Clinical review: Hypertension

Contributed by Dr Klaus Witte, associate professor in cardiology and consultant cardiologist, University of Leeds and Leeds Teaching Hospitals NHS Trust; Dr Thomas Craven, cardiology registrar ST3, Huddersfield Royal Infirmary; Dr Simon Thackray, consultant interventional cardiologist, North Lincolnshire and Goole NHS Trust

Section 1: Epidemiology and aetiology

Hypertension is a major risk factor for cardiovascular disease, with a prevalence of 31% in men and 26% in women. As a modifiable risk factor for ischaemic and haemorrhagic stroke and coronary artery disease, hypertension management has become a focus for primary care, with a solid evidence base demonstrating improved outcomes. Despite this, 16% of men and 10% of women still have untreated hypertensive disease.

The overwhelming majority of adult patients (>95%) with raised blood pressure have primary hypertension, otherwise known as essential hypertension. Very few patients are found to have secondary hypertension (see table 1), with chronic renal failure the most frequent cause, and renovascular disease, pheochromocytoma, Cushing’s syndrome and primary aldosteronism rarer, but readily identifiable causes. Overall, obesity, smoking, alcohol intake, ethnicity and family history are the most important factors that contribute to the development of hypertension. The prevalence of hypertension in the UK is higher in people of afro-Caribbean or south Asian origin.

Table 1 – Causes of secondary hypertension
Drug-induced NSAIDs, steroids, combined oral contraceptive, illicit drugs
Endocrine Disease Conn's and Cushing's syndromes, phaeochromocytoma, acromegaly, hyperthyroidism
Renal Disease Diabetic nephropathy, renovascular disease, glomerulonephritis, polycystic kidney disease, chronic pyelonephritis
Congenital Coarctation of the aorta
Other Aortic regurgitation, pre-eclampsia, obesity, excessive dietary salt or liquorice intake, acute porphyria

Adapted from Ramrakha and Hill, Oxford Handbook of Cardiology, 2012, Page 226-227

Section 2: Making the diagnosis

The majority of hypertensive patients are asymptomatic, with no identifiable findings on clinical examination. As such, the majority of diagnoses are made either as a result of screening or when investigating patients with sequelæ of hypertension, such as overt coronary artery disease (myocardial infarction) or a cerebrovascular event.

Nevertheless, physical examination is important to identify features of end organ damage (such as retinopathy, heart failure, aortic aneurysm, carotid or femoral bruit) and to highlight any features of conditions that could cause secondary hypertension such as the abdominal striae and cushingoid facies of Cushing’s syndrome, the enlarged facial and bony features of acromegaly, the radio-femoral delay of coarctation of the aorta or the heat intolerance, weight loss and goitre or eye signs of hyperthyroidism.

A hypertensive patient should undergo a series of simple investigations to assess for end-organ damage and associated modifiable conditions.

A urine dipstick for blood and protein may indicate hypertensive renal disease. An ECG can identify left ventricular hypertrophy (LVH) or presence of an arrhythmia and, if abnormal, should prompt a cardiac ultrasound scan (echocardiogram). Blood tests for serum total and HDL cholesterol, urea and electrolytes, eGFR and blood glucose are also advised.

Further investigations to look for causes of secondary hypertension are only warranted if the patient is young (less than 40 years), has a poor treatment response or presents as accelerated hypertension (BP more than 180/110 mmHg with signs of papilloedema and/or retinal haemorrhage).

In such cases a renal ultrasound scan can suggest the presence of renovascular disease; a unilateral small kidney for example should prompt definitive investigation with a renal magnetic resonance angiogram.

Blood or 24-hour urine collections to measure metadrenaline and normetadrenaline levels could be used to determine the presence of phaeochromocytoma and plasma aldosterone:renin ratio can detect primary aldosteronism. An overnight dexamethasone-suppression test is the first-line test for Cushing’s syndrome.

New guidance has put a greater emphasis on ambulatory blood pressure monitoring (ABPM) in the diagnosis of hypertension. If a clinic-recorded BP is greater than 140/90 mmHg on two or more clinic measurements, then ABPM or home blood pressure monitoring (HBPM) should be performed.3

An average BP of greater than 135/85 on ABPM of HBPM is diagnostic of hypertension and this should be calculated from a minimum of 14 APBM measurements or from a minimum of four days (ideally seven days) at twice-daily measurements for HBPM. This method of diagnosing hypertension has been shown to be cost-saving for the NHS by reducing over-diagnosis of hypertension by clinic BP.

Categorisation into the stages of hypertension (see table 2) helps focus on patients requiring immediate treatment (severe hypertension >180/110), or those that can be initially treated with lifestyle modification.

Table 2 – Stages of hypertension
Stage Diagnostic Criteria
Normotensive ABPM/HBPM < 135/85
Stage I ABPM/HBPM ≥ 135/85
Stage II ABPM/HBPM ≥ 150/95
Severe Hypertension Clinic BP ≥180/110mmHg

Section 3: Managing the condition

Patients with stage I hypertension under 80 years of age, with either end-organ damage or comorbidites (diabetes mellitus, renal disease, established cardiovascular disease or a 10 year cardiovascular risk of greater than 20%) should be treated.

Similarly, treatment should be started for patients with confirmed stage II hypertension (on ABPM) and severe hypertension (BP>180/110). The guidelines advise that older patients (>80years) with stage I hypertension should not receive treatment. Effective treatment often requires modification of lifestyle-related risk factors and use of antihypertensive medication.

Lifestyle advice
All hypertensive patients should be given lifestyle advice. This should include advice about exercise, weight loss and decreasing alcohol and salt intake as required. Smoking cessation advice should be offered as this contributes to cardiovascular risk; even if not directly proven to cause hypertension.

Antihypertensive medication
The therapeutic aims of medication in the majority of patients is to control BP to <140/90mmHg. Targets are lower (<135/85mmHg) in diabetics and higher (<150/90mmHg) in the elderly (>80 years).

Figure 1 shows an adapted treatment algorithm for hypertension. Important caveats to the traditional algorithm exist. Beta-receptor antagonists have a greater role in patients with established coronary artery disease and should be considered earlier in hypertensive patients following a myocardial infarction or after the diagnosis of angina or heart failure due to their prognostic benefit.

Calcium channel blockers might be less effective than other classes of antihypertensive agents at preventing heart failure, and as such these are often considered fourth line in patients at higher risk of heart failure.

Renal denervation
Despite optimal oral therapy many patients do not achieve adequate blood pressure control and remain at high risk. Such patients have been the recent focus of trials of non-pharmacological hypertensive therapies, with the most promising being percutaneous renal denervation (RDN).

The central role of the sympathetic nervous system in hypertension has been understood for decades, with surgical intervention to the nerves of the kidney often the only therapy available. The advent of reliable drug therapies along with the high incidence of major side-effects from surgery led to loss of interest in ‘renal denervation’.

Development of catheter-based denervation over the last seven years has allowed the creation of targeted localised nerve damage avoiding the severe side-effects. Performed under X-ray guidance and sedation, precisely targeted radio-frequency energy heats and destroys sympathetic nerves running along the wall of the renal artery into the kidney.

This leads to a significant and sustained drop of blood pressure in well-selected patients. Further trial work is on-going to identify the magnitude and duration of the effect and the best patients to target, which has the potential to act as a useful adjunct to drug therapy in hard to treat, high risk, or poorly compliant patients.

Section 4: Prognosis

Hypertension is exponentially associated with increased cardiovascular and cerebrovascular events leading to death or long-term disability. Conversely, long-term reductions in diastolic BP by just 6mmHg have been shown to result in 40% less cerebrovascular and 25% less coronary heart disease events and deaths. The benefits of BP reduction are greatest in those who achieve a target diastolic BP of <80mmHg.

Follow up
All hypertensive patients receiving treatment should have annual follow up to ensure continued control and reinforce medication compliance. Patients at risk of developing hypertension should be reassessed every five years.

Section 5: Case study

Terry is a 46-year-old male farmer with hypertension. He is overweight, has never smoked, has an acceptable alcohol intake and his occupation gives him reasonable levels of exercise. Despite a few years of trial and error and uptitration of his antihypertensive medications by his GP, Terry still suffers with uncontrolled hypertension.

Terry was taking amlodipine 5mg OD, bisoprolol 5mg OD, lisinopril 10mg OD, bendroflumethiazide 2.5mg OD and doxazosin 2mg OD. After a hospital admission for expressive dysphasia and disorientation Terry was diagnosed as having a TIA and his GP became more concerned over his uncontrolled hypertension and referred him for a specialist assessment by a cardiologist.

On assessment by the specialist, Terry's clinic BP was 167/89 and the patient confirmed that his home readings were often at a similar level. Terry's clinical examination was unremarkable. The specialist reviewed Terry's previous results and after completing more investigations excluded secondary hypertension.

The options were then discussed on how to treat Terry's resistant essential hypertension. The patient decided to opt for renal denervation as he had seen only slight improvement in his blood pressure despite his medications.

Terry's procedure went to plan with no complications and he returned for follow up over the next 12 months. The blood pressure reductions over consecutive follow up declined to 155/83, 149/78 and 142/75 at 3,6 and 12 months respectively. Terry is currently undergoing continued follow up and the specialist is hopeful that he will be able to start weaning his anti-hypertensive medications shortly should his BP continue to decline.

Section 6: Evidence base

  • Turnbull, F., Neal, B., Ninomiya, T., Algert, C., Arima, H. & MacMahon, S.: Trialists’Collaboration, B. P. L. T. (2008). Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials. BMJ, 336(7653), 1121-3.

This meta-analyses and meta-regression analysis of 31 trials showed no clear difference between age groups in the effects of lowering blood pressure or any difference between the effects of the drug classes on major cardiovascular events.

  • Czernichow S, Zanchetti A, Turnbull F, et al. Blood Pressure Lowering Treatment Trialists' Collaboration. The effects of blood pressure reduction and of different blood pressure-lowering regimens on major cardiovascular events according to baseline blood pressure: meta-analysis of randomized trials. J Hypertens 2011;29:4-16

This paper combines the results of 32 trials and demonstrates the effectiveness of blood pressure reduction in prevention of cardiovascular events showing that it does not depend upon starting blood pressure and that additional efforts in those meeting existing targets will produce further benefits.

  • Sever PS & Messerli FH; Hypertension management 2011: optimal combination therapy; European Heart Journal (2011) 32, 2499–2506

This paper gives comprehensive advice on when to uptitrate, combine and substitute antihypertensives and presents the argument for early introduction of combination therapy.

The guidelines

NICE Hypertension – clinical guideline 127: The clinical management of primary hypertension in adults. (diagnostic algorithm on page 37 and treatment algorithm on page 38)

Key learning points
  • An average BP of >135/85mmHg on ambulatory BP monitoring or home BP monitoring is diagnostic of hypertension
  • Patients with stage 1 hypertension under age 80, with either end organ damage or comorbidities, should be treated
  • Moderate or severe depression (consider drug therapy in combination with CBT or interpersonal therapy).
  • For most patients the therapeutic aim of medication is to control BP to <140/90mmHg
  • All hypertensive patients receiving treatment should have annual follow-up

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