Abstract Background Non-ST elevation acute coronary syndrome (NSTE-ACS) is one of the common cardiac emergencies that pose a diagnostic challenge, especially in the absence of EKG changes or elevation in cardiac markers. Coronary computed tomography angiography (CT) has an established role in the evaluation of stable chest pain with ESC giving it class I recommendation. The role of CCTA in the management of NSTE-ACS is less clear. Purpose To evaluate the hypothesis of CT efficacy in identifying and managing patients with NSTE-ACS in comparison to the standard of care (SOC). Methods We searched MEDLINE, EMBASE, and Cochrane Central for randomized controlled trials (RCT) that compared initial CT utilization vs SOC in patients presenting with acute chest pain with suspected or confirmed NSTE-ACS. SOC arm included initial evaluation and triaging by treating physician including but not limited to clinical observation, serial cardiac markers, stress testing, and invasive coronary angiography (ICA). Studies with follow-up data of 1 month or more were included. Outcomes evaluated were incidence of rehospitalization/ER visits post index visit, referral to ICA, and presence of significant lesion during ICA requiring revascularization. Results A total of 6,862 patients (3,663 in the CT arm and 3,199 in the SOC) were analyzed from 13 RCTs. No statistically significant difference was noted between two intervention arms with regards to repeat hospital visits [Odds ratio (OR): 1.02; 95% CI: 0.85–1.24; P=0.82; I2=0%], and referral to ICA (OR: 1.32: 95% CI: 0.95–1.83; P=0.10; I2=66). CT was however more likely to uncover significant lesions requiring revascularization compared to SOC arm (OR: 1.77; 95% CI: 1.32–2.37; P=0.0001; I2=23%]. Conclusion Our meta-analysis showed that in patients with suspected NSTE-ACS, CT is associated with similar rates of ICA referral and re-admissions albeit being more likely to uncover hemodynamically significant lesions that require revascularization. These findings are consistent with the finding of the recently published VERDICT trial that showed comparable efficacy between coronary CT and ICA. Further studies evaluating the long term cardiovascular outcomes are warranted. Funding Acknowledgement Type of funding sources: None.

SummaryThe interaction of lipoproteins with hepatitis C virus (HCV) has pathogenic and therapeutic implications. Our aim was to evaluate changes in the apolipoprotein profile of patients with chronic hepatitis C during and after successful cure with ledipasvir and sofosbuvir (LDV/SOF) with and without ribavirin (RBV). One hundred HCV genotype 1 patients who had achieved SVR‐12 after treatment with 12 weeks of LDV/SOF ± RBV were selected from the ION‐1 clinical trial. Frozen serum samples from baseline, end of treatment and week 4 of follow‐up were used to assay apolipoproteins (apoAI, apoAII, apoB, apoCII, apoCIII, apoE) using the Multiplex platform to assess for changes in the apolipoprotein levels. At the end of treatment compared to baseline, a significant reduction in apoAII levels (−14.97 ± 63.44 μg/mL, P = 0.0067) and apoE levels (−4.38 ± 12.19 μg/mL, P < 0.001) was noted. These declines from baseline in apoAII (−16.59 ±66.15 μg/mL, P = 0.0075) and apoE (−2.66 ± 12.64 μg/mL, P = 0.015) persisted at 4 weeks of post‐treatment follow‐up. In multivariate analysis, treatment with LDV/SOF + RBV was independently associated with reduction in apoE (beta = 5.31 μg/mL, P = 0.002) (compared to RBV‐free LDV/SOF) (P < 0.05). In contrast, apoCII levels overall increased from baseline to end of treatment (+2.74 ±11.76 μg/mL, P = 0.03) and persisted at 4 weeks of follow‐up (+4.46 ± 12.81 μg/mL from baseline, P = 0.0005). Subgroup analysis revealed an increase in apoCII during treatment only in patients receiving LDV/SOF without RBV (+5.52 ± 11.92 μg/mL, P = 0.0007) but not in patients receiving LDV/SOF + RBV (P = 0.638). Treatment with LDV/SOF ± RBV is associated with a persistent reduction in the apolipoprotein AII and E after achieving cure. These data suggest that treatment with LDV/SOF ± RBV may be associated with alterations in serum apolipoproteins which could potentially impact viral eradication.

STUDY QUESTION Do plasma levels of stromal cell-derived factor-1 (CXCL12, sometimes termed SDF-1) and the numbers of circulating endothelial progenitor cells (EPCs), EPC colony-forming units (EPC-CFU) and mature endothelial cells (ECs) differ between women with idiopathic heavy menstrual bleeding of endometrial origin (HMB-E) and controls and are they related to plasma levels of other angiogenic growth factors? SUMMARY ANSWER Angiogenesis is altered in women with HMB-E, characterized by a reduction in mean plasma levels of CXCL12, a low number of EPCs-CFUs and a high level of circulating ECs. WHAT IS KNOWN ALREADY Plasma levels of CXCL12 are significantly higher during the proliferative than the secretory phase of the menstrual cycle in healthy women and exhibit a negative correlation with blood EPC-CFUs. STUDY DESIGN, SIZE, DURATION A prospective cohort study in a university hospital setting. Between 2008 and 2009 10 HMB-E patients were recruited from Karolinska University Hospital. Ten healthy women were also included in the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS Ten healthy control women and 10 HMB-E patients, all with regular menstrual cycles, provided 4 blood samples during a single menstrual cycle: 2 in the proliferative phase, 1 at ovulation and 1 in the secretory phase. We assessed plasma levels of CXCL12, vascular endothelial growth factor A(165) (VEGFA), basic fibroblast growth factor (bFGF) and granulocyte and granulocyte-macrophage colony-stimulating factors by ELISA. We counted circulating EPC-CFUs by culture, and ECs and EPCs by flow cytometry and immunostaining for cell surface markers. MAIN RESULTS AND THE ROLE OF CHANCE Plasma levels of CXCL12 were significantly lower in HMB-E patients compared with control women (P < 0.0001), with a significant decrease (P = 0.013) between the proliferative phase and ovulation. VEGFA showed a trend towards the same decreasing pattern as CXCL12, although not statistically significant (P = 0.086), whereas systemic VEGFA levels in control women remained unchanged across the different phases of the menstrual cycle (P = 0.473). HMB-E patients had a lower number of EPC-CFUs compared with control women (P = 0.014), with a positive correlation between the level of CXCL12 and EPC-CFUs (r = 0.428; P = 0.047). Whilst the level of circulating endothelial cells in HMB-E patients was higher than in control women, this did not reach statistical significance. In contrast, the levels of the hematopoietic/EPC marker CD34 were significantly lower in HMB-E patients than control women (P < 0.020). LIMITATIONS, REASONS FOR CAUTION Small sample, unknown source of CXCL12, unknown balance between influx and efflux of EPCs from bone marrow and to the endometrium. WIDER IMPLICATIONS OF THE FINDINGS Our results indicate that CXCL12 may play an important role in physiological angiogenesis in the endometrium, and that low and dysregulated levels of CXCL12 in women with HMB-E could affect vessel quality, integrity and repair. STUDY FUNDING/COMPETING INTEREST(S) Financial support was provided through the regional agreement on medical training and clinical research (ALF) between the Stockholm County Council and Karolinska Institutet (number 20110258). This study was also supported by grants from the Swedish Labor Market Insurance. The authors have no conflict of interest to declare.

Conclusions: Serum endocan levels seem to be increased in NAFLD patients with CAD.These data suggest that increased serum endocan may be important for detecting endothelial cell damage in NAFLD patients.Additionally, endocan is potentially involved in the pathogenic mechanism of CAD in NAFLD patients.

Background Chronic hepatitis C virus (CH-C) infection is associated with metabolic conditions such as insulin resistance and type 2 diabetes (DM) and may increase the risk of cardiovascular diseases. Aim To assess the association of CH-C with risk factors for cardiovascular diseases using US population data. Methods The National Health and Nutrition Examination Surveys (NHANES) collected between 1999 and 2010 were used. Results Of 19741 participants considered eligible for the study. Of this cohort, 173 individuals (0.88%) had detectable HCV RNA and were considered to have CH-C. Compared with controls, CH-C patients were predominantly African American (23.5% vs. 10.5%, P<0.0001), men (66.6% vs. 46.1%, P=0.0001), more likely to be between 45 and 55years of age (41.9% vs. 20.4%, P=0.0001), had higher rate of insulin resistance (44.1% vs. 31.1%, P=0.0301), hypertension (40.1% vs. 28.9%, P=0.0201), and history of smoking (76.2% vs. 29.9%, P<0.0001). In multivariate analysis, in addition to known risk factors for insulin resistance, CH-C was independently associated with the presence of insulin resistance [OR (95% CI)=2.06 (1.193.57)], DM [OR=2.31 (1.184.54)] and hypertension [OR=2.06 (1.303.24)]. Independent predictors of cardiovascular diseases included older age, presence of obesity and smoking. CH-C was independently associated with congestive heart failure subtype of cardiovascular diseases but not ischaemic heart disease and stroke. Conclusion Chronic hepatitis C virus infection is independently associated with presence of metabolic conditions (insulin resistance, type 2 diabetes mellitus and hypertension) and congestive heart failure.