Bivalirudin vs. heparin on a background of ticagrelor and aspirin in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: A multicenter prospective cohort study.

Objective: Current guidelines recommend potent P2Y12 inhibitors such as ticagrelor over clopidogrel as part of the dual antiplatelet therapy (DAPT) after ST-segment elevation myocardial infarction (STEMI), irrespective of final management strategy. The aim of this multicenter prospective cohort study was to examine the efficacy and safety of bivalirudin with background ticagrelor and aspirin therapy in patients with STEMI undergoing primary percutaneous coronary intervention (PPCI). Methods: A total of 800 patients with STEMI who were undergoing PPCI and receiving treatment with aspirin and ticagrelor from three Hospitals between April 2019 and September 2021 were included in this study. The patients were assigned, according to the perioperative anticoagulant, to the bivalirudin group (n = 456) or the heparin group (n = 344). In this study, the primary endpoint was 30-day net adverse clinical events (NACEs), a composite of major adverse cardiac or cerebral events (MACCEs, a composite of cardiac death, recurrent myocardial infarction, ischemia-driven target vessel revascularization, or stroke), or any bleeding as defined by the Bleeding Academic Research Consortium (BARC) definition (grades 1-5). Results: The patients were followed up for 30 days after PPCI. The incidence of NACE was significantly lower in the bivalirudin group than in the heparin group (11.2 vs. 16.0%, P = 0.042), and this significance was mainly a consequence of the reduction in BARC 1 bleeding events in the bivalirudin group compared to the heparin group (3.2 vs. 7.1%, P = 0.010). Results from multivariate Cox regression analysis showed that bivalirudin significantly reduced 30-day NACE (HR: 0.676, 95% CI: 0.462-0.990, P = 0.042) and BARC1 bleeding events (HR: 0.429, 95% CI: 0.222-0.830, P = 0.010). No significant between-group differences were observed for MACCE, all-cause mortality, cardiac death, recurrent myocardial infarction, stroke, target vessel revascularization, stent thrombosis, and BARC2-5 bleeding events at 30 days. Conclusion: In patients with STEMI who were undergoing primary PCI and receiving treatment with aspirin and ticagrelor, bivalirudin was associated with decreased rates in NACE and minimal bleeding events without significant differences in the rates of MACCE or stent thrombosis when compared with heparin. Nevertheless, large randomized trials are warranted to confirm these observations. Clinical trial registration: The trial was registered at the Chinese Clinical Trial Registry (ChiCTR, http://www.chictr.org.cn; identifier [ChiCTR1900022529]). Registered on 15 April 2019. Registration title: Effect of bivalirudin combined with ticagrelor in patients with ST-segment elevation myocardial infarction during primary percutaneous coronary intervention.

Causal associations between blood pressure and the risk of myocardial infarction: A bidirectional Mendelian randomization study.

Introduction: Many observational studies imply elevated blood pressure (BP) as a leading risk factor for incident myocardial infarction (MI), but whether this relationship is causal remains unknown. In this study, we used bidirectional Mendelian randomization (MR) to investigate the potential causal association of BP levels with the risk of MI. Methods: Genetic variants associated with BP and MI traits were retrieved from the International Consortium of Blood Pressure (N = 7,57,601) and UKB (N = 3,61,194), obtaining 1,26,40,541 variants. We used two-sample MR (TSMR) analyses to examine the potential bidirectional causal association of systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) with MI. Results: The forward MR analysis identified a potentially causal association between MI and BP except PP[odds ratio (OR) SBP: 1.0008, P = 1.911 × 10-22; ORDBP: 1.0014, P = 1.788 × 10-28;odds ratio (OR)pp: 1.0092, P = 0.179]. However, the reverse analysis suggested no causal relation (betaSBP: 5.469, P = 0.763; betaDBP: 3.624, P = 0.588; betaPP: -0.074, P = 0.912). These findings were robust in sensitivity analyses such as the MR-Egger method, the maximum likelihood method and the MR pleiotropy residual sum and outlier test (MR-PRESSO). No horizontal pleiotropy (p = 0.869 for SBP, p = 0.109 for DBP and p = 0.978 for PP in the forward results and p = 0.168 for SBP, P = 0.892 for DBP and p = 0.989 for PP in the reverse results) was observed. Conclusions: Elevated SBP or DBP levels increase the risk of MI, but there is no causal relationship between MI and changes in BP including PP. Independent of other risk factors, optimal BP control might represent an important therapeutic target for MI prevention in the general population.

LncRNA HOXA11-AS promotes vascular endothelial cell injury in atherosclerosis by regulating the miR-515-5p/ROCK1 axis.

AIMS: Long non-coding RNA HOXA11-AS participated in heart disease. In this study, we aim to evaluate the potential roles of HOXA11-AS in atherosclerosis and its underlying mechanisms. METHODS AND RESULTS: The expression levels of HOXA11-AS in ox-LDL-treated HUVECs and arch tissues of high-fat diet-fed ApoE-/- mice (n = 10) were assessed by qRT-PCR. The effects of HOXA11-AS knockdown on the development of atherosclerosis were evaluated using in vitro and in vivo models. Luciferase reporter and RNA immunoprecipitation (RIP) assays verified the potential relationships between HOXA11-AS or ROCK1 and miR-515-5p. The interactive roles between HOXA11-AS and miR-515-5p and between miR-515-5p and ROCK1 were further characterized in ox-LDL-treated HUVECs. Our data showed that HOXA11-AS was significantly up-regulated (P < 0.001), whereas miR-515-5p was dramatically down-regulated in AS mice tissues (P < 0.001) and ox-LDL-treated HUVECs (P < 0.01). Ox-LDL could induce endothelial injuries by inhibiting cell proliferation (P < 0.001) and SOD synthesis (P < 0.001), promoting apoptosis (P < 0.01), ROS (P < 0.001), and MDA production (P < 0.001), increasing Bax (P < 0.001) and cleaved Caspase-3 (P < 0.001), and decreasing Bcl-2 (P < 0.001) and phosphorylated eNOS (P < 0.01). HOXA11-AS knockdown attenuated endothelial injuries via increasing eNOS phosphorylation. Luciferase assay and RIP results confirmed that miR-515-5p is directly bound to HOXA11-AS and ROCK1. HOXA11-AS promoted ox-LDL-induced HUVECs injury by directly inhibiting miR-515-5p from increasing ROCK1 expression and subsequently decreasing the expression and phosphorylation of eNOS. MiR-515-5p mimics could partially reverse the effects of HOXA11-AS knockdown. CONCLUSIONS: HOXA11-AS contributed to atherosclerotic injuries by directly regulating the miR-515-5p/ROCK1 axis. This study provided new evidence that HOXA11-AS might be a candidate for atherosclerosis therapy.

Methylophiopogonanone A suppresses ischemia/reperfusion-induced myocardial apoptosis in mice via activating PI3K/Akt/eNOS signaling pathway.

AIM: The dried tuber root of Ophiopogon japonicus has been used in the traditional Chinese medicine for treatment of myocardial ischemia and thrombosis. In this study we investigated the effects of methylophiopogonanone A (MO-A), a major homoisoflavonoid in Ophiopogon japonicus, on myocardial ischemia/reperfusion (I/R) injury. METHODS: Mice were pretreated with MO-A (10 mg·kg(-1)·d(-1), po) for 2 weeks and then subjected to transient occlusion of the left anterior descending coronary artery. Cardiac function was evaluated, and the infarct size and apoptosis index were assessed. The mechanisms underlying the cardio-protection of MO-A were analyzed in H9C2 rat cardiomyocytes subjected to hypoxia/reoxygenation (H/R). The cell viability and apoptosis were evaluated; apoptotic and relevant signaling proteins were analyzed. NO levels in the culture medium were assessed. RESULTS: In I/R mice, pretreatment with MO-A significantly reduced the infarct size (by 60.7%) and myocardial apoptosis (by 56.8%), and improved cardiac function. In H9C2 cells subjected to H/R, pretreatment with MO-A (10 µmol/L) significantly decreased apoptosis and cleaved caspase-3 expression, elevated the Bcl-2/Bax ratio and restored NO production. Furthermore, pretreatment with MO-A markedly increased the activation of PI3K/Akt/eNOS pathway in H9C2 cells subjected to H/R, and the protective effects of MO-A were abolished in the presence of the PI3K inhibitor wortmannin (100 nmol/L). CONCLUSION: MO-A attenuates I/R-induced myocardial apoptosis in mice via activating the PI3K/Akt/eNOS signaling pathway.

Total cholesterol content of erythrocyte membranes levels are associated with the presence of acute coronary syndrome and high sensitivity C-reactive protein.

In this study we assessed whether total cholesterol content of erythrocyte membranes (CEM) was associated with the presence of acute coronary syndrome (ACS) and high sensitivity C-reactive protein (hs-CRP). Consecutive angina patients were assessed; 98 had ACS and 45 had stable angina pectoris (SAP). CEM in the ACS group was significantly higher compared with the SAP group (p< 0.05). Multiple logistic regression analyses revealed a significant independent relation between CEM and the presence of ACS (OR 24.990, p<0.001). CEM was positively correlated with serum hs-CRP levels (r=0.328, p<0.001). These findings suggest a potential role of CEM as a marker of vulnerable plaque.