Hypertension

A. Presentation

Primary hypertension is asymptomatic until complcations develops.

Hypertensive encephalopathy (due to severe hypertension and cerebral oedema) is associated with:

• Somnolence
• Confusion
• Visual disturbances
• Nausea
• Vomiting

Early signs of hypertension

• A 4th heart sound
• Broad, notched p-wave on ECG

Late signs (retinal changes)

• Retinal haemorrhages
• Exudates
• Papilloedema
• Vascular accidents

Late signs (arteriolar nephrosclerosis)

• Polyuria
• Nocturia
• Diminished renal concentrating ability
• Proteinuria
• Microhaematuria
• Clyindruria
• Nitrogen retention

B. Investigation

Lab test

• FBC
• Urinalysis (to detect haematuria, proteinuria, cast ---> nephrosclerosis)
  If abnormal ---> do urine microscopy to assess morphology of the red cells (to determine the source of haematuria)
• Renal function test (---> renal failure)
• Serum Na+
  (if hypernatremia ---> possible Cushing's syndrome or hyperaldosteronism)
• Serum K+
  (if hypokalemia ---> possible hyperaldosteronism. Normal [K+] doesn't exclude)
• Fasting blood sugar
  (if hyperglycemia ---> possible diabetes or pheochromocytoma)
• Plasma lipids (for assessing atherosclerosis risk)
• Thyroid function test
• Serum uric acid (elevation is a relative contraindication to diuretic therapy)
• Urine vanillylmandelic acid (VMA) and homovanillic acid (HVA) (for detecting pheochromocytoma)

ECG

Highly specific but not sensitive for left ventricular hypertrophy.

Echocardiography

More sensitive than ECG in detecting LVH, but subject to interpretation variability.

Chest Xray

Usually not indicated because doesn't yield additional information

Renal ultrasound

To diagnose primary renal disease (e.g. polycystic kidney, obstructive uropathy) or renovascular abnormalities

Isotope renogram/renal arteriography/duplex doppler flow studies

To diagnose renovascular abnormalities

C. Treatment

For all patients with hypertension, lifestyle measures should be instituted first, then management plan depends on the risk profile.

Drug treatment

5 choices available:

1. Thiazide diuretics (first line)
2. Beta-blockers (first line)
3. ACE-inhibitors
4. Angiotensin II receptor antagonist (2nd line)
5. Calcium channel blockers

All have similar efficacy as monotherapy in lowering BP, but because of the large amount of available evidences for thiazide and beta-blockers, thiazide diuretics and beta-blockers are the first line treatment in uncomplicated hypertension.

Thiazide diuretics

e.g. bendrofluazide, chlorthalidone, chlorothiazide, hydrochlorothiazide, indapamine

• Good for:
  - uncomplicated hypertension;
  - hypertension with heart failure
• Bad for:
  - hypertension with gout

Reduces risk of stroke, cardiovascular morbidity and mortality, particularly in the elderly.

Side effects of thiazide diuretics:

• Impotence
• Gout
• Postural hypotension

Beta-blockers

e.g. atenolol, metoprolol

• Good for:
  - uncomplicated hypertension (except for oxprenolol, pindolol)
  - MI
  - angina
• Bad for:
  - asthma (esp. severe)
  - COPD (esp. severe)
  - bradycardia
  - heart block
  - severe peripheral vascular disease
  - decompensated heart failure

Atenolol, metoprolol, and propranolol have all been shown to reduce cardiovascular morbidity and mortality in patients following myocardial infarction.---> Atenolol, metoprolol, and propranolol are the first line treatment in MI.

Side effect of beta-blockers

• Lethargy
• Dyspnoea
• Impotence

ACE-inhibitors

e.g. captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril.

• Good for hypertension with:
  - diabetes;
  - heart failure;
  - LV dysfunction after MI
• Bad for hypertension with:
  - renovascular disease (e.g. bilateral renal artery stenosis);
  - pregnancy

2nd line treatment in uncomplicated hypertension.

1st line treatment in hypertensive patients with LV dysfunction (esp. after MI), heart failure, diabetes, or non-diabetic nephropathy.

Side effect of ACE-inhibitor:

• Dry cough
• Angioedema

Angiotensin II receptor antagonist (AIIRA)

e.g. irbesartan, losartan, candesartan.

• Bad for hypertension with renovascular disease

May be used as an alternative to ACE-inhibitors in patients with persistent troublesome dry cough.

Calcium channel blockers

Non-dihydropyridine: diltiazem, verapamil.

Dihydropyridine: amlodipine, felodipine, nifedipine.

• Good for hypertension with:
  - angina
• Bad for hypertension with:
  - heart failure (but not with amlodipine and felodipine);
  - bradycardia (but not with dihydropyridines)
  - heart block

Diltiazem has no advantage over diuretics or beta-blockers in terms of overall cardiovascular prevention (less stroke but more MI with diltiazem) or the total incidence of adverse effects.

Calcium channel blockers are inferior to other types of antihypertensive drugs in reducing the risk of several major complications of hypertension.

Use with caution in patients with heart failure. Verapamil and diltiazem are contraindicated in heart failures.

Side effects of calcium channel blockers:

• Headache
• Flushing
• Oedema
• Constipation

Effective drug combinations

• Thiazide diuretics + beta-blocker
• Thiazide diuretics + ACE-inhibitors/AIIRA (particularly in heart failure)
• Beta-blocker + dihydropyridine calcium channel blockers (particularly in coronary heart disease)
• ACE-inhibitors/AIIRA + calcium channel blockers (particularly diabetes or dyslipidemia)

Drug combinations to avoid

• ACE-inhibitors/AIIRA + potassium-sparing diuretics
• Beta-blocker + verapamil

Others

Consider the use of aspirin for primary or secondary prevention of coronary heart disease.

Lifestyle intervention

To help maintaining the change in the long term:

1. Give regular encouragement
2. Provide specific written instruction
3. Reivew progress regularly
4. Tailor to individual needs

Weight reduction

Can lower an average of 2mmHg per kg of weight lost.

Regular physical activity

At least 30minutes of moderate exercise on most days

Alcohol

Limit intake of alcohol to 2 standard drinks per day or less.

Salt

Response vary, and more likely in older patients

Low salt food =< 120mg of salt /100g

Aim for a dietary sodium intake of 40-100mmol/day.

Smoking cessation

The most important thing!

Health eating

Relaxation technique

?No evidence that it works, but it makes the patient feel better and increase compliance.

[treatment principles/general measures/medication regimes]

D. Other notes

[epidemilogy/risk factors/causes/mechanisms/compications/ddx/classification/staging/followups/prognosis/prognostic factors/prevention]

Risk factors

• Obesity
• High sodium intake
• Low potassium intake
• Alcohol (by increasing catecolamines)
• Cigarette smoking (by increasing norepinephrine)
• Polycythemia
• Nonsteroidal anti-inflammatory agents

Aetiology

2 types: primary (essential or idiopathic) and secondary.

90% to 95% of hypertension are primary.

The most common secondary cause is renal disease.

Secondary causes

Renal

• Acute glomerulonephritis
• Chronic renal disease
• Polycystic disease
• Renal artery stenosis (often by atheromatous plaque)
• Renal vasculitis
• Renin-producing tumours

Endocrine

• Adrenocortical hyperfunction
  - Cushing's syndrome
  - Primary aldosteronism (Conn's syndrome)
  - Congenital adrenal hyperplasia
  - Licorice ingestion
• Exogenous hormones
  - Glucocorticoids
  - Oesterogen
  - Sympathomimetics
  - Tyramine-containing foods
  - Monoamine oxidase (MAO) inhibitors
• Pheochromocytoma
• Acromegaly
• Hypothyroidism (Myxoedema)
• Hyperthyroidism (Thyrotoxicosis)
• Pregnancy-induced (pre-eclampsia, etc)

Cardiovascular

• Coarctation of aorta
• Polyarteritis nodosa
• Increased intravascular volume
• Increased cardiac output
• Rigidity of the aorta

Neurologic

• Psychogenic
• Increased intracranial pressure
• Sleep apnea
• Acute stress (e.g. surgery)

Drugs

• Alcohol
• Oral contraceptives
• Nonsteroidal anti-inflammatory drugs
  e.g. COX-2 inhibitors
• Corticosteroids
• Nasal decongestant
• Monoamine oxidase inhibitors (MAOi's)
• Venlafaxine
• Immunosuppressants
  e.g. cyclosporins
• Liquorice
• Steroid
• Cocaine
• Amphetamines

Complication

• Hypertensive cardiovascular disease
• Hypertensive cerebrovascular disease and dementia
• Hypertensive renal disease
• Aortic dissection
• Atherosclerotic complications
• Hyaline arteriolosclerosis (small vessel disease)
• Hyperplastic arteriolosclerosis (small vessel disease)

Hypertension is a more important risk factor for stroke than for atherosclerotic heart disease.

Hyaline arteriolosclerosis

• Encountered frequently in the elderly, with or without hypertension. With hypertension, the lesions are more generalised and more severe.
• Also common in diabetes.

Morphology:

The lesion consists of a homogenous, pink, hyaline thickening of the walls of arterioles with loss of underlying structural details and with narrowing of the lumen.

Mechanism:

Leakage of plasma components across vascular endothelium and increasing extracelluar matrix production by smooth muscle cells.

Hyaline arteriolosclerosis is a major morphologic feature of benign nephrosclerosis.

Hyperplastic arteriolosclerosis

• Related to more acute or severe hypertension, and is characteristic of, though not limited to, malignant hypertension.
• Kidney is the common site.

Morphology:

Under light microscopy: onion-skin, concentric, laminated thickening of the walls of arterioles with progressive narrowing of the lumens.

The lamination consists of smooth muscle cells and thickened reduplicated basement membrane.

Frequently accompanied by deposits of fibrinoid and acute necrosis of vessel walls (necrotizing arteriolitis).

History taking in hypertension cases

Present complain

• Known duration of hypertension and previous levels
• Previous anti-hypertensive therapy efficacy and adverse effects
• Symptoms suggestive of secondary hypertension, e.g. paroxysmal headache, sweating, palpitations that is suggestive of pheochromocytoma.

Other medical history

• Past history or current symptoms of ischaemic heart disease, heart failure, cerebrovascular disease, peripheral vascular disease or renal disease.
• Asthma, COPD, DM, dyslipidaemia, gout, sexual dysfunctions (if males) or other significant illness and their treatment.

Life style/social history

• Modifiable risk factors: obesity, alcohol intake, salt use, physical activity, smoking, saturated fat intake.

Drug/medication history

• Ingestion of prohypertensive substances.

Family history

• Family history of hypertension, DM, dyslipidaemia, stroke, premature coronary heart disease, renal disease.
• Personal, psychosocial, and environmental factors which could influence the course and outcome of antihypertensive care, including family situation, work environment and educational background.

Physical examination in hypertensive cases

• General features which may be consistent with a cause of secondary hypertension, e.g. Cushing's disease.
• Presence of other cardiovascular risk factors, e.g. obesity.

Cardiovascular system

• Heart size
• Evidence of heart failure
• Evidence of arterial disease: carotid, renal, peripheral absent femoral pulses or radiofemoral delay.

Respiratory system

• Basal crackles
• Wheeze

Abdomen

• Renal size
• Other masses (e.g. aortic aneurysm)
• Bruits

Optic fundi

• Arteries: tortuosity, thickening, narrowing (generalised or focal), AV nipping
• Background: haemorrhage, exudates
• Disc: papilloedema

Nervous system

• Evidence of previous neurological disease

Classification

• Optimal =< 120/80
• Normal <130/85
• High-normal 130-140/85-90
• Grade 1: 140-160/90-100
• Grade 2: 160-180/100-110
• Grade 3: >180/110

When systole and diastoic fall into different categories, the higher category should apply.

Follow-up of adults over 18y.o. after an initial BP test

• <130/85
  ---> Recheck in 2 years
• High-normal
  ---> Recheck in 1 year plus lifestyle advice
• Grade 1
  ---> Confirm within 2 months plus lifestyle advice
• Grade 2
  ---> Evaluate or refer within 1 month plus lifestyle advice
• Grade 3
  ---> Evaluate or refer within 1 week (or immediately depending on clinical situation)

Stratification of absolute cardiovascular risk to quantify prognosis

• Low risk (<15%)
  - Grade 1 AND no risk factors
• Med risk (15-20%)
  - Grade 1or2 AND =<2 risk factors.
• High risk (20-30%)
  - Grade 3 without no risk factors
  - Grade 1or2 AND >=3 risk factors (or DM/TOD)
• Very high risk (>30%)
  - Grade 3 with any risk factors
  - Any grade with any associated clinical condition (see below)

Patients with high or very high risk profiles should begin drug treatment immediately.

Risk factors - for the purpose of stratification

• Men >55 y.o.
• Women >65 y.o.
• Smoking
• Total cholesterol >6.5 mmol/L
• Family history of premature cardiovascular disease (onset <60 years)

TOD=Target-organ damage

• Left ventricular hypertrophy (ECG, echo, Xray)
• Proteinuria and/or slight elevation of plasma creatinine concentration (106-177umol/L)
• Ultrasound or radiological evidence of atherosclerotic plaque (coronary, carotid, iliac, and femoral arteries, aorta)
• Generalised or focal narrowing of the retinal arteries (Grade I and II)

Associated clinical conditions

Cerebrovascular disease

• Ischemic stroke
• Cerebral haemorrhage
• Transient ischaemic attack

Heart disease

• Myocardial infarction
• Angina
• Coronary revascularisation
• Congestive heart failure

Renal disease

• Diabetic nephropathy
• Renal failure (plasma creatinine >177umol/L)

Vascular disease

• Dissecting aneurysm
• Symptomatic arterial disease

Advanced hypertensive retinopathy

• Haemorrhages or exudates (Grade III)
• Papilloedema (Grade IV)