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National Clinical Guideline Centre (UK). Hypertension: The Clinical Management of Primary Hypertension in Adults: Update of Clinical Guidelines 18 and 34 [Internet]. London: Royal College of Physicians (UK); 2011 Aug. (NICE Clinical Guidelines, No. 127.)

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Hypertension: The Clinical Management of Primary Hypertension in Adults: Update of Clinical Guidelines 18 and 34 [Internet].

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8Assessing cardiovascular risk, target organ damage and secondary causes of hypertension

There are four key objectives in the assessment of a person with suspected hypertension; i) to confirm whether or not blood pressure is elevated (see section xxx); ii) to document the presence or absence of blood pressure related target organ damage damage (e.g. left ventricular hypertrophy, hypertensive retinopathy, increased albumin:creatinine ratio); iii) to evaluate the person’s cardiovascular risk either due to established cardiovascular disease or high cardiovascular disease risk states (e.g. diabetes or CKD), or by calculation of their 10 year CVD risk estimate (ref section and NICE guidance), and iv) to consider whether their may be secondary causes for the hypertension.

The risk of clinical events associated with hypertension is not only determined by the level of blood pressure but also by; i) the presence of target organ damage; ii) the presence of established cardiovascular disease (iscahemic heart disease or heart failure, cerebrovascular disease, peripheral vascular disease) or concomitant disease associated with high cardiovascular disease risk, e.g. diabetes or CKD; or iii) the calculated cardiovascular risk (estimated from factors such as age, gender, smoking history, etc.). Therefore, routine assessment of simple markers of target organ damage, a clinical history and examination to identify associated cardiovascular disease and when indicated, cardiovascular risk calculation, all form part of the routine assessment of a patient with suspected or confirmed hypertension. This assessment will also help clinicians to decide the appropriate blood pressure threshold at which to consider drug therapy for the treatment of hypertension and whether any additional therapies to reduce cardiovascular disease risk (e.g. statins and antiplatelet therapy) should also be offered to the patient.

The clinical history, examination and routine blood and urine tests will also alert the clinician to possible secondary causes of hypertension, some of which are potentially life threatening (e.g. phaeochromocytoma), and others which might be amenable to potentially curative interventions (e.g. Conn’s adenoma, fibromuscular dysplasia).

8.1.1. Hypertension and cardiovascular disease

An analysis of 61 prospective observational studies, involving nearly one million individuals, explored the relationship between blood pressure level and 12,000 strokes and 34,000 ischaemic heart disease events over an average of 13.2 years follow-up361. Across age bands from 40 to 89, reduction in usual diastolic blood pressure of 20 mmHg systolic or 10 mmHg diastolic blood pressure was associated with reductions in death from stroke and ischemic heart disease of about one half, slightly more in the youngest and slightly less in the oldest. Findings were similar for men and women, for different types of stroke, and consistent across the range of blood pressure (down to 115/75 mmHg).

An earlier analysis of nine observational studies, involving 420,000 individuals explored the relationship between blood pressure level and 843 subsequent strokes and 4,856 coronary events over an average of 7 years follow-up379. Reductions in usual diastolic blood pressure of 5, 7.5 and 10 mmHg were associated with reductions in stroke of 34%, 46% and 56% and coronary heart disease of 21%, 29% and 37% respectively. The relationship between blood pressure and disease was constant over a wide range suggesting there is no clear threshold below which further reduction in blood pressure becomes unbeneficial or harmful.

The implication of these two studies is that some or all of the predicted benefits, found by comparing individuals with different usual blood pressure levels, could be obtained by one patient maintaining a similar reduction.

A systematic review of 14 antihypertensive randomised drug trials (diuretics or beta-blockers compared with placebo) included 37,000 patients135. A mean reduction in diastolic blood pressure of 5–6 mmHg over 5 years achieved a relative reduction in stroke of 42% (95% CI: 33–50%) and CHD of 14% (95%CI: 4–22%). The authors concluded that virtually all of the epidemiologically observed benefit from reduced stroke and over half of the reduction in coronary heart disease could be achieved by lowering blood pressure.

8.2. Routine clinical investigations

A full cardiovascular assessment should be conducted in patients with persistently raised blood pressure who do not have established cardiovascular disease. There is no firm evidence from which to define the exact composition of assessment and recommendations are consensus-based. Medical history, physical examination, and limited diagnostic testing serve to identify an individual patient’s profile of cardiovascular risk factors including age and gender, smoking, hyperlipidaemia, diabetes, and family history of cardiovascular disease. Testing may detect diabetes and identify signs of developing target organ damage such as left ventricular hypertrophy and angina. It may also detect secondary causes of hypertension.

The guideline group identified the following tests as necessary to obtain an accurate profile of cardiovascular risk. These tests may help identify diabetes, evidence of hypertensive damage to the heart and kidneys, and secondary causes of hypertension such as kidney disease:

  • Urine strip test for blood and protein
  • Blood electrolytes and creatinine, and eGFR
  • Blood glucose
  • Serum total and HDL cholesterol
  • 12 lead electrocardiogram.

8.2.1. Urine testing for proteinuria

The presence of protein in urine identifies patients with kidney damage, but does not distinguish between patients who have renal disease and secondary hypertension and those in whom kidney damage is due to essential hypertension. The test consists of dipping a test strip, which is impregnated with chemicals which react to protein, into a sample pot of urine. After 30–60 seconds (or according to manufacturer’s instructions) the strip is read alongside a colour code provided. A more sensitive test for urine protein is available by requesting the local chemical biochemistry laboratory to assay microalbumin in a random specimen of urine. For further information refer to NICE Clinical Guideline 73.

8.2.2. Blood electrolyte, urea, creatinine, glucose and total/HDL cholesterol levels

These are measured in serum or plasma (glucose) using standard clinical biochemistry methods. Sodium and potassium levels are checked to exclude hypertension resulting from adrenal disease. Likewise, urea and creatinine measurements, which reflect kidney function, are measured to exclude kidney disease as a secondary cause of hypertension Glucose levels are tested to evaluate diabetes and cholesterol profiles are used to assess cardiovascular risk. 12 lead electrocardiogram. Refer to NICE guidance on Diabetes (Clinical Guidelines 15 and 87).

From an ECG it is possible to determine heart rate, rhythm, conduction abnormalities, left ventricular size and damage to specific regions of the heart muscle. The presence of electrocardiographic left ventricular hypertrophy is a variable used in cardiovascular risk calculators. An echocardiogram might be considered, to confirm or refute the presence of LVH suggested by ECG findings.

8.3. Cardiovascular Risk Assessment

Risk models have been developed (as charts, graphs or computer programmes) to allow clinicians to predict the likelihood of patients developing coronary or cardiovascular disease using lifestyle and clinical markers (See NICE Lipids Modification, CG67). Although they vary in detail, risk models may estimate an individual’s risk of coronary heart disease and stroke over the next ten years using their gender, age, diabetic status, smoking status, total serum cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and blood pressure. An important aspect of risk models is that they lead the clinician to address a patient’s overall profile of risk rather than treat one risk factor in isolation. Risk factors have a cumulative effect, and an individual with a number of modest risk factors may be at greater risk of developing cardiovascular disease than an individual with one high risk factor23. Since several risk factors are potentially modifiable, an important aspect is which of these to address and in what order.

8.4. Secondary Hypertension

  • An identifiable cause of hypertension is more likely when hypertension occurs in younger patients (less than 40 years of age), worsens suddenly, presents as accelerated hypertension (BP more than 180/110 mmHg with signs of papilloedema and/or retinal haemorrhage) or responds poorly to treatment. [III]
  • An elevated creatinine or reduced eGFR indicates renal disease. Labile or postural hypotension, headache, palpitations, pallor and diaphoresis are potential signs of pheochromocytoma. Hypokalaemia, abdominal or flank bruits, or a significant rise in serum creatinine when starting an ACEi or ARB may indicate renovascular hypertension. Isolated hypokalaemia may be due to hyperaldosteronism. Potential signs of Cushing syndrome include osteoporosis, truncal obesity, moon face, purple striae, muscle weakness, easy bruising, hirsutism, hyperglycemia, hypokalaemia, and hyperlipidaemia. [III]

Secondary hypertension refers to high blood pressure from an identifiable underlying cause. It may occur in up to 10% of hypertension cases, the most common cause being chronic renal disease. Other principal identifiable causes are renovascular hypertension, pheochromocytoma, Cushing syndrome, and primary aldosteronism. Signs and symptoms of the main causes of secondary hypertension and available diagnostic tests are summarised below, although many of these techniques are not provided in primary care but accessed through specialist referral. We retrieved no useful diagnostic studies which might establish primary care screening characteristics for secondary causes of hypertension as a basis for referral: current advice is simply to be aware of signs and symptoms and refer on the basis of a high index of suspicion and where the findings are likely to necessitate specialist management.

8.4.1. Renal and renovascular disease

Chronic kidney disease is the most common identifiable cause of hypertension occurring in 2% to 5% of patients182. The British National Formulary advises against routinely using ACEi or ARBs in patients with known or suspected renovascular disease26.

Signs and symptoms indicating that hypertension may be associated with renal disease are: young onset of hypertension (before 40 years of age), sudden onset of hypertension or progressive deterioration in middle age, accelerated hypertension (BP more than 180/110 mmHg with signs of papilloedema and/or retinal haemorrhage), oliguria (urine output <250 ml/day) or anuria (<50 ml/day), oedema, acidosis (acidic blood, <pH), abnormal serum urea or reduced eGFR, systolic or diastolic bruit467, drug resistant hypertension or increased creatinine with ACEi or ARB, hypertension onset > 60 years, DBP >110 mmHg, and anaemia (lowered red blood cell count) resulting in insufficient oxygen to tissues and organs. Although renal artery of an abdominal or flank bruit, it is an insensitive test (sensitivity=65%; specificity=90%). When present it is a good marker (positive likelihood ratio=6.5) but when absent does not rule out renal artery stenosis (negative likelihood ratio=0.4)182,505.

Renal disease may be diagnosed by elevated serum levels of urea or creatinine (found by a blood test) or reduced eGFR. Specialist investigation includes magnetic resonance angiography for imaging of the kidneys, and duplex ultrasound scanning directly measuring the size of the kidneys467, 35. Test sensitivities have been reported for these investigations182.

8.4.2. Pheochromocytoma

A pheochromocytoma is a tumour which produces and releases large amounts of adrenaline and noradrenaline (hormones) into the blood. It is rare and may occur in between 0.04% and 0.1% of patients; about 10% are malignant. Adrenaline causes an increase in heart rate and contractility, while noradrenaline increases systemic vascular resistance. Patients with signs and symptoms of pheochromocytoma need immediate specialist investigation given the seriousness of the condition and risk to the patient. The definitive treatment of pheochromocytoma is surgical removal of the tumour.

Signs and symptoms include a rapid heart rate, headache, high blood glucose levels, elevated basal metabolic rate, facial flushing, nervousness, sweating, decreased gastrointestinal movements and oedema.

Diagnostic techniques include plasma or 24 hour urine collections for metadrenaline and normetadrenaline 22,250. Following positive findings two types of imaging study may be used to locate the tumour: metaiodobenzyl-guanidine (MIBG) scintigraphy and computed tomography (CT).

8.4.3. Hyperaldosteronism (primary aldosteronism)

Aldosterone is a hormone that regulates sodium and water balance. Hyperaldosteronism can due to bilateral adrenal hyperplasia or Conn’s adenoma occurring in 0.01% to 0.03% of patients182,570], although its prevalence is contested and may be much higher [364.

Signs and symptoms include sodium retention, and hypokaelaemia leading to heart rhythm irregularities and possibly muscle weakness. The hypokaelaemia may only occur when diuretic-induced hypokalaemia is not explained by natural causes467.

Measurement of plasma aldosterone levels and plasma renin activity as the aldosterone:renin ratio may be used to detect primary aldosteronism250. As with any laboratory test, standardisation of laboratory assays is important.

8.4.4. Cushing’s syndrome

Cushing’s syndrome is a syndrome generated by excess glucocorticoids. Cushing’s Disease specifically refers to over-production of ACTH by the pituitary gland and is the most common form of the syndrome. Over-production of cortisol can also be due to a tumour in the adrenal gland, either benign (an adenoma), or malignant (a carcinoma) and in this variant is not dependent on ACTH. Production of ACTH in an organ or gland other than the pituitary or adrenal gland (e.g. thymus gland, lung, pancreas) is called ectopic corticotrophin-releasing production469. Cushing’s syndrome may occur in 0.1% to 0.6% of patients.

Signs and symptoms include hypertension, sudden onset of weight gain, central obesity, moon face, weakness, fatigue, backache, headache, glucose intolerance, oligomenorrhoea (infrequent menstruation), amenorrhoea (abnormal discontinuation of periods), increased thirst, increased urination, impotence, muscle atrophy, depression, insomnia, thinning of the skin, cutaneous hyperpigmentation (darkening of the skin), osteoporosis469.

Diagnosis of Cushing’s syndrome begins with a single dose overnight dexamethasone-suppression test. A differential diagnosis is achieved by measuring plasma ACTH together with either a long dexamethasone suppression test or a corticotrophin-releasing hormone (CRH) stimulation test217,437.

8.5. Other identifiable causes of hypertension

8.5.1. Hypothyroidism

Hypothyroidism is under production of the hormone thyroxine (which controls metabolism) by the thyroid gland. Hypertension in hypothyroid patients may result from altered levels of renin, angiotensin and aldosterone. After thyroid replacement therapy diastolic blood pressure returns to normal in patients with hypothyroidism suggesting a cause-and-effect relationship185,329,509. Signs and symptoms include lethargy, fatigue, weight loss, hair loss, confusion, nausea, bone pain, muscle weakness, slow heart rate. Hypothyroidism is associated with increased diastolic blood pressure75,572. Hypothyroidism is diagnosed by measuring thyroid stimulating hormone levels467.

8.5.2. Hyperthyroidism

Hyperthyroidism is the excessive secretion of thyroxine by the thyroid gland. Signs and symptoms include increased systolic blood pressure, increased metabolic rate, enlargement of the thyroid gland, tachycardia (increased heart rate), exophthalmia (abnormal protrusion of the eyeball in the orbit), oedema, dry hair and skin, weight gain, goitre (enlarged thyroid gland)314. Hyperthyroidism is diagnosed by measuring thyroid stimulating hormone levels467.

8.5.3. Obstructive sleep apnoea

Obstructive sleep apnoea is caused by the upper airway becoming obstructed during sleep. It is more prevalent in men. Signs and symptoms include daytime somnolence (unnatural drowsiness and sleepiness), obesity, snoring, lower extremity oedema, nocturia and morning headaches. The main diagnostic technique is a polysomnograph to monitor normal and abnormal physiological activity during sleep 250,467. Please refer to NICE Technology Appraisal 139 (www.http://guidance.nice.org.uk/TA139/Guidance/pdf/English) for guidance on continuous positive airway pressure (CPAP).

8.5.4. Coarctation of aorta

Coarctation of aorta is a congenital condition where a segment of the aorta is too narrow, reducing oxygenated blood flow around the body. Signs and symptoms include high blood pressure, decreased or delayed femoral pulse, abnormal chest radiograph. Diagnostic techniques: doppler or CT imaging of the aorta467.

8.5.5. Acromegaly

Acromegaly is due to excess production of growth hormone. Signs and symptoms of acromegaly include hypertension, cardiomegaly, enlarged facial features, enlarged jaw, headache and arthralgia, hypertrichosis, excessive sweating, tiredness, weakness, somnolence and impaired glucose tolerance360. Acromegaly is diagnosed by evidence of increased growth hormone secretion360.

8.5.6. Drugs

A number of medications are known to cause raised blood pressure. These include decongestant found in inhaled cold remedies, may raise diastolic blood pressure517,547. Oral contraceptive pills containing oestrogen may cause small, and occasionally pronounced, rises in blood pressure. In rare cases accelerated hypertension may occur535. Other drugs that may raise blood pressure include immunosuppressive agents, nonsteroidal anti-inflammatory drugs, COX-2 inhibitors, weight loss agents, stimulants (for example, cocaine), mineralocorticoids, antiparkinsonian agents, monoamine oxidase inhibitors, anabolic steroids, sympathomimetics467.

8.6. Recommendations

For NICE guidance on the early identification and management of chronic kidney disease see ‘Chronic kidney disease’ (NICE clinical guideline 73, 2008).

19.

Use a formal estimation of cardiovascular risk to discuss prognosis and healthcare options with people with hypertension, both for raised blood pressure and other modifiable risk factors. [2004]

20.

Estimate cardiovascular risk in line with the recommendations on Identification and assessment of CVD risk in ‘Lipid modification’ (NICE clinical guideline 67)h. [2008]

21.

For all people with hypertension offer to:

  • test for the presence of protein in the urine by sending a urine sample for estimation of the albumin:creatinine ratio and test for haematuria using a reagent strip
  • take a blood sample to measure plasma glucose, electrolytes, creatinine, estimated glomerular filtration rate, serum total cholesterol and HDL cholesterol
  • examine the fundi for the presence of hypertensive retinopathy
  • arrange for a 12-lead electrocardiograph to be performed. [2004, amended 2011]

8.7. Research recommendations

2.

In people aged under 40 with hypertension, what is the most accurate method of assessing the lifetime risk of cardiovascular events and the impact of therapeutic intervention on this risk?

Current short-term (over 10 years) risk estimates are likely to substantially underestimate the lifetime cardiovascular risk of younger people (aged under 40) with hypertension, because short-term risk assessment is powerfully influenced by age. Nevertheless, the lifetime risk associated with untreated stage 1 hypertension in this age group could be substantial. Lifetime risk assessments may be a better way to inform treatment decisions and evaluate the cost effectiveness of earlier intervention with pharmacological therapy.

Clinic blood pressure measurements must be used in the calculation of cardiovascular risk.

Footnotes

h

Clinic blood pressure measurements must be used in the calculation of cardiovascular risk.

Copyright © 2011, National Clinical Guideline Centre.

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