Effects of blood pressure lowering on cardiovascular events, in the context of regression to the mean: A systematic review of randomized trials

Abdul Salam, Emily Atkins, Johan Sundström, Yoichiro Hirakawa, Dena Ettehad, Connor Emdin, Bruce Neal, Mark Woodward, John Chalmers, Eivind Berge, Salim Yusuf, Kazem Rahimi, Anthony Rodgers, Blood Pressure Lowering Treatment Trialists’ Collaboration

Research output: Contribution to journalReview articlepeer-review

35 Citations (Scopus)


Objective:To assess the clinical relevance of regression to the mean for clinical trials and clinical practice.Methods:MEDLINE was searched until February 2018 for randomized trials of BP lowering with over 1000 patient-years follow-up per group. We estimated baseline mean BP, follow-up mean (usual) BP amongst patients grouped by 10mmHg strata of baseline BP, and assessed effects of BP lowering on coronary heart disease (CHD) and stroke according to these BP levels.Results:Eighty-six trials (349488 participants), with mean follow-up of 3.7 years, were included. Most mean BP change was because of regression to the mean rather than treatment. At high baseline BP levels, even after rigorous hypertension diagnosis, downwards regression to the mean caused much of the fall in BP. At low baseline BP levels, upwards regression to the mean increased BP levels, even in treatment groups. Overall, a BP reduction of 6/3mmHg lowered CHD by 14% (95% CI 11-17%) and stroke by 18% (15-22%), and these treatment effects occurred at follow-up BP levels much closer to the mean than baseline BP levels. In particular, more evidence was available in the SBP 130-139mmHg range than any other range. Benefits were apparent in numerous high-risk patient groups with baseline mean SBP less than 140mmHg.Conclusion:Clinical practice should focus less on pretreatment BP levels, which rarely predict future untreated BP levels or rule out capacity to benefit from BP lowering in high cardiovascular risk patients. Instead, focus should be on prompt, empirical treatment to maintain lower BP for those with high BP and/or high risk.

Original languageEnglish
Pages (from-to)16-23
Number of pages8
JournalJournal of Hypertension
Issue number1
Publication statusPublished - Jan 2019
Externally publishedYes


  • antihypertensive therapy
  • blood pressure
  • coronary heart disease
  • regression to the mean
  • stroke
  • systematic review


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