Abstract TAC282: Combination Therapy with ACEIs/ARBs and β-Blockers Reduces Basal Inflammation in Heart Failure Patients: A Cross-Sectional Observational Study

Introduction: Inflammation is increasingly recognized as a contributor to heart failure progression, and elevated basal inflammation can begin as early as stage A of the disease. While neurohormonal blockades with angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and β-blockers are standard for heart failure treatment, their specific effects on inflammatory biomarkers remain unclear. Hypothesis: We hypothesized that combination therapy with ACEIs/ARBs and β-blockers reduces basal inflammatory cytokine levels more effectively than monotherapy in heart failure patients. Methods: Following ACC/AHA guidelines, we conducted a cross-sectional observational study combining retrospective chart review and prospective blood collection at the American University of Beirut Medical Center. A total of 142 patients (mean age: 62.3 ± 14.2 years; 57.7% male) with stage A to C heart failure, were included. Patients were grouped by treatment: ACEIs/ARBs alone (42.3%), β-blockers alone (21.8%), or combination therapy of both (35.9%). Plasma levels of IL-1β, IL-2, IL-10, IFN-γ, and ACE2 were quantified using enzyme-linked immunosorbent assays (ELISA). Linear regression models adjusted for age, sex, heart failure stage, smoking status, and number of comorbidities, were implemented. Results: Patients on combination therapy had significantly lower IL-1β (B = -0.61, p = 0.007) and IL-2 (B = -2.04, p = 0.007) levels compared to those on ACEIs/ARBs alone. β-blocker monotherapy was associated with significantly elevated IFN-γ (B = 14.19, p = 0.011) that was not observed with dual treatment. ACE2 levels were significantly lower in the combination group (B = -1.67, p = 0.018) in unadjusted analysis, but this association was attenuated after adjustment (p = 0.07). IL-10 levels did not differ significantly between groups. Conclusion: Combination therapy with ACEIs/ARBs and β-blockers appears to more effectively suppress pro-inflammatory cytokines than monotherapy, independent of ACE2 expression. These findings highlight a potential anti-inflammatory advantage of dual therapy in heart failure. Limitations include modest sample size and overrepresentation of stage A patients, which may affect generalizability. Additional analyses of TNF-α, IL-6, and CRP are ongoing to strengthen our findings. Future studies will include RNA sequencing on isolated peripheral blood mononuclear cells (PBMCS) to further elucidate the immuno-modulatory mechanisms behind these findings.