Physicians' Academy for Cardiovascular Education

Blood pressure variability predicts CV events in diabetes type II

Literature - Hata et al., Circulation Sept 2013 - Circulation. 2013 Sep 17;128(12):1325-34


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

1. Chobanian AV, Bakris GL, Black HR, et al.; Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206–1252.
2. Mancia G, De Backer G, Dominiczak A, et al.; Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007;25:1105–1187.
3. Diabetes Australia Guideline Development Consortium. National Evidence Based Guidelines for the Management of Type 2 Diabetes Mellitus: Blood Pressure Control in Type 2 Diabetes. National Health and Medical Research Council (Australia). http://www.nhmrc.gov.au/guidelines/ publications/subject/Diabetes Accessed on August 3, 2012.
4. Rothwell PM, Howard SC, Dolan E, et al. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet. 2010;375:895–905.
5. Rothwell PM. Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension. Lancet. 2010;375:938–948.
6. Stehouwer CD, Henry RM, Ferreira I. Arterial stiffness in diabetes and the metabolic syndrome: a pathway to cardiovascular disease. Diabetologia. 2008;51:527–539.
7. Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic autonomic neuropathy. Diabetes Care. 2003;26:1553–1579.
8. ADVANCE Management Committee. Study rationale and design of ADVANCE: Action in Diabetes and Vascular Disease-Preterax and Diamicron MR Controlled Evaluation. Diabetologia. 2001;44:1118–1120.
9. ADVANCE Collaborative Group. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007;370:829–840.
10. ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560–2572.                              
 

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