziness, palpitations, fatigue. TOD symptoms: epistaxis, visual changes, angina, dyspnoea, stroke symptoms. Signs: displaced apex (LVH), S4, loud A₂, fundoscopic changes (KWB grading), renal bruit.
Target Organ Damage: Heart (LVH → HF), Brain (stroke), Kidneys (nephrosclerosis → CKD), Eyes (retinopathy), Peripheral arteries (PAD, aneurysm).
Malignant HTN: BP ≥ 220/120 + Grade 3–4 fundoscopy. Fibrinoid necrosis. Lethal without treatment.
Metabolic Syndrome: Central obesity → insulin resistance → HTN + dyslipidaemia + DM + NAFLD + PCOS.
Active Recall - Hypertension: Definition, Epidemiology, Risk Factors, Etiology, Pathophysiology, Classification, and Clinical Features
[1] Lecture slides: GC 058. High Blood Pressure.pdf (p9, p29, p30, p49, p50) [2] Senior notes: Ryan Ho Cardiology.pdf (p175–182) [3] Lecture slides: GC 058. High Blood Pressure.pdf (p49 — Harrison's 2005 Risk Factors for Adverse Prognosis) [4] Senior notes: Ryan Ho Endocrine.pdf (p57 — Mineralocorticoid Disorders) [5] Senior notes: maxim.md (Phaeochromocytoma section) [6] Senior notes: Ryan Ho Endocrine.pdf (p77, p117 — T2DM, Metabolic Syndrome, Obesity)
Differential Diagnosis of Hypertension
When you encounter a patient with elevated blood pressure, the clinical question is never simply "does this patient have hypertension?" — it is a multi-layered diagnostic challenge:
- Is the BP truly elevated? (Rule out pseudohypertension, white-coat effect, measurement artefact)
- Is this essential (primary) or secondary hypertension? (95% vs. 5%)
- If secondary, what is the specific cause? (Each has distinct pathophysiology, clinical clues, and management)
- What is the clinical context? (Chronic stable HTN vs. hypertensive crisis — and if crisis, is there TOD?)
The "differential diagnosis of hypertension" therefore operates at two levels: distinguishing essential from secondary HTN, and then differentiating among the specific secondary causes. Let me walk through both systematically.
Essential hypertension (95%) is a diagnosis of exclusion — you diagnose it when there is no identifiable secondary cause in a patient whose age, sex, risk factor profile, and clinical course are consistent with primary HTN [2].
Secondary hypertension (5%): distinct, identifiable cause [2]. Though only 5% overall, the prevalence is much higher in specific subgroups: up to 10–30% of patients with resistant hypertension [7].
When to Think Secondary
Indications to look for causes of secondary HTN (ACC/AHA 2017) [2]:
General clues:
- Age of onset: < 30 y or diastolic HTN for ≥ 65 y — essential HTN typically develops between 35–55 y. Outside this window, your suspicion for secondary causes should rise.
- Severity: accelerated or malignant HTN, disproportionate TOD for degree of HTN
- Course: abrupt onset, drug-resistant or exacerbation of previously controlled HTN
Specific clues:
- Unprovoked or excessive hypokalaemia (but note use of thiazide diuretics!)
- Renal HTN: palpable kidney, renal bruit, abnormal urinalysis
- Endocrine: S/S of phaeochromocytoma, unexplained hypokalaemia, signs of Cushing's syndrome
- Coarctation: radiofemoral delay
The mnemonic DANCER [2] organises the secondary causes. Below is a comprehensive table integrating the senior notes [2][7] and lecture material, with prevalence, clinical clues, pathophysiological reasoning, and screening approach for each.
Master Table: Secondary Causes of Hypertension
| Cause | Prevalence among HTN | Key Clinical Clues | Pathophysiology (Why does it cause ↑BP?) | Screening Test |
|---|---|---|---|---|
| D — Drugs | Very common if you look for it | Temporal relationship with drug initiation; resolves with drug cessation | Varies by drug class (see below) | Detailed drug/supplement history |
| A — Apnoea (OSA) | 25–50% of resistant HTN [7] | Resistant HTN, snoring, restless sleep, daytime sleepiness, obesity [7] | Intermittent hypoxia + arousal → ↑SNS, ↑endothelin-1, ↑oxidative stress, ↓NO → sustained daytime ↑SVR even after apnoea ceases | Clinical evaluation → Polysomnography [7] |
| N — Neurological | Uncommon | ↑ICP signs (headache worse supine, vomiting, papilloedema), acute stress | Cushing reflex: ↑ICP → brainstem ischaemia → massive ↑SNS → ↑BP to maintain CPP. Chronic stress/anxiety → sustained ↑SNS | Clinical context, CT/MRI brain |
| C — Coarctation of aorta | 0.1% [7] | Young HTN < 30 y, UL > LL BP, radiofemoral delay, continuous murmur at back/chest/abdomen [7] | Mechanical obstruction distal to left subclavian → ↑BP proximal to narrowing; renal hypoperfusion → ↑RAAS | Echocardiogram → CTA/MRA thorax [7] |
| E — Endocrine | ||||
| Primary aldosteronism | 8–20% [7] | Resistant HTN, hypokalaemia + alkalosis, muscle cramps, LL weakness, adrenal incidentaloma, arrhythmias (esp AF) with hypoK, FHx of early onset HT or stroke < 40 y [7] | ↑Aldosterone → ↑Na⁺ reabsorption (via ENaC) → volume expansion → ↑CO; also direct vascular inflammation and fibrosis | Plasma aldosterone-to-renin ratio (ARR) → Salt loading test [7] |
| Cushing's syndrome | < 0.1% [7] | Rapid weight gain esp central obesity, Cushingoid features, proximal myopathy, hyperglycaemia [7] | Cortisol excess → (1) mineralocorticoid action (overwhelms 11β-HSD2 → Na⁺ retention), (2) ↑SNS sensitivity, (3) ↑angiotensinogen production from liver, (4) ↓NO-mediated vasodilation | Overnight 1mg dexamethasone suppression test [7] |
| Phaeochromocytoma / Paraganglioma | 0.1–0.6% [7] | Resistant HTN, paroxysmal HTN or HTN crisis, spells of BP lability, headache, sweating, palpitations, pallor, adrenal incidentaloma, neurofibromatosis skin stigmata [7] | Catecholamine excess → α₁-mediated vasoconstriction (↑SVR) + β₁-mediated ↑HR/contractility (↑CO) | 24h urine fractionated metanephrines → Plasma metanephrines [7] |
| Hyperthyroidism | Uncommon | Heat intolerance, weight loss, tremor, tachycardia, goitre, lid lag | ↑T₃/T₄ → ↑β-adrenergic receptor expression → ↑HR, ↑contractility (↑CO) → systolic HTN [2] | TSH, free T₄ |
| Hypothyroidism | Uncommon | Cold intolerance, weight gain, constipation, bradycardia, dry skin | ↑SVR (mechanism not fully understood — likely ↑endothelin-1, ↓NO) → diastolic HTN [2] | TSH, free T₄ |
| Hyperparathyroidism | Uncommon | Stones, bones, abdominal groans, psychic moans | Hypercalcaemia → vasoconstriction + ↑vascular smooth muscle reactivity [2] | Serum Ca²⁺, PTH |
| Acromegaly | Rare | Coarsening of facial features, large hands/feet, prognathism, macroglossia, HTN (40%), LVH, cardiomyopathy [8] | GH/IGF-1 excess → ↑Na⁺ retention (direct renal effect), ↑SVR, cardiomyopathy | IGF-1, OGTT for GH suppression |
| R — Renal | ||||
| Renal artery stenosis (RAS) | 5–34% [7] (in resistant HTN populations) | Resistant HTN, abrupt onset or worsening, flash pulmonary oedema, early onset HTN esp in women, renal bruit [7]; ↑creatinine > 30% after starting ACEI/ARB | ↓Renal perfusion → ↑renin secretion from JG cells → ↑Ang II → vasoconstriction + aldosterone → Na⁺/H₂O retention. In unilateral RAS: contralateral kidney undergoes pressure natriuresis so volume may be near-normal initially (renin-dependent HTN). In bilateral RAS: volume-dependent HTN (can't natriurese) | Renal duplex USG → MRA → CT abdomen [7] |
| Renal parenchymal disease | 1–2% [7] | Haematuria, proteinuria, recurrent UTI, frequency, nocturia, FHx of polycystic kidney disease, other features of renal disease [7] | ↓Nephron mass → impaired Na⁺ excretion → volume overload; also ↑RAAS from renal ischaemia; ↑endothelin, ↓NO from damaged endothelium | Renal USG → Renal biopsy [7] |
Screening Tests — What Is Routinely Done?
From the senior notes [7], the asterisked tests are usually done routinely when screening for secondary hypertension:
- Plasma aldosterone-to-renin ratio (ARR)
- Renal duplex USG
- 24h urine fractionated metanephrines
- Overnight 1mg dexamethasone suppression test
Drug causes of secondary HTN [2] deserve special attention because they are the most common "secondary" cause in clinical practice and are completely reversible:
| Category | Examples | Mechanism |
|---|---|---|
| SNS-related | Caffeine, amphetamines, levodopa, MAOI, antidepressants, decongestants [2] | ↑Catecholamine release or ↓reuptake → ↑HR, ↑SVR |
| Fluid retention | OCP, anabolic steroids, mineralocorticoids, corticosteroids [2] | Na⁺/H₂O retention → volume expansion → ↑CO |
| Immunosuppressants | Cyclosporine [2], tacrolimus | Renal afferent arteriolar vasoconstriction → ↓GFR → Na⁺ retention; also ↑endothelin, ↑TGF-β |
| NSAIDs, COX-2 inhibitors | Ibuprofen, naproxen, celecoxib [2] | Inhibit renal vasodilatory prostaglandins (PGI₂, PGE₂) → afferent arteriolar constriction → Na⁺/H₂O retention; also blunt the effect of antihypertensives |
| Recreational/social | Alcohol, nicotine [2] | Alcohol: ↑SNS, ↑cortisol, direct vascular toxicity. Nicotine: acute ↑SNS (↑HR, ↑SVR), chronic endothelial damage |
| Anti-cancer agents | Chemotherapy, angiogenesis inhibitors, TKIs [2] (e.g., bevacizumab, sunitinib, sorafenib) | Anti-VEGF agents → ↓NO production → endothelial dysfunction → ↑SVR. This is a class effect — HTN occurs in up to 30-80% of patients on anti-VEGF therapy |
| Others | Liquorice, carbenoxolone | Inhibit 11β-HSD2 → cortisol acts on mineralocorticoid receptors → apparent mineralocorticoid excess → Na⁺ retention, hypoK |
| Erythropoietin (EPO) | ↑RBC mass → ↑blood viscosity → ↑SVR; also direct vasoconstriction via ↑endothelin | |
| Herbal medicines (common in HK!) | May contain undeclared steroids, sympathomimetics, or liquorice |
Hong Kong Clinical Pearl
Always ask about herbal medicines and over-the-counter remedies in HK patients. Some "arthritis" remedies from traditional medicine shops contain undeclared corticosteroids, which cause iatrogenic Cushing's and secondary HTN. Similarly, some "slimming teas" contain liquorice which inhibits 11β-HSD2 → apparent mineralocorticoid excess.
Within primary hyperaldosteronism (8–20% of HTN patients) [7], it is critical to distinguish between the two main subtypes because management differs completely [4][5]:
| Feature | Aldosterone-producing adenoma (Conn's, 30-40%) [4] | Bilateral idiopathic adrenal hyperplasia (BIAH, 60-70%) [4] |
|---|---|---|
| Laterality | Unilateral | Bilateral |
| Aldosterone driver | ACTH-dependent [4] | Angiotensin-dependent [4] |
| Biochemical severity | ↑Significant biochemical disturbance [4] | ↓Significant biochemical disturbance [4] |
| Plasma K | Very low to normal | Low to normal |
| Basal aldosterone | High to very high | High-normal to high |
| Basal PRA | Low | Low to low-normal |
| Salt-loading test | Failure/inadequate suppression | Failure/inadequate suppression |
| Postural test | ↓Aldosterone in 70-90% (due to ↓ACTH drive at noon) [4][5] | ↑Aldosterone in 90% (exaggerated response to ↑Ang in erect posture) [4][5] |
| Adrenal venous sampling | ↑ ipsilaterally, ↓ contralaterally | ↑ bilaterally |
| CT/MRI | Unilateral tumour | Normal or slightly enlarged bilaterally |
| Treatment | Unilateral laparoscopic adrenalectomy (4 weeks pre-op spironolactone to correct hypoK) [5] | Medical treatment: aldosterone antagonist (spironolactone/eplerenone), amiloride [4][5] |
Differentiated by salt-loaded balance study (9am supine + 1pm erect) [5]:
- Aldosterone-producing adenoma: paradoxical ↓aldosterone (ACTH-dependent production — aldosterone follows ACTH's diurnal rhythm, which drops by noon)
- BIAH: ↑aldosterone (sensitive to postural change via angiotensin)
D/dx of episodic sweating and/or flushing [8]:
- Oestrogen/testosterone deficiency (e.g., menopause, castration)
- Carcinoid syndrome (flushing, diarrhoea, wheeze)
- Phaeochromocytoma (sweat but do not flush) — this is a key distinguishing feature: phaeochromocytoma causes pallor (α₁-mediated vasoconstriction), not flushing
- Thyrotoxicosis (not usually episodic)
- Systemic mastocytosis (histamine release)
- Allergy
The 5 P's of phaeochromocytoma [5][8]:
- Pressure (HTN)
- Pain (headache, chest pain)
- Palpitation (tachycardia, tremor, LOW, fever)
- Perspiration
- Pallor (due to vasoconstrictive spells)
Before attributing hypertension to any cause, consider whether the BP is truly elevated:
| Condition | Mechanism | How to Identify |
|---|---|---|
| White-coat HTN | Alerting/anxiety response in clinical setting → ↑SNS → transiently ↑BP | ↑Office BP but normal ABPM/HBPM [2] |
| Pseudohypertension (Osler's manoeuvre) | Heavily calcified, non-compressible arteries (common in elderly, CKD, diabetics) → cuff over-reads because it needs more pressure to compress the rigid artery | Osler's sign: radial artery still palpable when cuff inflated above systolic BP. Confirm with intra-arterial measurement |
| Cuff too small | Undercuffing → cuff doesn't fully compress the artery → falsely ↑ reading | Use appropriate cuff size (bladder encircles ≥ 80% of arm circumference) |
| "Office-only" anxiety | Situational anxiety, pain, full bladder | Repeat after rest, empty bladder, comfortable setting |
Resistant HTN is defined as BP above goal despite optimal doses of ≥ 3 antihypertensive drugs from different classes (one of which should be a diuretic). The approach [2]:
AT-Home-GOAL [2]:
- Exclude pseudoresistance:
- Adherence — most common reason! Non-compliance is rampant.
- Timing of drugs — are they taken at the right time?
- Home and ambulatory BP — rule out white-coat effect
- Medical Rx adjustments:
- Greater dose of Rx
- Other classes: diuretics, aldosterone blocker
- Alternative Rx: combination with different MoA, loop diuretics if renal disease ± potent vasodilator
- Look for contributing factors: diet, obesity, drugs
- Reconsider secondary hypertension — the prevalence of secondary causes is much higher (up to 20-30%) in the resistant HTN population
- Referral to a specialist HTN centre
When a patient presents with BP > 180/120, the critical distinction is [2]:
| Hypertensive Emergency | Hypertensive Urgency | |
|---|---|---|
| Definition | BP > 180/120 + worsening/new TOD [2] | Severe ↑BP without new/worsening TOD [2] |
| Examples of TOD | ICH, APO, HTN encephalopathy [2] | — |
| Compelling indications for acute BP control | Aortic dissection, phaeochromocytoma crisis, eclampsia or severe pre-eclampsia [2] | — |
| Examples of urgency | — | Malignant HTN without acute TOD; HT associated with bleeding (post-op, severe epistaxis, retinal haemorrhage, CVA); severe HT + pregnancy/AMI/unstable angina; catecholamine excess or sympathomimetic overdose (rebound after withdrawal of clonidine or methyldopa, LSD, cocaine OD, interactions with MAOI) [2] |
The differential for what is causing the crisis includes:
- Uncontrolled/non-compliant essential HTN (most common)
- Phaeochromocytoma crisis
- Renal artery stenosis (acute worsening)
- Pre-eclampsia/eclampsia
- Sympathomimetic drugs (cocaine, amphetamines)
- Rebound HTN (clonidine or methyldopa withdrawal)
- Acute glomerulonephritis
- Scleroderma renal crisis
Related Differentials in Specific Clinical Contexts
This combination narrows the differential significantly:
| Condition | Renin | Aldosterone | Key Distinguishing Feature |
|---|---|---|---|
| Primary hyperaldosteronism | Low | High | ARR elevated; failure to suppress on salt loading [7] |
| Renovascular HTN (RAS) | High | High | Renal bruit, ↑Cr with ACEI, flash APO |
| Cushing's syndrome | Low-normal | Normal | Cushingoid features, cortisol elevated |
| Liquorice/carbenoxolone ingestion | Low | Low | History! Apparent mineralocorticoid excess (cortisol acting on MR) |
| Liddle syndrome | Low | Low | Young patient, AD family history, responds to amiloride not spironolactone |
| Diuretic use | High | High | Medication history |
| Chronic vomiting/diarrhoea | High | High | History, metabolic alkalosis (vomiting) or acidosis (diarrhoea) |
| Cause | Typical Patient | Key Clue |
|---|---|---|
| Coarctation | Male, young, known congenital heart disease | Radiofemoral delay, UL > LL BP [7] |
| Fibromuscular dysplasia | Young female | Renal bruit, abrupt onset HTN |
| Phaeochromocytoma (familial syndromes) | Family history of MEN2, VHL, NF1 | Paroxysmal symptoms, syndromic features |
| Renal parenchymal disease (GN, reflux nephropathy) | Childhood UTI history, haematuria | Abnormal urinalysis, small kidneys on USG |
| Primary aldosteronism (FH type I) | Strong FH of young HTN + stroke | Dexamethasone-suppressible (aldosterone from fasciculata under ACTH control) |
Exam Pearl — The Clinical Approach to the Lecture Slide Triad
The lecture slides [1] structure the clinical evaluation as three concentric circles:
Hypertension → CVS Risk Factors → Secondary Causes → Target Organ Damage → Prognosis [1]
This is the systematic framework for every HTN patient:
- Confirm HTN
- Assess global CVD risk (risk factors + 10-year CVD risk)
- Rule out secondary causes (DANCER)
- Evaluate TOD (heart, brain, kidney, eyes, vessels)
- Determine prognosis (risk stratification guides treatment intensity)
High Yield Summary — Differential Diagnosis of Hypertension
Level 1: Essential (95%) vs. Secondary (5%) — suspect secondary if onset < 30 y or diastolic HTN ≥ 65 y, resistant/malignant HTN, abrupt onset, hypokalaemia, or specific clinical clues.
Level 2 — Secondary causes (DANCER):
- D — Drugs (NSAIDs, OCP, steroids, sympathomimetics, anti-VEGF agents, herbal medicines)
- A — Apnoea (OSA, 25–50% of resistant HTN)
- N — Neurological (↑ICP, stress)
- C — Coarctation (young HTN, radiofemoral delay, UL > LL BP)
- E — Endocrine: primary aldosteronism (8–20%, ARR screen), Cushing's (DST), phaeochromocytoma (urine metanephrines), thyroid disease, hyperparathyroidism, acromegaly
- R — Renal: RAS (duplex USG), renal parenchymal disease (urinalysis, renal USG)
Primary aldosteronism subtypes: Adenoma (30-40%) vs. BIAH (60-70%) — differentiated by postural test: adenoma = paradoxical ↓aldo; BIAH = ↑aldo.
Phaeochromocytoma 5 P's: Pressure, Pain, Palpitation, Perspiration, Pallor.
Resistant HTN: Exclude pseudoresistance first (adherence, white-coat effect), then screen for secondary causes (AT-Home-GOAL).
Hypertensive crisis: Emergency (TOD present) vs. Urgency (no TOD) — different management timelines.
Always consider: Drug history (including herbals in HK), measurement artefact, white-coat HTN.
Active Recall - Differential Diagnosis of Hypertension
References
[1] Lecture slides: GC 058. High Blood Pressure.pdf (p33, p44, p50) [2] Senior notes: Ryan Ho Cardiology.pdf (p175–182) [4] Senior notes: Ryan Ho Endocrine.pdf (p57–59) [5] Senior notes: maxim.md (Conn's syndrome, Phaeochromocytoma sections) [7] Senior notes: Ryan Ho Cardiology.pdf (p178 — Secondary HTN screening table) [8] Senior notes: Ryan Ho Endocrine.pdf (p66, p111 — Phaeochromocytoma, Acromegaly)
Diagnostic Criteria, Diagnostic Algorithm, and Investigation Modalities for Hypertension
1. Diagnostic Criteria — When Do We Call It "Hypertension"?
Definition of HTN (ACC/AHA 2017) [2]:
| Category | SBP (mmHg) | DBP (mmHg) | |
|---|---|---|---|
| Normal | < 120 | and | < 80 |
| Elevated BP | 120–129 | and | < 80 |
| Stage 1 HTN | 130–139 | or | 80–89 |
| Stage 2 HTN | ≥ 140 | or | ≥ 90 |
| Hypertensive Crisis | > 180 | and/or | > 120 |
The ESC/ESH 2018 (still widely used in HK/European settings) retains ≥ 140/90 as the office-BP threshold for diagnosing hypertension in uncomplicated patients, while acknowledging 130–139/80–89 as "high-normal." In practice for HKUMed exams, know both frameworks. The key point is the same: the diagnosis must be confirmed by repeated measurements — a single elevated reading is not enough.
Because out-of-office measurements remove the alerting ("white-coat") response, their thresholds are set lower [2]:
| Measurement Method | HTN Threshold |
|---|---|
| Office BP | ≥ 140/90 (ESC) or ≥ 130/80 (ACC/AHA) |
| HBPM (Home) | ≥ 135/85 |
| ABPM — Daytime mean | ≥ 135/85 |
| ABPM — Night-time mean | ≥ 120/70 |
| ABPM — 24-hour mean | ≥ 130/80 |
Why different numbers? Office BP is measured in an environment that naturally raises sympathetic tone. ABPM integrates hundreds of readings over 24 hours in the patient's real environment — it better reflects the true haemodynamic burden on target organs. This is why ABPM is considered the gold standard [2].
Diagnosis is made [2] when:
- Hypertensive crisis, i.e. > 180/120 — diagnosed immediately (no need for confirmation)
- Evidence of TOD + ↑↑BP (≥ 160/100) — diagnosed immediately because TOD proves the BP has been chronically or severely elevated
- Otherwise, high office BP (≥ 130/80 or ≥ 140/90) should be confirmed by HBPM/ABPM — this step is essential to rule out white-coat HTN
Why Confirm with Out-of-Office BP?
Only relying on office BP risks missing out on white-coat and masked HTN [2]:
- White-coat hypertension: ↑office BP but normal ABPM/HBPM — prevalence 15–30%, especially in elderly and pregnant women. Risk is lower than sustained HTN but may be a precursor → follow-up and monitoring [2].
- Masked hypertension: normal office BP but ↑ABPM/HBPM — ↑risk > patients with known but uncontrolled HTN [2]. Missed if you only do office measurements. Common in smokers, alcohol users, those with workplace stress, and OSA patients.
Prevalence of different types of hypertension [9]:
| Diagnosis | General Population (%) | Specialty Clinic (%) |
|---|---|---|
| Essential hypertension | 92–94 | 65–85 |
| Renal parenchymal | 2–3 | 4–5 |
| Renovascular | 1–2 | 4–16 |
| Endocrine hypertension | 0.3–0.4 | 0.5–12 |
This table is critical — it shows that the proportion of secondary HTN rises dramatically in specialty clinic populations (where patients have been referred for resistant or atypical HTN). This is why secondary HTN screening is especially important in these settings.
The evaluation of a hypertensive patient has three aims [2]:
- Screen for CVD risk factors
- Rule out secondary hypertension
- Evaluate target organ damage
Let me lay out the complete diagnostic algorithm as a mermaid flowchart, then explain each step:
3. Investigation Modalities — Comprehensive Breakdown
I will organise investigations into three tiers:
- Tier 1: Routine initial evaluation (done for ALL hypertensive patients)
- Tier 2: Secondary HTN screening (done when red flags present)
- Tier 3: Target organ damage assessment (done to guide treatment intensity)
Tier 1: Routine Initial Evaluation
Routine initial evaluation — done for every patient diagnosed with HTN [2]:
| Domain | What to Ask | Why |
|---|---|---|
| Age | Consider secondary HTN < 35 y or > 55 y [2] | Essential HTN develops 35–55 y; outside this = ↑suspicion for secondary cause |
| Duration and previous BP levels | How long has BP been elevated? Previous recordings? [1] | Helps determine chronicity and trajectory |
| Family history of HTN | Essential HTN has a strong genetic basis [1] | Positive FHx supports essential HTN |
| Other CVD risk factors | Smoking, DM, lipid disorders, FHx of early CVD deaths [1] | Determines overall cardiovascular risk profile |
| Lifestyle | Diet, physical activity, family status, work [1] | Identifies modifiable risk factors; high salt intake particularly important in HK |
| Drug history | Prescription drugs, OTC, herbal medicines, supplements | Rule out drug-induced HTN (especially NSAIDs, steroids, herbal remedies in HK) |
| Symptoms of TOD | Headache, visual changes, chest pain, dyspnoea, neurological symptoms | Guides urgency of workup |
| Symptoms of secondary causes | Paroxysmal headache/sweating/palpitations, snoring, weight gain/striae | Directs specific secondary screening |
| Examination | What to Look For | Interpretation |
|---|---|---|
| BP/Pulse: bilateral arms, supine and standing [2] | Inter-arm difference > 20/10 → coarctation or subclavian stenosis. Orthostatic drop → autonomic dysfunction, phaeochromocytoma, over-treatment | Fundamental for diagnosis and for detecting coarctation |
| BMI and waist circumference [2] | Obesity (BMI > 30), central obesity (waist ≥ 90 cm male, ≥ 80 cm female in Asians) | Key modifiable risk factor; component of metabolic syndrome |
| CVS: standard + palpation/auscultation of all peripheral arteries [2] | Displaced/sustained apex → LVH. S4 → diastolic dysfunction. Renal bruit → RAS. Radiofemoral delay → coarctation. Carotid bruit → carotid stenosis | Screens for both TOD and secondary causes simultaneously |
| Fundoscopy [2] | Keith-Wagener-Barker grading (Grade 1–4) | Only place you can directly visualise arterioles; Grade 3–4 = malignant HTN |
| Investigation | What It Tests | Key Findings / Interpretation |
|---|---|---|
| RFT and electrolytes [2] | Baseline renal function; screen for renal parenchymal disease; r/o hyperaldosteronism and hyperparathyroidism [2] | ↑Creatinine/↓eGFR → renal cause. HypoK + alkalosis → primary aldosteronism. Hypercalcaemia → hyperparathyroidism (a secondary cause of HTN) [2] |
| Lipid profile [2] | Dyslipidaemia | Part of CVD risk assessment; component of metabolic syndrome |
| Serum fasting glucose [2] | R/o DM [2] | DM is a major CVD risk factor; also component of metabolic syndrome |
| ± Serum urate [2] | Baseline for hyperuricaemia | Hyperuricaemia associated with CVD; also relevant before starting thiazide diuretics (which raise urate) |
| ± Urinalysis [2] | Haematuria (r/o renal disease), UACR (albuminuria) [2] | Haematuria + proteinuria → glomerulonephritis. Albuminuria → early renal TOD or diabetic nephropathy. Microalbuminuria or eGFR < 60 mL/min is a CVD risk factor [1] |
| ECG [2] | LVH, MI, cardiac failure, heart block [2] | LVH on ECG (Sokolow-Lyon: SV1 + RV5/V6 ≥ 35 mm; Cornell: RaVL + SV3 > 28 mm male, > 20 mm female) → evidence of cardiac TOD. Ischaemic changes → concomitant CAD |
| ± Echocardiogram [2] | For LVH [2] | More sensitive than ECG for LVH detection. Also assesses diastolic function (E/A ratio, E/e'), EF, and wall motion abnormalities |
| Calculation of 10-year CVD risk [2] | Global risk assessment | Guides treatment threshold and intensity. Tools: ACC/AHA Pooled Cohort Equations, Framingham, SCORE2 |
Exam Pearl — The Logic Behind Routine Bloods
Every single routine blood test serves a dual purpose — it both risk-stratifies and screens for secondary causes:
- RFT: Is the kidney the victim (TOD) or the perpetrator (secondary cause)?
- Electrolytes: HypoK → Conn's? Hypercalcaemia → hyperPTH?
- Glucose: DM → both a risk factor and associated with metabolic syndrome
- Lipids: Dyslipidaemia → CVD risk and metabolic syndrome
- Urate: Baseline before thiazide; also an independent CVD risk marker
Tier 2: Secondary Hypertension Screening
Only done when red flags are present [2]. The table below integrates the senior notes screening table [7] with interpretation guidance:
Investigations of Conn's Syndrome — diagnosis includes biochemical tests as well as radiological images. Interpretation of biochemical tests can be difficult. [9]
Step 1: Initial Screen — Plasma Aldosterone-to-Renin Ratio (ARR) [4][7]
| Parameter | Value | Interpretation |
|---|---|---|
| Basal PRA | < 1 | Suppressed renin (volume expansion suppresses JG cells) |
| Basal aldosterone | ≥ 10 ng/dL | Elevated despite suppressed renin |
| ARR | > 30 | 90% sensitivity, 90% specificity [4] |
| Secondary hyperaldosteronism | ↑PRA, ↑Ald, ARR < 10 | Both elevated because RAAS is appropriately activated |
| Non-aldosterone mineralocorticoid excess | ↓PRA, ↓aldosterone | e.g., Cushing's, liquorice — mineralocorticoid effect but NOT from aldosterone |
Precautions before testing [4]:
- Exclude other causes of hypoK (diuretics, GI loss, RTA)
- Ensure reasonable Na intake (↓Na intake protects against hypoK by ↓tubular Na available for exchange → misleading results)
- Stop antihypertensives for ≥ 2 weeks before dynamic testing (MRA for ≥ 6 weeks) [4] — most drugs affect renin and aldosterone:
- Stop: diuretics (↑renin), BB/clonidine/methyldopa (↓renin), ACEI (↓ald), MRA (↓ald action → ↑renin), CCB (variable)
- Exception: α-blockers do not significantly affect results [4]
Step 2: Confirmatory — Salt Loading Test [4][7]
- Exception: spontaneous hypoK with aldosterone ≥ 20 → practically diagnostic (no need for confirmatory test) [4]
- Method: IV NS 1 litre/hour × 4 hours in sitting/recumbent position → load Na⁺ and volume [4]
- Monitor BP/pulse and watch for signs of fluid overload (especially if underlying HF) [4]
- Findings: measure renin + aldosterone post-salt loading
- Normal: suppression of both renin and aldosterone
- Primary hyperaldosteronism: failure or inadequate suppression (aldosterone still > 10) [4]
Step 3: Subtype Differentiation — Postural (Balance) Test [4]
- Process: PRA and aldosterone measured at early morning supine (8am after 8h recumbence) → ↑ACTH drive, ↓angiotensin drive; and lunchtime erect (12 noon after 4h ambulation) → ↓ACTH drive, ↑angiotensin drive [4]
- Adenoma (ACTH-dependent): higher aldosterone in the morning → paradoxical ↓ at noon [4]
- Hyperplasia (RAAS-dependent): higher aldosterone at noon → ↑ with upright posture [4]
- Caveat: considered not reliable enough alone [4] → also need:
Step 4: Imaging + Adrenal Venous Sampling [4]
| Modality | Adenoma | Hyperplasia |
|---|---|---|
| CT/MRI adrenals | Unilateral tumour | Normal or bilateral enlargement |
| Adrenal venous sampling (AVS) | ↑ ipsilaterally, ↓ contralaterally | ↑ bilaterally |
AVS is the gold standard for lateralisation — CT alone can miss small adenomas or pick up non-functioning incidentalomas. Always perform AVS before considering surgery.
- 24h urine fractionated metanephrines: Sensitivity 98%, Specificity 98% [8] — this is the preferred initial test
- Plasma fractionated metanephrines: Sensitivity 96–100%, Specificity 85–89% [8] — higher sensitivity but lower specificity (more false positives)
- Why metanephrines and not catecholamines? Catecholamines are released episodically (paroxysmal tumours may have normal levels between attacks), but metanephrines are produced continuously by catechol-O-methyltransferase (COMT) within the tumour → more reliable
- 24h urine for VMA: now superseded as less accurate [8]
Precaution: stop drugs affecting catecholamine secretion before testing (TCAs, levodopa, α-agonists, amphetamines) [8]
Localisation (after biochemical confirmation):
- CT abdomen/pelvis (most phaeochromocytomas are adrenal)
- ¹²³I-MIBG scintigraphy (metaiodobenzylguanidine — taken up by chromaffin tissue) — useful for extra-adrenal paragangliomas or metastatic disease
- ⁶⁸Ga-DOTATATE PET/CT — increasingly used, superior to MIBG for detecting extra-adrenal and metastatic disease
Initial testing based on three main modalities [10]:
- 24-hour urinary free cortisol (UFC) × 2 [10]
- Late-night salivary cortisol × 2 [10]
- 1 mg overnight dexamethasone suppression test (DST) [7][10]
The logic: Cushing's syndrome features loss of circadian rhythm and loss of normal negative feedback. Each test exploits a different aspect:
- UFC: integrates cortisol exposure over 24h → detects excess production
- Late-night salivary cortisol: cortisol should be at its nadir late at night → if elevated, circadian rhythm is lost
- 1 mg DST: dexamethasone should suppress ACTH → cortisol should fall → if it doesn't suppress (cortisol > 50 nmol/L [5]), the HPA axis is autonomous
If positive screening → ACTH-dependent vs. independent:
| Parameter | Cushing's Disease | Ectopic ACTH | Adrenal Tumour | Iatrogenic |
|---|---|---|---|---|
| Cortisol | ↑ | ↑ | ↑ | ↓ (endogenous) |
| ACTH | Normal–high | High | Almost invariably undetectable [8] | Low |
| LDDST | No suppression | No suppression | No suppression | — |
| HDDST | Usually suppressed [8] | Usually no suppression [8] | No suppression | — |
| CRH test | Exaggerated rise [8] | No significant rise [8] | — | — |
Screening: Renal duplex USG [7] — first-line non-invasive test
- Findings: ↑peak systolic velocity (PSV) > 200 cm/s at the stenosis; renal-to-aortic ratio > 3.5; tardus-parvus waveform in intra-renal arteries (delayed systolic upstroke, low amplitude)
- Sensitivity ~85%, specificity ~92% for significant stenosis (> 60%)
- Limitation: operator-dependent, poor views in obese patients or with bowel gas
- MRA — non-invasive, no radiation, no iodinated contrast; sensitivity/specificity > 90%. Avoid in severe CKD (gadolinium risk of nephrogenic systemic fibrosis if eGFR < 30)
- CT angiography [11] — excellent spatial resolution; can assess renal artery stenosis [11]. Requires iodinated contrast (nephrotoxicity risk)
- Conventional angiography (DSA) — gold standard but invasive; reserved for planned intervention (angioplasty/stenting)
Renal USG [7] — assesses kidney size, cortical thickness, corticomedullary differentiation, obstruction, cysts
- Small kidneys (< 9 cm) with thin cortex → chronic parenchymal disease
- Large bilateral kidneys with multiple cysts → ADPKD
- Asymmetric kidney size → unilateral RAS or reflux nephropathy
Urinalysis → haematuria + proteinuria → glomerular disease; sterile pyuria → TIN [7] Renal biopsy → generally required for diagnosis of GN [7]
Clinical evaluation → Polysomnography [7]
- Screening tools: STOP-BANG questionnaire, Epworth Sleepiness Scale
- Polysomnography: gold standard — measures AHI (apnoea-hypopnoea index)
- Mild OSA: AHI 5–15/hour
- Moderate: AHI 15–30/hour
- Severe: AHI > 30/hour
Echocardiogram → CTA/MRA thorax [7]
- Echo: can visualise the narrowing in the descending aorta, measure gradient across coarctation, assess for associated bicuspid aortic valve (present in ~50%)
- CTA/MRA: definitive imaging for anatomical delineation and surgical planning
| Target Organ | Investigation | Key Findings | Clinical Significance |
|---|---|---|---|
| Heart | ECG [2] | LVH (Sokolow-Lyon: SV₁ + RV₅ ≥ 35 mm), ischaemia, MI, heart block [2] | Cardiac TOD; LVH is an independent predictor of cardiovascular events |
| Echocardiogram [2] | LV mass index (↑ = LVH), diastolic dysfunction (E/e' ratio), EF, wall motion | More sensitive than ECG for LVH [2]. Diastolic dysfunction precedes systolic; E/e' > 14 suggests elevated filling pressures | |
| BNP/NT-proBNP | ↑ levels | Suggests heart failure (both HFpEF from diastolic dysfunction and HFrEF) | |
| Brain | CT brain (non-contrast) | Haemorrhagic stroke: acute = hyperdense, subacute = isodense, chronic = hypodense [11]. Common hypertensive haemorrhage sites: basal ganglia, cerebellum, brainstem [11] | Haemorrhagic stroke is a major HTN complication, especially in Chinese populations |
| MRI brain | White matter hyperintensities, lacunar infarcts | Chronic small vessel disease from longstanding HTN | |
| Kidneys | Serum creatinine, eGFR | ↑Cr, ↓eGFR | Hypertensive nephrosclerosis → CKD |
| UACR [2] | Microalbuminuria (UACR 3–30 mg/mmol) or macroalbuminuria (> 30 mg/mmol) | Earliest marker of hypertensive renal damage; also powerful independent CVD risk predictor | |
| Renal USG | Small kidneys, thin cortex | Chronic hypertensive nephrosclerosis | |
| Eyes | Fundoscopy [2] | Keith-Wagener-Barker grading (see Section 1 notes) | Grade 1–2: chronic arteriosclerotic changes. Grade 3–4: malignant HTN requiring urgent treatment |
| Vessels | Carotid duplex USG | Intima-media thickness (IMT) > 0.9 mm, plaques, stenosis | Subclinical atherosclerosis; ↑IMT is independent CVD predictor |
| ABI [12] | Normal 0.9–1.3; Claudication 0.4–0.9; Severe < 0.4; Calcified > 1.3 [12] | Screens for PAD; ABI < 0.9 is diagnostic of arterial occlusive disease. > 1.3 = calcified (common in DM/ESRD → use toe-brachial index instead) | |
| CTA/MRA aorta | Aortic dilatation, dissection | If suspected aortic complications | |
| Pulse wave velocity | ↑PWV | Arterial stiffness — emerging marker, especially relevant in ISH |
4. Special Investigations — Interpreting Key Findings
| Finding | Criteria | Significance |
|---|---|---|
| LVH — Voltage criteria | Sokolow-Lyon: SV₁ + RV₅ or RV₆ ≥ 35 mm. Cornell: RaVL + SV₃ > 28 mm (M) or > 20 mm (F) | Concentric LVH from chronic pressure overload. Independent predictor of CV events. Regression with treatment is a good prognostic sign |
| LV strain pattern | ST depression + T-wave inversion in lateral leads (V5, V6, I, aVL) | Indicates subendocardial ischaemia from LVH — the hypertrophied myocardium outstrips its blood supply |
| Left atrial enlargement | P-wave duration > 120 ms; notched P in lead II; biphasic P in V₁ with terminal negative component > 1 mm deep × > 40 ms wide | Consequence of ↑LV filling pressures (diastolic dysfunction → LA has to push against a stiff LV) |
| AF | Irregularly irregular rhythm, absent P waves | Common in HTN (LA dilatation from diastolic dysfunction → substrate for AF) |
| Ischaemic changes | ST-segment changes, pathological Q waves | Concomitant CAD from accelerated atherosclerosis |
| Parameter | Normal | Abnormal in HTN | Interpretation |
|---|---|---|---|
| LV mass index | < 95 g/m² (F), < 115 g/m² (M) | Elevated | Confirms LVH. Echo is more sensitive and specific than ECG |
| Relative wall thickness | < 0.42 | ≥ 0.42 with ↑mass → concentric LVH; < 0.42 with ↑mass → eccentric LVH | Concentric LVH = classic pressure-overload pattern in HTN. Eccentric suggests volume overload component |
| E/A ratio | > 1 (young adults) | < 1 (impaired relaxation) | Early diastolic dysfunction — the stiff LV relaxes poorly |
| E/e' ratio | < 8 normal | > 14 elevated | Estimates LV filling pressure; > 14 suggests elevated LVEDP → symptomatic diastolic dysfunction |
| LA volume index | < 34 mL/m² | Elevated | Integrates chronic diastolic dysfunction over time ("LA is the HbA1c of diastolic function") |
| LVEF | ≥ 55% | ↓ in late-stage | Preserved until late (HFpEF → HFrEF progression) |
| Parameter | Normal | Significance |
|---|---|---|
| 24h mean BP | < 130/80 | Threshold for diagnosing HTN by ABPM |
| Daytime mean | < 135/85 | Correlates with office BP |
| Night-time mean | < 120/70 | Normally BP dips 10–20% at night ("dipping") |
| Dipping pattern | 10–20% nocturnal ↓ | |
| Non-dipping (< 10% drop) or Reverse dipping (BP rises at night) | Abnormal | Associated with ↑TOD, ↑CV events. Seen in OSA, CKD, autonomic dysfunction, Cushing's syndrome, Conn's syndrome |
| Extreme dipping (> 20% drop) | Abnormal | ↑Risk of nocturnal ischaemic stroke |
| Morning BP surge | Exaggerated | ↑Risk of morning cardiac events (MI, stroke) — explains why CVD events peak 6–10 AM |
Indications for ABPM [2]:
- Office BP considerably variable or different from home BP
- Resistant HTN
- Suspected hypotensive episodes in elderly/DM
- ↑Office BP in pregnant women → suspect pre-eclampsia
Common Diagnostic Errors
-
Using a single office reading to diagnose HTN → Always confirm with repeat measurements on different occasions or HBPM/ABPM (unless crisis or obvious TOD).
-
Wrong cuff size → Too small cuff → falsely ↑ readings. Always ensure bladder encircles ≥ 80% of arm circumference.
-
Forgetting to check standing BP → Misses orthostatic hypotension (especially in elderly, diabetics, and those on multiple antihypertensives) and postural ↑BP in phaeochromocytoma.
-
Ignoring hypokalaemia → "Oh, they're on a thiazide" — yes, but even thiazide-induced hypoK should not be severe (K < 3.0). Unprovoked or excessive hypokalaemia [2] mandates screening for primary aldosteronism.
-
Not checking both arms → Misses coarctation and subclavian stenosis.
-
Interpreting ARR without proper drug washout → Most antihypertensives affect renin and aldosterone levels. Stop medications for ≥ 2 weeks (MRA for ≥ 6 weeks) [4] and ensure adequate Na intake before testing.
-
Relying on CT alone for Conn's lateralisation → Non-functioning adrenal incidentalomas are common (up to 4% of the population). AVS is the gold standard for lateralisation before adrenalectomy.
-
Forgetting ABI in calcified vessels → ABI > 1.3 in DM/ESRD patients is falsely reassuring (calcified, non-compressible arteries). Use toe-brachial index (TBI) instead [12].
High Yield Summary — Diagnosis of Hypertension
Diagnostic Thresholds: Office ≥ 140/90 (ESC) or ≥ 130/80 (ACC/AHA). HBPM ≥ 135/85. ABPM 24h ≥ 130/80. Confirm office readings with HBPM/ABPM unless crisis (> 180/120) or obvious TOD.
Three Aims of Evaluation: (1) CVD risk factors, (2) Rule out secondary HTN, (3) Assess TOD.
Tier 1 — Routine for ALL: History (age, FHx, drugs, lifestyle), bilateral arm BP supine/standing, BMI, fundoscopy, CVS exam. Bloods: RFT + electrolytes, fasting glucose, lipid profile. Urinalysis + UACR. ECG ± echo. 10-year CVD risk.
Tier 2 — Secondary Screening (if red flags):
- Conn's: ARR → salt loading test → postural test → CT + AVS. Precaution: drug washout ≥ 2 weeks.
- Phaeochromocytoma: 24h urine fractionated metanephrines (98% Sens/Spec) → CT → MIBG/PET.
- Cushing's: DST / UFC / late-night salivary cortisol → ACTH level → HDDST/CRH → imaging.
- RAS: Renal duplex USG → MRA → CTA → DSA.
- Renal parenchymal: Renal USG + urinalysis → biopsy.
- OSA: Polysomnography. Coarctation: Echo + CTA. Thyroid: TSH.
Tier 3 — TOD Assessment: Heart (ECG: LVH/strain; echo: mass, diastolic function), Brain (CT/MRI), Kidney (eGFR, UACR), Eyes (fundoscopy), Vessels (ABI, carotid USG).
ABPM patterns: Non-dipping/reverse dipping = ↑TOD risk. Morning surge = ↑AM cardiac events.
Prevalence in specialty clinics: Essential 65–85%, renal parenchymal 4–5%, renovascular 4–16%, endocrine 0.5–12%.
Active Recall - Diagnostic Criteria, Algorithm, and Investigations for Hypertension
References
[1] Lecture slides: GC 058. High Blood Pressure.pdf (p29, p30) [2] Senior notes: Ryan Ho Cardiology.pdf (p175–176) [4] Senior notes: Ryan Ho Endocrine.pdf (p58) [5] Senior notes: maxim.md (Cushing syndrome, Conn's syndrome sections) [7] Senior notes: Ryan Ho Cardiology.pdf (p178 — Secondary HTN screening table) [8] Senior notes: Ryan Ho Endocrine.pdf (p63, p66 — Cushing's summary, Phaeochromocytoma diagnosis) [9] Lecture slides: GC 066. I have fluctuating BP (1).pdf (p2, p15) [10] Senior notes: Ryan Ho Chemical Path.pdf (p29 — Diagnosis of Cushing Syndrome) [11] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p41, p43) [12] Senior notes: maxim.md (ABI section); Ryan Ho Cardiology.pdf (p214)
Management of Hypertension — Algorithm, Treatment Modalities, Indications, and Contraindications
Before diving into specific drugs, understand why and when we treat:
HTN itself is harmless. It is only treated because of its associated risks of TOD and clinical events. If there is ↑CVD risk or evidence of TOD, it is reasonable to start Tx early. [2]
Prognosis is mainly dependent on [2]:
- Concomitant CVS risk factors, especially DM (several × risk of CVD and CKD in HTN+DM patients)
- Target organ damage
Therefore, treatment decisions are risk-stratified — the higher the global cardiovascular risk, the lower the threshold to start pharmacotherapy and the more aggressive the target.
Treatment goals depend on risk profile (ACC/AHA 2017) [2]:
| Risk Category | BP Target |
|---|---|
| 10-year ASCVD risk ≥ 10% or pre-existing cardiovascular disease (including stable IHD, HF, CKD, stroke, DM) | ≤ 130/80 mmHg |
| 10-year ASCVD risk < 10% | ≤ 140/90 mmHg |
From the lecture slides [13]:
Target: < 150/90 or < 140/80 for young (< 65), DM and renal diseases [13]
The ESC 2018 and ISH 2020 guidelines nuance this further:
- First target for all: get below 140/90 within 3 months
- If tolerated in < 65 years: aim for SBP 120–130 mmHg
- In ≥ 65 years: aim SBP 130–139 mmHg (avoid < 120 due to falls/hypoperfusion risk)
- DM and CKD: < 130/80 if tolerated
Monitoring and Follow-up
Monitoring [14]:
- Reduce BP by at least 20/10 mmHg, ideally to < 140/90 mmHg
- Individualise for elderly based on frailty
- BP control — achieve target within 3 months
- Adverse effects
- Long-term adherence
- If BP still uncontrolled, or other issue, refer to care provider with hypertension expertise
Lifestyle measures [2]:
- Role: as initial therapy before starting medications; as adjunct to or facilitate step-down of medications
| Intervention | Recommendation | Expected BP Reduction | Mechanism |
|---|---|---|---|
| Weight reduction | If overweight or obese; aim BMI 20–25 kg/m² | 5–20 mmHg per 10 kg lost | ↓SNS activity, ↓insulin resistance, ↓RAAS activation, ↓arterial stiffness |
| Diet | ↓Na/fat, ↑fruit/vegetables, ↑K, DASH diet [2] | 8–14 mmHg | ↓Na → ↓volume; ↑K → vasodilation (endothelium-dependent NO release); DASH = Dietary Approaches to Stop Hypertension [2] |
| Salt restriction | < 5–6 g NaCl/day (< 2.4 g Na/day) | 2–8 mmHg | Directly ↓intravascular volume; also ↓tissue RAAS activation |
| Exercise | 30 min/day, most days in a week [2] | 4–9 mmHg | ↑Endothelial NO production, ↓SNS tone, ↓insulin resistance, ↓body weight |
| Alcohol moderation | ≤ 2 (M) or ≤ 1 (F) drinks/day [2] | 2–4 mmHg | ↓Direct vasotoxicity, ↓SNS activation, ↓caloric intake |
| Smoking cessation | Strongly advised | Minimal direct BP effect but huge CVD risk reduction | Major independent CVD risk factor; accelerates atherosclerosis |
DASH diet [2] is particularly effective: rich in fruits, vegetables, whole grains, low-fat dairy; low in saturated fat, cholesterol, and refined sugars. Combined with Na restriction, it can lower BP as much as a single drug.
5. First-Line Antihypertensive Drug Classes — The "A, C, D" System
Medical therapy [2]:
- First line: ACEI/ARB, CCB, thiazide diuretics (± BB)
- Any first-line drug should achieve ~10–15 mmHg ↓SBP
Note: Many recent studies suggest that β-blockers are less effective than the other three (A, C, D) [2]. Beta-blockers are therefore not considered first-line for uncomplicated HTN but are included when there is a specific indication for their use, e.g., heart failure, angina, post-MI, atrial fibrillation, or younger women with, or planning pregnancy [13][14].
ACE Inhibitors (e.g., enalapril, ramipril, perindopril, lisinopril)
- Name breakdown: "ACE" = Angiotensin-Converting Enzyme; "inhibitor" = blocks the enzyme
- Mechanism: Blocks ACE → ↓conversion of Ang I → Ang II → ↓vasoconstriction, ↓aldosterone, ↓cardiac remodelling. Also ↓degradation of bradykinin → ↑vasodilation (but this also causes cough).
- Benefits beyond BP: Renal protection (↓intraglomerular pressure by dilating efferent > afferent arteriole), cardioprotection (↓LVH, ↓post-MI remodelling), slows CKD progression
ARBs (e.g., losartan, valsartan, irbesartan, candesartan)
- Name breakdown: "ARB" = Angiotensin II Receptor Blocker; blocks the AT₁ receptor directly
- Mechanism: Blocks Ang II at the AT₁ receptor → same downstream effects as ACEI but without bradykinin accumulation → no cough
- Preferred when: ACEI-intolerant (cough in ~10–15%, especially in Chinese/Asian populations)
| Indications | Contraindications | |
|---|---|---|
| ACEI | HF, post-MI, DM nephropathy, CKD with proteinuria, LVH, metabolic syndrome | Pregnancy [13], previous angioneurotic oedema [13], hyperkalaemia (K > 5.5) [13], bilateral renal artery stenosis [13] |
| ARB | Same as ACEI; ACEI-intolerant (cough) | Pregnancy [13], hyperkalaemia (K > 5.5) [13], bilateral renal artery stenosis [13] |
Possible contraindication [13]: Women of child-bearing potential without reliable contraception
Why Bilateral RAS Is a Contraindication
In bilateral RAS (or RAS in a single functioning kidney), GFR is maintained by Ang II constricting the efferent arteriole. ACEI/ARB removes this compensatory mechanism → efferent arteriole dilates → ↓intraglomerular pressure → ↓GFR → acute kidney injury. In unilateral RAS with a normal contralateral kidney, ACEI/ARB can usually be used (the normal kidney compensates) — but monitor creatinine closely. A rise > 30% mandates stopping the drug and investigating for RAS.
Never Combine ACEI + ARB
Dual RAAS blockade (ACEI + ARB, or either + direct renin inhibitor) causes more harm than benefit — ↑hyperkalaemia, ↑AKI, ↑hypotension — without additional cardiovascular protection (ONTARGET trial). This is a common exam trap.
Two major subtypes:
| Dihydropyridines (DHP-CCBs) | Non-DHP-CCBs | |
|---|---|---|
| Examples | Amlodipine, felodipine, nifedipine (long-acting), isradipine, nicardipine | Verapamil, diltiazem |
| Primary site of action | Vascular smooth muscle L-type Ca²⁺ channels | Cardiac + vascular L-type Ca²⁺ channels |
| Main effect | Arteriolar vasodilation → ↓SVR | ↓Heart rate + ↓contractility + mild vasodilation |
| Reflex tachycardia | Yes (compensatory ↑SNS) | No (suppresses cardiac conduction) |
| Use in HTN | First-line, especially in elderly (arterial stiffness) and black patients [14] | Alternative if DHP not tolerated or if rate control needed (e.g., AF) |
Contraindications [13]:
| Drug | Compelling Contraindication | Possible Contraindication |
|---|---|---|
| DHP-CCBs | Tachyarrhythmia; Heart failure (HFrEF, class III or IV) [13] | Pre-existing severe leg oedema [13] |
| Verapamil / Diltiazem | Any high-grade sino-atrial or AV block; Bradycardia (HR < 60/min); Severe LV dysfunction (LVEF < 40%) [13] | Constipation (especially verapamil) [13] |
Why does amlodipine cause leg oedema? It preferentially dilates arterioles but NOT venules → ↑capillary hydrostatic pressure → transudation of fluid into interstitium → pedal oedema. This is NOT fluid overload — diuretics do not help. Adding ACEI/ARB can partially offset this (they also dilate venules, reducing the arteriolar-venular pressure gradient).
Note: sublingual nifedipine may precipitate ischaemic insult due to rapid ↓BP [2] — this is a classic exam point. Short-acting nifedipine causes precipitous BP drops → reflex tachycardia → myocardial ischaemia. It should NEVER be used for hypertensive urgency/emergency. Only long-acting preparations are appropriate.
Examples: hydrochlorothiazide (HCTZ), chlorthalidone, indapamide
- Name breakdown: "Thiazide" refers to the benzothiadiazine chemical structure; "diuretic" = promotes urine production
- Mechanism: Inhibits Na⁺/Cl⁻ co-transporter (NCC) in the distal convoluted tubule → ↑Na⁺ and water excretion → ↓plasma volume → ↓CO. Long-term: also direct arteriolar vasodilation (mechanism not fully understood, possibly via ↓intracellular Na⁺ → ↓Ca²⁺ entry → relaxation).
- Chlorthalidone and indapamide are "thiazide-like" — longer half-life, more potent, and more evidence for CVD outcome reduction than HCTZ.
Contraindications [13]:
| Compelling | Possible |
|---|---|
| Gout (thiazides ↓uric acid excretion → precipitate gout) [13] | Metabolic syndrome; Glucose intolerance; Pregnancy; Hypercalcaemia; Hypokalaemia [13] |
Why metabolic syndrome is a concern: thiazides worsen insulin resistance (↓K⁺ → impairs insulin secretion from β-cells), raise LDL, and raise uric acid — all detrimental in metabolic syndrome. In such patients, ACEI/ARB or CCB may be preferred.
Use thiazide diuretics if thiazide-like diuretics are not available [14]. Current evidence favours chlorthalidone or indapamide over HCTZ for outcomes.
Examples: metoprolol (cardioselective β₁), bisoprolol (cardioselective β₁), atenolol, carvedilol (α₁ + β₁/β₂), labetalol (α + β), nebivolol (β₁ + NO-mediated vasodilation)
- Mechanism: Block β₁ receptors → ↓HR, ↓contractility (↓CO), ↓renin secretion from JG cells. Some (carvedilol, labetalol) also block α₁ → additional vasodilation.
Consider beta-blockers at any treatment step, when there is a specific indication for their use, e.g., heart failure, angina, post-MI, atrial fibrillation, or younger women with, or planning pregnancy [13][14].
Contraindications [13]:
| Compelling | Possible |
|---|---|
| Asthma (β₂ blockade → bronchospasm) [13] | Metabolic syndrome; Glucose intolerance [13] |
| Any high-grade sino-atrial or AV block [13] | Athletes and physically active patients (impairs exercise capacity via ↓CO) [13] |
| Bradycardia (HR < 60/min) [13] |
Why Beta-Blockers Are No Longer First-Line for Uncomplicated HTN
The LIFE trial (losartan vs. atenolol) and meta-analyses showed that atenolol-based regimens had inferior cardiovascular protection compared with other first-line classes, particularly for stroke prevention, despite similar BP reduction. Possible reasons: (1) BB ↑central aortic pressure despite ↓brachial BP (poor pulse wave amplification); (2) metabolic side effects (weight gain, dyslipidaemia, glucose intolerance); (3) ↓exercise tolerance → reduced adherence to lifestyle measures. However, newer vasodilatory BBs (carvedilol, nebivolol) may not share these disadvantages.
Use combination early on if ≥ Stage 2 HTN + 20/10 mmHg above BP goal [2].
Choice of combination therapy: synergistic effect, different mechanisms, counteracting adverse effects [2]:
- Usually A + C or A + D → A + C + D [2][13][14]
- A + C combination was demonstrated to be superior in terms of cardiovascular outcome to A + D in the ACCOMPLISH trial [2]
The ISH 2020 step-up approach [14]:
| Step | Regimen | Notes |
|---|---|---|
| Step 1 | A + C or A + D (dual low-dose) | Consider monotherapy only in low-risk Grade 1 HTN or very old (≥ 80 y) or frailer patients [13][14] |
| Step 2 | A + C or A + D (dual full-dose) | Uptitrate to maximum tolerated doses |
| Step 3 | A + C + D (triple combination) | If still above target on dual therapy |
| Step 4 (Resistant HTN) | Add spironolactone 25–50 mg OD | Caution with spironolactone or other K-sparing diuretics when eGFR < 45 or K > 4.5 mmol/L [14] |
| Beyond Step 4 | Alpha-blocker, beta-blocker, vasodilator | Consider referral to specialist centre for further investigation [13][14] |
Abbreviation key [14]:
- A = ACE-Inhibitor or ARB
- C = DHP-CCB (Dihydropyridine Calcium Channel Blocker)
- D = Thiazide/thiazide-like diuretic
Consider A + D in post-stroke, very elderly, incipient HF, or CCB intolerance [14] Consider A + C or C + D in black patients [14]
Why these combinations work synergistically:
- A + C: ACEI/ARB blocks RAAS; CCB vasodilates. ACEI/ARB also counteracts the reflex ↑RAAS from CCB-induced vasodilation. ACEI/ARB dilates venules → offsets CCB-induced ankle oedema.
- A + D: Thiazide causes mild volume depletion → activates RAAS → would limit BP lowering. Adding ACEI/ARB blocks this compensatory RAAS activation → synergy. Thiazide causes hypoK; ACEI/ARB retains K → counteracts.
- A + C + D: Triple combination leverages all three mechanisms.
DO NOT combine ACEI + ARB — dual RAAS blockade causes harm without benefit (ONTARGET). DO NOT combine non-DHP CCB (verapamil/diltiazem) + beta-blocker — both suppress cardiac conduction → severe bradycardia, AV block, or heart failure.
2nd line Tx: considered if thiazide diuretics have been added [2]:
- Alpha-blocker (e.g., doxazosin) — α₁ blockade → arteriolar vasodilation. Useful in BPH + HTN. Avoid as monotherapy (ALLHAT trial: ↑HF risk).
- Aldosterone antagonist (spironolactone, eplerenone) — particularly effective in resistant HTN (PATHWAY-2 trial). S/E: hyperkalaemia, gynaecomastia (spironolactone).
- Vasodilator (hydralazine, minoxidil) — direct arteriolar smooth muscle relaxation. Potent but causes reflex tachycardia and fluid retention → always combine with BB + diuretic.
Co-morbidities → compelling indications or contraindications [2]:
| Comorbidity | Preferred Drug(s) | Why |
|---|---|---|
| Heart failure (HFrEF) | ACEI/ARB + BB + diuretic + MRA (+ ARNI if tolerated) | RAAS blockade ↓afterload + ↓remodelling; BB ↓HR + ↓remodelling; diuretic ↓congestion; MRA ↓aldosterone-mediated fibrosis |
| Post-MI | ACEI/ARB + BB (± MRA) | ↓Post-MI remodelling, ↓recurrent events, ↓mortality |
| Stable angina / CAD | BB + CCB (DHP) ± ACEI | BB ↓myocardial O₂ demand; DHP-CCB ↓SVR ↓afterload; ACEI ↓remodelling + anti-atherogenic |
| Atrial fibrillation (rate control) | BB or non-DHP CCB (verapamil/diltiazem) | Both slow AV node conduction → ↓ventricular rate |
| CKD with proteinuria | ACEI/ARB | ↓Intraglomerular pressure (efferent > afferent dilation) → ↓proteinuria → slows progression |
| Diabetic nephropathy | ACEI/ARB; consider SGLT2i (empagliflozin, dapagliflozin) | ACEI/ARB: renal protection. SGLT2i: additional renal + CV benefits (DAPA-CKD, CREDENCE trials) |
| Stroke prevention | ACEI/ARB + thiazide (or CCB) | A + D combination is particularly well-supported in post-stroke patients (PROGRESS trial) |
| Elderly / ISH | CCB or thiazide | Target arterial stiffness; both reduce SBP effectively |
| Pregnancy | Labetalol, nifedipine (long-acting), methyldopa | ACEI/ARB absolutely contraindicated in pregnancy [13] (teratogenic: renal agenesis, oligohydramnios) |
| Black patients | A + C or C + D [14] | Black patients tend to have low-renin HTN → less responsive to ACEI/ARB monotherapy; CCB and diuretics more effective |
| OSA-related HTN | CPAP + standard antihypertensives | CPAP treats root cause (intermittent hypoxia → ↓SNS); add drugs as per usual algorithm |
| Phaeochromocytoma | α-blockade FIRST (phenoxybenzamine) → then β-blockade (propranolol) [8] | β-blockade alone causes unopposed α-adrenergic activity → exacerbates HTN. ALWAYS initiate α-blockade before β-blockade → adequate α-blockade indicated by postural BP drop [8]. Alternative: DHP-CCB, metyrosine (inhibits catecholamine synthesis) [8] |
| Conn's syndrome (adenoma) | Laparoscopic adrenalectomy (4 weeks pre-op spironolactone to correct hypoK) [5][4] | Surgical cure; HTN can remain in 40–65% due to irreversible microcirculatory damage [4] |
| Conn's syndrome (BIAH) | Aldosterone antagonist (spironolactone/eplerenone), K-sparing diuretics (amiloride) [4] | Bilateral adrenalectomy would cause adrenal crisis; medical Rx is lifelong |
Recommendations for adherence to antihypertensive therapy [14]:
- Evaluate adherence at each visit and prior to escalation of treatment
- Strategies to improve adherence:
- Reducing polypharmacy — use of single pill combinations (SPCs)
- Once-daily dosing over multiple times per day
- Linking adherence behaviour with daily habits
- Providing adherence feedback to patients
- Home BP monitoring
- Reminder packaging of medications
- Empowerment-based counselling for self-management
- Electronic adherence aids (mobile phones, SMS)
- Multidisciplinary healthcare team approach (pharmacists)
- Objective indirect methods (pharmacy records, pill counting, electronic monitoring) and direct methods (witnessed intake, biochemical detection in urine/blood) are generally preferred over subjective methods to diagnose non-adherence [14]
Approach to Tx-resistant HTN: AT-Home-GOAL [2]:
| Step | Component | Detail |
|---|---|---|
| Exclude pseudoresistance | Adherence | Most common cause! Check pill counts, pharmacy records |
| Timing of drugs | Are they being taken at the correct time? | |
| Home and ambulatory BP | Rule out white-coat effect | |
| Medical Rx | Greater dose of Rx | Uptitrate before adding new agents |
| Other classes: diuretics, Ald blocker | Add spironolactone (PATHWAY-2 trial: most effective add-on in resistant HTN) | |
| Alternative Rx: Combination with different MoA; Loop diuretics if renal disease ± potent vasodilator | In CKD with eGFR < 30, thiazides are less effective → switch to loop diuretics | |
| Contributing factors | Diet, obesity, drugs | Including NSAIDs, herbal medicines |
| Reconsider | Secondary hypertension | Prevalence of secondary causes is 20–30% in resistant HTN |
| Refer | Specialist HTN centre | Consider referral to specialist centre for further investigation [13] |
12. Management of Hypertensive Crisis
Indications for immediate or early treatment for hypertension [13]:
| Hypertensive Emergency (immediate Rx — within 1 hour) | Hypertensive Urgency (early Rx — within 24 hours) | |
|---|---|---|
| Definition | BP > 180/120 + worsening/new TOD [2] | Severe ↑BP without new/worsening TOD [2] |
| Examples | Malignant HT (elevated BP with encephalopathy or nephropathy or papilloedema ± microangiopathic haemolytic anaemia), HT encephalopathy, acute heart failure, unstable angina/MI, dissecting aortic aneurysm, cerebral haemorrhage, renal failure, severe pre-eclampsia, adrenergic crisis [13] | HT with Grade III or IV retinal changes; severe preoperative or perioperative HT [13] |
| Setting | Admit to ICU/CCU with intra-arterial BP monitoring [2] | Monitor frequently, oral agents |
Principle of antihypertensive therapy: controlled reduction as rapid ↓ may precipitate CVA or MI [2]:
- Aim ≤ 25% ↓BP in 1st hour, then to 160/110 in next 2–6h, then cautiously to normal during next 24–48h [2]
- Aim SBP < 140 in 1st hour and < 120 in aortic dissection for those with compelling indications for acute BP control [2]
- Aim 170–180/100 in chronic HTN, elderly, acute CVA [2]
- Aim 140/80 in previously normotensive, post-cardiac or vascular surgery [2]
- Aim SBP 100–120 in acute aortic dissection [2]
Treatment of Hypertensive Emergencies [13]:
| Type of Emergency | Timeline, Target BP | First-Line Therapy | Alternative |
|---|---|---|---|
| HTN crisis with retinopathy, microangiopathy, or acute renal insufficiency | Several hours, MAP −20% to −25% | Labetalol | Nitroprusside, Nicardipine |
| Hypertensive encephalopathy | Immediate, MAP −20% to −25% | Labetalol | Nicardipine, Nitroprusside |
| Acute aortic dissection | Immediate, SBP < 110 mmHg | Nitroprusside + metoprolol | Labetalol |
| Acute pulmonary oedema | Immediate, MAP 60–100 mmHg | Nitroprusside with loop diuretic | Nitroglycerin |
| Acute coronary syndrome | Immediate, MAP 60–100 mmHg | Nitroglycerin | Labetalol |
| Acute ischaemic stroke, BP > 220/120 | 1 hour, MAP −15% | Labetalol | Nicardipine, Nitroprusside |
| Cerebral haemorrhage, SBP > 180 or MAP > 130 | 1 hour, SBP < 180, MAP < 130 | Labetalol | Nicardipine, Nitroprusside |
| Acute ischaemic stroke with indication for thrombolysis, BP > 185/110 | 1 hour, MAP < −15% | Labetalol | Nicardipine, Nitroprusside |
| Cocaine/XTC intoxication | Several hours, SBP < 140 | Phentolamine (after benzodiazepines) | Nitroprusside |
| Phaeochromocytoma crisis | Immediate | Phentolamine | Nitroprusside |
| Perioperative HTN during/after CABG | Immediate | Nicardipine | Nitroglycerin |
| During or after craniotomy | Immediate | Nicardipine | Labetalol |
| Severe pre-eclampsia/eclampsia | Immediate, BP < 160/105 | Labetalol (+ MgSO₄ + oral antihypertensives) | Nicardipine |
| Drug | Mechanism | Dosing | Key Points |
|---|---|---|---|
| Labetalol | Combined α₁ + β₁/β₂ blockade → ↓SVR + ↓HR/contractility | 20 mg IV over 2 min → repeat 40 mg IV bolus if uncontrolled by 15 min → then 0.5–2 mg/min infusion (300 mg/d) → followed by 100–400 mg PO BD [2] | Most versatile emergency drug; safe in most scenarios including stroke and pre-eclampsia |
| Sodium nitroprusside | Direct NO donor → vasodilates both arterioles AND venules → ↓preload + ↓afterload | 0.25–10 μg/kg/min IV infusion [2] | Especially good for acute LV failure, rapid onset of action [2]. Check BP Q2 min till stable, then Q30 min. Protect from light by wrapping, discard after every 12h. Do NOT give in pregnancy or for > 48h (risk of thiocyanide intoxication) [2] |
| Hydralazine | Direct arteriolar vasodilator (opens K⁺ channels → smooth muscle hyperpolarisation) | 5–10 mg slow IV over 20 min, repeat Q30 min [2] | Avoid in MI, aortic dissection [2] (causes reflex tachycardia → ↑myocardial O₂ demand + ↑aortic shear stress). Safe in pregnancy |
| Phentolamine | Non-selective α-blocker → vasodilation | 5–10 mg IV bolus, repeat 10–20 min PRN [2] | For catecholamine crisis [2] (phaeochromocytoma, cocaine/amphetamine toxicity) |
| Nicardipine | IV DHP-CCB → arteriolar vasodilation | 5–15 mg/h IV infusion | Smooth onset, no bolus needed, predictable dose-response. Good for neurosurgical and perioperative settings |
| Nitroglycerin | Primarily venodilator (also some arteriolar) → ↓preload | 5–200 μg/min IV | Preferred in ACS (coronary vasodilation) and APO (↓preload). Less potent arteriolar dilator than nitroprusside |
| Secondary Cause | Definitive Treatment | Bridging/Adjunct Medical Therapy |
|---|---|---|
| Conn's adenoma | Laparoscopic adrenalectomy [4][5] | Spironolactone pre-op for ~4 weeks to correct hypoK and electrolyte balance [5]. Post-op: monitor K (rebound hyperK), monitor Ald (test of cure), continue anti-HTN Rx as needed [4] |
| BIAH | Medical lifelong | Aldosterone antagonist 1st line (spironolactone, eplerenone); K-sparing diuretic 2nd line (amiloride) [4]. Bilateral adrenalectomy would lead to adrenal crisis [5] |
| Phaeochromocytoma | Surgical removal (laparoscopic/robotic) [8] | Pre-op: α-blockade (phenoxybenzamine) → β-blockade (propranolol) for ≥ 7–14 days; ↑Na diet (> 5 g/d) and fluids to reverse catecholamine-induced volume contraction [8]. Post-op: monitor BP, HR, H'stix (risk of HTN crisis, hypotension, rebound hypoglycaemia) [8] |
| Cushing's syndrome | Treat underlying cause (transsphenoidal surgery, adrenalectomy, treat ectopic source) [5] | Anti-HTN Rx as needed; peri-op steroid cover |
| RAS (atherosclerotic) | Medical therapy preferred in most; angioplasty/stenting if: flash APO, resistant HTN, progressive CKD | ACEI/ARB (if unilateral with normal contralateral kidney — monitor Cr), CCB, diuretics |
| RAS (fibromuscular dysplasia) | Percutaneous transluminal angioplasty (PTAS) [11] — high cure rates in FMD | — |
| CKD | BP control + proteinuria control → slow progression | ACEI/ARB (↓proteinuria), salt restriction, loop diuretics if eGFR < 30, avoid nephrotoxins |
| OSA | CPAP (most consistently effective treatment) [15] + weight loss + sleep hygiene | Standard antihypertensives as adjunct |
| Coarctation | Surgical repair or balloon angioplasty/stenting | Anti-HTN Rx peri-operatively; monitor for re-coarctation |
High Yield Summary — Management of Hypertension
Targets: < 130/80 if high risk (DM, CKD, CVD, ASCVD risk ≥ 10%); < 140/90 if low risk. Achieve within 3 months.
Lifestyle: Salt restriction (< 5-6 g/day), DASH diet, weight loss, exercise 30 min/day, alcohol moderation. Applies to ALL patients.
First-line drugs (A, C, D): ACEI/ARB, DHP-CCB, Thiazide. BB only if specific indication (HF, post-MI, angina, AF, pregnancy).
Combination strategy (ISH 2020): Step 1: A+C or A+D (dual low-dose SPC) → Step 2: full-dose → Step 3: A+C+D → Step 4: +Spironolactone → Beyond: alpha-blocker/BB/vasodilator + specialist referral.
Key contraindications: ACEI/ARB: pregnancy, bilateral RAS, K > 5.5, angioedema. DHP-CCB: HFrEF III-IV, tachyarrhythmia. Non-DHP CCB: AV block, bradycardia, LVEF < 40%. Thiazide: gout. BB: asthma, high-grade AV block.
Never combine: ACEI + ARB. Non-DHP CCB + BB.
Resistant HTN (AT-Home-GOAL): Exclude pseudoresistance (adherence, white-coat) → uptitrate → add spironolactone → reconsider secondary causes → refer.
Hypertensive emergency: ICU, IABP. Aim ≤ 25% ↓ in 1st hour → 160/110 over 2-6h → normalise over 24-48h. Key drugs: labetalol, nitroprusside, nicardipine. Aortic dissection: SBP < 110-120 immediately. Sublingual nifedipine is CONTRAINDICATED.
Phaeochromocytoma: Alpha-block FIRST (phenoxybenzamine) → then beta-block. Never beta-block alone (unopposed alpha → ↑BP crisis).
Adherence: Single pill combinations, once-daily dosing, patient empowerment, HBPM, multidisciplinary team.
Active Recall - Management of Hypertension
References
[2] Senior notes: Ryan Ho Cardiology.pdf (p175–183) [4] Senior notes: Ryan Ho Endocrine.pdf (p59) [5] Senior notes: maxim.md (Conn's syndrome, Phaeochromocytoma, Cushing syndrome sections) [8] Senior notes: Ryan Ho Endocrine.pdf (p67 — Phaeochromocytoma management) [11] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p84 — PTAS) [13] Lecture slides: GC 058. High Blood Pressure.pdf (p67, p69, p73, p80, p81, p83) [14] Lecture slides: GC 058. High Blood Pressure.pdf (p86, p87 — ISH 2020) [15] Senior notes: Ryan Ho Respiratory.pdf (p161 — OSA management)
Complications of Hypertension
The complications of hypertension flow directly from the fundamental pathophysiology established in Part 1: chronic elevation in blood pressure exerts mechanical shear stress on the arterial wall and promotes neurohormonal activation (RAAS, SNS, endothelin) → these dual insults cause:
- Large artery disease (accelerated atherosclerosis, aneurysmal degeneration, dissection)
- Small artery/arteriolar disease (hyaline arteriosclerosis, lipohyalinosis, fibrinoid necrosis)
- Target organ damage through ischaemia, pressure overload, and vascular remodelling
Consequences: leads to target organ damage (TOD) → clinical events → death [2]
I will systematically cover complications organ by organ, explaining the "why" from first principles, then address the special catastrophic complications (malignant HTN, hypertensive crisis).
1. Cardiac Complications
The heart is simultaneously exposed to pressure overload (↑afterload from ↑SVR) and coronary atherosclerosis (from endothelial dysfunction and lipid deposition).
Pathology: chronic pressure overload → ventricular remodelling [7]
Why does LVH develop? According to Laplace's Law:
When pressure (afterload) chronically increases, wall stress rises. The myocardium compensates by thickening — concentric hypertrophy — to normalise wall stress. This is initially adaptive but eventually maladaptive:
- Adaptive phase: Thicker walls reduce wall stress → preserved systolic function
- Maladaptive phase: Hypertrophied myocytes become fibrotic, have ↓capillary density (relative ischaemia), and develop impaired relaxation
Consequences of LVH:
- Diastolic dysfunction → the stiff LV fills poorly → ↑LV filling pressures → pulmonary congestion → exertional dyspnoea → HFpEF (Heart Failure with preserved Ejection Fraction)
- Arrhythmias — disorganised myocardial fibres + fibrosis create re-entrant circuits → atrial fibrillation (from LA dilatation due to ↑filling pressures) and ventricular arrhythmias → sudden cardiac death
- Subendocardial ischaemia — ↑myocardial O₂ demand (↑muscle mass) but ↓supply (↓capillary density, ↑diastolic wall tension compresses intramural coronaries) → "LV strain" pattern on ECG (ST depression + T inversion in lateral leads)
LVH is an independent predictor of cardiovascular events — even after correcting for BP level. This is why echocardographic LVH assessment matters.
Cardiac complications: ventricles → LVH, HFpEF [7]
The progression:
- Concentric LVH → diastolic dysfunction → HFpEF (most common initial pattern in HTN)
- Progressive myocyte death and fibrosis → eccentric dilatation → HFrEF
- In malignant HTN: acute ↑afterload overwhelms compensatory mechanisms → acute LV failure [2]
Others: AF, coronary artery disease [7]
HTN accelerates atherosclerosis through:
- ↑Endothelial shear stress → endothelial injury → ↑LDL entry into vessel wall → foam cell formation → plaque
- ↑Smooth muscle proliferation → plaque growth
- ↑Inflammatory mediators (Ang II is pro-inflammatory) → plaque instability → rupture → ACS
Combined with LVH-induced ↑O₂ demand, this creates a devastating supply-demand mismatch → angina, MI, ischaemic cardiomyopathy.
- LVH → diastolic dysfunction → ↑LA pressure → LA dilatation → structural substrate for AF
- AF then → loss of atrial "kick" (contributes 20-30% of CO) → further haemodynamic compromise
- AF + HTN → ↑stroke risk (CHA₂DS₂-VASc scoring)
Cardiac Complications — Summary
Cardiac [7]:
- LVH → diastolic dysfunction → HFpEF → eventually HFrEF
- Coronary artery disease → angina, MI
- Atrial fibrillation → thromboembolic stroke
- Acute LV failure (in malignant HTN / hypertensive emergency)
These are the leading cause of death in hypertensive patients.
2. Cerebrovascular Complications
Nervous system: cerebrovascular accident [3]
Stroke is the most devastating complication of HTN in the Chinese/HK population — it is more common than IHD as the first presentation of HTN-related vascular disease in Asians.
Ischaemic stroke (75-80% of all strokes) [16]
HTN promotes ischaemic stroke via multiple mechanisms:
- Large artery atherosclerosis: HTN accelerates atheroma in carotid bifurcation, vertebrobasilar system, intracranial arteries → artery-to-artery embolism or in-situ thrombosis
- Small vessel disease: hypertensive lipohyalinosis (commonest cause of small vessel disease) [16] → occlusion of perforating arteries → lacunar infarcts (small deep infarcts in basal ganglia, thalamus, internal capsule, pons)
- Cardioembolism: HTN → AF (see above) → thrombus in LA appendage → cerebral embolism
Lacunar syndromes (classic small vessel/HTN-related strokes):
- Pure motor hemiparesis (posterior limb of internal capsule)
- Pure sensory stroke (thalamus)
- Ataxic hemiparesis (pons/internal capsule)
- Dysarthria-clumsy hand syndrome (pons)
Haemorrhagic stroke: mostly related to hypertension [11]
This is the hallmark "hypertensive complication" — and a leading cause of stroke-related death.
Pathophysiology:
- Chronic HTN → lipohyalinosis of small perforating arteries (lenticulostriate, thalamoperforating, paramedian pontine arteries) → weakened vessel walls → formation of Charcot-Bouchard microaneurysms → rupture under acute ↑BP → ICH
Aetiology of ICH (in order of prevalence) [15]:
- Hypertensive arteriopathy (rupture of capillary microaneurysms): deep ICH — more central
- Common sites: pons, cerebellum, putamen, thalamus [11][15]
- Cerebral amyloid angiopathy (CAA): lobar ICH — more peripheral [15]
- Others: coagulopathy, structural vascular lesions (Berry aneurysms, AVM), drugs (cocaine) [15]
Appearance on CT [11]:
- Acute: hyperdense (fresh blood is radiodense due to haemoglobin)
- Subacute: isodense (haemoglobin degradation)
- Chronic: hypodense (liquefaction)
The location tells you the cause:
| Location | Likely Cause |
|---|---|
| Putamen (most common) | Hypertensive arteriopathy (lenticulostriate arteries) |
| Thalamus | Hypertensive arteriopathy (thalamoperforating arteries) |
| Pons | Hypertensive arteriopathy (paramedian pontine branches) |
| Cerebellum | Hypertensive arteriopathy (cerebellar branches of PICA/SCA) |
| Lobar (cortical/subcortical) | Cerebral amyloid angiopathy, AVM, tumour |
HTN encephalopathy: cerebral oedema → insidious onset of headache, N/V followed by non-localising neurological symptoms (confusion, restlessness), visual disturbances, transient paralysis, seizure, coma [2]
Why does it happen? Normal cerebral autoregulation maintains constant cerebral blood flow (CBF) across a MAP range of ~60–150 mmHg by adjusting arteriolar tone. When BP exceeds the upper autoregulatory limit:
- Arterioles can no longer vasoconstrict sufficiently → forced dilatation → breakthrough hyperperfusion
- Blood-brain barrier breakdown → vasogenic cerebral oedema
- This is often most pronounced posteriorly (posterior reversible encephalopathy syndrome = PRES) → visual symptoms
It is reversible with controlled BP reduction — this is why it's called "reversible encephalopathy." However, if untreated, it can progress to herniation and death.
- Same pathophysiology as ischaemic stroke but symptoms resolve within 24 hours
- TIA is a warning sign — 90-day stroke risk is 10-20% without treatment
Cerebrovascular Complications — Key Points
- HTN is the single most important modifiable risk factor for both ischaemic AND haemorrhagic stroke
- In HK/Chinese populations, stroke (especially haemorrhagic) is relatively more common as the presenting complication of HTN compared to Western populations
- Common sites of hypertensive ICH: pons, cerebellum, putamen, thalamus [11][15] — all deep structures supplied by perforating arteries prone to lipohyalinosis
- Hypertensive encephalopathy = breakthrough cerebral hyperperfusion → vasogenic oedema → reversible with BP control
3. Renal Complications
The kidney is both a cause and a victim of hypertension — a vicious cycle.
Renal: impaired renal function [3]
Pathophysiology:
- Chronic HTN → hyaline arteriosclerosis of the afferent arterioles → narrowed lumen → ↓glomerular perfusion → glomerular ischaemia → progressive nephron loss → CKD
- Additionally: ↑intraglomerular pressure (if afferent arteriosclerosis is not uniform) → glomerular hyperfiltration → glomerulosclerosis → further nephron loss
- The remaining nephrons compensate by hyperfiltration → further damage → progressive GFR decline
This creates a vicious cycle: CKD → impaired Na⁺ excretion → volume overload → worsening HTN → further renal damage.
Two forms:
- Benign nephrosclerosis: slow progression over years/decades; most common cause of ESRD attributed to HTN
- Malignant nephrosclerosis: in malignant HTN → fibrinoid necrosis of arterioles → rapid ↓GFR → acute RF with oliguria, proteinuria [2]
CKD is an independent risk factor for cardiovascular disease [17]:
- ↑Prevalence of traditional risk factors: HTN, smoking, DM, dyslipidaemia
- Medial vascular calcification due to ↑Ca balance + ↑PO₄
- ↑Atherosclerosis due to ↑inflammatory state, ↑cytokines, uraemia
Once CKD develops from hypertensive nephrosclerosis, the patient faces the full spectrum of CKD complications:
- Volume overload → oedema, pulmonary oedema [17]
- Hyperkalaemia [17]
- Metabolic acidosis
- Anaemia (↓EPO production)
- Renal osteodystrophy (↓vitamin D activation, ↑PO₄, secondary hyperparathyroidism)
- Uraemic bleeding (platelet dysfunction from uraemic toxins) [17]
- Uraemic pericarditis
- Eventually ESRD requiring RRT (dialysis or transplant)
- Early sign of hypertensive renal damage — appears before GFR decline
- Microalbuminuria or eGFR < 60 mL/min is itself a CVD risk factor [1]
- Represents endothelial dysfunction in glomerular capillaries — a "window" into systemic endothelial health
4. Retinal Complications (Hypertensive Retinopathy)
Eyes: retinal exudates and haemorrhages, papilloedema [3]
Hypertensive retinopathy: majority asymptomatic ± blurring of vision associated with headache [2]
The retina provides a direct window into the microvascular effects of HTN. The pathological process follows a predictable sequence [18]:
Phase 1 — Arteriosclerosis (chronic HTN):
- Prolonged ↑BP → ↑shear stress → arterial sclerosis and hyalinisation [18]
- Vessel wall sclerosis → light reflex becomes more diffuse → copper wiring (red-brown appearance) → further involvement → silver wiring (silvery vessels with no blood column seen) [18]
- Vasospasm occurs in prolonged ↑BP → focal/diffuse narrowing of arterioles [18]
- AV nipping: arteriolar thickening → venous compression at AV junction → "hour-glass" venous constrictions [18]
Phase 2 — Fibrinoid necrosis (acute severe HTN / malignant HTN):
- Acute ↑↑BP → endothelial damage → arteriolar smooth muscle degeneration → endothelial stretching → breakdown of blood-retinal barrier [18]
- → Leakage of transudate and macromolecules → flame/dot-and-blot haemorrhage and hard exudates [18]
- Endothelial dysfunction → plasma clotting → retinal ischaemia → fluffy cotton wool spots [18]
- Leakage + ischaemia at optic disc → papilloedema + disc haemorrhage [18]
Fundoscopy: classification based on Modified Scheie classification [18]:
| Malignant Hypertension | Chronic Arteriosclerotic Changes | |
|---|---|---|
| Grade 1 | Barely detectable arterial narrowing | Stage 1: Widening of arteriole reflex |
| Grade 2 | Obvious arterial narrowing with focal irregularities | Stage 2: Arteriovenous crossing sign |
| Grade 3 | G2 + retinal haemorrhages, exudates, cotton wool spots, or retinal oedema | Stage 3: Copper-wire arteries |
| Grade 4 | G3 + papilloedema | Stage 4: Silver-wire arteries |
Complications of hypertensive retinopathy [18]:
- Retinal vascular disease: CRAO/BRAO, CRVO/BRVO, retinal arterial macroaneurysms
- Retinal ischaemia: neovascularisation (vitreous haemorrhage, rhegmatogenous retinal detachment), epiretinal membrane
- ↑Progression of DM retinopathy (HTN is a major accelerating factor!)
- Chronic papilloedema: optic nerve atrophy → permanent visual loss
CRVO: acute sudden onset painless blurring of vision [2] — caused by thrombus in the central retinal vein at the lamina cribrosa, where the artery and vein share a common adventitial sheath. HTN-induced arteriosclerosis compresses the vein → stasis → thrombosis.
5. Vascular Complications
Vessels: macrovascular atherosclerosis + microvascular hyaline arteriosclerosis [7]
- HTN → ↑wall stress on the aorta → medial degeneration (↓elastin, ↑collagen) → aneurysmal dilatation
- Abdominal aortic aneurysm (AAA) — infrarenal is most common site
- Risk of rupture increases with size: Aneurysm < 5 cm = 20% rupture at 5 years; > 5 cm = 50% [19]
HTN is the most important risk factor for aortic dissection [19]:
Pathophysiology:
- Tear in aortic intima → blood passes into aortic media → creates a false lumen separating intima from media/adventitia [19]
- False lumen dilation depends on BP, size of entry tear, depth of dissection plane [19]
- HTN → chronically weakened media (cystic medial degeneration) → prone to tearing under acute ↑BP stress
Complications of dissection [19]:
- Type A:
- Dissection into aortic valvular annulus → Aortic regurgitation
- Dissection into pericardium → Cardiac tamponade
- Dissection into coronary artery ostia → Myocardial infarction
- Focal neurological deficits from cerebrovascular ischaemia
- Type B:
- Dissection into abdominal aortic branches → Coeliac / Renal / Lower limb ischaemia
- Focal neurological deficits from spinal ischaemia
- HTN accelerates atherosclerosis in the lower limb arteries → intermittent claudication → critical limb ischaemia
- Also carotid artery stenosis → ↑stroke risk; mesenteric atherosclerosis → chronic mesenteric ischaemia
- Accelerated atherosclerosis at the carotid bifurcation
- Significance: major source of artery-to-artery embolism causing ischaemic stroke
Malignant hypertension: defined as BP ≥ 220/120 + Grade 3–4 fundal changes [2]
This represents a catastrophic, self-perpetuating vascular emergency. The pathophysiology is a vicious cycle:
- Severe ↑BP → fibrinoid necrosis of arterioles → endothelial damage → platelet aggregation → intravascular thrombosis [2]
- Renal arteriolar damage → ↓renal perfusion → ↑renin → ↑Ang II → further ↑BP
- Red cells shear through damaged microcirculation → microangiopathic haemolytic anaemia (MAHA) with schistocytes
- Cycle escalates rapidly unless interrupted
Clinical presentation: ↑BP + rapidly progressive TOD [2]:
- Retina: papilloedema, retinal haemorrhages and exudates
- HTN encephalopathy: severe headache, vomiting, visual disturbances, transient paralyses, convulsions, stupor and coma
- Heart: acute LV failure
- Kidneys: acute RF with oliguria, proteinuria
Rare but lethal: < 1% of HTN population, 25–50% 5-year mortality if untreated [2]
Malignant HT is defined as elevated BP with encephalopathy or nephropathy or papilloedema ± microangiopathic haemolytic anaemia [13]
| Target Organ | Complication | Pathophysiology |
|---|---|---|
| Heart | LVH → HFpEF → HFrEF | Pressure overload → concentric hypertrophy → fibrosis → dysfunction |
| CAD → Angina, MI | Accelerated atherosclerosis + ↑O₂ demand from LVH | |
| AF | LA dilatation from diastolic dysfunction → re-entry substrate | |
| Acute LV failure | Acute ↑afterload overwhelms myocardium (malignant HTN) | |
| Brain | Ischaemic stroke (lacunar, large vessel, cardioembolic) | Lipohyalinosis → lacunar; atherosclerosis → large vessel; AF → embolic |
| Haemorrhagic stroke (ICH) | Charcot-Bouchard microaneurysm rupture in perforating arteries | |
| HTN encephalopathy | Breakthrough hyperperfusion → vasogenic oedema | |
| TIA | Same as ischaemic stroke but transient | |
| Vascular dementia | Chronic small vessel disease → lacunar infarcts → cognitive decline | |
| Kidneys | Hypertensive nephrosclerosis → CKD → ESRD | Afferent arteriolar hyalinosis → glomerular ischaemia → nephron loss |
| Malignant nephrosclerosis | Fibrinoid necrosis → acute renal failure | |
| Proteinuria / Microalbuminuria | Glomerular endothelial dysfunction → ↑permeability | |
| Eyes | Hypertensive retinopathy (Grade 1–4) | Arteriosclerosis → fibrinoid necrosis → haemorrhage/exudates/papilloedema |
| CRAO / BRAO / CRVO / BRVO | Atherothrombosis / compressive occlusion at AV crossing | |
| Optic nerve atrophy | Chronic papilloedema → axonal damage | |
| Vessels | Aortic aneurysm (AAA/TAA) | Medial degeneration from chronic ↑wall stress |
| Aortic dissection | Intimal tear → false lumen propagation | |
| PAD | Accelerated atherosclerosis in lower limb arteries | |
| Carotid stenosis | Atherosclerosis at carotid bifurcation → embolic stroke risk |
Understanding complications feeds directly into management:
| Complication | Treatment Implication |
|---|---|
| LVH / HFpEF / HFrEF | ACEI/ARB (↓remodelling), BB (↓HR, ↓remodelling), MRA (↓fibrosis) |
| Post-MI | ACEI/ARB + BB — proven mortality benefit |
| AF | Rate control (BB or non-DHP CCB), anticoagulation (CHA₂DS₂-VASc) |
| CKD with proteinuria | ACEI/ARB (↓intraglomerular pressure, ↓proteinuria), SGLT2i (renal + CV benefit) |
| Post-stroke | Long-term BP control (A + D particularly evidence-based — PROGRESS trial) |
| Aortic dissection | Immediate SBP < 110–120 + ↓HR (BB + nitroprusside) |
| Malignant HTN | ICU admission, controlled IV BP reduction (≤25% in 1st hour) |
High Yield Summary — Complications of Hypertension
Cardiac (leading cause of death): LVH → diastolic dysfunction → HFpEF → HFrEF. CAD → MI. AF → thromboembolic stroke.
Cerebrovascular (leading cause of disability): Ischaemic stroke (lacunar from lipohyalinosis; large vessel from atherosclerosis; embolic from AF). Haemorrhagic stroke (Charcot-Bouchard microaneurysm rupture; common sites: putamen, thalamus, pons, cerebellum). HTN encephalopathy (breakthrough hyperperfusion → vasogenic oedema → reversible with treatment).
Renal: Hypertensive nephrosclerosis (afferent arteriolar hyalinosis → glomerular ischaemia → CKD). Malignant nephrosclerosis (fibrinoid necrosis → AKI). CKD creates a vicious cycle (↓Na excretion → volume overload → ↑BP).
Retinal: Graded by Modified Scheie (Grade 1–4). Grade 3–4 defines malignant HTN. Complications include CRAO/CRVO, neovascularisation, optic atrophy.
Vascular: AAA/TAA, aortic dissection (HTN is #1 risk factor), PAD, carotid stenosis.
Malignant HTN: BP ≥ 220/120 + Grade 3–4 retinopathy. Fibrinoid necrosis + intravascular thrombosis → MAHA + encephalopathy + AKI + APO. Self-perpetuating vicious cycle. 25–50% 5-year mortality untreated.
Key concept: Stroke is the predominant presenting complication in Chinese/HK populations (more so than IHD in Western populations).
Active Recall - Complications of Hypertension
References
[1] Lecture slides: GC 058. High Blood Pressure.pdf (p29 — CVD risk factors) [2] Senior notes: Ryan Ho Cardiology.pdf (p179, p182 — TOD, malignant HTN) [3] Lecture slides: GC 058. High Blood Pressure.pdf (p49 — Risk factors for adverse prognosis, end-organ damage) [7] Senior notes: Ryan Ho Cardiology.pdf (p178 — TOD table) [11] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p41 — Haemorrhagic stroke) [13] Lecture slides: GC 058. High Blood Pressure.pdf (p80 — Malignant HT definition) [15] Senior notes: maxim.md (ICH aetiology and management) [16] Senior notes: Ryan Ho Neurology.pdf (p74 — Cerebrovascular diseases, aetiology) [17] Senior notes: Ryan Ho Urogenital.pdf (p105, p109 — CKD complications, CV risk) [18] Senior notes: Ryan Ho Opthalmology.pdf (p72–73 — Hypertensive retinopathy pathophysiology and classification) [19] Senior notes: felixlai.md (Aortic dissection pathogenesis and complications)
High Yield Summary
Definition: HTN = abnormally ↑BP. Treated because of TOD risk, not symptoms.
Epidemiology: ~1 billion worldwide; ~20% prevalence in HK. Most common cause of CVD globally. Stroke is the predominant complication in Chinese populations.
BP = CO × SVR — every cause of HTN acts through one or both.
Essential HTN (95%): Polygenic + environmental (salt, obesity, alcohol, sedentary). Pathogenesis: ↑SNS + abnormal renal Na⁺ handling + ↑RAAS + endothelial dysfunction + arterial stiffness. Young = ↑SNS/RAAS; Elderly = arterial degeneration.
Secondary HTN (5%): DANCER — Drugs, Apnoea, Neurological, Coarctation, Endocrine, Renal. Suspect if < 30 y onset, resistant HTN, abrupt onset, hypokalaemia, or specific clinical clues.
Classification: ACC/AHA 2017: Stage 1 ≥ 130/80, Stage 2 ≥ 140/90, Crisis > 180/120. White-coat HTN: ↑office, normal ABPM. Masked HTN: normal office, ↑ABPM (higher risk!).
Clinical Features: Usually asymptomatic. Symptoms when present: headache (occipital, morning), dizziness, palpitations, fatigue. TOD symptoms: epistaxis, visual changes, angina, dyspnoea, stroke symptoms. Signs: displaced apex (LVH), S4, loud A₂, fundoscopic changes (KWB grading), renal bruit.
Target Organ Damage: Heart (LVH → HF), Brain (stroke), Kidneys (nephrosclerosis → CKD), Eyes (retinopathy), Peripheral arteries (PAD, aneurysm).
Malignant HTN: BP ≥ 220/120 + Grade 3–4 fundoscopy. Fibrinoid necrosis. Lethal without treatment.
Metabolic Syndrome: Central obesity → insulin resistance → HTN + dyslipidaemia + DM + NAFLD + PCOS.
High Yield Summary
Level 1: Essential (95%) vs. Secondary (5%) — suspect secondary if onset < 30 y or diastolic HTN ≥ 65 y, resistant/malignant HTN, abrupt onset, hypokalaemia, or specific clinical clues.
Level 2 — Secondary causes (DANCER):
- D — Drugs (NSAIDs, OCP, steroids, sympathomimetics, anti-VEGF agents, herbal medicines)
- A — Apnoea (OSA, 25–50% of resistant HTN)
- N — Neurological (↑ICP, stress)
- C — Coarctation (young HTN, radiofemoral delay, UL > LL BP)
- E — Endocrine: primary aldosteronism (8–20%, ARR screen), Cushing's (DST), phaeochromocytoma (urine metanephrines), thyroid disease, hyperparathyroidism, acromegaly
- R — Renal: RAS (duplex USG), renal parenchymal disease (urinalysis, renal USG)
Primary aldosteronism subtypes: Adenoma (30-40%) vs. BIAH (60-70%) — differentiated by postural test: adenoma = paradoxical ↓aldo; BIAH = ↑aldo.
Phaeochromocytoma 5 P's: Pressure, Pain, Palpitation, Perspiration, Pallor.
Resistant HTN: Exclude pseudoresistance first (adherence, white-coat effect), then screen for secondary causes (AT-Home-GOAL).
Hypertensive crisis: Emergency (TOD present) vs. Urgency (no TOD) — different management timelines.
Always consider: Drug history (including herbals in HK), measurement artefact, white-coat HTN.
High Yield Summary
Diagnostic Thresholds: Office ≥ 140/90 (ESC) or ≥ 130/80 (ACC/AHA). HBPM ≥ 135/85. ABPM 24h ≥ 130/80. Confirm office readings with HBPM/ABPM unless crisis (> 180/120) or obvious TOD.
Three Aims of Evaluation: (1) CVD risk factors, (2) Rule out secondary HTN, (3) Assess TOD.
Tier 1 — Routine for ALL: History (age, FHx, drugs, lifestyle), bilateral arm BP supine/standing, BMI, fundoscopy, CVS exam. Bloods: RFT + electrolytes, fasting glucose, lipid profile. Urinalysis + UACR. ECG ± echo. 10-year CVD risk.
Tier 2 — Secondary Screening (if red flags):
- Conn's: ARR → salt loading test → postural test → CT + AVS. Precaution: drug washout ≥ 2 weeks.
- Phaeochromocytoma: 24h urine fractionated metanephrines (98% Sens/Spec) → CT → MIBG/PET.
- Cushing's: DST / UFC / late-night salivary cortisol → ACTH level → HDDST/CRH → imaging.
- RAS: Renal duplex USG → MRA → CTA → DSA.
- Renal parenchymal: Renal USG + urinalysis → biopsy.
- OSA: Polysomnography. Coarctation: Echo + CTA. Thyroid: TSH.
Tier 3 — TOD Assessment: Heart (ECG: LVH/strain; echo: mass, diastolic function), Brain (CT/MRI), Kidney (eGFR, UACR), Eyes (fundoscopy), Vessels (ABI, carotid USG).
ABPM patterns: Non-dipping/reverse dipping = ↑TOD risk. Morning surge = ↑AM cardiac events.
Prevalence in specialty clinics: Essential 65–85%, renal parenchymal 4–5%, renovascular 4–16%, endocrine 0.5–12%.
High Yield Summary
Targets: < 130/80 if high risk (DM, CKD, CVD, ASCVD risk ≥ 10%); < 140/90 if low risk. Achieve within 3 months.
Lifestyle: Salt restriction (< 5-6 g/day), DASH diet, weight loss, exercise 30 min/day, alcohol moderation. Applies to ALL patients.
First-line drugs (A, C, D): ACEI/ARB, DHP-CCB, Thiazide. BB only if specific indication (HF, post-MI, angina, AF, pregnancy).
Combination strategy (ISH 2020): Step 1: A+C or A+D (dual low-dose SPC) → Step 2: full-dose → Step 3: A+C+D → Step 4: +Spironolactone → Beyond: alpha-blocker/BB/vasodilator + specialist referral.
Key contraindications: ACEI/ARB: pregnancy, bilateral RAS, K > 5.5, angioedema. DHP-CCB: HFrEF III-IV, tachyarrhythmia. Non-DHP CCB: AV block, bradycardia, LVEF < 40%. Thiazide: gout. BB: asthma, high-grade AV block.
Never combine: ACEI + ARB. Non-DHP CCB + BB.
Resistant HTN (AT-Home-GOAL): Exclude pseudoresistance (adherence, white-coat) → uptitrate → add spironolactone → reconsider secondary causes → refer.
Hypertensive emergency: ICU, IABP. Aim ≤ 25% ↓ in 1st hour → 160/110 over 2-6h → normalise over 24-48h. Key drugs: labetalol, nitroprusside, nicardipine. Aortic dissection: SBP < 110-120 immediately. Sublingual nifedipine is CONTRAINDICATED.
Phaeochromocytoma: Alpha-block FIRST (phenoxybenzamine) → then beta-block. Never beta-block alone (unopposed alpha → ↑BP crisis).
Adherence: Single pill combinations, once-daily dosing, patient empowerment, HBPM, multidisciplinary team.
High Yield Summary
Cardiac (leading cause of death): LVH → diastolic dysfunction → HFpEF → HFrEF. CAD → MI. AF → thromboembolic stroke.
Cerebrovascular (leading cause of disability): Ischaemic stroke (lacunar from lipohyalinosis; large vessel from atherosclerosis; embolic from AF). Haemorrhagic stroke (Charcot-Bouchard microaneurysm rupture; common sites: putamen, thalamus, pons, cerebellum). HTN encephalopathy (breakthrough hyperperfusion → vasogenic oedema → reversible with treatment).
Renal: Hypertensive nephrosclerosis (afferent arteriolar hyalinosis → glomerular ischaemia → CKD). Malignant nephrosclerosis (fibrinoid necrosis → AKI). CKD creates a vicious cycle (↓Na excretion → volume overload → ↑BP).
Retinal: Graded by Modified Scheie (Grade 1–4). Grade 3–4 defines malignant HTN. Complications include CRAO/CRVO, neovascularisation, optic atrophy.
Vascular: AAA/TAA, aortic dissection (HTN is #1 risk factor), PAD, carotid stenosis.
Malignant HTN: BP ≥ 220/120 + Grade 3–4 retinopathy. Fibrinoid necrosis + intravascular thrombosis → MAHA + encephalopathy + AKI + APO. Self-perpetuating vicious cycle. 25–50% 5-year mortality untreated.
Key concept: Stroke is the predominant presenting complication in Chinese/HK populations (more so than IHD in Western populations).
Dyslipidaemia
Dyslipidaemia is an abnormal elevation or reduction of lipids (cholesterol, triglycerides, or both) in the blood, increasing the risk of atherosclerotic cardiovascular disease.
Nstemi
Non-ST-elevation myocardial infarction (NSTEMI) is an acute coronary syndrome characterized by myocardial necrosis with elevated cardiac biomarkers but without persistent ST-segment elevation on electrocardiography.