Changes in Circulating Monocyte Subsets (CD16 Expression) and Neutrophil-to-Lymphocyte Ratio Observed in Patients Undergoing Cardiac Surgery

Abstract

BackgroundThe characteristics of circulating inflammatory cells (leukocytes) in patients undergoing heart surgery remains poorly understood. Recently, neutrophil-to-lymphocyte ratio (NLR) and specific monocyte subsets (based on CD14/CD16 expression) have been suggested as markers of inflammation and predictors of outcomes. The present study aims to characterize the influence cardiac surgery with cardiopulmonary bypass has on specific circulating leukocytes.MethodsAll enrolled patients had blood samples taken pre- (0 days), early post- (5 days), and late post- (90 days) surgery. Complete blood counts were performed and whole leukocyte isolations were obtained from blood samples and analyzed with flow cytometry. Fluorophore-linked antibodies (CD45, CD11b, CD14, and CD16) were added to the blood cell isolations and later assessed by flow cytometry.ResultsSeventeen patients were enrolled and samples obtained at 0, 5, and 90 days. We demonstrated a significant increase in NLR (2.2-fold; p = 0.0028) and CD16 mean fluorescence index (MFI-measure fluorescence intensity shift of CD16 in a gated cell population) early at day 5 (2.0-fold; p = 0.0051). Both NLR and CD16 MFI levels generally returned to normal by day 90. There was a significant positive correlation between NLR and CD16 MFI (r2 = 0.29; p = 0.0064). Adverse cardiovascular event (AE) was defined as prolonged length of hospitalization or readmission to hospital for cardiac reasons after discharge was seen in 59% of patients (no deaths occurred). In an unadjusted analysis of AE, we identified NLR as a likely predictor of AE, which meant that patients developing AE had a significantly higher baseline NLR (p = 0.0065), something that was not observed with CD16 MFI (p = 0.2541).ConclusionCardiac surgery is associated with a significant increase in NLR and CD16 MFI (non-classical monocytes) early after surgery corresponding to the early inflammatory phase after surgery. Furthermore, we have, for the first time, identified a significant correlation between NLR and CD16 MFI. While the mechanism for this relationship remains unclear, our findings support the use of a simple test of NLR as a biomarker of inflammation for predicting outcomes in cardiac surgery patients.

Elevated circulating CD14++CD16+ intermediate monocytes are independently associated with extracardiac complications after cardiac surgery

“…Another study emphasized the relevance of CD16 expression of circulating monocytes by measuring the mean fluorescence index (MFI) of CD16 in patients undergoing cardiac surgery pre-operation and at day 5 and 90. In agreement with our data, elevated MFI of CD16 was observed at day 5 after operation 6 . This small study (n = 17 patients), however, did not identify an association between CD16 and outcome 6 .…”

“…In agreement with our data, elevated MFI of CD16 was observed at day 5 after operation 6 . This small study (n = 17 patients), however, did not identify an association between CD16 and outcome 6 . In a larger study, Mon3 have been associated with advanced vascular dysfunction in patients undergoing cardiopulmonary bypass 13 .…”

“…Monocytes are a key player in cardiovascular disease and atherosclerosis, and elevated CD14−CD16+ non-classical monocytes have been correlated with endothelial dysfunction and vascular oxidative stress 12,13 . Several smaller studies (comprising 10-20 patients) have reported alterations in monocyte populations after cardiac surgery 6,14 , but the pathogenic involvement and the clinical relevance of these findings have remained elusive. In order to identify associations between monocyte subpopulations and complications after cardiac surgery, we conducted a prospective observational trial in 104 consecutive cardiac surgery patients, in which we obtained detailed circulating immune cell characteristics by multi-color flow cytometry before and sequentially after surgery.…”

Recovery free of heart failure after acute coronary syndrome and coronary revascularization

“…The size of the atrial piece to be collected is several‐fold larger than the whole heart of mice, suggesting that sufficient tissue will be available to allow for the analysis of inflammatory and repair mediators that may facilitate freedom from HF. In support of our REACH programme, we have recently published prospective data (Phase II) looking at specific markers of macrophages (CD16) and ratios of neutrophils and lymphocytes suggesting some mechanistic links to the development of adverse events like HF 17. While these findings are early, they clearly support our translational approach to link clinical data to biological mechanisms prospectively.…”

“…In support of our REACH programme, we have recently published prospective data (Phase II) looking at specific markers of macrophages (CD16) and ratios of neutrophils and lymphocytes suggesting some mechanistic links to the development of adverse events like HF. 17 While these findings are early, they clearly support our translational approach to link clinical data to biological mechanisms prospectively.…”