Hypertension

Hypertension is persistently raised blood pressure: clinic readings of 140/90 mmHg or more on repeated measurement (or 130/80 mmHg or more in some definitions). It is usually asymptomatic. It is the leading modifiable cause of stroke, heart failure, myocardial infarction, chronic kidney disease, dementia and death worldwide, and the commonest chronic condition found in primary care in Africa.

Confirm the diagnosis by out of office measurement:

• Home average 135/85 mmHg or more.
• Daytime ambulatory average 135/85 mmHg or more.
• 24 hour average 130/80 mmHg or more.

Clinical relevance. Control rates are low (often under 20% in sub Saharan Africa). Most hypertension is primary (essential), but 5% to 10% is secondary and potentially curable. Causes are renal parenchymal disease, renal artery stenosis, primary aldosteronism, obstructive sleep apnoea, phaeochromocytoma, Cushing syndrome, coarctation and drugs.

Young onset (under 40), resistant disease, sudden worsening, hypokalaemia or marked target organ damage should prompt a search.

Classification of office blood pressure (adults).

• Optimal: under 120/80 mmHg. Normal: 120 to 129/80 to 84. High normal: 130 to 139/85 to 89.
• Grade 1: 140 to 159/90 to 99. Grade 2: 160 to 179/100 to 109. Grade 3: 180 or more/110 or more.
• Isolated systolic hypertension: systolic 140 or more with diastolic under 90.
• White coat hypertension (high clinic, normal out of office) and masked hypertension (normal clinic, high out of office).

Scope. This article covers chronic hypertension, its diagnosis and initial treatment; severe hypertension with organ damage appears here only in the red flags and admission criteria.

Cardiovascular risk. Total risk guides treatment: age, sex, smoking, lipids, diabetes, kidney disease, target organ damage, established cardiovascular disease, family history.

History.

• Duration, previous readings, home monitoring, symptoms (usually none; headache, dizziness, palpitations, visual disturbance, nocturia, chest pain, breathlessness, claudication, neurological symptoms).
• Cardiovascular risk: smoking, alcohol, diet (salt, processed food), physical activity, weight gain, diabetes, lipids, family history of hypertension, early cardiovascular disease, kidney disease, stroke.
• Secondary clues:
  • Snoring and daytime sleepiness (sleep apnoea).
  • Episodic headache, sweating, palpitations (phaeochromocytoma).
  • Muscle weakness, cramps, polyuria (hypokalaemia in aldosteronism).
  • Weight gain, bruising, striae (Cushing syndrome).
  • Renal disease, haematuria, family history of polycystic kidney disease.
  • Heat intolerance, weight loss (hyperthyroidism).
  • Claudication, cold legs (coarctation, atherosclerosis).
  • Pregnancy and pre-eclampsia history.
• Drugs and substances: NSAIDs, corticosteroids, oral contraceptives (oestrogen), decongestants, stimulants, cocaine, amphetamines, liquorice, ciclosporin, tacrolimus, erythropoietin, antidepressants (venlafaxine), tyrosine kinase and VEGF inhibitors, herbal products, excess alcohol and caffeine.
• Previous antihypertensive drugs, side effects, adherence and barriers (cost, beliefs, side effects).

Measurement technique.

• Seated, rested 5 minutes, back supported, arm at heart level, correct cuff size (bladder encircling 80% of arm), no talking, no caffeine or smoking for 30 minutes.
• Take two readings 1 to 2 minutes apart, repeated if they differ by over 10 mmHg.
• Measure in both arms at the first visit. Use the arm with higher readings; a difference over 15 mmHg suggests vascular disease.
• Take standing readings at 1 and 3 minutes in older adults and diabetes.
• Confirm with home blood pressure monitoring (twice daily for 4 to 7 days, discard the first day, average the rest) or 24 hour ambulatory monitoring (also shows nocturnal dipping and white coat effect).

Examination.

• Weight, height, body mass index, waist; pulse (rhythm, rate), blood pressure both arms; radio-femoral delay; fundoscopy (hypertensive retinopathy: arteriolar narrowing, haemorrhages, exudates, papilloedema).
• Cardiac: apex displacement, fourth sound, murmurs, signs of heart failure; carotid, renal, femoral bruits; abdominal masses (polycystic kidneys, aneurysm); peripheral pulses.
• Cushingoid features, thyroid, neurological signs.
• Oedema and signs of kidney disease.

Red flags.

• Blood pressure 180/120 mmHg or more with symptoms or organ damage.
• Young age (under 40) at onset, sudden onset, severe or resistant disease.
• Hypokalaemia, haematuria or proteinuria, abdominal bruit, flash pulmonary oedema, creatinine rise after ACE inhibitor.
• Paroxysms of headache, sweating, palpitations.
• Differential arm pressures or femoral delay.
• Pregnancy with hypertension.
• Papilloedema, new neurological deficit, chest pain.

Primary (essential) hypertension (about 90% to 95%). Multifactorial: genetic, salt sensitivity, obesity, inactivity, ageing, alcohol, sleep apnoea, stress.

Secondary hypertension.

• Renal parenchymal: chronic kidney disease, glomerulonephritis, diabetic nephropathy, polycystic kidney disease, reflux nephropathy, obstructive uropathy, schistosomal nephropathy.
• Renovascular: atherosclerotic renal artery stenosis, fibromuscular dysplasia, Takayasu arteritis.
• Endocrine: primary aldosteronism (Conn syndrome, bilateral hyperplasia), Cushing syndrome, phaeochromocytoma and paraganglioma, hyperthyroidism, hypothyroidism, hyperparathyroidism, acromegaly, congenital adrenal hyperplasia, Liddle syndrome, apparent mineralocorticoid excess.
• Vascular: coarctation of the aorta, aortic stiffness, aortic regurgitation.
• Sleep apnoea, pregnancy related (chronic, gestational, pre-eclampsia).
• Drugs and substances: NSAIDs, corticosteroids, oestrogen containing contraceptives, decongestants, stimulants, cocaine, ciclosporin, tacrolimus, liquorice, erythropoietin, excess alcohol.
• Neurological: raised intracranial pressure, autonomic dysreflexia, Guillain-Barre syndrome, porphyria.
• Pseudo hypertension: calcified arteries in older adults, small cuff in obesity, anxiety (white coat effect).

1. Diagnose with repeated measurement and confirmation by home or ambulatory monitoring. If clinic pressure is 180/110 mmHg or more with target organ damage, treat urgently without waiting.
2. Basic tests (all newly diagnosed):
   • Urinalysis for protein, blood and glucose.
   • Urine albumin to creatinine ratio (over 3 mg/mmol abnormal).
   • Urea, creatinine, estimated glomerular filtration rate, electrolytes (potassium, sodium), calcium.
   • Fasting glucose or HbA1c; lipid profile; uric acid; thyroid stimulating hormone; full blood count.
   • 12 lead ECG (left ventricular hypertrophy by Sokolow-Lyon: S in V1 plus R in V5 or V6 over 35 mm).
   • Fundoscopy.
3. Further tests as features suggest: echocardiography (left ventricular hypertrophy, systolic and diastolic function), carotid ultrasound, ankle-brachial index, pulse wave velocity, chest radiograph, renal ultrasound.
4. Secondary hypertension work up when suspected:

• Aldosterone to renin ratio. Screen positive when aldosterone is over 10 ng/dL and the ratio over 20 to 30 with suppressed renin. Draw midmorning, correct potassium, and stop spironolactone and eplerenone for 4 to 6 weeks if possible. Then do saline suppression or captopril challenge, and adrenal vein sampling to lateralise.
• Plasma free metanephrines (supine) or 24 hour urinary fractionated metanephrines, then CT or MRI of abdomen and adrenals, and genetic testing.
• Overnight dexamethasone 1 mg test (08:00 cortisol under 50 nmol/L excludes), late night salivary cortisol, or 24 hour urinary free cortisol.
• Renal artery duplex ultrasound, CT angiography or MR angiography; renal scintigraphy.
• Sleep study (Epworth score over 10, snoring).
• Renal ultrasound and kidney biopsy for parenchymal disease.
• Thyroid function, parathyroid hormone, calcium, IGF-1 for acromegaly.
• Echocardiography or CT for coarctation.

1. Estimate 10 year cardiovascular risk with a validated calculator.
2. Pregnancy: urine protein to creatinine ratio, liver function, platelets, uric acid.

Limits. Clinic readings overestimate pressure (white coat effect in 15% to 30%); morning surge and nocturnal hypertension are missed. Aldosterone to renin ratio is affected by drugs and potassium. Imaging may show incidental adrenal nodules.

Goals.

• Most adults under 65: reduce office pressure to under 130/80 mmHg (not under 120/70) within 3 months.
• Adults 65 to 79: under 140/90 initially, then under 130/80 if tolerated.
• Age 80 or older, or frail: under 150/90 (under 140/90 if tolerated).
• Diabetes and chronic kidney disease: under 130/80 mmHg.
• Avoid systolic pressure under 110 mmHg or symptomatic hypotension.

Lifestyle (all patients, each reduces systolic pressure by roughly 2 to 10 mmHg).

• Salt under 5 g daily (2 g sodium), potassium rich diet (fruit, vegetables, legumes) if renal function allows.
• Weight loss to a body mass index under 25 where possible (about 1 mmHg for each kilogram lost).
• Dietary Approaches to Stop Hypertension style or Mediterranean diet; reduce processed food, sugar sweetened drinks, red meat.
• Regular aerobic activity 150 minutes weekly plus resistance training twice weekly.
• Alcohol limits (under 14 units weekly, ideally less; men 2 drinks and women 1 drink daily maximum).
• Stop smoking; reduce caffeine; sleep 7 to 8 hours; treat sleep apnoea (continuous positive airway pressure); stress reduction.

Drug treatment thresholds.

• Start at once for grade 2 or 3 (160/100 or more).
• Start at once for grade 1 (140/90) if cardiovascular risk is high: 10 year risk 10% or more, diabetes, chronic kidney disease, established cardiovascular disease or target organ damage.
• Grade 1 at low risk: lifestyle for 3 to 6 months first.
• Consider treating high normal pressure in very high risk (coronary disease).
• Older adults: treat from 140/90. In frail adults over 80 use caution.

First line combination therapy. Single pill combinations improve adherence and control.

Start two drug therapy for most patients with blood pressure 20/10 mmHg or more over target: ACE inhibitor or angiotensin receptor blocker plus a calcium channel blocker or a thiazide like diuretic.

In people of African ancestry, start with a calcium channel blocker, thiazide like diuretic, or both. ACE inhibitors and angiotensin receptor blockers are less effective alone but effective in combination; they remain preferred in diabetes, chronic kidney disease and heart failure.

• ACE inhibitor: ramipril 2.5 mg daily increasing to 10 mg (maximum 20 mg), lisinopril 5 mg daily increasing to 20 mg (maximum 40 mg), perindopril 4 mg daily increasing to 8 mg (maximum 16 mg), enalapril 5 mg daily to 20 mg twice daily.
• ACE inhibitor monitoring: check creatinine and potassium at 1 to 2 weeks (accept a rise in creatinine up to 30%). Avoid in pregnancy, bilateral renal artery stenosis, angioedema, hyperkalaemia. Cough occurs in 10% to 15%.
• Angiotensin receptor blocker: losartan 50 mg daily to 100 mg, valsartan 80 mg to 320 mg, telmisartan 40 mg to 80 mg, candesartan 8 mg to 32 mg.
• Calcium channel blocker: amlodipine 5 mg daily increasing to 10 mg (oedema, flushing, gum hyperplasia), nifedipine modified release 30 to 60 mg daily (maximum 90 mg), felodipine 5 mg to 10 mg, lercanidipine 10 mg to 20 mg. Use a non dihydropyridine (verapamil, diltiazem) when rate control is needed.
• Thiazide like diuretic: indapamide 1.5 mg modified release or 2.5 mg daily, chlortalidone 12.5 mg to 25 mg daily (maximum 50 mg), hydrochlorothiazide 12.5 mg to 25 mg daily (maximum 50 mg).
• Thiazide like diuretic monitoring: check sodium, potassium, urate, glucose at 2 weeks. Adverse effects are hypokalaemia, hyponatraemia, gout, impaired glucose tolerance. They are less effective if eGFR under 30 (use chlortalidone or loop diuretic).
• Combination tablets (for example amlodipine with perindopril, losartan with hydrochlorothiazide) to improve adherence.
• Beta blockers (bisoprolol 2.5 mg to 10 mg daily; nebivolol 5 mg daily; carvedilol 12.5 to 25 mg twice daily) are for coronary disease, heart failure, rate control, pregnancy (labetalol), or young patients with tachycardia. They are not first line otherwise.
• Resistant to three drugs: add spironolactone 25 mg daily increasing to 50 mg (check potassium and creatinine at 1 and 4 weeks; gynaecomastia), or eplerenone 50 mg to 100 mg.
• Alternatives for resistant disease:
  • Amiloride 5 to 10 mg.
  • Bisoprolol.
  • Doxazosin 1 mg at night increasing to 4 to 8 mg (orthostatic hypotension).
  • Clonidine 0.05 to 0.1 mg twice daily (rebound on withdrawal).
  • Hydralazine 25 mg twice daily increasing to 100 mg twice daily (with a beta blocker and diuretic).
  • Minoxidil 2.5 to 5 mg daily.
  • Renal denervation in specialist centres.

Management of specific groups.

• Diabetes: ACE inhibitor or angiotensin receptor blocker (especially with albuminuria), plus calcium channel blocker or thiazide like diuretic; target under 130/80.
• Chronic kidney disease: ACE inhibitor or angiotensin receptor blocker for albuminuria, add diuretic (loop diuretic if eGFR under 30), target under 130/80.
• Heart failure with reduced ejection fraction: ACE inhibitor or sacubitril-valsartan, beta blocker, mineralocorticoid antagonist, sodium glucose co-transporter 2 inhibitor; avoid non dihydropyridine calcium channel blockers.
• Coronary disease: beta blocker plus ACE inhibitor, calcium channel blocker.
• Stroke: lower blood pressure (indapamide with perindopril), target under 130/80 after the acute phase.
• Atrial fibrillation: beta blocker or non dihydropyridine for rate control, ACE inhibitor or angiotensin receptor blocker.
• Pregnancy drugs: labetalol 100 mg twice daily increasing to 400 mg three times daily (maximum 2.4 g), nifedipine modified release 10 to 20 mg twice daily (maximum 60 mg twice daily), or methyldopa 250 mg two to three times daily (maximum 3 g).
• Pregnancy precautions: avoid ACE inhibitors, angiotensin receptor blockers, renin inhibitors and spironolactone. Start treatment at 140/90. Give low dose aspirin 75 to 150 mg nightly from 12 weeks in high risk women.
• Primary aldosteronism: spironolactone 25 to 100 mg daily (up to 400 mg) or eplerenone; unilateral adenoma: adrenalectomy.
• Phaeochromocytoma: alpha blockade first (phenoxybenzamine 10 mg twice daily increasing to 1 mg/kg daily, or doxazosin 2 mg to 16 mg), then beta blocker, then surgery.
• Renal artery stenosis: ACE inhibitor with caution (monitor creatinine); stenting only in selected patients; fibromuscular dysplasia: angioplasty.
• Cushing syndrome and coarctation: specific surgery or intervention.
• Sleep apnoea: continuous positive airway pressure.

Adherence. Use once daily dosing, single pill combinations, a clear plan, home blood pressure monitoring, pill organisers and reminders, and address cost and side effects. Review within 2 to 4 weeks after changes until controlled, then every 3 to 6 months. Use a stepwise approach: add or titrate every 2 to 4 weeks.

Prevention of cardiovascular events. Atorvastatin 20 mg daily (40 to 80 mg in established disease, with LDL target under 1.8 mmol/L or 1.4 in very high risk); aspirin 75 mg daily only for established cardiovascular disease; glycaemic control; smoking cessation.

Monitoring. Home or clinic blood pressure at each visit. Check creatinine, eGFR and potassium after starting or increasing ACE inhibitors, angiotensin receptor blockers, diuretics and mineralocorticoid antagonists (1 to 2 weeks, then annually). Each year check urine albumin to creatinine ratio, lipids, glucose and ECG, and review target organ damage. Echocardiography every 1 to 3 years if hypertrophy.

Referral and escalation. Specialist hypertension clinic for resistant disease, suspected secondary causes, young onset, or pregnancy. Nephrology for chronic kidney disease. Endocrinology for adrenal disease. Cardiology for heart disease. Same day assessment for blood pressure 180/120 mmHg or more with symptoms.

Admission. Hypertensive emergency (encephalopathy, acute heart failure, aortic dissection, acute coronary syndrome, stroke, acute kidney injury, eclampsia, retinal haemorrhage with papilloedema), severe hypertension in pregnancy (160/110 or more), or blood pressure over 220/120 with symptoms.

Safety netting. Return urgently for chest pain, breathlessness, severe headache, confusion, visual loss, weakness or speech difficulty, fits, or blood pressure over 180/120 with symptoms. Do not stop treatment suddenly.

Special groups. Children and adolescents: use age, sex and height percentiles; secondary causes (renal, coarctation) predominate. Older adults: treat carefully, avoid orthostatic hypotension, and use long acting agents. Pregnancy: treat from 140/90 with labetalol or nifedipine, and monitor blood pressure after delivery.

People of African ancestry: higher prevalence, earlier onset and more target organ damage; calcium channel blockers and diuretics are effective. Diabetes and kidney disease: stricter targets. HIV: hypertension is common; check drug interactions between antiretrovirals and amlodipine.