Adjust Age and Blood Pressure Thresholds in Hypertension Guidelines to Improve Cardiovascular Risk Management

Managing Hypertension is a Key Element of Reducing Risk for Cardiovascular Disease. Professor Kazem Rahimi Outlines Why Findings From the Blood Pressure Lowering Treatment Trialists' Collaboration Should be Reflected in Updates to UK, European, and US Guidance

Introduction

High blood pressure (BP)—defined in many guidelines as systolic blood pressure (SBP) greater than or equal to 140 mmHg or diastolic blood pressure (DBP) greater than or equal to 90 mmHg^1–3—is one of the most important risk factors for cardiovascular disease (CVD).⁴ The prevalence of hypertension is increasing: in 2019, the number of people aged 30–79 years with hypertension globally was more than 1 billion, double the number with the condition in 1990.⁵

High BP is known to have an independent and continuous relationship with a range of cardiovascular events, including haemorrhagic and ischaemic stroke, heart failure, myocardial infarction (MI), peripheral arterial disease, atrial fibrillation, valvular heart disease, and sudden cardiac death,² and is associated with an increased risk of end-stage renal disease, cognitive decline, and dementia.² The relationship between elevated BP and an increased risk of events is present across a wide spectrum of BP values down to relatively low values.² 

Raised BP is a leading preventable cause of CVD mortality and disease burden around the world,⁴ and is therefore one of the World Health Organization's global targets for the prevention of non-communicable diseases.⁶ 

Hypertension Control Remains a Largely Unmet Challenge for Public Health Systems

A number of evidence-based guidelines on hypertension have been published. Recent updates include: 

• NICE guideline on the diagnosis and management of hypertension in adults (2019, updated March 2022)¹
• European Society of Cardiology/ European Society of Hypertension (ESH) guidelines for the management of arterial hypertension (2018, solo update from the ESH published June 2023)^2,7
• International Society of Hypertension global hypertension practice guidelines (2020)³
• American College of Cardiology/American Heart Association (in collaboration with other US professional and stakeholder organisations) guideline for the prevention, detection, evaluation, and management of high blood pressure (2017).⁸

Although clinical practice guidelines support effective management, variations in recommendations between separate bodies can be confusing, with additional differences for population subgroups adding further complexity.⁹ 

In 2021, Philip et al⁹ investigated the variation in global hypertension guidelines. They found that definition, staging, and target BP were largely consistent across the 48 guidelines studied, but there were extensive differences in recommendations on pharmacological treatment in some patient groups. This complexity can impede clinical management and treatment, and may be one of the reasons that hypertension control remains a largely unmet objective for public health systems.¹⁰ 

Suboptimal diagnosis and treatment are also an issue in hypertension management. A global screening campaign found that significant numbers of people were undiagnosed or untreated, and BP control was achieved for only 60% of those on medication for hypertension.^10,11 Similarly, a survey of 12 high-income countries showed antihypertensive treatment coverage was at best 80%, with rates of BP control less than 70%, even in the best performing countries.¹²

The COVID-19 pandemic has had an additional impact on CVD prevention and management, as highlighted by an investigation of the UK's national medical records of dispensed hypertension medication.^13,14 It noted a marked decline in the number of people initiated on antihypertensive drugs between March 2020 and July 2021, with 491,306 fewer treatment initiations than would have been expected based on 2019 levels.^13,14 It was estimated that this could result in more than 13,000 additional CVD events if these individuals remain untreated over their lifetime.^13,14 Identification and treatment of these people is a priority. 

Recent Meta-analyses Suggest Important Changes to Practice are Needed

Blood Pressure Thresholds for Initiating Treatment Should be Lowered

In 2021, the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) published a paper on pharmacological BP lowering for primary and secondary prevention of CVD across different levels of BP. Individual participant data from 48 randomised controlled trials (RCTs) of BP lowering medications were investigated, with the primary outcome being a major cardiovascular event, encompassing fatal or non-fatal stroke, MI, ischaemic heart disease, and heart failure.¹⁵

The analysis found that a reduction of 5 mmHg in SBP reduced the risk of major cardiovascular events by around 10%. The benefits of treatment were noted irrespective of BP level when initiating therapy, both in participants with previous CVD diagnoses and those with no history of heart disease.¹⁵ It concluded that a fixed degree of pharmacological BP lowering had a similar effect on both primary and secondary prevention of major CVD, and that this occurred at levels not recommended for treatment—investigators therefore concluded that the perception that BP lowering treatment is only effective above a certain threshold is not tenable.¹⁵ 

Implications for Clinical Practice and Guidance 

For primary prevention, most guidelines adhered to in the UK recommend treatment for people with BP of 140/90 mmHg or above.^1–3,8 Guidelines also define the level to which BP should be reduced,^1–3,8 implying that pharmacotherapy below this threshold would be ineffective or detrimental.¹⁵ The meta-analysis study group calls for the recommendations to be revised, on the basis that a fixed and modest decrease leads to similar reductions in the relative risk of cardiovascular events, irrespective of BP at initiation, or presence of CVD.¹⁵ In addition, BP lowering treatment should be considered for anyone at sufficiently high risk of CVD.

As evidence now shows that therapy is as effective at BP levels below 140/90 mmHg as it is above, confining treatment to those above will result in missed treatment opportunities for those just below the cut-off. Clinicians must change their approach from 'hypertension is a disease that requires treatment' to 'blood pressure is a continuous risk factor that requires ongoing management regardless of level'. For people at risk of CVD, pharmacological treatment to lower BP should be a key risk prevention step, irrespective of BP status.¹⁵

NICE updated its hypertension guidance in March 2022,¹ but did not incorporate the findings on equal efficacy above and below 140/90 mmHg.¹⁵ It is likely that the next iteration of the NICE guideline will include a treatment cut-off, which it is hoped will be lowered to 120/70 mmHg, in line with evidence from RCTs.¹⁵ Likewise, all of the other guidelines currently used in clinical practice were published in advance of the meta-analysis, and recommend antihypertensive treatment from the 140/90 mmHg threshold—these also need to be addressed.^2,3,7,8 

Remove Age-related Blood Pressure Thresholds in Current Guidelines 

Older people are often under-represented in clinical trials, and there is a lack of evidence on the use of BP lowering medications, particularly in those whose BP is not substantially raised. When data on benefits versus harms is limited, guidance can differ, and is often cautionary. For example, in people aged more than 80 years with stage 1 hypertension (defined by NICE as clinic BP 140/90–159/99 mmHg), NICE raises the threshold for consideration of antihypertensive drug treatment to 150/90 mmHg or above, and highlights that clinical judgement should be used in those with frailty or multimorbidity.¹

The BPLTTC therefore investigated age- and BP-stratified effects of BP lowering pharmacotherapy on cardiovascular outcomes in a meta-analysis of individual participant level data from 51 RCTs.¹⁶ The primary outcome was a major cardiovascular event. At the time of publication, the study represented the most detailed analysis of BP lowering treatment effect by age.¹⁶ 

It found that event rates were lower in the intervention group than the comparator group at all ages, including those aged 85 years and above.¹⁶ A pharmacological reduction of 5 mmHg in SBP significantly lowered the risk of major cardiovascular events in almost all age groups, including those aged 75–84 years,¹⁶ with diminishing relative risk reductions as age increased (most likely because there were fewer participants at 85 years of age and older); however, absolute risk reductions appeared to be greatest in the oldest age groups, due to a higher rate of cardiovascular events at older ages.¹⁶ 

Implications for Clinical Practice and Guidance 

The study's authors question the emphasis many guidelines place on patients' age or BP when initiating pharmacotherapy.¹⁶ Although the findings for people aged 85 years or older at study entry were less compelling (likely because of smaller numbers of participants), the overall patterns suggest worthwhile reductions in cardiovascular outcomes for all age groups.¹⁶ They conclude that pharmacological BP reduction should be considered an important treatment option for prevention of cardiovascular events in people aged 80 years and above, and guidelines should be simplified by removing age-related thresholds.¹⁶

Other experts agree, and suggest going even further, advocating the removal of all hypertension treatment thresholds above 120/70 mmHg, which they say are likely to be of more harm than benefit if patients at increased cardiovascular risk do not receive effective treatment because they sit below arbitrary thresholds.¹⁷ 

Is Antihypertensive Treatment Suitable for Older People with Multimorbidity and Polypharmacy?

Other under-represented groups for whom evidence is lacking include those with multimorbidity and polypharmacy, and generalisations for these groups are uncertain.¹⁶ The Antihypertensive Treatment Evaluation in Multimorbidity and Polypharmacy Trial investigated the effects of different intensities of antihypertensive medications on changes in BP and safety outcomes in older, home-based patients with multimorbidity and polypharmacy, and the findings were recently presented at the European Society of Hypertension congress (23–26 June 2023, Milan, Italy).¹⁸ 

This was a small study of 230 people with a mean age of 76 years. Participants were randomised to receive up to two more or two fewer classes of antihypertensive medications.¹⁸ The primary outcome was change in home-measured BP and prescribed antihypertensive treatments.¹⁸ 

Mean SBP gradually decreased in the group being given a greater number of antihypertensive drugs, and remained mostly unchanged in those receiving fewer antihypertensive medications;¹⁸ 13 months after randomisation, the mean SBP was 122 mmHg in the group allocated more antihypertensives versus 133 mmHg in the group receiving fewer of them.¹⁸ At the end of the trial, the mean difference in SBP between the cohorts was 11 mmHg. Investigators also noted that the substantial reduction in BP to 122 mmHg was not associated with an increased risk of serious adverse events.¹⁸ Although dizziness and fatigue were more common in those prescribed more antihypertensives, this did not translate into a change in health-related quality of life, cognitive function, or frailty scores.

These findings add further weight to the argument that older people, including those with multimorbidity and polypharmacy, should not be denied access to antihypertensive medication based on arbitrary thresholds, or for fear of serious adverse events. A larger trial in older people with multimorbidity and polypharmacy is planned.¹⁸ 

Presence of Type 2 Diabetes Should not Affect Blood Pressure Thresholds

The BPLTTC has also examined whether the threshold for BP lowering treatment should differ between people with and without type 2 diabetes.¹⁹ Guidelines invariably distinguish between these patients, and define different thresholds and targets for treatment of hypertension in the presence of diabetes, with patient age also a factor.² A meta-analysis of data from 51 RCTs—the primary outcome of which was the risk of developing a major cardiovascular event—found that a reduction in SBP of 5 mmHg decreased the risk of major cardiovascular events in both cohorts.¹⁹ A weaker relative treatment effect was noted in those with type 2 diabetes; however, absolute risk reductions did not differ substantially between the two groups, because participants with type 2 diabetes had a higher absolute cardiovascular risk.¹⁹ 

Implications for Clinical Practice and Guidance 

The study concluded that adopting different BP thresholds, intensities of BP lowering, or drug classes between people with and without type 2 diabetes is not warranted.¹⁹ 

Reducing Blood Pressure is an Effective Strategy for Prevention of New-onset Type 2 Diabetes

Can a decrease in BP also contribute to the prevention of new-onset type 2 diabetes? A BPLTTC meta-analysis investigated this proposition, analysing data from 19 RCTs,²⁰ and found that a 5 mmHg reduction in SBP reduced the risk of type 2 diabetes across all trials by 11%.²⁰ Further analysis from 22 trials comparing the effects of five classes of antihypertensive drugs with placebo highlighted that angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor II blockers (ARBs) had the strongest protective effect, resulting in a 16% reduction in a person's relative risk of developing diabetes.²⁰ 

Implications for Clinical Practice and Guidance 

Current clinical guidelines do not provide clear recommendations on BP lowering as a strategy for type 2 diabetes prevention.²⁰ Clinicians should consider the protective effect of selected classes of antihypertensive medications—specifically, ACE inhibitors and ARBs—which may reduce a person's risk of developing type 2 diabetes.²⁰ 

Conclusion

Treatment thresholds in clinical guidelines for initiating medications to lower BP are currently too high and, based on recent meta-analyses, should be reduced to a starting BP of 120/70 mmHg for people at high risk of CVD. Age and a BP measurement that is above this threshold should not be barriers to prescribing effective treatments, such as antihypertensive medications: there is now clear evidence to support the effectiveness of reducing BP for older people, even when levels are not substantially raised. The decision on starting treatment will depend on individual risk factors for CVD, potential side effects, and patient choice.