Translating Evidence of HDL and Plaque Regression Di Bartolo, Belinda A; Psaltis, Peter J; Bursill, Christina A ...
Arteriosclerosis, thrombosis, and vascular biology,
2018-September, Letnik:
38, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Considerable evidence from preclinical and population studies suggests that HDLs (high-density lipoproteins) possess atheroprotective properties. Reports from HDL infusion studies in animals and ...early clinical imaging trials reported evidence of plaque regression. These findings have stimulated further interest in developing new agents targeting HDL. However, the results of more recent imaging studies in the setting of high-intensity statin use have been disappointing. As the concept of plaque changes with HDL therapeutics evolves and imaging technology to evaluate these effects advances, there will become increasing opportunity to determine the effects of HDL agents on atherosclerotic plaque (Graphic Abstract).
Spontaneous coronary artery dissection (SCAD) is an uncommon, non-iatrogenic, non-atherosclerotic cause of acute coronary syndrome. A lack of large prospective cohort studies and randomised ...controlled trials means that important questions about clinical characteristics and outcomes of patients with SCAD are yet to be fully answered.
A literature search of PUBMED, EMBASE and SCOPUS was undertaken up to and including the 23rd January 2020. Studies reporting any cohort of 10 or more SCAD patients presenting with acute coronary syndrome, with appropriate clinical follow-up data were included in the analysis. Incidences of major adverse cardiovascular events (MACE), myocardial infarction and SCAD recurrence were meta-analysed using Poisson regression.
19 studies, totalling p=2,172 patients, were included in the analysis. There was significant heterogeneity across the studies in all baseline characteristics and clinical outcomes. Prevalence of traditional cardiovascular risk factors was low; however, hypertension had a prevalence of 45% (95% CI; 35-54) and fibromuscular dysplasia (FMD) was present in 68% (95% CI; 61-74). Across all cohorts, the incidence of MACE in patients with SCAD was 7.80 per 100 person years (n=19, p=2172, 95% CI; 4.50-13.54) and SCAD recurrence was 5.49 per 100 person years (n=13, p=1408, 95% CI; 3.75-8.02).
This meta-analysis confirms that SCAD is not an inconsequential cause of acute coronary syndrome and heralds the need for further prospective research to identify predictors of recurrent events and therapies to prevent them.
•SCAD predominantly affects women and is associated with fibromuscular dysplasia.•Of the cardiovascular risk factors, hypertension has the highest prevalence.•Incidence of recurrence in SCAD patients 5.49 per 100 person years.•Further research with transparent reporting is needed to better understand SCAD.
An overview of PCI in the very elderly Shanmugam, Vimalraj Bogana; Harper, Richard; Meredith, Ian ...
Journal of geriatric cardiology : JGC,
03/2015, Letnik:
12, Številka:
2
Journal Article
Odprti dostop
Cardiovascular disease, and in particular ischemic heart disease （IHD）, is a major cause of morbidity and mortality in the very elderly （〉 80 years） worldwide. These patients represent a rapidly ...growing cohort presenting for percntaneous coronary intervention （PCI）, now constituting more than one in five patients treated with PCI in real-world practice. Furthermore, they often have greater ischemic burden than their younger counterparts, suggesting that they have greater scope of benefit from coronary revascularization therapy. Despite this, the very elderly are frequently under-represented in clinical revascularization trials and historically there has been a degree of physician reluctance in referring them for PCI procedures, with perceptions of disappointing outcomes, low success and high complication rates. Several issues have contributed to this, including the tendency for older patients with IHD to present late, with atypical symptoms or non-diagnostic ECGs, and reservations regarding their procedural risk-to-benefit ratio, due to shorter life expectancy, presence of comorbidities and increased bleeding risk from antiplatelet and anticoagulation medications. However, advances in PCI technology and techniques over the past decade have led to better outcomes and lower risk of complications and the existing body of evidence now indicates that the very elderly actually derive more relative benefit from PCI than younger populations. Importantly, this applies to all PCI settings： elective, urgent and emergency. This review discusses the role of PCI in the very elderly presenting with chronic stable IHD, non ST-elevation acute coronary syndrome, and ST-elevation myocardial infarction. It also addresses the clinical challenges met when considering PCI in this cohort and the ongoing need for research and development to further improve outcomes in these challenging patients.
Diabetes mellitus affects millions of people worldwide and is associated with devastating vascular complications. A number of these complications, such as impaired wound healing and poor coronary ...collateral circulation, are characterised by impaired ischaemia-driven angiogenesis. There is increasing evidence that high-density lipoproteins (HDL) can rescue diabetes-impaired angiogenesis through a number of mechanisms, including the modulation of endothelial cell metabolic reprogramming. Endothelial cell metabolic reprogramming in response to tissue ischaemia is a driver of angiogenesis and is dysregulated by diabetes. Specifically, diabetes impairs pathways that allow endothelial cells to upregulate glycolysis in response to hypoxia adequately and impairs suppression of mitochondrial respiration. HDL rescues the impairment of the central hypoxia signalling pathway, which regulates these metabolic changes, and this may underpin several of its known pro-angiogenic effects. This review discusses the current understanding of endothelial cell metabolism and how diabetes leads to its dysregulation whilst examining the various positive effects of HDL on endothelial cell function.
Atherosclerosis is the build-up of fatty plaques within blood vessel walls, which can occlude the vessels and cause strokes or heart attacks. It gives rise to both structural and biomolecular changes ...in the vessel walls. Current single-modality imaging techniques each measure one of these two aspects but fail to provide insight into the combined changes. To address this, our team has developed a dual-modality imaging system which combines optical coherence tomography (OCT) and fluorescence imaging that is optimized for a porphyrin lipid nanoparticle that emits fluorescence and targets atherosclerotic plaques. Atherosclerosis-prone apolipoprotein (Apo)e
mice were fed a high cholesterol diet to promote plaque development in descending thoracic aortas. Following infusion of porphyrin lipid nanoparticles in atherosclerotic mice, the fiber-optic probe was inserted into the aorta for imaging, and we were able to robustly detect a porphyrin lipid-specific fluorescence signal that was not present in saline-infused control mice. We observed that the nanoparticle fluorescence colocalized in areas of CD68
macrophages. These results demonstrate that our system can detect the fluorescence from nanoparticles, providing complementary biological information to the structural information obtained from simultaneously acquired OCT.
A review on the biomechanics of coronary arteries Carpenter, Harry J.; Gholipour, Alireza; Ghayesh, Mergen H. ...
International journal of engineering science,
February 2020, 2020-02-00, 20200201, Letnik:
147
Journal Article
Recenzirano
Globally, cardiovascular diseases are seen as one of the largest economic burdens on society and the single largest cause of death, with atherosclerosis the leading cause of myocardial infarction ...(heart attack). Due to the complex interactions in the coronary vasculature, medical imaging technology is unable to recognise correlations between artery and fluid mechanics and disease initiation and progression, hence, biomechanical analysis of coronary arteries in patient-specific models is necessary to provide critical information in clinical settings; large variability in modelling approaches, parameters and results still, however, hamper accurate and reliable model development. This review aims to assist in filling that gap by presenting an overview of research efforts to date, from both theoretical and experimental perspectives, to assist in addressing the challenge of developing a reliable and accurate biomechanical model of human coronary arteries. Studies have been categorised primarily on their approach, either purely theoretical, purely experimental/clinical or a combined theoretical and experimental/clinical approach as well as then divided into structural, fluid, and fluid–structure interaction (FSI) analysis. From research efforts to date it is clear that the development of FSI models to incorporate the effects of shear-thinning, non-Newtonian flows in viscoelastic, realistic artery and plaque morphologies developed from in vivo, high resolution imaging is critical for accurate determination of disease initiation/progression, including atherosclerosis, plaque formation, and failure mechanisms. The inclusion of micro-constituents such as micro-calcification, endothelial cell layer, collagen cross-linking, vascular smooth muscle cell contractility and constitutive blood equations also affects stress magnitude, distribution and failure mechanisms and should be adequately accounted for. A set of appendices are also provided where studies are summarised and assessed based on their approach to modelling and are categorised by considering the imaging modality used, methodology, material and blood properties, type of coronary artery, approach to the study (theoretical, experimental, in vitro & in vivo), number of patients/specimens and a general description. It is hoped this review will assist in furthering the field of coronary artery biomechanics and contribute to developing accurate and reliable patient-specific models capable of improving our understanding of cardiovascular biomechanics and hence, the initiation/progression of related diseases to address the growing global morbidity, mortality and economic challenge of cardiovascular disease and myocardial infarction.
Background There is minimal published data on outcomes of patients presenting with ST elevation myocardial infarction (STEMI) due to an ectatic infarct-related artery (EIRA). The aim of this study ...was to analyse the clinical characteristics and outcomes of these patients presenting for primary percutaneous coronary intervention (P-PCI) in comparison with non-EIRA. Methods Of the 1834 patients who presented at our institution for P-PCI between February 2008 and November 2013, 25 (1.4%) were identified as having an EIRA. These patients were compared with those with non-EIRA (80 patients) who were age, gender and lesion matched. Further sub-group analysis on in-hospital and long-term outcomes was done comparing EIRA stented and non-stented patients. Clinical events evaluated include death, recurrent infarction, unstable angina, or target lesion revascularisation (TLR). Results Baseline characteristics were similar between patients with EIRA and non-EIRA although none of those with EIRA had diabetes mellitus. By comparison to the non-EIRA group, the major procedural differences for patients with EIRA were (1) a greater incidence of large thrombus burden (96.0% vs 22.5%, p = 0.0001), (2) increased usage of peri-procedural glycoprotein IIb/IIIa inhibitors (72.0% vs 37.5%, p = 0.01) and post-procedural anticoagulation (28.0% vs 5.0%, p = 0.004), (3) larger mean stent dimension (3.9 ± 0.8 mm vs 3.4 ± 0.6 mm, p = 0.04) and (4) a higher percentage of P-PCI cases that did not have stent deployment (44.0% vs 7.5%, p = 0.0001). Patients with STEMI from EIRA had similar in-hospital outcomes but a higher long-term incidence of composite cardiovascular events at mean follow-up of 36.6 ± 14.1 months (44.0% vs 16.3% for non-EIRA, p = 0.01). Although patients with EIRA who received stenting had better in-hospital outcomes than the non-stented cohort (composite cardiovascular event rate: 0.0% vs 36.4%, p = 0.03), long-term outcomes were comparable (35.7% vs 54.6%, p = 0.59) due to a relatively high frequency of non-fatal MI and unstable angina in both groups. Conclusion Patients with STEMI due to EIRA carry worse long-term outcomes than those with non-EIRA. While successful stent deployment in the setting of EIRA improves procedural and inpatient success rates, it does not necessarily convey benefit to long-term event rates due to recurrent acute coronary syndromes.
Multimodal microendoscopes enable co‐located structural and molecular measurements in vivo, thus providing useful insights into the pathological changes associated with disease. However, different ...optical imaging modalities often have conflicting optical requirements for optimal lens design. For example, a high numerical aperture (NA) lens is needed to realize high‐sensitivity fluorescence measurements. In contrast, optical coherence tomography (OCT) demands a low NA to achieve a large depth of focus. These competing requirements present a significant challenge in the design and fabrication of miniaturized imaging probes that are capable of supporting high‐quality multiple modalities simultaneously. An optical design is demonstrated which uses two‐photon 3D printing to create a miniaturized lens that is simultaneously optimized for these conflicting imaging modalities. The lens‐in‐lens design contains distinct but connected optical surfaces that separately address the needs of both fluorescence and OCT imaging within a lens of 330 µm diameter. This design shows an improvement in fluorescence sensitivity of >10x in contrast to more conventional fiber‐optic design approaches. This lens‐in‐lens is then integrated into an intravascular catheter probe with a diameter of 520 µm. The first simultaneous intravascular OCT and fluorescence imaging of a mouse artery in vivo is reported.
Two‐photon 3D printing enables the development of micro‐lenses simultaneously optimized for multiple imaging modalities. The lens‐in‐lens design is incorporated into a 0.33 mm lens capable of high sensitivity fluorescence measurements in parallel with optical coherence tomography over a large depth of focus. This is demonstrated in an endoscopic probe for in vivo imaging inside the blood vessel of a mouse.
RATIONALE:Macrophages regulate blood vessel structure and function in health and disease. The origins of tissue macrophages are diverse, with evidence for local production and circulatory renewal.
...OBJECTIVE:We identified a vascular adventitial population containing macrophage progenitor cells and investigated their origins and fate.
METHODS AND RESULTS:Single-cell disaggregates from adult C57BL/6 mice were prepared from different tissues and tested for their capacity to form hematopoietic colony-forming units. Aorta showed a unique predilection for generating macrophage colony-forming units. Aortic macrophage colony-forming unit progenitors coexpressed stem cell antigen-1 and CD45 and were adventitially located, where they were the predominant source of proliferating cells in the aortic wall. Aortic Sca-1CD45 cells were transcriptionally and phenotypically distinct from neighboring cells lacking stem cell antigen-1 or CD45 and contained a proliferative (Ki67) Linc-KitCD135CD115CX3CR1Ly6CCD11b subpopulation, consistent with the immunophenotypic profile of macrophage progenitors. Adoptive transfer studies revealed that Sca-1CD45 adventitial macrophage progenitor cells were not replenished via the circulation from bone marrow or spleen, nor was their prevalence diminished by depletion of monocytes or macrophages by liposomal clodronate treatment or genetic deficiency of macrophage colony-stimulating factor. Rather adventitial macrophage progenitor cells were upregulated in hyperlipidemic ApoE and LDL-R mice, with adventitial transfer experiments demonstrating their durable contribution to macrophage progeny particularly in the adventitia, and to a lesser extent the atheroma, of atherosclerotic carotid arteries.
CONCLUSIONS:The discovery and characterization of resident vascular adventitial macrophage progenitor cells provides new insight into adventitial biology and its participation in atherosclerosis and provokes consideration of the broader existence of local macrophage progenitors in other tissues.
•EEG slowing and reduced functional connectivity associate with delirium in older adults.•Hyperexcitability and increased functional connectivity associate with delirium in children.•Very little is ...known about delirium vulnerability and the long-term effects on brain function.
Delirium is a common neurocognitive disorder in hospital settings, characterised by fluctuating impairments in attention and arousal following an acute precipitant. Electroencephalography (EEG) is a useful method to understand delirium pathophysiology. We performed a systematic review to investigate associations between delirium and EEG measures recorded prior, during, and after delirium. A total of 1,655 articles were identified using PsycINFO, Embase and MEDLINE, 31 of which satisfied inclusion criteria. Methodological quality assessment was undertaken, resulting in a mean quality score of 4 out of a maximum of 5. Qualitative synthesis revealed EEG slowing and reduced functional connectivity discriminated between those with and without delirium (i.e. EEG during delirium); the opposite pattern was apparent in children, with cortical hyperexcitability. EEG appears to have utility in differentiating those with and without delirium, but delirium vulnerability and the long-term effects on brain function require further investigation. Findings provide empirical support for the theory that delirium is a disorder of reduced functional brain integration.
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