Abstract Body (Do not enter title and authors here): Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) identify subclinical heart failure (HF) in type 2 diabetes (T2D). The contribution of changes in cardiac biomarkers to HF risk, particularly HF subtypes, is unclear. Whether HF risk associated with cardiac biomarkers is modifiable with an intensive lifestyle intervention (ILI) targeting weight loss is unknown.
Methods: Adults with T2D and overweight/obesity in the Look Action for Health in Diabetes (AHEAD) trial without prevalent HF were included. NT-proBNP and hs-cTnT were measured at baseline, 1- and 4-years (Roche Diagnostics). Adjusted Cox models were created to evaluate the associations of baseline, 1- and 4-year change in NT-proBNP and hs-cTnT with risk of HF with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). Interaction testing was performed to evaluate heterogeneous effects of the ILI vs diabetes support and education (DSE) across baseline cardiac biomarkers.
Results: Of the 3,959 participants included, 212 had incident HF (108 HFpEF, 84 HFrEF) over 12 years. Higher baseline NT-proBNP and hs-cTnT were each significantly associated with higher risk of HFpEF and HFrEF (Table). Increases in NT-proBNP over 1- and 4-years were significantly associated with higher risk of HFpEF and HFrEF with a similar pattern of association for hs-cTnT and HF subtypes. After accounting for risk factor changes, the association of 1- and 4-year changes in NT-proBNP, but not hs-cTnT, with risk of HF subtypes remained significant. There was a significant interaction between NT-proBNP and ILI for risk of HFpEF but not HFrEF (p-int = 0.001). The ILI reduced HFpEF risk among participants with elevated (≥125 pg/mL) but not non-elevated NT-proBNP (<125 pg/mL) (ILI vs DSE HR [95% CI]: 0.48 [0.25-0.93] and 1.67 [0.94-2.94], respectively). No significant treatment group by hs-cTnT interactions were identified.
Conclusions: In T2D, longitudinal changes in cardiac biomarkers, particularly NT-proBNP, are significantly associated with HF risk, independent of risk factor changes. In Look AHEAD, elevated NT-proBNP may identify individuals who are more likely to benefit from the ILI for HFpEF prevention.