Hypertension in adults: the silent killer

Key practice points:

• The line separating blood pressure measurements from being “normotensive” and “hypertensive” is not clear-cut. Consider any elevated readings in the context of a patient’s overall cardiovascular disease (CVD) risk. The balance between these two factors will influence subsequent management decisions.
• Consider using 24-hour ambulatory or at-home monitoring to confirm persistently elevated clinic blood pressure readings, if resources are available
• Any patient with persistently elevated blood pressure readings should be encouraged to make lifestyle changes, e.g. weight loss, increased exercise, dietary changes including reducing sodium intake, limiting alcohol consumption, smoking cessation. Early adoption of meaningful changes could delay or prevent the need for antihypertensive medicines later in life. However, this may not be achievable for all patients.
• For patients with severe hypertension (e.g. ≥ 160/100 mmHg), antihypertensive treatment should be initiated immediately, in addition to lifestyle changes, regardless of the patient’s CVD risk (although CVD risk should still be calculated)
• For all other patients with a blood pressure persistently ≥ 130/80 mmHg, treatment decisions should be based on their five-year CVD risk calculated using New Zealand primary prevention equations:
  • CVD < 5%: antihypertensive treatment is not recommended; proceed with lifestyle changes
  • CVD 5 – 15%: consider antihypertensive treatment if blood pressure measurements are ≥ 140/90 mmHg, in addition to lifestyle changes
  • CVD ≥ 15%: antihypertensive treatment is recommended, in addition to lifestyle changes
• Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), calcium channel blockers and thiazide/thiazide-like diuretics are all first-line antihypertensives:
  • The choice of antihypertensive and combination of treatment depends on patient co-morbidities (e.g. diabetes, renal impairment) and other characteristics (e.g. pregnancy)
  • Beta-blockers are no longer first-line unless specifically indicated for a co-morbidity
• Initial treatment with two low-dose antihypertensives together (i.e. dual antihypertensive treatment) provides a more significant blood pressure-lowering effect for most patients compared with high dose monotherapy, while also reducing the risk of adverse effects. Initial monotherapy remains appropriate for certain patient groups, e.g. those within 20/10 mmHg of their blood pressure target, committing to major lifestyle changes, elderly (e.g. aged ≥ 80 years) or frail.
• Blood pressure targets should be individualised according to the patient’s CVD risk, co-morbidities and treatment objectives
• For patients not achieving blood pressure targets despite the use of two antihypertensives, the doses of existing medicines can be increased if they are close to their goal, or a third antihypertensive can be added if not
• If targets are still not being achieved despite use of three antihypertensives, reassess adherence to medicine and lifestyle changes as well as possible secondary causes, prior to considering the addition of another medicine, e.g. spironolactone or a beta-blocker. N.B. 24-hour ambulatory or at-home monitoring should also be strongly considered at this stage to confirm the patient’s true blood pressure, if not already completed.

Hypertension is a continuum requiring regular review

Hypertension is a common incidental clinical finding in primary care.¹ While transient increases in blood pressure are normal and can occur for a variety of reasons, persistent elevation represents an important modifiable risk factor for many conditions including stroke, myocardial infarction, heart failure, atrial fibrillation, kidney disease and cognitive decline.^{1, 2} However, most people with hypertension are asymptomatic, giving rise to the moniker “silent killer” due to its insidious, chronic and progressive nature.³

International guidelines vary in the thresholds used to define hypertension.^{1, 4 ,5} While it has previously been common practice in New Zealand to consider any clinic blood pressure ≥ 140/90 mmHg as being “hypertensive”, blood pressure measurements alone are now considered insufficient to define and guide the management of hypertension in primary care.⁶ Blood pressure has a normal distribution across the general population and the cardiovascular disease (CVD) risk associated with increasing measurements is continuous.⁴ If additional factors are present that elevate cardiovascular risk further, a patient is more likely to experience a cardiovascular event, even if their blood pressure is within 130 – 139/85 – 89 mmHg:^{4, 5} the line between normotension and hypertension is therefore not clear-cut.

Hypertension is prevalent yet undertreated in New Zealand

The age-standardised mean systolic blood pressure in people in New Zealand is increasing due to a range of factors, including higher rates of obesity and sedentary lifestyles, as well as the increased consumption of foods containing a high content of fat, sugar and salt.⁷ Hypertension is often under-treated; Māori, Pacific and Asian peoples with hypertension have significantly lower rates of antihypertensive use compared with European/Other peoples (Figure 1), a trend which has remained consistent over time.⁸ While not all patients with hypertension require pharmacological treatment (see: “When to initiate antihypertensive medicines”), these disparities need to be recognised and addressed across primary care to achieve more equitable health outcomes.

Diagnosing hypertension

Treatment for hypertension often involves lifelong exposure to multiple medicines and their potential adverse effects.⁵ Therefore, it is essential that hypertension is accurately diagnosed in primary care, but this can be challenging as most patients with hypertension are asymptomatic.

If a patient has a clinic blood pressure measurement ≥ 130/80 mmHg a clinical evaluation should be conducted to:

1. Confirm the elevated blood pressure
2. Assess CVD risk
3. Determine if any end organ damage has occurred
4. Identify any causes of secondary hypertension

1. Confirming elevated blood pressure

To achieve a more accurate assessment, it is recommended that two or more blood pressure measurements are taken, at least two minutes apart. Ideally, an additional measurement should also be taken in the patient’s other arm in case there is a significant difference.^{5, 9} Consistent systolic blood pressure differences ≥ 10 mmHg between arms are associated with an increased risk of cardiovascular disease.⁵

If blood pressure measurements are elevated at a single appointment, another reading should ideally be taken at a separate appointment on a different day to confirm a diagnosis of hypertension.⁹ N.B. Ensure an appropriate blood pressure cuff size is used.

Consider an out-of-clinic blood pressure assessment

Even when standardised methods for blood pressure measurement are used, clinic readings do not always reflect true blood pressure due to patient-specific psychological, physiological and behavioural factors.⁵ On average, measurements are 5 – 10 mmHg higher in this setting compared with at-home or ambulatory monitoring.⁵ Therefore, 24-hour ambulatory monitoring (the “gold standard”) or at-home monitoring should be considered if resources are available to confirm a diagnosis of hypertension and to rule out:

• White-coat hypertension if measurements are consistently elevated despite the absence of obvious risk factors
• Masked hypertension if clinic blood pressure is consistently normal but there are clinical features consistent with hypertension, e.g. signs of end organ damage

For further information on 24-hour ambulatory or at-home monitoring, see: “Out-of-clinic blood pressure testing in primary care” at bpac.org.nz/BPJ/2016/May/blood-pressure.aspx

2. Perform a CVD risk assessment

CVD risk assessment forms the basis for discussions about prognosis and treatment options with the patient and provides information about other factors affecting cardiovascular management, e.g. diabetes, and the prevention of myocardial infarction and stroke.

A five-year CVD risk assessment should be performed in all patients with a blood pressure persistently ≥ 130/80 mmHg (see: “When to initiate antihypertensive medicines”). In addition, five-year CVD risk assessments are recommended from age 45 years in males and 55 years in females. However, it is recommended that assessments should be:⁶

• 10 years earlier for people with personal or family history risk factors for CVD or diabetes
• 15 years earlier for people of Māori, Pacific or South-Asian ethnicity
• 20 years earlier for people with severe mental illness
• From diagnosis for people with type 1 or 2 diabetes

The five-year CVD risk thresholds have been established based on the New Zealand primary prevention equations (derived from the PREDICT study), which incorporate a wider range of variables.⁶ Most patient management systems will have an integrated CVD risk assessment tool. Alternatively, an online CVD risk calculator, with the option of using PREDICT data, is available from: cvdcalculator.com. These tools also provide a pictorial representation of the potential benefits and harms with and without intervention to inform shared decision making with the patient if antihypertensive treatment is ultimately indicated (see: “When to initiate antihypertensive medicines”).

If you do not have an integrated CVD risk assessment module installed in your practice management system (PMS), contact BPAC Clinical Solutions (bpacsolutions.co.nz/contact/) for information about their Primary Care Suite which includes a CVD risk assessment tool. This tool can be accessed via bestpractice Decision Support in your PMS and pre-populates relevant data from patient records to improve useability.

3. Investigate for end organ damage and co-morbidities

After confirming elevated blood pressure and assessing the patient’s five-year CVD risk, further investigations should include (at a minimum):^{1, 5, 9}

• Dipstick urine test for blood or protein
• Quantification of urinary protein, e.g. by assessing albumin:creatinine ratio (ACR)
• Laboratory investigations for electrolytes and creatinine (eGFR), lipids, HbA_1c
• An ECG to assess for signs of left ventricular hypertrophy, atrial fibrillation or evidence of historical ischaemic heart disease. Consider referring for an echocardiogram if indicated.

Assess for other symptoms indicative of end organ damage, e.g. chest pain, breathlessness, visual disturbances, transient focal weakness.

Consider ophthalmoscopic examination of the fundus, particularly in patients reporting visual disturbances, as persistently elevated blood pressure can cause retinopathy, choroidopathy and optic neuropathy.⁴ Key features include copper (or silver) wiring, arteriovenous nicking and retinal haemorrhages.¹⁰

For further information on hypertensive retinopathy and example images, see: www.msdmanuals.com/professional/eye-disorders/retinal-disorders/hypertensive-retinopathy

4. Consider secondary causes of hypertension

Most patients diagnosed with hypertension have primary (or essential) hypertension, where there is no clinically identifiable cause.¹¹ While the pathophysiology of primary hypertension is not fully understood, it is thought to involve a complex interplay of genetic predisposition, environmental factors and age-associated stiffening of blood vessels.²

In approximately one in ten patients with hypertension, increased blood pressure measurements are associated with an underlying condition or stressor (secondary hypertension).² If these factors can be more effectively managed or resolved, it may prevent unnecessary pharmacological intervention. Secondary causes of hypertension should be suspected in young adults (e.g. aged < 30 years) without a family history of hypertension or other risk factors.

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The options for managing hypertension

Lifestyle modifications are important for all patients

Healthy lifestyle advice should be given to all patients with persistently elevated blood pressure measurements and reinforced if a diagnosis of hypertension is ultimately made. There is clear evidence from clinical trials that lifestyle changes can reduce mean blood pressure measurements and even prevent hypertension if they are sustained.²

Key modifications to make where applicable include:^{2, 4, 5, 12}

• Weight loss. Even small losses help reduce blood pressure (systolic blood pressure is estimated to decrease approximately 1 – 2 mmHg/kg lost).

  For further information on methods for weight loss, see: bpac.org.nz/2022/weight-loss.aspx

• A healthy diet with reduced sodium intake (< 1.5 g/day is optimal but aim for at least a 1 g/day reduction) and optimised potassium intake (3.5 – 5.0 g/day). Other important features include the diet being rich in vegetables, fruit, whole grains, low-dairy and reduced saturated/total fat. International guidelines are increasingly recommending the dietary approaches to stop hypertension (DASH) diet.⁵ Smartphone apps, e.g. “FoodSwitch”, can help people assess nutritional content of labelled products and identify healthier alternatives.
• Increasing physical activity, e.g. regular moderate intensity exercise such as walking for at least 30 minutes per day, five days per week, if possible. However, any increase in exercise engagement is likely beneficial.
• Reducing alcohol consumption
• Smoking cessation

The effectiveness of recommending “lifestyle changes” to control blood pressure varies between patients in primary care. Long-term behavioural modifications can be difficult to make and even harder to maintain. For some patients, despite their best efforts, lifestyle changes will be insufficient to make a clinically significant difference to their blood pressure, but they remain an important aspect of hypertension management even if antihypertensives are introduced.

When to initiate antihypertensive medicines

Patients with a blood pressure of ≥ 160/100 mmHg should be initiated on antihypertensive treatment immediately, in addition to lifestyle changes, regardless of their five-year CVD risk.⁶

For all other patients with a blood pressure persistently ≥ 130/80 mmHg, the 2018 Ministry of Health cardiovascular risk consensus statement recommends calculating their five-year CVD risk to guide antihypertensive medicine decisions. In patients with:⁶

• Five-year CVD risk < 5%: antihypertensive treatment is not recommended; proceed with lifestyle changes
• Five-year CVD risk 5 – 15%: consider antihypertensive treatment if blood pressure is ≥ 140/90 mmHg, in addition to lifestyle changes
• Five-year CVD risk ≥ 15%: antihypertensive treatment is recommended, in addition to lifestyle changes

For further information see: “Cardiovascular disease risk assessment and management for primary care” (available at: www.health.govt.nz/publication/cardiovascular-disease-risk-assessment-and-management-primary-care)

Choosing a suitable antihypertensive

All first-line antihypertensives have a comparable blood pressure lowering effect and therefore all are suitable choices for patients without complicating factors or interacting medicines (see: “Consider patient co-morbidities and characteristics”).^{2, 5}

In New Zealand, funded first-line options include (see Table 1 for dosing recommendations):^{12, 13}

• Angiotensin-converting-enzyme (ACE) inhibitors
• Angiotensin-II receptor blockers (ARBs). N.B. Despite previously being regarded as a second-line option after ACE inhibitors, ARBs are now considered to provide comparable benefit for treating patients with hypertension and are often better tolerated.
• Calcium channel blockers
• Thiazide and thiazide-like diuretics

Practice point: ACE inhibitors and ARBs should generally not be prescribed in combination unless under specialist supervision primarily due to the increased risk of renal impairment and hyperkalaemia. Concurrent use is broadly contraindicated in patients with renal impairment or diabetic nephropathy. However, there is some evidence that dual ACE inhibitor/ARB treatment is effective for preventing end-stage kidney disease.

Treatment can be initiated with a single antihypertensive or with two antihypertensives together at low doses (dual antihypertensive treatment; see: “Initial use of two low-dose antihypertensives can be a good starting point for many patients”). Antihypertensive treatment generally takes four-to-six weeks to reach maximum effect.⁹

For further information on ACE inhibitors, see “Prescribing ACE inhibitors: time to reconsider old habits” at: bpac.org.nz/2021/ace.aspx

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Table 1. Recommended adult dosing for commonly used antihypertensive medicines in New Zealand.¹³ N.B. Lower initial dosing of ACE inhibitors/ARBs (e.g. half the initial dose) and more gradual titration may be required for elderly or frail patients, or in patients with renal impairment, cardiac decompensation, volume depletion or concomitant diuretic use. For further information on dosing recommendations, refer to the New Zealand Formulary: www.nzf.org.nz/nzf_1168.

^*Cilazapril is another ACE inhibitor that was previously used extensively in New Zealand, however, it is no longer funded for new patients.

^†Quinapril with hydrochlorothiazide is another fixed-dose combination treatment that was used in New Zealand, however, it is no longer available due to a stock impurity issue. For further information, see: “Warning: the fixed-dose combination antihypertensive Accuretic (quinapril with hydrochlorothiazide) should no longer be used”.

Beta-blockers are no longer considered a first-line antihypertensive unless there is a clinical need

Beta-blockers are less effective at reducing stroke risk compared with other antihypertensive medicines and are often poorly tolerated.⁵ However, beta-blockers may be preferred early in treatment for patients with some co-morbidities, such as ischaemic heart disease (as they also help to decrease heart rate, increase diastolic filling time, decrease cardiac contractility and reduce myocardial oxygen demand) or atrial fibrillation (as they help to control heart rate).⁵

Consider patient co-morbidities and characteristics

Two-thirds of patients with hypertension have a co-morbidity, which may in turn influence the suitability of the antihypertensive used (Table 2).^{4, 5, 16} For example, in patients with hypertension and gout, losartan is often favoured due to its dual blood pressure lowering/uricosuric effects, while thiazide diuretics should be avoided as they promote urate reabsorption in proximal renal tubules.^{4, 5}

Other patient characteristics may also affect the choice of antihypertensive. For example, ACE inhibitors or ARBs are sometimes favoured in patients aged under 55 years due to the potential for a more significant reduction in renin levels.^{1, 17} However, exposure to ACE inhibitors and ARBs increases the risk of fetal abnormalities when used during pregnancy.¹⁸ Therefore, any females planning or considering pregnancy should ideally use an alternative medicine, or switch from an ACE inhibitor/ARB to another option once the pregnancy is confirmed.¹⁸ Recommended antihypertensives during pregnancy include labetalol, nifedipine and methyldopa.¹⁸

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Table 2. Antihypertensive recommendations based on patient co-morbidities and characteristics.^{1, 4, 5, 16}

Initial use of two low-dose antihypertensives can be a good starting point for many patients

The blood pressure lowering effect of any single antihypertensive at its optimal dose has been estimated to be < 10 mmHg on average.¹⁹ Therefore, initial monotherapy is unlikely to be effective in many patients with hypertension (despite previously being standard practice) and multiple medicines are frequently required to achieve treatment targets. As such, international guidelines now recommend a more pragmatic approach to treatment, with initial use of two low-dose antihypertensives together (dual antihypertensive treatment) being indicated in many cases (Figure 2).⁵ For further information, see “A closer look at the evidence supporting initial treatment with two low-dose antihypertensives”. While selection may be influenced by patient co-morbidities (Table 2), an ACE inhibitor or ARB with a dihydropyridine calcium channel blocker such as amlodipine has been demonstrated to be the most effective combination based on evidence from the ACCOMPLISH trial.²⁰ Single antihypertensive use may still be a suitable starting point for some, e.g. elderly patients or those already close to their blood pressure target.

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Figure 2. A pragmatic approach to antihypertensive treatment for patients with hypertension.⁵

^* Blood pressure should be monitored at least every four-to-six weeks during medicine titration until blood pressure targets have been achieved. The frequency of follow-up in the long-term depends on a range of patient-specific factors, e.g. the severity of hypertension in the context of the patient’s overall CVD risk.⁴

^†Such as a beta-blocker or an alpha-blocker

Consider individualised blood pressure targets

Numerous clinical trials have addressed the concept of the “optimal” blood pressure target for patients with hypertension, and there are discrepancies in recommendations between different international guidelines. In 2018, New Zealand Ministry of Health guidelines specified a target clinic blood pressure of < 130/80 mmHg for most people.⁶ However, there has been a shift in some international guidelines to instead use individualised blood pressure targets based on the patient’s CVD risk, co-morbidities and treatment objectives (Table 3).^{4, 5} There is strong evidence supporting a lower clinic blood pressure target (i.e. < 130/80 mmHg) for patients with a high CVD risk.⁴ However, the absolute benefits are likely outweighed by the potential harms in those with a lower CVD risk, and therefore a more conservative target is often more appropriate for this group (i.e. < 140 mmHg).^{4, 24}

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Table 3. Recommendations for individualising patient blood pressure targets.^{4, 5}

Poor medicine adherence is a significant barrier to achieving targets

Poor adherence to antihypertensive treatment is a common issue for many patients with hypertension and is an indicator of poor prognosis.⁵ Reasons for non-adherence are often multi-faceted and can be difficult to address in primary care.

Potential strategies to encourage and improve adherence include:⁵

• Educating patients at the time of the initial prescription about their medicine(s) and how it works; this message should be reinforced at each appointment. In particular, if a decision is made to initially prescribe two low dose antihypertensives together, emphasise why it is important that both are taken consistently, i.e. to maximise blood pressure control while reducing the risk of adverse effects (compared with high dose monotherapy).
• Selecting antihypertensives with once daily dosing
• Reducing polypharmacy, e.g. using a fixed-dose combination, if available
• Using pill boxes, blister packaging or electronic reminders (e.g. smartphone apps)
• If adverse effects are problematic, consider night-time dosing, which can limit the perception of adverse effects. Further benefits for night-time dosing have been suggested, however, the evidence at present is inconsistent (see: “Night-time antihypertensive dosing: does it reduce the risk of CVD events?”).

Intensifying treatment over the short-term

Patients starting antihypertensive treatment should initially be reviewed at least every four-to-six weeks to assess the efficacy of their regimen.⁹ Shorter review times may be considered for some patients, e.g. every two weeks if the patient’s measurement was significantly elevated at baseline. If a target is not achieved, the next step depends on how well the patient tolerates treatment and how close they are to their objective (Figure 2):⁵

• If the patient is close to their target blood pressure and the antihypertensive medicine(s) are well tolerated: increase the dose of their existing antihypertensive(s) and re-emphasise the importance of lifestyle changes
• If the patient is not close to their target blood pressure and adherence is not an issue: add an additional antihypertensive and re-emphasise the importance of lifestyle changes, e.g. for patients who started with two low dose antihypertensives such as an ACE inhibitor (or ARB) and a calcium channel blocker, add a thiazide diuretic

Resistant hypertension

If a patient’s clinic blood pressure remains > 140/90 mmHg after treatment with an ACE inhibitor or an ARB, plus a calcium channel blocker and a thiazide diuretic at their optimal (or maximally tolerated) dose, then their hypertension is considered “resistant”.⁵ Patient adherence to treatment and possible secondary causes should be re-examined, and an added emphasis placed on lifestyle changes.⁵ In addition, if the patient is taking optimal, or maximum tolerated, doses of antihypertensive medicines, an appropriate specialist opinion is recommended, if this has not been sought already.⁵

Ultimately, an additional antihypertensive medicine may be required. Options to consider include:^{5, 9, 13}

• Spironolactone – appropriate in combination with another diuretic if serum potassium is ≤ 4.4 mmol/L and eGFR is ≥ 45 mL/min/1.73m². Spironolactone may be particularly beneficial as many patients with resistant hypertension have high aldosterone levels (even if they do not have clinically apparent primary hyperaldosteronism); spironolactone impairs aldosterone binding to mineralocorticoid receptors which limits vascular resistance. N.B. Spironolactone should be introduced cautiously with ongoing monitoring of serum potassium and creatinine.
• Beta-blocker – no longer considered a first-line antihypertensive for patients with uncomplicated hypertension but may be useful if indicated for a co-morbidity, e.g. atrial fibrillation. All beta-blockers have comparable blood pressure lowering effects.
• Alpha-blocker (e.g. doxazosin) – beneficial for lowering blood pressure but should be used with caution in females as these medicines may sometimes cause urinary stress incontinence and loss of bladder control. A scenario where alpha-blockers may be considered is in males with hypertension who also have benign prostatic hyperplasia to alleviate nocturia.

Longer-term follow-up and monitoring

Once a blood pressure target has been achieved, continued long-term follow-up is important to ensure levels are maintained, and to reinforce the importance of medicine adherence and a healthy lifestyle. Guidelines suggest patients with hypertension should be reviewed three-to-six-monthly.^{5, 9} However, less frequent review may be more practical for some patients with stable blood pressure measurements, e.g. annually in otherwise healthy patients who are also committing to lifestyle changes and take their medicines regularly. These appointments also provide an opportunity to monitor electrolytes, renal function and albumin/creatinine ratio, in addition to checking for any emerging signs of end organ disease and associated conditions, e.g. retinopathy, heart failure.