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Abstract: Background: The presence of effort induced angina, positive exercise stress test responses and angiographically normal coronary arteries defines cardiac syndrome X (CSX). Its pathogenesis, although mostly attributed to endothelial dysfunction and coronary microcirculation abnormalities, is incompletely understood. The soluble CD40 ligand (sCD40L) has multiple autocrine, paracrine and endocrine actions that may lead to endothelial dysfunction and atherothrombosis. We sought to investigate the relationship among sCD40L levels and ischemic burden in patients with CSX and whether sCD40L levels are increased in patients with CSX compared to control subjects. Methods: We assessed 30 prospectively enrolled patients with CSX and 28 apparently healthy subjects matched for coronary risk factors. All CSX patients and control subjects underwent myocardial perfusion scintigraphy. The summed difference score is taken to be an index of ischemic burden. This was classified as mildly, moderately and severely abnormal. White blood cells, sCD40L and C-reactive protein (CRP) concentrations were measured at peak exercise. Results: At peak exercise, sCD40L levels were significantly greater in CSX patients than in the control group (P =0.008). Similarly, white blood cell count and CRP levels were higher in patients with CSX than in normal controls (P =0.02). After multivariable adjustment, sCD40L (P =0.03) was the only independent predictor of severe ischemic burden in CSX patients. Conclusions: The present study showed for the first time that sCD40L is associated with ischemic burden in patients with CSX. The potential role of this inflammatory molecule in the pathogenesis of CSX deserves investigation in future studies. [ABSTRACT FROM AUTHOR]

Abstract: Background: Left ventricle remodeling (LVR) is a relatively common and unfavourable event occurring after acute myocardial infarction. A link exists between inflammation and LVR. Neopterin, a marker of inflammation and macrophage activation, is a predictor of left ventricular dysfunction in patients with coronary artery disease. We therefore sought to assess whether both neopterin and brain natriuretic peptide (BNP), a marker of LV dysfunction and patient outcome, correlate with LVR in patients with ST-segment elevation myocardial infarction (STEMI). Methods: We prospectively assessed 108 STEMI patients (age 64±11 years; 85% male) undergoing primary percutaneous coronary intervention (PCI) who were assessed echocardiographycally assessment was performed at 96±10h after the onset of symptoms and 12month after STEMI. LVR was defined as >20% increase in LV end-diastolic volume at 12months of follow-up compared to baseline. Neopterin and BNP serum concentrations were measured immediately before primary PCI. Results: At 1 year, 21 patients (19%) showed LVR and 87 (81%) had no LVR. Patients with LVR had higher levels of neopterin at study entry (7.45±1.04 vs 5.19±1.39nmol/L; p <0.001). After adjustment for relevant confounders, neopterin levels were found to be an independent predictor of LVR (OR ranging from [3.10, CI 95% 1.928–4.990, p <0.001] to [3.32, CI 95% 1.999–5.532, p <0.001]). ROC analysis showed an area under the curve of 0.901 for neopterin (CI 95% 0.84–0.96, p <0.0001) compared to 0.579 for BNP (CI 95% 0.409–0.748) regarding LVR. Conclusions: In STEMI patients undergoing primary PCI, high neopterin levels – but not BNP – predict LVR at 1-year follow-up. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: CD40 ligand has been suggested to play a pathogenic role in atherogenesis and coronary artery disease progression. Clinical studies suggest that intravenous (IV) abciximab administration attenuates the acute inflammatory response associated with percutaneous coronary intervention (PCI). The anti-inflammatory effects of intracoronary (IC) versus IV administration of abciximab have not been systematically investigated. We assessed changes in soluble CD40 ligand (sCD40L) concentrations in response to IC versus IV abciximab in patients with ST-elevation myocardial infarction (STEMI) undergoing thrombus-aspirating device during primary PCI. Methods: Patients were randomized to receive IC (n =25) or IV (n =25) bolus abciximab followed in every case by a 12-h IV abciximab infusion. sCD40L was measured immediately before the administration of abciximab (baseline) and 60min post bolus administration. Results: Clinical baseline and angiographic characteristics were similar in both patient groups. Similarly, there were no significant differences in baseline serum sCD40L levels in the IC group compared to IV group (116.6±42.13pg/mL vs 124.9±43.04pg/mL, P =0.49). At 60min post PCI, however, sCD40L levels decreased by 23% (P <0.001) in the IC group and by 11% (P <0.001) in the IV group. sCD40L levels 60min post PCI were significantly reduced, particularly in the IC group compared to the IV group (73.04±12.21pg/mL vs 99.92±25.89pg/mL, P <0.001). Conclusion: In STEMI patients undergoing primary PCI, IC bolus administration of abciximab was associated with a larger reduction in sCD40L levels compared to standard IV bolus. Whether this more powerful anti-inflammatory effect of IC abciximab translates into improved clinical outcomes deserves investigation. [Copyright &y& Elsevier]

Abstract: Objective: To investigate the possible association between admission ischemia modified albumin (IMA) levels and ST-segment resolution (STR) in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). Materials and Methods: We studied 117 patients with a first STEMI within 6h of the onset of pain. Admission serum IMA concentration was measured using a validated assay. The worst single electrocardiogram lead before and 90min after primary PCI was analyzed, and patients were divided into two groups according to the degree of STR: complete (≥70%) or incomplete (<70%). Results: Of the 117 patients, 70 (60%) had complete STR, and 47 (40%) incomplete STR. Serum IMA concentrations were significantly higher in patients that had incomplete STR (0.383±0.060A.U. vs. 0.297±0.056A.U., p <0.001). IMA levels >0.325A.U. demonstrated a sensitivity of 91.4% and a specificity of 45.7% for the diagnosis of incomplete STR; the area under the receiver operator characteristic curve was 0.849 (95% CI 0.77–0.92, p =0.0001). Moreover, IMA values were an independent predictor of incomplete STR even after adjustment for potential confounders (OR 2.34; 95% CI 1.20–4.64, p = 0.01). Conclusions: IMA may be a useful biomarker for the identification of incomplete STR in STEMI patients presenting to hospital within 6h of the onset of pain. [Copyright &y& Elsevier]

Abstract: Introduction: It has been proposed that reactive oxygen species (ROS) generated during myocardial ischemia–reperfusion modify the N-terminus of serum albumin resulting in ischemia-modified albumin (IMA) formation. Likewise, several recent publications provide evidence that melatonin, a circadian endogenously produced indolamine, is a direct scavenger of ROS. We sought to investigate the relationship between IMA and melatonin in ST- elevation myocardial infarction (STEMI). Methods: We compared IMA and melatonin levels in 27 patients with STEMI undergoing primary angioplasty and 20 age- and gender-matched healthy normal subjects. Blood samples were drawn at 02:00h (night period) and 09:00h (day period) while patients were resting, to assess IMA and melatonin. Results: In both groups, melatonin concentrations maintained a diurnal variation, but the difference between nocturnal and diurnal levels was less in the STEMI-patients than in the control group (p <0.001). In contrast to findings about melatonin, IMA levels showed no diurnal variations in control subjects. However, the STEMI group showed a diurnal fluctuation with significantly higher levels at 02:00h (p <0.01). The association between IMA and melatonin remained statistically significant after adjustment for cardiovascular risk factors. An inverse correlation between IMA and melatonin at 02:00h and at 09:00h was observed, with respective r-values of −0.42 (p <0.03) and −0.57 (p <0.002). Conclusions: Circulating IMA is negatively correlated to melatonin in STEMI-patients. Our results suggest that melatonin might exert a beneficial effect as a radical scavenger in a human model of myocardial ischemia–reperfusion. [Copyright &y& Elsevier]

Abstract: Introduction: The purpose of this study was to compare serum matrix metalloproteinase (MMP)-9 levels in a population of type 2 diabetic versus non-diabetic patients hospitalized with ST-segment elevation myocardial infarction (STEMI) and to examine the relationship between serum MMP-9 levels and the incidence of in-hospital cardiac events, including death and cardiogenic shock. Methods: We recruited 120 patients with STEMI, of whom 48 were type 2 diabetic and 72 non-diabetic. Serum MMP-9 levels were measured on admission, using a commercially available ELISA. The primary study endpoint was cardiac death in-hospital and cardiogenic shock. Results: Mean serum MMP-9 levels were significantly higher in type 2 diabetic patients compared to non-diabetic patients (240±52ng/mL versus 185±47ng/mL; P <0.0001). In multivariable analysis, type 2 diabetes was an independent factor for mortality [OR: 1.75 (1.40–2.30); P =0.005] and cardiogenic shock [OR: 1.55 (1.20–1.70); P =0.03] when the variable MMP-9 level was not introduced into the model, but it was less significantly associated with mortality [OR: 1.60 (1.40–2.10); P =0.01] and no longer associated with cardiogenic shock when MMP-9 was in the model. Conclusion: After STEMI, type 2 diabetes is independently associated with high serum MMP-9 levels. This elevated MMP-9 is strongly associated with the increased incidence of in-hospital mortality and cardiogenic shock observed in type 2 diabetes. Our findings clearly indicate that serum MMP-9 provides a highly valuable prognostic information on in-hospital outcome after STEMI, in particular in type 2 diabetic patients. [Copyright &y& Elsevier]