All hypertension ultimately results from increased cardiac output (CO), increased total peripheral resistance (TPR), or both. ^[4]

In young hypertensives: The initial phase is often a high-CO state driven by sympathetic overactivity, RAAS activation, and increased renal sodium reabsorption. Over time, structural vascular remodelling (arteriolar hypertrophy, endothelial dysfunction) shifts the physiology to a high-TPR state.

In elderly hypertensives: Arterial stiffness dominates → ISH as described above. Renal disease and aldosterone excess also contribute. ^[1]

1. RAAS (Renin-Angiotensin-Aldosterone System): Angiotensin II is a potent arteriolar vasoconstrictor and stimulates aldosterone → Na+/water retention → ↑ blood volume → ↑ BP. This is why ACEI/ARBs are so effective.
2. Sympathetic nervous system: ↑ catecholamines → ↑ HR, ↑ contractility, ↑ vasoconstriction.
3. Renal sodium handling: Guyton's pressure-natriuresis curve is shifted rightward in essential HTN — the kidneys need a higher perfusion pressure to excrete the same amount of sodium.
4. Endothelial dysfunction: ↓ nitric oxide, ↑ endothelin-1 → vasoconstriction.
5. Arterial stiffness: Particularly in ageing.

• Excess dietary sodium (DASH diet evidence)
• Obesity → insulin resistance → sympathetic activation + sodium retention
• Alcohol excess
• Physical inactivity
• Stress

• Positive family history (essential HTN is polygenic)
• Specific monogenic forms exist but are rare (e.g., Liddle syndrome, GRA)

• Patient seated for ≥ 5 minutes, back supported, legs uncrossed, arm at heart level
• Appropriate cuff size (bladder covers ≥ 80% of arm circumference)
• No caffeine, exercise, or smoking for 30 minutes prior
• Take ≥ 2 readings, 1–2 minutes apart; use the average
• Measure in BOTH arms initially — if persistent difference > 15–20 mmHg, use the higher arm (and investigate for subclavian stenosis or coarctation)
• Check standing BP (at 1 and 3 minutes) in elderly, diabetics, those on antihypertensives — to detect orthostatic hypotension

• Use a validated electronic (oscillometric) upper-arm cuff device; mercury sphygmomanometers are banned in most countries
• For auscultatory devices: use 1st Korotkoff sound for SBP, 5th Korotkoff sound for DBP
• Take 3 measurements at each visit, 1 minute apart; use the average of the last 2 readings
• A smaller cuff overestimates BP; a larger cuff underestimates BP
• BP measured at 2–3 office visits ≥ 140/90 mmHg indicates hypertension

Out-of-office thresholds are lower than office thresholds. In this ESC/ISH table the usual diagnostic comparison is 140/90 in clinic versus 135/85 at home or by daytime ABPM—not “10 mmHg lower” for both components. ^[1][14]

Self-measurement of BP at home is of clinical value and its prognostic significance is now demonstrated. ^[1]

Advantages:

• More readings → better representation of true BP
• Detects white-coat effect
• Improves patient adherence
• Assesses therapeutic coverage (trough drug effect)

Should be discouraged when: it causes patient anxiety or leads to self-modification of treatment. ^[1]

A reproducible home series: take 2 seated measurements at least 1 minute apart, morning and evening, for at least 4 days (ideally 7); discard day 1 and average the remainder. Use a validated upper-arm device and do not change medication from isolated readings without a clinician-agreed plan. NICE uses this protocol to confirm diagnosis when ABPM is unsuitable. ^[15]

Indications for ABPM: considerable variability of office BP, marked discrepancy between office vs. home BP, resistant HTN, suspected hypotensive episodes (especially elderly and DM), suspected pre-eclampsia in pregnancy. ^[1]

ABPM provides night-time readings — this is a unique advantage over HBPM. Night-time BP (the "dipping" pattern) has strong prognostic value. Non-dippers (< 10% nocturnal fall) and reverse dippers have worse cardiovascular outcomes. ^[5]

The lecture's illustrated 24-hour trace should be read by its mean daytime, night-time and 24-hour BP, not by the highest single spike. A morning rise is physiological; its interpretation depends on the whole profile. A commonly used minimum-quality benchmark is about 20 valid awake and 7 valid asleep readings, although local laboratory criteria vary. ^[1]

Out-of-office BP measurements (HBPM and ABPM) correlate more strongly with target organ damage markers (LVH, albumin excretion) than office BP. ABPM shows the highest correlation in all comparisons. ^[1]

Definition: Office BP is persistently elevated whereas BP outside clinic is normal, usually diagnosed by ambulatory or home BP monitoring. Prevalence: 15–30% of general population, commonly in elderly and pregnant women. ^[1]

Lecture-era wording: risk is lower than sustained hypertension and the patient should be reassured. ^[1]

Current safety correction: white-coat hypertension is not “no risk.” Confirm it with ABPM/HBPM, assess overall cardiovascular risk and hypertension-mediated organ damage, give lifestyle advice, and repeat office plus out-of-office monitoring because progression to sustained hypertension is common. Medication is not automatic, but may be considered when risk or organ damage is high; avoid both reflex treatment and blanket reassurance. ^[14]

Why does it happen? An exaggerated alerting/anxiety response to the clinical environment activating the sympathetic nervous system → transient BP elevation.

Clinical implications:

• Consider it whenever clinic and out-of-office readings disagree
• In non-emergency diagnosis, confirm persistent office elevation with ABPM/HBPM before labelling or intensifying treatment
• These patients need regular follow-up as they may develop sustained HTN over time

The opposite: Normal office BP but elevated out-of-office BP. This is more dangerous than white-coat HTN because it goes undetected and carries cardiovascular risk similar to sustained HTN.

The slide's cohort graph shows roughly 11 events/1000 patient-years with normal BP, 12 with white-coat hypertension, 30 with masked hypertension and 25 with sustained uncontrolled hypertension. Treat these as one study's visual comparison, not universal event rates; the durable message is that masked hypertension is not benign. ^[1]

Screen more actively with young onset (especially < 40 years), abrupt onset or worsening, resistant hypertension, severe hypertension/emergency, disproportionate HMOD, or a specific clue such as kidney disease/renal bruit, episodic catecholamine symptoms, spontaneous or diuretic-associated hypokalaemia, adrenal mass, Cushingoid features, OSA, or radiofemoral delay. “New onset after 55” alone is too nonspecific to be a rule. The 2025 Endocrine Society additionally suggests PA screening in all people with hypertension, conditional on local resources. ^[14][16]

A — Accuracy of diagnosis, Apnea (OSA). B — Bruit (renal artery stenosis), Bad kidney (renal failure, polycystic kidney). C — Catecholamine (phaeochromocytoma), Cushing, Coarctation. D — Diet (salt/alcohol/obesity), Drugs (NSAIDs, COX-2 inhibitors, estrogens/OCP, immunosuppressants, EPO, sympathomimetics, steroids). E — Erythropoietin, Endocrine (hyperaldosteronism, thyroid disease, hyperparathyroidism). ^[1]

Visual physiology: autonomous aldosterone expands sodium/volume and suppresses renin, so the characteristic biochemical signal is inappropriately high aldosterone with low renin. Hypokalaemic metabolic alkalosis is a severe phenotype, but most patients are not identified by hypokalaemia alone. ^[1][16]

Screening → Confirmation → Subtyping algorithm:

1. Measure aldosterone, renin and K⁺ in the morning while seated; avoid sodium restriction and interpret medication interference and local assay cut-offs.
2. Suppressed renin + inappropriately high aldosterone/ARR is a positive screen. Correct hypokalaemia and repeat if it could have caused a false-negative aldosterone.
3. Aldosterone-suppression testing is selective, chiefly when an intermediate result must be clarified before pursuing surgical cure; overt renin-independent secretion or a plan for medical treatment may bypass it.
4. If surgery is desired and appropriate, obtain adrenal CT plus AVS for reliable lateralisation. A possible AVS exception is a patient < 35 years with marked PA, hypokalaemia and a > 1 cm unilateral adenoma.
   • Lateralisation → unilateral laparoscopic adrenalectomy (APA)
   • No lateralisation → pharmacological therapy with MRA (IHA/GRA)

Clinical findings: narrow upper airway (neck circumference > 42 cm men / > 39 cm women), macroglossia, non-dipper pattern on ABPM, tachycardia and/or bradycardia, LVH, cor pulmonale, pulmonary hypertension, obesity, peripheral oedema. ^[1]

Screening pathway:

1. Screening questionnaire (e.g., Epworth Sleepiness Scale)
2. Polysomnography → classify by AHI:
   • AHI 5–15/h → mild
   • AHI 15–30/h → moderate
   • AHI > 30/h → severe

The slide shows CTA/MRA and pre-/post-stent renal angiograms. Those images demonstrate anatomy, not that every stenosis needs a stent. Routine revascularisation for atherosclerotic renal artery stenosis has not improved outcomes over good medical therapy in unselected patients. Refer selected high-risk syndromes—recurrent flash pulmonary oedema/heart failure, rapidly declining kidney function with bilateral/solitary-kidney disease, or truly refractory hypertension—for specialist consideration; angiography is generally reserved for cases in which intervention is being considered. ^[17]

OSA treatment: Weight reduction, CPAP, mandibular advancement splints. The polysomnography diagram shows repeated obstruction followed by sympathetic and BP surges; CPAP treats the OSA and usually produces only a modest average BP reduction, so antihypertensive treatment may still be required. ^[1]

The slide's “ABCD” mnemonic lists ACEI/ARB, beta-blocker, CCB and diuretic. In current uncomplicated hypertension, the core first-line classes are a RAS blocker, dihydropyridine CCB and thiazide/thiazide-like diuretic; beta-blockers are usually chosen for a separate indication such as angina/post-MI, HFrEF, rate control or pregnancy. ^[1][14]

First-line combinations: CCB + ACEI/ARB OR ACEI/ARB + Diuretic. Triple: CCB + ACEI/ARB + Diuretic. Rationale: synergistic effects, act on different mechanisms, counteracting adverse effects. ^[1]

Why combine early? Most hypertensive patients (especially Grade 2+) will need ≥ 2 drugs. Using low doses of two complementary agents gives better BP reduction with fewer side effects than maximising one drug. Single-pill combinations (SPC/fixed-dose combinations) improve adherence. ^[1]

Grade 1 HTN (140–159/90–99):

1. Start lifestyle interventions
2. Start drug treatment in high-risk patients (CVD, CKD, DM, organ damage, or aged 50–80 years)
3. For all others: start drugs if BP remains elevated after 3–6 months of lifestyle intervention

Grade 2 HTN (≥ 160/100):

1. Start drug treatment immediately
2. Start lifestyle intervention concurrently

The slide splits treatment into “Black” and “non-Black” pathways. Preserve that distinction only as historical guideline recognition, not as a biological rule. Current ESC practice generally starts most patients who need medication with a low-dose, preferably single-pill ACEI/ARB + DHP-CCB or thiazide/thiazide-like diuretic, then uses triple therapy if required. Choose and review treatment using comorbidities, kidney function, potassium, prior response, adverse effects, pregnancy potential, access and patient preference rather than race alone. ^[14]

No ACEI/ARB in women who are pregnant or planning pregnancy. ^[1]

Spironolactone caution: use with care when eGFR < 45 mL/min/1.73 m² or K⁺ > 4.5 mmol/L. ^[1]

Key monitoring parameters for each drug class: ^[1]

Step 1: Exclude pseudoresistance — check adherence, timing of drug, confirm with home/ambulatory BP. Step 2: Look for contributing factors — high salt diet, obesity, interfering agents (NSAIDs, OCP). Step 3: Second look for secondary HTN. Step 4: Medical Rx — increase doses, add aldosterone blocker (spironolactone), use loop diuretic in renal disease, add potent vasodilator. Step 5: Referral. ^[1]

Common causes of pseudoresistance:

• Poor adherence (most common!)
• White-coat effect
• Incorrect BP measurement (wrong cuff size)
• Drug interactions (NSAIDs negating antihypertensive effect)

Spironolactone is the best-studied fourth-line add-on after an optimised triple regimen, provided potassium and kidney function permit; check K⁺/renal function after initiation and titration. ^[1]

BP control should ideally be reassessed with the combined use of office BP, ABPM, and/or HBPM. ^[1]

The slides use the older labels “malignant hypertension” and “hypertensive urgency.” The decisive modern distinction is not a BP number alone:

• Hypertensive emergency: severe BP elevation with new or worsening acute hypertension-mediated organ damage (for example encephalopathy, aortic dissection, acute pulmonary oedema/ACS, acute kidney injury with microangiopathy, eclampsia or selected stroke presentations). Admit for monitored, condition-specific treatment, usually IV.
• Asymptomatic markedly elevated BP: no acute organ damage. Recheck technique, address pain/anxiety and missed/interfering drugs, adjust oral therapy and arrange reliable follow-up. Rapid IV lowering can cause harm and is not justified by the number alone. ^[19]
• Malignant/accelerated hypertension: a phenotype of severe hypertension with advanced retinopathy (bilateral haemorrhages/cotton-wool spots ± papilloedema), often with microangiopathy or acute kidney injury. A DBP > 140 is neither required nor sufficient. The mortality figures on slide 79 are historical and predate modern treatment. ^[1][14]

Indication for IV treatment: HT encephalopathy (including malignant HTN, eclampsia), acute LV failure due to HTN, dissecting aneurysm. ^[1]

Historical slide warning: avoid indiscriminate rapid BP reduction in acute stroke because cerebral perfusion may fall. ^[1]

Why? In chronic HTN, the autoregulation curve shifts rightward. The brain has adapted to higher perfusion pressures. If you abruptly drop BP, cerebral blood flow falls below the ischaemic threshold → watershed infarction. ^[7]

Current safety correction: stroke is not a blanket contraindication to BP treatment; targets depend on ischaemic versus haemorrhagic stroke and reperfusion status. Outside a condition-specific pathway, a common emergency strategy is to reduce MAP by no more than about 20–25% initially, but aortic dissection, eclampsia, acute stroke and catecholamine crisis have their own targets. ^[19][20][21]

Drugs safe in pregnancy: Labetalol, nifedipine (modified-release), methyldopa. ^[8]

Avoid/contraindicated in pregnancy: ACEI and ARBs are contraindicated because of fetal toxicity. Atenolol is generally avoided because of fetal-growth concerns. Diuretics are not a universal absolute contraindication, but are not first choice for treating pregnancy hypertension and require specialist consideration of volume status. ^[8][23]

From 2020 MCQ Q10: A 40-year-old woman at 13 weeks gestation with BP 150/98, no proteinuria → Chronic hypertension (HTN present before 20 weeks). ^[9]

From 2023 MCQ Q13: A 20-year-old at 34 weeks with new BP 150/100 and proteinuria 3+ → Pre-eclampsia. ^[10]

From 2021 SAQ Q1: Pre-eclampsia with seizure → Eclampsia; treatment = IV MgSO₄. Antihypertensives in pregnancy: labetalol, nifedipine (and methyldopa). ^[11]

KDIGO suggests standardised office SBP < 120 mmHg when tolerated in adults with non-dialysis CKD and high BP. This is an SBP target tied to a strict measurement method, not a universal “< 120/80” target. ^[18]

• ACEI/ARB are preferred if albuminuria is present (renoprotective — dilate efferent arteriole → ↓ intraglomerular pressure → ↓ proteinuria progression)
• Check BP, creatinine/eGFR and K⁺ within about 2–4 weeks after starting or increasing ACEI/ARB (earlier if high risk). A ≥30% fall in eGFR/roughly > 30% creatinine rise should trigger assessment of volume depletion, NSAIDs, renal artery disease and other causes rather than automatic permanent withdrawal
• Avoid combining ACEI + ARB
• Loop diuretics are often preferred for clinically important volume overload in advanced CKD, but thiazide-like agents can still lower BP at eGFR < 30; “thiazides are ineffective” is too absolute
• Newer agents: SGLT2 inhibitors and finerenone (non-steroidal MRA) have renal and CV benefit in CKD + DM ^[6]

Coexistence of DM and HTN dramatically amplifies CVD risk (see “Bad Companions” slide). ACEI/ARBs are specifically preferred when albuminuria or CKD is present; diabetes alone does not make them superior to every other first-line class. Address glycaemia, lipids, smoking and weight; use antiplatelet therapy only for a separate cardiovascular indication, not routinely for primary prevention. ^[18]

Historical ISH 2020 monitoring slide:

• Reduce BP by at least 20/10 mmHg, initially to < 140/90 mmHg; this is a pragmatic minimum goal, not the current ESC 2024 target for a well-tolerating treated adult
• Achieve target within 3 months; individualise for elderly based on frailty
• Monitor for adverse effects and long-term adherence at every visit
• If BP remains uncontrolled, refer to a provider with hypertension expertise

Strategies to improve medication adherence: ^[1]

• Use single-pill combinations (SPC) to reduce polypharmacy
• Prefer once-daily dosing over multiple-times-per-day dosing
• Link adherence behaviour with daily habits
• Provide adherence feedback to patients
• Encourage home BP monitoring
• Use reminder packaging, electronic aids (mobile phone reminders, SMS)
• Employ a multidisciplinary team approach (e.g., pharmacists for adherence monitoring)
• Evaluate adherence at each visit before escalating therapy

Observational plots in the lecture show higher event rates at very low achieved BP, but they cannot by themselves prove that treatment caused harm: frailty, cancer, heart failure and other illnesses can both lower BP and raise risk (reverse causation). The practical message is to pursue the evidence-based target while checking standing BP, symptoms, falls, renal function and perfusion—especially in frailty, stiff-artery disease and autonomic dysfunction. ESC 2024 targets SBP 120–129 if tolerated rather than imposing a universal hard floor of 120/70. ^[14]