White Cell Subtypes Research Articles

Abstract 13224: Which White Cell Subtypes Predict the Presence of Coronary Artery Disease in High Risk Patients Over 55 Years Old?

Introduction: Inflammation has an important role in initiation and progression of coronary artery disease (CAD). Different white cell count (WCC) subtypes may reflect different mechanisms of this complex disease, and may be valuable clinically in risk stratification and detection of patients with CAD. Studies on the correlation between WCC subtypes and CAD have yielded conflicting results. Hypothesis: We hypothesized that WCC subtypes are associated with the presence of CAD in high-risk patients over 55 years old. Methods: We analyzed 622 patients over the age of 55 from the BRAVEHEART and MINACS cohort who were referred for coronary angiogram at our institution. Univariate and multivariate logistic regression models were used to compare different WCC subtypes as predictors of presence of CAD, defined as ≥50% stenosis of 1 or more coronary arteries. We adjusted for age, sex and conventional cardiac risk factors. Results: On univariate analysis, patients with CAD had significantly more CVD risk factors compared to control patients. Markers associated with CAD were lower lymphocytes (tertile 2 OR 0.61, 95% CI 0.39-0.98, p=0.040, tertile 3 OR 0.70, 95% CI 0.44-1.12, p=0.139), and higher monocytes (tertile 3 OR 2.51, 95% CI 1.45-4.34, p=0.001), neutrophil-lymphocyte ratio (NLR) (OR 1.70, 95% CI 1.07-2.68, p=0.024), and monocyte-lymphocyte ratio (MLR) (tertile 3 OR 2.62, 95% CI 1.61-4.26, p<0.001). After adjustment for CVD risk factors, lower lymphocytes (tertile 2 OR 0.40, 95% CI 0.22-0.73, p=0.003, tertile 3 OR 0.50, 95% CI 0.27-0.93, p=0.028), and higher monocytes (tertile 3 OR 2.38, 95% CI 1.23-4.61, p=0.010), NLR (tertile 3 OR 1.91, 95% CI 1.08-3.38, p=0.025), and MLR (tertile 3 OR 2.26, 95% CI 1.23-4.14, p=0.009) were associated with CAD. Conclusions: In high-risk patients over 55 years old, lower lymphocytes, and higher monocytes, NLR and MLR were associated with angiographically determined CAD independent of other risk factors. Monocytes and MLR were the strongest correlates of CAD in high-risk patients over 55. Whether these can be used as biomarkers of CAD in high risk patients warrants further study.

Fall in circulating mononuclear cell mitochondrial DNA content in human sepsis

Loss of mitochondrial DNA (mtDNA) has been described in whole blood samples from a small number of patients with sepsis, but the underlying mechanism and clinical implications of this observation are not clear. We have investigated the cellular basis of the mtDNA depletion in sepsis, and determined clinical correlates with mtDNA depletion. Whole blood samples were obtained from 147 consecutive patients with severe sepsis admitted to a General Critical Care Unit in a University Hospital and 83 healthy controls. In a separate study of 13 patients with severe sepsis, blood was obtained for immediate cell sorting by flow cytometry. MtDNA content was determined in whole blood DNA by PCR methods, and subsequently in the 13 samples where white cell subtypes were separated. The mtDNA content of peripheral blood in human subjects was lower in patients with sepsis than controls (P < 0.0001). By studying leukocyte subsets in a subgroup of 13 patients, we showed that this was largely due to an increase in the proportion of circulating neutrophils, which contained approximately 3-fold less mtDNA than mononuclear leukocytes. However, isolated monocytes (P = 0.041) and lymphocytes (P = 0.021) from septic patients showed clear evidence of mtDNA depletion, which correlated with the APACHE II score (P = 0.015). In severe sepsis much of the apparent whole blood mtDNA depletion is due to a change in the differential leukocyte count. However mtDNA depletion in mononuclear cells occurs in patients with sepsis and correlates with disease severity.