TY - JOUR
T1 - The complement lectin pathway protein MAp19 and out-of-hospital cardiac arrest
T2 - Insights from two randomized clinical trials
AU - Bro-Jeppesen, John
AU - Jeppesen, Anni Nørgaard
AU - Haugaard, Simon
AU - Troldborg, Anne
AU - Hassager, Christian
AU - Kjaergaard, Jesper
AU - Kirkegaard, Hans
AU - Wanscher, Michael
AU - Hvas, Anne-Mette
AU - Thiel, Steffen
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - Cardiac arrest
KW - complement
KW - targeted temperature management
UR - http://www.scopus.com/inward/record.url?scp=85105788852&partnerID=8YFLogxK
U2 - 10.1177/2048872619870031
DO - 10.1177/2048872619870031
M3 - Journal article
C2 - 31538810
SN - 2048-8726
VL - 9
SP - S145-S152
JO - European Heart Journal: Acute Cardiovascular Care
JF - European Heart Journal: Acute Cardiovascular Care
IS - 4_Suppl
ER -