C ARDIOVASCUL AR SYSTEM NEPHROLOGY

Hypertension in adults: the silent killer

Hypertension is a common finding among patients in primary care; ideal pharmacological treatment, however,
continues to be debated. What is agreed is that chronic hypertension can cause a wide-range of cardiovascular
disease and end-organ damage if left untreated or insufficiently controlled. Management often requires multiple
medicines in addition to lifestyle changes to achieve blood pressure targets and reduce overall cardiovascular risk.

KEY PR AC TICE POINTS

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

www.bpac.org.nz January 2023 1

 This is a revision of a previously published article. define and guide the management of hypertension in primary
What’s new for this update: care.6 Blood pressure has a normal distribution across the
A general article revision general population and the cardiovascular disease (CVD) risk
Changes to the recommendations for initiating associated with increasing measurements is continuous.4 If
antihypertensives based on a patient’s five-year additional factors are present that elevate cardiovascular risk
CVD risk rather than blood pressure measurements further, a patient is more likely to experience a cardiovascular
in isolation event, even if their blood pressure is within 130 – 139/85 – 89
Updated information on funded and available mmHg:4, 5 the line between normotension and hypertension is
antihypertensive options therefore not clear-cut.
Changes to the approach for initiating treatment,
Risk factors for hypertension include:5 age ≥
i.e. many people should be initiated on two low-
65 years, male sex, excess body weight, sedentary
dose antihypertensives rather than starting with a
lifestyle, diabetes, high LDL-C/triglycerides,
single antihypertensive and increasing the dose
sustained increased resting heart rate (> 80 beats/
Discussion on individualising blood pressure
min), a personal or family history of cardiovascular
targets
disease or hypertension (genetics), early-onset
Review of the conflicting evidence for night-time
menopause, smoking (current or past), and
versus morning antihypertensive dosing
psychosocial or socioeconomic factors
Hypertension is a continuum requiring
regular review Hypertension is prevalent yet undertreated in New
Hypertension is a common incidental clinical finding in Zealand
primary care.1 While transient increases in blood pressure The age-standardised mean systolic blood pressure in people
are normal and can occur for a variety of reasons, persistent in New Zealand is increasing due to a range of factors, including
elevation represents an important modifiable risk factor for higher rates of obesity and sedentary lifestyles, as well as the
many conditions including stroke, myocardial infarction, heart increased consumption of foods containing a high content of
failure, atrial fibrillation, kidney disease and cognitive decline.1, 2 fat, sugar and salt.7 Hypertension is often under-treated; Māori,
However, most people with hypertension are asymptomatic, Pacific and Asian peoples with hypertension have significantly
giving rise to the moniker “silent killer” due to its insidious, lower rates of antihypertensive use compared with European/
chronic and progressive nature.3 Other peoples (Figure 1), a trend which has remained
International guidelines vary in the thresholds used to consistent over time.8 While not all patients with hypertension
define hypertension.1, 4 ,5 While it has previously been common require pharmacological treatment (see: “When to initiate
practice in New Zealand to consider any clinic blood pressure antihypertensive medicines” on page 5), these disparities need
≥ 140/90 mmHg as being “hypertensive”, blood pressure to be recognised and addressed across primary care to achieve
measurements alone are now considered insufficient to more equitable health outcomes.

Prevalence of hypertension Antihypertensive use % untreated

Total 22.5% 16.7% 25.8%

Māori 23.6% 14.6% 38.1%

Pacific 28.1% 11.9% 57.7%

Asian 16.2% 8.6% 46.9%

European/Other 22.2% 18.1% 18.5%

Figure 1. Prevalence of hypertension versus rates of antihypertensive use in New Zealand by ethnicity.8 Data obtained from the
2020/21 Ministry of Health New Zealand Health Survey. The percentage of patients not taking an antihypertensive was calculated
using the datasets for “Raised blood pressure (measured)” and “High blood pressure (medicated)”.

2 January 2023 www.bpac.org.nz

Diagnosing hypertension consistent with hypertension, e.g. signs of end organ
damage
Treatment for hypertension often involves lifelong exposure
to multiple medicines and their potential adverse effects.5 For further information on 24-hour ambulatory or
Therefore, it is essential that hypertension is accurately at-home monitoring, see: “Out-of-clinic blood pressure
diagnosed in primary care, but this can be challenging as most testing in primary care” at bpac.org.nz/BPJ/2016/May/
patients with hypertension are asymptomatic. blood-pressure.aspx
If a patient has a clinic blood pressure measurement
≥ 130/80 mmHg a clinical evaluation should be conducted to:
2. Perform a CVD risk assessment
1. Confirm the elevated blood pressure
2. Assess CVD risk CVD risk assessment forms the basis for discussions about
3. Determine if any end organ damage has occurred prognosis and treatment options with the patient and provides
information about other factors affecting cardiovascular
4. Identify any causes of secondary hypertension
management, e.g. diabetes, and the prevention of myocardial
1. Confirming elevated blood pressure infarction and stroke.

To achieve a more accurate assessment, it is recommended A five-year CVD risk assessment should be performed in all
that two or more blood pressure measurements are taken, at patients with a blood pressure persistently ≥ 130/80 mmHg
least two minutes apart. Ideally, an additional measurement (see: “When to initiate antihypertensive medicines” on page 5).
should also be taken in the patient’s other arm in case there In addition, five-year CVD risk assessments are recommended
is a significant difference.5, 9 Consistent systolic blood pressure from age 45 years in males and 55 years in females. However,
differences ≥ 10 mmHg between arms are associated with an it is recommended that assessments should be:6
increased risk of cardiovascular disease.5 10 years earlier for people with personal or family
If blood pressure measurements are elevated at a single history risk factors for CVD or diabetes
appointment, another reading should ideally be taken at a 15 years earlier for people of Māori, Pacific or South-Asian
separate appointment on a different day to confirm a diagnosis ethnicity
of hypertension.9 N.B. Ensure an appropriate blood pressure 20 years earlier for people with severe mental illness
cuff size is used.
From diagnosis for people with type 1 or 2 diabetes
Consider the need for referral or urgent care if the The five-year CVD risk thresholds have been established based
patient’s blood pressure is ≥ 180/110 mmHg and on the New Zealand primary prevention equations (derived
there are signs of end organ damage (malignant from the PREDICT study), which incorporate a wider range of
hypertension), e.g. abnormalities on ECG, or if variables.6 Most patient management systems will have an
the patient is pregnant. For further information, integrated CVD risk assessment tool. Alternatively, an online
see: “Investigate for end organ damage and CVD risk calculator, with the option of using PREDICT data, is
co-morbidities” available from: cvdcalculator.com. These tools also provide a
pictorial representation of the potential benefits and harms
Consider an out-of-clinic blood pressure assessment with and without intervention to inform shared decision
Even when standardised methods for blood pressure making with the patient if antihypertensive treatment is
measurement are used, clinic readings do not always reflect ultimately indicated (see: “When to initiate antihypertensive
true blood pressure due to patient-specific psychological, medicines” on page 5).
physiological and behavioural factors. 5 On average,
measurements are 5 – 10 mmHg higher in this setting compared If you do not have an integrated CVD risk
with at-home or ambulatory monitoring.5 Therefore, 24-hour assessment module installed in your patient
ambulatory monitoring (the “gold standard”) or at-home management system (PMS), contact BPAC Clinical
monitoring should be considered if resources are available to Solutions (bpacsolutions.co.nz/contact/) for
confirm a diagnosis of hypertension and to rule out: information about their Primary Care Suite which
White-coat hypertension if measurements are includes a CVD risk assessment tool. This tool can be
consistently elevated despite the absence of obvious risk accessed via bestpractice Decision Support in your PMS
factors and pre-populates relevant data from patient records
Masked hypertension if clinic blood pressure is to improve useability.
consistently normal but there are clinical features

www.bpac.org.nz January 2023 3

3. Investigate for end organ damage and Certain medicines, e.g. oral contraceptives and
co-morbidities corticosteroids, non-steroidal anti-inflammatory
drugs (NSAIDs), ciclosporin and decongestants, e.g.
After confirming elevated blood pressure and assessing the phenylephrine
patient’s five-year CVD risk, further investigations should Obstructive sleep apnoea
include (at a minimum):1, 5, 9 Aortic coarctation, suggested by a diminished or delayed
Dipstick urine test for blood or protein femoral pulse and low or unobtainable blood pressure in
Quantification of urinary protein, e.g. by assessing the legs, or abnormal differences in the upper and lower
albumin:creatinine ratio (ACR) extremity arterial pulses
Laboratory investigations for electrolytes and creatinine Renovascular or primary renal disease
(eGFR), lipids, HbA1c Renal parenchymal disease, including glomerulonephritis,
An ECG to assess for signs of left ventricular hypertrophy, suggested by a history of urinary tract infection or
atrial fibrillation or evidence of historical ischaemic heart obstruction, haematuria, analgesic misuse or a family
disease. Consider referring for an echocardiogram if history of polycystic kidney disease
indicated. Endocrine disorders, e.g. Cushing’s syndrome (excessive
cortisol production), Conn’s syndrome (also known as
Assess for other symptoms indicative of end organ damage, e.g. hyperaldosteronism, involving excessive aldosterone
chest pain, breathlessness, visual disturbances, transient focal production), phaeochromocytoma (a rare adrenal gland
weakness. tumour), hypo-/hyperthyroidism
Consider ophthalmoscopic examination of the fundus,
particularly in patients reporting visual disturbances, as The options for managing hypertension
persistently elevated blood pressure can cause retinopathy, Lifestyle modifications are important for all patients
choroidopathy and optic neuropathy.4 Key features include Healthy lifestyle advice should be given to all patients with
copper (or silver) wiring, arteriovenous nicking and retinal persistently elevated blood pressure measurements and
haemorrhages.10 reinforced if a diagnosis of hypertension is ultimately made.
There is clear evidence from clinical trials that lifestyle changes
For further information on hypertensive retinopathy and can reduce mean blood pressure measurements and even
example images, see: www.msdmanuals.com/professional/ prevent hypertension if they are sustained.2
eye-disorders/retinal-disorders/hypertensive-retinopathy
Key modifications to make where applicable include:2, 4, 5, 12
4. Consider secondary causes of hypertension
Weight loss. Even small losses help reduce blood
Most patients diagnosed with hypertension have primary (or pressure (systolic blood pressure is estimated to
essential) hypertension, where there is no clinically identifiable decrease approximately 1 – 2 mmHg/kg lost).
cause.11 While the pathophysiology of primary hypertension
For further information on methods for weight
is not fully understood, it is thought to involve a complex
loss, see: bpac.org.nz/2022/weight-loss.aspx
interplay of genetic predisposition, environmental factors and
age-associated stiffening of blood vessels.2 A healthy diet with reduced sodium intake
In approximately one in ten patients with hypertension, (< 1.5 g/day is optimal but aim for at least a 1 g/day
increased blood pressure measurements are associated with reduction) and optimised potassium intake (3.5
an underlying condition or stressor (secondary hypertension).2 – 5.0 g/day). Other important features include the diet being
If these factors can be more effectively managed or resolved, rich in vegetables, fruit, whole grains, low-dairy and reduced
it may prevent unnecessary pharmacological intervention. saturated/total fat. International guidelines are increasingly
Secondary causes of hypertension should be suspected in recommending the dietary approaches to stop hypertension
young adults (e.g. aged < 30 years) without a family history of (DASH) diet.5 Smartphone apps, e.g. “FoodSwitch”, can help
hypertension or other risk factors. people assess nutritional content of labelled products and
identify healthier alternatives.
Secondary causes of hypertension include: 5, 6, 9
Increasing physical activity, e.g. regular moderate
High alcohol intake, e.g. consistently having > 10
intensity exercise such as walking for at least 30
standard drinks per week for females or > 15 standard
minutes per day, five days per week, if possible.
drinks for males
However, any increase in exercise engagement is
Illicit drugs, e.g. amphetamine or cocaine use
likely beneficial.

4 January 2023 www.bpac.org.nz

 Choosing a suitable antihypertensive
Reducing alcohol consumption
All first-line antihypertensives have a comparable blood
pressure lowering effect and therefore all are suitable choices
Smoking cessation
for patients without complicating factors or interacting
medicines (see: “Consider patient characteristics and co-
The effectiveness of recommending “lifestyle changes” to morbidities” on Page 7).2, 5
control blood pressure varies between patients in primary
care. Long-term behavioural modifications can be difficult to In New Zealand, funded first-line options include (see Table 1
make and even harder to maintain. For some patients, despite for dosing recommendations):12, 13
their best efforts, lifestyle changes will be insufficient to make a Angiotensin-converting-enzyme (ACE) inhibitors
clinically significant difference to their blood pressure, but they Angiotensin-II receptor blockers (ARBs). N.B. Despite
remain an important aspect of hypertension management previously being regarded as a second-line option
even if antihypertensives are introduced. after ACE inhibitors, ARBs are now considered to
provide comparable benefit for treating patients with
When to initiate antihypertensive medicines hypertension and are often better tolerated.
Patients with a blood pressure of ≥ 160/100 mmHg should be Calcium channel blockers
initiated on antihypertensive treatment immediately, in addition Thiazide and thiazide-like diuretics
to lifestyle changes, regardless of their five-year CVD risk.6
Practice point: ACE inhibitors and ARBs should
For all other patients with a blood pressure persistently ≥ generally not be prescribed in combination unless under
130/80 mmHg, the 2018 Ministry of Health cardiovascular risk specialist supervision primarily due to the increased risk
consensus statement recommends calculating their five-year of renal impairment and hyperkalaemia. Concurrent
CVD risk to guide antihypertensive medicine decisions. In use is broadly contraindicated in patients with renal
patients with:6 impairment or diabetic nephropathy. However, there is
Five-year CVD risk < 5%: antihypertensive treatment is some evidence that dual ACE inhibitor/ARB treatment is
not recommended; proceed with lifestyle changes effective for preventing end-stage kidney disease.
Five-year CVD risk 5 – 15%: consider antihypertensive
treatment if blood pressure is ≥ 140/90 mmHg, in Treatment can be initiated with a single antihypertensive
addition to lifestyle changes or with two antihypertensives together at low doses (dual
Five-year CVD risk ≥ 15%: antihypertensive treatment is antihypertensive treatment; see: “Initial use of two low-dose
recommended, in addition to lifestyle changes antihypertensives can be a good starting point for many
patients” on Page 8). Antihypertensive treatment generally
For further information see: “Cardiovascular takes four-to-six weeks to reach maximum effect.9
disease risk assessment and management for primary
care” (available at: www.health.govt.nz/publication/ For further information on ACE inhibitors, see “Prescribing
cardiovascular-disease -risk-assessment-and- ACE inhibitors: time to reconsider old habits” at: bpac.org.
management-primary-care) nz/2021/ace.aspx

replacement supply without impurities will be available). No new

Warning: the fixed-dose combination
patients should be initiated on Accuretic, and those currently
antihypertensive Accuretic (quinapril with
taking it should be switched to an alternative treatment.14 Given
hydrochlorothiazide) should no longer be used
that no alternative brand to Accuretic is available in New Zealand,
Voluntary recalls of the combination antihypertensive Accuretic patients who require a fixed-dose combination treatment may
(quinapril with hydrochlorothiazide) have been occurring be changed to losartan with hydrochlorothiazide.13, 14 Another
worldwide since March, 2022, after the supplier (Pfizer) advised option is concurrent use of any ACE inhibitor (e.g. quinapril
that batches had been contaminated with nitrosamines.14 Long- or another choice) or ARB and a thiazide or thiazide-like
term exposure to nitrosamines has been associated with a small diuretic (Table 1).13 There are no funded brands of medicine
cumulative risk of cancer.15 with hydrochlorothiazide as the only active ingredient in New
Zealand; suitable alternatives include bendroflumethiazide,
PHARMAC has advised that Accuretic will be delisted in early chlortalidone or indapamide (for further information, see: nzf.
2023 (N.B. Pfizer has provided no certain timeline as to when a org.nz/nzf_998).

www.bpac.org.nz January 2023 5

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.

Initial dose
Class Funded option as of Jan, 2023 Dose range
(may be lower in some patients)

ACE inhibitors* Enalapril 5 mg, once daily Usual maintenance dose 20 mg,
once daily; maximum 40 mg,
once daily

Lisinopril 10 mg, once daily Usual maintenance dose 20 mg,

once daily;
maximum 80 mg, once daily

Perindopril 4 mg, once daily in the morning Maximum 8 mg, once daily

Quinapril 10 mg, once daily Usual maintenance dose 20 – 40

mg, daily in 1 – 2 divided doses;
maximum 80 mg, daily

Ramipril 2.5 mg, once daily Maximum 10 mg, daily

ARBs Candesartan 8 mg, once daily Usual maintenance dose 8 mg,

once daily; maximum 32 mg,
once daily

Losartan 50 mg, once daily Usual maintenance dose 50 mg,

once daily; maximum 100 mg,
once daily

Calcium Amlodipine 5 mg, once daily Maximum 10 mg, once daily

channel
Diltiazem 180 – 240 mg, once daily Usual maintenance dose 240 –
blockers
(modified release) 360 mg, once daily

Felodipine 5 mg, once daily in the morning Usual maintenance dose 5 – 10

mg, once daily

Verapamil (immediate release) 80 mg, two or three times daily Maximum 160 mg, two or three
times daily

Verapamil 120 – 240 mg, once daily Maximum 240 mg, twice daily
(modified release)

Thiazide and Bendroflumethiazide 2.5 mg, once daily in the morning Maximum doses of 10 mg, daily
thiazide-like have been used; however, doses
diuretics higher than 2.5 mg, daily increase
the risk of adverse effects and
have a limited additional blood
pressure lowering effect

Chlortalidone 12.5 – 25 mg, once daily in the

morning

Indapamide 2.5 mg, once daily in the morning

Fixed-dose Losartan + hydrochlorothiazide 1 tablet (50 mg losartan + 12.5 mg Maximum 2 tablets, once daily
combination hydrochlorothiazide), once daily
treatment†

* 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” on Page 5.

6 January 2023 www.bpac.org.nz

Beta-blockers are no longer considered a first-line antihypertensive used (Table 2).4, 5, 16 For example, in patients
antihypertensive unless there is a clinical need with hypertension and gout, losartan is often favoured due
Beta-blockers are less effective at reducing stroke risk to its dual blood pressure lowering/uricosuric effects, while
compared with other antihypertensive medicines and are often thiazide diuretics should be avoided as they promote urate
poorly tolerated.5 However, beta-blockers may be preferred reabsorption in proximal renal tubules.4, 5
early in treatment for patients with some co-morbidities, such Other patient characteristics may also affect the choice
as ischaemic heart disease (as they also help to decrease heart of antihypertensive. For example, ACE inhibitors or ARBs are
rate, increase diastolic filling time, decrease cardiac contractility sometimes favoured in patients aged under 55 years due to
and reduce myocardial oxygen demand) or atrial fibrillation (as the potential for a more significant reduction in renin levels.1, 17
they help to control heart rate).5 However, exposure to ACE inhibitors and ARBs increases the
risk of fetal abnormalities when used during pregnancy.18
Consider patient co-morbidities and characteristics Therefore, any females planning or considering pregnancy
Two-thirds of patients with hypertension have a co- should ideally use an alternative medicine, or switch from
morbidity, which may in turn influence the suitability of the an ACE inhibitor/ARB to another option once the pregnancy

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

Co-morbidity or characteristic Potentially Beneficial Avoid

Chronic kidney disease ACE inhibitors or ARBs High salt intake

Calcium channel blockers Thiazides in patients with more than mild
Loop diuretics (if eGFR < 30 mL/min/1.73 m2) renal impairment

Diabetes Type 1 – ACE inhibitors or ARBs then thiazide Beta-blockers

(or thiazide-like) diuretic or calcium channel High dose thiazide diuretics (low doses are
blocker acceptable)
Type 2 – ACE inhibitors

Heart failure or asymptomatic Beta-blockers (dose adjustments may be Non-dihydropyridine calcium channel
left ventricular dysfunction required for patients with renal dysfunction) blockers (e.g. diltiazem, verapamil)
Beta-blockers in uncontrolled heart failure

Acute myocardial infarction Beta-blockers without intrinsic No specific cautions

sympathomimetic activity, e.g. carvedilol
ACE inhibitors or ARBs

Atrial fibrillation Beta-blockers No specific cautions

Rate limiting calcium channel blocker, e.g.
diltiazem
ACE inhibitors or ARBs

Angina Beta-blockers No specific cautions

Calcium channel blockers
ACE inhibitors or ARBs

Cerebrovascular disease, i.e. ACE inhibitors or ARBs Beta-blockers

stroke Calcium channel blockers Thiazide diuretics in very elderly patients
Low-dose thiazide diuretics or those with poor daily fluid intake as they
could contribute to hypoperfusion

Asthma/COPD No specific recommendations Beta-blockers, however, low-dose bisoprolol

(or metoprolol) can be used if required
in patients with asthma/COPD and heart
failure

Gout Losartan (has a uricosuric effect) Thiazide diuretics

Pregnancy Labetalol ACE inhibitors and ARBs

Nifedipine
Methyldopa

www.bpac.org.nz January 2023 7

is confirmed.18 Recommended antihypertensives during Consider individualised blood pressure
pregnancy include labetalol, nifedipine and methyldopa.18 targets
N.B. Chronic hypertension before pregnancy is a risk
factor for pre-eclampsia and therefore all females planning Numerous clinical trials have addressed the concept of the
a pregnancy should ideally have their blood pressure treated “optimal” blood pressure target for patients with hypertension,
and controlled first, if possible. and there are discrepancies in recommendations between
different international guidelines. In 2018, New Zealand
For further information on hypertension in pregnancy, see: Ministry of Health guidelines specified a target clinic blood
Diagnosis and Treatment of Hypertension and Pre-eclampsia pressure of < 130/80 mmHg for most people.6 However, there
in Pregnancy in Aotearoa New Zealand (2022 update). has been a shift in some international guidelines to instead use
individualised blood pressure targets based on the patient’s
Initial use of two low-dose antihypertensives can be a CVD risk, co-morbidities and treatment objectives (Table
good starting point for many patients 3).4, 5 There is strong evidence supporting a lower clinic blood
The blood pressure lowering effect of any single pressure target (i.e. < 130/80 mmHg) for patients with a high
antihypertensive at its optimal dose has been estimated to CVD risk.4 However, the absolute benefits are likely outweighed
be < 10 mmHg on average.19 Therefore, initial monotherapy by the potential harms in those with a lower CVD risk, and
is unlikely to be effective in many patients with hypertension therefore a more conservative target is often more appropriate
(despite previously being standard practice) and multiple for this group (i.e. < 140 mmHg).4, 24
medicines are frequently required to achieve treatment
targets. As such, international guidelines now recommend a Intensive blood pressure management
more pragmatic approach to treatment, with initial use of two The potential benefit of using a stricter blood pressure target
low-dose antihypertensives together (dual antihypertensive (systolic blood pressure < 120 mmHg) in patients with high
treatment) being indicated in many cases (Figure 2).5 For further CVD risk has been investigated in large multi-centre clinical
information, see: “A closer look at the evidence supporting trials such as SPRINT and ACCORD.25, 26 These studies have
initial treatment with two low-dose antihypertensives”, Page 10. yielded mixed results, and there is debate as to whether any
While selection may be influenced by patient co-morbidities evidence of benefit outweighs the potential harms in real-
(Table 2), an ACE inhibitor or ARB with a dihydropyridine world populations, particularly when strict eligibility criteria is
calcium channel blocker such as amlodipine has been used in randomised controlled trials.27 In addition, it remains
demonstrated to be the most effective combination based on uncertain whether intensive blood pressure lowering has a
evidence from the ACCOMPLISH trial.20 Single antihypertensive uniform effect and tolerance across all age groups.27 Findings
use may still be a suitable starting point for some, e.g. elderly from the 2021 Chinese STEP study indicate that intensive
patients or those already close to their blood pressure target. blood pressure management may be beneficial in some older

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

24-hour ambulatory or at-home

Clinic measurement
measurement

“High” CVD risk,

including current atherosclerotic CVD, heart failure, < 130/80 mmHg < 125/80 mmHg
reduced ejection fraction, diabetes, CKD, aged ≥ 65
years, five-year CVD risk of ≥ 15%

“Lower” CVD risk

< 140/90 mmHg < 135/90 mmHg
None of the above risk factors

Discuss treatment goals to guide decision making; targets can be more

Frailty, dementia, limited life expectancy lenient and antihypertensive doses may need to be reduced or stopped
entirely depending on patient-specific factors.

8 January 2023 www.bpac.org.nz

patients, however, it is uncertain how applicable these findings and overall health; the relative importance of each should
are to Western populations which have different patterns of be determined by the patient’s preference and the clinician’s
CVD and lifestyle factors.28 expertise.
There are currently no recommendations for applying
intensive targets in primary care. If this decision is being For further discussion on intensive blood pressure
considered for any reason, it should realistically take into management, see “Go low or no? Managing blood pressure in
consideration other CVD risk factors the patient may have, primary care” at: bpac.org.nz/2017/blood-pressure.aspx
their co-morbidities, family history, concurrent medicines

Is the patient one or more of:

Low-dose monotherapy
Within 20/10 mmHg of their blood
e.g. an ACE inhibitor or ARB
pressure target? Yes to any?
Elderly (e.g. aged ≥ 80 years)?
Frail?
Committing to major lifestyle changes? Target not Target
achieved? achieved?

No?

Two low-dose antihypertensives

Consider increasing dose or trialling
e.g. an ACE inhibitor/ARB + a calcium
another first-line medicine
channel blocker

Target not achieved?

Consider increasing dose(s) if Continue treatment with consistent

close to target long-term follow-up (e.g. 3–6 monthly)*
Target
achieved?
Target not achieved?

Add a third antihypertensive

e.g. an ACE inhibitor/ARB + a calcium channel
blocker + a thiazide diuretic
Target
Target not achieved? achieved?

Consider increasing dose(s) if close to

target
Arrange 24-hour ambulatory or
at-home monitoring if not already Continue three
Consider referral
completed antihypertensives +
to secondary
Re-consider and address any secondary Target not add spironolactone Target not care
causes or adherence issues achieved? or other medicine† achieved?

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.4 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.
† Such as a beta-blocker or an alpha-blocker

www.bpac.org.nz January 2023 9

 A closer look at the evidence supporting initial treatment with two low-dose
antihypertensives

Half the standard dose of any first-line antihypertensive combination of pathophysiological processes, countering
still provides approximately 80% of the maximal blood it using medicines with different mechanisms of action is
pressure lowering effect.19 In addition, two low-dose therefore thought to improve treatment efficacy.22 Safety
antihypertensives used together are approximately five is sometimes cited as a concern when prescribing two
times more effective at lowering blood pressure than low dose antihypertensives together, however, the risk of
doubling the dose of a single antihypertensive (Figure adverse effects is often actually greater with a high dose
3).21 Given that hypertension is almost always caused by a of a single antihypertensive.23

0.19
Thiazide diuretic
1.04

0.23
ACE inhibitor
1.00

0.20
Beta-blocker
1.16

Calcium channel 0.37

blocker 0.89

0.22
All classes
1.01

0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6

Incremental systolic blood pressure reduction ratio of observed to expected effects
Doubling the dose of the same Adding an antihypertensive
antihypertensive* from another class†

Figure 3. Two low-dose antihypertensives used together have a greater blood pressure-lowering effect than doubling
the dose of one antihypertensive.
* From a standard initial dose to twice the standard initial dose
† Both antihypertensives at the standard initial dose
N.B. An incremental effect of 1.0 indicates that the systolic blood pressure-lowering effect is exactly additive, 0.5 indicates a sub-additive effect
(equivalent to 50% of the additive effect). Figure adapted from Wald DS, et al., 2009.21

10 January 2023 www.bpac.org.nz

Poor medicine adherence is a significant barrier to
achieving targets
Poor adherence to antihypertensive treatment is a common Age alone is not a reason to dial back
issue for many patients with hypertension and is an indicator treatment
of poor prognosis.5 Reasons for non-adherence are often multi- The risk of falls or orthostatic hypotension are often cited as
faceted and can be difficult to address in primary care. concerns when considering blood pressure management
in elderly patients (e.g. those aged ≥ 80 years), however,
Potential strategies to encourage and improve adherence there is no reason to withhold antihypertensives in
include:5 anyone based on age alone.4, 29 Routine treatment should
Educating patients at the time of the initial prescription generally be offered to elderly patients for as long as they
about their medicine(s) and how it works; this message wish to take it.4 It is their “biological age”, rather than their
should be reinforced at each appointment. In particular, “chronological age”, that may be a reason for avoiding use
if a decision is made to initially prescribe two low based on individual treatment goals. Nevertheless, blood
dose antihypertensives together, emphasise why it pressure management is one of the few interventions that
is important that both are taken consistently, i.e. to reduces mortality risk in frail, elderly people.4
maximise blood pressure control while reducing the
risk of adverse effects (compared with high dose Read the evidence
monotherapy). The 2008 Hypertension in the Very Elderly trial (HYVET)
Selecting antihypertensives with once daily dosing treated patients aged over 80 years with hypertension
Reducing polypharmacy, e.g. using a fixed-dose averaging 173/91 mmHg for an average of 1.8 years with
combination, if available indapamide and perindopril to a blood pressure target
Using pill boxes, blister packaging or electronic less than 150/80 mmHg.30 Stroke rates were reduced by
reminders (e.g. smartphone apps) 30%, heart failure mortality by 64% and all-cause mortality
by 21%. Despite this study being published almost 15
If adverse effects are problematic, consider night-time
years ago, it is one of the few randomised controlled
dosing, which can limit the perception of adverse
trials that specifically investigates the benefits of blood
effects. Further benefits for night-time dosing have
pressure management in people aged > 80 years (most
been suggested, however, the evidence at present is
exclude such patients).
inconsistent (see: “Night-time antihypertensive dosing:
does it reduce the risk of CVD events?” on Page 12).
If antihypertensive treatment is initiated in an elderly
patient, starting with low-dose monotherapy is generally
Intensifying treatment over the short-term recommended, and this approach may be more tolerable
Patients starting antihypertensive treatment should initially be as gradually reducing blood pressure is less likely to
reviewed at least every four-to-six weeks to assess the efficacy cause adverse effects, e.g. postural hypotension.29 Close
of their regimen.9 Shorter review times may be considered monitoring and more lenient targets are also appropriate,
for some patients, e.g. every two weeks if the patient’s and the treatment intensity should be reduced if there
measurement was significantly elevated at baseline. If a target are any concerning emerging features, e.g. cognitive
is not achieved, the next step depends on how well the patient impairment.29 If an elderly patient is already taking
tolerates treatment and how close they are to their objective multiple antihypertensives and becomes progressively
(Figure 2):5 more frail over time, it may be suitable to reconsider the
If the patient is close to their target blood treatment intensity depending on treatment priorities, e.g.
pressure and the antihypertensive medicine(s) lower doses or de-escalating treatment to monotherapy.
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

www.bpac.org.nz January 2023 11

 Night-time antihypertensive dosing: does it reduce the risk of CVD events?

Blood pressure is associated with circadian variability; dosing is routinely recommended in primary care for
in many people, blood pressure drops during the night the sole purpose of greater CVD protection. Since being
by 10 – 20% (versus daytime measurements), before published, concerns have been raised around the trial
increasing upon waking in the morning – a phenomenon design, conduct and the potential mechanism of effect.33
known as the “morning surge”.31 People with hypertension In addition, the question “why would an antihypertensive
who lack this morning surge due to persistently elevated work better depending on the time of day it is taken once it
nocturnal measurements (“non-dippers”) are more likely reaches a steady state?”† remains unaddressed.33
to have end organ damage, and have an increased risk of In October, 2022, findings released from the
cardiovascular events.31 prospective multi-centre TIME trial (N = 21,104) indicate
The 2019 Hygia Chronotherapy trial (N = 19,168) that night-time antihypertensive dosing provides no
demonstrated that night-time antihypertensive dosing additional protection against myocardial infarction, stroke
was associated with a lower mean systolic blood and vascular death compared with morning dosing over
pressure while sleeping, and reduced the relative risk of five years.34 No additional harms associated with night-
primary CVD outcomes by 45% compared with morning time dosing were reported.34 Therefore, in contrast to the
administration.*32 This corresponded to an absolute Hygia trial conclusions, these outcomes suggest patients
risk reduction of 5.4% for night-time versus morning should simply take their antihypertensive medicines at
antihypertensive dosing over the median 6.3 years of the time of day most convenient for them and which
follow-up.32 Study authors proposed that night-time minimises adverse effects.
dosing of antihypertensives enhanced their effects * Primary CVD outcomes was defined as a composite endpoint of
through “circadian rhythm-dependent influences both on myocardial infarction, coronary revascularisation, heart failure,
their pharmacokinetics and pharmacodynamics as well as ischaemic stroke, haemorrhagic stroke and CVD death.
on the mechanisms of blood pressure regulation”.32 † Steady state occurs when rate of drug absorption equals the
While the Hygia trial findings appear promising at first elimination rate, i.e. the concentration consistently remains within
the range expected to achieve a desired treatment effect.
glance, further investigation is required before night-time

12 January 2023 www.bpac.org.nz

Resistant hypertension such techniques (e.g. those with hypertension resistant to
all suitable pharmacological treatment options) should be
If a patient’s clinic blood pressure remains > 140/90 mmHg discussed with a cardiologist.
after treatment with an ACE inhibitor or an ARB, plus a calcium
channel blocker and a thiazide diuretic at their optimal
Longer-term follow-up and monitoring
(or maximally tolerated) dose, then their hypertension is
considered “resistant”.5 Patient adherence to treatment and Once a blood pressure target has been achieved, continued
possible secondary causes should be re-examined, and an long-term follow-up is important to ensure levels are
added emphasis placed on lifestyle changes.5 In addition, if maintained, and to reinforce the importance of medicine
the patient is taking optimal, or maximum tolerated, doses of adherence and a healthy lifestyle. Guidelines suggest patients
antihypertensive medicines, an appropriate specialist opinion with hypertension should be reviewed three-to-six-monthly.5, 9
is recommended, if this has not been sought already.5 However, less frequent review may be more practical for some
patients with stable blood pressure measurements, e.g.
Ultimately, an additional antihypertensive medicine may be annually in otherwise healthy patients who are also
required. Options to consider include:5, 9, 13 committing to lifestyle changes and take their medicines
Spironolactone – appropriate in combination with regularly. These appointments also provide an opportunity to
another diuretic if serum potassium is ≤ 4.4 mmol/L monitor electrolytes, renal function and albumin/creatinine
and eGFR is ≥ 45 mL/min/1.73m2. Spironolactone ratio, in addition to checking for any emerging signs of end
may be particularly beneficial as many patients with organ disease and associated conditions, e.g. retinopathy,
resistant hypertension have high aldosterone levels heart failure.
(even if they do not have clinically apparent primary
hyperaldosteronism); spironolactone impairs aldosterone
Acknowledgement: Thank you to Dr. John Edmond,
binding to mineralocorticoid receptors which limits
Consultant Cardiologist, Te Whatu Ora Southern, Senior
vascular resistance. N.B. Spironolactone should be
Clinical Lecturer, Dunedin School of Medicine, University of
introduced cautiously with ongoing monitoring of serum
Otago and Dr. Joan Leighton, General Practitioner, Te Whatu
potassium and creatinine.
Ora Waitaha Canterbury, for expert review of this article.
Beta-blocker – no longer considered a first-line
antihypertensive for patients with uncomplicated South Link Article supported by the South Link
Education Trust
hypertension but may be useful if indicated for a Education Trust
co-morbidity, e.g. atrial fibrillation. All beta-blockers have N.B. Expert reviewers do not write the articles and are not responsible for
comparable blood pressure lowering effects. the final content. bpacnz retains editorial oversight of all content.

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.

Novel techniques for treating patients with resistant

hypertension
A range of novel procedure- and device-based strategies
have been investigated for the management of resistant
hypertension. For example, renal sympathetic nerve
denervation is a catheter-based technique used to ablate
specific portions of renal artery nerves, thereby limiting
sympathetic activity and the associated effects on blood
pressure.35 Despite promising results in clinical trials,36 there
is currently insufficient evidence to support routine use of
this and other novel treatments in patients with resistant
hypertension.4 Patients who may potentially benefit from

www.bpac.org.nz January 2023 13

References
1. National Institute for Health and Care Excellence (NICE). Hypertension in 21. Wald DS, Law M, Morris JK, et al. Combination therapy versus monotherapy
adults: diagnosis and management. 2019. Available from: https://www.nice. in reducing blood pressure: meta-analysis on 11,000 participants from 42
org.uk/guidance/ng136/resources/hypertension-in-adults-diagnosis-and- trials. The American Journal of Medicine 2009;122:290–300. doi:10.1016/j.
management-pdf-66141722710213 (Accessed Jan, 2023). amjmed.2008.09.038
2. Oparil S, Acelajado MC, Bakris GL, et al. Hypertension. Nat Rev Dis Primers 22. Mancia G, Rea F, Corrao G, et al. Two-drug combinations as first-step
2018;4:18014. doi:10.1038/nrdp.2018.14 antihypertensive treatment. Circ Res 2019;124:1113–23. doi:10.1161/
3. Murtagh J, Rosenblatt J. Murtagh’s General Practice. 5th ed. McGraw-Hill CIRCRESAHA.118.313294
Australia Pty Ltd 23. Law MR. Value of low dose combination treatment with blood pressure
lowering drugs: analysis of 354 randomised trials. BMJ 2003;326:1427–0.
4. Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the
doi:10.1136/bmj.326.7404.1427
management of arterial hypertension. European Heart Journal 2018;39:3021–
24. Arguedas JA, Leiva V, Wright JM. Blood pressure targets in adults with
104. doi:10.1093/eurheartj/ehy339.
hypertension. Cochrane Database of Systematic Reviews 2020;2020.
5. Unger T, Borghi C, Charchar F, et al. 2020 International Society of Hypertension
doi:10.1002/14651858.CD004349.pub3
global hypertension practice guidelines. Hypertension 2020;75:1334–57.
25. The SPRINT Research Group. A randomized trial of intensive versus standard
doi:10.1161/HYPERTENSIONAHA.120.15026.
blood-pressure control. N Engl J Med 2015;373:2103–16. doi:10.1056/
6. Ministry of Health. Cardiovascular disease risk assessment and management
NEJMoa1511939
for primary care. 2018. Available from: https://www.health.govt.nz/system/
26. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J
files/documents/publications/cardiovascular-disease-risk-assessment-
Med 2010;362:1575–85. doi:10.1056/NEJMoa1001286
management-primary-care-feb18-v4_0.pdf (Accessed Jan, 2023).
27. Camafort M, Redón J, Pyun WB, et al. Intensive blood pressure lowering: a
7. McLean RM, Williams S, Mann JI, et al. Blood pressure and hypertension in
practical review. Clin Hypertens 2020;26:21. doi:10.1186/s40885-020-00153-z
New Zealand: results from the 2008/09 Adult Nutrition Survey. N Z Med J
28. Zhang W, Zhang S, Deng Y, et al. Trial of intensive blood-pressure control in
2013;126:66–79.
older patients with hypertension. N Engl J Med 2021;385:1268–79. doi:10.1056/
8. Ministry of Health (MOH). New Zealand Health Survey 2020/21. 2022. Available NEJMoa2111437
from: https://www.health.govt.nz/publication/methodology-report-2021-22- 29. Aronow WS. Managing hypertension in the elderly: What’s new?
new-zealand-health-survey (Accessed Jan, 2023). American Journal of Preventive Cardiology 2020;1:100001. doi:10.1016/j.
9. National Heart Foundation of Australia. Guideline for the diagnosis and ajpc.2020.100001
management of hypertension in adults. 2016. Available from: https://www. 30. Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients
heartfoundation.org.au/getmedia/c83511ab-835a-4fcf-96f5-88d770582ddc/ 80 years of age or older. N Engl J Med 2008;358:1887–98. doi:10.1056/
PRO-167_Hypertension-guideline-2016_WEB.pdf (Accessed Jan, 2023). NEJMoa0801369
10. Cheung CY, Biousse V, Keane PA, et al. Hypertensive eye disease. Nat Rev Dis 31. Kario K. Nocturnal hypertension: new technology and evidence. Hypertension
Primers 2022;8:14. doi:10.1038/s41572-022-00342-0 2018;71:997–1009. doi:10.1161/HYPERTENSIONAHA.118.10971
11. Leontsinis I, Mantzouranis M, Tsioufis P, et al. Recent advances in managing 32. Hermida RC, Crespo JJ, Domínguez-Sardiña M, et al. Bedtime hypertension
primary hypertension. Fac Rev 2020;9. doi:10.12703/b/9-4. treatment improves cardiovascular risk reduction: the Hygia Chronotherapy
12. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/ Trial. European Heart Journal 2020;41:4565–76. doi:10.1093/eurheartj/ehz754
AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, 33. Turgeon RD, Althouse AD, Cohen JB, et al. Lowering nighttime blood pressure
evaluation, and management of high blood pressure in adults: Executive with bedtime dosing of antihypertensive medications: controversies in
Summary: A report of the American College of Cardiology/American Heart hypertension - con side of the argument. Hypertension 2021;78:871–8.
Association Task Force on Clinical Practice Guidelines. Circulation 2018;138. doi:10.1161/HYPERTENSIONAHA.121.16501
doi:10.1161/CIR.0000000000000597 34. Mackenzie IS, Rogers A, Poulter NR, et al. Cardiovascular outcomes in
13. New Zealand Formulary (NZF). NZF v127. 2022. Available from: https://nzf.org. adults with hypertension with evening versus morning dosing of usual
nz/nzf_1 (Accessed Jan, 2023). antihypertensives in the UK (TIME study): a prospective, randomised,
14. PHARMAC. Accuretic (quinapril and hydrochlorothiazide) tablets: Supply issue. open-label, blinded-endpoint clinical trial. The Lancet 2022;400:1417–25.
2022. Available from: https://pharmac.govt.nz/medicine-funding-and-supply/ doi:10.1016/S0140-6736(22)01786-X
medicine-notices/accuretic/ (Accessed Jan, 2023). 35. Akinseye OA, Ralston WF, Johnson KC, et al. Renal sympathetic denervation:
a comprehensive review. Current Problems in Cardiology 2021;46:100598.
15. Li K, Ricker K, Tsai FC, et al. Estimated cancer risks associated with nitrosamine
doi:10.1016/j.cpcardiol.2020.100598
contamination in commonly used medications. Int J Environ Res Public Health
36. Bhatt DL, Vaduganathan M, Kandzari DE, et al. Long-term outcomes after
2021;18:9465. doi:10.3390/ijerph18189465
catheter-based renal artery denervation for resistant hypertension: final follow-
16. Kennard L, O’Shaughnessy KM. Treating hypertension in patients with medical
up of the randomised SYMPLICITY HTN-3 Trial. The Lancet 2022;400:1405–16.
comorbidities. BMJ 2016;:i101. doi:10.1136/bmj.i101
doi:10.1016/S0140-6736(22)01787-1
17. Sinnott S-J, Douglas IJ, Smeeth L, et al. First line drug treatment for
hypertension and reductions in blood pressure according to age and ethnicity:
cohort study in UK primary care. BMJ 2020;:m4080. doi:10.1136/bmj.m4080.
18. Te Whatu Ora - Health New Zealand. Diagnosis and treatment of hypertension
and pre-eclampsia in pregnancy in Aotearoa New Zealand. A clinical practice
guideline. Available from: https://www.tewhatuora.govt.nz/about-us/
publications/diagnosis-and-treatment-of-hypertension-and-pre-eclampsia-in-
pregnancy-in-aotearoa-new-zealand (Accessed Jan, 2023).
19. Atkins ER, Chow CK. Low-dose combination therapy for initial treatment This article is available online at:
of hypertension. Curr Hypertens Rep 2020;22:65. doi:10.1007/
www.bpac.org.nz/2023/hypertension.aspx
s11906-020-01069-7.
20. Magvanjav O, Cooper-Dehoff RM, McDonough CW, et al. Combination © Copyright BPAC NZ Limited (bpacnz) 2023. All rights reserved.
antihypertensive therapy prescribing and blood pressure control in a real- This resource is the subject of copyright which is owned by bpacnz. You may access
world setting. American Journal of Hypertension 2020;33:316–24. doi:10.1093/ it, but you may not reproduce it or any part of it except in the limited situations
ajh/hpz196. described in the terms of use on our website.

14 January 2023 www.bpac.org.nz