Background: The aim of this study was to evaluate the prognostic values of five lymphocyte-based inflammatory indices (platelet-lymphocyte ratio [PLR], neutrophil-lymphocyte ratio [NLR], monocyte-lymphocyte ratio [MLR], systemic immune inflammation index [SII], and system inflammation response index [SIRI]) in patients with acute coronary syndrome (ACS).Methods: A total of 1,701 ACS patients who underwent percutaneous coronary intervention (PCI) were included in this study and followed up for major adverse cardiovascular events (MACE) including all-cause death, non-fatal ischemic stroke, and non-fatal myocardial infarction. The five indices were stratified by the optimal cutoff value for comparison. The association between each of the lymphocyte-based inflammatory indices and MACE was assessed by the Cox proportional hazards regression analysis.Results: During the median follow-up of 30 months, 107 (6.3%) MACE were identified. The multivariate COX analysis showed that all five indices were independent predictors of MACE, and SIRI seemingly performed best (Hazard ratio [HR]: 3.847; 95% confidence interval [CI]: [2.623–5.641]; p < 0.001; C-statistic: 0.794 [0.731–0.856]). The addition of NLR, MLR, SII, or SIRI to the Global Registry of Acute Coronary Events (GRACE) risk score, especially SIRI (C-statistic: 0.699 [0.646–0.753], p < 0.001; net reclassification improvement [NRI]: 0.311 [0.209–0.407], p < 0.001; integrated discrimination improvement [IDI]: 0.024 [0.010–0.046], p < 0.001), outperformed the GRACE risk score alone in the risk predictive performance.Conclusion: Lymphocyte-based inflammatory indices were significantly and independently associated with MACE in ACS patients who underwent PCI. SIRI seemed to be better than the other four indices in predicting MACE, and the combination of SIRI with the GRACE risk score could predict MACE more accurately.

Omentin-1, a novel adipocytokine mainly expressed in visceral adipose tissue, has been found to inhibit the inflammatory response and improve insulin resistance as well as other obesity-related disorders. This study investigated the association between omentin-1 expression in human epicardial adipose tissue (EAT) and coronary atherosclerosis. Serum samples, and paired biopsies from EAT and subcutaneous adipose tissue (SAT), were obtained from patients with and without coronary artery disease (CAD, n = 28 and NCAD, n = 12, respectively) during elective cardiac surgery. Coronary angiography was performed to identify CAD presence. Serum omentin-1 and adiponectin levels were measured by ELISA. mRNA expression of omentin-1 and adiponectin was detected in adipose tissue by quantitative real-time PCR, and omentin-1 protein expression was evaluated by immunohistochemistry. Correlation and multivariate linear regression analyses were performed to determine the association between omentin-1 expression and clinical risk factors. mRNA and protein expression of omentin-1 were higher in EAT than paired SAT in patients with CAD and NCAD. Compared with NCAD patients, CAD patients had lower omentin-1 and adiponectin mRNA levels in EAT and serum levels as well as lower omentin-1 protein levels. Among patients with CAD, omentin-1 expression was lower in EAT surrounding coronary segments with stenosis than those without stenosis, in terms of mRNA and protein, whereas adiponectin mRNA level in EAT did not seem to differ between stenotic and non-stenotic coronary segments in CAD patients. In multivariate linear regression analysis, CAD was an independent predictor of EAT omentin-1 mRNA expression (beta = −0.57, 95 % CI −0.89 to −0.24; P = 0.001) and serum omentin-1 levels (beta = −0.35, 95 % CI −0.67 to −0.03; P = 0.036). Circulating and EAT-derived omentin-1 levels were reduced in patients with CAD. Omentin-1 expression in patients with CAD was lower in EAT adjacent to coronary stenotic segments than non-stenotic segments.

Backgrounds: Omentin-1 is a novel cytokine that is primarily released by the epicardial adipose tissue. Molecular structure analysis revealed that it contained a fibrinogen-like domain. Clinical studies have demonstrated that the expression of omentin-1 is tightly associated with the development of cardiovascular diseases, but the receptor by which omentin-1 modulates macrophage function has not been identified yet.Objective: This study sought to investigate the effect of omentin-1 on already-established atherosclerosis (AS) lesions in both ApoE−/− and Ldlr^−/− mice and further, study its underlying mechanisms.Methods and Results: We investigated the effect of omentin-1 on the plaque phenotype by implanting a minipump in ApoE−/− and Ldlr^−/− mice. In vivo studies showed that the infusion of omentin-1 increased the collagen content and mitigated the formation of the necrotic core in both animal models. Immunohistochemistry and immunofluorescence analysis revealed that omentin-1 suppressed inflammatory cytokines expression, macrophage infiltration, and apoptosis within the plaque. An immunoprecipitation experiment and confocal microscopy analysis confirmed the binding of omentin-1 to the integrin receptors αvβ3 and αvβ5. The cell studies demonstrated that omentin-1 suppressed the apoptosis and inflammatory cytokines expression induced by the oxidized low-density lipoprotein in the macrophage. In addition, omentin-1 promoted the phosphorylation of the integrin-relevant signaling pathway as well as the Akt and AMPK in the macrophage. The addition of the inhibitor of the integrin receptor or interfering with the expression of the integrin subunit αv (ITGAV) both significantly abrogated the bioeffects induced by omentin-1. A flow cytometry analysis indicated that the antibodies against αvβ3 and αvβ5 had a competitive effect on the omentin-1 binding to the cell membrane.Conclusions: The administration of adipokine omentin-1 can inhibit the necrotic cores formation and pro-inflammatory cytokines expression within the AS lesion. The mechanisms may include the suppression of apoptosis and pro-inflammatory cytokines expression in the macrophage by binding to the integrin receptors αvβ3 and αvβ5.

Aims: This study aimed to investigate the association of elevated RC levels with adverse cardiovascular outcomes in acute coronary syndrome (ACS) patients with and without diabetes. Methods: We analyzed data from 1716 patients with ACS undergoing percutaneous coronary intervention. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol. RC ＞75th percentile of the cohort (＞0.79 mmol/L) was defined as abnormally elevated RC. Cox-regression models and Kaplan-Meier analyses were used to assess the relationship between RC ＞0.79 mmol/L and major adverse cardiovascular events (MACE).Results: During a median follow-up of 927 days, a total of 354 patients had at least one event. In the overall population, compared with those with RC ≤ 0.79 mmol/L, patients with RC ＞0.79 mmol/L had a significantly higher risk of MACE after adjustment for potential confounders (hazard ratio: 1.572, 95% confidence interval: 1.251-1.975, P＜0.001). In addition, RC ＞0.79 mmol/L was associated with an increased risk of MACE of 66.7% (P=0.001) and 50.1% (P=0.022) in the diabetic and non-diabetic subgroups (P for interaction=0.073), respectively. The addition of RC significantly improved the predictive ability of baseline models for MACE in diabetic patients (all P＜0.05), but not in non-diabetic patients (all P＞0.05). Conclusion: Abnormally elevated RC was significantly associated with worse prognosis in both diabetic and non-diabetic patients with ACS; however, the prognostic value of RC might be superior among diabetic patients.

Previous studies have demonstrated that secreted frizzled-related protein 4 (SFRP4) is associated with impaired glucose and triglyceride metabolism in patients with stable coronary artery disease. In the present study, we investigated human epicardial adipose tissue (EAT)-derived and circulating SFRP4 levels in patients with coronary artery disease (CAD). Plasma samples and adipose biopsies from EAT and subcutaneous adipose tissue (SAT) were collected from patients with CAD (n = 40) and without CAD (non-CAD, n = 30) during elective cardiac surgery. The presence of CAD was identified by coronary angiography. SFRP4 mRNA and protein expression levels in adipose tissue were detected by quantitative real-time PCR and immunohistochemistry, respectively. Plasma SFRP4 concentrations were measured by an enzyme-linked immunosorbent assay (ELISA). Correlation analysis and multivariate linear regression analysis were used to determine the association of SFRP4 expression with atherosclerosis as well as clinical risk factors. SFRP4 mRNA and protein expression levels were significantly lower in EAT than in paired SAT in patients with and without CAD (all P < 0.05). Compared to non-CAD patients, CAD patients had higher SFRP4 expression levels in EAT (both mRNA and protein levels) and in plasma. Multivariate linear regression analysis showed that CAD was an independent predictor of SFRP4 expression levels in EAT (beta = 0.442, 95% CI 0.030–0.814; P = 0.036) and in plasma (beta = 0.300, 95% CI 0.056–0.545; P = 0.017). SAT-derived SFRP4 mRNA levels were independently associated with fasting insulin levels (beta = 0.382, 95% CI 0.008–0.756; P = 0.045). In addition, plasma SFRP4 levels were positively correlated with BMI (r = 0.259, P = 0.030), fasting insulin levels (r = 0.306, P = 0.010) and homeostasis model assessment of insulin resistance (HOMA-IR) values (r = 0.331, P = 0.005). EAT-derived and circulating SFRP4 expression levels were increased in patients with CAD. EAT SFRP4 mRNA levels and plasma SFRP4 concentrations were independently associated with the presence of CAD.

Periprocedural heparin bridging therapy aims to reduce the risk of thromboembolic events in patients requiring an interruption in their anticoagulation therapy for the purpose of an elective procedure. The efficacy and safety of heparin bridging therapy has not been well established. To compare through meta-analysis the effects of heparin bridging therapy on the risk of major bleeding and thromboembolic events of clinical significance among patients taking oral anticoagulants. We searched PubMed, EMBASE and the Cochrane library from January 2005 to July 2016. Studies were included if they reported clinical outcomes of patients receiving heparin bridging therapy during interruption of oral anticoagulant for operations. Data were pooled using random-effects modeling. A total of 25 studies, including 6 randomized controlled trials and 19 observational studies, were finally included in this analysis. Among all the 35,944 patients, 10,313 patients were assigned as heparin bridging group, and the other 25,631 patients were non-heparin bridging group. Overall, compared with patients without bridging therapy, heparin bridging therapy increased the risk of major bleeding (OR = 3.23, 95%CI: 2.06–5.05), minor bleeding (OR = 1.52, 95%CI: 1.06–2.18) and overall bleeding (OR = 2.83, 95%CI: 1.86–4.30).While there was no significant difference in thromboembolic events (OR = 0.99,95%CI: 0.49–2.00), stroke or transient ischemic attack(OR = 1.45, 95%CI: 0.93–2.26,) or all-cause mortality (OR = 0.71, 95%CI: 0.31–1.65). Heparin-bridging therapy increased the risk of major and minor bleeding without decreasing the risk of thromboembolic events and all cause death compared to non-heparin bridging.