Amanda Hunter - Academia.edu (original) (raw)

Papers by Amanda Hunter

Research paper thumbnail of Global association of air pollution and heart failure: a systematic review and meta-analysis

The Lancet, 2013

Background Acute exposure to air pollution has been linked to myocardial infarction, but its effe... more Background Acute exposure to air pollution has been linked to myocardial infarction, but its effect on heart failure is uncertain. We did a systematic review and meta-analysis to assess the association between air pollution and acute decompensated heart failure including hospitalisation and heart failure mortality.

Research paper thumbnail of Use of Coronary Computed Tomographic Angiography to Guide Management of Patients With Coronary Disease

Journal of the American College of Cardiology, 2016

In a prospective, multicenter, randomized controlled trial, 4,146 patients were randomized to rec... more In a prospective, multicenter, randomized controlled trial, 4,146 patients were randomized to receive standard care or standard care plus coronary computed tomography angiography (CCTA). The purpose of this study was to explore the consequences of CCTA-assisted diagnosis on invasive coronary angiography, preventive treatments, and clinical outcomes. In post hoc analyses, we assessed changes in invasive coronary angiography, preventive treatments, and clinical outcomes using national electronic health records. Despite similar overall rates (409 vs. 401; p = 0.451), invasive angiography was less likely to demonstrate normal coronary arteries (20 vs. 56; hazard ratios [HRs]: 0.39 [95% confidence interval (CI): 0.23 to 0.68]; p < 0.001) but more likely to show obstructive coronary artery disease (283 vs. 230; HR: 1.29 [95% CI: 1.08 to 1.55]; p = 0.005) in those allocated to CCTA. More preventive therapies (283 vs. 74; HR: 4.03 [95% CI: 3.12 to 5.20]; p < 0.001) were initiated after CCTA, with each drug commencing at a median of 48 to 52 days after clinic attendance. From the median time for preventive therapy initiation (50 days), fatal and nonfatal myocardial infarction was halved in patients allocated to CCTA compared with those assigned to standard care (17 vs. 34; HR: 0.50 [95% CI: 0.28 to 0.88]; p = 0.020). Cumulative 6-month costs were slightly higher with CCTA: difference 462(95462 (95% CI: 462(95303 to $621). In patients with suspected angina due to coronary heart disease, CCTA leads to more appropriate use of invasive angiography and alterations in preventive therapies that were associated with a halving of fatal and non-fatal myocardial infarction. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590).

Research paper thumbnail of A role for the long non-coding RNA SENCR in commitment and function of endothelial cells

Molecular therapy : the journal of the American Society of Gene Therapy, Jan 22, 2016

Despite the increasing importance of long non-coding RNA in physiology and disease, their role in... more Despite the increasing importance of long non-coding RNA in physiology and disease, their role in endothelial biology remains poorly understood. Growing evidence has highlighted them to be essential regulators of human embryonic stem cell differentiation. SENCR, a vascular-enriched long non-coding RNA, overlaps the Friend Leukemia Integration virus 1 (FLI1) gene, a regulator of endothelial development. Therefore, we wanted to test the hypothesis that SENCR may contribute to mesodermal and endothelial commitment as well as in endothelial function. We thus developed new differentiation protocols allowing generation of endothelial cells from human embryonic stem cells using both directed and haemogenic routes. The expression of SENCR was markedly regulated during endothelial commitment using both protocols. SENCR did not control the pluripotency of pluripotent cells; however its overexpression significantly potentiated early mesodermal and endothelial commitment. In HUVEC, SENCR induce...

Research paper thumbnail of Abstract 9900: Air Pollution and Stroke: A Systematic Review and Meta-Analysis

Circulation, Nov 25, 2014

Research paper thumbnail of Chapter 11. Mechanism of Action of Combustion-derived Nanoparticles

Issues in Toxicology, 2015

Research paper thumbnail of Effect of engineered nanoparticles on platelet activation and thrombus formation in man

Research paper thumbnail of Vessel wall endothelial cells, but not circulating endothelial progenitor cells, have impaired function in premature coronary artery disease

Research paper thumbnail of Impaired vascular function and repair in patients with premature coronary artery disease

European journal of preventive cardiology, Jan 14, 2015

Endothelial dysfunction is central to the pathogenesis of coronary artery disease, but the role o... more Endothelial dysfunction is central to the pathogenesis of coronary artery disease, but the role of local and circulating endothelial progenitor cells in maintaining vascular health is poorly understood. We hypothesised that impaired local and circulating vascular repair mechanisms predispose to endothelial dysfunction and the premature onset of coronary artery disease. Patients with premature coronary artery disease (n = 16) and healthy age- and sex-matched controls (n = 16) underwent venous occlusion plethysmography with intra-arterial infusion of acetylcholine and sodium nitroprusside. Numbers of circulating endothelial progenitor cells were directly quantified in whole blood by flow cytometry. Endothelial cells were isolated from the blood vessel wall and from peripheral blood mononuclear cells, and expanded in vitro for phenotypic and functional characterisation and analysis of microRNA expression levels. A dose-dependent increase in forearm blood flow (p < 0.001) was attenua...

Research paper thumbnail of Short term exposure to air pollution and stroke: systematic review and meta-analysis

BMJ (Clinical research ed.), 2015

To review the evidence for the short term association between air pollution and stroke. Systemati... more To review the evidence for the short term association between air pollution and stroke. Systematic review and meta-analysis of observational studies Medline, Embase, Global Health, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science searched to January 2014 with no language restrictions. Studies investigating the short term associations (up to lag of seven days) between daily increases in gaseous pollutants (carbon monoxide, sulphur dioxide, nitrogen dioxide, ozone) and particulate matter (<2.5 µm or <10 µm diameter (PM2.5 and PM10)), and admission to hospital for stroke or mortality. Admission to hospital and mortality from stroke. From 2748 articles, 238 were reviewed in depth with 103 satisfying our inclusion criteria and 94 contributing to our meta-estimates. This provided a total of 6.2 million events across 28 countries. Admission to hospital for stroke or mortality from stroke was associated with an increase in concentrations of carbon ...

Research paper thumbnail of CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial

Lancet, Jan 13, 2015

The benefit of CT coronary angiography (CTCA) in patients presenting with stable chest pain has n... more The benefit of CT coronary angiography (CTCA) in patients presenting with stable chest pain has not been systematically studied. We aimed to assess the effect of CTCA on the diagnosis, management, and outcome of patients referred to the cardiology clinic with suspected angina due to coronary heart disease. In this prospective open-label, parallel-group, multicentre trial, we recruited patients aged 18-75 years referred for the assessment of suspected angina due to coronary heart disease from 12 cardiology chest pain clinics across Scotland. We randomly assigned (1:1) participants to standard care plus CTCA or standard care alone. Randomisation was done with a web-based service to ensure allocation concealment. The primary endpoint was certainty of the diagnosis of angina secondary to coronary heart disease at 6 weeks. All analyses were intention to treat, and patients were analysed in the group they were allocated to, irrespective of compliance with scanning. This study is registere...

Research paper thumbnail of Combustion-derived air pollution and cardiovascular disease

British journal of hospital medicine (London, England : 2005), 2012

Air pollution is a modifiable risk factor for cardiovascular disease that affects the entire popu... more Air pollution is a modifiable risk factor for cardiovascular disease that affects the entire population and is thus a major public health concern. It is important to understand how air pollution increases cardiovascular risk to develop strategies to protect susceptible individuals and reduce the effect of air pollution on cardiovascular health.

Research paper thumbnail of Effect of wood smoke exposure on vascular function and thrombus formation in healthy fire fighters

Particle and Fibre Toxicology, 2014

BackgroundMyocardial infarction is the leading cause of death in fire fighters and has been linke... more BackgroundMyocardial infarction is the leading cause of death in fire fighters and has been linked with exposure to air pollution and fire suppression duties. We therefore investigated the effects of wood smoke exposure on vascular vasomotor and fibrinolytic function, and thrombus formation in healthy fire fighters.MethodsIn a double-blind randomized cross-over study, 16 healthy male fire fighters were exposed to wood smoke (~1 mg/m3 particulate matter concentration) or filtered air for one hour during intermittent exercise. Arterial pressure and stiffness were measured before and immediately after exposure, and forearm blood flow was measured during intra-brachial infusion of endothelium-dependent and -independent vasodilators 4¿6 hours after exposure. Thrombus formation was assessed using the ex vivo Badimon chamber at 2 hours, and platelet activation was measured using flow cytometry for up to 24 hours after the exposure.ResultsCompared to filtered air, exposure to wood smoke increased blood carboxyhaemoglobin concentrations (1.3% versus 0.8%; P¿&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;¿0.001), but had no effect on arterial pressure, augmentation index or pulse wave velocity (P¿&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;¿0.05 for all). Whilst there was a dose-dependent increase in forearm blood flow with each vasodilator (P¿&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;¿0.01 for all), there were no differences in blood flow responses to acetylcholine, sodium nitroprusside or verapamil between exposures…

Research paper thumbnail of High-sensitivity troponin I concentrations are a marker of an advanced hypertrophic response and adverse outcomes in patients with aortic stenosis

European heart journal, Jan 7, 2014

High-sensitivity cardiac troponin I (cTnI) assays hold promise in detecting the transition from h... more High-sensitivity cardiac troponin I (cTnI) assays hold promise in detecting the transition from hypertrophy to heart failure in aortic stenosis. We sought to investigate the mechanism for troponin release in patients with aortic stenosis and whether plasma cTnI concentrations are associated with long-term outcome. Plasma cTnI concentrations were measured in two patient cohorts using a high-sensitivity assay. First, in the Mechanism Cohort, 122 patients with aortic stenosis (median age 71, 67% male, aortic valve area 1.0 ± 0.4 cm(2)) underwent cardiovascular magnetic resonance and echocardiography to assess left ventricular (LV) myocardial mass, function, and fibrosis. The indexed LV mass and measures of replacement fibrosis (late gadolinium enhancement) were associated with cTnI concentrations independent of age, sex, coronary artery disease, aortic stenosis severity, and diastolic function. In the separate Outcome Cohort, 131 patients originally recruited into the Scottish Aortic S...

Research paper thumbnail of High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study

BMJ (Clinical research ed.), 2015

To evaluate the diagnosis of myocardial infarction using a high sensitivity troponin I assay and ... more To evaluate the diagnosis of myocardial infarction using a high sensitivity troponin I assay and sex specific diagnostic thresholds in men and women with suspected acute coronary syndrome. Prospective cohort study. Regional cardiac centre, United Kingdom. Consecutive patients with suspected acute coronary syndrome (n=1126, 46% women). Two cardiologists independently adjudicated the diagnosis of myocardial infarction by using a high sensitivity troponin I assay with sex specific diagnostic thresholds (men 34 ng/L, women 16 ng/L) and compared with current practice where a contemporary assay (50 ng/L, single threshold) was used to guide care. Diagnosis of myocardial infarction. The high sensitivity troponin I assay noticeably increased the diagnosis of myocardial infarction in women (from 11% to 22%; P<0.001) but had a minimal effect in men (from 19% to 21%, P=0.002). Women were less likely than men to be referred to a cardiologist or undergo coronary revascularisation (P<0.05 fo...

Research paper thumbnail of Lyophilised reconstituted human platelets increase thrombus formation in a clinical ex vivo model of deep arterial injury

Thrombosis and Haemostasis, 2012

Platelets are the principal component of the innate haemostatic system that protect from traumati... more Platelets are the principal component of the innate haemostatic system that protect from traumatic bleeding. We investigated whether lyophilised human platelets (LHPs) could enhance clot formation within platelet-free and whole blood environments using an ex vivo model of deep arterial injury. Lyophilised human platelets were produced from stored human platelets and characterised using conventional, fluorescent and electron microscopic techniques. LHPs were resuspended in platelet-free plasma (PFP) obtained from citrated whole human blood to form final concentrations of 0, 20 and 200 x 10⁹ LHPs/L. LHPs with recalcified PFP or whole blood were perfused through the chamber at low (212 s⁻¹) and high (1,690 s⁻¹) shear rates with porcine aortic tunica media as thrombogenic substrate. LHPs shared morphological characteristics with native human platelets and were incorporated into clot generated from PFP or whole blood. Histomorphometrically measured mean thrombus area increased in a dose-dependent manner following the addition of LHPs to PFP under conditions of high shear [704 μm² ± 186 μm² (mean ± SEM), 1,511 μm² ± 320 μm² and 2,378 μm² ± 315 μm², for LHPs at 0, 20 and 200 x 10⁹ /l, respectively (p= 0.012)]. Lyophilised human platelets retain haemostatic properties when reconstituted in both PFP and whole blood, and enhance thrombus formation in a model of deep arterial injury. These data suggest that LHPs have the potential to serve as a therapeutic intervention during haemorrhage under circumstances of trauma, and platelet depletion or dysfunction.

Research paper thumbnail of Global association of air pollution and heart failure: a systematic review and meta-analysis

The Lancet, 2013

Background Acute exposure to air pollution has been linked to myocardial infarction, but its effe... more Background Acute exposure to air pollution has been linked to myocardial infarction, but its effect on heart failure is uncertain. We did a systematic review and meta-analysis to assess the association between air pollution and acute decompensated heart failure including hospitalisation and heart failure mortality.

Research paper thumbnail of Nanoparticle Enhanced Mri: A Novel Method of Investigating Myocardial Inflammation

Journal of the American College of Cardiology, 2013

Background: "Ultrasmall superparamagnetic particles of iron-oxide" (USPIOs; diameter <30 nm)) can... more Background: "Ultrasmall superparamagnetic particles of iron-oxide" (USPIOs; diameter <30 nm)) can be used as a novel contrast media with MRI. They are internalised by inlammatory cells. We sought out to assess whether USPIOs could be used to measure in vivo myocardial cellular inlammation.

Research paper thumbnail of High Sensitive Troponin Predicts Long–Term Prognosis in Patients with Aortic Stenosis

Journal of the American College of Cardiology, 2013

Background: Cardiac troponins are excellent prognostic markers in patients with stable coronary d... more Background: Cardiac troponins are excellent prognostic markers in patients with stable coronary disease and heart failure, but its role in aortic stenosis is unknown. We investigated whether baseline high sensitive troponin I (hsTnI) is associated with severity and outcome in patients with aortic stenosis.

Research paper thumbnail of Fire Simulation Exposure Causes Impairment of Endothelial Function and Increased Thrombogenicity in Healthy Firefighters

Journal of the American College of Cardiology, 2014

ABSTRACT The risk of acute myocardial infarction in firefighters is increased during fire suppres... more ABSTRACT The risk of acute myocardial infarction in firefighters is increased during fire suppression duties, and is likely to reflect a combination of factors including extreme physical exertion and heat exposure. We assess the effects of physical exertion and heat exposure on vascular function and thrombosis in firefighters.

Research paper thumbnail of Controlled Exposures to Air Pollutants and Risk of Cardiac Arrhythmia

Environmental Health Perspectives, 2014

Research paper thumbnail of Global association of air pollution and heart failure: a systematic review and meta-analysis

The Lancet, 2013

Background Acute exposure to air pollution has been linked to myocardial infarction, but its effe... more Background Acute exposure to air pollution has been linked to myocardial infarction, but its effect on heart failure is uncertain. We did a systematic review and meta-analysis to assess the association between air pollution and acute decompensated heart failure including hospitalisation and heart failure mortality.

Research paper thumbnail of Use of Coronary Computed Tomographic Angiography to Guide Management of Patients With Coronary Disease

Journal of the American College of Cardiology, 2016

In a prospective, multicenter, randomized controlled trial, 4,146 patients were randomized to rec... more In a prospective, multicenter, randomized controlled trial, 4,146 patients were randomized to receive standard care or standard care plus coronary computed tomography angiography (CCTA). The purpose of this study was to explore the consequences of CCTA-assisted diagnosis on invasive coronary angiography, preventive treatments, and clinical outcomes. In post hoc analyses, we assessed changes in invasive coronary angiography, preventive treatments, and clinical outcomes using national electronic health records. Despite similar overall rates (409 vs. 401; p = 0.451), invasive angiography was less likely to demonstrate normal coronary arteries (20 vs. 56; hazard ratios [HRs]: 0.39 [95% confidence interval (CI): 0.23 to 0.68]; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) but more likely to show obstructive coronary artery disease (283 vs. 230; HR: 1.29 [95% CI: 1.08 to 1.55]; p = 0.005) in those allocated to CCTA. More preventive therapies (283 vs. 74; HR: 4.03 [95% CI: 3.12 to 5.20]; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) were initiated after CCTA, with each drug commencing at a median of 48 to 52 days after clinic attendance. From the median time for preventive therapy initiation (50 days), fatal and nonfatal myocardial infarction was halved in patients allocated to CCTA compared with those assigned to standard care (17 vs. 34; HR: 0.50 [95% CI: 0.28 to 0.88]; p = 0.020). Cumulative 6-month costs were slightly higher with CCTA: difference 462(95462 (95% CI: 462(95303 to $621). In patients with suspected angina due to coronary heart disease, CCTA leads to more appropriate use of invasive angiography and alterations in preventive therapies that were associated with a halving of fatal and non-fatal myocardial infarction. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590).

Research paper thumbnail of A role for the long non-coding RNA SENCR in commitment and function of endothelial cells

Molecular therapy : the journal of the American Society of Gene Therapy, Jan 22, 2016

Despite the increasing importance of long non-coding RNA in physiology and disease, their role in... more Despite the increasing importance of long non-coding RNA in physiology and disease, their role in endothelial biology remains poorly understood. Growing evidence has highlighted them to be essential regulators of human embryonic stem cell differentiation. SENCR, a vascular-enriched long non-coding RNA, overlaps the Friend Leukemia Integration virus 1 (FLI1) gene, a regulator of endothelial development. Therefore, we wanted to test the hypothesis that SENCR may contribute to mesodermal and endothelial commitment as well as in endothelial function. We thus developed new differentiation protocols allowing generation of endothelial cells from human embryonic stem cells using both directed and haemogenic routes. The expression of SENCR was markedly regulated during endothelial commitment using both protocols. SENCR did not control the pluripotency of pluripotent cells; however its overexpression significantly potentiated early mesodermal and endothelial commitment. In HUVEC, SENCR induce...

Research paper thumbnail of Abstract 9900: Air Pollution and Stroke: A Systematic Review and Meta-Analysis

Circulation, Nov 25, 2014

Research paper thumbnail of Chapter 11. Mechanism of Action of Combustion-derived Nanoparticles

Issues in Toxicology, 2015

Research paper thumbnail of Effect of engineered nanoparticles on platelet activation and thrombus formation in man

Research paper thumbnail of Vessel wall endothelial cells, but not circulating endothelial progenitor cells, have impaired function in premature coronary artery disease

Research paper thumbnail of Impaired vascular function and repair in patients with premature coronary artery disease

European journal of preventive cardiology, Jan 14, 2015

Endothelial dysfunction is central to the pathogenesis of coronary artery disease, but the role o... more Endothelial dysfunction is central to the pathogenesis of coronary artery disease, but the role of local and circulating endothelial progenitor cells in maintaining vascular health is poorly understood. We hypothesised that impaired local and circulating vascular repair mechanisms predispose to endothelial dysfunction and the premature onset of coronary artery disease. Patients with premature coronary artery disease (n = 16) and healthy age- and sex-matched controls (n = 16) underwent venous occlusion plethysmography with intra-arterial infusion of acetylcholine and sodium nitroprusside. Numbers of circulating endothelial progenitor cells were directly quantified in whole blood by flow cytometry. Endothelial cells were isolated from the blood vessel wall and from peripheral blood mononuclear cells, and expanded in vitro for phenotypic and functional characterisation and analysis of microRNA expression levels. A dose-dependent increase in forearm blood flow (p < 0.001) was attenua...

Research paper thumbnail of Short term exposure to air pollution and stroke: systematic review and meta-analysis

BMJ (Clinical research ed.), 2015

To review the evidence for the short term association between air pollution and stroke. Systemati... more To review the evidence for the short term association between air pollution and stroke. Systematic review and meta-analysis of observational studies Medline, Embase, Global Health, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science searched to January 2014 with no language restrictions. Studies investigating the short term associations (up to lag of seven days) between daily increases in gaseous pollutants (carbon monoxide, sulphur dioxide, nitrogen dioxide, ozone) and particulate matter (<2.5 µm or <10 µm diameter (PM2.5 and PM10)), and admission to hospital for stroke or mortality. Admission to hospital and mortality from stroke. From 2748 articles, 238 were reviewed in depth with 103 satisfying our inclusion criteria and 94 contributing to our meta-estimates. This provided a total of 6.2 million events across 28 countries. Admission to hospital for stroke or mortality from stroke was associated with an increase in concentrations of carbon ...

Research paper thumbnail of CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial

Lancet, Jan 13, 2015

The benefit of CT coronary angiography (CTCA) in patients presenting with stable chest pain has n... more The benefit of CT coronary angiography (CTCA) in patients presenting with stable chest pain has not been systematically studied. We aimed to assess the effect of CTCA on the diagnosis, management, and outcome of patients referred to the cardiology clinic with suspected angina due to coronary heart disease. In this prospective open-label, parallel-group, multicentre trial, we recruited patients aged 18-75 years referred for the assessment of suspected angina due to coronary heart disease from 12 cardiology chest pain clinics across Scotland. We randomly assigned (1:1) participants to standard care plus CTCA or standard care alone. Randomisation was done with a web-based service to ensure allocation concealment. The primary endpoint was certainty of the diagnosis of angina secondary to coronary heart disease at 6 weeks. All analyses were intention to treat, and patients were analysed in the group they were allocated to, irrespective of compliance with scanning. This study is registere...

Research paper thumbnail of Combustion-derived air pollution and cardiovascular disease

British journal of hospital medicine (London, England : 2005), 2012

Air pollution is a modifiable risk factor for cardiovascular disease that affects the entire popu... more Air pollution is a modifiable risk factor for cardiovascular disease that affects the entire population and is thus a major public health concern. It is important to understand how air pollution increases cardiovascular risk to develop strategies to protect susceptible individuals and reduce the effect of air pollution on cardiovascular health.

Research paper thumbnail of Effect of wood smoke exposure on vascular function and thrombus formation in healthy fire fighters

Particle and Fibre Toxicology, 2014

BackgroundMyocardial infarction is the leading cause of death in fire fighters and has been linke... more BackgroundMyocardial infarction is the leading cause of death in fire fighters and has been linked with exposure to air pollution and fire suppression duties. We therefore investigated the effects of wood smoke exposure on vascular vasomotor and fibrinolytic function, and thrombus formation in healthy fire fighters.MethodsIn a double-blind randomized cross-over study, 16 healthy male fire fighters were exposed to wood smoke (~1 mg/m3 particulate matter concentration) or filtered air for one hour during intermittent exercise. Arterial pressure and stiffness were measured before and immediately after exposure, and forearm blood flow was measured during intra-brachial infusion of endothelium-dependent and -independent vasodilators 4¿6 hours after exposure. Thrombus formation was assessed using the ex vivo Badimon chamber at 2 hours, and platelet activation was measured using flow cytometry for up to 24 hours after the exposure.ResultsCompared to filtered air, exposure to wood smoke increased blood carboxyhaemoglobin concentrations (1.3% versus 0.8%; P¿&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;¿0.001), but had no effect on arterial pressure, augmentation index or pulse wave velocity (P¿&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;¿0.05 for all). Whilst there was a dose-dependent increase in forearm blood flow with each vasodilator (P¿&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;¿0.01 for all), there were no differences in blood flow responses to acetylcholine, sodium nitroprusside or verapamil between exposures…

Research paper thumbnail of High-sensitivity troponin I concentrations are a marker of an advanced hypertrophic response and adverse outcomes in patients with aortic stenosis

European heart journal, Jan 7, 2014

High-sensitivity cardiac troponin I (cTnI) assays hold promise in detecting the transition from h... more High-sensitivity cardiac troponin I (cTnI) assays hold promise in detecting the transition from hypertrophy to heart failure in aortic stenosis. We sought to investigate the mechanism for troponin release in patients with aortic stenosis and whether plasma cTnI concentrations are associated with long-term outcome. Plasma cTnI concentrations were measured in two patient cohorts using a high-sensitivity assay. First, in the Mechanism Cohort, 122 patients with aortic stenosis (median age 71, 67% male, aortic valve area 1.0 ± 0.4 cm(2)) underwent cardiovascular magnetic resonance and echocardiography to assess left ventricular (LV) myocardial mass, function, and fibrosis. The indexed LV mass and measures of replacement fibrosis (late gadolinium enhancement) were associated with cTnI concentrations independent of age, sex, coronary artery disease, aortic stenosis severity, and diastolic function. In the separate Outcome Cohort, 131 patients originally recruited into the Scottish Aortic S...

Research paper thumbnail of High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study

BMJ (Clinical research ed.), 2015

To evaluate the diagnosis of myocardial infarction using a high sensitivity troponin I assay and ... more To evaluate the diagnosis of myocardial infarction using a high sensitivity troponin I assay and sex specific diagnostic thresholds in men and women with suspected acute coronary syndrome. Prospective cohort study. Regional cardiac centre, United Kingdom. Consecutive patients with suspected acute coronary syndrome (n=1126, 46% women). Two cardiologists independently adjudicated the diagnosis of myocardial infarction by using a high sensitivity troponin I assay with sex specific diagnostic thresholds (men 34 ng/L, women 16 ng/L) and compared with current practice where a contemporary assay (50 ng/L, single threshold) was used to guide care. Diagnosis of myocardial infarction. The high sensitivity troponin I assay noticeably increased the diagnosis of myocardial infarction in women (from 11% to 22%; P<0.001) but had a minimal effect in men (from 19% to 21%, P=0.002). Women were less likely than men to be referred to a cardiologist or undergo coronary revascularisation (P<0.05 fo...

Research paper thumbnail of Lyophilised reconstituted human platelets increase thrombus formation in a clinical ex vivo model of deep arterial injury

Thrombosis and Haemostasis, 2012

Platelets are the principal component of the innate haemostatic system that protect from traumati... more Platelets are the principal component of the innate haemostatic system that protect from traumatic bleeding. We investigated whether lyophilised human platelets (LHPs) could enhance clot formation within platelet-free and whole blood environments using an ex vivo model of deep arterial injury. Lyophilised human platelets were produced from stored human platelets and characterised using conventional, fluorescent and electron microscopic techniques. LHPs were resuspended in platelet-free plasma (PFP) obtained from citrated whole human blood to form final concentrations of 0, 20 and 200 x 10⁹ LHPs/L. LHPs with recalcified PFP or whole blood were perfused through the chamber at low (212 s⁻¹) and high (1,690 s⁻¹) shear rates with porcine aortic tunica media as thrombogenic substrate. LHPs shared morphological characteristics with native human platelets and were incorporated into clot generated from PFP or whole blood. Histomorphometrically measured mean thrombus area increased in a dose-dependent manner following the addition of LHPs to PFP under conditions of high shear [704 μm² ± 186 μm² (mean ± SEM), 1,511 μm² ± 320 μm² and 2,378 μm² ± 315 μm², for LHPs at 0, 20 and 200 x 10⁹ /l, respectively (p= 0.012)]. Lyophilised human platelets retain haemostatic properties when reconstituted in both PFP and whole blood, and enhance thrombus formation in a model of deep arterial injury. These data suggest that LHPs have the potential to serve as a therapeutic intervention during haemorrhage under circumstances of trauma, and platelet depletion or dysfunction.

Research paper thumbnail of Global association of air pollution and heart failure: a systematic review and meta-analysis

The Lancet, 2013

Background Acute exposure to air pollution has been linked to myocardial infarction, but its effe... more Background Acute exposure to air pollution has been linked to myocardial infarction, but its effect on heart failure is uncertain. We did a systematic review and meta-analysis to assess the association between air pollution and acute decompensated heart failure including hospitalisation and heart failure mortality.

Research paper thumbnail of Nanoparticle Enhanced Mri: A Novel Method of Investigating Myocardial Inflammation

Journal of the American College of Cardiology, 2013

Background: "Ultrasmall superparamagnetic particles of iron-oxide" (USPIOs; diameter <30 nm)) can... more Background: "Ultrasmall superparamagnetic particles of iron-oxide" (USPIOs; diameter <30 nm)) can be used as a novel contrast media with MRI. They are internalised by inlammatory cells. We sought out to assess whether USPIOs could be used to measure in vivo myocardial cellular inlammation.

Research paper thumbnail of High Sensitive Troponin Predicts Long–Term Prognosis in Patients with Aortic Stenosis

Journal of the American College of Cardiology, 2013

Background: Cardiac troponins are excellent prognostic markers in patients with stable coronary d... more Background: Cardiac troponins are excellent prognostic markers in patients with stable coronary disease and heart failure, but its role in aortic stenosis is unknown. We investigated whether baseline high sensitive troponin I (hsTnI) is associated with severity and outcome in patients with aortic stenosis.

Research paper thumbnail of Fire Simulation Exposure Causes Impairment of Endothelial Function and Increased Thrombogenicity in Healthy Firefighters

Journal of the American College of Cardiology, 2014

ABSTRACT The risk of acute myocardial infarction in firefighters is increased during fire suppres... more ABSTRACT The risk of acute myocardial infarction in firefighters is increased during fire suppression duties, and is likely to reflect a combination of factors including extreme physical exertion and heat exposure. We assess the effects of physical exertion and heat exposure on vascular function and thrombosis in firefighters.

Research paper thumbnail of Controlled Exposures to Air Pollutants and Risk of Cardiac Arrhythmia

Environmental Health Perspectives, 2014