The alternative complement pathway is longitudinally associated with adverse cardiovascular outcomes. The CODAM...

Area of Science:

• Immunology
• Cardiovascular Medicine
• Complement System Biology

Background:

• The alternative pathway of complement activation is a potent immune response that can be spontaneously activated in blood vessels.
• Vascular activation of the alternative pathway is implicated in vascular damage and the development of cardiovascular disease (CVD).

Purpose of the Study:

• To investigate the association between functional components of the alternative complement pathway and cardiovascular risk.
• To determine if properdin, factor D (FD), and Bb levels predict cardiovascular events (CVE), CVD, low-grade inflammation (LGI), endothelial dysfunction (ED), and carotid intima-media thickness (cIMT).

Main Methods:

• A longitudinal study of 573 individuals followed for seven years.
• Measurement of properdin, factor D (FD), and Bb at baseline.
• Generalized estimating equations used to analyze associations with CVE, CVD, LGI, ED, and cIMT, including incident events in a subgroup free of CVD at baseline.

Main Results:

• Properdin showed a positive association with longitudinal and incident cardiovascular events (CVE) and endothelial dysfunction (ED).
• Factor D (FD) and Bb were positively associated with low-grade inflammation (LGI) and endothelial dysfunction (ED).
• No significant associations were found between FD, Bb, and CVE or CVD, nor between properdin and overall CVD, LGI, or cIMT.

Conclusions:

• The alternative complement pathway, especially properdin, plays a role in vascular damage and adverse cardiovascular outcomes.
• Elevated properdin may enhance the risk of cardiovascular events through mechanisms involving endothelial dysfunction.
• Factor D and Bb are linked to inflammatory and endothelial dysfunction processes, contributing to cardiovascular risk.