Abstract Body: Background: Elevated levels of biomarkers of neurohormonal stress (NT-proBNP) and myocardial injury (hs-TnT) are associated with an increased risk of heart failure (HF) in diabetes. While sex differences in these biomarker profiles and the HF epidemiology are well-established, it is unclear if the prognostic association of biomarkers with the risk of HF differs by sex.
Methods: The study included participants of the LookAHEAD trial with overweight/obesity and T2DM. NT-proBNP and hs-TnT were measured at baseline, 1- and 4-year follow-up. HFpEF (LV EF> 50%) and HFrEF (LV EF <50) incidence were adjudicated based on HF hospitalization reports using a well-established protocol. Separate adjusted Cox models were constructed to assess the associations of baseline and longitudinal biomarker changes with the risk of HF subtypes, including sex*biomarker interaction terms.
Results: The study included 3959 participants (age: 59 years, 59.3% women, BMI=36 kg/m²) with 108 HFpEF (men vs women: 3.3% vs 2.3%) and 84 HFrEF (men vs women: 2.9% vs 1.6%) events over 12.4 years of follow-up. At baseline, higher NT-proBNP levels were more strongly associated with the risk of HFpEF in females than males (P-int=0.02). In contrast, the association between NT-proBNP and the HFrEF risk was significant and comparable for both sexes (Table). The association of elevated hs-TnT levels with the risk of HFpEF did not differ by sex. In contrast, the risk of HFrEF associated with hs-TnT was significantly modified by sex, with a greater risk noted among males (vs. females, Table). Among those with biomarker assessment on follow-up, an increase in NT-proBNP levels over time was more strongly associated with risk of HFpEF in females than males (P-int=0.01). In contrast, the association between an increase in NT-proBNP levels over time and HFrEF risk did not differ by sex. Repeated measures of hs-TnT over time were not associated with the risk of either HF subtype, with no significant interaction by sex.
Conclusion: Among individuals with T2DM with overweight/obesity, the prognostic relevance of cardiac biomarkers for HF outcomes varies by sex. Elevated baseline levels and increase in NT-proBNP over time are more strongly associated with HFpEF risk in females than males. In contrast, elevated hs-TnT is more strongly associated with the risk of HFrEF in males. Further research is needed to determine if sex-specific biomarker screening strategies can inform HF prevention in high-risk individuals.