Hypertension

01Definition and overview

Cardiovascular risk rises steadily with blood pressure from about 115/75 mmHg upwards, so any cut-off is a convention. European guidance uses three categories of clinic pressure:

Hypertension is often also graded by the clinic pressure: grade 1 is 140 to 159/90 to 99, grade 2 is 160 to 179/100 to 109, and grade 3 is 180/110 or more. Readings outside the clinic are lower, so their thresholds for hypertension are lower:

Comparing clinic and outside readings defines the phenotypes:

• White coat hypertension: high in the clinic, normal outside. The risk is between normal and hypertensive, and drugs are not usually started for it.
• Masked hypertension: normal in the clinic, high outside; it carries a risk close to sustained hypertension and is treated by the outside readings.
• Isolated systolic hypertension: a high systolic with a normal diastolic, the commonest form in older people, from stiff large arteries.
• Resistant hypertension: a pressure that stays at 140/90 or more despite lifestyle measures and three drugs, including a diuretic, at full or tolerated doses, confirmed by outside readings with good adherence.
• Orthostatic hypotension: a fall of 20 mmHg systolic or 10 mmHg diastolic within 3 minutes of standing, common in older people and in diabetes, and worsened by the drugs.

02Etiology and pathophysiology

Primary and secondary hypertension

About 90 per cent of patients have primary (formerly essential) hypertension, with no single cause. Hundreds of gene variants each add a little, and the environment adds the rest: a high salt and low potassium diet, obesity, alcohol, physical inactivity, and age, as the large arteries stiffen. It is commoner in people of Black African and African-Caribbean descent.

The rest have a secondary cause, more often in young patients:

Hypertension in pregnancy is covered in hypertensive disorders of pregnancy.

How the pressure stays high

Blood pressure is the cardiac output multiplied by the peripheral resistance. The kidneys normally excrete more salt and water whenever the pressure rises, which brings it back down; in hypertension this relationship is reset to a higher pressure. The renin-angiotensin-aldosterone system and the sympathetic nervous system retain salt and constrict the arterioles, and the small arteries thicken and narrow, which fixes the resistance at a higher level. Stiff large arteries in older people return the pressure wave early, raising the systolic and lowering the diastolic pressure.

1. 1

   Pressure load

   A persistently high pressure stretches and injures the walls of the arteries and loads the left ventricle.
2. 2

   Adaptation

   The left ventricle thickens, the small arteries remodel, and atherosclerosis accelerates in the large ones.
3. 3

   Organ damage

   Hypertension-mediated organ damage appears without symptoms: left ventricular hypertrophy, albuminuria, retinal changes, white matter lesions in the brain.
4. 4

   Events

   Over years this leads to stroke, myocardial infarction, heart failure, atrial fibrillation, chronic kidney disease, aortic disease and dementia.

Organ damage

• Heart: left ventricular hypertrophy, stiffness and heart failure, first with a preserved ejection fraction; atrial fibrillation; coronary disease.
• Brain: ischaemic stroke, intracerebral haemorrhage, lacunar infarcts, white matter disease and vascular dementia.
• Kidneys: albuminuria and nephrosclerosis leading to chronic kidney disease, which itself raises the pressure.
• Eyes: hypertensive retinopathy, graded as mild (arteriolar narrowing, arteriovenous nicking), moderate (haemorrhages, microaneurysms, cotton wool spots, hard exudates) or severe (moderate signs with swelling of the optic disc).
• Arteries: peripheral arterial disease, aortic aneurysm and dissection.

03Clinical features

Hypertension is usually silent and is found by measurement, which is why adults are screened. Headache and nosebleeds are not reliable signs. Symptoms come from organ damage (breathlessness, angina, transient neurological symptoms), from a secondary cause, or from a hypertensive emergency.

The examination measures the pressure in both arms at the first visit (a difference of more than 10 mmHg means the higher arm is used, and suggests arterial disease), lying or sitting and standing, and records the weight and waist. It looks for organ damage (a heaving apex, a fourth heart sound, signs of heart failure, retinal changes, weak pulses) and for secondary causes: radio-femoral delay, an abdominal bruit, enlarged kidneys, the features of Cushing syndrome or thyroid disease.

04Diagnosis and management

Measuring correctly

The patient sits for 5 minutes with the back supported, legs uncrossed and the arm supported at heart level, with a validated device and a cuff whose bladder encircles at least 80 per cent of the arm's circumference. Three readings are taken 1 to 2 minutes apart, and the average of the last two is used. In atrial fibrillation a manual (auscultatory) reading is more reliable.

Confirming the diagnosis

A raised clinic pressure is confirmed with readings outside the clinic, ambulatory monitoring or home readings taken twice in the morning and twice in the evening for about a week, unless the pressure is very high or there is organ damage. Ambulatory monitoring also shows the night-time pressure.

Tests for every patient

• ECG, for left ventricular hypertrophy and atrial fibrillation.
• Urine albumin-to-creatinine ratio and dipstick; creatinine and eGFR; sodium and potassium.
• Glucose or HbA1c and lipids, to estimate the cardiovascular risk.
• Echocardiography when the ECG is abnormal or there are signs of heart disease; fundoscopy in severe hypertension and in diabetes.
• Screening for primary aldosteronism, which European guidance now suggests considering for all adults with confirmed hypertension; a full search for secondary causes in patients under 40 and in severe or resistant hypertension.

When to treat

The target is a systolic pressure of 120 to 129 mmHg, and a diastolic of 70 to 79, if it is tolerated. In patients aged 85 or more, frail patients, patients with symptomatic orthostatic hypotension or a limited life expectancy, the pressure is lowered as far as is reasonably achievable, and the standing pressure is checked.

Lifestyle

Stopping smoking does not lower the pressure but reduces the overall risk.

Drugs

1. 1

   Start

   Two drugs at low doses, preferably in one pill: an ACE inhibitor or ARB with a calcium channel blocker or a thiazide-like diuretic. One drug alone suits an elevated pressure in a high-risk patient, and patients aged 85 or more, frail or with orthostatic hypotension.
2. 2

   If not controlled

   Three drugs, an ACE inhibitor or ARB with a calcium channel blocker and a thiazide-like diuretic, again in one pill if possible.
3. 3

   Resistant hypertension

   Out-of-office readings and adherence are checked first, interfering drugs stopped and secondary causes sought. Spironolactone is the usual fourth drug; eplerenone, amiloride, a beta-blocker, an alpha-blocker or a central drug are alternatives. Patients are referred to a specialist, and renal denervation, a catheter procedure that interrupts the renal nerves, can be considered in selected patients with an eGFR above 40.

Specific situations change the choice. In diabetes or kidney disease with albuminuria, an ACE inhibitor or ARB is part of every regimen, with an SGLT2 inhibitor where indicated. In heart failure with a reduced ejection fraction the heart failure drugs come first. ACE inhibitors, ARBs and mineralocorticoid antagonists are avoided in pregnancy; labetalol, nifedipine and methyldopa are used instead. A statin is added according to the overall cardiovascular risk; aspirin is not used for primary prevention.

Hypertensive emergency

A hypertensive emergency is a severely raised pressure, usually 180/110 mmHg or more, with acute organ damage. A severely raised pressure without acute damage is not an emergency: it is treated with oral drugs and early follow-up, and rapid lowering is avoided.

The emergencies include:

• malignant hypertension: severe retinopathy with flame haemorrhages, cotton wool spots or disc swelling, often with acute kidney injury and microangiopathic haemolysis;
• hypertensive encephalopathy: headache, confusion, seizures, reduced consciousness, often with posterior reversible brain oedema on MRI;
• acute stroke and intracerebral haemorrhage; acute coronary syndrome; acute pulmonary oedema; aortic dissection; severe pre-eclampsia and eclampsia; phaeochromocytoma crisis; cocaine or amphetamine toxicity.

Outside these situations, the pressure is not lowered to normal at once, because the brain and kidneys have adapted to it and a sudden fall can cause stroke, myocardial infarction or kidney injury. Sublingual nifedipine is never used. Once the patient is stable, oral treatment is started and secondary causes are sought.

05Epidemiology

About 1.3 billion adults aged 30 to 79 have hypertension worldwide, double the number in 1990, about a third of adults. Prevalence rises steeply with age, to more than half of people over 60. Around half of those affected do not know it, and only about 1 in 5 has the pressure controlled worldwide; in Europe control remains under half. Raised blood pressure is the leading risk factor for death in the world, linked to about 10 million deaths a year. It is commoner in men until middle age and in women afterwards, in people of Black African descent, and with obesity, high salt intake and alcohol. About 1 in 10 patients have a secondary cause, and more when it is looked for systematically, most often primary aldosteronism, which is found in a higher share of resistant hypertension. About 1 in 10 treated patients have resistant hypertension.

06Prognosis

From about 115/75 mmHg upwards, each 20 mmHg higher systolic pressure, or 10 mmHg higher diastolic, roughly doubles the risk of death from stroke and coronary disease in middle age. Treatment reverses much of this: each 10 mmHg fall in systolic pressure reduces major cardiovascular events by about a fifth, stroke and heart failure by about a quarter, and death from any cause by about an eighth. Aiming lower, for a systolic pressure below 120 rather than 140, prevented further events and deaths in a large trial of patients at high risk without diabetes or previous stroke, at the cost of more side effects such as low pressure and kidney injury; its unattended automated readings run lower than usual clinic readings.

The outlook depends on how early and how well the pressure is controlled and on the other risk factors. Left ventricular hypertrophy and albuminuria often regress with treatment. Untreated malignant hypertension killed most patients within a year or two; with treatment most now survive, although many are left with chronic kidney disease.