38 research outputs found

    Association of global coagulation profiles with cardiovascular risk factors and atherosclerosis: A sex disaggregated analysis from the BioHEART-CT study

    Get PDF
    Background: Although the association between dysregulated coagulation and atherosclerosis is well recognized, individual assays have been of minimal value in understanding disease susceptibility. Here we investigated the association of global coagulation profiles with coronary artery disease with consideration of sex differences. Methods and Results: The study included patients from the BioHEART-CT (The BioHEART Study: Assessing Patients With Suspected Cardiovascular Disease for New Disease Markers and Risk Factors) biobank who had computed tomography coronary angiograms scored for coronary artery calcium score (CACS) and Gensini score. The cohort included 206 adult patients who were referred for clinically indicated computed tomography coronary angiography and had a median of 2 major cardiac risk factors; 50% were women and the average age was 62.6 years (±9.9 years). The overall hemostatic potential (OHP) and calibrated automated thrombography generation assays were performed on platelet-poor plasma. CACS and Gensini score in men were significantly correlated in bivariate analysis with measures from the OHP assay, and regression models predicting disease severity by CACS or Gensini score were improved by adding the OHP assay variables in men but not in women. The calibrated automated thrombography generation assay demonstrated a more hypercoagulable profile in women than in men. The OHP assay showed hypercoagulable profiles in women with hyperlipidemia and men with obesity. Conclusions: The OHP assay identified hypercoagulable profiles associated with different risk factors for each sex and was associated with CACS and Gensini score severity in men, emphasizing the associations between increased fibrin generation and reduced fibrinolysis with cardiac risk factors and early atherosclerosis. Registration Information: www.anzctr.org.au. Identifier: ACTRN12618001322224.Katharine A. Kott, Marie-Christine Morel-Kopp, Stephen T. Vernon, Yuki Takagi, Belinda A. Di Bartolo, Karlheinz Peter, Jean Y. Yang, Stuart M. Grieve, Christopher Ward, Gemma A. Figtre

    Patient endothelial colony-forming cells to model coronary artery disease susceptibility and unravel the role of dysregulated mitochondrial redox signalling

    Get PDF
    Mechanisms involved in the individual susceptibility to atherosclerotic coronary artery disease (CAD) beyond traditional risk factors are poorly understood. Here, we describe the utility of cultured patient-derived endothelial colony-forming cells (ECFCs) in examining novel mechanisms of CAD susceptibility, particularly the role of dysregulated redox signalling. ECFCs were selectively cultured from peripheral blood mononuclear cells from 828 patients from the BioHEART-CT cohort, each with corresponding demographic, clinical and CT coronary angiographic imaging data. Spontaneous growth occurred in 178 (21.5%) patients and was more common in patients with hypertension (OR 1.45 (95% CI 1.03–2.02), p = 0.031), and less likely in patients with obesity (OR 0.62 [95% CI 0.40–0.95], p = 0.027) or obstructive CAD (stenosis > 50%) (OR 0.60 [95% CI 0.38–0.95], p = 0.027). ECFCs from patients with CAD had higher mitochondrial production of superoxide (O2 −–MitoSOX assay). The latter was strongly correlated with the severity of CAD as measured by either coronary artery calcium score (R2 = 0.46; p = 0.0051) or Gensini Score (R2 = 0.67; p = 0.0002). Patient-derived ECFCs were successfully cultured in 3D culture pulsatile mini-vessels. Patient-derived ECFCs can provide a novel resource for discovering mechanisms of CAD disease susceptibility, particularly in relation to mitochondrial redox signalling.Marie Besnier, Meghan Finemore, Christine Yu, Katharine A. Kott, Stephen T. Vernon, Nicole A. Seebacher, Elijah Genetzakis, Anamarija Furman, Owen Tang, Ryan L. Davis, Thomas Hansen, Peter J. Psaltis, Kristen J. Bubb, Steven G. Wise, Stuart M. Grieve, Belinda A. Di Bartolo, and Gemma A. Figtre

    Incorporating a polygenic risk score-triaged coronary calcium score into cardiovascular disease examinations to identify subclinical coronary artery disease (ESCALATE): Protocol for a prospective, nonrandomized implementation trial

    Get PDF
    Background: Identifying and targeting established modifiable risk factors has been a successful strategy for reducing the burden of coronary artery disease (CAD) at the population-level. However, up to 1-in-4 patients who present with ST elevation myocardial infarction do so in the absence of such risk factors. Polygenic risk scores (PRS) have demonstrated an ability to improve risk prediction models independent of traditional risk factors and self-reported family history, but a pathway for implementation has yet to be clearly identified. The aim of this study is to examine the utility of a CAD PRS to identify individuals with subclinical CAD via a novel clinical pathway, triaging low or intermediate absolute risk individuals for noninvasive coronary imaging, and examining the impact on shared treatment decisions and participant experience. Trial Design: The ESCALATE study is a 12-month, prospective, multicenter implementation study incorporating PRS into otherwise standard primary care CVD risk assessments, to identify patients at increased lifetime CAD risk for noninvasive coronary imaging. One-thousand eligible participants aged 45 to 65 years old will enter the study, which applies PRS to those considered low or moderate 5-year absolute CVD risk and triages those with CAD PRS ≥80% for a coronary calcium scan. The primary outcome will be the identification of subclinical CAD, defined as a coronary artery calcium score (CACS) >0 Agatston units (AU). Multiple secondary outcomes will be assessed, including baseline CACS ≥100 AU or ≥75th age-/sexmatched percentile, the use and intensity of lipid- and blood pressure-lowering therapeutics, cholesterol and blood pressure levels, and health-related quality of life (HRQOL). Conclusion: This novel trial will generate evidence on the ability of a PRS-triaged CACS to identify subclinical CAD, as well as subsequent differences in traditional risk factor medical management, pharmacotherapy utilization, and participant experience.Michael P. Gray, Yemima Berman, Giordano Bottà, Stuart M. Grieve, Amy Ho, Jessica Hu, Karice Hyun, Jodie Ingles, Garry Jennings, Gary Kilov, Jean-Frederic Levesque, Peter Meikle, Julie Redfern, Tim Usherwood, Stephen T. Vernon, Stephen J. Nicholls, and Gemma A. Figtree, On behalf of the PPP-CAD Collaborator

    <sup>17</sup>O NMR of water in ordered environments

    No full text
    Two NMR experiments are designed for selective excitation of spin I=5/2 nuclei that exhibit residual quadrupolar splittings. The I=5/2 Jeener-Broekaert experiment is preferred to the four-quantum filtration experiment as it is shown to be a more sensitive technique in experimental practice. Both techniques are applied to (17)O-enriched water in biological systems. The occurrence of water which displays a residual (17)O quadrupolar splitting is demonstrated for the first time in a model biological system and an excised tissue sample. The resulting (17)O NMR spectra are shown to have the characteristics predicted in computer-simulated I=5/2 NMR spectra

    Differences in channel and hillslope geometry record a migrating uplift wave at the Mendocino Triple Junction

    Get PDF
    Tectonic plate motion, and the resulting change in land surface elevation, has been shown to have a fundamental impact on landscape morphology. Changes to uplift rates can drive a response in fluvial channels, which then drives changes to hillslopes. Because hillslopes respond on different time scales than fluvial channels, investigating the geometry of channels and hillslopes in concert provides novel opportunities to examine how uplift rates may have changed through time. Here we perform coupled topographic analysis of channel and hillslope geometry across a series of catchments at the Mendocino triple junction (MTJ) in northern California, USA. These catchments are characterized by an order-of-magnitude difference in uplift rate from north to south. We find that dimensionless hillslope relief closely matches the uplift signal across the area and is positively correlated with channel steepness. Furthermore, the range of uncertainty in hillslope relief is lower than that of channel steepness, suggesting that it may be a more reliable recorder of uplift in the MTJ region. We find that hilltop curvature lags behind relief in its response to uplift, which in turn lags behind channel response. These combined metrics show the northward migration of the MTJ and the corresponding uplift field from topographic data alone

    An evaluation of the environmental changes in fisheries involved in the Marine Stewardship Council certification scheme

    No full text
    There is ongoing debate regarding the value of market-based instruments, such as certification schemes, as an approach to improving the environmental impact of fisheries. This article evaluates the effects of the Marine Stewardship Council on the environmental performance of fisheries over the period before and after certification. A large number of fisheries (n = 447) have undertaken pre-assessments, and in most cases (83%), the auditors recommended that significant improvements should be made before entering full assessment. In cases where substantial improvements were required, the proportion of performance indicators scoring over 80 (considered by the Marine Stewardship Council to be the point of best practice) increased by 22% between pre-assessment and certification. Significant improvements continued after certification, characterized by a 16% increase in the proportion of performance indicators scoring over 80 over a period of five years. Increases in scores assigned by auditors were significantly correlated with increases in real environmental performance (such as increases in stock biomass or the development of protected areas) and improvements in information, which led to increasing certainty that impacts were within sustainable limits. Although results show that certification is associated with real environmental benefits, most improvements are made by fisheries that require significant changes to enter the program
    corecore