Intensive lifestyle intervention, cardiac biomarkers, and cardiovascular outcomes in diabetes: LookAHEAD cardiac biomarker ancillary study

Background

NT-proBNP and 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

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 LookAHEAD trial underwent NT-proBNP and hs-cTnT measurement at baseline (N=3,984), 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 (GMR). 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[95% CI]: 1.14[1.08-1.20]), but this difference was attenuated by 4-years (GMR[95% CI]: 1.01[0.96-1.07]). The ILI (vs. DSE) led to lower hs-cTnT at 1-year (GMR[95% CI]: 0.94[0.91-0.97]) and 4-years (GMR[95% CI]: 0.93 [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 ASCVD outcome and HF 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 HF 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 while only changes in NT-proBNP predicted HF risk.