Intensive Lifestyle Intervention, Cardiac Biomarkers, and Cardiovascular Outcomes in Diabetes: Look AHEAD Cardiac Biomarker Ancillary Study

Kershaw V Patel; Zainali Chunawala; Subodh Verma; Matthew W Segar; Katelyn R Garcia; Chiadi E Ndumele; Thomas J Wang; James L Januzzi Jr; Antoni Bayes-Genis; Javed Butler; Carolyn S P Lam; Christie M Ballantyne; James A de Lemos; Alain G Bertoni; Mark Espeland; Ambarish Pandey

doi:10.1016/j.jacc.2024.11.004

Intensive Lifestyle Intervention, Cardiac Biomarkers, and Cardiovascular Outcomes in Diabetes: Look AHEAD Cardiac Biomarker Ancillary Study

J Am Coll Cardiol. 2024 Nov 15:S0735-1097(24)10417-2. doi: 10.1016/j.jacc.2024.11.004. Online ahead of print.

Authors

Kershaw V Patel¹, Zainali Chunawala², Subodh Verma³, Matthew W Segar⁴, Katelyn R Garcia⁵, Chiadi E Ndumele⁶, Thomas J Wang², James L Januzzi Jr⁷, Antoni Bayes-Genis⁸, Javed Butler⁹, Carolyn S P Lam¹⁰, Christie M Ballantyne¹¹, James A de Lemos², Alain G Bertoni¹², Mark Espeland¹³, Ambarish Pandey¹⁴

Affiliations

¹ Department of Cardiology, Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas, USA.
² Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
³ Division of Cardiac Surgery, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
⁴ Department of Cardiology, Texas Heart Institute, Houston, Texas, USA.
⁵ Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Wake Forest University, Winston-Salem, North Carolina, USA.
⁶ Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
⁷ Massachusetts General Hospital, Harvard Medical School, Baim Institute for Clinical Research, Boston, Massachusetts, USA.
⁸ Cardiology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
⁹ Baylor Scott and White Research Institute, Dallas, Texas, USA; Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
¹⁰ National Heart Centre Singapore, Duke-National University of Singapore, Singapore.
¹¹ Department of Medicine, Baylor College of Medicine and Texas Heart Institute, Houston, Texas, USA.
¹² Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
¹³ Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Wake Forest University, Winston-Salem, North Carolina, USA; Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
¹⁴ Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Electronic address: ambarish.pandey@utsouthwestern.edu.

PMID: 39551169
DOI: 10.1016/j.jacc.2024.11.004

Abstract

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are associated with cardiovascular outcomes and are recommended for measurement in type 2 diabetes (T2D). However, the effects of an intensive lifestyle intervention (ILI) targeting weight loss on cardiac biomarkers and the prognostic association of changes in these biomarkers with risk of adverse cardiovascular outcomes in T2D are not well-established.

Objectives: This study sought to evaluate the effects of an ILI on cardiac biomarkers and the association of changes in cardiac biomarkers with risk of cardiovascular outcomes in T2D.

Methods: Participants of the Look AHEAD (Action for Health in Diabetes) trial underwent NT-proBNP and hs-cTnT measurement at baseline (N = 3,984) and 1 and 4 years. The effects of the ILI (vs diabetes support and education [DSE]) on cardiac biomarkers were assessed using adjusted linear mixed-effect models and summarized as geometric mean ratios (GMRs). Associations of longitudinal changes in cardiac biomarkers with risk of cardiovascular outcomes were assessed using adjusted Cox models.

Results: Average baseline NT-proBNP and hs-cTnT was 77 and 10.7 ng/L, respectively. The ILI (vs DSE) led to an increase in NT-proBNP at 1 year (GMR: 1.14; 95% CI: 1.08-1.20), but this difference was attenuated by 4 years (GMR: 1.01; 95% CI: 0.96-1.07). The ILI (vs DSE) led to lower hs-cTnT at 1 year (GMR: 0.94; 95% CI: 0.91-0.97) and 4 years (GMR: 0.93; 95% CI: 0.90-0.96). Participants with meaningful weight loss by 1 year (≥5% vs <5%) had a significant increase in NT-proBNP in the short term (year 1), which attenuated in the long-term follow-up (year 4). Meaningful 1-year weight loss was significantly associated with reduction in hs-cTnT in the long term. In adjusted Cox models, increase in NT-proBNP was significantly associated with higher risk of the composite atherosclerotic cardiovascular disease (ASCVD) outcome and incident heart failure independent of baseline measure of the cardiac biomarker and changes in risk factors. In contrast, longitudinal increase in hs-cTnT was significantly associated with higher risk of the composite ASCVD outcome but not incident heart failure in the most adjusted model.

Conclusions: Among adults with T2D, an ILI led to a significant reduction in hs-cTnT on follow-up but a transient increase in NT-proBNP levels at 1 year that attenuated over time. Longitudinal assessment of NT-proBNP and hs-cTnT provide prognostic information for ASCVD risk, whereas only changes in NT-proBNP predicted HF risk.

Keywords: biomarkers; cardiovascular disease; intensive lifestyle intervention; obesity; type 2 diabetes.