Increased Complement Factor B and Bb Levels Are Associated with Mortality in Patients with Severe Aortic Stenosis

Area of Science:

• Immunology
• Cardiovascular Medicine
• Complement System

Background:

• Inflammation plays a key role in aortic stenosis (AS) development and progression.
• The specific role of the complement system, a vital part of innate immunity, in AS remains largely unknown.

Purpose of the Study:

• To investigate the hypothesis that circulating levels of complement factor B (FB) are elevated in severe symptomatic AS and can predict patient outcomes.
• To explore the association of FB and its fragments with disease severity, inflammation, and cardiac function in AS patients.

Main Methods:

• Plasma levels of FB, Bb, and terminal complement complex were measured using enzyme immunoassays in three patient cohorts with severe symptomatic AS, mild-to-moderate or severe asymptomatic AS, and healthy controls.
• Statistical analyses, including survival analysis and correlation studies, were performed to assess the relationship between complement levels and clinical outcomes, adjusting for covariates.

Main Results:

• Symptomatic AS patients exhibited significantly higher plasma FB levels compared to healthy controls (2.9- and 2.8-fold increases).
• FB levels correlated with markers of systemic inflammation (CRP), cardiac function (NT-proBNP), and cardiac necrosis (Troponin T).
• High FB and Bb levels were significantly associated with increased mortality risk in patients with symptomatic AS, even after multivariable adjustment (HR 1.37).

Conclusions:

• Elevated circulating levels of complement factor B (FB) and Bb fragment are associated with adverse outcomes in patients with symptomatic aortic stenosis.
• Increased FB levels observed even in asymptomatic AS patients suggest the complement system's involvement early in the disease process.
• These findings highlight the potential of complement system components as prognostic biomarkers and therapeutic targets in aortic stenosis.