HypertensionHypertension

Physiology, Pathophysiology and Clinical Physiology, Pathophysiology and Clinical ManagementsManagements

Jun TaoJun Tao

Stroke and Ischemic Heart Disease (IHD) Stroke and Ischemic Heart Disease (IHD) Mortality Rate in Each Decade of Age, Versus Mortality Rate in Each Decade of Age, Versus Usual Systolic BP at the Start of that DecadeUsual Systolic BP at the Start of that Decade

Mo

rtal

ity*

Usual SBP (mmHg)

50–59 y

60–69 y

70–79 y

80–89 y

StrokeAge at risk

256

128

64

32

16

8

4

2

1

0 120 140 160 180

IHD

Usual SBP (mmHg)

50–59 y

60–69 y

70–79 y

80–89 y

Age at risk

40–49 y

256

128

64

32

16

8

4

2

1

0 120 140 160 180

*Floating absolute risk and 95% CIReproduced from The Lancet, 360, Lewington et al. pp. 1903–13

Copyright © 2002, with permission from Elsevier

IntroductionIntroduction

Primary hypertension is a Primary hypertension is a clinical syndrome characterized clinical syndrome characterized by the increase in systemic by the increase in systemic arterial pressure. arterial pressure.

95% 0f the patients with 95% 0f the patients with hypertension are primary hypertension are primary hypertension with unknown causes hypertension with unknown causes and 5% secondary hypertension with and 5% secondary hypertension with definitive causes. definitive causes.

Hypertension affects approximately 1 bilHypertension affects approximately 1 billion individual worldwide. In China the ilion individual worldwide. In China the incidence of hypertension is about 180 mncidence of hypertension is about 180 million individuals. illion individuals.

Primary hypertensionPrimary hypertension

Etiology and pathogenesisEtiology and pathogenesis

TheThe pathogenesis of primary pathogenesis of primary hypertension is still unclear. There hypertension is still unclear. There are many factors associate with it. are many factors associate with it.

Genetic factorsGenetic factors Sodium intakeSodium intake Renin agiotensin systemsRenin agiotensin systems Sympathetic nervous systemSympathetic nervous system Endothelial dysfunctionEndothelial dysfunction Insulin resistanceInsulin resistance Other factorsOther factors

Genetic factorsGenetic factors The offsprings of the hypertensive pThe offsprings of the hypertensive p

arents are prone to suffering from essenarents are prone to suffering from essential hypertension compared with that witial hypertension compared with that without hypertensive family.thout hypertensive family.

Sodium intake Sodium intake

The mechanisms leading to The mechanisms leading to hypertension are due to increased hypertension are due to increased blood volume and the content of the blood volume and the content of the sodium in the smooth muscle cells sodium in the smooth muscle cells enhance following subsequent enhance following subsequent calcium increase.calcium increase.

RAAS systemRAAS system ReninRenin→→Angiotensinogen Angiotensinogen →→ Angiotensin Angiotensin

II→→ Angiothesin II Angiothesin II → → IncreaseIncrease systemic asystemic a

rterial pressurerterial pressure

Sympathetic nervous activationSympathetic nervous activation

The activation of Sympathetic The activation of Sympathetic nervous can augment periphery nervous can augment periphery resistant which increase systemicresistant which increase systemic arterialarterial pressure.pressure.

Endothelial dysfunctionEndothelial dysfunction Endothelium-derived vasodilating factors:Endothelium-derived vasodilating factors: NO; PGI2; EDHF.NO; PGI2; EDHF. Endothelial-derived vasoconstricting factorEndothelial-derived vasoconstricting factor

s:ET; AGII; Superoxide anion.s:ET; AGII; Superoxide anion.

Insulin resistanceInsulin resistance

Increased absorbability to sodiumIncreased absorbability to sodium

Increased sympathetic nervous Increased sympathetic nervous activationactivation

Increased cellular contents in sodium Increased cellular contents in sodium and and calciumcalcium

Caused vascular wall hypertrophyCaused vascular wall hypertrophy

Other factorsOther factors

ObesityObesity

SmokingSmoking

Intake alcoholIntake alcohol

OSASOSAS

Low calcium , magnesium and Low calcium , magnesium and potassium.potassium.

PathologyPathology Systemic atherosclerosis develops with iSystemic atherosclerosis develops with i

ncreased intimal-medium thickness leancreased intimal-medium thickness leading to ischemic alterations in target orgding to ischemic alterations in target organs such as heart, brain, kidney and perians such as heart, brain, kidney and peripheral artery. pheral artery.

Blood vessel changeBlood vessel change

Aorta and large arteriesAorta and large arteries recurrent pulsatile stress produces uncoirecurrent pulsatile stress produces uncoi

ling, disruption and calcification of elassling, disruption and calcification of elasstic fibres. At the same time, relatively inetic fibres. At the same time, relatively inelastic collagen is increased.lastic collagen is increased.

This is a result of ageing as well as hypThis is a result of ageing as well as hypertension : both processes therefore cauertension : both processes therefore cause loss of the normal elastic reservoir fuse loss of the normal elastic reservoir funtion of the aorta and large arteries.ntion of the aorta and large arteries.

This explains one curious feature This explains one curious feature of elderly hypertensive patients. of elderly hypertensive patients. Diastolic blood pressure in patients Diastolic blood pressure in patients with isolated systolic hypertension is with isolated systolic hypertension is inversely related to prognosis.inversely related to prognosis.

Medium-sized arteriesMedium-sized arteries The predominant pathological change The predominant pathological change

is wall thickening caused by increased dis wall thickening caused by increased deposition of collagenous material.eposition of collagenous material.

Resistance vesselResistance vessel The characteristic structural change in The characteristic structural change in

smaller arteries and arterioles responsibsmaller arteries and arterioles responsible for peripheral vascular resistance is ale for peripheral vascular resistance is an increase in wall:lumen ratio.n increase in wall:lumen ratio.

In recent years it has become clear thaIn recent years it has become clear that what was thought to be a trophic respot what was thought to be a trophic response is largely if not entirely due to rearranse is largely if not entirely due to rearrangement of smooth muscle cells around ngement of smooth muscle cells around a smaller lumen.a smaller lumen.

Specific organ changes in Specific organ changes in hypertensionhypertension

The heartThe heart Angina and myocardial infarction in thAngina and myocardial infarction in th

e hypertensive patient are usually due te hypertensive patient are usually due to coronary atheroma.o coronary atheroma.

Left ventricular hypertrophy is Left ventricular hypertrophy is demonstrable in about 50 per cent of demonstrable in about 50 per cent of untreated hypertensive patients untreated hypertensive patients when echocardiography is used, and when echocardiography is used, and in 5 to 10 per cent with in 5 to 10 per cent with electrocardiography using electrocardiography using conventional criteria.conventional criteria.

Hpertrophy of left ventricleHpertrophy of left ventricle

Central nervous systemCentral nervous system Cerebral infarction in a hypertensive pCerebral infarction in a hypertensive p

atient is usually attributable to atheromatient is usually attributable to atheroma of one of the larger cerebral arteries (ua of one of the larger cerebral arteries (usually the middle cerebral artery) and acsually the middle cerebral artery) and accounts for about 80 percent of the strokcounts for about 80 percent of the strokes which these patients suffer.es which these patients suffer.

Intracerebral haemorrhage accounts fIntracerebral haemorrhage accounts for 10 to 15 percent, usually the result of or 10 to 15 percent, usually the result of rupture of a small intracerebral degenerrupture of a small intracerebral degenerative microaneurysm.ative microaneurysm.

The kidneyThe kidney The long-term renal damage produceThe long-term renal damage produce

d by glomerular hypertension probably d by glomerular hypertension probably accountd for progressive glomeruloscleraccountd for progressive glomerulosclerosis in essential hypertension.osis in essential hypertension.

Atheromatous renal vascular disease Atheromatous renal vascular disease much more commonly causes renal impmuch more commonly causes renal impairment in elderly hypertensive subjects airment in elderly hypertensive subjects than younger patients with treated mild than younger patients with treated mild to moderate hypertension.to moderate hypertension.

肾动脉硬化肾动脉硬化

致密的肾盂

X 线影象

Malignant hypertension: Fibrinoid necrosis of damaged arteriole of kidney

RetinopathyRetinopathy Keith-Wagener classificationKeith-Wagener classification

Stage I: constriction of retinal arterioles only.Stage I: constriction of retinal arterioles only. Stage II: constriction and sclerosis of retinal artStage II: constriction and sclerosis of retinal art

erioles.erioles. Stage III: hemorrhages and exudates in additioStage III: hemorrhages and exudates in additio

n to vascular changes.n to vascular changes. Stages IV: papilledema.Stages IV: papilledema.

SymptomsSymptoms

HeadacheHeadache

the classic hypertensive headache is the classic hypertensive headache is present on walking in the morning, present on walking in the morning, situated in the occipital region of the situated in the occipital region of the head, radiating to the frontal area, head, radiating to the frontal area, throbbing in quality, and wears off throbbing in quality, and wears off during the course of the day.during the course of the day.

Most headaches in hypertensive Most headaches in hypertensive patients are tension headaches not patients are tension headaches not directly related to blood pressure. directly related to blood pressure. Nevertheless, effective treatment of Nevertheless, effective treatment of hypertension reduces the incidence hypertension reduces the incidence of headache.of headache.

EpistaxisEpistaxis Whilst epistaxis is not associated with Whilst epistaxis is not associated with

mild hypertension, it is much more commild hypertension, it is much more common in moderate to severe hypertensiomon in moderate to severe hypertension. n.

Nocturia Nocturia this is one of the most frequent clinicallthis is one of the most frequent clinicall

y apparent consequences of blood pressy apparent consequences of blood pressure elevation resulting from reduction in ure elevation resulting from reduction in urine-concentrating capacity.urine-concentrating capacity.

Others Others

dizziness; dizziness;

flushed face; flushed face;

fatigue;fatigue;

palpitation.palpitation.

Symptoms associated with target organ Symptoms associated with target organ damagedamage

Cardiovascular systemCardiovascular system Effort dyspnoea and orthopnoea suggEffort dyspnoea and orthopnoea sugg

est cardiac failure. Increased left ventricest cardiac failure. Increased left ventricular mass is associated with decreased cular mass is associated with decreased compliance and impaired cardiac output ompliance and impaired cardiac output response to exercise.response to exercise.

Central nervous systemCentral nervous system Extensive disease of the perforating aExtensive disease of the perforating a

rteries may give rise to a lacunar state crteries may give rise to a lacunar state characterized by progressive pseudobulbharacterized by progressive pseudobulbar plasy and dementia.ar plasy and dementia.

Renal systemRenal system Haematuria suggest the malignant phaHaematuria suggest the malignant pha

se of hypertension in the absence of any se of hypertension in the absence of any other cause.other cause.

RetinopathyRetinopathy Scotomas suggest fundal haemorrhageScotomas suggest fundal haemorrhage

s or exudates, whilst blurring of vision is s or exudates, whilst blurring of vision is associated with papilloedema.associated with papilloedema.

Complications Complications

Hypertensive emergenciesHypertensive emergencies Hypertensive encephalopathyHypertensive encephalopathy Cerebrovascular diseaseCerebrovascular disease Heart failureHeart failure Chronic kidney disease Dissection of aortaDissection of aorta

physical examination physical examination

SBP>=140 mmHg or DBP>=90 SBP>=140 mmHg or DBP>=90 mmHg.mmHg.

Loud aortic second soundLoud aortic second sound Other physical signs indicate target Other physical signs indicate target

organ damageorgan damage

Diagnosis Diagnosis

Diagnosis of primary hypertension Diagnosis of primary hypertension depends on repeatedly depends on repeatedly demonstrating higher –than-normal demonstrating higher –than-normal systolic and /or diastolic BP and systolic and /or diastolic BP and excluding secondary hypertension.excluding secondary hypertension.

Category Systolic blood

pressure (mmHg)

Diastolic blood

pressure

(mmHg) Optimal blood pressure <120 <80

Normal blood pressure <130 <85

High-normal blood pressure 130-139 85-89

Grade 1 Hypertension (mild) 140-159 90-99

Grade 2 Hypertension (moderate) 160-179 100-109

Grade 3 Hypertension (severe) >180 >110

Isolated Systolic Hypertension (Grade 1) 140-159 <90

Isolated Systolic Hypertension (Grade 2) >160 <90

CVD Risk FactorsCVD Risk Factors Hypertension* Cigarette smoking Obesity* (BMI >30 kg/m2) Physical inactivity Dyslipidemia* 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 of the metabolic syndrome.

Blood pressure （ mmHg ）

Grade 1(SBP 140

～ 159 or DBP 90 ～

99)

Grade 2(SBP 160～ 179 or DBP 100

～ 109)

Grade 3(SBP ≥180 or DBP

≥110)

No other risk factors Low-risk Medium-risk High-risk

1 ～ 2 risk factors Moderate-risk Medium-risk

Very High-risk

3 or more risk factors ，or diabetes ， or targ

et organ damageHigh-risk High-risk Very High-risk

complicationsVery High-ris

k Very High-risk Very High-risk

Cardiovascular risk category of hypertension

Laboratory examinationsLaboratory examinations

Serum potassium, creatine, blood glucSerum potassium, creatine, blood glucose, blood lipids, complete blood counose, blood lipids, complete blood count, uric acid, ECG, cardiac and chest x-rat, uric acid, ECG, cardiac and chest x-ray exam and funduscopic exam for retiny exam and funduscopic exam for retinopathy.opathy.

ABPMABPM Double peaks and one hollowDouble peaks and one hollow

Goals of TherapyGoals of Therapy

Reduce CVD and renal morbidity and mortality.

Treat to BP <140/90 mmHg or BP <130/80 mmHg in patients with diabetes or chronic kidney disease.

Achieve SBP goal especially in persons >50 years of age.

Blood Pressure Reduction of 2 mmHg Decreases Blood Pressure Reduction of 2 mmHg Decreases the Risk of Cardiovascular Events by 7–10%the Risk of Cardiovascular Events by 7–10%

Meta-analysis of 61 prospective, Meta-analysis of 61 prospective, observational studiesobservational studies

1 million adults1 million adults12.7 million person-years12.7 million person-years

2 mmHg decrease in mean SBP 10% reduction in

risk of stroke mortality

7% reduction in risk of ischaemic heart disease mortality

Lewington et al. Lancet 2002;360:1903–13

Lifestyle ModificationLifestyle Modification

Weight reduction:Weight reduction:

the trial of hypertension the trial of hypertension prevention produced an average prevention produced an average weight loss of 3.8 kg at 18 months, weight loss of 3.8 kg at 18 months, reduction of SBP and DBP by 2.9 reduction of SBP and DBP by 2.9 and 2.3 mm Hg.and 2.3 mm Hg.

Exercise:Exercise:

Following increased physical Following increased physical activity, BP falls up 6-7 mm Hg for activity, BP falls up 6-7 mm Hg for both SBP and DBP.both SBP and DBP.

Sodium restrictionSodium restriction Alcohol reduction and smoking Alcohol reduction and smoking

cessationcessation Stress reduction/relaxing trainingStress reduction/relaxing training Dietary changes: low salt intake; Dietary changes: low salt intake;

potassium, magnesium and calcium potassium, magnesium and calcium supplementation; others.supplementation; others.

Algorithm for Treatment of Algorithm for Treatment of HypertensionHypertension

Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease)

Initial Drug Choices

Drug(s) for the compelling indications

Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB)

as needed.

With Compelling Indications

Lifestyle Modifications

Stage 2 Hypertension (SBP >160 or DBP >100 mmHg)

2-drug combination for most (usually thiazide-type diuretic and

ACEI, or ARB, or BB, or CCB)

Stage 1 Hypertension(SBP 140–159 or DBP 90–99 mmH

g) Thiazide-type diuretics for most.

May consider ACEI, ARB, BB, CCB,

or combination.

Without Compelling Indications

Not at Goal Blood Pressure

Optimize dosages or add additional drugs until goal blood pressure is achieved.

Consider consultation with hypertension specialist.

Drug treatment Drug treatment

DiureticsDiuretics ß -Blockersß -Blockers Calcium channel blockersCalcium channel blockers ACE inhibitorsACE inhibitors Angiotensin II receptor blockersAngiotensin II receptor blockers α-Adrenergic blockersα-Adrenergic blockers

Diuretics Diuretics

Indications : cardiac failureIndications : cardiac failure

elderly patientselderly patients

systolic hypertension in systolic hypertension in elderlyelderly

ß –Blockersß –BlockersIndications :anginaIndications :angina after myocardial infarctionafter myocardial infarction tachyarrhythmiastachyarrhythmias cardiac failure (with care)cardiac failure (with care)Contraindications :asthma and chronic obContraindications :asthma and chronic ob

structive airway diseasestructive airway disease peripheral vascular diseaseperipheral vascular disease

Calcium antagonists:Calcium antagonists:Indications :systolic hypertension in the elIndications :systolic hypertension in the el

derlyderlyContraindications:heart block (verapamil Contraindications:heart block (verapamil

and diltiazem)and diltiazem)

ACEIACEIIndications: cardiac failureIndications: cardiac failure left ventricular dysfunctionleft ventricular dysfunction after myocardiac infarction (higher- risafter myocardiac infarction (higher- ris

k patients)k patients) diabetic nephropathy and other proteindiabetic nephropathy and other protein

uric renal diseaseuric renal diseaseContraindications: pregnancyContraindications: pregnancy renovascular diseaserenovascular disease sodium and fluid depletionsodium and fluid depletion hyperkalaemiahyperkalaemia

ARBARB

Indications: as for ACEI in presence of Indications: as for ACEI in presence of ACEI induced cough or intoleranceACEI induced cough or intolerance

Contraindications: as for ACEIContraindications: as for ACEI

α-Adrenergic blockersα-Adrenergic blockersIndications: prostatismIndications: prostatismContraindications: urinary incontienceContraindications: urinary incontience

，

Compelling and possible indications, contraindications, and cautions for the major classes of antihypertensive drugs Class of drug

Compelling indications

Possible indications

Caution

Compelling contra-indications

Alpha-blockers

Benign prostatic hypertrophy

Postural hypotension, heart failure

Urinary incontinence

ACE-inhibitors

Heart failure, LV dysfunction, post MI or established CVD, Type I diabetic nephropathy, 2o stroke prevention

Chronic renal disease, Type II diabetic nephropathy, proteinuric renal disease

Renal impairment

PVD Pregnancy, renovascular disease

ARBs ACE inhibitor-intolerance, Type II diabetic nephropathy, hypertension with LVH, heart failure in ACE-intolerant patients, post MI

LV dysfunction post MI, intol-erance of other antihypertensive drugs, proteinuric renal disease, chronic renal disease,

heart failure

Renal impairment PVD

Pregnancy, renovascular disease

Compelling and possible indications, contraindications, and cautions for the major classes of antihypertensive drugs Class of drug

Compelling indications

Possible indications

Caution

Compelling contraindications

Beta-blockers MI, Angina

Heart failure Heart failure, PVD,

Diabetes (except with CHD)

Asthma/COPD, Heart block

CCBs (dihydropyridine)

Elderly, ISH Angina - -

CCBs (rate limiting)

Angina Elderly Combination with beta-blockade

Heart block Heart failure

Thiazide/thiazide-like diuretics

Elderly ISH Heart failure 2 o stroke prevention

Gout

Classification and Management Classification and Management of BP for adultsof BP for adults

BP BP classificaticlassificati

onon

SBP* SBP* mmHmmH

gg

DBP* DBP* mmHg mmHg

Lifestyle Lifestyle modificatmodificat

ionion

Initial drug therapyInitial drug therapy

Without compelling Without compelling indication indication

With With compelling compelling indicationsindications

Normal Normal <120 <120 and <80 and <80 Encourage Encourage

Prehypertension Prehypertension 120–139 120–139 or 80–89 or 80–89 Yes Yes No antihypertensive drug No antihypertensive drug indicated. indicated.

Drug(s) for compelling iDrug(s) for compelling indications. ndications. ‡‡

Stage 1 Stage 1 Hypertension Hypertension

140–159 140–159 or 90–99 or 90–99 Yes Yes Thiazide-type diuretics for most.Thiazide-type diuretics for most. May consider ACEI, ARB, BB, May consider ACEI, ARB, BB, CCB, or combination. CCB, or combination.

Drug(s) for the compelliDrug(s) for the compelling indications.ng indications.‡‡

Other antihypertensive Other antihypertensive drugs (diuretics, ACEI, drugs (diuretics, ACEI, ARB, BB, CCB) as neeARB, BB, CCB) as needed. ded.

Stage 2 Stage 2 Hypertension Hypertension

>>160 160 or or >>100 100 Yes Yes Two-drug combination for mostTwo-drug combination for most†† (usually thiazide-type diuretic a(usually thiazide-type diuretic and ACEI or ARB or BB or CCB).nd ACEI or ARB or BB or CCB).

*Treatment determined by highest BP category.†Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension.‡Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmHg.

Other medications for hypertensive patients

Primary prevention

(1) Aspirin: use 75mg daily if patient is aged 50 years with blood pressure controlled to <150/90 mm Hg and either; target organ damage, diabetes mellitus, or 10 year risk of cardiovascular disease of 20% (measured by using the new Joint British Societies’ cardiovascular disease risk chart)

(2) Statin: use sufficient doses to reach targets if patient is aged up to at least 80 years, with a 10 year risk of cardiovascular disease of 20% (measured by using the new Joint British Societies’ cardiovascular disease risk chart) and with total cholesterol concentration 3.5mmol/l

(3) Vitamins—no benefit shown, do not prescribe

Secondary prevention (including patients with type 2 diabetes)

(1) Aspirin: use for all patients unless contraindicated

(2) Statin: use sufficient doses to reach targets if patient is aged up to at least 80 years with a total cholesterol concentration 3.5 mmol/l

(3) Vitamins— no benefit shown, do not prescribe

Other medications for hypertensive patients

Targets for lipid lowering

Ideal - TC<4.0mmol/lor LDL <2.0mmol/lor 25% in TCor 30% in LDL-Cwhichever is the greater

‘Audit’ - TC <5.0mmol/lor LDL <3.0mmol/lor 25% in TCor 30% in LDL-Cwhichever is the greater

Lipid targets

Some key points of the 2007 Some key points of the 2007 ESH and ESC guidelinesESH and ESC guidelines

CVD Risk FactorsCVD Risk Factors

There are some new risk factors :There are some new risk factors : fasting blood glucose 5.6fasting blood glucose 5.6 ～～ 6.9mmol/L 6.9mmol/L

;; pulse pressure (in the elderly)pulse pressure (in the elderly)

Target organ damageTarget organ damage

ECG shows Left ventricular hypertrophy;ECG shows Left ventricular hypertrophy;PWV>12 m/s ;PWV>12 m/s ;ABI<0.9; ABI<0.9; GFR<50ml/GFR<50ml/ （（ min·1.75mmin·1.75m22 ） ） creatinine clearance rate <60ml/mincreatinine clearance rate <60ml/min

ESH - ESC Guidelines, J Hypertens 2008ESH - ESC Guidelines, J Hypertens 2008

-BP < 140/90 mmHg in all hypertensive patients

< 130/80 mmHg in hypertensive patients with diabetes or renal disease

-Control of all cardiovascular risk factors

-BP < 140/90 mmHg in all hypertensive patients

< 130/80 mmHg in hypertensive patients with diabetes or renal disease

-Control of all cardiovascular risk factors

Goals of treatmentGoals of treatment

About drug treatmentAbout drug treatment

Diuretics, ß –Blockers, Calcium channel blockeDiuretics, ß –Blockers, Calcium channel blockers, ACE inhibitors and Angiotensin II receptor brs, ACE inhibitors and Angiotensin II receptor blockers can be used in onset and maintenane tlockers can be used in onset and maintenane therapy.herapy.

Diuretics combined with ß –Blockers is not suiDiuretics combined with ß –Blockers is not suitable for metabolic syndrome or high-risk diabtable for metabolic syndrome or high-risk diabetes patients.etes patients.

Low-dose combination therapy as first Low-dose combination therapy as first line treatment of mild-to-moderate line treatment of mild-to-moderate hypertensionhypertension

Screening and treatment of Screening and treatment of secondary forms of secondary forms of

hypertensionhypertension1.1. Renal parenchymal diseaseRenal parenchymal disease2.2. Renovascular hypertensionRenovascular hypertension3.3. PhaeochromocytomaPhaeochromocytoma4.4. Primary aldosteronismPrimary aldosteronism5.5. Cushing’syndromeCushing’syndrome6.6. Obstructive sleep apnoeaObstructive sleep apnoea7.7. Coarctation of aortaCoarctation of aorta8.8. Drug-induced hypertensionDrug-induced hypertension