Effects of glucose and blood pressure reduction on subclinical cardiac damage: Results from ADVANCE

Abstract

Objective: Observational data suggest a potential for subclinical cardiac damage from intensive blood glucose or blood pressure (BP) control, particularly in adults with very low blood glucose and BP levels. However, this has not been tested in a randomized trial.

Methods: The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Research Controlled Evaluation (ADVANCE) study was a factorial, randomized trial designed to test the effects of intensive blood glucose (hemoglobin A1c ≤6.5% versus usual care) and intensive BP (combination of perindopril-indapamide versus placebo) control on vascular events in adults with diabetes. Using mixed effects tobit models, we determined the effect of the randomized interventions on change in subclinical cardiac injury (high sensitivity cardiac troponin T [hs-cTnT]) and strain (N-terminal b-type pro natriuretic peptide [NT-proBNP]), 1 year after randomization.

Results: Among the 682 participants, mean age was 66.1 (SD, 6.5) years; 40% were women. Mean baseline hemoglobin A1c was 7.4% (SD, 1.5) and systolic/diastolic BP was 147 (SD,21)/81 (SD,11) mmHg. After 1 year, intensive versus standard glucose control did not significantly change hs-cTnT (1.5%; 95%CI:-4.9,8.2) or NT-proBNP (-10.3%; 95%CI: -20.2%,0.9%). Intensive versus standard BP control also did not affect hs-cTnT (-2.9%; 95%CI: -8.9,3.6), but did significantly lower NT-proBNP by 21.6% (95%CI:-30.2%,-11.9%). Changes in systolic BP at 1 year (versus baseline) were strongly associated with NT-proBNP (P = 0.004), but not hs-cTnT (P = 0.95).

Conclusions: In adults with diabetes, intensive BP control reduced NT-proBNP without increasing hs-cTnT, supporting the benefits and safety of intensive BP control in adults with diabetes. This trial is registered at clinicaltrials.gov, number: NCT00145925.

Keywords: Blood glucose treatment; Blood pressure treatment; Diabetes; High sensitivity cardiac troponin T; N-terminal b-type pro natriuretic peptide; Trial.

Conflict of interest statement

Declaration of Competing Interest

The authors have no conflicts of interest to report.

Copyright © 2022 Elsevier B.V. All rights reserved.

Figures

Fig. 1.

Geometric means (95% CI) of (A) high sensitivity cardiac troponin T and (B) N-terminal pro b type natriuretic peptide at baseline and year 1 according to the four individual treatment assignments. Squares represent standard glucose and standard blood pressure control, diamonds represent intensive glucose and standard blood pressure control, circles represent standard glucose and intensive blood pressure control, and triangles represent intensive glucose and intensive blood pressure control. Geometric means in these figures are estimated from mixed effects tobit models; both the 6580 baseline-only biomarker subsamples as well as the 682 with specimens at baseline and year 1 contributed to this estimation. Numbers corresponding to this figure may be found in Supplement Table ST3.