Addition of SBP variability improves risk stratification of diabetic patients

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

Literature - Ohkuma T, Woodward M, Jun M, et al. - Hypertension. 2017;70: published online ahead of print


All CVD risk scores include a BP factor that is prone to visit-to-visit variability (VVV) [1,2]. Moreover, increased BP variability is a risk factor for macrovascular and microvascular events and death itself, independently of other CV risk factors [3].

In this analysis of the ADVANCE study, the long-term impact of SBP variability and its predictive ability for vascular complications and mortality was assessed, in T2DM patients. The primary outcome was the composite of MI, stroke, CV death, requirement for chronic renal-replacement therapy, death from renal disease or all-cause mortality.

Main results

  • During a median of 7.6 years of follow-up, 1476 patients developed a major macrovascular event, 122 experienced a major renal event, and there were 1550 deaths.
  • The risk of the primary outcome increased log-linearly with increasing SBP SD after adjustment for mean SBP and other CV risk factors (P for trend <0.001). The highest tenth associated with a 39% greater risk of the primary outcome compared with the lowest tenth (HR: 1.39; 95% CI: 1.15–1.69).
  • Similar statistically significant adjusted trends were observed for all-cause mortality (P for trend <0.001) and major macrovascular events (P for trend =0.007). The corresponding HRs for the highest tenth compared with the lowest tenth of SBP SD were 1.67 (95% CI: 1.31–2.14) and 1.17 (95% CI: 0.92–1.49), respectively.
  • After adjustment for mean SBP and other CV risk factors, there was no statistically significant trend in the risk of either CV death or major renal events (P values were 0.07 and 0.11, respectively). However, in both cases, there was a statistically significant difference between the extreme tenths: the HRs for the highest tenth compared with the lowest tenth were 1.53 (95% CI: 1.001–2.33) and 2.97 (95% CI: 1.10–8.01), respectively.
  • For MI and stroke, there was no evidence of either a trend (P values were 0.13 and 0.33, respectively) or a difference in risk between those in the top and bottom 10% of the distribution of SDs (HR: 1.08; 95% CI: 0.72–1.63, and 1.08; 95% CI: 0.77–1.53, respectively).
  • For the primary outcome, the addition of SBP SD to the model with established CV risk factors, including mean SBP, significantly improved the C statistic (from 0.6459 to 0.6499; P=0.003).
  • For macrovascular disease and death, the discrimination of events was significantly improved by adding SBP SD to the prediction model.
  • For major renal disease, the change in C statistic was not statistically significant.


In diabetic patients, the SBP visit-to-visit variability is an independent predictor of vascular complications and death, which improves the predictive ability of traditional risk factors, including mean SBP. These results support the use of SBP variability for individual risk stratification, and they suggest that the reduction of SBP variability may be an important therapeutic target in these patients.


1. Kannel WB, McGee D, Gordon T. A general cardiovascular risk profile: the Framingham Study. Am J Cardiol. 1976;38:46–51.

2. Ueda P, Woodward M, Lu Y, et al. Laboratory-based and office-based risk scores and charts to predict 10-year risk of cardiovascular disease in 182 countries: a pooled analysis of prospective cohorts and health surveys. Lancet Diabetes Endocrinol. 2017;5:196–213.

3. Hata J, Arima H, Rothwell PM, et al; ADVANCE Collaborative Group. Effects of visit-to-visit variability in systolic blood pressure on macrovascular and microvascular complications in patients with type 2 diabetes mellitus: the ADVANCE trial. Circulation. 2013;128:1325–1334.

Find this article online at Hypertension

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