Case one:

Beth, aged 55 years, has had a raised BP for approximately 3 years. At a visit to her GP 3 months ago, her BP was found to be 190/110 mmHg (sitting) and she was treated with irbesartan 300 mg per day. However, on this drug regimen, her BP control has been inadequate. This in part is due to poor compliance with her medication.

On presentation, she complains of heaviness in the occipital region and retro-orbital discomfort on waking, and gives a history of nocturia (which has previously been investigated by a urologist). When examined, Beth has a BP of 150/100 mmHg (lying) and 140/105 mmHg (standing) with an otherwise normal clinical examination.

Answer 1

Beth needs to be fully investigated to determine whether her elevated BP is of a primary or secondary nature. It is recommended in the Hypertension management guide for doctors 2004 recently released by the Heart Foundation that specialist referral should be considered if secondary hypertension is suspected. The complete list of investigations that should be conducted is:

• a complete blood examination
• a full biochemical screen which includes electrolyte levels, creatinine, urate, glucose and liver function tests
• an assessment of thyroid function
• an electrocardiogram
• an echocardiogram
• clinic testing of the urine for protein and sugar
• a microurine (in view of her past history of nocturia).

Depending on the clinical findings, Beth will need to be investigated for the more common causes of secondary hypertension such as renovascular disease, primary hyperaldosteronism, and Cushing syndrome. These investigations are most readily arranged in a specialist hypertension clinic.

An estimation of a fasting plasma homocysteine level may also be useful as homocysteine is now widely recognised as a risk factor for vascular disease.

The guidelines for the management of hypertension were recently revised by a group in the USA called the Joint National Committee (JNC). The most recent version of these guidelines (JNC7) was released in May 2003. In JNC6 (the previous version of the guidelines), hypertension was defined as systolic BP ³140 mmHg or diastolic pressure ³90 mmHg in patients not taking antihypertensive drugs based on at least two readings.

Optimal BP was considered to be <120/80 mmHg with "normal" defined as <130/85 mmHg and high-normal defined as <140/90 mmHg. In JNC7, "normal" has replaced "optimal" as the classification for BP <120/80 mmHg and "prehypertension" has replaced "normal" and "high normal" for BP values between 120/80 mmHg and 140/90 mmHg. JNC7 recommends treating systolic and diastolic BP to targets that are less than 140/90 mmHg in patients without comorbidities. In the Heart Foundation's Hypertension management guide for doctors 2004, it is recommended that adults under 65 years should have a target of <130/85 mmHg.

In patients with hypertension who have concurrent renal disease or diabetes mellitus, the BP goal should be less than 130/80 mmHg. The angiotensin converting enzyme (ACE) inhibitors and angiotensin 2 antagonists have been shown to provide significant benefits in patients with type 2 diabetes, both at early (microalbuminuria) and late (proteinuria) stages of renal decline. Thus, a drug from one of these two groups, including irbesartan would be an appropriate first line agent if Beth had these two conditions coexisting. Obviously good glycaemic control, in addition to the reduction in BP to optimal values, and blockade of the renin angiotensin system, is important in the preservation of the patient's renal function.

A large number of pharmacological agents (belonging to several different categories) are available for the treatment of hypertension. These include:

• low dose thiazide diuretics
• beta receptor antagonists
• ACE inhibitors
• calcium channel blockers
• angiotensin 2 antagonists.

Two further groups are sometimes used in particular situations:

• direct vasodilators, and
• alpha receptor antagonists.

In the case of Beth, her GP has already prescribed irbesartan, an agent which belongs to the angiotensin 2 antagonists category in the above list. Allowing for some "slippage" due to poor compliance, it is more than likely that she would require a second agent to optimise BP control. In general, more than 50% of hypertensive patients require more than one drug to achieve their target.

Feedback

While members of several of the antihypertensive drug classes could be used in conjunction with irbesartan to optimise BP control, a decision was made to choose a calcium channel blocker (of the dihyropyridine variety) to assist in management. The particular agent selected was lercanidipine. It was introduced at a dose of 10 mg per day with significant improvement in control to 140/85 mmHg (lying) and 130/90 mmHg (standing). Attention was paid to all the other cardiovascular risk factors operating in Beth.