Shedding of membrane complement inhibitors CD59 and CD46 into the circulation is associated with poor prognosis in acute coronary syndrome patients: a cohort study

Introduction: The role of the complement inhibitory proteins CD46 and CD59 in the immune response to an acute coronary syndrome (ACS) is unknown. We investigated the relationships between the shedding of CD46 and CD59 into the circulation, reflected by plasma levels of soluble CD46 and CD59, and the risk for post-ACS complications.

Methods: We measured plasma sCD46 and sCD59 in a cohort of 546 ACS patients within 24 h after hospital admission, and after 6-weeks in a subgroup of 114 patients. Study outcomes were incident heart failure (HF), major adverse cardiovascular events (MACE) and mortality during a median follow-up period of up to 3.3 years. Echocardiography at 1-year was performed in the follow-up subgroup.

Results: Elevated sCD46 and sCD59 were correlated with increased levels of inflammatory mediators and metalloproteinases in plasma, and were associated with increased risk for MACE in Cox proportional hazard models adjusted for cardiovascular risk factors and revascularization [HR 95% CI 1.24 (1.02-1.52), p = 0.034 for sCD46 and 1.18 (1.00-1.38), p = 0.049 for sCD59]. Elevated sCD59 was also associated with higher incidence of HF [HR 95% CI 1.41 (1.15-1.74), p = 0.001], and with lower left ventricular ejection fraction at 1-year post-ACS (Spearman r = - 0.234, p = 0.020). We found no associations between plasma levels of the proteins at 6 weeks and outcomes.

Conclusions: Shedding of the complement regulators CD46 and CD59 in plasma in the acute phase of ACS is associated with a negative prognosis. Plasma sCD46 and sCD59 could reflect the degree of local immune activation and serve as prognostic biomarkers in ACS patients.