Debora Battaglia

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.

Sex-related differences in association of oxidative stress status with coronary artery disease

OBJECTIVE To assess oxidative stress status in coronary artery disease (CAD) patients according to gender. DESIGN Case-controlled, observational, retrospective study. SETTING Clinical and research center. PATIENT(S) A total of 55 postmenopausal women and 108 men (mean age: 66 ± 9 years), including 72 patients with angiographically proven CAD (CAD(+), 19 women) and a group of 91 age-matched controls (CAD(-), 36 women). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Oxidant/antioxidant balance as a global index (oxidative index) obtained using two commercial assays (d-ROMs and OXY Adsorbent Test, respectively) for estimation of levels of reactive oxygen metabolites and total antioxidant status. RESULT(S) There was a statistically significant difference in oxidative stress status between men and women who were CAD(-) (-0.424 ± 1.3 vs. 0.64 ± 1.1 arbitrary units, respectively), but the CAD(+) women had oxidative stress levels almost three times those of the CAD(+) men (2.45 ± 2.5 vs. 0.9 ± 1.6 arbitrary units, respectively). After adjustment in the multivariate model, age and oxidative stress status in women and diabetes and age in men remained as statistically significant predictors of positive CAD findings. CONCLUSION(S) Oxidative stress status was a powerful predictor of CAD in women. This result may have important implications for the differences between sexes in CAD physiopathology.

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.

Effects of menopause and tibolone on different cardiovascular biomarkers in healthy women

Background and aim. The effects of tibolone on cardiovascular risk is not yet fully understood today. We designed this study to assess the effect of the menopausal status and tibolone treatment (2.5 mg/day for 3 months) on different biomarkers of cardiovascular risk in healthy women. Methods. Blood arterial pressure were measured, and blood samples collected for glucose, lipid profile (total cholesterol, high density lipoproteins, HDL, low density lipoproteins, and triglycerides), inflammatory (C-reactive protein, Interleukin-6, IL-6, tumor necrosis factor α, TNFα) and oxidative stress (hydroperoxides and antioxidant capacity) evaluation in 15 premenopausal (mean age: 30 ± 4 years) and 15 postmenopausal (mean age: 52 ± 3, mean time from menopause 1.4 ± 0.4 years) women before and after tibolone treatment. Results. The menopausal status is associated with increased systolic and diastolic pressure (p < 0.05), higher IL-6 (p < 0.05) and TNFα (p < 0.01), and lower antioxidants (p < 0.01). However, blood pressure (p < 0.05), glucose (p < 0.05), TNFα (p < 0.05) and HDL (p < 0.05) fell after tibolone, which did not significantly affect levels of the other biochemical parameters. Conclusions. As menopause is associated with increased blood pressure, inflammation and oxidative stress, tibolone restores blood pressure and has beneficial effect on inflammation and glycemia without worsening oxidative stress, although it also reduces HDL levels. Such modifications should be taken into account when tailoring menopausal therapies to specific requirements of each woman.

Carcinoembryonic antigen concentrations in patients with acute coronary syndrome

Abstract Background: Carcinoembryonic antigen (CEA), one of the most widely used tumor markers, has been recently associated with carotid atherosclerosis. The aim of our study was to evaluate whether CEA concentrations have a role in coronary artery disease (CAD). Methods: Serum CEA concentrations were evaluated in 89 patients, including 50 patients with acute coronary syndrome (ACS) (Group I, 44 with acute myocardial infarction, six with unstable angina, 38 males, 65±2 years) and 39 patients with stable CAD (Group II, 33 males, 66±3 years). In addition, 33 subjects (16 males, 62±2 years) were also included as a control group (Group III). Results: ACS was significantly associated with increased mean CEA concentrations (3.1±0.3 vs. 1.75±0.1 and 1.7± 0.2 ng/mL in Groups I, II and III, respectively, p<0.001). Increased CEA concentrations remained an independent determinant for ACS (OR=3.1, 95% CI=1.2–7.9, p<0.05) after correcting for other significant risk factors. Conclusions: CEA might represent a potential new candidate biomarker for the prediction of risk associated with ACS. Clin Chem Lab Med 2010;48:1339–43.

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.

Elevated soluble receptor for advanced glycation end product levels in patients with acute coronary syndrome and positive cardiac troponin I.

ObjectivesHigh levels of soluble receptor for advanced glycation end products (sRAGE) have been shown to have an atheroprotective role; however, no data are available on this molecule in acute coronary syndromes (ACS). We evaluated sRAGE levels in patients with non-ST segment elevation ACS (NSTE-ACS) or with chronic stable angina. MethodsWe studied 265 patients, 190 of whom had NSTE-ACS and 75 had chronic stable angina. ResultsPlasma sRAGE values were comparable in the two groups (P=0.19). However, in the patients with NSTE-ACS, sRAGE levels were significantly higher in patients with cardiac troponin-I (cTnI) of more than or equal to 0.04 µg/l compared with those with cTnI of less than 0.04 µg/l [758 (493–1536 ) pg/ml vs. 454 (167–899) pg/ml; P=0.0037]. A significant correlation (r=0.323, P=0.0045) was found between sRAGE and cTnI levels in patients with NSTE-ACS. ConclusionPlasma sRAGE levels are elevated in patients with NSTE-ACS with positive cTnI, suggesting that they could be related to myocardial cell damage.

Gender differences for uric acid as predictor of hard events in patients referred for coronary angiography

AIM To assess gender differences in uric acid (UA) as predictor for hard events (HE, mortality and nonfatal myocardial infarction) in a large cohort of patients referred for coronary angiography. Design & patients: 3020 inpatients (2177 males, age: 68 ± 9 years, mean ± SD) were retrospectively studied, collecting data from the Institute electronic databank which included demographic, clinical, instrumental and follow-up data. RESULTS Although the Kaplan-Meier survival estimates showed a significantly worst outcome in female patients, high UA did not remained a significant predictor for HE after adjustment. Moreover, UA correlated with antioxidant capacity in both sexes. CONCLUSION Hyperuricemia was not an independent risk for HE, and being correlated with antioxidant capacity, its elevation appears more likely compensatory than causative for HE.

Procoagulant activity of circulating microparticles is associated with the presence of moderate calcified plaque burden detected by multislice computed tomography

Background Circulating microparticles (MPs) have been reported to be associated with coronary artery disease (CAD). In this study, we explored the relationship between MPs procoagulant activity and characteristics of atherosclerotic plaque detected by 64-slice computed tomography angiography (CTA). Methods In 127 consecutive patients with CAD but without acute coronary syndrome and who underwent 64-slice CTA, MPs procoagulant activity in plasma (by a thrombin generation test), soluble form of lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) and N(epsilon)-(carboxymethyl) lysine (CML) circulating levels (by ELISA) were measured. A quantitative volumetric analysis of the lumen and plaque burden of the vessel wall (soft and calcific components), for the three major coronary vessels, was performed. The patients were classified in three groups according to the presence of calcium volume: non-calcified plaque (NCP) group (calcium volume (%) = 0), moderate calcified plaque (MCP) group (0 < calcium volume (%) < 1), and calcified plaque (CP) group (calcium volume (%) ≥ 1). Results MPs procoagulant activity and CML levels were higher in MCP group than in CP or NCP group (P = 0.009 and P = 0.027, respectively). MPs procoagulant activity was positively associated with CML (r = 0.317, P < 0.0001) and sLOX-1 levels (r = 0.216, P = 0.0025). Conclusions MPs procoagulant activity was higher in the MCP patient group and correlated positively with sLOX-1 and CML levels, suggesting that it may characterize a state of blood vulnerability that may locally precipitate plaque instability and increase the risk of subsequent major cardiovascular events.

Low magnesium is not a significant predictor of hard events in acute myocardial infarction

Background Although magnesium (Mg) has recognized cardioprotective properties and hypomagnesemia is common in patients with acute myocardial infarction (AMI), data regarding the role of Mg as prognostic factor for adverse events are scarce, as well as there are conflicting results on the use of Mg as adjuvant therapy in AMI. Aim To evaluate the role of Mg as predictor for hard events (HE, all cause death, and nonfatal myocardial infarction) in AMI patients. Design and patients We studied 406 AMI patients (306 males, age: 67 ± 12 years, mean ± SD). Patient data were collected from the Institute electronic databank which saves demographic, clinical, instrumental, therapeutical and follow-up data of all patients admitted to our Coronary Unit. Results During a mean follow-up period of 21 ± 18 months, the combined endpoint accounted for 63 HE, 44 (11%) deaths (35 cardiac deaths), 19 (5%) nonfatal MI. The multiple regression model identified glycemia as the only independent determinant of Mg in AMI pts. (T value = − 2.8, standard coefficient = − 0.15, p < 0.01). The Kaplan–Meier survival estimates failed to show a significantly worst outcome in patients presenting low Mg (< 0.783 mmol/L, 25th percentile). Aging (> 67 years—50th percentile), and ejection fraction (< 40%) remained as prognostic factors for HE in the adjusted Cox multivariate proportional hazard model (HR = 2.8, 95% CI = 1.6–5, p < 0.001; HR = 3.2, 95% CI = 1.9–5.3 p < 0.001, respectively). Conclusion The present findings do not support a significant role of low Mg as predictor for HE in AMI.