Prognostic Value of Variability in Systolic Blood Pressure Related to Vascular Events and Premature Death in Type 2 Diabetes Mellitus: The ADVANCE-ON Study

Toshiaki Ohkuma, Mark Woodward, Min Jun, Paul Muntner, Jun Hata, Stephen Colagiuri, Stephen Harrap, Giuseppe Mancia, Neil Poulter, Bryan Williams, Peter Rothwell, John Chalmers, ADVANCE Collaborative Group

Research output: Contribution to journalArticlepeer-review


Visit-to-visit variability in systolic blood pressure (SBP) is a risk factor for cardiovascular events. However, whether it provides additional predictive information beyond traditional risk factors, including mean SBP, in the long term is unclear. The ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) was a randomized controlled trial in patients with type 2 diabetes mellitus; ADVANCE-ON (ADVANCE-Observational) followed-up patients subsequently. In these analyses, 9114 patients without major macrovascular or renal events or death during the first 24 months were included. Data on SBP from 6 visits during the first 24 months after randomization were used to estimate visit-to-visit variability in several ways: the primary measure was the standard deviation. Events accrued during the following 7.6 years. The primary outcome was a composite of major macrovascular and renal events and all-cause mortality. Standard deviation of SBP was log-linearly associated with an increased risk of the primary outcome (P<0.001) after adjustment for mean SBP and other cardiovascular risk factors. The hazard ratio (HR; 95% confidence interval [CI]) in the highest, compared with the lowest, tenth of the standard deviation was 1.39 (1.15-1.69). Results were similar for major macrovascular events alone and all-cause mortality alone (both P<0.01). Addition of standard deviation of SBP significantly improved 8-year risk classification (continuous net reclassification improvement, 5.3%). Results were similar for other measures of visit-to-visit variability, except maximum SBP. Visit-to-visit variability in SBP is an independent predictor of vascular complications and death, which improves risk prediction beyond that provided by traditional risk factors, including mean SBP.

Original languageEnglish
Pages (from-to)461-468
Number of pages8
Issue number2
Publication statusPublished - Aug 2017


  • Aged
  • Analysis of Variance
  • Antihypertensive Agents
  • Blood Pressure
  • Cardiovascular Diseases
  • Diabetes Mellitus, Type 2
  • Female
  • Humans
  • Hypertension
  • Male
  • Middle Aged
  • Mortality, Premature
  • Outcome and Process Assessment (Health Care)
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Journal Article
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't


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