Eduard Shantsila

University of Birmingham, Birmingham, England, United Kingdom

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Publications (131)653.87 Total impact

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    ABSTRACT: Increased combined free light chains (cFLC) are strongly prognostic of death in general populations and in patients with chronic kidney disease, but scarce data are available on cFLC in heart failure (HF). We aimed to assess the dynamics and prognostic significance of cFLC levels in patients following admission with acute heart failure (AHF). cFLC measurements were compared in 49 patients with AHF, 37 patients with stable HF, 43 patients with stable coronary artery disease and without HF (‘disease controls’), and 37 healthy controls. The association of cFLC with death and/or rehospitalisation was assessed. Patients with AHF had significantly elevated cFLC levels, compared to other groups (p<0.001). Patients with stable HF showed higher levels of cFLC than healthy controls. In AHF, cFLC levels correlated with cystatin C (Spearman r=0.63, p<0.001), and creatinine (Spearman r=0.47, p=0.002). During 3 months follow up brain natriuretic peptide (BNP) reduced significantly (p=0.017), but cFLC did not change significantly. In a multivariate Cox regression analysis, the higher quartiles of cFLC were significantly associated with death/readmission (hazard ratio (HR) 8.34 [95% CI 2.38-29.22] p=0.0009) after adjustment for age, gender, BNP and cystatin C levels. Higher quartiles of cFLC were prognostic for death alone (HR 14.0 [95% CI 1.72-113.8], p=0.014). In conclusion, raised serum cFLC concentrations in patients with AHF were independently associated with prognosis. In AHF, elevated cFLC levels persist long after clinical stabilisation, which may reflect immune disturbances and/or the reduced capacity of (perhaps functionally impaired) kidneys and the endothelium to eliminate them.
    The American Journal of Cardiology 10/2014; · 3.43 Impact Factor
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    ABSTRACT: Objectives Arterial and systolic elastance are important parameters determining effective functional interaction of heart and vessels. The aims of this study were to (i) compare arterial [arterial elastance index (EaI)] and ventricular [End-systolic elastance (Ees) and End-diastolic elastance (Eed)] elastance in subjects with obstructive sleep apnoea (OSA) and patients with treated ‘high-risk’ hypertension (HHT), and (ii) test whether these parameters in OSA patients can be improved by continuous positive airway pressure (CPAP) therapy. Methods Echocardiographic parameters of cardiac and vascular stiffness (EaI, Ees and Eed) were quantified in 28 patients with OSA (mean [SD] age 51 [11] years, 79% male) and 28 treated subjects with HHT (mean [SD] age 48 [12] years, 61% male). Twenty three OSA patients were treated with CPAP for median of 26 weeks. Ea was calculated from stroke volume and systolic BP and adjusted by body area (EaI). Both study groups had preserved and comparable left ventricle (LV) contractility. Results There was no significant differences in arterial elastance index (EaI, p=0.94), end-systolic elastance (Ees, p=0.5), end-diastolic elastance (Eed, p=0.63) and arterial-ventricular interaction (Ees/Ea, p=0.62) between OSA and HHT groups. After CPAP therapy, there was a significant reduction in arterial elastance index (EaI; paired t-test, p=0.013), and arterial-ventricular interaction (Ees/Ea; paired t-test, p=0.004). End-systolic elastance (Ees, p=0.17), end-diastolic elastance (Eed, p=0.66) parameters did not change significantly. Conclusions OSA patients and HHT patients have similar parameters of elastance and ventricular-arterial coupling. CPAP treatment in OSA patients significantly improved ventricular-arterial coupling.
    Journal of the American Society of Hypertension 09/2014; · 2.68 Impact Factor
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    ABSTRACT: "Lone" atrial fibrillation (AF) is generally used to refer to patients with AF in the absence of structural heart disease. When the decision for oral anticoagulation is discussed, "lone" AF refers to patients who do not have established stroke risk factors. Imaging is often used to rule out structural heart disease, e.g. coronary artery disease, peripheral vascular disease, mitral stenosis or left ventricular (LV) dysfunction. Imaging of the heart has a central role in establishing the "lone" aspect in patients with "lone"AF, similar to the measurement of blood glucose and blood pressure: Patients with structural heart disease, defined as e.g. reduced LV ejection fraction, clinical evidence for heart failure, or evidence for coronary artery disease, will not be considered as patients with "lone" AF. The search for these conditions requires some cardiac imaging, often done by echocardiography and non-invasive tests for coronary artery disease or ischemia. Increasingly, brain imaging is used to define the clinical diagnosis of a stroke, thus also contributing to the detection of stroke risk factors. Cerebral imaging in AF patients without competing causes for silent strokes or microbleeds ("lone" AF, rather used in the context of anticoagulation, i.e. clinical absence of structural heart disease) would allow to better understand the contribution of AF to these brain lesions. The assumption that silent strokes are likely drivers of cognitive dysfunction, and the fact that microbleeds put patients at risk for intracerebral hemorrhage, illustrates the need to collect information on brain imaging. In this review article, we summarize current data on heart and brain imaging in patients with "lone" AF and discuss their clinical implications for risk assessment and management of patients with "lone" AF.
    Current Pharmaceutical Design 08/2014; · 3.29 Impact Factor
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    ABSTRACT: Aim. To characterize blood monocyte subsets in patients with different degrees of carotid atherosclerosis and pathological carotid plaque neovascularization. Methods. Assessment of carotid plaque neovascularization using contrast ultrasonography and flow cytometric quantification of monocyte subsets and their receptors involved in inflammation, angiogenesis, and tissue repair was done in 40 patients with carotid stenosis ≥ 50% and CAD (CS > 50), 40 patients with carotid stenosis < 50% and documented CAD (CS < 50), 40 hypercholesterolaemic controls (HC group), and 40 normocholesterolaemic controls (NC). Results. CS > 50 and CS < 50 groups had increased counts of Mon1 ('classical' CD14++ CD16-CCR2 + cells) compared to HCs (P = 0.03, and P = 0.009). Mon3 ('non-classical' CD14 + CD16++ CCR2- cells) were only increased in CS < 50 compared with HCs (P < 0.01). Both CS>50 and CS < 50 groups showed increased expression of proinflammatory interleukin-6 receptor on Mon1 and Mon2 ('intermediate' CD14++ CD16 + CCR2+ cells); TLR4, proangiogenic Tie2 on all subsets (P < 0.01 for all). In multivariate regression analysis only high Mon1 count was a significant predictor of carotid stenosis (P = 0.04) and intima-media thickness (P = 0.02). In multivariate regression analysis only the Mon1 subset was significantly associated with severe, grade 2 neovascularization (P = 0.034). Conclusion. In this pilot study classical monocytes (Mon1) represent the only monocyte subset predictive of the severity of carotid and systemic atherosclerosis, such as carotid intima-media thickness, degree of carotid stenosis, and presence of carotid intraplaque neovascularization.
    Annals of Medicine 07/2014; · 4.73 Impact Factor
  • Gregory Yh Lip, Eduard Shantsila
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    ABSTRACT: Advances in pharmacological and devices therapy have greatly improved prognosis in patients with systolic heart failure. Despite this congestive heart failure still bears a very grim prognosis, particularly in patients with more advances stages of the disease that are so frequently seen on hospital wards. Which pathogenic pathways may need to be addressed to improve prognosis in heart failure? The current treatment of this condition is primarily focused on performance of the heart itself, and aims to inhibit unfavorable cardiac remodeling (e.g., amelioration of impact of activated catecholamine and renin-angiotensin-aldosterone systems), optimization of cardiac hemodynamics (e.g., cardiac resynchronization therapy) and prevention of life threatening arrhythmia (e.g., insertion of implantable defibrillators). However, accumulating evidence suggests that thrombotic complications may play a major role in morbidity and outcomes in heart failure patients, especially as the cardiac 'targets' (largely neurohuneral) are being better managed.
    Circulation 06/2014; · 14.95 Impact Factor
  • Angie Ghattas, Eduard Shantsila, Helen Griffiths, G Lip
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    ABSTRACT: Monocytes, with 3 different subsets, are implicated in the initiation and progression of the atherosclerotic plaque contributing to plaque instability and rupture. Mon1 are the "classical" monocytes with inflammatory action, whilst Mon3 are considered reparative with fibroblast deposition ability. The function of the newly described Mon2 subset is yet to be fully described. In PCI era, fewer patients have globally reduced left ventricular ejection fraction post infarction, hence the importance of studying regional wall motion abnormalities and deformation at segmental levels using longitudinal strain. Little is known of the role for the 3 monocyte subpopulations in determining global strain in ST elevation myocardial infarction patients (STEMI).
    Heart (British Cardiac Society) 06/2014; 100(Suppl 3):A19-A20. · 6.02 Impact Factor
  • Richard Brown, Eduard Shantsila, Chetan Varma, Gregory Lip
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    ABSTRACT: Studies have shown higher in-hospital mortality for female patients and ethnic minorities admitted to hospital with acute ST elevation myocardial infarction (STEMI). Pre-hospital delay is associated with increased in-hospital mortality. We assessed the impact of gender and ethnicity on symptom-to-door-time in patients presenting with STEMI.
    Heart (British Cardiac Society) 06/2014; 100(Suppl 3):A18. · 6.02 Impact Factor
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    ABSTRACT: Aims The multiple roles of monocytes in atherogenesis, including inflammation, angiogenesis and repair are attributed to the existence of different monocyte sub-populations. Scarce data are available on changes in phenotype and functional status of human monocyte subsets in patients with coronary artery disease (CAD), especially when monocytes are evaluated as three distinct subsets. Methods and results Surface expression of receptors implicated in inflammation, repair and activation status (intracellular IKKβ) of monocyte subsets was assessed by flow cytometry in 53 patients with CAD and compared to 50 age- and sex-matched healthy controls. Monocyte subsets were defined as CD14++CD16−CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2), and CD14+CD16++CCR2− (Mon3). Plasma levels of inflammatory cytokines (FACSArray) and fibrinolytic factors (ELISA) were measured in CAD. CAD was associated with reduced expression of CD14 on Mon1 (p = 0.02) and Mon3 (p = 0.036), higher expression of IL6 receptor on Mon1 (p = 0.025) and Mon2 (p = 0.015), CXCR4 on Mon1 (p = 0.035) and Mon3 (p = 0.003), and CD34 on all subsets (all p < 0.007). Monocyte CD163 expression correlated negatively with interleukin (IL)-6 levels (p < 0.01 for all subsets). Expression of vascular endothelial growth factor receptor-1 correlated positively with plasminogen activator inhibitor (PAI)-1 antigen levels (r = 0.47, p = 0.006). In vitro, monocyte subsets derived from CAD patients showed significantly altered responses to endotoxin stimulation compared to monocytes from healthy controls. Conclusions There is a complex interplay between phenotype and activity of monocytes and plasma cytokines and fibrinolytic factors. These findings support the presence of unique roles for the three human monocyte subsets in atherogenesis and CAD pathogenesis.
    Atherosclerosis 05/2014; 234(1):4–10. · 3.71 Impact Factor
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    ABSTRACT: This study aimed to examine the mechanisms of cellular activation by small-size platelet microparticles (sPMP) and to present the performance of high-resolution flow cytometry for the analysis of subcellular entities from different origins. Plasma counts of sPMP were analysed in coronary artery disease patients (n = 40) and healthy controls (n = 40). The effect of sPMP and platelet debris (PD) in pathophysiologically relevant doses on platelet and monocyte activation parameters and thrombogenesis was investigated via flow cytometry and thromboelastometry. New generation flow cytometry identifies differences in size, levels and surface molecules of sPMP derived in the absence of stimulus, thrombin activation and platelet disruption. Addition of sPMP resulted in platelet degranulation and P-selectin redistribution to the membrane (P = 0·019) in a dose and time-dependent manner. Blood clotting time decreased after addition of sPMP (P = 0·005), but was not affected by PD. Blocking P-selectin (CD62P) in sPMP markedly reverted the effect on thrombus kinetics (P = 0·035). Exposure to sPMP stimulated monocyte expression of intercellular adhesion molecule-1 (P < 0·03) and decreased monocyte interleukin-6 receptor density (P < 0·01). These results implicate sPMP as a direct source of downstream platelet and monocyte activation. In pathological coronary artery disease conditions, higher levels of sPMP favour a prothrombotic state, partly through P-selectin expression.
    British Journal of Haematology 04/2014; · 4.94 Impact Factor
  • Gregory Yh Lip, Eduard Shantsila
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    ABSTRACT: Patients with chronic heart failure (heart failure) are at risk of thromboembolic events, including stroke, pulmonary embolism and peripheral arterial embolism, whilst coronary ischaemic events also contribute to the progression of heart failure. Long-term oral anticoagulation is established in certain patient groups, including patients with heart failure and atrial fibrillation, but there is wide variation in the indications and use of oral anticoagulation in the broader heart failure population. To determine whether long-term oral anticoagulation reduces total deaths, cardiovascular deaths and major thromboembolic events in patients with heart failure. We updated the searches in June 2030 in the electronic databases CENTRAL (Issue 6, 2013) in The Cochrane Library, MEDLINE (OVID, 1946 to June week 1 2013) and EMBASE (OVID, 1980 to 2013 week 23). Reference lists of papers and abstracts from national and international cardiovascular meetings were studied to identify unpublished studies. Relevant authors were contacted to obtain further data. No language restrictions were applied. Randomised controlled trials (RCTs) comparing oral anticoagulants with placebo in adults with heart failure, and with treatment duration at least one month. Non-randomised studies were also included for assessing side effects. Inclusion decisions were made in duplicate and any disagreement between review authors was resolved by discussion or a third party. Two review authors independently assessed trials for inclusion and assessed the risks and benefits of antithrombotic therapy using relative measures of effects, such as odds ratio, accompanied by the 95% confidence intervals. Two RCTs were identified. One compared warfarin, aspirin and no antithrombotic therapy and the second compared warfarin with placebo in patients with idiopathic dilated cardiomyopathy. Three small prospective controlled studies of warfarin in heart failure were also identified, but they were over 50 years old with methods not considered reliable by modern standards. In both WASH 2004 and HELAS 2006, there were no significant differences in the incidence of myocardial infarction, non-fatal stroke and death between patients taking oral anticoagulation and those taking placebo. Four retrospective non-randomised cohort analyses and four observational studies of oral anticoagulation in heart failure included differing populations of heart failure patients and reported contradictory results. Based on the two major randomised trials (HELAS 2006; WASH 2004), there is no convincing evidence that oral anticoagulant therapy modifies mortality or vascular events in patients with heart failure and sinus rhythm. Although oral anticoagulation is indicated in certain groups of patients with heart failure (for example those with atrial fibrillation), the available data does not support the routine use of anticoagulation in heart failure patients who remain in sinus rhythm.
    Cochrane database of systematic reviews (Online) 03/2014; 3:CD003336. · 5.94 Impact Factor
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    ABSTRACT: Circulating blood microparticles are likely to play a significant role as messengers of biological information. Their accurate quantification and characterisation is challenging and needs to be carefully designed with preferable usage of fresh minimally-processed blood samples. Utilisation of flow cytometers specifically designed for analysis of small-size particles is likely to provide considerable methodological advantages and should be the preferable option. This viewpoint manuscript provides a critical summary of the key methodological aspects of microparticle analysis.
    Thrombosis and Haemostasis 02/2014; 111(6). · 5.76 Impact Factor
  • Eduard Shantsila, Gregory Y H Lip
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    ABSTRACT: Pathophysiologically, there is a prothrombotic state evident in heart failure (HF). This is particularly evident within atria in patients whose course of the disease is complicated by concomitant atrial fibrillation (AF). A predisposition for thrombogenesis exists in patients with dilated dysfunctional cardiac chambers, such as those seen in patients with large myocardial infarction, left ventricular (LV) aneurysm or dilated cardiomyopathy. Based on subgroup analyses of recent phase 3 randomized trials, the novel oral anticoagulants are equally effective and safe in AF patients with HF or without HF. This appears to be true regarding both HF with systolic LV dysfunction and with preserved LVEF. However, patients with HF with preserved LVEF with more strict definition (ie, LVEF ≥ 55 %) have not been analyzed specifically. There is no information from clinical trial regarding possible utility of the novel oral anticoagulants in HF patients in sinus rhythm. Further research is required to cover gaps in knowledge on utility of these medications in a substantial proportion of HF patients not included in major clinical trials on novel oral anticoagulants.
    Current Treatment Options in Cardiovascular Medicine 02/2014; 16(2):285.
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    ABSTRACT: New vessel formation inside the arterial wall and atherosclerotic plaques plays a critical role in pathogenesis of heart attacks and strokes. The two known mechanisms resulting in the formation of new vessels within the plaque are: (1) local ischaemia, and (2) inflammation. Blood monocytes play important role in both processes. Firstly, they express receptors for vascular endothelial growth factor (VEGF) and some of them may serve as circulating ancestors of endothelial cells. Secondly, monocytes are associated with inflammation by synthesis of inflammatory molecules following their activation (e.g., after stimulation of Toll-like receptors).Neovascularisation is a reparative response to ischemia, and includes three processes; angiogenesis, arterogenesis, and vasculogenesis. Angiogenesis, the formation of new capillary vessels is known to occur in response to a hypoxic environment. The interaction between leukocytes and vascular wall via over-expression of various molecules facilitates the migration of inflammatory cells into the plaque microenvironment. Monocytes are intimately involved in tissue damage and repair and an imbalance of these processes may have detrimental consequences for plaque development and stability. Importantly, monocytes are comprised of distinct subsets with different cell surface markers and functional characteristics and this heterogeneity may be relevant to angiogenic processes in atherosclerosis. The aim of this review article is to present an overview of the available evidence supporting a role for monocytes in angiogenesis and atherosclerosis.
    Journal of the American College of Cardiology 10/2013; · 15.34 Impact Factor
  • Eduard Shantsila, Gregory Y H Lip
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    ABSTRACT: Heart failure and atrial fibrillation are major problems of modern cardiology with important clinical, prognostic, and socioeconomic implications. The risks are high morbidity, impaired quality of life, poor outcome, and increased risk of stroke. Oral anticoagulation with vitamin K antagonists or novel licensed medicines should be considered unless contraindicated. Possible benefits of sinus rhythm maintenance are not entirely clear and need to be explored further. Relatively scarce data are available on stroke prevention in atrial fibrillation in heart failure with preserved ejection fraction; this requires further research.
    Heart Failure Clinics 10/2013; 9(4):427-35. · 1.41 Impact Factor
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    ABSTRACT: Introduction: Animal studies show that von Willebrand factor (vWF) deficiency is associated with lower risks for atherosclerosis and atherothrombosis, including events such as acute myocardial infarction and ischemic stroke. vWF enables the binding of platelets along the damaged vessels leading to thrombogenesis. Interruption of this early stage of thrombus formation may prevent downstream amplification of the inflammatory and thrombotic processes that contribute to the plaque instability. Areas covered: Increased levels of vWF have been related to the atherothrombotic complications and endothelial damage. Therefore, vWF has been suggested as a useful biomarker of endothelial damage/dysfunction. Preliminary data from Phase II trials in patients with acute myocardial infarction and thrombotic disorders have been promising, but many unanswered questions remain regarding the optimal therapeutic use of vWF blockade. This article describes the molecular structure of vWF, its functions and its interactions with the platelet membrane glycoprotein (GP) receptors GPIb and GPIIb-IIIa, as well as collagen. In addition, the article provides an overview of most promising investigational compounds tested as antithrombotic agents targeting vWF. Methods: Preclinical and clinical data for vWF blockage are discussed. Expert opinion: The therapeutic approaches aiming to block the collagen-vWF-platelet axis have potentially beneficial effects for prevention and treatment of cardiovascular disease. However, the evidence directly associating vWF blockage with beneficial clinical outcomes is limited and needs further research. Optimal treatment regimes need to be established in relation of specific clinical circumstances and conditions.
    Expert Opinion on Therapeutic Targets 09/2013; 18(1). · 4.90 Impact Factor
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    ABSTRACT: Three functionally distinct monocyte subsets have been identified. Statins are of undoubted effect in atherosclerosis and have numerous pleiotropic effects that contribute to their clinical success, but the effect of these drugs on monocyte subsets is unclear. We hypothesised a beneficial effect of statins on key receptor expression by monocyte subsets. Effects of temporal (2 weeks) cessation of statin therapy by 66 patients with stable coronary artery disease on monocyte subsets [CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2) and CD14+CD16++CCR2- (Mon3)], their aggregates with platelets and their expression of a number of receptors involved in inflammation (IL-6 receptor), adhesion [vascular cell adhesion molecule (VCAM)], angiogenesis [vascular endothelial growth factor (VEGF)] and repair were assessed by flow cytometry. Statin cessation did not lead to any significant changes in absolute numbers of monocyte subsets or the degree of their aggregation with platelets. All monocyte subsets showed significant downregulation of expression of vascular endothelial factor receptor 2, Tie2 and Toll-like receptor-4 (TLR4; all changes P < 0·01). Expression of CXCR4 was only reduced in Mon1 cells (P = 0·013). There was no significant change in the expression of CD14, CD16, CCR4, IL6 receptor and VCAM (all P = NS). Statin withdrawal does not affect counts of any of monocyte subsets, but leads to downregulation of expression of TLR4 and receptors related to angiogenesis on all subsets, as well as a decrease in density of CXCR4 expression on 'classical' Mon1. These data provide further support of pleiotropic effects of statins and their effects on monocyte pro-angiogenic and proreparative characteristics.
    European Journal of Clinical Investigation 09/2013; · 3.37 Impact Factor
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    ABSTRACT: Despite improvements in interventional and pharmacological therapy of atherosclerotic disease, it is still the leading cause of death in the developed world. Hence there is a need for further development of effective therapeutic approaches. This requires better understanding of the molecular mechanisms and pathophysiology of the disease. Atherosclerosis has long been identified as having an inflammatory component contributing to its pathogenesis, whilst the available therapy primarily targets hyperlipidemia and prevention of thrombosis. Acknowledging a pleotropic anti-inflammatory effect to some therapies, such as acetyl salicylic acid and the statins, none of the currently approved medicines for management of either stable or complicated atherosclerosis has inflammation as a primary target. Monocytes, as representatives of the innate immune system, play a major role in the initiation, propagation and progression of atherosclerosis from a stable to an unstable state. Experimental data supports a role of monocytes in acute coronary syndromes and in outcome post infarction; however, limited research has been done in humans. Analysis of expression of various cell surface receptors allows characterization of the different monocyte subsets phenotypically, whilst downstream assessment of inflammatory pathways provides an insight in their activity. In this review we discuss the functional role of monocytes and their different subpopulations in atherosclerosis, acute coronary syndromes, cardiac healing and recovery with an aim of critical evaluation of potential future therapeutic targets in atherosclerosis and its complications. We will also discuss technical difficulties of delineating different monocyte subpopulations, understanding their differentiation potential and function.
    Journal of the American College of Cardiology 08/2013; · 15.34 Impact Factor
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    ABSTRACT: Abstract We aimed to provide evidence that blood monocytes belonging to all subsets predominantly circulate in constant and usually reversible interactions with platelets, which are predominantly [Ca2+] dependent. The proportions of monocyte-platelet aggregates (MPAs) attributable to individual monocyte subsets in fresh and promptly processed heparin-anticoagulated blood from 10 healthy subjects (median age 35 years, 50% male) were analysed by flow cytometry and compared to samples anticoagulated with a potent [Ca2+] chelator, ethylenediaminetetraacetic acid (EDTA). Additional experiments with [Ca2+] depletion or supplementation were also performed. Monocytes subsets were defined as CD14++CD16-CCR2+ cells (Mon1), CD14++CD16+CCR2+ cells (Mon2) and CD14+CD16++CCR2- cells (Mon3). Vast majority of monocytes showed aggregation with platelets in heparinised samples, but most monocytes were free of platelets when EDTA was used (p < 0.001 for all subsets). Addition of the heparinised blood to EDTA-containing vacutainers reduced the proportion of MPAs to values seen in the directly EDTA-anticoagulated blood (p = 0.005 for all subsets). Supplementation with CaCl2 resulted in dose-dependent increase in MPAs (p < 0.001 for all subsets). Although the overall trend for the monocyte-platelet interactions was applicable to all monocyte subsets, the proportion of MPAs in heparinised samples was lowest for Mon3 (p < 0.0001). In contrast, Mon3 showed the highest proportion of MPAs in EDTA-anticoagulated samples (p = 0.004). In healthy subjects monocytes circulate in constant, but predominantly reversible and [Ca2+]-dependent aggregation with platelets. These observations may reflect a complex involvement of platelets in regulation of monocyte activity.
    Platelets 07/2013; · 2.63 Impact Factor
  • Stavros Apostolakis, Gregory Yh Lip, Eduard Shantsila
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    ABSTRACT: Introduction: Strategies to prevent stroke recurrences and stroke-related morbidity and mortality are a major concern for healthcare systems worldwide. Antithrombotic therapy is the cornerstone for the secondary prevention of ischemic stroke. Areas covered: This article is an overview of currently used antithrombotic therapies in the management of ischaemic stroke with special focus on their pharmacokinetic properties and how these properties may influence their clinical utility. This review covers both antiplatelet drugs and antitcoagulants used in the primary and secondary prevention of ischaemic stroke. Expert opinion: The role of aspirin in the early management of stroke is well established. Furthermore, antiplatelet drugs (aspirin, aspirin/dypiridamol and clopidogrel) are the cornerstone of secondary prevention of ischaemic stroke, while their role in the primary prevention is less well established. There are limited data on the use of novel antiplatelet agents for the management of stroke patients. Anticoagulation has not been associated with clinical benefits when used early in the management of acute ischaemic stroke. Long-term therapy with vitamin K antagonists provides prognostic benefit in patients with atrial fibrillation and additional stroke risk factors. New oral anticoagulants have demonstrated at least similar efficacy with vitamin K anatagonists in preventing stroke in patients with atrial fibrillation.
    Expert Opinion on Drug Metabolism &amp Toxicology 06/2013; · 2.94 Impact Factor
  • B J Wrigley, E Shantsila, L D Tapp, G Y H Lip
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    ABSTRACT: The objective of this study was to evaluate the expression of cell adhesion molecule (CAM) receptors (integrins) on monocyte subsets in heart failure (HF) and examine their prognostic implication.Increased levels of soluble CAMs have been observed in patients with HF, but the precise mechanism of monocyte adhesion to the vascular endothelium remains unknown. Patients with acute HF (AHF, n=51) were compared to those with stable HF (SHF, n=42) and stable coronary artery disease (CAD, n=44) without HF. Expression of integrins-receptors to intercellular adhesion molecule-1 (ICAM-1R) and vascular CAM-1 (VCAM-1R) on monocyte subsets was assessed by flow cytometry. Monocyte subsets were defined as CD14++CD16-CCR2+ ('classical', Mon1), CD14++CD16+CCR2+ ('intermediate', Mon2), and CD14+CD16++CCR2- ('non-classical', Mon3). Compared to patients with SHF, those with AHF had significantly higher expression of ICAM-1R on Mon2 (p=0.01). Compared to those with stable CAD, patients with SHF had a significantly higher expression of ICAM-1R on Mon2 (p=0.025).Compared to SHF, patients with AHF had a similar expression of VCAM-1R on both Mon1 and Mon3 but significantly higher expression on Mon2 (p=0.019). There were no significant differences between SHF and CAD in monocyte expression of VCAM-1R. In multivariate Cox regression analysis, VCAM-1R expression on Mon2 was associated with adverse clinical outcome (death or rehospitalisation) in AHF [HR 1.07 (1.01-1.14), p=0.029]. In conclusion, HF is associated with increased monocyte expression of integrins-receptors to both ICAM-1 and VCAM-1, being particularly linked to Mon2 subset. Expression of VCAM-1R on Mon2 may have prognostic value in patients with AHF.
    Thrombosis and Haemostasis 06/2013; 110(1). · 5.76 Impact Factor

Publication Stats

1k Citations
653.87 Total Impact Points


  • 2008–2014
    • University of Birmingham
      Birmingham, England, United Kingdom
  • 2013
    • Aston University
      • School of Life and Health Sciences
      Birmingham, England, United Kingdom
  • 2006–2013
    • University Hospitals Birmingham NHS Foundation Trust
      • Department of Medicine
      Birmingham, ENG, United Kingdom
  • 2012
    • Sandwell and West Birmingham Hospitals NHS Trust
      Birmingham, England, United Kingdom
  • 2006–2012
    • Birmingham City University
      Birmingham, England, United Kingdom
  • 2009
    • University Hospitals Coventry and Warwickshire NHS Trust
      • Department of Cardiology
      Coventry, England, United Kingdom
    • Republican Science-Practical Center Cardiology
      Myenyesk, Minsk, Belarus
    • WWF United Kingdom
      Londinium, England, United Kingdom