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Background: The fear of contagion during the coronavirus disease-2019 (COVID-19) pandemic may have potentially refrained patients with ST-segment elevation myocardial infarction (STEMI) from accessing the emergency system, with subsequent impact on mortality.Objectives: The ISACS-STEMI COVID-19 registry aims to estimate the true impact of the COVID-19 pandemic on the treatment and outcome of patients with STEMI treated by primary percutaneous coronary intervention (PPCI), with identification of "at-risk" patient cohorts for failure to present or delays to treatment.Methods: This retrospective registry was performed in European high-volume PPCI centers and assessed patients with STEMI treated with PPPCI in March/April 2019 and 2020. Main outcomes are the incidences of PPCI, delayed treatment, and in-hospital mortality.Results: A total of 6,609 patients underwent PPCI in 77 centers, located in 18 countries. In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.811; 95% confidence interval: 0.78 to 0.84; p < 0.0001). The heterogeneity among centers was not related to the incidence of death due to COVID-19. A significant interaction was observed for patients with arterial hypertension, who were less frequently admitted in 2020 than in 2019. Furthermore, the pandemic was associated with a significant increase in door-to-balloon and total ischemia times, which may have contributed to the higher mortality during the pandemic.Conclusions: The COVID-19 pandemic had significant impact on the treatment of patients with STEMI, with a 19% reduction in PPCI procedures, especially among patients suffering from hypertension, and a longer delay to treatment, which may have contributed to the increased mortality during the pandemic. (Primary Angioplasty for STEMI During COVID-19 Pandemic [ISACS-STEMI COVID-19] Registry; NCT04412655). [ABSTRACT FROM AUTHOR]

Background T cells and macrophages are implicated in the pathogenesis of aortic aneurysm (AA) and atherosclerosis. We recently demonstrated that a vaccine using an apoB-100–related peptide p210 reduces atherosclerosis with favorable modulation of CD8 + T cells in apolipoprotein E–deficient (apoE −/− ) mice. Objectives This study hypothesized that a p210 vaccine could reduce AA formation in the angiotensin II (Ang II)–induced AA model. Methods Male apoE −/− mice were immunized with p210 vaccine and implanted with an Ang II–releasing pump for 4 weeks. Flow cytometry assessed T cell activation and phenotype. Interleukin-6 (IL-6) and monocyte chemotactic protein 1 (MCP-1) expression were assessed using reverse transcription polymerase chain reaction. We used ex vivo aortic explants to test monocyte adhesion and in vitro cocultures to evaluate CD8 + T cell function. Results The p210 vaccine activated CD8 + T cells and reduced AA formation and mortality due to AA rupture, which was attenuated by CD8 + T cell depletion. Vaccination decreased expression of IL-6 and MCP-1 and reduced macrophage infiltration in the aorta. Cytotoxic T-lymphocyte assay showed that CD8 + T cells from p210-immunized mice had higher lytic activity against Ang II–stimulated macrophages. The p210 vaccine decreased splenic Th17 cells, and in vitro coculture of CD4 + and CD8 + T cells showed that CD8 + T cells from p210-immunized mice inhibited the polarization of CD4 + T cells into Th17 cells. IL-17A −/− mice infused with a higher dose of Ang II did not develop AA rupture. Conclusions A p210 vaccine protected against Ang II–induced AA formation and mortality by reducing macrophage infiltration in the aorta and decreasing Th17 cell polarization. Our findings provide a potentially novel immunomodulating approach against AA. [ABSTRACT FROM AUTHOR]

In this study, we examined whether a reconstituted high-density lipoprotein (HDL) utilizing recombinant apolipoprotein A-IMilano (apo A-IM)/phospholipid complex (PC) could restore normal endothelial function in hypercholesterolemic apolipoprotein (apo) E-null mice.We have previously shown antiatherosclerotic and vasculoprotective effects of recombinant apo A-IM.A perfused vessel preparation was used to examine vascular responses in control wild-type, untreated, and treated apo E-null mice. Aortic tissue cholesterol content and platelet aggregation were also measured.Endothelium-dependent vasodilator responses to acetycholine were significantly inhibited in untreated apo E-null mice compared with control wild-type mice (p < 0.001). Treatment of the mice for five weeks with once every-other-day intravenous bolus injections of apo A-IM/PC restored endothelium-dependent dilation in a dose-dependent manner (p < 0.01 at 80 mg/kg dose). The improvement in endothelial function was associated with a reduction in aortic cholesterol content and reduced platelet aggregability and occurred despite severe and persistent hypercholesterolemia. Neither treatment with free protein nor phospholipid carrier alone produced any significant effects. We performed additional experiments in vitro in isolated rabbit carotid arteries to compare the effects on lysophosphatidylcholine (LPC)-induced endothelial dysfunction. Treatment with apo A-IM/PC prevented impairment of endothelium-dependent vasodilator responses to acetylcholine to a greater degree than either wild-type apo A-I or plasma-derived HDL.Our results indicate a rapid improvement in endothelial dysfunction with recombinant apo A-IM/PC that is associated with mobilization of tissue cholesterol. Taken together with previously established antiatherosclerotic and antithrombotic effects, these findings suggest significant vasculoprotective effects with apo A-IM/PC therapy. [Copyright &y& Elsevier]