Explore the vast range of titles available.

Atherosclerotic coronary artery disease (CAD) results from build-up of cholesterol-rich plaques in the walls of the coronary arteries and is a leading cause of death. Inflammation is central to atherosclerosis. Uncontrolled inflammation makes coronary plaques “unstable” and vulnerable to rupture or erosion, leading to thrombosis and myocardial infarction (MI). As multiple inflamed plaques often co-exist in the coronary system, patients are at risk of repeated atherothrombotic cardiovascular events after MI, with rates of 10–12% at one year and 18–20% at three years. This is largely because current therapies for CAD, such as lipid-lowering statins, do not adequately control plaque inflammation. New anti-atherosclerotic agents are therefore needed, especially those that better target inflammation. The recent positive results for the anti-interleukin-1-beta (IL-1β) monoclonal antibody, Canakinumab, in the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) clinical trial has provided a major stimulant to the field. It highlights that not only is inflammation important from a pathogenic and risk prediction perspective in CAD, but that reducing inflammation can be beneficial. The challenge is now to find the best strategies to achieve this in real-world practice. This review outlines the role that inflammation plays in atherosclerosis and provides an update on anti-inflammatory therapies currently being investigated to target atherosclerosis.

Background Insertable cardiac monitors (ICMs) are small subcutaneously implanted devices that detect changes in R-wave amplitudes (RWAs), effective in arrhythmia-monitoring. Although ICMs have proven to be immensely successful, electrical artefacts are frequent and can lead to misdiagnosis. Thus, there is a growing need to sustain and increase efficacy in detection rates by gaining insight into various patient-specific factors such as body postures and activities. Methods RWAs were measured in 15 separate postures, including supine, lying on the right-side (RS) or left-side (LS) and sitting, and two separate ICM orientations, immediately after implantation of Confirm Rx™ ICM in 99 patients. Results The patients (53 females and 46 males, mean ages 66.62 ± 14.7 and 66.40 ± 12.25 years, respectively) had attenuated RWAs in RS, LS and sitting by ~ 26.4%, ~ 27.8% and ~ 21.2% respectively, compared to supine. Gender-based analysis indicated RWAs in RS (0.32 mV (0.09–1.03 mV), p  < 0.0001) and LS (0.37 mV (0.11–1.03 mV), p  = 0.004) to be significantly attenuated compared to supine (0.52 mV (0.20–1.03 mV) for female participants. Similar attenuation was not evident for male participants. Further, parasternally oriented ICMs ( n  = 44), attenuated RWAs in RS (0.37 mV(0.09–1.03 mV), p  = 0.05) and LS (0.34 mV (0.11–1.03 mV), p  = 0.02) compared to supine (0.48 mV (0.09–1.03 mV). Similar differences were not observed in participants with ICMs in the 45°-relative-to-sternum ( n  = 46) orientation. When assessing the combined effect of gender and ICM orientation, female participants demonstrated plausible attenuation in RWAs for RS and LS postures compared to supine, an effect not observed in male participants. Conclusion This is the first known study depicting the effects on RWA due to body postures and activities immediately post-implantation with an overt impact by gender and orientation of ICM. Future work assessing the cause of gender-based differences in RWAs may be critical. Trial registration: Clinical Trials, NCT03803969. Registered 15 January 2019 – Retrospectively registered, https://clinicaltrials.gov/NCT03803969

High-density lipoproteins (HDL) have received considerable interest as a target for the development of novel anti-atherosclerotic agents beyond conventional approaches to lipid lowering. While a number of approaches have focused on modifying remodeling and expression pathways implicated in the regulation of HDL levels, an additional approach involves simply infusions of delipidated HDL. Several groups have advanced HDL infusions to clinical development with intriguing signs suggesting potentially favorable impacts at the level of the artery wall. The findings of early studies of infusional HDL therapies will be reviewed.

Converging evidence indicates that extra-embryonic yolk sac is the source of both macrophages and endothelial cells in adult mouse tissues. Prevailing views are that these embryonically derived cells are maintained after birth by proliferative self-renewal in their differentiated states. Here we identify clonogenic endothelial-macrophage (EndoMac) progenitor cells in the adventitia of embryonic and postnatal mouse aorta, that are independent of Flt3-mediated bone marrow hematopoiesis and derive from an early embryonic CX 3 CR1 + and CSF1R + source. These bipotent progenitors are proliferative and vasculogenic, contributing to adventitial neovascularization and formation of perfused blood vessels after transfer into ischemic tissue. We establish a regulatory role for angiotensin II, which enhances their clonogenic and differentiation properties and rapidly stimulates their proliferative expansion in vivo. Our findings demonstrate that embryonically derived EndoMac progenitors participate in local vasculogenic responses in the aortic wall by contributing to the expansion of endothelial cells and macrophages postnatally. The extraembryonic yolk sac is a major location for developmental hematopoiesis, but it is unclear whether non-bone marrow sources contribute during adulthood. Here they show that embryonically derived endothelial-macrophage progenitor cells located in the aorta are a bipotent source of macrophage and endothelial cells later in life.

Background and aim: poor quality of life (QoL) has been identified as an independent risk factor for mortality and major cardiac events (MACE) in patients with cardiovascular disease (CVD). The aim of this study was to assess health-related quality of life (HRQoL) at baseline and its association with outcome in patients with coronary artery disease presenting for percutaneous coronary intervention (PCI). The outcome was measured by mortality and MACE at 1-year, and whether there was any difference for sex and different age groups. Methods and results: all patients prospectively enrolled into the GenesisCare Outcome Registry (GCOR) over a 11-year period were included in the study. The EQ-5D-5L and VAS patient survey were used for assessment of baseline HRQoL. Of the 15,198 patients, only 6591 (43.4%) completed the self-assessment. Women had significantly more impairment of all five dimensions of the EQ-5D-5L survey, and their self-reported QoL was significantly lower than men (68.3 in women vs. 71.9 in men, p < 0.001). Poor QoL was strongly associated with increased mortality (HR 2.85; 95% CI 1.76 to 4.62, p < 0.001) and MACE (HR 1.40; 95% CI 1.10 to 1.79, p = 0.01). A similar trend was noted for women and men, but did not reach significance in women due to the smaller number of female patients. Conclusion: poor HRQoL is associated with subsequent mortality and MACE in patients undergoing PCI. By not assessing quality of life as a standard of care, an opportunity is lost to identify high-risk patients who may benefit from targeted interventions to improve health outcomes.

Objective: The effect of baseline differences between men and women on early outcomes after percutaneous coronary intervention (PCI). Design, setting, participants: This is an observational study of all participants in the GenesisCare Cardiovascular Outcomes Registry, undergoing PCI. The registry holds data for both emergency and elective procedures. Data was collected on 10,989 consecutive patients from 12 Australian Private Hospitals, including baseline demographics, co-morbidities, risk factors, PCI procedures, and lesion characteristics. Main outcome measures: Outcome was measured for complications (in-hospital death, peri-procedural myocardial infarctions, and bleeding events), at discharge and at 30-days for death, myocardial infarction, target lesion revascularisation (TLR), major adverse cardiac events (MACE), and unplanned readmissions. Results: Women represented 23% of the study population, were significantly older, with a higher rate of hypertension and hyperlipidaemia. Heart failure was more common in women and was associated with a significantly higher average ejection fraction than in men. Women had a lower rate of pre-existing coronary artery disease (CAD), had less complex CAD, and needed fewer stents. Periprocedural complications were similar, but major bleeding was more common in women. The 30-day outcome was similar between men and women for death, myocardial infarction, target lesion revascularisation (TLR), major adverse cardiovascular events (MACE), and unplanned readmissions. Conclusions: Although significant differences were observed between women and men in both clinical presentation and complexity of disease, the 30-day outcome was similar for death and MACE. Women had a higher rate of major bleeding events, and lower adherence to statins and dual antiplatelet therapy (DAPT).

Background and aim: Unplanned cardiac readmissions in patients with percutaneous intervention (PCI) is very common and is seen as a quality indicator of in-hospital care. Most studies have reported on the 30-day cardiac readmission rates, with very limited information being available on 1-year readmission rates and their association with mortality. The aim of this study was to investigate the impact of biological sex at 1-year post-PCI on unplanned cardiac readmissions. Methods and results: Patients enrolled into the GenesisCare Cardiovascular Outcomes Registry (GCOR-PCI) from December 2008 to December 2020 were included in the study. A total of 13,996 patients completed 12 months of follow-up and were assessed for unplanned cardiac readmissions. All patients with unplanned cardiac readmissions in the first year of post-PCI were followed in year 2 (post-PCI) for survival status. The rate of unplanned cardiac readmissions was 10.1%. Women had a 29% higher risk of unplanned cardiac readmission (HR 1.29, 95% CI 1.11 to 1.48; p = 0.001), and female sex was identified as an independent predictor of unplanned cardiac readmissions. Any unplanned cardiac readmission in the first year was associated with a 2.5-fold higher risk of mortality (HR 2.50, 95% CI 1.67 to 3.75; p < 0.001), which was similar for men and women. Conclusion: Unplanned cardiac readmissions in the first year post-PCI was strongly associated with increased all-cause mortality. Whilst the incidence of all-cause mortality was similar between women and men, a higher incidence of unplanned cardiac readmissions was observed for women, suggesting distinct predictors of unplanned cardiac readmissions exist between women and men.

The cellular origins of vasa vasorum are ill-defined and may involve circulating or local progenitor cells. We previously discovered that murine aortic adventitia contains Sca-1 + CD45 + progenitors that produce macrophages. Here we investigated whether they are also vasculogenic. In aortas of C57BL/6 mice, Sca-1 + CD45 + cells were localised to adventitia and lacked surface expression of endothelial markers (<1% for CD31, CD144, TIE-2). In contrast, they did show expression of CD31, CD144, TIE-2 and VEGFR2 in atherosclerotic ApoE −/− aortas. Although Sca-1 + CD45 + cells from C57BL/6 aorta did not express CD31, they formed CD31 + colonies in endothelial differentiation media and produced interconnecting vascular-like cords in Matrigel that contained both endothelial cells and a small population of macrophages, which were located at branch points. Transfer of aortic Sca-1 + CD45 + cells generated endothelial cells and neovessels de novo in a hindlimb model of ischaemia and resulted in a 50% increase in perfusion compared to cell-free control. Similarly, their injection into the carotid adventitia of ApoE −/− mice produced donor-derived adventitial and peri-adventitial microvessels after atherogenic diet, suggestive of newly formed vasa vasorum. These findings show that beyond its content of macrophage progenitors, adventitial Sca-1 + CD45 + cells are also vasculogenic and may be a source of vasa vasorum during atherogenesis.

Background: Readmissions within 1 year after percutaneous coronary intervention (PCI) are common (18.6–50.4% in international series) and a burden to patients and health services, however their long-term implications are not well characterised. We compared predictors of 30-day (early) and 31-day to 1-year (late) unplanned readmission and the impact of unplanned readmission on long-term clinical outcomes post-PCI. Methods: Patients enrolled in the GenesisCare Cardiovascular Outcomes Registry (GCOR-PCI) from 2008 to 2020 were included in the study. Multivariate logistic regression analysis was performed to identify predictors of early and late unplanned readmission. A Cox proportion hazards regression model was used to explore the impact of any unplanned readmission during the first year post-PCI on the clinical outcomes at 3 years. Finally, patients with early and late unplanned readmission were compared to determine which group was at the highest risk of adverse long-term outcomes. Results: The study comprised 16,911 consecutively enrolled patients who underwent PCI between 2009–2020. Of these, 1422 patients (8.5%) experienced unplanned readmission within 1-year post-PCI. Overall, the mean age was 68.9 ± 10.5 years, 76.4% were male and 45.9% presented with acute coronary syndromes. Predictors of unplanned readmission included increasing age, female gender, previous CABG, renal impairment and PCI for acute coronary syndromes. Unplanned readmission within 1 year of PCI was associated with an increased risk of MACE (adjusted HR 1.84 (1.42–2.37), p < 0.001) and death over a 3-year follow-up (adjusted HR 1.864 (1.34–2.59), p < 0.001) compared with those without readmission within 1-year post-PCI. Late compared with early unplanned readmission within the first year of PCI was more frequently associated with subsequent unplanned readmission, MACE and death between 1 and 3 years post-PCI. Conclusions: Unplanned readmissions in the first year following PCI, particularly those occurring more than 30 days after discharge, were associated with a significantly higher risk of adverse outcomes, such as MACE and death at 3 years. Strategies to identify patients at high risk of readmission and interventions to reduce their greater risk of adverse events should be implemented post-PCI

Organic fluorescent probes are widely used to detect key biomolecules; however, they often lack the photostability required for extended intracellular imaging. Here we report a new hybrid nanomaterial (peroxynanosensor, PNS), consisting of an organic fluorescent probe bound to a nanodiamond, that overcomes this limitation to allow concurrent and extended cell-based imaging of the nanodiamond and ratiometric detection of hydrogen peroxide. Far-red fluorescence of the nanodiamond offers continuous monitoring without photobleaching, while the green fluorescence of the organic fluorescent probe attached to the nanodiamond surface detects hydrogen peroxide on demand. PNS detects basal production of hydrogen peroxide within M1 polarised macrophages and does not affect macrophage growth during prolonged co-incubation. This nanosensor can be used for extended bio-imaging not previously possible with an organic fluorescent probe, and is spectrally compatible with both Hoechst 33342 and MitoTracker Orange stains for hyperspectral imaging.