Quantitative Proteomic Analysis of Diabetes Mellitus in Heart Failure With Preserved Ejection Fraction

Area of Science:

• Cardiology
• Endocrinology
• Proteomics

Background:

• Diabetes mellitus (DM) is linked to increased heart failure hospitalization and mortality, particularly in heart failure with preserved ejection fraction (HFpEF).
• Understanding the molecular mechanisms underlying this association is crucial for developing targeted therapies.

Purpose of the Study:

• To identify specific plasma proteins associated with DM in HFpEF patients.
• To investigate the role of identified proteins in mediating the increased cardiovascular risk in this population.

Main Methods:

• Proteomics analysis using SomaScan assays on plasma samples from TOPCAT and Penn Heart Failure Study participants.
• Statistical analysis to identify differentially expressed proteins between DM and non-DM HFpEF patients.
• Mediation analysis to quantify the role of specific proteins in the DM-HFpEF risk association.

Main Results:

• Ten proteins showed significantly different expression in HFpEF patients with DM.
• Apolipoprotein M was identified as a key mediator.
• Apolipoprotein M accounted for 72% of the association between DM and the composite outcome of cardiovascular death, aborted cardiac arrest, and HF hospitalization.

Conclusions:

• Apolipoprotein M is a significant mediator of the increased risk of adverse cardiovascular outcomes in HFpEF patients with diabetes mellitus.
• These findings highlight apolipoprotein M as a potential therapeutic target for managing cardiovascular risk in diabetic HFpEF patients.