Alternative Complement Pathway in Carotid Atherosclerosis: Low Plasma Properdin Levels Associate With Long-Term Cardiovascular Mortality

Abstract

BACKGROUND: Complement activation may promote atherosclerosis. Yet, data on the to which extent complement, and more specifically the alternative complement pathway, is activated in patients with carotid atherosclerosis and related to adverse outcome in these patients, are scarce. METHODS AND RESULTS: We measured, by ELISA, plasma levels of factor D, properdin, C3bBbP (C3 convertase), and factor H in patients with advanced carotid atherosclerosis in a Discovery (n=324) and in a Validation (n=206) cohort in relation to adverse outcome (mean follow-up 7.8 and 6.6 years, respectively). Our major findings were as follows. Compared with healthy controls, patients with carotid atherosclerosis had increased plasma levels of factor D, properdin, and C3bBbP (P<0.001), but not factor H, an inhibitor of the alternative complement pathway, compared with controls. Although patients with carotid atherosclerosis had elevated levels of properdin compared with controls, within these patients, low plasma levels of properdin (ie,