Physicians' Academy for Cardiovascular Education

Association between cumulative systolic blood pressure load and MACE in T2DM

Cumulative Systolic Blood Pressure Load and Cardiovascular Risk in Patients With Diabetes

Literature - Wang N, Harris K, Hamet P, et al. - J Am Coll Cardiol. 2022 Sep 20;80(12):1147-1155. doi: 10.1016/j.jacc.2022.06.039

Introduction and methods


As standard measures of blood pressure (BP) do not acknowledge that BP fluctuates over time, the most recently recorded BP measurement may not reflect previous BP control. Therefore, a measure that accounts for both the magnitude and duration of exposure to elevated BP is needed. An example of such a measure is the cumulative BP load, which has been associated with target organ damage [1].

Previously, the effects of BP lowering and intensive blood glucose–lowering treatment on vascular outcomes were evaluated in patients with T2DM in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron - Modified Release Controlled Evaluation) trial [2-4].

Aim of the study

The authors sought to assess the association between the cumulative systolic BP (SBP) load over 24 months and the occurrence of MACE in the ADVANCE trial and its post-trial follow-up study, ADVANCE-ON.


The ADVANCE trial was an international, 2 × 2 factorial RCT in which 11,140 T2DM patients at high risk of CV events were randomly assigned to either perindopril/indapamide 4 mg/1.25 mg or matching placebo and to either an intensive glucose control regimen based on gliclazide modified release (aiming to achieve HbA1c ≤6.5%) or standard glucose control based on local guidelines of participating countries. Post-trial follow-up data were obtained from 8494 patients of a total of 10,082 patients who were alive when the randomized treatment phase of the ADVANCE trial was completed [5].

For the current post-hoc analysis, data from 9338 patients with SBP measures at 3, 4, 6, 12, 18, and 24 months were collected. Based on BP measurements at these 6 clinic visits, cumulative SBP load, mean BP, SBP TITRE, and visit-to-visit variability in SBP were calculated. Cumulative SBP load was defined as the area under the curve (AUC) for SBP values ≥130 mmHg divided by the AUC for all measured SBP values. SBP TITRE (TIme at TaRgEt) was calculated as the percentage of time a patient spent at SBP target (defined as <130 mmHg) over the exposure period. Visit-to-visit variability in SBP was calculated as the SD of the SBP values at the 6 clinic visits.


The primary endpoint was MACE, defined as the composite outcome of CV death, nonfatal MI, and nonfatal stroke. Secondary endpoints were components of the primary endpoint and all-cause mortality.

Main results

Effects of SBP measures on CV outcomes

Independent association of cumulative SBP load or visit-to-visit variability in SBP with CV outcomes

Prognostic value of SBP measures compared with traditional CVD risk factors


In a post-hoc analysis of the ADVANCE trial and its follow-up study, a higher cumulative SBP load was associated with CV events and death in T2DM patients independent of traditional CVD risk factors. Cumulative SBP load was a independent predictor of CV events. In addition, cumulative SBP load was a better predictor of MACE than mean SBP, SBP TITRE, or visit-to-visit variability in SBP.

As cumulative SBP load encompasses both duration (similar to SBP TITRE) and magnitude (similar to mean SBP) of SBP exposure, the authors believe their study “reinforces not only the importance of treating the degree of SBP elevation, but also the need for early intervention to minimize the duration of elevated SBP exposure.”


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Find this article online at J Am Coll Cardiol.

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