Hypertension - diagnosis, targets, stepped pharmacotherapy, secondary causes

1. Definition and clinical relevance

Hypertension is a sustained elevation of arterial blood pressure that, over time, drives cardiovascular, cerebrovascular and renal disease.

A disease of ageing:

• Blood pressure rises gradually with age in a roughly linear relationship
• Rare in children and adolescents
• Diagnosis under 30 years should prompt evaluation for secondary causes rather than accepting primary (essential) hypertension

Continuous variable, not a threshold:

• Blood pressure is normally distributed with no single diagnostic cut-off
• Each 2 mmHg rise in systolic pressure increases ischaemic heart disease mortality by roughly 7%
• Each 2 mmHg rise increases stroke mortality by roughly 10%
• Risk is graded and continuous

Part of comprehensive cardiovascular risk reduction:

• Must be managed as part of overall cardiovascular risk strategy, not as an isolated number
• Randomised trial evidence confirms lowering blood pressure reduces cardiorenal events and overall mortality

Why it matters:

• Common, largely asymptomatic and highly treatable
• Most cases managed in primary care
• Effective control prevents stroke, myocardial infarction, heart failure and chronic kidney disease

2. Key values, thresholds and decision rules

Hypertension should never be diagnosed on a single reading. At least two follow-up measurements are required, and when clinic readings are elevated, out-of-office confirmation with ambulatory blood pressure monitoring (ABPM) or home blood pressure monitoring (HBPM) is preferred to exclude "white coat" hypertension.

Measurement technique

• If a repeat clinic measurement differs from the first, take a third and record the lower of the readings.
• If clinic BP on repeat testing is ≥140/90 mmHg in a person not known to be hypertensive, offer ABPM or HBPM to confirm.
• ABPM measures BP every 20 minutes in the daytime (less frequently at night) over 24 hours.
• If hypertension is not confirmed on ABPM/HBPM, recheck BP periodically, and more frequently if readings are close to 140/90 mmHg.

Diagnostic thresholds

Who to treat with drugs

Adding and adjusting therapy

• Add only one agent at a time and wait about 4 weeks between dosage adjustments.
• In the elderly, start low and go slow: commence at about half the normal adult dose. Isolated systolic hypertension is worth treating, and healthy patients over 75 can be treated similarly to younger adults.

Cardiovascular co-therapy

• Prescribe a statin if hypertension is complicated by CVD (irrespective of baseline lipids), or for primary prevention in patients over 40 years with a 10-year CVD risk ≥10%.
• Do not offer calcium, magnesium or potassium supplements as a method to lower BP.

3. Approach: presentation and differential

History

Hypertension is usually asymptomatic and found on screening. Take a targeted history covering:

• Cardiovascular risk and end-organ damage: previous stroke/TIA, myocardial infarction, angina, peripheral vascular disease, renal impairment, diabetes.
• Lifestyle contributors: dietary salt, body weight, alcohol (excessive intake can cause hypertension and make it hard to treat).
• Medication and substance history: including illicit drugs and alternative or complementary remedies, which can raise BP.
• Clues to a secondary cause: young age at onset, absence of family history, difficult-to-control or accelerated hypertension.
• Obstructive sleep apnoea symptoms.

Features that raise the probability of a secondary cause and warrant a lower threshold for investigation include age under 35 (especially without a family history), accelerated or malignant hypertension, and hypokalaemia.

Examination

• Confirm BP with correct technique; check both arms where relevant.
• Look for target organ damage and signs of a secondary cause:
  • Epigastric or renal bruits suggest renal artery stenosis (the low-pitched bruit is best heard over the flank/epigastrium).
  • Abdominal aortic aneurysm or a pulsatile mass.
  • Flank masses suggest polycystic kidneys.
  • Delayed or absent femoral pulses (radiofemoral delay) suggest coarctation of the aorta.
  • Truncal obesity with pigmented striae suggests Cushingoid states.
• Fundoscopy and cardiac examination for hypertensive end-organ effects.

Differential

Consider the causes of secondary hypertension (5-10% of cases):

• Renal: parenchymal disease (proteinuria, abnormal urine sediment), renal artery stenosis.
• Endocrine: primary hyperaldosteronism (now recognised as more often due to bilateral adrenal hyperplasia than a classical Conn's adenoma; may be genetic), phaeochromocytoma, Cushing's syndrome.
• Vascular: coarctation of the aorta.
• Other: obstructive sleep apnoea, drug- and alcohol-related hypertension.

4. Investigations

Bedside

• Urinalysis for proteinuria and abnormal urine sediment (a sensitive pointer to renal parenchymal disease).
• Repeat/serial BP measurement, ABPM or HBPM to confirm the diagnosis and detect white coat hypertension.

Bloods

• Assessment for end-organ damage and cardiovascular risk: renal function and electrolytes (hypokalaemia below 3.5 mmol/L raises suspicion of hyperaldosteronism, though it is frequently absent), glucose, and lipids.
• Aldosterone-to-renin ratio (ARR) is now used in the routine investigation of hypertension to screen for primary hyperaldosteronism. It is not practical to screen every patient for endocrine causes; target those at higher risk (young, malignant, or hypokalaemic).

Imaging

• Imaging for secondary causes when clinically indicated (for example, renal and renovascular imaging when renal artery stenosis is suspected, adrenal imaging in confirmed hyperaldosteronism).

5. Management

Manage hypertension as one component of overall cardiovascular risk reduction. Combine lifestyle change with antihypertensive drug therapy where indicated, and support adherence at every visit.

Step 1: Lifestyle and population measures

• Diet: reduce dietary sodium (this is more beneficial in older than younger patients), improve overall diet quality.
• Weight: reduce body weight if overweight or obese.
• Alcohol: restrict intake; excess alcohol both causes hypertension and undermines treatment.
• Physical activity and smoking cessation as part of comprehensive risk reduction.

Step 2: Drug therapy

• Choose an agent based on patient characteristics and comorbidities.
• Add one agent at a time, waiting about 4 weeks between dose changes to assess response.
• Guiding principles from combination logic:
  • Do not combine an ACE inhibitor with an ARB (increased side effects for little benefit).
  • In hypertension with coexisting coronary disease, select agents useful for both.
  • In hypertension with heart failure, combine appropriate agents accordingly.
  • Agents lacking adverse metabolic effects may be preferred where there is coexisting diabetes or lipid abnormalities.
  • Beta blockers are not routine first-line therapy unless useful for a coexisting condition, and should be used cautiously in anyone with a history of wheeze/asthma.
  • Alpha-antagonists such as prazosin may be used as monotherapy or in combination in selected cases.

Step 3: Special populations

• Elderly: start at about half the standard dose and up-titrate slowly; treat isolated systolic hypertension; older patients may respond well to non-pharmacological measures, especially salt reduction.
• Children: hypertension is rare and requires evaluation. ACE inhibitors or calcium-channel blockers are preferable, with diuretics as second agents; avoid ACE inhibitors in postpubertal females because of teratogenicity risk.

Step 4: Failure to respond / referral

• If hypertension fails to respond to therapy, reconsider an underlying renal or adrenal lesion that may have been missed.
• Refer for expert evaluation:
  • Young patients with hypertension.
  • Patients with uncontrolled hypertension despite three or more antihypertensives (resistant hypertension).
• Additional options in specialist settings include renal sympathetic denervation for selected resistant cases.

Blood pressure in hospital

Inpatient BP readings require careful interpretation and management, and acute severe hypertension should be handled according to the clinical context rather than treated reflexively against a single reading.

6. Australian-specific considerations

• Hypertension is predominantly a primary care condition in Australia, integrated with structured, proactive chronic disease care: recall systems, regular BP rechecks and coordinated follow-up support long-term control.
• Adopt a patient-centred approach that finds common ground on the problem and management plan, uses motivational interviewing for lifestyle change, and leverages local partnerships and community supports.
• Manage hypertension within absolute cardiovascular risk assessment, aligning statin and antihypertensive decisions with the patient's overall risk rather than the BP number alone.
• Prescribing should follow current Australian therapeutic guidance (eTG / Therapeutic Guidelines and the Australian Medicines Handbook) for agent selection and dosing.
• Refer early to specialist services for suspected secondary causes, resistant hypertension and young-onset disease, which are supported by local nephrology, endocrinology and hypertension clinics.

Clinical pearls

• Never diagnose on one reading: require at least two follow-up measurements and confirm with ABPM or HBPM to exclude white coat hypertension.
• Under 30-35 years, think secondary: young onset, no family history, hypokalaemia or malignant hypertension should trigger investigation, including the aldosterone-to-renin ratio.
• One drug at a time, 4 weeks apart: patient adherence and steady titration beat aggressive polypharmacy.
• Never combine ACE inhibitor with ARB: more side effects, little added benefit.
• Be wary of beta blockers in wheezers: avoid or use cautiously in asthma and reactive airways.
• Start low, go slow in the elderly: