Causal impact of gut microbiota and associated metabolites on pulmonary arterial hypertension: a bidirectional Mendelian randomization study.

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) exhibit a distinct gut microbiota profile; however, the causal association between gut microbiota, associated metabolites, and PAH remains elusive. We aimed to investigate this causal association and to explore whether dietary patterns play a role in its regulation. METHODS: Summary statistics of gut microbiota, associated metabolites, diet, and PAH were obtained from genome-wide association studies. The inverse variance weighted method was primarily used to measure the causal effect, with sensitivity analyses using the weighted median, weighted mode, simple mode, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger methods. A reverse Mendelian randomisation analysis was also performed. RESULTS: Alistipes (odds ratio [OR] = 2.269, 95% confidence interval [CI] 1.100-4.679, P = 0.027) and Victivallis (OR = 1.558, 95% CI 1.019-2.380, P = 0.040) were associated with an increased risk of PAH, while Coprobacter (OR = 0.585, 95% CI 0.358-0.956, P = 0.032), Erysipelotrichaceae (UCG003) (OR = 0.494, 95% CI 0.245-0.996, P = 0.049), Lachnospiraceae (UCG008) (OR = 0.596, 95% CI 0.367-0.968, P = 0.036), and Ruminococcaceae (UCG005) (OR = 0.472, 95% CI 0.231-0.962, P = 0.039) protected against PAH. No associations were observed between PAH and gut microbiota-derived metabolites (trimethylamine N-oxide [TMAO] and its precursors betaine, carnitine, and choline), short-chain fatty acids (SCFAs), or diet. Although inverse variance-weighted analysis demonstrated that elevated choline levels were correlated with an increased risk of PAH, the results were not consistent with the sensitivity analysis. Therefore, the association was considered insignificant. Reverse Mendelian randomisation analysis demonstrated that PAH had no causal impact on gut microbiota-derived metabolites but could contribute to increased the levels of Butyricicoccus and Holdemania, while decreasing the levels of Clostridium innocuum, Defluviitaleaceae UCG011, Eisenbergiella, and Ruminiclostridium 5. CONCLUSIONS: Gut microbiota were discovered suggestive evidence of the impacts of genetically predicted abundancy of certain microbial genera on PAH. Results of our study point that the production of SCFAs or TMAO does not mediate this association, which remains to be explained mechanistically.

The prognostic value of collateral circulation in coronary chronic total occlusion underwent percutaneous coronary intervention.

BACKGROUND: The prognostic value of coronary collateral circulation (CC) in patients undergoing chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is underdetermined. The purpose of the study was to assess the prognostic value of current two CC grading systems and their association with long-term outcomes in patients with CTO underwent PCI. METHODS: We consecutively enrolled patients with single-vessel CTO underwent PCI between January 2010 and December 2013. All patients were categorized into well-developed or poor-developed collaterals group according to angiographic Werner's CC (grade 2 vs. grade 0-1) or Rentrop (grade 3 vs. grade 0-2) grading system. The primary endpoint was 5-year cardiac death. RESULTS: Of 2452 enrolled patients, the overall technical success rate was 74.1%. Well-developed collaterals were present in 686 patients (28.0%) defined by Werner's CC grade 2, and in 1145 patients (46.7%) by Rentrop grade 3. According to Werner's CC grading system, patients with well-developed collaterals had a lower rate of 5-year cardiac death compared with those with poor-developed collaterals (1.6% vs. 3.3%, P = 0.02), those with suboptimal recanalization was associated with higher rate of 5-year cardiac death compared with optimal recanalization (4.7% vs. 0.8%, P = 0.01) and failure patients (4.7% vs. 1.6%, P = 0.12). However, the similar effect was not shown in Rentrop grading system. CONCLUSIONS: In patients with the single-vessel CTO underwent PCI, well-developed collaterals by Werner's CC definition were associated with lower rate of 5-year cardiac death. Werner's CC grading system had a greater prognostic value than Rentrop grading system in patients with CTO underwent PCI.

Nicorandil-Pretreated Mesenchymal Stem Cell-Derived Exosomes Facilitate Cardiac Repair After Myocardial Infarction via Promoting Macrophage M2 Polarization by Targeting miR-125a-5p/TRAF6/IRF5 Signaling Pathway.

Background: Exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) have been considered as a promising cell-free therapeutic strategy for ischemic heart disease. Cardioprotective drug pretreatment could be an effective approach to improve the efficacy of MSC-exo. Nicorandil has long been used in clinical practice for cardioprotection. This study aimed to investigate whether the effects of exosomes derived from nicorandil pretreated MSC (MSCNIC-exo) could be enhanced in facilitating cardiac repair after acute myocardial infarction (AMI). Methods: MSCNIC-exo and MSC-exo were collected and injected into the border zone of infarcted hearts 30 minutes after coronary ligation in rats. Macrophage polarization was detected 3 days post-infarction, cardiac function as well as histological pathology were measured on the 28th day after AMI. Macrophages were separated from the bone marrow of rats for in vitro model. Exosomal miRNA sequencing was conducted to identify differentially expressed miRNAs between MSCNIC-exo and MSC-exo. MiRNA mimics and inhibitors were transfected to MSCs or macrophages to explore the specific mechanism. Results: Compared to MSC-exo, MSCNIC-exo showed superior therapeutic effects on cardiac functional and structural recovery after AMI and markedly elevated the ratio of CD68+ CD206+/ CD68+cells in infarcted hearts 3 days post-infarction. The notable ability of MSCNIC-exo to promote macrophage M2 polarization was also confirmed in vitro. Exosomal miRNA sequencing and both in vivo and in vitro experiments identified and verified that miR-125a-5p was an effector of the roles of MSCNIC-exo in vivo and in vitro. Furthermore, we found miR-125a-5p promoted macrophage M2 polarization by inhibiting TRAF6/IRF5 signaling pathway. Conclusion: This study suggested that MSCNIC-exo could markedly facilitate cardiac repair post-infarction by promoting macrophage M2 polarization by upregulating miR-125a-5p targeting TRAF6/IRF5 signaling pathway, which has great potential for clinical translation.

Diagnostic performance of intravascular ultrasound-based fractional flow reserve in evaluating of intermediate left main stenosis.

BACKGROUND: The recently introduced ultrasonic flow ratio (UFR), is a novel fast computational method to derive fractional flow reserve (FFR) from intravascular ultrasound (IVUS) images. In the present study, we evaluate the diagnostic performance of UFR in patients with intermediate left main (LM) stenosis. METHODS: This is a prospective, single center study enrolling consecutive patients with presence of intermediated LM lesions (diameter stenosis of 30%-80% by visual estimation) underwent IVUS and FFR measurement. An independent core laboratory assessed offline UFR and IVUS-derived minimal lumen area (MLA) in a blinded fashion. RESULTS: Both UFR and FFR were successfully achieved in 41 LM patients (mean age, 62.0 ± 9.9 years, 46.3% diabetes). An acceptable correlation between UFR and FFR was identified (r = 0.688, P < 0.0001), with an absolute numerical difference of 0.03 (standard difference: 0.01). The area under the curve (AUC) in diagnosis of physiologically significant coronary stenosis for UFR was 0.94 (95% CI: 0.87-1.01), which was significantly higher than angiographic identified stenosis > 50% (AUC = 0.66, P < 0.001) and numerically higher than IVUS-derived MLA (AUC = 0.82; P = 0.09). Patient level diagnostic accuracy, sensitivity and specificity for UFR to identify FFR ≤ 0.80 was 82.9% (95% CI: 70.2-95.7), 93.1% (95% CI: 82.2-100.0), 58.3% (95% CI: 26.3-90.4), respectively. CONCLUSION: In patients with intermediate LM diseases, UFR was proved to be associated with acceptable correlation and high accuracy with pressure wire-based FFR as standard reference. The present study supports the use of UFR for functional evaluation of intermediate LM stenosis.

Baseline high-sensitivity C-reactive protein and glycosylated hemoglobinA1c predict adverse outcomes in patients with chronic coronary syndromes undergoing percutaneous coronary intervention.

Introduction: This study explored the ability of high-sensitivity C-reactive protein (hs-CRP) and glycosylated hemoglobin A1c (HbA1c) to predict adverse cardiac and cerebrovascular outcomes in patients with chronic coronary syndromes (CCS) undergoing percutaneous coronary intervention (PCI). Methods: In total, 4083 consecutive patients with CCS undergoing PCI were investigated throughout 2013 at a single center. The primary endpoint was all-cause death at the 5-year follow-up. Hs-CRP and HbA1c data were collected on admission. Results: The highest quartile of hs-CRP had a significantly increased the risk of all-cause death, with an adjusted HR of 1.747 (95 % CI 1.066-2.863), while, there was no difference in all-cause death among the groups of HbA1c after adjustment, with an adjusted HR of 1.383 (95 % CI 0.716-2.674). The highest quartiles for hs-CRP and HbA1c in the study population had a significantly increased risk of major adverse cardiac and cerebrovascular events (MACCE), with an adjusted hazard ratios (HR) of 1.263 (95 % confidence intervals [CI] 1.032-1.545) for hs-CRP and an adjusted HR of 1.417 (95 % CI 1.091-1.840) for HbA1c. Remarkably, the incidence of all-cause death and that of MACCE were significantly increased when both hs-CRP and HbA1c were elevated (HR 1.971, 95 % CI 1.079-3.601, P = 0.027 and HR 1.560, 95 % CI 1.191-2.042), P = 0.001, respectively). Addition of hs-CRP and HbA1c to conventional risk factors significantly improved prediction of the risk of all cause death (net reclassification index 0.492, P < 0.001; integrated discrimination improvement 0.007, P = 0.011) and MACCE (net reclassification index 0.160, P < 0.001; integrated discrimination improvement 0.006, P < 0.001). Conclusions: Hs-CRP and HbA1c can serve as independent predictors of MACCE in patients with CCS undergoing PCI. Furthermore, a combination of hs-CRP and HbA1c could predict all cause death and MACCE better than each component individually.

Association between living alone and all-cause mortality of young and middle-aged patients with acute myocardial infarction: analysis of the China Acute Myocardial Infarction (CAMI) registry.

BACKGROUND: Lack of social support is a known predictor of the prognosis after acute myocardial infarction (AMI). Although as a common factor associated with social support, there are limited data on long-term prognostic impact of living status in young and middle-aged patients with AMI. METHODS: We analyzed data from the China Acute Myocardial Infarction (CAMI) Registry, consecutive AMI young and middle-aged patients admitted at 108 hospitals in China between January 2013 and September 2014 were included. Eligible patients were assigned to living alone and not living alone groups based on their living status. The primary endpoint was 2-year all-cause mortality. The secondary endpoints included in-hospital mortality and 2-year major adverse cardiac and cerebrovascular events (MACCEs; a composite of all-cause mortality, MI, or stroke). Multilevel logistic and multilevel Cox regression models were used to evaluate the effect of living status on short-term and long-term outcomes. RESULTS: A total of 8307 consecutive AMI young and middle-aged patients were included, 192 (2.3%) patients were living alone. Of the analyzed patients, living alone was associated with 2-year all-cause mortality and MACCEs among all analyzed patients after multivariate adjustment (adjusted hazard ratio [HR] = 2.171 [1.210-3.895], P = 0.009; adjusted HR = 2.169 [1.395-3.370], P = 0.001), but not with poorer in-hospital mortality. CONCLUSIONS: The analysis suggested that living alone was associated with both 2-year all-cause mortality and MACCEs in AMI young and middle-aged patients but did not show an extra effect on the in-hospital mortality after covariate adjustment. TRIAL REGISTRATION: Trial registration number: NCT01874691; Registered 31 October 2012.

Top Five Stories of the Cellular Landscape and Therapies of Atherosclerosis: Current Knowledge and Future Perspectives.

Atherosclerosis (AS) is characterized by impairment and apoptosis of endothelial cells, continuous systemic and focal inflammation and dysfunction of vascular smooth muscle cells, which is documented as the traditional cellular paradigm. However, the mechanisms appear much more complicated than we thought since a bulk of studies on efferocytosis, transdifferentiation and novel cell death forms such as ferroptosis, pyroptosis, and extracellular trap were reported. Discovery of novel pathological cellular landscapes provides a large number of therapeutic targets. On the other side, the unsatisfactory therapeutic effects of current treatment with lipid-lowering drugs as the cornerstone also restricts the efforts to reduce global AS burden. Stem cell- or nanoparticle-based strategies spurred a lot of attention due to the attractive therapeutic effects and minimized adverse effects. Given the complexity of pathological changes of AS, attempts to develop an almighty medicine based on single mechanisms could be theoretically challenging. In this review, the top stories in the cellular landscapes during the initiation and progression of AS and the therapies were summarized in an integrated perspective to facilitate efforts to develop a multi-targets strategy and fill the gap between mechanism research and clinical translation. The future challenges and improvements were also discussed.

Long-Term Prognosis of Different Reperfusion Strategies for ST-Segment Elevation Myocardial Infarction in Chinese County-Level Hospitals: Insight from China Acute Myocardial Infarction Registry.

Objective: To evaluate the long-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) treated with different reperfusion strategies in Chinese county-level hospitals. Methods: A total of 2,514 patients with STEMI from 32 hospitals participated in the China Acute Myocardial Infarction registry between January 2013 and September 2014. The success of fibrinolysis was assessed according to indirect measures of vascular recanalization. The primary outcome was 2-year mortality. Results: Reperfusion therapy was used in 1,080 patients (42.9%): fibrinolysis ( n= 664, 61.5%) and primary percutaneous coronary intervention (PCI) ( n= 416, 38.5%). The most common reason for missing reperfusion therapy was a prehospital delay > 12 h (43%). Fibrinolysis [14.5%, hazard ratio ( HR): 0.59, 95% confidence interval ( CI) 0.44-0.80] and primary PCI (6.8%, HR= 0.32, 95% CI: 0.22-0.48) were associated with lower 2-year mortality than those with no reperfusion (28.5%). Among fibrinolysis-treated patients, 510 (76.8%) achieved successful clinical reperfusion; only 17.0% of those with failed fibrinolysis underwent rescue PCI. There was no difference in 2-year mortality between successful fibrinolysis and primary PCI (8.8% vs. 6.8%, HR = 1.53, 95% CI: 0.85-2.73). Failed fibrinolysis predicted a similar mortality (33.1%) to no reperfusion (33.1% vs. 28.5%, HR= 1.30, 95% CI: 0.93-1.81). Conclusion: In Chinese county-level hospitals, only approximately 2/5 of patients with STEMI underwent reperfusion therapy, largely due to prehospital delay. Approximately 30% of patients with failed fibrinolysis and no reperfusion therapy did not survive at 2 years. Quality improvement initiativesare warranted, especially in public health education and fast referral for mechanical revascularization in cases of failed fibrinolysis.

T cell receptor ß repertoires in patients with COVID-19 reveal disease severity signatures.

Background: The immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial in maintaining a delicate balance between protective effects and harmful pathological reactions that drive the progression of coronavirus disease 2019 (COVID-19). T cells play a significant role in adaptive antiviral immune responses, making it valuable to investigate the heterogeneity and diversity of SARS-CoV-2-specific T cell responses in COVID-19 patients with varying disease severity. Methods: In this study, we employed high-throughput T cell receptor (TCR) ß repertoire sequencing to analyze TCR profiles in the peripheral blood of 192 patients with COVID-19, including those with moderate, severe, or critical symptoms, and compared them with 81 healthy controls. We specifically focused on SARS-CoV-2-associated TCR clonotypes. Results: We observed a decrease in the diversity of TCR clonotypes in COVID-19 patients compared to healthy controls. However, the overall abundance of dominant clones increased with disease severity. Additionally, we identified significant differences in the genomic rearrangement of variable (V), joining (J), and VJ pairings between the patient groups. Furthermore, the SARS-CoV-2-associated TCRs we identified enabled accurate differentiation between COVID-19 patients and healthy controls (AUC > 0.98) and distinguished those with moderate symptoms from those with more severe forms of the disease (AUC > 0.8). These findings suggest that TCR repertoires can serve as informative biomarkers for monitoring COVID-19 progression. Conclusions: Our study provides valuable insights into TCR repertoire signatures that can be utilized to assess host immunity to COVID-19. These findings have important implications for the use of TCR ß repertoires in monitoring disease development and indicating disease severity.

Triglyceride glucose index predicts in-hospital mortality in patients with ST-segment elevation myocardial infarction who underwent primary angiography.

OBJECTIVES: To assess the correlation between triglyceride glucose (TyG) index and in-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 2190 patients with STEMI who underwent primary angiography within 12 h from symptom onset were selected from the prospective, nationwide, multicenter CAMI registry. TyG index was calculated with the formula: Ln [fasting triglycerides (mmol/L) × fasting glucose (mmol/L)/2]. Patients were divided into three groups according to the tertiles of TyG index. The primary endpoint was in-hospital mortality. RESULTS: Overall, 46 patients died during hospitalization, in-hospital mortality was 1.5%, 2.2%, 2.6% for tertile 1, tertile 2, and tertile 3, respectively. However, TyG index was not significantly correlated with in-hospital mortality in single-variable logistic regression analysis. Nonetheless, after adjusting for age and sex, TyG index was significantly associated with higher mortality when regarded as a continuous variable (adjusted OR = 1.75, 95% CI: 1.16-2.63) or categorical variable (tertile 3 vs. tertile 1: adjusted OR = 2.50, 95% CI: 1.14-5.49). Furthermore, TyG index, either as a continuous variable (adjusted OR = 2.54, 95% CI: 1.42-4.54) or categorical variable (tertile 3 vs. tertile 1: adjusted OR = 3.57, 95% CI: 1.24-10.29), was an independent predictor of in-hospital mortality after adjusting for multiple confounders in multivariable logistic regression analysis. In subgroup analysis, the prognostic effect of high TyG index was more significant in patients with body mass index < 18.5 kg/m2 (P interaction = 0.006). CONCLUSIONS: This study showed that TyG index was positively correlated with in-hospital mortality in STEMI patients who underwent primary angiography, especially in underweight patients.

Levosimendan Reverses Cardiac Malfunction and Cardiomyocyte Ferroptosis During Heart Failure with Preserved Ejection Fraction via Connexin 43 Signaling Activation.

PURPOSE: In recent decades, the occurrence of heart failure with preserved ejection fraction (HFpEF) has outweighed that of heart failure with reduced ejection fraction by degrees, but few drugs have been demonstrated to improve long-term clinical outcomes in patients with HFpEF. Levosimendan, a calcium-sensitizing cardiotonic agent, improves decompensated heart failure clinically. However, the anti-HFpEF activities of levosimendan and underlying molecular mechanisms are unclear. METHODS: In this study, a double-hit HFpEF C57BL/6N mouse model was established, and levosimendan (3 mg/kg/week) was administered to HFpEF mice aged 13 to 17 weeks. Different biological experimental techniques were used to verify the protective effects of levosimendan against HFpEF. RESULTS: After four weeks of drug treatment, left ventricular diastolic dysfunction, cardiac hypertrophy, pulmonary congestion, and exercise exhaustion were significantly alleviated. Junction proteins in the endothelial barrier and between cardiomyocytes were also improved by levosimendan. Among the gap junction channel proteins, connexin 43, which was especially highly expressed in cardiomyocytes, mediated mitochondrial protection. Furthermore, levosimendan reversed mitochondrial malfunction in HFpEF mice, as evidenced by increased mitofilin and decreased ROS, superoxide anion, NOX4, and cytochrome C levels. Interestingly, after levosimendan administration, myocardial tissue from HFpEF mice showed restricted ferroptosis, indicated by an increased GSH/GSSG ratio; upregulated GPX4, xCT, and FSP-1 expression; and reduced intracellular ferrous ion, MDA, and 4-HNE levels. CONCLUSION: Regular long-term levosimendan administration can benefit cardiac function in a mouse model of HFpEF with metabolic syndromes (namely, obesity and hypertension) by activating connexin 43-mediated mitochondrial protection and sequential ferroptosis inhibition in cardiomyocytes.

Individual or familial diabetes in relation to eight cardiovascular diseases: A two-sample Mendelian randomization study.

BACKGROUND AND AIMS: Diabetes is associated with increased risk of certain cardiovascular diseases, yet the causality remains to be determined. Meanwhile, given that first-degree relatives share 50% of genes, the effect of familial diabetes is also worthy of attention. Therefore, we sought to investigate the causal relations of individual or familial diabetes with eight cardiovascular diseases, including myocardial infarction, hypertension, atrial fibrillation, heart failure, cardiac death, pulmonary embolism, transient ischemic attack, and ischemic stroke. METHODS AND RESULTS: Applying two-sample Mendelian randomization, we selected instruments for genetic predisposition to individual or familial diabetes based on published genome-wide association studies. The primary analyses were conducted using the random-effects inverse-variance weighted method. We found that genetically predicted individual diabetes was causally associated with higher risks of myocardial infarction (odd ratio [OR] = 1.09; 95% confidence interval [CI]: 1.05-1.13; P < 0.0001), hypertension (OR = 1.08; 95% CI: 1.03-1.13; P = 0.0006), and ischemic stroke (OR = 1.10; 95% CI: 1.05-1.15; P < 0.0001). Genetically predicted paternal diabetes could increase the risk of ischemic stroke (OR = 1.16; 95% CI: 1.04-1.30; P = 0.0061). Genetically predicted maternal diabetes could increase the risk of myocardial infarction (OR = 1.18; 95% CI: 1.09-1.29; P = 0.0001). Genetically predicted siblings' diabetes was causally associated with higher risks of myocardial infarction (OR = 1.17; 95% CI: 1.08-1.27; P = 0.0001) and hypertension (OR = 1.19; 95% CI: 1.06-1.34; P = 0.0036). No significant differences were observed in other outcomes. CONCLUSION: This study supports causal effects of not only individual but also familial diabetes on the development of cardiovascular diseases, which will help realize the potential effect of family history in the prevention of cardiovascular diseases.

Prolonged dual antiplatelet therapy after drug-eluting stent implantation improves long-term prognosis for acute coronary syndrome: five-year results from a large cohort study.

BACKGROUND: To investigate the most appropriate dual antiplatelet therapy (DAPT) duration for patients with acute coronary syndrome (ACS) after drug-eluting stent (DES) implantation in the largest cardiovascular center of China. METHODS: We enrolled 5,187 consecutive patients with ACS who received DES from January to December 2013. Patients were divided into four groups based on DAPT duration: standard DAPT group (11-13 months, n=1,568) and prolonged DAPT groups (13-18 months [n=308], 18-24 months [n=2,125], and >24 months [n=1,186]). Baseline characteristics and 5-year clinical outcomes were recorded. RESULTS: Baseline characteristics were similar across the four groups. Among the four groups, those with prolonged DAPT (18-24 months) had the lowest incidence of major adverse cardiovascular and cerebrovascular events (MACCEs) (14.1% vs. 11.7% vs. 9.6% vs. 24.2%, P<0.001), all-cause death (4.8% vs. 3.9% vs. 2.1% vs. 2.6%, P<0.001), cardiac death (3.1% vs. 2.6% vs. 1.4% vs. 1.9%, P=0.004), and myocardial infarction (MI) (3.8% vs. 4.2% vs. 2.5% vs. 5.8%, P<0.001). The incidence of bleeding was not different among the four groups (9.9% vs. 9.4% vs. 11.0% vs. 9.4%, P=0.449). Cox multivariable analysis showed that prolonged DAPT (18-24 months) was an independent protective factor for MACCEs (hazard ratio [HR] 0.802, 95% confidence interval [CI] 0.729-0.882, P<0.001), all-cause death (HR 0.660, 95% CI 0.547-0.795, P<0.001), cardiac death (HR 0.663, 95% CI 0.526-0.835, P<0.001), MI (HR 0.796, 95% CI 0.662-0.957, P=0.015), and target vessel revascularization (HR 0.867, 95% CI 0.755-0.996, P=0.044). Subgroup analysis for high bleeding risk showed that prolonged DAPT remained an independent protective factor for all-cause death and MACCEs. CONCLUSION: For patients with ACS after DES, appropriately prolonging the DAPT duration may be associated with a reduced risk of adverse ischemic events without increasing the bleeding risk.

Association of beta-blocker therapy at discharge with clinical outcomes in patients without heart failure or left ventricular systolic dysfunction after acute coronary syndrome: An updated systematic review and meta-analysis.

BACKGROUND: Beta-blockers are the standard treatment for acute coronary syndrome (ACS) based on evidence from the prethrombolytic era. We sought to examine the effect of beta-blocker treatment on patients without heart failure or left ventricular systolic dysfunction after ACS in the contemporary percutaneous coronary intervention (PCI) era. METHODS: We systematically searched PubMed, Web of Science, Cochrane Library, ClinicalTrials.gov and Google Scholar for studies comparing beta-blockers versus no beta-blockers in ACS patients in the contemporary PCI era. The primary outcome was all-cause death. Pooling unadjusted and multivariable adjusted results were calculated under random-effects models. RESULTS: Data from 15 studies (n=205,672), including 1 randomized trial, were analysed. Compared with no beta-blockers, beta-blocker therapy at discharge may reduce the risk of all-cause death (odds ratio [OR] 0.66, 95% confidence interval [CI]: 0.50-0.86; I2=81.9%). Subgroup analysis according to single or multicentre studies indicated similar results. Prospective studies suggested that all-cause death was less common in the beta-blocker group. After multivariable adjustment, a lower risk of all-cause death was still observed with beta-blockers (OR: 0.74, 95% CI: 0.59-0.94; I2=40.1%). No differences existed in major adverse cardiovascular events (MACE), cardiac death, myocardial infarction, heart failure, revascularization or stroke, before and after multivariable adjustment. CONCLUSIONS: In patients without heart failure or left ventricular systolic dysfunction after ACS in the contemporary PCI era, beta-blocker therapy may still be beneficial due to a potential reduced risk of all-cause death.

Impact of Marital Status on Management and Outcomes of Patients With Acute Myocardial Infarction: Insights From the China Acute Myocardial Infarction Registry.

Background Acute myocardial infarction (AMI) is one of the leading causes of mortality worldwide, whereas social support is a known predictor of the prognosis after AMI. As a common factor influencing social support, the impact of marital status on care quality, in-hospital mortality, and long-term prognosis of patients with AMI remains largely unknown. Methods and Results The present study analyzed data from the CAMI (China Acute Myocardial Infarction) registry involving 19 912 patients with AMI admitted at 108 hospitals in China between January 2013 and September 2014 and aimed to evaluate marital status-based differences in acute management, medical therapies, and short-term and long-term outcomes. The primary end point was 2-year all-cause death. The secondary end points included in-hospital death and 2-year major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke). After multivariable adjustment, 1210 (6.1%) unmarried patients received less reperfusion treatment in patients with both ST-segment-elevation myocardial infarction and non-ST-segment-elevation myocardial infarction (adjusted odds ratio [OR], 0.520 [95% CI, 0.437-0.618]; P<0.0001; adjusted OR, 0.489 [95% CI, 0.364-0.656]; P<0.0001). Being unmarried was not associated with poorer in-hospital outcome but with long-term all-cause mortality and major adverse cardiac and cerebrovascular events in both ST-segment-elevation myocardial infarction (adjusted hazard ratio [HR], 1.225 [95% CI, 1.031-1.456]; P=0.0209; adjusted HR, 1.277 [95% CI, 1.089-1.498]; P=0.0027) and non-ST-segment-elevation myocardial infarction (adjusted HR, 1.302 [95% CI, 1.036-1.638]; P=0.0239; adjusted HR, 1.368 [95% CI, 1.105-1.694]; P=0.0040) populations. Conclusions The present study suggests that being unmarried is independently related to less reperfusion received, but could not explain the higher in-hospital mortality rate after covariate adjustment. Being unmarried is associated with a substantially increased risk of adverse events over at least the first 24 months after AMI. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01874691.

[Baroreflex ActivationTherapy for Heart Failure].

Heart failure (HF) is the endstage of multiple cardiovascular diseases.Impaired autonomic regulation and sympathetic-parasympathetic imbalance are considered key factors in HF progression.Baroreflex activation therapy (BAT),a novel device-based therapy which stimulates the carotid sinuses and regulates autonomic function,has demonstrated good efficacy in treating HF and improving prognosis.This review summarized the results of the latest relevant studies to provide support for further study of BAT.

The underlying pathological mechanism of ferroptosis in the development of cardiovascular disease.

Cardiovascular diseases (CVDs) have been attracting the attention of academic society for decades. Numerous researchers contributed to figuring out the core mechanisms underlying CVDs. Among those, pathological decompensated cellular loss posed by cell death in different kinds, namely necrosis, apoptosis and necroptosis, was widely regarded to accelerate the pathological development of most heart diseases and deteriorate cardiac function. Recently, apart from programmed cell death revealed previously, ferroptosis, a brand-new cellular death identified by its ferrous-iron-dependent manner, has been demonstrated to govern the occurrence and development of different cardiovascular disorders in many types of research as well. Therefore, clarifying the regulatory function of ferroptosis is conducive to finding out strategies for cardio-protection in different conditions and improving the prognosis of CVDs. Here, molecular mechanisms concerned are summarized systematically and categorized to depict the regulatory network of ferroptosis and point out potential therapeutic targets for diverse cardiovascular disorders.

Effect of Cheese Intake on Cardiovascular Diseases and Cardiovascular Biomarkers.

BACKGROUND: A growing number of cohort studies revealed an inverse association between cheese intake and cardiovascular diseases, yet the causal relationship is unclear. OBJECTIVE: To assess the causal relationship between cheese intake, and cardiovascular diseases and cardiovascular biomarkers. METHODS: A two-sample Mendelian randomization (MR) analysis based on publicly available genome-wide association studies was employed to infer the causal relationship. The effect estimates were calculated using the random-effects inverse-variance-weighted method. RESULTS: Cheese intake per standard deviation increase causally reduced the risks of type 2 diabetes (odds ratio (OR) = 0.46; 95% confidence interval (CI), 0.34-0.63; p = 1.02 × 10-6), heart failure (OR = 0.62; 95% CI, 0.49-0.79; p = 0.0001), coronary heart disease (OR = 0.65; 95% CI, 0.53-0.79; p = 2.01 × 10-5), hypertension (OR = 0.67; 95% CI, 0.53-0.84; p = 0.001), and ischemic stroke (OR = 0.76; 95% CI, 0.63-0.91; p = 0.003). Suggestive evidence of an inverse association between cheese intake and peripheral artery disease was also observed. No associations were observed for atrial fibrillation, cardiac death, pulmonary embolism, or transient ischemic attack. The better prognosis associated with cheese intake may be explained by lower body mass index (BMI; effect estimate = -0.58; 95% CI, from -0.88 to -0.27; p = 0.0002), waist circumference (effect estimate = -0.49; 95% CI, from -0.76 to -0.23; p = 0.0003), triglycerides (effect estimate = -0.33; 95% CI, from -0.50 to -0.17; p = 4.91 × 10-5), and fasting glucose (effect estimate = -0.20; 95% CI, from -0.33 to -0.07; p = 0.0003). There was suggestive evidence of a positive association between cheese intake and high-density lipoprotein. No influences were observed for blood pressure or inflammation biomarkers. CONCLUSIONS: This two-sample MR analysis found causally inverse associations between cheese intake and type 2 diabetes, heart failure, coronary heart disease, hypertension, and ischemic stroke.

Effects of chronic obstructive pulmonary disease on long-term prognosis of patients with coronary heart disease post-percutaneous coronary intervention.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and cardiovascular diseases are often comorbid conditions, their co-occurrence yields worse outcomes than either condition alone. This study aimed to investigate COPD impacts on the five-year prognosis of patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). METHODS: Patients with CHD who underwent PCI in 2013 were recruited, and divided into COPD group and non-COPD group. Adverse events occurring among those groups were recorded during the five-year follow-up period after PCI, including all-cause death and cardiogenic death, myocardial infarction, repeated revascularization, as well as stroke and bleeding events. Major adverse cardiac and cerebral events were a composite of all-cause death, myocardial infarction, repeated revascularization and stroke. RESULTS: A total of 9843 patients were consecutively enrolled, of which 229 patients (2.3%) had COPD. Compared to non-COPD patients, COPD patients were older, along with poorer estimated glomerular filtration rate and lower left ventricular ejection fraction. Five-year follow-up results showed that incidences of all-cause death and cardiogenic death, as well as major adverse cardiac and cerebral events, for the COPD group were significantly higher than for non-COPD group (10.5% vs. 3.9%, 7.4% vs. 2.3%, and 30.1% vs. 22.6%, respectively). COPD was found under multivariate Cox regression analysis, adjusted for confounding factors, to be an independent predictor of all-cause death [odds ratio (OR) = 1.76, 95% CI: 1.15-2.70, P = 0.009] and cardiogenic death (OR = 2.02, 95% CI: 1.21-3.39, P = 0.007). CONCLUSIONS: COPD is an independent predictive factor for clinical mortality, in which CHD patients with COPD are associated with worse prognosis than CHD patients with non-COPD.

Impact of percutaneous coronary intervention on chronic total occlusion in the non-infarct-related artery in patients with STEMI: a systematic review and meta-analysis.

OBJECTIVES: We sought to compare the clinical outcomes between culprit-only percutaneous coronary intervention (PCI) versus multivessel PCI (MV-PCI) in patients with ST-segment elevation myocardial infarction (STEMI) accompanied by chronic total occlusion (CTO) in the non-infarct-related artery(non-IRA). DESIGN: Studies that compared culprit-only PCI versus MV-PCI in patients with STEMI accompanied by CTO in the non-IRA were included. Random odds ratio (OR) and 95% confidence interval (CI) were calculated. RESULTS: Eight studies with 2,259 patients were included. The results suggested that in patients with STEMI accompanied by CTO in the non-IRA, culprit-only PCI was associated with higher risks of all-cause mortality (OR: 2.89; 95% CI: 2.09-4.00; I2 = 0.0%), cardiac death (OR: 3.12; 95% CI: 2.05-4.75; I2 = 16.8%), stroke (OR: 2.80; 95% CI: 1.04-7.53; I2 = 0.0%), major adverse cardiovascular event (MACE; OR: 2.06; 95% CI: 1.39-3.06; I2 = 54.0%), and heart failure (OR: 1.99; 95% CI: 1.22-3.24; I2 = 0.0%) compared with staged MV-PCI, which were mainly derived from retrospective studies. No differences were observed in myocardial infarction or revascularization. Pooled multivariable adjusted results consistently indicated that staged MV-PCI was superior to culprit-only PCI. CONCLUSIONS: For patients with STEMI accompanied by CTO in the non-IRA, staged MV-PCI may be better compared with culprit-only PCI due to potential reduced risks of all-cause mortality, cardiac death, stroke, MACE, and heart failure. Meanwhile, further randomized trials are warranted to confirm or refute our findings.