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.

Hata J, Arima H, Rothwell PM, et al.; ADVANCE Collaborative Group.
Circulation. 2013 Sep 17;128(12):1325-34. doi: 10.1161/CIRCULATIONAHA.113.002717

Background

Elevated blood pressure (BP) is a major modifiable risk factor for macrovascular disease in patients with diabetes mellitus. Guidelines recommend diagnostic and therapeutic approaches in these patients based on an average of BP over a given time period [1-3]. However, it has recently been published that visit-to-visit variability in systolic BP (SBP) and maximum SBP are independently associated with future risk of stroke and other cardiovascular (CV) events, in patients with previous transient ischemic attack or stroke [4]. Episodic peaks in BP might be important in short-term triggering of vascular events [5].
Arterial stiffness and abnormal autonomic function, both common complications of diabetes, may contribute to increased  variability of BP [6,7]. It is as yet unclear how visit-to-visit BP variability and maximum SBP may affect the risk of macrovascular and microvascular complications in patients with type 2 diabetes mellitus. This study therefore aimed to assess this by analysing data from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial [8-10]. Visit-to-visit variability in SBP was defined by using standard deviation (SD) and coefficient of variation (CV, defined as SD/mean), based on observations on 6 measure occasions.

Main results

• Risk of major macrovascular and microvascular events  (primary outcome) and all-cause mortality rose progressively (statistically significant trend) with higher SBP SD, even after correction for mean SBP and other CV risk factors.
• Multivariable-adjusted HR for the highest as compared to the lowest SD group was 1.69 (95%CI: 1.24-2.31) for macro- and microvascular events and 2.08 (95%CI: 1.30-3.31) for all-cause mortality.
• Higher maximum SBP was significantly associated with risk of the combined primary outcomes, major macrovascular events and all-cause mortality (all significant trends).
• Multivariable-adjusted HRs in the highest maximum SBP group were 2.68 (95% CI:1.57–4.59) for the combined primary outcomes, 3.64 (95% CI: 1.73–7.66) for macrovascular events, 2.18 (95% CI: 1.04–4.58) for microvascular events, and 2.44 (95% CI: 1.14–5.23) for all-cause mortality.
• Sensitivity analyses showed that the effects of SD and maximum SBP on risk of combined macro- and microvascular outcomes events were similar in patients with and without changes in BP-lowering medication.
• SD and maximum SBP were positively associated with all-cause mortality, while mean SBP was not.

Conclusion

This study shows that visit-to-visit SBP variability is positively associated with the risk of major macrovascular and microvascular events and mortality, even after correction for mean SBP, other CV risk factors and randomised treatments. Similar observations were seen for maximum SBP.
Thus, also in patients with type 2 diabetes, visit-to-visit variability in and maximum SBP are predictive of macrovascular and microvascular complications and of mortality.

References

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