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Background: Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of renal tubular damage. We investigated the incidence and possible implications of elevated NGAL levels (suggesting renal damage) compared to both functional and damage markers (manifested as serum creatinine [sCr] elevation) and no NGAL/sCr change, among -ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). Methods: We included 131 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn 24 h following PCI. We used the terms NGAL(–) or NGAL(+) with levels ≥100 ng/mL suggesting renal tubular damage and the terms. sCr(–) or sCr(+) to consensus diagnostic increases in sCr defining acute kidney injury. Patients were also assessed for in hospital-adverse outcomes. Results: Of the study patients, 56 (42%) were NGAL(–)/sCr(–), 58 (44%) NGAL(+)/sCr(–), and 18 (14%) were both NGAL(+)/sCr(+). According to the 3 study groups, there was a stepwise increase in the proportion of left ventricular ejection fraction ≤45% (43 vs. 60. vs. 72%; p = 0.04), in-hospital adverse outcomes (9 vs. 14 vs. 56%; p < 0.001) and their combination. Specifically, more NGAL(+)/sCr(–) patients developed the composite endpoint when compared to NGAL(–)/sCr(–) patients (64 vs. 46%; OR 2.1, [95% CI 1.1–4.5], p = 0.05). A similar and consistent increase was observed in peak sCr, length of hospital stay, and C-reactive protein levels. Conclusions: Elevated NGAL levels suggesting renal tubular damage, increased inflammation, or both are common among STEMI patients and are associated with adverse outcomes even in the absence of diagnostic increase in sCr. [ABSTRACT FROM AUTHOR]

Objectives: We have recently shown that the transient receptor potential vanilloid 2 (TRPV2) channel is exclusively upregulated in rat/murine peri-infarct monocytes/macrophages following an acute myocardial infarction (AMI), and that this overexpression might be detrimental for cardiac recovery. We aimed to characterize the expression levels of TRPV2 in peripheral blood mononuclear cells (PBMCs) of AMI patients relative to individuals with normal coronaries, and to analyze potential associations with inflammatory and cardiac ischemic markers. Methods: Patients who underwent coronary angiography due to AMI or chest pain were prospectively included. PBMCs were isolated from whole blood by Ficoll gradient centrifugation. TRPV2 expression was analyzed by real-time PCR. C-reactive protein (CRP) and troponin I (TpI) levels were determined at the central chemistry laboratory; interleukin 6 and insulin-like growth factor (IGF)-1 levels were tested by ELISA. Results: Following AMI, the number of TRPV2-expressing PBMCs was reduced when compared to in patients with normal coronaries. An inverse correlation was documented between the numbers of circulating macrophages and TRPV2 expression. Additionally, TRPV2 expression was inversely correlated with CRP and TpI and directly correlated with serum IGF-1. Conclusions: We assume that peripheral TRPV2 downregulation occurs concomitantly with the accumulation of TRPV2-white blood cells in the peri-infarct zone. TRPV2 may thus represent a novel target for treatment in the acute phase after MI. [ABSTRACT FROM AUTHOR]

Aims: Shift work disrupts the normal circadian rhythm and is associated with risk factors for coronary artery disease (CAD) and a higher incidence of CAD morbidity and mortality. Cardiac computed tomography angiography (CCTA) is a robust noninvasive modality for assessing the presence, extent, and severity of CAD. We sought to investigate whether shift workers are prone to a higher burden of CAD compared to non-shift workers. Methods: We conducted a historically prospective study in consecutive patients who underwent CCTA and answered a telephonic questionnaire. Due to significant differences in age and gender, we compared 89 wellmatched pairs of shift workers and non-shift workers with the use of propensity scores. Results: Our cohort consisted of 349 participants, of whom 94 (26.9%) were shift workers. The mean age was 50.7 years, and 62.5% were males. After pairing, we showed that shift workers had a higher prevalence of CAD than non-shift workers (74.2 vs. 53.9%, respectively, p = 0.01), and a lower prevalence of coronary calcium scores of zero (46.8 vs. 63.4%, respectively, p = 0.034). Stenosis >50% was more prevalent in shift workers than in nonshift workers (20.2 vs. 11.2%, respectively, p = 0.006), and the extent of CAD (defined as the presence of ≥ 1-vessel disease) tended to be higher in shift workers than in non-shift workers (25.8 vs. 13.5%, respectively, p = 0.06). Conclusions: In this CCTA study, we showed in a well-matched cohort of consecutive patients that shift workers had a higher prevalence and extent of CAD than non-shift workers. [ABSTRACT FROM AUTHOR]

Objectives: Previous studies investigating the prognostic value of HbA1c in patients undergoing coronary angiography reported a mixed pattern of results. Therefore, we aimed to better define the prognostic power of HbA1c among coronary catheterized patients. Methods: Patients undergoing coronary angiography (n = 3,749) were divided into four groups according to HbA1c levels (<5,5-6,6-7 and >7%). Cox regression models assessed long-term mortality after adjusting for multiple covariates. Results: Baseline clinical profiles differed in HbA1c groups, with a higher prevalence of comor-bidities in the groups with higher HbA1c levels. Median follow-up was 1,745 days (interquartile range 1,007-2,171). A J-shaped association curve was observed between HbA1c levels and all-cause mortality rates, with patients in the lowest and highest HbA1c groups suffering from significantly higher mortality rates compared to in-between groups (hazard ratio 1.9, 95% CI 1.32-2.74, p = 0.001, and hazard ratio 1.58,95% CI 1.29-1.95, p < 0.001, for the lowest and highest HbA1c groups, respectively). This association persisted after adjustmentforanemia, nutritional status, renal function, cardiovascular risk factors and inflammatory biomarkers. Conclusions: HbA1c levels <5 or >7% are predictors of all-cause mortality in patients undergoing coronary angiography. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to examine the effects of colchicine, currently in clinical trials for acute myocardial infarction (AMI), on the viability of cardiac cells using a cell line model of AMI. Methods: HL-1, a murine cardiomyocyte cell line, and H9C2, a rat cardiomyoblast cell line, were incubated with TNFa or sera derived from rats that underwent AMI or sham operation followed by addition of colchicine. In another experiment, HL-1/H9C2 cells were exposed to anoxia with or without subsequent addition of colchicine. Cell morphology and viability were assessed by light microscopy, flow cytometry and Western blot analyses for apoptotic markers. Results: Cellular viability was similar in both sera; however, exposing both cell lines to anoxia reduced their viability. Adding colchicine to anoxic H9C2, but not to anoxic HL-1, further increased their mortality, at least in part via enhanced apoptosis. Under any condition, colchicine induced detachment of H9C2 cells from their culture plates. This phenomenon did not apply to HL-1 cells. Conclusions: Colchicine enhanced cardiomyoblast mortality under in vitro conditions mimicking AMI and reduced their adherence capability. HL-1 was not affected by colchicine; nevertheless, no salvage effect was observed. We thus conclude that colchicine may not inhibit myocardial apoptosis following AMI. [ABSTRACT FROM AUTHOR]

Background: Cardiac events are the main cause of death among patients with end-stage renal failure. Even a mild renal disease is currently considered a major risk factor for cardiovascular complications following myocardial infarction (MI). The aim of the present study was to detect histological, sera and urine characteristics of kidney injury in cardiorenal syndrome (CRS) compared to chronic kidney disease (CKD) with an intact cardiac function. Methods: We employed a rat model for CRS, in which an acute MI (AMI) was induced 4 weeks after establishment of subtotal nephrectomy. Four weeks later, left ventricular function was assessed by echocardiography and changes in renal performance were examined using histological and biochemical parameters. Results: Increased interstitial fibrosis as well as renal inflammation were observed in renal sections derived from CRS rats, compared to subtotal nephrectomy (CKD)-only animals. Moreover, we found that even though AMI on the background of CKD was not associated with a further decrease in creatinine clearance or a further increase in sera BUN levels compared to CKD only, a significant long-term elevation in urine neutrophil gelatinase-associated lipocalin (Ngal) levels was detectable post-MI induction. Conclusions: AMI in the CKD setting is associated with accelerated renal fibrosis and long-term elevated urine Ngal values, suggesting that cardiac dysfunction contributes to accelerated intrinsic kidney injury in CKD. The data indicate that elevated urine Ngal may potentially serve as an early non-invasive laboratory parameter for a left ventricular dysfunction-related renal injury. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: In an attempt to reconsider our local strategy, we evaluated patients with viral/idiopathic pericarditis in order to assess the diagnostic yield of our standard infectious panel, the characteristics of myocardial involvement, the utility of investigating myocardial involvement and the incidence of coronary evaluation tests. Methods: Seventy-six consecutive cases of idiopathic/viral acute pericarditis treated between March 2005 and March 2008 were retrospectively enrolled. Telephonic questionnaires were answered by all. Results: Myopericarditis was recorded in 45/71 (63.4%) consecutive patients. Sore throat on presentation (38 vs. 12%; p = 0.027) was the only symptom independently associated with myopericarditis. The following clinical features were significantly correlated with pericarditis rather than myopericarditis: age (42 ± 16 vs. 32 ± 12; p = 0.008), C-reactive protein (131 ± 75 vs. 78 ± 58; p = 0.009) and lower CPK and troponin levels (mean 96 vs. mean 489; p < 0.001 and mean 0 vs. mean 10; p < 0.001, respectively). The infectious panel revealed 6 positive results. After an average 3 years' fol- low-up, recurrence was documented in 5 patients (7%). No patient initially regarded idiopathic developed systemic disease during follow-up. Conclusions: Among patients presenting with presumed idiopathic/viral pericarditis, myopericarditis is relatively common and has a benign evolution. Extensive serological investigation with a broad infectious panel proved to be diagnostically and therapeutically futile in our area. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Increased red cell aggregability might have unfavorable rheological effects in the microcirculation. It has been suggested that thrombolysis-related hypofibrinogenemia might be associated with a reduced erythrocyte adhesiveness/aggregation. We followed the reduction in erythrocyte adhesiveness/aggregation using a simple slide test and image analysis that measures the spaces that are formed between the aggregated erythrocytes. A significant (p = 0.01) reduction in the degree of erythrocyte adhesiveness/aggregation was noted in patients with acute myocardial infarction who received thrombolysis as opposed to individuals with Braunwald Class IIIB unstable angina who had normal fibrinogen concentrations. No change was found in the Westergren erythrocyte sedimentation rate, which is an indirect method to detect changes in aggregability of red blood cells. The present study shows the superiority of using a direct measurement of red blood cell adhesiveness/aggregation. This extremely rapid, cheap and almost bedside methodology to detect changes in erythrocyte adhesiveness/aggregation might be useful to detect changes of hemorheological relevance following thrombolysis.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: Risk factors like hypertension, diabetes mellitus, dyslipidemia and smoking contribute to the pathogenesis of atherothrombosis. We investigated whether the multiplicity of risk factors for atherothrombosis is associated with leukocyte activation. Methods: We examined the availability of CD11b/CD18 antigen on the surface of peripheral blood polymorphonuclear leukocytes and monocytes in patients with acute ischemic heart and brain conditions. Results: There was a highly significant (p < 0.00001) increment in the availability of the CD11b/CD18 antigen on the surface of the polymorphonuclear leukocytes in patients with multiple (2 or more) vascular risk factors [mean fluorescence intensity (MFI) ± SD, 210 ± 102] as opposed to individuals with none or 1 risk factor for atherothrombosis (MFI 159 ± 73). Similar results were observed on the monocytes: 309 ± 151 and 235 ± 97, respectively (p < 0.00001). Conclusion: The multiplicity of risk factors for atherothrombosis is associated with the up-regulation of CD11b/CD18 antigen on the surface of peripheral blood polymorphonuclear leukocytes and monocytes, suggesting the presence of an increased inflammatory response and leukocyte activation in these individuals. [ABSTRACT FROM AUTHOR]

Objective: While both play a role in the transcriptional response of hypoxic endothelial cells (ECs), hypoxia-inducible factor-1α (HIF-1α) and HIF-2α differ in their transactivation sites, pointing at potentially different target genes. We studied the discrete and common effects of HIF-1α and HIF-2α on the cytokine expression and vasculogenic properties of ECs. Methods and Results: H5V and bovine aortic ECs were transfected to express HIF-1α, HIF-2α or both. Overexpression of HIF-1α or HIF-2α and, to a greater extent, cotransfection of HIF-1α and HIF-2α resulted in EC activation, as revealed by analysis of the adhesion capacities and adhesion molecule surface expression of ECs. From the paracrine aspect, conditioned medium from HIF-expressing ECs was found to promote the migration and tube formation capacity of wild-type ECs, mostly following HIF-1α and HIF-2α coexpression. Antibody arrays revealed altered expression of multiple cytokines, pointing at consistent additive effects of HIF-1α and HIF-2α on angiogenic protein expression. Finally, HIF-1α and HIF-2α additively promoted vessel formation in vivo, as demonstrated by a Matrigel angiogenesis assay. Conclusion: Our results further clarify the functional roles of HIF-1α and HIF-2α in ECs and for the first time demonstrate a common contribution of HIF-1α and HIF-2α to vasculogenesis. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]