Complement and contact system activation in acute congestive heart failure patients

Abstract

Recent experimental data indicate a pathogenic role of complement activation in congestive heart failure (CHF). The aim of this study was to evaluate contact and complement systems activation in patients hospitalized for an acute episode of CHF. Forty-two of 80 consecutive patients admitted at our hospital with confirmed diagnosis of acute CHF were enrolled. They underwent blood sampling within 24 h from admission (T0) and at clinical stability (T1). Patients were stratified for ejection fraction (EF) based on echocardiographic test. We measured plasma levels of C3, C4, sC5b-9 and cleaved high molecular weight kininogen (contact activation marker). At T1, C3 levels increased significantly compared to T0 (97 ± 2 versus 104 ± 3% of total pooled plasma, P < 0·01). Classifying patients according to EF, only patients with preserved EF presented a significant increase of C3 from T0 to T1 (99 ± 3 versus 108 ± 4%, P = 0·03). When the sample was stratified according to clinical outcome, C3 (98 ± 3 versus 104 ± 4%, P = 0·03) and sC5b-9 levels (204 ± 10 versus 230 ± 11 ng/ml, P = 0·03) were increased in patients who had positive outcome after hospitalization. CHF patients with preserved EF and positive outcome after hospitalization showed higher levels of sC5b-9 in the T1 period compared with T0 (211 ± 14 versus 243 ± 14 ng/ml, P = 0·04). Our results suggest that the complement system reacts differently if CHF occurs with preserved or reduced EF. This finding is interesting if we consider the difference in epidemiology, pathogenesis and possible therapeutic approaches of these two clinical entities.

Keywords: complement system; contact system; heart failure; immune system; ventricular function.

Figure 1

Level of C3 (a), C4 (b), sC5b‐9 (c) and cleaved high molecular weight kininogen (HK) (d) in the whole sample of patients with congestive heart failure (CHF), as well as in the heart failure with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF) groups during admission (T0 = white bars) and after the clinical stability (T1 = grey bars) periods. *Difference versus the T0 period in the same group, P < 0·05.

Figure 2

Level of C3 (a), C4 (b), sC5b‐9 (c) and cleaved high molecular weight kininogen (HK) (d) in the whole sample of patients with congestive heart failure (CHF), as well as in the heart failure with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF) groups during admission (T0) and after the clinical stability (T1) periods based on clinical outcome. *Difference versus the T0 period in the same group, P < 0·05.