Inflammation in Obesity-Related HFpEF: The STEP-HFpEF Program

Area of Science:

• Cardiology
• Metabolic Diseases
• Pharmacology

Background:

• Inflammation plays a key role in obesity-related heart failure with preserved ejection fraction (HFpEF).
• Semaglutide demonstrated benefits in the STEP-HFpEF program, including symptom improvement, weight reduction, and decreased C-reactive protein (CRP).
• Limited data exist on inflammation prevalence, characteristics, and semaglutide's efficacy across different inflammation levels in HFpEF.

Purpose of the Study:

• To characterize baseline features of HFpEF patients with varying inflammation levels (CRP).
• To assess if semaglutide's efficacy is influenced by baseline CRP levels in HFpEF.
• To determine the relationship between CRP reduction and weight loss with semaglutide treatment.

Main Methods:

• Secondary analysis of pooled STEP-HFpEF and STEP-HFpEF DM trial data.
• Patients stratified by baseline CRP levels (<2, ≥2 to <10, ≥10 mg/L).
• Evaluated changes in dual primary endpoints (health status, body weight) and secondary endpoints (6MWD, composite) by baseline CRP categories.

Main Results:

• 71% of 1,145 patients had elevated CRP (≥2 mg/L); higher CRP correlated with younger age, female sex, higher BMI, worse health status, and shorter 6MWD.
• Semaglutide improved HF symptoms, limitations, body weight, 6MWD, and composite endpoints consistently across CRP categories (P-interaction nonsignificant).
• Semaglutide significantly reduced CRP levels compared to placebo, irrespective of baseline CRP or weight loss magnitude (P-interaction = 0.32 for CRP reduction).

Conclusions:

• Inflammation is highly prevalent in obesity-related HFpEF.
• Semaglutide offers consistent benefits for HF symptoms, function, and weight across all baseline inflammation levels.
• Semaglutide effectively reduces inflammation in HFpEF, independent of baseline CRP or weight loss achieved.