Circulating Monocyte Chemoattractant Protein-1 in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction Treated with Mild Hypothermia: A Biomarker Substudy of SHOCK-COOL Trial

Abstract

Background: There is evidence that monocyte chemoattractant protein-1 (MCP-1) levels reflect the intensity of the inflammatory response in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI) and have a predictive value for clinical outcomes. However, little is known about the effect of mild therapeutic hypothermia (MTH) on the inflammatory response in patients with CS complicating AMI. Therefore, we conducted a biomarker study to investigate the effect of MTH on MCP-1 levels in patients with CS complicating AMI. Methods: In the randomized mild hypothermia in cardiogenic shock (SHOCK-COOL) trial, 40 patients with CS complicating AMI were enrolled and assigned to MTH (33 °C) for 24 h or normothermia at a 1:1 ratio. Blood samples were collected at predefined time points at the day of admission/day 1, day 2 and day 3. Differences in MCP-1 levels between and within the MTH and normothermia groups were assessed. Additionally, the association of MCP-1 levels with the risk of all-cause mortality at 30 days was analyzed. Missing data were accounted for by multiple imputation as sensitivity analyses. Results: There were differences in MCP-1 levels over time between patients in MTH and normothermia groups (P for interaction = 0.013). MCP-1 levels on day 3 were higher than on day 1 in the MTH group (day 1 vs day 3: 21.2 [interquartile range, 0.25–79.9] vs. 125.7 [interquartile range, 87.3–165.4] pg/mL; p = 0.006) and higher than in the normothermia group at day 3 (MTH 125.7 [interquartile range, 87.3–165.4] vs. normothermia 12.3 [interquartile range, 0–63.9] pg/mL; p = 0.011). Irrespective of therapy, patients with higher levels of MCP-1 at hospitalization tended to have a decreased risk of all-cause mortality at 30 days (HR, 2.61; 95% CI 0.997–6.83; p = 0.051). Conclusions: The cooling phase of MTH had no significant effect on MCP-1 levels in patients with CS complicating AMI compared to normothermic control, whereas MCP-1 levels significantly increased after rewarming. Trial registration: NCT01890317.

Circulating Galectin-3 in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction Treated with Mild Hypothermia: A Biomarker Sub-Study of the SHOCK-COOL Trial

“…High levels of angiopoietin-2 are independently associated with increased short- and long-term mortality risk [ 44 ]. Similarly, we have previously shown that monocyte chemoattractant protein-1 levels on admission may be associated with short-term mortality [ 45 ]. However, these studies all suffer from limitations such as single-center, inadequate sample size, and small number of events.…”

Cell-Free Double-Stranded DNA to DNase Ratio Predicts Outcome after Primary Survived Cardiac Arrest

“…Only when comparing patients with a dsDNA/DNase ratio above and below the empirical cut-off, significantly higher MCP-1 levels could be shown in the group with higher dsDNA burden after 24 h, whereas only a trend remained after 96 h. MCP-1 functions chemotactically and recruits monocytes to the affected tissue during inflammatory processes. Interestingly, Cheng et al demonstrated an association of higher MCP-1 levels and lower 30-day mortality in a cohort of cardiogenic shock patients after acute myocardial infarction [ 24 ]. Moreover, in their work, biomarker levels increased within the first three days, whereas a decreasing trend was observed in our study.…”

“…Interestingly, MCP-1 was recently shown to prime neutrophils for NET formation in a cohort of STEMI patients [ 25 ], highlighting a potential connection between both parameters also in CA patients. As mentioned above, balanced inflammation is certainly crucial for a beneficial outcome, which may also explain the different findings of various authors regarding the effect of elevated MCP-1 levels [ 24 , 26 ]. Importantly, patients with unfavorable outcome showed decreased DNase activity 96 h after ICU admission, suggesting that a decreased repair capacity might play a role in patients with poor outcome, in addition to increased inflammation and cell death.…”