Angela Papa

Predictive value of elevated neutrophil–lymphocyte ratio on cardiac mortality in patients with stable coronary artery disease

BACKGROUND An association between white blood cell count (WBC), severity of coronary artery disease (CAD) and survival has been described in patients with acute coronary syndrome. Our aim was to analyze the predictive ability for cardiac events of differential WBC, which is still not well characterized, against established risk factors in angiographically proven CAD patients. METHODS We prospectively evaluated complete blood count, biomarkers of inflammation [(C-reactive protein (CRP) and serum iron (SI)], glucose/lipid metabolism [(fasting glucose (FG), total, high-density lipoprotein (HDL) and low-density lipoprotein cholesterol] and established risk factors in 422 consecutive ischemic patients with angiographically documented stable CAD. On a 3-year follow-up, cardiac death and non-fatal myocardial infarction (MI) were considered as end-points. RESULTS At multivariate analysis neutrophil to lymphocyte ratio (N/L) emerged as independent predictor of cardiac death (HR 8.13; p=0.02) together with CRP, left ventricular ejection fraction (LVEF), FG, HDL and SI. CRP, LVEF, and HDL showed an independent prognostic value for cardiac death and non-fatal MI. Event-free survival according to N/L tertiles was 99% for the first tertile (1.23+/-0.26), 96.5% for the second (2.05+/-0.29), and 88.8% for the third one (5.19+/-3.81). CONCLUSIONS N/L is an independent predictor of cardiac mortality in stable CAD patients.

Plasma N-e-(carboxymethyl)lysine levels are associated with the extent of vessel injury after coronary arterial stenting

ObjectiveIn animal models, increased tissue receptor for advanced glycation end products and its ligands, including N-ϵ-(carboxymethyl)lysine (CML), are critically implicated in postprocedural intimal hyperplasia after balloon injury. In patients undergoing percutaneous coronary interventions with stenting, we investigated whether plasma levels of CML and the soluble form of receptor for advanced glycation end products (sRAGE) changed during poststenting follow-up. MethodsWe studied 81 patients with coronary artery disease who underwent successful percutaneous coronary interventions. Plasma levels of CML and sRAGE were measured before intervention, and at 1 day and 180 days of follow-up. ResultsCML levels increased significantly at day 1 after stenting and persisted at an elevated level at 180 days (P=0.013), whereas sRAGE levels increased significantly at 180 days (P=0.011). CML levels were significantly higher in multivessel-treated patients than in single-vessel-treated patients both at 1 day and 180 days of follow-up. In addition, CML values were positively associated with the extent of stent area at 1 day and 180 days of follow-up (r=0.278, P=0.022 and r=0.315, P=0.012, respectively). In logistic regression analysis, only the extent of stent area predicted adverse clinical events at 180-day follow-up (P=0.03, odds ratio=14.25, confidence interval=1.25–162.2). ConclusionThis study supports the hypothesis that increased circulating levels of CML occurred in the presence of vascular injury. This persistent rise of CML could amplify an inflammatory phenomenon triggered by stent placement and thus contributes to coronary artery disease progression.

Routine laboratory tests to risk-stratify patients with chronic coronary artery disease

BACKGROUND Several biohumoral variables, taken individually, are predictors of prognosis in patients with chronic coronary artery disease (CAD). We hypothesized that taken together, laboratory tests provide prognostic information that is additive to a complete diagnostic work-up. METHODS We prospectively examined 2370 consecutive patients with chronic CAD, as shown by a >50% coronary stenosis (in 95% of patients), previous coronary revascularization (in 31% of patients), and/or previous myocardial infarction (MI, in 54% of patients). We tested the ability of laboratory and clinical variables to predict future cardiac events (cardiac death and non-fatal MI). RESULTS During follow-up (median, 46 months), 147 patients (6.2%) died from cardiac causes and 81 (3.4%) experienced a non-fatal MI. Using multivariate analysis, after adjustment for clinical variables (including left ventricular ejection fraction and angiographic extent of coronary stenoses), a high-density lipoprotein cholesterol (HDLc) concentration<35 mg/dL (p<0.0001), a neutrophil-to-lymphocyte ratio >2.4 (p=0.0014), and an fT3 serum level<2.1 pg/mL with normal thyrotropin (low-T3 syndrome) (p=0.0260) showed an independent and incremental prognostic value, and were associated with an increase in the rate of cardiac events of 86%, 57% and 41%, respectively. When these variables were added to clinical and instrumental variables, the prognostic power of the model increased significantly (global chi-square improvement: from 157.01 to 185.07, p<0.0001). CONCLUSION Low HDLc, high neutrophil-to-lymphocyte ratio and low-T3 syndrome, both individually and taken together, provide prognostic information that is independent of and incremental to the main clinical and instrumental findings.

Synthetic analogues of flavonoids with improved activity against platelet activation and aggregation as novel prototypes of food supplements.

We investigated the ability of quercetin and apigenin to modulate platelet activation and aggregation, and compared the observed efficacy with that displayed by their synthetic analogues 2-phenyl-4H-pyrido[1,2-a]pyrimidin-4-ones, 1-4, and 2,3-diphenyl-4H-pyrido[1,2-a]pyrimidin-4-ones, 5-7. Platelet aggregation was explored through a spectrophotometric assay on platelet-rich plasma (PRP) treated with the thromboxane A2 mimetic U46619, collagen and thrombin in presence/absence of various bioisosteres of flavonoids (12.5-25-50-100 μM). The platelet density, (mean platelet component, MPC), was measured by the Advia 120 Hematology System as a marker surrogate of platelet activation. The induced P-selectin expression, which reflects platelet degranulation/activation, was quantified by flow cytometry on PRP. Our synthetic compounds modulated significantly both platelet activation and aggregation, thus turning out to be more effective than the analogues quercetin and apigenin when tested at a concentration fully consistent with their use in vivo. Accordingly, they might be used as food supplements to increase the efficacy of natural flavonoids.

α-1 Protein evaluation to stratify heart failure patients.

Heart failure is a pathological condition characterized by cardiac dysfunction and neuroendocrine system activation. The aim of this study was to evaluate serum α-1 proteins in the characterization of heart failure patients. The study included 69 patients with documented heart failure disease and 44 healthy individuals. We included 12 out of 69 patients with preserved (>50%) left ventricular ejection fraction. α-1 protein levels were evaluated using routine capillary electrophoresis. Markers of inflammation, such as interleukin-6 (IL-6) and tumor necrosis factor-α, were measured with UltraSensitive ELISA Kits. C-reactive protein and brain natriuretic peptide were determined by automated assays. No difference in α-1 protein levels between patients with reduced versus preserved left ventricular ejection fraction was observed. IL-6, tumor necrosis factor-α, and C-reactive protein concentrations were significantly increased in patients with respect to the control group (P <0.001, P <0.01, and P <0.05, respectively). A progressive increase in α-1 protein levels across NYHA classes (P = 0.0077) was observed. Brain natriuretic peptide median value of the patient group was 287 ng/l (92–602 ng/l) and was significantly associated with α-1 proteins and IL-6 levels (P <0.05 and P <0.01, respectively). Considering recent findings and our preliminary data, we hypothesized that the overexpression of α-1 antitrypsin (AAT) protein (and probably elevated AAT levels) is a compensatory mechanism as a consequence of the loss of the antiprotease activity, induced by the increase of oxidative stress in heart failure patients. In conclusion, we assume that α-1 proteins and AAT could contribute to the prognostic stratification of heart failure patients.

Comparing the performance of three panels rules of blood smear review criteria on an Italian multicenter evaluation

The aims of this study were to compare the diagnostic accuracy of blood smear review criteria, by means of three different panel rules, those proposed by: the International Consensus Group for Hematology [41‐ICGH rules], the Italian Survey [IS rules] and the Working Group on Hematology‐SIBioC (WGH) consensus rules (WGH rules).

Performance evaluation of the automated nucleated red blood cell count of five commercial hematological analyzers

Recent automated hematology analyzers (HAs) can identify and report nucleated red blood cells (NRBC) count as a separate population out of white blood cells (WBC). The aim of this study was to investigate the analytical performances of NRBC enumeration on five top of the range HAs.