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Observational Study
. 2022 Sep 20;80(12):1147-1155.
doi: 10.1016/j.jacc.2022.06.039.

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

Nelson Wang  1 , Katie Harris  2 , Pavel Hamet  3 , Stephen Harrap  4 , Giuseppe Mancia  5 , Neil Poulter  6 , Bryan Williams  6 , Sophia Zoungas  7 , Mark Woodward  2 , John Chalmers  8 , Anthony Rodgers  2
Affiliations
Free article
Observational Study

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

Nelson Wang et al. J Am Coll Cardiol. .
Free article

Abstract

Background: Standard measures of blood pressure (BP) do not account for both the magnitude and duration of exposure to elevated BP over time.

Objectives: The purpose of this study was to assess the association between cumulative systolic blood pressure (SBP) load and risk of cardiovascular events in patients with type 2 diabetes.

Methods: A post hoc analysis of patients with type 2 diabetes followed by the ADVANCE-ON (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation - Observational Study). Cumulative SBP load was defined as the area under curve for SBP values ≥130 mm Hg divided by the area under curve for all measured SBP values over a 24-month exposure period. HRs for the association between cumulative SBP load with major cardiovascular events and death were estimated using Cox models.

Results: Over a median 7.6 years of follow-up, 1,469 major cardiovascular events, 1,615 deaths, and 660 cardiovascular deaths were observed in 9,338 participants. Each 1-SD increase in cumulative SBP load was associated with a 14% increase in major cardiovascular events (HR: 1.14; 95% CI: 1.09-1.20), 13% increase in all-cause mortality (HR: 1.13; 95% CI: 1.13-1.18), and 21% increase in cardiovascular death (HR: 1.21; 95% CI: 1.13-1.29). For the prediction of cardiovascular events and death, cumulative SBP load outperformed mean SBP, time-below-target SBP, and visit-to-visit SBP variability in terms of Akaike information criterion and net reclassification indexes.

Conclusions: Cumulative SBP load may provide better prediction of major cardiovascular events compared with traditional BP measures among patients with type 2 diabetes. These findings reinforce the importance of both the magnitude and duration of exposure to elevated SBP in assessing cardiovascular risk. (Action in Diabetes and Vascular Disease Preterax and Diamicron MR Controlled Evaluation Post Trial Observational Study [ADVANCE-ON]; NCT00949286).

Keywords: blood pressure; diabetes mellitus; prevention.

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Conflict of interest statement

Funding Support and Author Disclosures Dr Mancia has received honoraria from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Medtronic, Menarini, Merck, Novartis, Recordati, Sandoz, Sanofi and Servier; and has received personal fees from Boehringer Ingelheim, Daiichi-Sankyo, Ferrer, Medtronic, Menarini International, Merck, Novartis, Recordati, and Servier outside the submitted work. Dr Poulter has received personal speaker fees from Servier, Takeda, and Novo Nordisk; has performed advisory board activities from AstraZeneca and Novo Nordisk; and has received grants for his research group relating to diabetes mellitus from Diabetes UK, National Institute for Health and Care Research Efficacy and Mechanism Evaluation Programme (EME), Julius Clinical and the British Heart Foundation, with a pending grant from Novo Nordisk. Dr Williams has received honoraria from Servier for lectures. Dr Zoungas has received fees from Sanofi, AstraZeneca, Novo Nordisk, and Merck Sharp & Dohme Australia outside of the submitted work. Dr Woodward has received consultancy fees from Amgen and Kirin; and is supported by NHMRC grants APP1149987 and APP1174120. Dr Chalmers has received research grants from the National Health and Medical Research Council (NHMRC) and from Servier for the ADVANCE trial and ADVANCE-ON post-trial follow-up; has received honoraria for speaking about these studies at scientific meetings; has received a research grant from Idorsia for the SPIRIT study of Resistant Hypertension; and has received support from NHMRC Program Grant (APP1149987). Dr Rodgers is one of the inventors on several patents filed by The George Institute for Global Health on Compositions for the Treatment of Hypertension; none of the inventors have a financial interest in these planned products; is seconded to work for George Health Enterprises (the social enterprise arm of The George Institute for Global Health); has received investment to develop fixed-dose combination products containing aspirin, statin, and BP-lowering drugs; and sits on a Data and Safety Monitoring Board for Idorsia. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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