SBP variability is a stronger predictor of CV events than mean SBP


Long-term follow-up of ASCOT-BPLA showed systolic blood pressure (SBP) variability was a strong predictor of CV outcomes independent of mean SBP, even in patients with well-controlled SBP. Additionally, amlodipine-based treatment reduced the risk of CV events compared with atenolol-based treatment.

This summary is based on the publication of Gupta A, Whiteley WN, Godec T, et al. - Legacy benefits of blood pressure treatment on cardiovascular events are primarily mediated by improved blood pressure variability: the ASCOT trial. Eur Heart J. 2024 Jan 31:ehad814 [Online ahead of print]. doi: 10.1093/eurheartj/ehad814

Introduction and methods


Observational studies have demonstrated blood pressure variability (BPV) is an important predictor of morbidity and mortality [1,2]. However, it is unclear what the long-term effect of a period of pharmacological BP control but with possible BPV is, as indicated by the results of the ASCOT-BPLA (Anglo-Scandinavian Cardiac Outcomes Trial–Blood Pressure-Lowering Arm) trial [3-7].

Aim of the study

In the ASCOT Legacy study, a long-term follow-up study of the ASCOT-BPLA trial, the authors investigated the impact of in-trial visit-to-visit systolic BPV and mean systolic BP (SBP) on long-term fatal and nonfatal CV outcomes. They also compared the time to first occurrence of prespecified CV events between 2 antihypertensive treatment strategies.


In the original ASCOT-BPLA trial, 19,257 patients with hypertension aged 40–79 years at randomization who had ≥3 additional CVD risk factors but no history of prior coronary heart disease (CHD) events, currently treated angina, stroke, or TIA within 3 months were randomized to a amlodipine-based (amlodipine plus perindopril if necessary) or atenolol-based (atenolol plus bendroflumethiazide if necessary) treatment strategy. The trial was stopped prematurely in December 2004 (after a median follow-up duration of 5.5 years) at the recommendation of the Data Safety and Monitoring Board because of a significantly higher mortality rate in patients allocated to the atenolol-based treatment compared with those receiving amlodipine-based treatment.

In the ASCOT Legacy study, 8580 participants from the UK (4305 assigned to amlodipine-based treatment strategy and 4275 to atenolol-based treatment strategy) were followed up for a median duration of 17 years (IQR: 9–19; maximum: 21), using linked hospital and mortality records. Data of 7092 participants with completed records were available for the post-trial analysis.


Prespecified CV events were: fatal and nonfatal stroke, nonfatal MI and fatal CHD, total coronary events, fatal and nonfatal HF, total CV events and procedures, AF, CV death, and all-cause mortality.

Main results

Impact of in-trial systolic BPV and mean SBP on later CV events

  • In an analysis adjusted for baseline confounders and occurrence of stroke or MI historically or during the trial up to the post-trial period, the mean in-trial SBP was a predictor of post-trial long-term CV outcomes, including total CV events (adjusted HR: 1.14; 95%CI: 1.10–1.17; P<0.001), total stroke (adjusted HR: 1.19; 95%CI: 1.11–1.26; P<0.001), nonfatal MI and fatal CHD (adjusted HR: 1.19; 95%CI: 1.12–1.27; P<0.001), and CV death (adjusted HR: 1.22; 95%CI: 1.16–1.29; P<0.001), for each 10.0 mmHg of SD increase in mean SBP.
  • Further adjustment for mean in-trial SBP indicated visit-to-visit systolic BPV was a stronger predictor of CV outcomes (per 5.0 mmHg of SD rise in systolic BPV), such as total CV events (adjusted HR: 1.22; 95%CI: 1.18–1.26; P<0.001), total stroke (adjusted HR: 1.20; 95%CI: 1.11–1.29; P<0.001), nonfatal MI and fatal CHD (adjusted HR: 1.25; 95%CI: 1.16–1.35; P<0.001), and CV death (adjusted HR: 1.28; 95%CI: 1.20–1.37; P<0.001).
  • In the group with mean in-trial SBP <140 mmHg, patients in the highest third of systolic BPV (13.00–50.06 mmHg) showed an absolute increase in CV events of 16% (17 events per 1000 patient-years) compared with the lowest third (1.15–9.30 mmHg) over the 15-year post-trial follow-up period. Moreover, 53% of all CV events occurred in patients with well-controlled SBP (i.e., <140 mmHg; this comprised 44% of trial population).
  • Patients with mean SBP <133 mmHg over a 5-year period had a 31% increased risk of total CV events if their systolic BPV ranged from 9.31 to 12.99 mmHg and a 65% excess risk if systolic BPV was 13.00–50.06 mmHg.

Effect of antihypertensive treatments on first CV events

  • Analysis of the maximum 21-year follow-up data showed that in-trial amlodipine-based treatment was associated with a reduced risk of stroke (adjusted HR: 0.82; 95%CI: 0.72–0.93; P=0.003), total CV events (adjusted HR: 0.93; 95%CI: 0.88–0.98; P=0.008), total coronary events (adjusted HR: 0.92; 95%CI: 0.86–0.99; P=0.024), and AF (adjusted HR: 0.91; 95%CI: 0.83–0.99; P=0.030) compared with the atenolol-based treatment strategy.
  • There was weaker evidence for a decreased risk of CV death (adjusted HR: 0.91; 95%CI: 0.82–1.01; P=0.073), and no significant differences in the incidence of nonfatal MI and fatal CHD, total HF, and all-cause mortality were found between treatments (all P>0.05).


In this long-term (up to 21 years) follow-up study of the ASCOT-BPLA trial, in-trial systolic BPV was a strong predictor of CV outcomes independent of mean SBP, even in patients with well-controlled SBP but high systolic BPV. In addition, an amlodipine-based treatment strategy during the trial was associated with reduced risks of total CV events, stroke, coronary events, and AF compared with atenolol-based treatment.

The authors point out that “[t]he original results of ASCOT-BPLA influenced national and international guidelines for hypertension. The current observations extend the benefits reported in the trial for the amlodipine-based treatment regimen and highlight the increasing importance of visit-to-visit systolic BPV in the prediction of long-term CV outcomes.”

Find this article online at Eur Heart J.


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2. Stevens SL, Wood S, Koshiaris C, Law K, Glasziou P, Stevens RJ, et al. Blood pressure variability and cardiovascular disease: systematic review and meta-analysis. BMJ 2016;354:i4098.

3. Dahlöf B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005;366:895–906.

4. Poulter NR, Wedel H, Dahlöf B, Sever PS, Beevers DG, Caulfield M, et al. Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA). Lancet 2005;366:907–13.

5. Rothwell PM, Howard SC, Dolan E, O’Brien E, Dobson JE, Poulter NR, et al. Effects of β-blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke. Lancet Neurol 2010;9:469–80.

6. Gupta A, Mackay J, Whitehouse A, Godec T, Collier T, Pocock S, et al. Long-term mortality after blood pressure-lowering and lipid-lowering treatment in patients with hypertension in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Legacy study: 16-year follow-up results of a randomised factorial trial. Lancet 2018;392:1127–37.

7. Whiteley WN, Gupta AK, Godec T, Rostamian S, Whitehouse A, Mackay J, et al. Long-term incidence of stroke and dementia in ASCOT. Stroke 2021;52:3088–96.

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