Publications by authors named "Christopher J Boos"

68 Publications

Marching to the Beet: The effect of dietary nitrate supplementation on high altitude exercise performance and adaptation during a military trekking expedition.

Nitric Oxide 2021 Sep 27;113-114:70-77. Epub 2021 May 27.

Carneige School of Sport, Leeds Beckett University, Leeds, LS16 5LF, UK.

Purpose: The aim was to investigate the effect of dietary nitrate supplementation (in the form of beetroot juice, BRJ) for 20 days on salivary nitrite (a potential precursor of bioactive nitric oxide), exercise performance and high altitude (HA) acclimatisation in field conditions (hypobaric hypoxia).

Methods: This was a single-blinded randomised control study of 22 healthy adult participants (12 men, 10 women, mean age 28 ± 12 years) across a HA military expedition. Participants were randomised pre-ascent to receive two 70 ml dose per day of either BRJ (~12.5 mmol nitrate per day; n = 11) or non-nitrate calorie matched control (n = 11). Participants ingested supplement doses daily, beginning 3 days prior to departure and continued until the highest sleeping altitude (4800 m) reached on day 17 of the expedition. Data were collected at baseline (44 m altitude), at 2350 m (day 9), 3400 m (day 12) and 4800 m (day 17).

Results: BRJ enhanced the salivary levels of nitrite (p = 0.007). There was a significant decrease in peripheral oxygen saturation and there were increases in heart rate, diastolic blood pressure, and rating of perceived exertion with increasing altitude (p=<0.001). Harvard Step Test fitness scores significantly declined at 4800 m in the control group (p = 0.003) compared with baseline. In contrast, there was no decline in fitness scores at 4800 m compared with baseline (p = 0.26) in the BRJ group. Heart rate recovery speed following exercise at 4800 m was significantly prolonged in the control group (p=<0.01) but was unchanged in the BRJ group (p = 0.61). BRJ did not affect the burden of HA illness (p = 1.00).

Conclusions: BRJ increases salivary nitrite levels and ameliorates the decline in fitness at altitude but does not affect the occurrence of HA illness.
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http://dx.doi.org/10.1016/j.niox.2021.05.002DOI Listing
September 2021

The Relationship Between Ambulatory Arterial Stiffness Index and Cardiovascular Outcomes in Women.

Cardiol Res 2021 Jun 14;12(3):161-168. Epub 2021 May 14.

Department of Cardiology, Poole Hospital NHS Foundation Trust, Longfleet Rd., Poole, Dorset, BH15 2JB, UK.

Background: The ambulatory arterial stiffness index (AASI) obtained during ambulatory blood pressure monitoring (ABPM) has been cited as an independent predictor of major adverse cardiovascular events (MACEs) including cardiovascular death, stroke and worsening chronic kidney disease (CKD) among mixed-sex adult populations. This study aimed to determine the relationship between AASI and MACE and its predictive precision in women.

Methods: This work follows the guidelines of the STROBE initiative for cohort studies. This was a retrospective single-center observational study of adult women (aged 18 - 75 years), who underwent 24-h ABPM for the diagnosis of hypertension or its control. The primary endpoint was a composite MACE of cardiovascular death, acute limb ischemia, stroke, acute coronary syndrome (ACS), or progression to stage V CKD.

Results: A total of 219 women aged 57.4 ± 13.3 years were followed up for a median (interquartile range (IQR)) of 25.5 (18.3 - 31.3) months. Overall, 16 (7.3%) patients suffered one or more MACE events. AASI was significantly higher in patients with known coronary artery disease (CAD), diabetes mellitus, peripheral vascular disease (PVD), heart failure, previous stroke, or transient ischemic attack (TIA). AASI was a significant predictor of MACE (area under the curve: 0.78; P < 0.001) with an optimal cut-off of ≥ 0.56. On Kaplan-Meier analysis AASI ≥ 0.56 was significantly associated with MACE (log-rank test, P < 0.001). The only independent predictors of MACE on Cox proportional hazard analysis were diabetes mellitus, low high-density lipoprotein (HDL) levels, cumulative AASI values, or AASI ≥ 0.56.

Conclusions: An AASI of ≥ 0.56 is an independent predictor of MACE in women. A further validation study in a larger cohort of women is recommended.
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http://dx.doi.org/10.14740/cr1189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139754PMC
June 2021

The relationship between ambulatory arterial stiffness, inflammation, blood pressure dipping and cardiovascular outcomes.

BMC Cardiovasc Disord 2021 Mar 16;21(1):139. Epub 2021 Mar 16.

Department of Cardiology, University Hospital Dorset NHS Foundation Trust, Longfleet Rd., Poole, BH15 2JB, UK.

Background: The ambulatory arterial stiffness index (AASI) is an indirect measure of arterial stiffness obtained during ambulatory blood pressuring monitoring (ABPM). Its relationship to nocturnal blood pressure dipping status and major adverse cardiovascular events (MACE) are controversial and its association with vascular inflammation has not been examined. We aimed to investigate the relationship between the AASI, inflammation and nocturnal blood pressure dipping status and its association with MACE.

Methods: Adults (aged 18-80 years) who underwent 24-h ABPM for the diagnosis of hypertension or its control were included. The inflammatory markers measured were the neutrophil-lymphocyte (NLR), platelet-lymphocyte (PLR) and monocyte-lymphocyte ratios (MLR). The primary MACE was a composite of cardiovascular death, acute limb ischaemia, stroke or transient ischaemic attack (TIA) or acute coronary syndrome.

Results: A total of 508 patients (51.2% female) aged 58.8 ± 14.0 years were included; 237 (46.7%) were normal-dippers (≥ 10% nocturnal systolic dip), 214 (42.1%) were non-dippers (0-10% dip) and 57 (11.2%) were reverse-dippers (< 0% dip). The AASI was significantly higher among reverse (0.56 ± 0.16) and non-dippers (0.48 ± 0.17) compared with normal dippers (0.39 ± 0.16; p < 0.0001) and correlated with the NLR (r = 0.20; 95% CI 0.11 to 0.29: < 0.0001) and systolic blood pressure dipping % (r = - 0.34; - 0.42 to - 0.26: p < 0.0001). Overall 39 (7.7%) patients had ≥ 1 MACE which included a total of seven cardiovascular deaths and 14 non-fatal strokes/TIAs. The mean follow up was 113.7 ± 64.0 weeks. Increasing NLR, but not AASI or systolic dipping, was independently linked to MACE (overall model Chi-square 60.67; p < 0.0001) and MLR to cardiovascular death or non-fatal stroke/TIA (overall model Chi-square 37.08; p < 0.0001).

Conclusions: In conclusion AASI was associated with blood pressure dipping and chronic inflammation but not independently to MACE. The MLR and NLR were independent predictors of MACE.
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http://dx.doi.org/10.1186/s12872-021-01946-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968202PMC
March 2021

Study protocol for a prospective, longitudinal cohort study investigating the medical and psychosocial outcomes of UK combat casualties from the Afghanistan war: the ADVANCE Study.

BMJ Open 2020 10 30;10(10):e037850. Epub 2020 Oct 30.

Occupational and Environmental Medicine, National Heart and Lung Institute, Imperial College, London, UK.

Introduction: The Afghanistan war (2003-2014) was a unique period in military medicine. Many service personnel survived injuries of a severity that would have been fatal at any other time in history; the long-term health outcomes of such injuries are unknown. The rme Serices Truma and Rehabilitatio Outom (ADVANCE) study aims to determine the long-term effects on both medical and psychosocial health of servicemen surviving this severe combat related trauma.

Methods And Analysis: ADVANCE is a prospective cohort study. 1200 Afghanistan-deployed male UK military personnel and veterans will be recruited and will be studied at 0, 3, 6, 10, 15 and 20 years. Half are personnel who sustained combat trauma; a comparison group of the same size has been frequency matched based on deployment to Afghanistan, age, sex, service, rank and role. Participants undergo a series of physical health tests and questionnaires through which information is collected on cardiovascular disease (CVD), CVD risk factors, musculoskeletal disease, mental health, functional and social outcomes, quality of life, employment and mortality.

Ethics And Dissemination: The ADVANCE Study has approval from the Ministry of Defence Research Ethics Committee (protocol no:357/PPE/12) agreed 15 January 2013. Its results will be disseminated through manuscripts in clinical/academic journals and presentations at professional conferences, and through participant and stakeholder communications.

Trial Registration Number: The ADVANCE Study is registered at ISRCTN ID: ISRCTN57285353.
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http://dx.doi.org/10.1136/bmjopen-2020-037850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604820PMC
October 2020

Carbohydrate Supplementation and the Influence of Breakfast on Fuel Use in Hypoxia.

Med Sci Sports Exerc 2021 04;53(4):785-795

Carnegie School of Sport, Leeds Beckett University, Leeds, UNITED KINGDOM.

Purpose: This study investigated the effect of carbohydrate supplementation on substrate oxidation during exercise in hypoxia after preexercise breakfast consumption and omission.

Methods: Eleven men walked in normobaric hypoxia (FiO2 ~11.7%) for 90 min at 50% of hypoxic V˙O2max. Participants were supplemented with a carbohydrate beverage (1.2 g·min-1 glucose) and a placebo beverage (both enriched with U-13C6 D-glucose) after breakfast consumption and after omission. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate carbohydrate (exogenous and endogenous [muscle and liver]) and fat oxidation.

Results: In the first 60 min of exercise, there was no significant change in relative substrate oxidation in the carbohydrate compared with placebo trial after breakfast consumption or omission (both P = 0.99). In the last 30 min of exercise, increased relative carbohydrate oxidation occurred in the carbohydrate compared with placebo trial after breakfast omission (44.0 ± 8.8 vs 28.0 ± 12.3, P < 0.01) but not consumption (51.7 ± 12.3 vs 44.2 ± 10.4, P = 0.38). In the same period, a reduction in relative liver (but not muscle) glucose oxidation was observed in the carbohydrate compared with placebo trials after breakfast consumption (liver, 7.7% ± 1.6% vs 14.8% ± 2.3%, P < 0.01; muscle, 25.4% ± 9.4% vs 29.4% ± 11.1%, P = 0.99) and omission (liver, 3.8% ± 0.8% vs 8.7% ± 2.8%, P < 0.01; muscle, 19.4% ± 7.5% vs 19.2% ± 12.2%, P = 0.99). No significant difference in relative exogenous carbohydrate oxidation was observed between breakfast consumption and omission trials (P = 0.14).

Conclusion: In acute normobaric hypoxia, carbohydrate supplementation increased relative carbohydrate oxidation during exercise (>60 min) after breakfast omission, but not consumption.
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http://dx.doi.org/10.1249/MSS.0000000000002536DOI Listing
April 2021

The Relationship between Military Combat and Cardiovascular Risk: A Systematic Review and Meta-Analysis.

Int J Vasc Med 2019 22;2019:9849465. Epub 2019 Dec 22.

Academic Department of Military Rehabilitation, Defence Medical Rehabilitation Centre, Near Loughborough, Stanford Hall Estate, Nottinghamshire LE12 5QW, UK.

Background And Objectives: Cardiovascular disease (CVD) is a leading cause of death among military veterans with several reports suggesting a link between combat and related traumatic injury (TI) to an increased CVD risk. The aim of this paper is to conduct a widespread systematic review and meta-analysis of the relationship between military combat ± TI to CVD and its associated risk factors.

Methods: PubMed, EmbaseProQuest, Cinahl databases and Cochrane Reviews were examined for all published observational studies (any language) reporting on CVD risk and outcomes, following military combat exposure ± TI versus a comparative nonexposed control population. Two investigators independently extracted data. Data quality was rated and rated using the 20-item AXIS Critical Appraisal Tool. The risk of bias (ROB using the ROBANS 6 item tool) and strength of evidence (SOE) were also critically appraised.

Results: From 4499 citations, 26 studies (14 cross sectional and 12 cohort; 78-100% male) met the inclusion criteria. The follow up period ranged from 1 to 43.6 years with a sample size ranging from 19 to 621901 participants in the combat group. Combat-related TI was associated with a significantly increased risk for CVD (RR 1.80: 95% CI 1.24-2.62; = 59%, = 0.002) and coronary heart disease (CHD)-related death (risk ratio 1.57: 95% CI 1.35-1.83; = 0%, = 0.77: < 0.0001), although the SOE was low. Military combat (without TI) was linked to a marginal, yet significantly lower pooled risk (low SOE) of cardiovascular death in the active combat versus control population (RR 0.90: CI 0.83-0.98; = 47%, = 0.02). There was insufficient evidence linking combat ± TI to any other cardiovascular outcomes or risk factors.

Conclusion: There is low SOE to support a link between combat-related TI and both cardiovascular and CHD-related mortality. There is insufficient evidence to support a positive association between military combat ± any other adverse cardiovascular outcomes or risk factors. Data from well conducted prospective cohort studies following combat are needed.
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http://dx.doi.org/10.1155/2019/9849465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942813PMC
December 2019

The association between PTSD and cardiovascular disease and its risk factors in male veterans of the Iraq/Afghanistan conflicts: a systematic review.

Int Rev Psychiatry 2019 02 1;31(1):34-48. Epub 2019 May 1.

a King's Centre for Military Health Research, Psychological Medicine , King's College London , London , UK.

Military personnel with Post-Traumatic Stress Disorder (PTSD) can experience high levels of mental and physical health comorbidity, potentially indicating a high level of functional impairment that can impact on both military readiness and later ill-health. There is strong evidence to implicate PTSD as a contributory factor to Cardiovascular Disease (CVD) among serving personnel and veterans. This systematic review focusses on the association between PTSD and cardiovascular disease/risk factors in male, military serving and ex-serving personnel who served in the Iraq/Afghanistan conflicts. PUBMED, MEDLINE, PILOTS, EMBASE, PSYCINFO, and PSYCARTICLES were searched using PRISMA guidelines. Three hundred and forty-three records were identified, of which 20 articles were selected. PTSD was positively associated with the development of CVD, specifically circulatory diseases, including hypertension. PTSD was also positively associated with the following risk factors: elevated heart rate, tobacco use, dyslipidaemia, and obesity. Conflicting data is presented regarding heart rate variability and inflammatory markers. Future studies would benefit from a standardized methodological approach to investigating PTSD and physical health manifestations. It is suggested that clinicians offer health advice for CVD at an earlier age for ex-/serving personnel with PTSD.
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http://dx.doi.org/10.1080/09540261.2019.1580686DOI Listing
February 2019

Recovery time and heart rate variability following extreme endurance exercise in healthy women.

Physiol Rep 2018 Nov;6(21):e13905

Defence Medical Services, Lichfield, United Kingdom.

The relationship between autonomic function and recovery following prolonged arduous exercise in women has not been examined. We undertook an exploratory study that aimed to examine the temporal change in linear and nonlinear measures of heart rate variability (HRV) following prolonged arduous exercise in the form of first all-female (mean age 32.7 ± 3.1 years) team to attempt an unassisted Antarctic traverse. HRV analysis was performed before and 1, 4, and 15 days postexpedition. The traverse was completed in 61 days. There was a significant paired reduction in heart rate, LnLF, LF:HF, DFAα1 between baseline and 15 days postexercise in the same environment. Conversely, RMSSD, LnHF and HFnu, SD1:SD2, and SampEn significantly increased. DFAα2 levels significantly fell from baseline to Day 1 postexercise. In conclusion, we observed a significant latent increase in relative parasympathetic dominance and RR interval irregularity at 15 days post prolonged arduous exercise, versus pre-exercise baseline, in a group of very fit and healthy adult women.
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http://dx.doi.org/10.14814/phy2.13905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209688PMC
November 2018

The relationship between anxiety and acute mountain sickness.

PLoS One 2018 21;13(6):e0197147. Epub 2018 Jun 21.

Research Institute, for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, United Kingdom.

Introduction: Whilst the link between physical factors and risk of high altitude (HA)-related illness and acute mountain sickness (AMS) have been extensively explored, the influence of psychological factors has been less well examined. In this study we aimed to investigate the relationship between 'anxiety and AMS risk during a progressive ascent to very HA.

Methods: Eighty health adults were assessed at baseline (848m) and over 9 consecutive altitudes during a progressive trek to 5140m. HA-related symptoms (Lake Louise [LLS] and AMS-C Scores) and state anxiety (State-Trait-Anxiety-Score [STAI Y-1]) were examined at each altitude with trait anxiety (STAI Y-2) at baseline.

Results: The average age was 32.1 ± 8.3 years (67.5% men). STAI Y-1 scores fell from 848m to 3619m, before increasing to above baseline scores (848m) at ≥4072m (p = 0.01). STAI Y-1 scores correlated with LLS (r = 0.31; 0.24-0.3; P<0.0001) and AMS-C Scores (r = 0.29; 0.22-0.35; P<0.0001). There was significant main effect for sex (higher STAI Y-1 scores in women) and altitude with no sex-x-altitude interaction on STAI Y-1 Scores. Independent predictors of significant state anxiety included female sex, lower age, higher heart rate and increasing LLS and AMS-C scores (p<0.0001). A total of 38/80 subjects (47.5%) developed AMS which was mild in 20 (25%) and severe in 18 (22.5%). Baseline STAI Y-2 scores were an independent predictor of future severe AMS (B = 1.13; 1.009-1.28; p = 0.04; r2 = 0.23) and STAI Y-1 scores at HA independently predicted AMS and its severity.

Conclusion: Trait anxiety at low altitude was an independent predictor of future severe AMS development at HA. State anxiety at HA was independently associated with AMS and its severity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197147PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013200PMC
November 2018

High Altitude Affects Nocturnal Non-linear Heart Rate Variability: PATCH-HA Study.

Front Physiol 2018 16;9:390. Epub 2018 Apr 16.

The Defence Medical Services, Lichfield, United Kingdom.

High altitude (HA) exposure can lead to changes in resting heart rate variability (HRV), which may be linked to acute mountain sickness (AMS) development. Compared with traditional HRV measures, non-linear HRV appears to offer incremental and prognostic data, yet its utility and relationship to AMS have been barely examined at HA. This study sought to examine this relationship at terrestrial HA. Sixteen healthy British military servicemen were studied at baseline (800 m, first night) and over eight consecutive nights, at a sleeping altitude of up to 3600 m. A disposable cardiac patch monitor was used, to record the nocturnal cardiac inter-beat interval data, over 1 h (0200-0300 h), for offline HRV assessment. Non-linear HRV measures included Sample entropy (SampEn), the short (α1, 4-12 beats) and long-term (α2, 13-64 beats) detrend fluctuation analysis slope and the correlation dimension (D2). The maximal rating of perceived exertion (RPE), during daily exercise, was assessed using the Borg 6-20 RPE scale. All subjects completed the HA exposure. The average age of included subjects was 31.4 ± 8.1 years. HA led to a significant fall in SpO and increase in heart rate, LLS and RPE. There were no significant changes in the ECG-derived respiratory rate or in any of the time domain measures of HRV during sleep. The only notable changes in frequency domain measures of HRV were an increase in LF and fall in HFnu power at the highest altitude. Conversely, SampEn, SD1/SD2 and D2 all fell, whereas α1 and α2 increased ( < 0.05). RPE inversely correlated with SD1/SD2 ( = -0.31; = 0.002), SampEn ( = -0.22; = 0.03), HFnu ( = -0.27; = 0.007) and positively correlated with LF ( = 0.24; = 0.02), LF/HF ( = 0.24; = 0.02), α1 ( = 0.32; = 0.002) and α2 ( = 0.21; = 0.04). AMS occurred in 7/16 subjects (43.8%) and was very mild in 85.7% of cases. HRV failed to predict AMS. Non-linear HRV is more sensitive to the effects of HA than time and frequency domain indices. HA leads to a compensatory decrease in nocturnal HRV and complexity, which is influenced by the RPE measured at the end of the previous day. HRV failed to predict AMS development.
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http://dx.doi.org/10.3389/fphys.2018.00390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911497PMC
April 2018

Changes in balance and joint position sense during a 12-day high altitude trek: The British Services Dhaulagiri medical research expedition.

PLoS One 2018 17;13(1):e0190919. Epub 2018 Jan 17.

Institute for Sport, Physical Activity & Leisure, Leeds Beckett University, Leeds, United Kingdom.

Postural control and joint position sense are essential for safely undertaking leisure and professional activities, particularly at high altitude. We tested whether exposure to a 12-day trek with a gradual ascent to high altitude impairs postural control and joint position sense. This was a repeated measures observational study of 12 military service personnel (28±4 years). Postural control (sway velocity measured by a portable force platform) during standing balance, a Sharpened Romberg Test and knee joint position sense were measured, in England (113m elevation) and at 3 research camps (3619m, 4600m and 5140m) on a 12-day high altitude trek in the Dhaulagiri region of Nepal. Pulse oximetry, and Lake Louise scores were also recorded on the morning and evening of each trek day. Data were compared between altitudes and relationships between pulse oximetry, Lake Louise score, and sway velocity were explored. Total sway velocity during standing balance with eyes open (p = 0.003, d = 1.9) and during Sharpened Romberg test with eyes open (p = 0.007, d = 1.6) was significantly greater at altitudes of 3619m and 5140m when compared with sea level. Anterior-posterior sway velocity during standing balance with eyes open was also significantly greater at altitudes of 3619m and 5140m when compared with sea level (p = 0.001, d = 1.9). Knee joint position sense was not altered at higher altitudes. There were no significant correlations between Lake Louise scores, pulse oximetry and postural sway. Despite a gradual ascent profile, exposure to 3619 m was associated with impairments in postural control without impairment in knee joint position sense. Importantly, these impairments did not worsen at higher altitudes of 4600 m or 5140 m. The present findings should be considered during future trekking expeditions when developing training strategies targeted to manage impairments in postural control that occur with increasing altitude.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0190919PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771604PMC
February 2018

Myocardial blood flow reserve is impaired in patients with aortic valve calcification and unobstructed epicardial coronary arteries.

Int J Cardiol 2017 Dec 15;248:427-432. Epub 2017 Jun 15.

Department of Cardiology, Sunshine Coast Hospital and Health Services, University of the Sunshine Coast and University of Queensland, Queensland, Australia. Electronic address:

Background: Although calcific aortic valve disease (CAVD) is associated with coronary atherosclerosis, it is not known whether early CAVD is associated with coronary microcirculatory dysfunction (CMD). We sought to investigate the relationship between myocardial blood flow reserve (MBFR) - a measure of CMD, and early CAVD in the absence of obstructive epicardial coronary artery disease. We also determined whether this relationship was independent of coronary artery disease (CAD) and hs-CRP, a marker of systemic inflammation.

Methods: 183 patients with chest pain and unobstructed coronary arteries were studied. Aortic valve calcification score (AVCS), coronary total plaque length (TPL), and coronary calcium score were quantified from multislice CT. MBFR was assessed using vasodilator myocardial contrast echocardiography. Hs-CRP was measured from venous blood using a particle-enhanced immunoassay.

Results: Mean (±SD) participant age was 59.8 (9.6) years. Mean AVCS was 68 (258) AU, TPL was 15.6 (22.2) mm, and median coronary calcification score was 43.5AU. Mean MBFR was 2.20 (0.52). Mean hs-CRP was 2.52 (3.86) mg/l. Multivariable linear regression modelling incorporating demographics, coronary plaque characteristics, MBFR, and inflammatory markers, demonstrated that age (β=0.05, 95% CI: 0.02, 0.08, P=0.007), hs-CRP (β=0.09, CI: 0.02, 0.16, P=0.010) and diabetes (β=1.03, CI: 0.08, 1.98, P=0.033), were positively associated with AVCS. MBFR (β=-0.87, CI: -1.44, -0.30, P=0.003), BMI (β=-0.11, CI: -0.21, -0.01, P=0.033), and LDL (β=-0.32, CI: -0.61, -0.03, P=0.029) were negatively associated with AVCS. TPL and coronary calcium score were not independently associated with AVCS when included in the regression model.

Conclusion: Coronary microvascular function as determined by measurement of myocardial blood flow reserve is independently associated with early CAVD. This effect is independent of the presence of coronary artery disease and also systemic inflammation.
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http://dx.doi.org/10.1016/j.ijcard.2017.06.023DOI Listing
December 2017

Smartphone-Enabled Heart Rate Variability and Acute Mountain Sickness.

Clin J Sport Med 2018 Jan;28(1):76-81

Research Institute for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, United Kingdom.

Introduction: The autonomic system and sympathetic activation appears integral in the pathogenesis of acute mountain sickness (AMS) at high altitude (HA), yet a link between heart rate variability (HRV) and AMS has not been convincingly shown. In this study we investigated the utility of the smartphone-derived HRV score to predict and diagnose AMS at HA.

Methods: Twenty-one healthy adults were investigated at baseline at 1400 m and over 10 days during a trek to 5140 m. HRV was recorded using the ithlete HRV device.

Results: Acute mountain sickness occurred in 11 subjects (52.4%) at >2650 m. HRV inversely correlated with AMS Scores (r = -0.26; 95% CI, -0.38 to -0.13: P < 0.001). HRV significantly fell at 3700, 4100, and 5140 m versus low altitude. HRV scores were lower in those with both mild (69.7 ± 14.0) and severe AMS (67.1 ± 13.1) versus those without AMS (77.5 ± 13.1; effect size n = 0.043: P = 0.007). The HRV score was weakly predictive of severe AMS (AUC 0.74; 95% CI, 0.58-0.89: P = 0.006). The change (delta) in the HRV Score (compared with baseline at 1400 m) was a moderate diagnostic marker of severe AMS (AUC 0.80; 95% CI, 0.70-0.90; P = 0.0004). A fall in the HRV score of >5 had a sensitivity of 83% and specificity of 60% to identify severe AMS (likelihood ratio 1.9). Baseline HRV at 1400 m was not predictive of either AMS at higher altitudes.

Conclusions: The ithlete HRV score can be used to help in the identification of severe AMS; however, a baseline score is not predictive of future AMS development at HA.
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http://dx.doi.org/10.1097/JSM.0000000000000427DOI Listing
January 2018

Atrial fibrillation and heart failure: Factors influencing the choice of oral anticoagulant.

Int J Cardiol 2017 Jan 30;227:863-868. Epub 2016 Sep 30.

Department of Cardiology, Poole Hospital NHS Foundation Trust, Poole, UK; Dept of Postgraduate Medical Education, Bournemouth University, UK.

Atrial fibrillation (AF) and heart failure (HF) frequently coexist. AF is identified in approximately one third of patients with HF and is linked to increased morbidity and mortality than from either condition alone. AF is relatively more common in HF with preserved ejection fraction (HFpEF) than with reduced ejection fraction (HFrEF). Nevertheless, the risk of stroke and systemic embolism (SSE) is significantly increased with both HF types and the absolute risk is heavily influenced by the presence and severity of associated additional stroke risk factors. The European Society of Cardiology has very recently introduced a third HF subtype entitled HF with mid-range ejection fraction (HFmrEF). At present oral anticoagulation is recommended for all patients with AF and HF, independent of HF type. In addition to warfarin there are currently four non-vitamin K oral anticoagulants (NOACs, previously called novel oral anticoagulants) that have been approved for the prevention of SSE. They consist of one direct thrombin inhibitor, dabigatran and three factor Xa inhibitors: rivaroxaban, apixaban and, most recently, edoxaban. In this review article we present an overview of the evidence to support the use of NOACs for the prevention of SSE in patients with AF and HF and review the influence of HF subtype and co-morbidities on the potential choice of oral anticoagulant.
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http://dx.doi.org/10.1016/j.ijcard.2016.09.086DOI Listing
January 2017

Anticoagulation in atrial fibrillation and chronic heart failure: the risk and drug of choice.

Curr Opin Cardiol 2016 Mar;31(2):229-34

aDepartment of Cardiology, Poole Hospital NHS Foundation Trust, Poole bDepartment of Postgraduate Medical Education, Bournemouth University, Bournemouth, UK.

Purpose Of Review: This review seeks to provide an evidence-based update on the issue of atrial fibrillation and chronic heart failure with an emphasis on anticoagulation and the expanding use of the novel oral anticoagulants (NOACs).

Recent Findings: There is an increasing appreciation of the important reciprocal relationship between atrial fibrillation and heart failure and the negative prognostic impact that each condition has on the other. There are now four NOACs approved for stroke prevention in atrial fibrillation. There are increasing data to support their use in atrial fibrillation with heart failure, including in patients with nonmechanical or rheumatic valvular disease, and to facilitate direct current cardioversion. The choice of NOAC is heavily dependent on individual patient characteristics.

Summary: The use of and indications for NOACs for patients with heart failure and atrial fibrillation are rapidly increasing.
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http://dx.doi.org/10.1097/HCO.0000000000000245DOI Listing
March 2016

Atrial fibrillation (chronic).

BMJ Clin Evid 2015 May 20;2015. Epub 2015 May 20.

University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK.

Introduction: Atrial fibrillation is a supraventricular tachyarrhythmia characterised by the presence of fast and uncoordinated atrial activation leading to reduced atrial mechanical function. Risk factors for atrial fibrillation include increasing age, male sex, co-existing cardiac and thyroid disease, pyrexial illness, electrolyte imbalance, cancer, and co-existing infection.

Methods And Outcomes: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of oral medical treatments to control heart rate in people with chronic (defined as longer than 1 week for this review) non-valvular atrial fibrillation? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results: We found four studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions: In this systematic review we present information relating to the effectiveness and safety of the following interventions: beta-blockers (rate-limiting, with or without digoxin), calcium-channel blockers (with or without digoxin), and digoxin.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439734PMC
May 2015

Novel oral anticoagulants and stroke prevention in atrial fibrillation and chronic heart failure.

Heart Fail Rev 2014 May 25;19(3):391-401. Epub 2013 Jun 25.

Heart failure (HF) and atrial fibrillation (AF) frequently coexist and share a reciprocal relationship. The presence of AF increases the propensity to HF and can worsen its severity as well as escalating the risk of stroke. Despite the proven efficacy of vitamin K antagonists and warfarin for stroke prevention in AF, their use is beset by numerous problems. These include their slow onset and offset of action, unpredictability of response, the need for frequent coagulant monitoring and serious concerns around the increased risks of intracranial and major bleeding. Three recently approved novel anticoagulants (dabigatran, rivaroxaban and apixaban) are already challenging warfarin use in AF. They have a predictable therapeutic response and a wide therapeutic range and do not necessitate coagulation monitoring. In this article, the relationship between HF and AF and the mechanisms for their compounded stroke risk are reviewed. The evidence to support the use of these three NOACs amongst patients with AF and HF is further explored.
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http://dx.doi.org/10.1007/s10741-013-9398-3DOI Listing
May 2014

The effects of prolonged acute hypobaric hypoxia on novel measures of biventricular performance.

Echocardiography 2013 May 11;30(5):534-41. Epub 2013 Jan 11.

Department of Cardiology, Poole Hospital NHS Foundation Trust, Dorset, United Kingdom.

Background: There are limited data on the effects of prolonged acute hypoxia on individual and global measures of biventricular function.

Aims: The aim of this study was to assess its effects on conventional and novel measures of biventricular function, including the recently defined E'/(A'×S') (EAS) index, obtained using pulsed-wave tissue Doppler Imaging (PWTDI) and associated blood brain natriuretic peptide (BNP) levels.

Methods: In this study, 14 healthy subjects aged 30.5 years were assessed at baseline and at >150 minutes following hypobaric hypoxia (HH) to the equivalent altitude of 4800 m for a total of 180 minutes. The combined EAS index (E'/(A' × S')) was calculated at the mitral and tricuspid annulus using data from the peak systolic (S') early (E') and late (A') diastolic filling.

Results: It was seen that HH increased resting heart rate (63.4 ± 8.4 vs. 85.2 ± 10.2/min; P < 0.0001), cardiac output (4.6 ± 0.7 L/min vs. 6.1 ± 1.2 L/min; P < 0.0001), peak pulmonary artery systolic pressure (PASP) (26.3 ± 2.0 mmHg vs. 37.2 ± 6.3 mmHg; P < 0.0001), and reduced SpO2 (98.5 ± 1.1 vs. 72.9 ± 8.1%; P < 0.0001). There was a significant reduction in mitral (0.19 ± 0.06 vs. 0.11 ± 0.03; P < 0.0001) and tricuspid (0.12 ± 0.04 vs. 0.09 ± 0.03; P = 0.03) EAS indices, but no change in left or right ventricular myocardial performance (Tei) indices, global left ventricular (LV) longitudinal systolic strain, BNP levels, or estimated filling pressures (E/E'). Only reducing SpO2 remained as an independent predictor of PASP on multivariate analysis (overall R(2) = 0.77; P < 0.0001). The right and LV EAS indices were significantly correlated (r = 0.45; 95% CI: 0.07-0.7; P = 0.02).

Conclusion: The conclusion from this study was that acute prolonged HH does not adversely affect resting global biventricular function and there is evidence of linked right and LV responses.
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http://dx.doi.org/10.1111/echo.12088DOI Listing
May 2013

Electrocardiographic abnormalities in medically screened military aircrew.

Aviat Space Environ Med 2012 Nov;83(11):1055-9

Centre of Postgraduate Medical Research & Education, Bournemouth University, Bournemouth, UK.

Background: The European Society of Cardiology (ESC) recently published its updated recommendations for electrocardiogram (ECG) interpretation in athletes. It distinguishes ECG changes related to physical training (group 1 abnormalities) from training-unrelated changes (group 2) which may represent underlying electrical and structural heart disorders implicated in exercise related sudden cardiac death. This study sought to prospectively apply the ESC screening criteria to a large cohort of screened military aircrew.

Methods: This was a prospective observational study. The 12-lead ECGs of 868 consecutively evaluated healthy aircrew were analyzed for the presence of ESC-defined group 1 and 2 abnormalities.

Results: The average age was 39.6 (11.2) yr (95.4% male). Overall, 402 (46.3%) of ECGs could be classified as entirely normal. However, 466 ECGs (53.7%) were abnormal. Group 1 abnormalities were identified in 400 (46.1%) persons with 66 (7.6%) persons classified as having group 2 abnormalities. The most commonly identified group 1 ECG changes were sinus bradycardia (32.5%), early repolarization (11.8%), and isolated voltage criteria of left ventricular hypertrophy (10.1%). The most commonly noted group 2 abnormalities were left-axis deviation/left anterior hemiblock (2.4%), T-wave inversion (1.6%), and ST-segment depression (1.3%). Prolongation of the QTC > 0.46 s was observed in 0.69% of ECGs.

Conclusions: The vast majority of ECGs performed in military aircrew could be classified as representing likely normal physiological changes. Training unrelated ECG changes, suggestive of possible genuine cardiac pathology, were observed in only a minority of persons who should be considered for further investigation.
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http://dx.doi.org/10.3357/asem.3276.2012DOI Listing
November 2012

Atrial fibrillation (chronic).

BMJ Clin Evid 2011 Nov 10;2011. Epub 2011 Nov 10.

University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK.

Introduction: Atrial fibrillation is a supraventricular tachyarrhythmia characterised by the presence of fast and uncoordinated atrial activation leading to reduced atrial mechanical function. Risk factors for atrial fibrillation include increasing age, male sex, co-existing cardiac and thyroid disease, pyrexial illness, electrolyte imbalance, cancer, and co-existing infection.

Methods And Outcomes: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of oral medical treatments to control heart rate in people with chronic (defined as longer than 1 week for this review) non-valvular atrial fibrillation? What is the effect of different treatment strategies (rate versus rhythm) for people with persistent non-valvular atrial fibrillation? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results: We found 23 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions: In this systematic review we present information relating to the effectiveness and safety of the following interventions: beta-blockers (with or without digoxin), calcium channel blockers (with or without digoxin), calcium channel blockers (rate-limiting), digoxin, and rate versus rhythm control strategies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262479PMC
November 2011

Management of amiodarone-related thyroid problems.

Ther Adv Endocrinol Metab 2011 Jun;2(3):115-26

Department of Endocrinology, Poole Hospital NHS Foundation Trust, Poole, UK.

Amiodarone is a highly effective and well-established antiarrrhythmic drug. It can be used to treat supraventricular and ventricular tachyarrhythmias and has the added advantage of being well tolerated in patients with impaired left ventricular systolic function with a low incidence of arrhythmic events, such as torsades de pointes. However, owing to its marked lipid affinity, it is highly concentrated in tissues and is linked to a number of adverse effects, including thyroid dysfunction. Amiodarone can lead to both hypothyroidism (amiodarone-induced hypothyroidism) and less commonly hyperthyroidism (amiodarone-induced thyrotoxicosis) and relates to high iodine content within the molecule as well as to several unique intrinsic properties of amiodarone. Dronedarone is a recently approved antiarrhythmic drug. It is structurally very similar to amiodarone, however the iodine moiety, present with amiodarone has been removed and replaced with a methylsulfonamide group to reduce fat solubility and adverse effects. We present an overview of the effects of amiodarone on thyroid function and the treatment options available, as well as a brief insight into dronedarone and its potential as an alternative to amiodarone.
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http://dx.doi.org/10.1177/2042018811398516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3474631PMC
June 2011

Plasma haemoxygenase-1 in coronary artery disease. A comparison with angiogenin, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 and vascular endothelial growth factor.

Thromb Haemost 2010 Nov 13;104(5):1029-37. Epub 2010 Sep 13.

Haemostasis, Thrombosis and Vascular Biology Unit, University of Birmingham Centre of Cardiovascular Sciences, City Hospital, Birmingham, UK.

It was the aim of this study to determine plasma haemoxygenase-1 (HO-1) across the spectrum of health, angina but normal coronary arteries (NCA), stable coronary artery disease (CAD), and acute coronary syndromes (ACS), and relationships with angiogenin, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1, and vascular endothelial growth factor. Plasma markers were measured (ELISA) in peripheral venous citrated plasma from 50 healthy subjects, 30 with NCA, 70 with stable CAD and 24 with an ACS, and from patient's aortic root, coronary ostium, coronary sinus and femoral artery. Human umbilical vein endothelial cells (HUVECs) were cultured with or without tumour necrosis factor (TNF), and platelets were probed. HO-1 was raised in stable CAD (p<0.05) and increased further in ACS (p<0.01) compared to healthy controls and NCA. HO-1 correlated only with MMP-9, and then only in the healthy controls. There were no major differences from cardiac or peripheral sites. HO-1 was present in HUVECs and 24-hour HUVEC supernatants but release was abolished by TNF. Platelets had no HO-1. In conclusion, HO-1 is raised in stable CAD and ACS and may arise from the endothelium but not the platelet. This may have implications for our understanding of the pathophysiology of CAD and its acute presentation as ACS.
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http://dx.doi.org/10.1160/TH09-11-0802DOI Listing
November 2010

A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2.

Ophthalmology 2010 Jun 22;117(6):1078-1086.e2. Epub 2010 Apr 22.

Department of Medical Retina, Moorfields Eye Hospital, London, United Kingdom.

Purpose: To report the findings at 1 year of a study comparing repeated intravitreal bevacizumab (ivB) and modified Early Treatment of Diabetic Retinopathy Study (ETDRS) macular laser therapy (MLT) in patients with persistent clinically significant diabetic macular edema (CSME).

Design: Prospective, randomized, masked, single-center, 2-year, 2-arm clinical trial.

Participants: A total of 80 eyes of 80 patients with center-involving CSME and at least 1 prior MLT.

Methods: Subjects were randomized to either ivB (6 weekly; minimum of 3 injections and maximum of 9 injections in the first 12 months) or MLT (4 monthly; minimum of 1 treatment and maximum of 4 treatments in the first 12 months).

Main Outcome Measures: The primary end point was the difference in ETDRS best-corrected visual acuity (BCVA) at 12 months between the bevacizumab and laser arms.

Results: The baseline mean ETDRS BCVA was 55.7+/-9.7 (range 34-69) in the bevacizumab group and 54.6+/-8.6 (range 36-68) in the laser arm. The mean ETDRS BCVA at 12 months was 61.3+/-10.4 (range 34-79) in the bevacizumab group and 50.0+/-16.6 (range 8-76) in the laser arm (P = 0.0006). Furthermore, the bevacizumab group gained a median of 8 ETDRS letters, whereas the laser group lost a median of 0.5 ETDRS letters (P = 0.0002). The odds of gaining > or =10 ETDRS letters over 12 months were 5.1 times greater in the bevacizumab group than in the laser group (adjusted odds ratio, 5.1; 95% confidence interval, 1.3-19.7; P = 0.019). At 12 months, central macular thickness decreased from 507+/-145 microm (range 281-900 microm) at baseline to 378+/-134 microm (range 167-699 microm) (P<0.001) in the ivB group, whereas it decreased to a lesser extent in the laser group, from 481+/-121 microm (range 279-844 microm) to 413+/-135 microm (range 170-708 microm) (P = 0.02). The median number of injections was 9 (interquartile range [IQR] 8-9) in the ivB group, and the median number of laser treatments was 3 (IQR 2-4) in the MLT group.

Conclusions: The study provides evidence to support the use of bevacizumab in patients with center-involving CSME without advanced macular ischemia.
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http://dx.doi.org/10.1016/j.ophtha.2010.03.045DOI Listing
June 2010

A technique to overcome high defibrillation thresholds for an implantable cardioverter defibrillator.

Cardiol Young 2009 Jun 19;19(3):291. Epub 2009 Feb 19.

Department of Cardiology, University Hospital, Metchley Road, Edgbaston, Birmingham, United Kingdom.

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http://dx.doi.org/10.1017/S1047951109003618DOI Listing
June 2009

Assessment of endothelial damage/dysfunction: a focus on circulating endothelial cells.

Methods Mol Med 2007 ;139:211-24

Haemostasis Thrombosis &Vascular Biology Unit, University Department of Medicine, City Hospital, England, UK.

Endothelial injury represents a major initiating step in the pathogenesis of vascular disease and atherosclerosis. The identification and quantification of circulating endothelial cells (CECs) has evolved as a novel marker of endothelial function. As a technique, it correlates with other markers of endothelial function such as flow-mediated dilation, the measurement of von Willebrand factor, and tissue plasminogen activator. Quantification of CECs is difficult due to low numbers, variable morphology, and a lack of standardization in current techniques used. CECs appear to be a different population of cells to endothelial progenitor cells. Increased CECs have been noted in a number of disease states and is evolving as a novel method of assessment of both disease severity and response to treatment.
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http://dx.doi.org/10.1007/978-1-59745-571-8_13DOI Listing
October 2008

Atrial fibrillation (chronic).

BMJ Clin Evid 2008 Apr 30;2008. Epub 2008 Apr 30.

Department of Cardiology, University Hospital, Birmingham, UK.

Introduction: Atrial fibrillation is a supraventricular tachyarrhythmia, which is characterised by the presence of fast and uncoordinated atrial activation leading to reduced atrial mechanical function. Risk factors for atrial fibrillation include increasing age, coexisting cardiac and thyroid disease, pyrexial illness, electrolyte imbalance, cancer, and coexisting infection.

Methods And Outcomes: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of oral medical treatments to control heart rate in people with chronic (defined as longer than 1 week for this review) non-valvular atrial fibrillation? What is the effect of different treatment strategies (rate vs. rhythm) for people with persistent non-valvular atrial fibrillation? We searched: Medline, Embase, The Cochrane Library and other important databases up to August 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results: We found 18 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions: In this systematic review we present information relating to the effectiveness and safety of the following interventions: beta-blockers (with or without digoxin), calcium channel blockers (with or without digoxin), calcium channel blockers (rate limiting), digoxin, and rate versus rhythm control strategies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907948PMC
April 2008

Effects of percutaneous coronary intervention on peripheral venous blood circulating endothelial cells and plasma indices of endothelial damage/dysfunction.

Chest 2007 Dec;132(6):1920-6

Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, UK.

Background: The relationship between endothelial damage/dysfunction and coronary artery disease is well recognized. However, the effects of percutaneous coronary intervention (PCI) [stenting/angioplasty] on circulating markers of endothelial damage/dysfunction (eg, von Willebrand factor [vWF], soluble E-selectin [sEsel] levels, and more recently circulating endothelial cells [CECs]) has been less well defined.

Aims And Methods: We investigated the effects of both diagnostic coronary angiography (CA) [n = 15; blood sampling immediately before CA and 15 min after CA] and PCI (n = 38; blood sampling before PCI, 15 min after PCI, and 24 h after PCI) on levels of CECs, vWF, and sEsel across comparable patient groups. We also included a cohort of comparable healthy control subjects in order to compare baseline levels of three endothelial markers.

Results: There were no differences in baseline levels of CECs, vWF, or sEsel between the three study groups (healthy control subjects, CA, PCI; all p = not significant). Following CA (before to 15 min after), there were no significant changes in vWF and CECs (p = not significant). Following PCI, there were significant increases observed at 15 min after PCI and at 24 h after PCI (when compared with pre-PCI levels) in CECs (p = 0.0006), vWF (p = 0.007), and sEsel (p = 0.024).

Conclusion: We observed significant increases in three endothelial markers (CECs, vWF, and sEsel) with elective PCI but not CA. This is in keeping with endothelial damage/dysfunction following PCI.
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http://dx.doi.org/10.1378/chest.07-1693DOI Listing
December 2007
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