Key Learning Points: ESC/ESH Guidance on Arterial Hypertension

Dr Kevin Fernando Examines European Guidance on Hypertension, Offering Eight Key Learning Points for UK Primary Care Practitioners

Hypertension is common in the UK: in 2015, it was estimated that more than one in four adults in England (approximately 13.5 million people) were living with high blood pressure (BP), and that the condition contributed to 75,000 deaths in that year alone.^1–3 The prevalence of high BP in the UK has remained consistent in recent years, despite improved identification,^2,3 and it remains a significant concern for the health system. The clinical management of hypertension is thought to cost the NHS up to £2.1 billion each year, and the condition accounts for around 12% of visits to primary care.¹ Furthermore, hypertension is the biggest cause of cardiovascular morbidity and mortality worldwide, and the third biggest risk factor for disease in the UK.^3–5

Good control of BP is a cost-effective approach to reducing premature cardiovascular morbidity and mortality, but BP is generally poorly controlled in people with hypertension in the UK. This is demonstrated by a serial cross-sectional study of people with treated hypertension in England between 1994 and 2011, which identified progressive improvements in participants’ mean BP in this period, but also found that BP was controlled in only 37% of participants.⁶

Unfortunately, there is considerable debate about the optimal approach to BP targets and pharmacological therapy for hypertension—a fact that may, in itself, contribute to the suboptimal management of hypertension globally—and there are many conflicting guidelines (both national and international) on the topic. In this article, I will consider the 2018 European Society of Cardiology (ESC)/European Society of Hypertension (ESH) guideline for the management of arterial hypertension,⁷ and the associated 2021 ESH practice guideline for office and out-of-office BP measurement.⁸ In doing so, I will offer key learning and practice-changing points to help clinicians to improve the diagnosis and management of hypertension in primary care.

1. Use ABPM and HBPM Effectively in the Diagnosis of Hypertension

The ESC and the ESH define hypertension as the presence of a systolic BP of 140 mmHg or greater, a diastolic BP of 90 mmHg or greater, or both, measured in the clinic.^7,8 However, in line with NICE, the ESC/ESH guidelines emphasise that diagnosis should be based on out-of-clinic measurements where feasible.^7,8

In the UK, 24-hour ambulatory blood pressure monitoring (ABPM) is the gold standard for all individuals with suspected hypertension, and is the method preferred by NICE for confirming a diagnosis; as ABPM is not widely available or suitable for everyone, home blood pressure monitoring (HBPM) is considered the next best alternative.¹ The ESC/ESH guidelines do not make as significant a distinction between the two methods, recommending ABPM and HBPM equally.^7,8

HBPM

Ideally, HBPM should be assessed based on measurements from 7 consecutive days.⁷ Furthermore, when using home measurements, an average value of 135/85 mmHg or greater defines hypertension.^1,7 See Table 1 for further recommendations on HBPM interpretation from ESC/ESH and NICE guidelines, which align significantly.

Table 1: Comparison of ESC/ESH and NICE Recommendations on HBPM^1,7

ABPM

ABPM also requires minor adjustments for interpreting readings. When interpreting 24-hour ABPM, the ESC/ESH-recommended thresholds for hypertension diagnosis are as follows:⁷ 

• 130/80 mmHg or greater for a 24-hour average
• 135/85 mmHg or greater for a daytime (awake) average, which indicates daytime hypertension
• 120/70 mmHg or greater for a night-time (asleep) average, which indicates night-time hypertension.

Night-time and Daytime Measurements

It is also important to consider nocturnal BP, as it is generally accepted that people who are ‘nondippers’ (their BP falls by less than 10% at night) or ‘reverse dippers’ (their BP rises at night) have a higher risk of adverse cardiovascular outcomes.^7,9

Interestingly, the authors of a recent retrospective cohort study concluded that not measuring night-time BP put all groups other than ‘dippers’ (whose BP falls by 10% or more at night) at risk of a missed diagnosis of hypertension.¹⁰ The authors challenged the current practice of using HBPM over ABPM, recommending that primary care should offer ABPM to all individuals aged 60 years or over, as a minimum, when diagnosing hypertension.¹⁰ This would need to be balanced against tolerability and resource availability for ABPM, but is interesting to consider. 

Other Considerations When Measuring BP

As part of an initial BP assessment, it is useful to check for any inter-arm difference in BP, both to ensure that the measurement is correct (the arm with a consistently higher BP should be favoured) and to identify potential comorbidities.^1,7 If there is a consistent inter-arm systolic BP difference of greater than 20 mmHg, investigation for arterial disease should be considered.^7,8 For example, a clinician may choose to check their patient’s ankle brachial pressure index (ABPI)—an ABPI below 0.8 is suggestive of arterial disease or mixed arterial and venous disease.¹¹

Additionally, standing BP should be measured in those with hypertension and symptoms of postural hypotension, particularly in people who:^7,8

• are aged 65 years or above
• have a neurodegenerative disease (for example, Parkinson’s disease or dementia)
• are living with diabetes.

BP should be measured after 1 minute of standing, then again after 3 minutes.^7,8 A diagnosis of postural hypotension can be established when there is a reduction in systolic BP of 20 mmHg or greater, or 10 mmHg for diastolic BP, within 3 minutes of standing.^7,8

The British and Irish Hypertension Society provides excellent resources for healthcare professionals on implementing HBPM in clinical practice, encompassing HBPM protocols, home BP diaries, and effective instruction for patients—bihsoc.org/resources.¹²

2. Adopt Appropriate Target Ranges When Aiming to Lower BP

In all patients with hypertension, the ESC and the ESH recommend aiming initially for a clinic BP of less than 140/90 mmHg (all target BPs in the guidance are based on clinic measurement).⁷ In people aged under 65 years, this target should be reduced to a BP of less than 130/80 mmHg if treatment is well tolerated.⁷

Clinicians should consider a diastolic BP target of less than 80 mmHg for all people with hypertension, independent of their comorbidities and risk level.⁷ Treated systolic BP should not drop below 120 mmHg.⁷

Age and Frailty

The 2018 ESC/ESH guideline acknowledges that the categorisation of patients by age is complex.⁷ The guideline provides distinct recommendations for ‘older’ people (aged 65–80 years) and ‘very old’ people (aged over 80 years), but emphasises that biological age (rather than chronological age) should be a key determinant in decisions about initiating drug treatment and BP targets in these individuals.⁷

In most individuals aged over 65 years, a target systolic BP of 130–139 mmHg is recommended, but no lower.⁷ This BP target is recommended at any level of cardiovascular risk, in people both with and without established cardiovascular disease (CVD).⁷ Because of increased risk, close monitoring of adverse effects is advocated in this cohort⁷—for example, for acute kidney injury associated with renin–angiotensin–aldosterone system (RAAS) inhibitors.

For individuals aged over 80 years specifically, the guideline recommends that treatment should be initiated only if the person’s clinic systolic BP is 160 mmHg or greater.⁷ Older people with frailty, particularly those aged over 80 years, may also require more holistic and individualised treatment, such as a higher target BP than standard, and consideration should be given to de-escalation of therapies where appropriate.⁷ However, the evidence clearly demonstrates that controlled hypertension in those aged over 80 years is associated with reductions in mortality, stroke, and heart failure, so treatment to lower BP in these individuals is warranted (where tolerated).⁷

Diabetes

For people living with diabetes and hypertension, the ESC/ESH guidance recommends that:⁷

• in those aged under 65 years, the target BP should be less than 130/80 mmHg, and even lower if tolerated (but no less than 120 mmHg systolic)
• in those aged 65 years and older, BP targets should be 130–140 mmHg (systolic) and less than 80 mmHg (diastolic).

Interestingly, clinicians are advised to pay more attention to appointment-to-appointment BP variability in people living with diabetes, as greater variability is associated with increased cardiorenal risk.⁷

3. Promote Lifestyle Changes for All Patients With Hypertension

The 2018 ESC/ESH guideline emphasises the importance of healthy lifestyle choices for people living with hypertension, as they can prevent or delay the development of high BP and reduce future cardiovascular risk.⁷ For grade 1 hypertension in particular (people with a clinic systolic BP of 140–159 mmHg and/or a clinic diastolic BP of 90–99 mmHg), effective lifestyle changes may delay or prevent their need for pharmacological treatment.⁷ As such, lifestyle interventions remain a first-line treatment option for hypertension in the ESC/ESH guidance and in the NICE guideline, and should be discussed and implemented at all patient contacts.^1,7 

Although effective lifestyle changes have significant synergistic effects on the need for hypertensive medication, lifestyle interventions should not cause any delay in drug therapy.⁷ This is especially true for people:⁷

• at high cardiovascular risk
• with evidence of hypertension-related end-organ damage (for example, proteinuria, left-ventricular hypertrophy, or retinopathy)
• with grade 2 (a clinic systolic BP of 160–179 mmHg and/or a clinic diastolic BP of 100–109 mmHg) or grade 3 (a clinic systolic BP of 180 mmHg or greater and/or a clinic diastolic BP of 110 mmHg or greater) hypertension at any level of cardiovascular risk.

The guidance highlights the importance of dietary sodium restriction: maximum sodium intake should be 2 g daily (around 5 g, or one teaspoon, of salt) in both people with known hypertension and the general population.⁷ The ESC/ESH also recommends limiting alcohol intake to 14 units weekly for men with hypertension and 8 units weekly for women with hypertension, and drink-free days during the week and avoidance of binge-drinking are also recommended.⁷

I recently developed a Primary Care Hack¹³ on lifestyle changes for managing hypertension, detailing the current recommendations in the UK and their approximate effects on reducing systolic and diastolic BP.

4. Initiate Drug Treatment at an Appropriate Time

Analogous to the modern management of type 2 diabetes, the choice of immediate or delayed (following a period of lifestyle change) initiation of pharmacological treatment for hypertension should be guided by the person’s individual level of cardiovascular risk (see Figure 1).^1,7 Drug treatment should be initiated after an individualised period of lifestyle change for low-to-moderate-risk individuals who have grade 1 hypertension, do not exhibit signs of end-organ damage, and are aged under 65 years.⁷

However, for higher-risk individuals with grade 1 hypertension and high cardiovascular risk or evidence of hypertension-mediated organ damage (for example, those living with diabetes or with evidence of left-ventricular hypertrophy), drug therapy should be started immediately alongside lifestyle change.⁷ Prompt initiation of drug treatment alongside lifestyle changes is also recommended for all people with grade 2 or 3 hypertension, as they are at higher cardiovascular risk.⁷ 

The ESC/ESH guideline contains a useful table (bit.ly/2B4ADWz) that classifies risk based on blood pressure, cardiovascular risk factors, hypertension-mediated organ damage, and comorbidities, and is based on the Systematic COronary Risk Evaluation (SCORE).^7,14,15 Importantly:⁷

• all individuals with established CVD are considered at very high risk
• all individuals with grade 3 hypertension are considered at high or very high risk
• individuals with grade 1 hypertension are considered at low risk if they have no other cardiovascular risk factors and at moderate risk if they have one or two risk factors
• individuals with grade 2 hypertension are considered at moderate risk if they have no other cardiovascular risk factors and moderate-to-high risk if they have one or two risk factors
• asymptomatic CVD (such as hypertension-mediated organ damage or diabetes without organ damage) significantly increases a patient’s risk—for example, people with grade 1 hypertension and asymptomatic CVD are at high cardiovascular risk.

5. Consider the Potential of Initial Dual Therapy, and Escalate Treatment When Necessary

The ESC/ESH guideline also features a useful flowchart outlining the core drug treatment strategy for people with hypertension (bit.ly/2B4ADWz).⁷ This strategy can be summarised as follows:⁷

• initial therapy—dual combination (angiotensin-converting enzyme [ACE] inhibitor or angiotensin receptor blocker [ARB] with a calcium channel blocker [CCB] or a diuretic), single pill; consider monotherapy in low-risk grade 1 hypertension (people with a systolic BP below 150 mmHg) or patients who are very old or frail
• second-line therapy—triple combination (ACE inhibitor or ARB with a CCB and a diuretic), single pill
• third-line therapy (for resistant hypertension)—triple combination with spironolactone or another drug (another diuretic, alpha-blocker, or beta-blocker), two pills; consider referral to a specialist centre for further investigation. 

This core strategy is also applicable to most patients with hypertension-mediated organ damage, cerebrovascular disease, diabetes, or peripheral arterial damage.⁷

Favouring Initial Dual Therapy Over Monotherapy

Notably, regarding the initiation of drug treatment for individuals with hypertension, the 2018 ESC/ESH guideline recommends dual therapy for most people, ideally delivered in a combination tablet.⁷ The recommended combination is an ACE inhibitor or ARB in combination with a CCB or diuretic.⁷ It is recommended that monotherapy is considered primarily in people who:⁷

• are at low cardiovascular risk with grade 1 hypertension, particularly if their systolic BP is less than 150 mmHg
• have high-normal BP (clinic systolic BP of 130–139 mmHg and/or clinic diastolic BP of 85–89 mmHg)
• are over 80 years of age, or have frailty.

This is a significant change in practice for many healthcare professionals in the UK, where combination therapy is traditionally frowned upon because of its cost and side effects.

The rationale behind this recommendation is that most individuals will require combination therapy to achieve a BP target of less than 130/80 mmHg, and that a more active approach should help to reduce clinical inertia and improve patient adherence to treatment.⁷ The guideline cites considerable evidence to demonstrate that taking a combination of medications—and therefore simultaneously targeting multiple pathophysiological pathways that drive hypertension—generally improves a person’s initial response to BP treatment, as well as having a steeper dose–response effect than escalating doses of monotherapy.⁷

Beta-Blockers

Beta-blockers are only recommended in specific situations that necessitate their use—for example, in people with angina, post-myocardial infarction, who have heart failure with reduced ejection fraction, or for heart rate control in people with atrial fibrillation.⁷

Triple Therapy

If dual therapy is ineffective for achieving mutually agreed BP targets, the ESC and the ESH recommend intensifying treatment to triple therapy (usually with an ACE inhibitor or ARB, a CCB, and a diuretic), again in a single combination tablet where possible.⁷

The Australian QUARTET study, published in 2021 and investigating strategies to tackle treatment inertia in BP control, is particularly relevant to this recommendation.¹⁶ The authors found that participants achieved and maintained a greater reduction in BP when treated with a simple, varied treatment strategy—a quadruple combination of quarter doses of four BP therapies in a single pill—than when treated with monotherapy.¹⁶ Importantly, this quadruple combination was well tolerated, with no significant difference in adverse-effect-related treatment withdrawals compared with the control group.¹⁶

Resistant Hypertension, Spironolactone, and Primary Aldosteronism

For people with resistant hypertension (hypertension that optimal triple therapy fails to reduce to the person’s BP target), the addition of the mineralocorticoid receptor antagonist spironolactone at a dosage of 25–50 mg per day is recommended when appropriate.⁷ This recommendation is supported by the findings of the 2015 PATHWAY-2 trial, which found that spironolactone was the most effective add-on drug for the treatment of resistant hypertension, compared with doxazosin, bisoprolol, or placebo.¹⁷

If the introduction of spironolactone is inadvisable, clinicians may wish to consider another diuretic (such as eplerenone, amiloride, or a loop diuretic such as furosemide), doxazosin, or bisoprolol instead.⁷ Caution is advisable in these cases, however, as spironolactone is often poorly tolerated because of the risk of hyperkalaemia in people whose baseline potassium level or renal function is inadequate (their plasma potassium concentration is 4.5 mmol/l or greater, or their estimated glomerular filtration rate [eGFR] is 45 ml/min/1.72 m² or lower) but some of these alternative drugs are also not indicated in this situation.⁷

The ESC/ESH guideline’s recommendations also align with past research suggesting that resistant hypertension is often driven by sodium retention, either through excess dietary intake or another cause.^7,18–21 One notable cause is primary aldosteronism (also known as Conn’s syndrome), which is underappreciated as the leading cause of secondary hypertension and affects around 5–13% of all individuals with hypertension, or as many as 29% of people with resistant hypertension.^19,22 In line with this, it is recommended that clinicians screen for secondary causes in their patients with resistant hypertension, and in particular for possible aldosteronism.^7,23 Clinicians can screen for aldosteronism effectively by checking a person’s aldosterone-to-renin ratio (ARR), as an elevated ARR is strong evidence of primary aldosteronism.^21–23

6. Recommend that Patients Take Medication at a Time that Suits Them

It is worth noting that the ESC and the ESH do not recommend a particular time for taking antihypertensive medication.⁷ There has been considerable debate over the years about when people should take antihypertensive drugs for optimal impact on BP control and cardiovascular outcomes, and previous studies have suggested that evening doses may have better outcomes than morning ones.²⁴ However, the TIME study, published in 2022, found no significant differences between morning and evening dosing in terms of major cardiovascular outcomes.²⁴

Therefore, to minimise adverse effects and improve adherence, it seems best to advise patients to take their medication at a time that is convenient for them.²⁴ The most effective antihypertensive tablets are the ones that a person will actually take.

7. Adapt Treatment for Particular Patient Groups

Certain groups require adaptation of their treatment to take into account their individual clinical situation.

Coronary Artery Disease and Other Established CVD

People with established CVD, including coronary artery disease (CAD), are by definition at very high cardiovascular risk (see Figure 1).⁷ A high-normal BP threshold of 130–139 mmHg/85–89 mmHg is therefore recommended for initiating drug treatment in people with established CVD, and especially for people with CAD, as there is particularly strong evidence of benefit in this group.⁷ However, it is particularly important that diastolic BP should not drop below 70 mmHg in these individuals, as this may impair myocardial perfusion.⁷

Chronic Kidney Disease

In people living with chronic kidney disease (CKD) and hypertension, initial combination therapy should consist of an RAAS inhibitor (usually an ACE inhibitor or an ARB) to help reduce albuminuria, and either a CCB or a diuretic.⁷ In both diabetic and nondiabetic CKD, the standard systolic BP target should be 130–139 mmHg.⁷

Loop diuretics (such as furosemide) should be considered over thiazide and thiazide-like diuretics (such as indapamide) for antihypertensive therapy when a person’s eGFR is less than 30 ml/min/1.72 m², as the latter are far less effective, or indeed ineffective, below this threshold.⁷ The ESC and the ESH also emphasise the significant risk of hyperkalaemia that is associated with spironolactone, specifically advising against its use when a person’s eGFR is less than 45 ml/min/1.72 m² or their plasma potassium concentration is 4.5 mmol/l or greater.⁷

Hypertension and Pregnancy

In women with hypertension who are pregnant or planning pregnancy, ACE inhibitors, ARBs, and direct renin inhibitors are contraindicated in pregnancy because of adverse fetal and neonatal outcomes, and diuretics should be avoided where possible.⁷ Preferred pharmacological treatment options for hypertension in pregnancy include methyldopa, labetalol, and CCBs.⁷

8. Manage Concomitant Cardiovascular Risk as Appropriate

For people with hypertension and a cardiovascular risk that is moderate or higher, BP reduction alone is not considered the optimal method for reducing future risk. These individuals will likely benefit from statin therapy, as the ESC and the ESH highlight that statins reduce a person’s risk of myocardial infarction and stroke even when BP is controlled.⁷

The 2018 ESC/ESH guideline only recommends antiplatelet therapy, such as low-dose aspirin, for secondary prevention of CVD in people with hypertension, and does not recommend it for primary prevention in this group.⁷

Summary

The diagnosis and treatment of hypertension is a fundamental aspect of daily practice in primary care. However, it remains an area in which best practice is hotly debated. These guidelines from the ESC and the ESH provide an interesting alternative to UK guidance, reminding clinicians of the importance of diagnosing hypertension effectively, preventing therapeutic inertia, and considering the optimal therapy for each individual.