Hypertension is the most important single modifiable risk factor for cardiovascular disease prevention. An estimated 1.28 billion adults aged 30–79 years have hypertension worldwide.1 Around 16 million adults in the UK suffer with hypertension, which is roughly a third of the adult population.2 The benefits of lowering blood pressure (BP) are firmly established down to 140/90 mmHg. More recently, several randomised-controlled trials (RCTs) have assessed the benefits of lowering targets further to <120 mmHg systolic. ACCORD, SPRINT, RESPECT, ESPRIT and BPROAD RCTs compared a systolic blood pressure (SBP) target of <120 mmHg versus <140 mmHg.3–7 The ACCORD trial recruited patients with diabetes, and RESPECT recruited patients with stroke.3,4 Both of these RCTs demonstrated no significant difference in their pre-specified primary outcomes of major cardiovascular events in ACCORD, and recurrence of stroke in RESPECT. The ACCORD trial found more serious adverse events with intensive BP targeting, and the RESPECT trial ended early due to slow recruitment and funding.3,4 Both had a relatively small number of participants, which may have contributed to the negative result seen in these studies.
SPRINT, ESPRIT and BPROAD were three large RCTs with 9,361, 11,255 and 12,821 participants, respectively, that support a more intensive SBP target closer to 120 mmHg.5–7 These trials recruited patients ≥50 years old at high cardiovascular risk with SBP 130–180 mmHg.5–7 The primary composite outcome in all three trials focused on similar major cardiovascular outcomes: myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, coronary or non-coronary revascularisation, stroke, decompensated heart failure or death from cardiovascular causes. The mean SBP achieved in SPRINT, ESPRIT and BPROAD trials (intensive vs. standard groups) were 121.4 vs. 136.2 mmHg, 119.1 vs. 134.8 mmHg, and 121.6 vs. 133.2 mmHg, respectively.5–7 All three trials demonstrated significant benefit from intensive BP reduction, with hazard ratios of 0.73 (95% confidence interval [CI] 0.63 to 0.86) in SPRINT, 0.88 (95%CI 0.78 to 0.99) in ESPRIT and 0.79 (95%CI 0.69 to 0.90) in BPROAD.5–7 There was no significant difference in the overall number of serious adverse events between the two groups in the three trials. Serious adverse events were defined as events that were fatal, life-threatening, caused hospitalisation or resulted in significant harm to participants. However, there was an increased incidence of symptomatic hypotension in the intensive treatment group in SPRINT (99 vs. 58 participants) and BPROAD (8 vs. 1 participants).5,7 Electrolyte abnormalities and acute kidney injury/acute renal failure were also more common in the intensive treatment arm of the SPRINT trial (138 vs. 104 participants and 193 vs. 115 participants, respectively).5 In ESPRIT, syncope was more common in the intensive treatment group (24 vs. 8 participants).6 The absolute numbers affected by serious adverse events were low in all three trials, indicating that lowering SBP to ~120 mmHg was generally safe.
Achieving target
SPRINT and BPROAD both just failed to achieve the pre-defined systolic target of <120 mmHg, whereas ESPRIT achieved this with a mean SBP of 119.1 mmHg. This demonstrates that reaching a lower target can be challenging. SPRINT used unattended blood pressures, whereas ESPRIT and BPROAD used attended office BP measurements, similar to those used in ACCORD and RESPECT trials.5–7 However, BPROAD also used home BP measurements to adjust antihypertensives during the COVID-19 pandemic.7 Instruction videos and a BP monitor were provided to take accurate measurements at home.7 Generally, unattended and home BP is 5–10 mmHg lower than the corresponding clinic BP. Although ESPRIT was conducted partly during the COVID-19 pandemic, they still relied on office BP measurements with longer time duration to reach BP targets.6 We can conclude that all three studies demonstrate safe reduction of systolic BP to <130 mmHg, to allow for real-world discrepancies in BP measurements, and the difficulties that are faced in many healthcare settings where very close monitoring cannot be provided to avoid side effects seen in current studies.
Guidelines
Concerns about potential serious adverse events caused by stricter BP targets have led some guideline committees to not recommend specific targets below 140 mmHg. Indeed, current National Institute for Health and Care Excellence (NICE) guidelines, updated in 2023, advocate for a clinic BP target of <140/90 mmHg in patients under 80 years.8 There is a tighter target of <130/80 mmHg in those with type 1 diabetes or chronic kidney disease (CKD) and a urine albumin to creatinine ratio (ACR) of ≥70 mg/mmol. In patients ≥80 years old, a clinic BP target of <150/90 mmHg is advocated, with a stricter target of <140/90 mmHg in patients with CKD and urine ACR <70 mg/mmol, and <130/80 mmHg with CKD and urine ACR of ≥70 mg/mmol. The current guideline also advocates for patients with significant postural drops, or symptoms of postural hypotension, to be treated to a BP target based on standing blood pressure.8
The latest European Society of Cardiology (ESC) guidelines, published August 2024, continue to define hypertension as a clinic SBP of ≥140 mmHg or diastolic BP of ≥90 mmHg. A new category of ‘elevated BP’ was also introduced, and includes a clinic SBP of 120–139 mmHg or diastolic BP of 70–89 mmHg.9 Drug therapy is not indicated for everyone in this ‘elevated BP’ category, but considered when the cardiovascular disease risk is high. In patients with hypertension, the aim set by the ESC is to lower BP to a systolic of 120–129 mmHg, where this is tolerated.9 The same SBP target of 120–129 mmHg is recommended in patients with diabetes or moderate-to-severe CKD (with estimated glomerular filtration rate [eGFR] >30 ml/min/1.73 m2) or history of stroke or transient ischaemic attack (TIA).9 There is a more lenient target in patients with symptomatic orthostatic hypotension, those who are 85 years and above, frail or have limited life-expectancy, where a BP as low as reasonably achievable is the aim. A target range of SBP 120–129 mmHg was set, rather than a fixed target, to allow flexibility for patients and clinicians, as there is difficulty in measuring BP in a controlled or systematic way, as it would have been done in the RCTs.9 These guidelines were influenced primarily by STEP, SPRINT and ESPRIT trials, as well as meta-analyses of several studies.5,6,10,11
Conclusion
In conclusion, if patients are able to tolerate a lower BP target it will bring benefit and reduce the overall risk of major adverse cardiovascular events. We will need to personalise the approach to BP control to achieve this. A practical SBP target of <130 mmHg seems to be safe, based on current RCT evidence.
Conflicts of interest
None declared.
Funding
None.
References
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8. National Institute for Health and Care Excellence. Hypertension in adults: diagnosis and management. NG136. London: NICE, 2023. Available from: https://www.nice.org.uk/guidance/ng136/chapter/Recommendations#monitoring-treatment-and-blood-pressure-targets
9. McEvoy JW, McCarthy CP, Bruno RM et al.; ESC Scientific Document Group. 2024 ESC guidelines for the management of elevated blood pressure and hypertension. Eur Heart J 2024;45:3912–4018. https://doi.org/10.1093/eurheartj/ehae178
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