Elevated Presepsin Is Associated With Perioperative Major Adverse Cardiovascular and Cerebrovascular Complications in Elevated-Risk Patients Undergoing Noncardiac Surgery: The Leukocytes and Cardiovascular Perioperative Events Study
Authors: Handke Jessica , Scholz Anna S. , Gillmann Hans-Jörg , Janssen Henrike , Dehne Sarah , Arens Christoph , Kummer Laura , Uhle Florian , Weigand Markus A. , Motsch Johann , Larmann Jan 
Published: September 2018

BACKGROUND:
Perioperative major adverse cardiovascular and cerebrovascular events (MACCEs) are incompletely understood, and risk prediction is imprecise. Atherogenic leukocytes are crucial in cardiovascular events. However, it is unclear if surgical interventions affect leukocyte counts or activation status. Therefore, we investigated whether noncardiac surgery in patients with elevated cardiovascular risk is associated with changes in atherogenic leukocyte subsets and if these changes are related to perioperative MACCEs.

METHODS:
We enrolled 40 patients in this single-center prospective observational cohort study. Total leukocytes and subpopulations, including classical, intermediate, and nonclassical monocytes and natural killer and regulatory T cells, were quantified before surgery, at 2 and 6 hours after skin incision, and at postoperative days 1 and 2 (POD1+2). The monocyte activation marker presepsin (sCD14-ST) was measured post hoc to determine differentiation of classical to nonclassical monocytes. We evaluated presepsin for prediction of the composite primary end point MACCE (cardiovascular death, myocardial infarction, myocardial ischemia, and stroke) at 30 days. Its additive value to risk assessment based on high-sensitive cardiac troponin T and N-terminal probrain natriuretic peptide (NT-proBNP) was analyzed.

RESULTS:
We evaluated 38 patients, of whom 5 (13%) reached MACCE. In the entire cohort, classical monocytes continuously increased and peaked at POD1 (0.35 [0.23–0.43] cells per nanoliter blood [nL−1] vs 0.45 [0.31–0.66] cells·nL−1, preoperative [pre-OP] vs POD1, P = .002). Intermediate monocytes doubled by POD1 (0.017 [0.013–0.021] vs 0.036 [0.022–0.043] cells·nL−1, pre-OP versus POD1, P = .0003). Nonclassical monocytes decreased (0.022 [0.012–0.032] vs 0.012 [0.005–0.023] cells·nL−1, pre-OP vs 6 hours, P = .003). In our patient population, we did not detect changes in any of the other predefined leukocyte subsets investigated. In patients experiencing a MACCE, classical monocyte expansion was reduced (0.081 [−0.16 to 0.081] cells·nL−1 vs 0.179 [0.081 to 0.292] cells·nL−1, MACCE versus non-MACCE, P = .016). Patients in the event group presented with elevated pre-OP presepsin (1528 [406–1897] pg·mL−1 vs 123 [82.2–174] pg·mL−1, MACCE versus non-MACCE, P = .0001). Presepsin was associated with MACCE (area under the curve = 0.964, [0.846–0.998], P = .001). Presepsin above the calculated threshold >184 pg·mL−1 was superior to high-sensitive cardiac troponin T for improvement of NT-proBNP-based risk prediction (28 [74%] vs 22 [58%] correctly classified patients, P = .014).

CONCLUSIONS:
Noncardiac surgery was associated with an increase in atherogenic leukocyte subsets. In a post hoc analysis, elevated pre-OP presepsin was associated with MACCE and improved NT-proBNP-based risk assessment. After validation in an independent data set, a presepsin cutoff of 184 pg·mL−1 might qualify to complement NT-proBNP-based risk prediction, thereby increasing the proportion of correctly identified high-risk patients.