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Abstract Background Myocardial infarction (MI) is a major cause of mortality and morbidity worldwide. The intercellular communication in post-infarction angiogenesis remains unclear. Methods In this study, we explored the role and mechanism of action of M2 macrophage-derived exosomes (M2-exos) in angiogenesis after MI. M2-exos were harvested and injected intramyocardially at the onset of MI. Two distinct endothelial cells (ECs) were cultured with M2-exos to explore the direct effects on angiogenesis. Results We showed that M2-exos improved cardiac function, reduced infarct size, and enhanced angiogenesis after MI. Moreover, M2-exos promoted angiogenesis in vitro; the molecules loaded in the vesicles were responsible for its proangiogenic effects. We further validated that higher abundance of miR-132-3p in M2-exos, which recapitulate their functions, was required for the cardioprotective effects exerted by M2-exos. Mechanistically, miR-132-3p carried by M2-exos down-regulate the expression of THBS1 through direct binding to its 3´UTR and the proangiogenic effects of miR-132-3p were largely reversed by THBS1 overexpression. Conclusion Our findings demonstrate that M2-exos promote angiogenesis after MI by transporting miR-132-3p to ECs, and by binding to THBS1 mRNA directly and negatively regulating its expression. These findings highlight the role of M2-exos in cardiac repair and provide novel mechanistic understanding of intercellular communication in post-infarction angiogenesis.

Abstract Background Although multiple measures of blood pressure variability (BPV) have been proposed, whether they are better than mean blood pressure in predicting target organs is unclear. We aimed to determine the relationship between short term BPV and target organ injury. Methods This study was a retrospective study, and 635 inpatients in the Department of Cardiology from 2015 to 2020 were selected. We divided participants into four groups on the basis of the quartiles of BPV. One‐way analysis of variance was used to compare the differences between the groups, and linear regression was used to analyze the relationship between BPV and target organ damage. Results The average age of 635 patients was 74.36 ± 6.50 years old. Among them, 354 of 627 patients had diminished renal function (56.5%), 221of 604 patients had associated left ventricular hypertrophy (36.6%), and 227 of 231 patients had carotid plaque formation (98.3%). The baseline data indicated significant differences in fasting glucose, total cholesterol, low‐density lipoprotein, creatinine, glomerular filtration rate, sex, calcium channel blocker use, and the rate of diminished renal function. Multiple linear regression analysis showed that BPV was negatively correlated with renal injury (creatinine: r = 0.306, p

Abstract. Background:. Atherosclerosis-related diseases represent significant health issues among adults globally. Despite their widespread impact, comprehensive data concerning the global and national burden and trends of these diseases remain sparse. Our objective is to examine the trends in the burden of atherosclerosis among adults from 1990 to 2019 at both global and national levels. Methods:. We reported the average annual percentage changes (AAPCs) in prevalence, incidence, mortality, and disability-adjusted life years (DALYs) of atherosclerosis-related diseases (ischemic heart disease [IHD], ischemic stroke, and peripheral arterial disease [PAD]) at the global and national levels among individuals based on a trend analysis of the Global Burden of Diseases Study (GBD) 2019. We further analyzed these global trends as a function of age, gender, and the social development index. We also used joinpoint regression analysis to identify the year with the most substantial changes in global trends. Results:. Globally, the AAPC of IHD incidence rose from 1990 to 2019 (0.20; 95% confidence interval [CI], 0.12-0.28), with substantial surges in 1995, 2001, 2005, 2010, and 2017. Conversely, AAPC of IHD mortality rates exhibited a different trend until a rise in 2014. The AAPC of incidence rates of ischemic stroke and PAD also escalated during the same period, with respective 0.43 (95% CI, 0.39-0.48) and 0.13 (95% CI, 0.06-0.21). For ischemic stroke, both incidence and mortality soared in 2014, while PAD incidence declined in 1994 and 1998, then sharply climbed in 2016. Nationally, the Northern Mariana Islands experienced the steepest increase in IHD and PAD incidence and mortality between 1990 and 2019. China saw a significant rise in ischemic stroke incidence, whereas the highest mortality rate increase occurred in Timor-Leste. By sociodemographic index (SDI) quintile, low-middle-, middle-, and high-middle-SDI countries all showed upward trends in IHD, ischemic stroke, and PAD incidence. Simultaneously, IHD and ischemic stroke mortality rates, as well as DALYs, dropped in the low-, high-middle-, and high-SDI nations. However, PAD mortality rates and DALYs saw an uptick across all SDI quintiles. Regarding age demographics, a global decrease in the AAPC IHD incidence as noted in individuals above 55 years old, in contrast to an increase in the 20-55 age group during this period. AAPC of mortality rates for IHD, ischemic stroke, and PAD decreased across all ages. The AAPC showed an increase in IHD incidence in both genders. Conversely, IHD's DALYs saw a reduction in both males and females. Ischemic stroke patterns mirrored these trends, whereas all measures for PAD exhibited growth for both sexes. Conclusions:. From 1990 to 2019, there was an overall increasing trend in the global incidence of all three clinical manifestations of atherosclerosis. Between 1990 and 2019, both the mortality rate and DALYs for IHD and ischemic stroke declined across all age groups. Overall, the burden of atherosclerosis-related diseases has not significantly decreased and even shows signs of trending upward. These findings strongly suggest that despite some progress made, efforts to control atherosclerosis diseases globally need to be intensified.

Abstract Background A lthough the triglyceride-glucose (TyG) index has been shown to closely correlate with cardiometabolic outcomes and predict cardiovascular events in many groups, it remains unclear whether obese status in young and middle-aged adults is associated with long-term unfavorable cardiovascular events. This warrants further investigation. Methods This retrospective cohort study analyzed data from the National Health and Nutrition Examination Survey spanning the years 1999–2018, with follow-up for mortality status until December 31, 2019. To categorize participants based on the TyG level, the optimal critical value was determined through restricted cubic spline function analysis, dividing them into high and low TyG groups. The study assessed the relationship between TyG and cardiovascular events and all-cause mortality in young and middle-aged adults stratified by obesity status. Kaplan‒Meier and Cox proportional risk models were used to analyze the data. Results During a follow-up period of 123 months, a high TyG index increased the risk of cardiovascular events by 63% (P = 0.040) and the risk of all-cause mortality by 32% (P = 0.010) in individuals after adjusting for all covariates. High TyG was shown to be linked to cardiovascular events in obese people (Model 3: HR = 2.42, 95% CI = 1.13–5.12, P = 0.020); however, there was no significant difference in TyG groups for nonobese adults in Model 3 (P = 0.08). Conclusions TyG was independently associated with harmful long-term cardiovascular events in young and middle-aged US populations, with a stronger association observed in those who were obese.

Abstract. Background:. Limited data are available on the comparison of clinical outcomes of complete vs. incomplete percutaneous coronary intervention (PCI) for patients with chronic total occlusion (CTO) and multi-vessel disease (MVD). The study aimed to compare their clinical outcomes. Methods:. A total of 558 patients with CTO and MVD were divided into the optimal medical treatment (OMT) group (n = 86), incomplete PCI group (n = 327), and complete PCI group (n = 145). Propensity score matching (PSM) was performed between the complete and incomplete PCI groups as sensitivity analysis. The primary outcome was defined as the occurrence of major adverse cardiovascular events (MACEs), and unstable angina was defined as the secondary outcome. Results:. At a median follow-up of 21 months, there were statistical differences among the OMT, incomplete PCI, and complete PCI groups in the rates of MACEs (43.0% [37/86] vs. 30.6% [100/327] vs. 20.0% [29/145], respectively, P = 0.016) and unstable angina (24.4% [21/86] vs. 19.3% [63/327] vs. 10.3% [15/145], respectively, P = 0.010). Complete PCI was associated with lower MACE compared with OMT (adjusted hazard ratio [HR] = 2.00; 95% confidence interval [CI] = 1.23–3.27; P = 0.005) or incomplete PCI (adjusted HR = 1.58; 95% CI = 1.04–2.39; P = 0.031). Sensitivity analysis of PSM showed similar results to the above on the rates of MACEs between complete PCI and incomplete PCI groups (20.5% [25/122] vs. 32.6% [62/190], respectively; adjusted HR = 0.55; 95% CI = 0.32–0.96; P = 0.035) and unstable angina (10.7% [13/122] vs. 20.5% [39/190], respectively; adjusted HR = 0.48; 95% CI = 0.24–0.99; P = 0.046). Conclusions:. For treatment of CTO and MVD, complete PCI reduced the long-term risk of MACEs and unstable angina, as compared with incomplete PCI and OMT. Complete PCI in both CTO and non-CTO lesions can potentially improve the prognosis of patients with CTO and MVD.

Objective: This study aimed to assess the effects of coronary collateral circulation (CCC) on the prognosis of patients with chronic total occlusion (CTO) under different treatment strategies. Methods: We analyzed a total of 1124 patients who were diagnosed with CTO and divided them into groups with good CCC (grade 2 to 3, n = 539) or poor CCC (grade 0 to 1, n = 531). The primary outcome was cardiac death during follow-up; the secondary outcome was major adverse cardiovascular events (MACEs). We also performed subgroup analyses in groups with and without CTO revascularization (CTO-R and CTO-NR, respectively), and sensitivity analyses excluding patients who received failed CTO-PCI to further investigate the effect of CCC. Results: During a median follow-up duration of 23 months, we did not detect any significant differences between the good CCC group and the poor CCC group in terms of cardiac death (4.2% vs 4.1%; adjusted hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.56–1.83; p = 0.970) and MACEs (23.6% vs 23.2%; adjusted HR, 1.07; 95% CI, 0.84–1.37; p = 0.590). Subgroup analyses according to CTO revascularization showed similar results. In addition, we observed no differences in sensitivity analyses when patients who received failed CTO-PCI were excluded. Conclusion: Good CCC was not associated with a lower risk of cardiac death or MACEs among patients with CTO, regardless of whether the patients received CTO revascularization treatment.

Abstract Background Despite many significant advances in treatment and management, cardiovascular disease remains the main cause of the global disease burden. Nutrition-related disease is a modifiable cardiovascular risk factor. However, few studies have examined the relationship between nutrition-related diseases and cardiovascular mortality. Objective We aimed to investigate the association of nutrition-related diseases with cardiovascular mortality based on a large nationally representative community population. Design We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999–2006 with mortality follow-up through December 31, 2015. Finally, 12,469 participants were analyzed. Each participant was assigned to one of four groups: normal nutrition without sarcopenia, sarcopenia with normal nutrition, malnutrition without sarcopenia, and malnutrition-sarcopenia syndrome. Survival curves and Cox regressions based on the NHANES recommended weights were used to assess the association between nutrition-related diseases and cardiovascular mortality. Results Of the 12,469 patients included in the study and divided into four groups, malnutrition-sarcopenia syndrome had the highest 5- and 10-year cardiovascular mortality rates. After adjustment for related factors, sarcopenia with normal nutrition (hazard ratio [HR]: 1.62, 95% confidence interval [CI]: 1.28–2.06; P

Abstract Background Chronic total occlusion (CTO) is a critical and unique subgroup of coronary lesions. This study aimed to investigate the correlation between the Selvester QRS score and late gadolinium enhancement cardiac magnetic resonance imaging (LGE‐CMRI) in quantifying myocardial scarring to provide a simple and feasible method for treating CTO. Methods The medical records of 134 patients with absolute CTO who underwent coronary angiography between May 1, 2014 and December 30, 2017 were retrospectively reviewed. All patients were grouped according to the CTO location (right coronary artery [RCA] CTO, left artery descending [LAD] CTO, left circumflex [LCX] CTO, and multivessel CTO groups). The degree of myocardial scarring was determined according to the Selvester QRS score and using the LGE‐CMRI. All patients were followed up for at least 12 months. Results Among the 62 CTO patients, 55 had occlusion of a single vessel and seven had occlusion of multiple vessels, of which 27 (43.55%) were in the RCA CTO group, 16 (25.81%) in the LAD CTO group, 12 (19.35%) in the LCX CTO group, and 7 (11.29%) in the multivessel CTO group. The area under the receiver operating characteristic curve for the QRS score that was used to determine the degree of myocardial scarring was 0.806, with a sensitivity and specificity of 94.7% and 42.1%, respectively. The Selvester QRS score and LGE‐CMRI measures of scar size were correlated in the RCA CTO, LCX CTO, and multivessel CTO groups (r = 0.466, 0.593, and 0.775, respectively). Conclusion The Selvester QRS score was feasible for detecting myocardial scarring in patients with CTO.

Multiple pathophysiological pathways are activated during the process of myocardial injury. Various cardioprotective strategies protect the myocardium from ischemia, infarction, and ischemia/reperfusion (I/R) injury through different targets, yet the clinical translation remains limited. Caveolae and its structure protein, caveolins, have been suggested as a bridge to transmit damage-preventing signals and mediate the protection of ultrastructure in cardiomyocytes under pathological conditions. In this review, we first briefly introduce caveolae and caveolins. Then we review the cardioprotective strategies mediated by caveolins through various pathophysiological pathways. Finally, some possible research directions are proposed to provide future experiments and clinical translation perspectives targeting caveolin based on the investigative evidence.

Objective The American Heart Association (AHA) proposed the concept of ideal cardiovascular health (CVH) to reduce the risk of cardiovascular mortality. We attempted to broaden the impact of CVH and further contribute to AHA 2030 goals by identifying the relationship between CVH and non-cardiovascular diseases such as sarcopenia.Design Cross-sectional surveySetting National Health and Nutrition Examination Survey conducted in the USA from 2011 to 2018.Participants This study included participants with reliable first 24-hour dietary recall and ≥20 years of age and excluded those who could not diagnose sarcopenia or insufficient data to calculate the CVH scores.Primary and secondary outcome measures The prevalence of sarcopenia as measured by dual-energy X-ray absorptiometry.Results This cohort study involving 9326 adults≥20 years comprised 4733 females (50.0%). The number of intermediate or ideal and poor CVH participants was 5654 and 3672 with mean CVH score of 9.70±0.03 and 5.66±0.04, respectively. After adjusting for related confounding factors, intermediate or ideal CVH was associated with an odds reduction of sarcopenia than poor CVH (adjusted OR (aOR): 0.36, 95% CI 0.26 to 0.50, p5, the odds of sarcopenia decreased by up to 84% (aOR: 0.16, 95% CI 0.08 to 0.30).Conclusions Our findings suggest a relationship between the CVH and the prevalence of sarcopenia in adults. The results of our study can contribute to achieving the 2030 public health goal of achieving CVH for all, which may be supported by efforts to reduce the prevalence of sarcopenia.

Abstract Background In this study, we compared the outcomes of medical therapy (MT) with successful percutaneous coronary intervention (PCI) in chronic total occlusions (CTO) patients with and without type 2 diabetes mellitus. Methods A total of 2015 patients with CTOs were stratified. Diabetic patients (n = 755, 37.5%) and non-diabetic patients (n = 1260, 62.5%) were subjected to medical therapy or successful CTO-PCI. We performed a propensity score matching (PSM) to balance the baseline characteristics. A comparison of the major adverse cardiac events (MACE) was done to evaluate long-term outcomes. Results The median follow-up duration was 2.6 years. Through multivariate analysis, the incidence of MACE was significantly higher among diabetic patients compared to the non-diabetic patients (adjusted hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.09–1.61, p = 0.005). Among the diabetic group, the rate of MACE (adjusted HR 0.61, 95% CI 0.42–0.87, p = 0.006) was significantly lower in the successful CTO-PCI group than in the MT group. Besides, in the non-diabetic group, the prevalence of MACE (adjusted HR 0.85, 95% CI 0.64–1.15, p = 0.294) and cardiac death (adjusted HR 0.94, 95% CI 0.51–1.70, p = 0.825) were comparable between the two groups. Similar results as with the early detection were obtained in propensity-matched diabetic and non-diabetic patients. Notably, there was a significant interaction between diabetic or non-diabetic with the therapeutic strategy on MACE (p for interaction = 0.036). Conclusions For treatment of CTO, successful CTO-PCI highly reduces the risk of MACE in diabetic patients when compared with medical therapy. However, this does not apply to non-diabetic patients.

Objectives: There are little data on the long-term clinical outcomes of medical therapy (MT) compared with revascularization in patients with chronic total occlusions (CTOs). Methods: Between January 2007 and December 2016, a total of 1655 patients with ≥1 CTO were enrolled in our center and were divided into the MT group (n = 800) and revascularization group (n = 855) according to the initial treatment strategy. Propensity score matching was also performed to adjust for baseline characteristics. The primary outcome was cardiac death. Results: After 2 years of follow-up, there was no significant difference between the two groups with regard to the prevalence of cardiac death (MT vs. revascularization: 6.6% vs. 4.2%, adjusted hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.60–1.49, p = 0.820). In the propensity-matched population (406 pairs), there were no significant differences in the prevalence of cardiac death (MT vs. revascularization: 5.4% vs. 4.7%, HR 0.88, 95% CI 0.48–1.63, p = 0.694), except for target vessel revascularization (TVR) (0.44, 0.31–0.63,

Background: Acute myocardial infarction (AMI)-induced excessive myocardial fibrosis exaggerates cardiac dysfunction. However, serum Wnt2 or Wnt4 level in AMI patients, and the roles in cardiac fibrosis are largely unkown. Methods: AMI and non-AMI patients were enrolled to examine serum Wnt2 and Wnt4 levels by ELISA analysis. The AMI patients were followed-up for one year. MI mouse model was built by ligation of left anterior descending branch (LAD). Findings: Serum Wnt2 or Wnt4 level was increased in patients with AMI, and the elevated Wnt2 and Wnt4 were correlated to adverse outcome of these patients. Knockdown of Wnt2 and Wnt4 significantly attenuated myocardial remodeling and cardiac dysfunction following experimental MI. In vitro, hypoxia enhanced the secretion and expression of Wnt2 and Wnt4 in neonatal rat cardiac myocytes (NRCMs) or fibroblasts (NRCFs). Mechanistically, the elevated Wnt2 or Wnt4 activated β-catenin /NF-κB signaling to promote pro-fibrotic effects in cultured NRCFs. In addition, Wnt2 or Wnt4 upregulated the expression of these Wnt co-receptors, frizzled (Fzd) 2, Fzd4 and (low-density lipoprotein receptor-related protein 6 (LRP6). Further analysis revealed that Wnt2 or Wnt4 activated β-catenin /NF-κB by the co-operation of Fzd4 or Fzd2 and LRP6 signaling, respectively. Interpretation: Elevated Wnt2 and Wnt4 activate β-catenin/NF-κB signaling to promote cardiac fibrosis by cooperation of Fzd4/2 and LRP6 in fibroblasts, which contributes to adverse outcome of patients with AMI, suggesting that systemic inhibition of Wnt2 and Wnt4 may improve cardiac dysfunction after MI.

Background: The safety and efficacy associated with the use of proton pump inhibitors (PPIs) by patients with coronary artery disease receiving dual antiplatelet therapy (DAPT) remain unclear.Methods: The evaluated outcomes included combined major adverse cardiovascular events (MACEs), myocardial infarction (MI), all-cause mortality, and gastrointestinal (GI) bleeding. A random effects meta-analysis, stratified by study design, was performed and heterogeneity was assessed using the I2 statistic.Results: In total, 6 randomized controlled trials (RCTs) (6930 patients) and 16 observational studies (183,546 patients) were included. Analysis of RCTs showed that there were no significant differences in the incidences of MACEs (risk ratio [RR] = 0.89 [95% confidence interval (CI) = 0.75–1.05]), MI (RR = 0.93 [95% CI = 0.76–1.15]), and all-cause mortality (RR = 0.79 [95% CI = 0.50–1.23]) in the PPI groups vs. the non-PPI groups. Pooled data from observational studies revealed an inconsistent association between the use of each PPI subtype and the increased risks of MACEs during clopidogrel treatment. There was no increased risk of MACEs or all-cause mortality associated with the use of PPIs (as a class) and other P2Y12 inhibitors. Both the RCTs and observational studies revealed that the use of PPIs significantly reduced the risks of GI bleeding.Conclusion: The use of PPIs was associated with a reduced risk of GI bleeding in patients treated with DAPT after percutaneous coronary intervention or acute coronary syndrome. There was no clear evidence of an association between the use of PPIs and adverse cardiovascular events.Clinical Trial Registration: identifier [CRD42020190315]

Aims: To determine the agreement between two-dimensional transthoracic echocardiography (2DTTE) and cardiovascular magnetic resonance (CMR) in left ventricular (LV) function [including end-systolic volume (LVESV), end-diastolic volume (LVEDV), and ejection fraction (LVEF)] in chronic total occlusion (CTO) patients.Methods: Eighty-eight CTO patients were enrolled in this study. All patients underwent 2DTTE and CMR within 1 week. The correlation and agreement of LVEF, LVESV, and LVEDV as measured by 2DTTE and CMR were assessed using Pearson correlation, Kappa analysis, and Bland–Altman method.Results: The mean age of patients enrolled was 57 ± 10 years. There was a strong correlation (r = 0.71, 0.90, and 0.80, respectively, all P < 0.001) and a moderately strong agreement (Kappa = 0.62, P < 0.001) between the two modalities in measurement of LV function. The agreement in patients with EF ≧50% was better than in those with an EF

Background: The number of coronary chronic total occlusion (CTO) patients with left ventricular (LV) systolic dysfunction is significant, but the clinical outcomes of these patients are rarely reported. The present retrospective cohort study aimed to investigate the long-term outcomes of successful recanalization vs. optimal medical therapy (MT) for CTOs in patients with preserved and impaired LV systolic function.Methods: A total of 1,895 patients with CTOs were stratified according to LV function. Of these, 1,420 patients (74.9%) with LV ejection fraction (LVEF) >45% and 475 patients (25.1%) with LVEF ≤45% were treated with optimal MT or successful CTO percutaneous coronary intervention (PCI). A 1:1 propensity score matching (PSM) was conducted to reduce the impact of potential confounding on the outcomes. The primary outcome was the frequency of major adverse cardiac events (MACEs).Results: Throughout a 2.6-year follow-up and after adjusting for confounders, among patients with preserved LV function, successful CTO PCI was associated with reduced incidence of MACE (14.2 vs. 23.9%, adjusted HR 0.63, 95% CI 0.48–0.83, p = 0.001) compared to MT. There was no significant difference in MACE occurrence (29.6 vs. 28.9%, adjusted HR 1.05, 95% CI: 0.71–1.56, p = 0.792) between successful recanalization and MT in patients with LV systolic dysfunction. The primary outcome among patients with impaired and preserved LV systolic function after PSM was similar to that from earlier findings before PSM was conducted. A significant interaction between LV function and therapeutic strategy for MACE was observed (interaction p = 0.038).Conclusions: Compared to MT alone for management of patients with CTOs, successful CTO PCI may reduce the risk of MACE in patients with preserved LV systolic function, but not in patients with LV dysfunction.

Background: The number of coronary chronic total occlusion (CTO) patients with renal insufficiency is huge, and limited data are available on the impact of renal insufficiency on long-term clinical outcomes in CTO patients. We aimed to investigate clinical outcomes of CTO percutaneous coronary intervention (PCI) vs. medical therapy (MT) in CTO patients according to baseline renal function.Methods: In the study population of 2,497, 1,220 patients underwent CTO PCI and 1,277 patients received MT. Patients were divided into four groups based on renal function: group 1 [estimated glomerular filtration rate (eGFR) ≥ 90 ml/min/1.73 m2], group 2 (60 ≤ eGFR

Background: To date, the benefit of successful revascularization of chronic total occlusions (CTOs) on prognosis remains uncertain, and there is a paucity of data on the impact of successful revascularization for CTO patients on long-term cardiovascular survival. This study aimed to investigate the long-term cardiovascular survival for patients with successful and unsuccessful CTO revascularization in a large cohort of patients.Methods: There were 1,655 consecutive patients with at least one CTO included and were grouped into successful revascularization (n = 591) and unsuccessful revascularization (n = 1,064). Propensity score matching (PSM) was carried out to balance the clinical and the angiographic characteristics. Cardiac mortality was defined as the primary endpoint. Major adverse cardiac event (MACE) was assessed as a “secondary endpoint.”Results: After 3.6 years of follow-up, there was no significant difference between the successful and the unsuccessful revascularization groups in the rate of cardiac mortality [adjusted hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.59–1.58, p = 0.865]. After the PSM analysis (371 pairs) between the two groups, the cardiac mortality rate values (HR 0.51, 95% CI 0.23–1.15, p = 0.104) were equivalent, whereas the adjusted risk of MACE (HR 0.43, 95% CI 0.32–0.58, p = 0.001) and target-vessel revascularization (HR 0.41, 95% CI 0.29–0.58, p < 0.001) were significantly higher in patients with unsuccessful revascularization.Conclusion: For the treatment of CTO patients, successful revascularization was not associated with a lesser risk for cardiac mortality as compared with unsuccessful revascularization. However, successful revascularization reduced MACE and target-vessel revascularization.

Background. Circulating monocytes play a critical role in the pathogenesis of atherosclerosis. Monocyte homing to sites of atherosclerosis is primarily initiated by selectin. Thus, blockade of the interaction of selectins and their ligands holds a significant role in monocyte homing which might be a potential approach to treat atherosclerosis. Here, we investigated the efficacy of a novel peptide analogue of selectin ligands IELLQAR in atherosclerosis. Methods and Results. In this study, we firstly measured the effect of the IELLQAR selectin-binding peptide on the inhibition of binding of selectins to monocytes by flow cytometry, which exhibited a dose-dependent inhibitory effect on the binding of the P-, E-, and L-selectins to monocytes, especially the inhibition of P-selectin binding to human peripheral blood monocytes (PBMCs) (half maximal inhibitory concentration (IC50~5 μM)) and THP-1 cells (IC50~10 μM). Furthermore, IELLQAR inhibited P-selectin-induced activation of CD11b on the surface of monocytes and decreased adhesion of monocytes to the endothelium. ApoE-/- mice with or without IELLQAR (1 or 3 mg/kg) fed a Western-type diet (WTD) or which had disturbed blood flow-induced shear stress underwent partial left carotid artery ligation (PLCA) to induce atherosclerosis. In the WTD- and PLCA-induced atherosclerosis models, atherosclerotic plaque formation and monocyte/macrophage infiltration of the arterial wall both decreased in ApoE-/- mice treated with the IELLQAR peptide. Our results also revealed that IELLQAR inhibited the differentiation of monocytes into macrophages through P-selectin-dependent activation of the nuclear factor- (NF-) κB and mammalian target of rapamycin (mTOR) pathways. Conclusion. Collectively, our results demonstrated that IELLQAR, a peptide analogue of selectin ligands, inhibited selectin binding to monocytes, which led to subsequent attenuation of atherosclerosis via inhibition of monocyte activation. Hence, use of the IELLQAR peptide provides a new approach and represents a promising candidate for the treatment of atherosclerosis in the early stage of disease.

Background. There is a paucity of information about the gender differences in clinical outcomes of successful percutaneous coronary intervention (PCI) compared with medical therapy (MT) in patients with coronary chronic total occlusions (CTOs). Objectives. We aimed to investigate the impact of gender on long-term clinical outcomes associated with successful CTO-PCI versus MT in patients with CTOs. Methods. Between January 2007 and December 2016, a total of 1702 patients with ≥1 CTO were enrolled. After exclusion, 1294 patients with 1520 CTOs were analyzed and were divided into the female group (n = 304, 23.5%) and the male group (n = 990, 76.5%). The patients in the female or male group were assigned to a MT group or successful CTO-PCI group according to the treatment strategy. In the female group, they were divided into two groups: 177 patients in the MT group and 127 patients in the successful CTO-PCI group. In the male group, they were divided into two groups: 623 patients in the MT group and 367 patients in the successful CTO-PCI group. The primary outcome was cardiac death. The secondary outcome was major adverse cardiac event (MACE). Results. The median overall follow-up duration was 3.6 (IQR, 2.1–5.0) years, there were no significant differences between the MT and successful CTO-PCI groups with respect to the prevalence of cardiac death (MT vs. successful PCI: 6.8% vs. 3.9%, p=0.287) and MACE (20.9% vs. 21.3%, p=0.810) in female patients. In the male group, the occurrence of cardiac death (MT vs. successful PCI: 6.6% vs. 3.8%, p=0.066) was similar between the two groups. The MACE rate (30.0% vs. 18.5%, p

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