The complement lectin pathway protein MAp19 and out-of-hospital cardiac arrest: Insights from two randomized clinical trials

Aim: Activation of the complement system is known to be a potent inducer of systemic inflammation, which is an important component of post-cardiac arrest syndrome. Mannan-binding-lectin associated protein of 19 kDa (MAp19) is suggested to be a regulatory component of the lectin pathway of complement activation. The aims of this study were to describe serial levels of MAp19 protein in comatose survivors of out-of-hospital cardiac arrest (OHCA), to evaluate the effect of two different regimes of targeted temperature management and to investigate the possible association between levels of MAp19 and mortality.

Methods: In this post-hoc study, we analysed data from two large randomized controlled studies: 'Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest' (TTM) and 'Targeted temperature management for 48 versus 24 h and neurological outcome after out-of-hospital cardiac arrest' (TTH). We measured serial levels of MAp19 in 240 patients within 72 h after OHCA and in 82 healthy controls. The effect of targeted temperature management on MAp19 levels was analysed according to temperature allocation in main trials.

Results: MAp19 levels were significantly lower in OHCA patients within 48 h after OHCA (p-values <0.001) compared with healthy controls. A target temperature at 33°C compared with 36°C for 24 h was associated with significantly lower levels of MAp19 (-57 ng/mL (95% confidence interval (CI): -97 to -16 mg/mL), p=0.006). Target temperature at 33°C for 48 h compared with 24 h was not associated with a difference in MAp19 levels (-31 ng/mL (95% CI: -120 to 60 mg/mL), p=0.57). Low MAp19 levels at admission were associated with higher 30-day mortality (12% vs. 38%, p_log-rank =0.0008), also in adjusted analysis (two-fold higher, hazard ratio =0.48 (95% CI: 0.31 to 0.75), p=0.001). Analysis of MAp19 levels at 24-72 h showed they were not associated with 30-day mortality.

Conclusion: Survivors after OHCA have lower levels of MAp19 protein compared with healthy controls. A targeted temperature management at 33°C compared with 36°C was associated with significantly lower MAp19 levels, whereas target temperature at 33°C for 48 h compared with 24 h did not influence MAp19 protein levels. Low MAp19 levels at admission were independently associated with increased mortality.