54 results on '"Townend, Jonathan N"'
Search Results
2. Risk for subsequent hypertension and cardiovascular disease after living kidney donation: is it clinically relevant?
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Ferro, Charles J and Townend, Jonathan N
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CARDIOVASCULAR diseases , *CHRONIC kidney failure , *LIFE expectancy , *KIDNEYS ,CARDIOVASCULAR disease related mortality - Abstract
The first successful live donor kidney transplant was performed in 1954. Receiving a kidney transplant from a live kidney donor remains the best option for increasing both life expectancy and quality of life in patients with end-stage kidney disease. However, ever since 1954, there have been multiple questions raised on the ethics of live kidney donation in terms of negative impacts on donor life expectancy. Given the close relationship between reduced kidney function in patients with chronic kidney disease (CKD) and hypertension, cardiovascular disease and cardiovascular mortality, information on the impact of kidney donation on these is particularly relevant. In this article, we review the existing evidence, focusing on the more recent studies on the impact of kidney donation on all-cause mortality, cardiovascular mortality, cardiovascular disease and hypertension, as well as markers of cardiovascular damage including arterial stiffness and uraemic cardiomyopathy. We also discuss the similarities and differences between the pathological reduction in renal function that occurs in CKD, and the reduction in renal function that occurs because of a donor nephrectomy. Kidney donors perform an altruistic act that benefits individual patients as well as the wider society. They deserve to have high-quality evidence on which to make informed decisions. [ABSTRACT FROM AUTHOR]
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- 2022
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3. Heart disease and stroke statistics 2023 update from the American Heart Association—implications for nephrology.
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Edwards, Nicola C, Ferro, Charles J, and Townend, Jonathan N
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HEART diseases , *STROKE , *DISEASE risk factors , *CARDIOVASCULAR diseases risk factors , *CHRONIC kidney failure , *STATISTICS - Abstract
The annual American Heart Association (AHA) and National Institutes of Health statistical report details the most up to date statistics related to heart disease, stroke and cardiovascular risk factors, primarily within the USA. Although not a formal systematic review or meta-analysis, this 600 page report provides the most comprehensive and best summary of cardiovascular statistics for the year in question. Although data are collated from USA data registries, it serves as a critical resource for clinicians, policymakers, administrators and researchers in the northern and southern hemispheres. In this special report, we have chosen to highlight aspects of the document that are relevant to nephrologists, given the overlap of cardiovascular and renal disease. These include (i) key and emerging cardiovascular data signals in the general and chronic kidney disease (CKD) populations, (ii) ethnic and socio-economic disparity, (iii) environmental and behavioural factors that drive high levels of cardiovascular disease and which are key components of the AHA's eight components of the Life Essential cardiovascular health score, and (iv) the impact of COVID-19 both directly and indirectly on heart health. We provide some commentary and critical analysis of both the data and of the production of such data sets suggesting that similar data on CKD could also be published and linked to the AHA and other datasets. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Evaluating the effects of sevelamer carbonate on cardiovascular structure and function in chronic renal impairment in Birmingham: the CRIB-PHOS randomised controlled trial.
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Chue, Colin D., Townend, Jonathan N., Steeds, Richard P., and Ferro, Charles J.
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SERUM , *ECHOCARDIOGRAPHY , *MAGNETIC resonance imaging , *TONOMETRY ,CARDIOVASCULAR disease related mortality - Abstract
Background: Serum phosphate is an independent predictor of cardiovascular morbidity and mortality in patients with chronic kidney disease and the general population. There is accumulating evidence that phosphate promotes arterial stiffening through structural vascular alterations such as medial calcification, which are already apparent in the early stages of chronic kidney disease. Aim: To determine the effects of phosphate binding with sevelamer carbonate on left ventricular mass and function together with arterial stiffness in patients with stage 3 chronic kidney disease. Methods/Design: A single-centre, prospective, randomised, double-blind, placebo-controlled trial of 120 subjects with stage 3 chronic kidney disease recruited from University Hospitals Birmingham NHS Foundation Trust. Baseline investigations include transthoracic echocardiography and cardiac magnetic resonance imaging to assess ventricular mass, volumes and function, applanation tonometry to determine pulse wave velocity and pulse wave analysis as surrogate measures of arterial stiffness and dual energy x-ray absorptiometry scanning to determine bone density. During an open-label run in phase, subjects will receive 1600 mg sevelamer carbonate with meals for four weeks. They will then be randomised to either continue sevelamer carbonate or receive an identical placebo (60 subjects per arm) for the remaining 36 weeks. Four-weekly monitoring of serum electrolytes and bone biochemistry will be performed. All baseline investigations will be repeated at the end of the treatment period. The primary endpoint of the study is a reduction in left ventricular mass after 40 weeks of treatment. Secondary endpoints are: i) change in aortic compliance; ii) change in arterial stiffness; iii) change in arterial elastance; iv) change in left ventricular systolic and diastolic elastance; v) change in left ventricular function; and vi) change in bone density. Trial Registration: This trial is registered at ClinicalTrials.gov: NCT00806481 and Current Controlled Trials: ISRCTN35254279. [ABSTRACT FROM AUTHOR]
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- 2011
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5. Arterial stiffness in chronic kidney disease: causes and consequences.
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Chue, Colin D., Townend, Jonathan N., Steeds, Richard P., and Ferro, Charles J.
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ARTERIAL diseases , *CHRONIC kidney failure , *ETIOLOGY of diseases , *DISEASE complications , *CARDIOVASCULAR diseases , *PATHOLOGICAL physiology , *COHORT analysis - Abstract
Chronic kidney disease is associated with elevated cardiovascular risk, and heart failure and arrhythmias are the biggest causes of cardiovascular death in this population. Increased arterial stiffness is a hallmark of chronic kidney disease and is associated with adverse alterations in cardiac structure and function that may predispose to an increased risk of cardiovascular death. These changes are already apparent in early kidney disease, which is highly prevalent in the developed world. The mechanisms underlying increased arterial stiffness in chronic kidney disease are undoubtedly complex, but an understanding is paramount to enable the development of novel therapeutic strategies to prevent or reverse this pathophysiology and therefore reduce the cardiovascular disease burden in this high-risk cohort. [ABSTRACT FROM AUTHOR]
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- 2010
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6. Validation of the conductance catheter method for measurement of ventricular volumes under varying conditions relevant to cardiac surgery.
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Al-Khalidi, Abdul-Hakam, Townend, Jonathan N., Al-Khalidi, A H, Townend, J N, Bonser, R S, and Coote, J H
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CATHETERIZATION , *CARDIAC surgery , *BIOLOGICAL models , *CARDIAC catheterization , *CARDIOVASCULAR system physiology , *COMPARATIVE studies , *HEART ventricles , *HEART beat , *RESEARCH methodology , *MEDICAL cooperation , *RESEARCH , *VISCOSITY , *PRODUCT design , *EVALUATION research ,RESEARCH evaluation - Abstract
The development of the conductance catheter method has enabled continuous measurement of intraventricular volume in vivo, thus making assessment of pump performance of the heart in vivo possible using pressure-volume analysis. However, this method has not been validated under conditions where pump rate, conductance, viscosity, and temperature of the fluid in the heart chamber is changed as happens in cardiac surgery. To validate the method, pressure-volume data were measured by conductance catheter in a physical model of the human left ventricle. The volume, salinity, viscosity, and temperature of the fluid inside the model were rigorously controlled. The measured pressure-volume data were compared with the actual values to assess the accuracy and dependence of the conductance-measured volumes on salinity, viscosity, temperature, and pump rate. Conductance-measured volumes were not significantly different over a range of heart rates extending from 60 to 100 beats/min, and they were not significantly different over a salinity range of 0.2 to 2 normal saline, a viscosity range of 2.7 to 3.5 centipoise, or over a temperature range of 20 degrees C to 39 degrees C. The percentage errors between actual stroke volumes and conductance-derived volumes were of the order of 10% on average. Our data shows that for a broad range of conditions normally encountered during cardiac surgery, there is no dependence of conductance-measured volume on heart rate, viscosity, temperature, or salinity, provided the correct value of fluid resistivity is used. [ABSTRACT FROM AUTHOR]
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- 1998
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7. Coronary Atherosclerotic Plaque Activity and Risk of Myocardial Infarction.
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Wang, Kang-Ling, Balmforth, Craig, Meah, Mohammed N., Daghem, Marwa, Moss, Alastair J., Tzolos, Evangelos, Kwiecinski, Jacek, Molek-Dziadosz, Patrycja, Craig, Neil, Bularga, Anda, Adamson, Philip D., Dawson, Dana K., Arumugam, Parthiban, Sabharwal, Nikant K., Greenwood, John P., Townend, Jonathan N., Calvert, Patrick A., Rudd, James H.F., Verjans, Johan W., and Berman, Daniel S.
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MYOCARDIAL infarction , *ATHEROSCLEROTIC plaque , *POSITRON emission tomography , *CORONARY artery disease , *CORONARY arteries - Abstract
Total coronary atherosclerotic plaque activity across the entire coronary arterial tree is associated with patient-level clinical outcomes. We aimed to investigate whether vessel-level coronary atherosclerotic plaque activity is associated with vessel-level myocardial infarction. In this secondary analysis of an international multicenter study of patients with recent myocardial infarction and multivessel coronary artery disease, we assessed vessel-level coronary atherosclerotic plaque activity using coronary 18F-sodium fluoride positron emission tomography to identify vessel-level myocardial infarction. Increased 18F-sodium fluoride uptake was found in 679 of 2,094 coronary arteries and 414 of 691 patients. Myocardial infarction occurred in 24 (4%) vessels with increased coronary atherosclerotic plaque activity and in 25 (2%) vessels without increased coronary atherosclerotic plaque activity (HR: 2.08; 95% CI: 1.16-3.72; P = 0.013). This association was not demonstrable in those treated with coronary revascularization (HR: 1.02; 95% CI: 0.47-2.25) but was notable in untreated vessels (HR: 3.86; 95% CI: 1.63-9.10; P interaction = 0.024). Increased coronary atherosclerotic plaque activity in multiple coronary arteries was associated with heightened patient-level risk of cardiac death or myocardial infarction (HR: 2.43; 95% CI: 1.37-4.30; P = 0.002) as well as first (HR: 2.19; 95% CI: 1.18-4.06; P = 0.013) and total (HR: 2.50; 95% CI: 1.42-4.39; P = 0.002) myocardial infarctions. In patients with recent myocardial infarction and multivessel coronary artery disease, coronary atherosclerotic plaque activity prognosticates individual coronary arteries and patients at risk for myocardial infarction. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2024
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8. Prevalence and Impact of Concomitant Atrial Fibrillation in Patients Undergoing Percutaneous Coronary Intervention for Acute Myocardial Infarction.
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Shakeel, Iqra, Sharma, Harish, Hodson, James, Iqbal, Hamna, Tashfeen, Rashna, Ludman, Peter F., Steeds, Richard P., Townend, Jonathan N., Doshi, Sagar N., and Nadir, M. Adnan
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MYOCARDIAL infarction , *PERCUTANEOUS coronary intervention , *ATRIAL fibrillation - Abstract
Background: Concomitant atrial fibrillation (AF) is associated with an adverse prognosis in patients with acute myocardial infarction (MI). However, it remains unclear whether this is due to a causal effect of AF or whether AF acts as a surrogate marker for comorbidities in this population. Furthermore, there are limited data on whether coronary artery disease distribution impacts the risk of developing AF. Methods: Consecutive patients admitted with acute MI and treated using percutaneous coronary intervention (PCI) at a single centre were retrospectively identified. Associations between AF and major adverse cardiac and cerebrovascular events (MACCEs) over a median of five years of follow-up were assessed using Cox regression, with adjustment for confounding factors performed using both multivariable modelling and a propensity-score-matched analysis. Results: AF was identified in N = 65/1000 (6.5%) of cases; these patients were significantly older (mean: 73 vs. 65 years, p < 0.001), with lower creatinine clearance (p < 0.001), and were more likely to have a history of cerebrovascular disease (p = 0.011) than those without AF. In addition, patients with AF had a greater propensity for left main stem (p = 0.001) or left circumflex artery (p = 0.004) involvement. Long-term MACCE rates were significantly higher in the AF group than in the non-AF group (50.8% vs. 34.2% at five years), yielding an unadjusted hazard ratio (HR) of 1.86 (95% CI: 1.32–2.64, p < 0.001). However, after adjustment for confounding factors, AF was no longer independently associated with MACCEs, either on multivariable (adjusted HR: 1.25, 95% CI: 0.81–1.92, p = 0.319) or propensity-score-matched (HR: 1.04, 95% CI: 0.59–1.82, p = 0.886) analyses. Conclusions: AF is observed in 6.5% of patients admitted with acute MI, and those with AF are more likely to have significant diseases involving left main or circumflex arteries. Although unadjusted MACCE rates were significantly higher in patients with AF, this effect was not found to remain significant after adjustment for comorbidities. As such, this study provided no evidence to suggest that AF is independently associated with MACCEs. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Anticoagulant strategies for the patient with chronic kidney disease.
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Law, Jonathan P., Pickup, Luke, Townend, Jonathan N., and Ferro, Charles J.
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THROMBOSIS risk factors , *HEMORRHAGE risk factors , *ANTICOAGULANTS , *CHRONIC kidney failure , *DECISION making in clinical medicine , *TREATMENT duration , *PHARMACODYNAMICS , *ADULTS ,CHRONIC kidney failure complications ,DEVELOPED countries - Abstract
Chronic kidney disease (CKD) is a global health problem affecting up to 14% of the adult population in developed countries. On the basis of current guidelines, patients with CKD will often fulfil criteria for both short-term and long-term anticoagulation. Paradoxically, patients with CKD are not only at a higher risk of thrombosis, they are also at increased risk of bleeding. Furthermore, the pharmacokinetics and pharmacodynamics of many anticoagulant therapies are significantly affected by renal dysfunction. In addition, patients with advanced CKD are often systematically excluded from major clinical trials. As such, the decision on whether to anticoagulate or not, and if so with what agent, poses significant challenges. A solid understanding of the condition in question and the available treatments is required to make an informed judgement call. An in-depth appreciation of the advantages and disadvantages of the currently available anticoagulants is a key element in the decision-making process. [ABSTRACT FROM AUTHOR]
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- 2020
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10. Sudden cardiac death in chronic renal disease: aetiology and risk reduction strategies.
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Pickup, Luke C, Law, Jonathan P, Townend, Jonathan N, and Ferro, Charles J
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ETIOLOGY of diseases , *CARDIAC arrest , *KIDNEY diseases , *TACHYARRHYTHMIAS , *VENTRICULAR arrhythmia , *CHRONIC diseases , *MEDICAL research - Published
- 2021
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11. Management of heart failure in patients with kidney disease—updates from the 2021 ESC guidelines.
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Edwards, Nicola C, Price, Anna M, Steeds, Richard P, Ferro, Charles J, and Townend, Jonathan N
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HEART failure , *IMPLANTABLE cardioverter-defibrillators , *ARTIFICIAL implants , *KIDNEY diseases , *HEART failure patients , *KIDNEY failure , *BUNDLE-branch block , *CARDIAC pacing - Abstract
The wide overlap between the syndromes of chronic kidney disease (CKD) and chronic heart failure (HF) means that familiarity with the 2021 European Society of Cardiology guidelines is of importance to nephrologists. The common risk factors for the two syndromes together with the adverse cardiac structural remodelling associated with CKD means that many kidney disease patients experience breathlessness and fall within the HF phenotypes categorized in the guidelines. The management of HF is evolving rapidly leading to significant changes in the latest guideline iteration. The 2021 guidelines have changed from the 2016 version firstly by an increased focus on identifying the three phenotypes of HF to guide appropriate evidence-based management. Secondly, a new and simplified treatment algorithm for HF with reduced ejection fraction involving the rapid sequential initiation and up-titration of four 'pillars' of drug treatment—angiotensin-converting enzyme inhibitors or angiotensin-neprilysin inhibitors, beta blockers, mineralocorticoid receptor antagonists and now, thanks to convincing trial data, sodium-glucose co-transporter 2 inhibitors. Thirdly, guidelines for device therapy have been changed with down-graded advice on indications for primary prevention implantable cardioverter defibrillator therapy for patients with non-ischaemic HF and for cardiac resynchronization therapy with left bundle branch block (LBBB) and a QRS duration <150 ms. There are updated treatment plans for HF associated with non-cardiovascular comorbidities including CKD. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Chronic activation of human cardiac fibroblasts in vitro attenuates the reversibility of the myofibroblast phenotype.
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Hall, Caitlin, Law, Jonathan P., Reyat, Jasmeet S., Cumberland, Max J., Hang, Shaun, Vo, Nguyen T. N., Raniga, Kavita, Weston, Chris J., O'Shea, Christopher, Townend, Jonathan N., Gehmlich, Katja, Ferro, Charles J., Denning, Chris, and Pavlovic, Davor
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INDUCED pluripotent stem cells , *FIBROBLASTS , *PHENOTYPES , *YOUNG'S modulus , *MYOFIBROBLASTS , *ARRHYTHMIA , *MUSCLE growth - Abstract
Activation of cardiac fibroblasts and differentiation to myofibroblasts underlies development of pathological cardiac fibrosis, leading to arrhythmias and heart failure. Myofibroblasts are characterised by increased α-smooth muscle actin (α-SMA) fibre expression, secretion of collagens and changes in proliferation. Transforming growth factor-beta (TGF-β) and increased mechanical stress can initiate myofibroblast activation. Reversibility of the myofibroblast phenotype has been observed in murine cells but has not been explored in human cardiac fibroblasts. In this study, chronically activated adult primary human ventricular cardiac fibroblasts and human induced pluripotent stem cell derived cFbs (hiPSC-cFbs) were used to investigate the potential for reversal of the myofibroblast phenotype using either subculture on soft substrates or TGF-β receptor inhibition. Culture on softer plates (25 or 2 kPa Young's modulus) did not alter proliferation or reduce expression of α-SMA and collagen 1. Similarly, culture of myofibroblasts in the presence of TGF-β inhibitor did not reverse myofibroblasts back to a quiescent phenotype. Chronically activated hiPSC-cFbs also showed attenuated response to TGF-β receptor inhibition and inability to reverse to quiescent fibroblast phenotype. Our data demonstrate substantial loss of TGF-β signalling plasticity as well as a loss of feedback from the surrounding mechanical environment in chronically activated human myofibroblasts. [ABSTRACT FROM AUTHOR]
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- 2023
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13. The importance of selecting controls in kidney donor outcome studies.
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Moody, William E and Townend, Jonathan N
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ORGAN donors , *KIDNEY transplantation , *HEALTH - Abstract
A letter to the editor is presented in response to the article which discusses the importance of selecting kidney donors for examining effects of kidney donation on long term health outcomes.
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- 2014
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14. Door-to-Balloon Time in Acute Myocardial Infarction.
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Townend, Jonathan N.
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LETTERS to the editor , *MYOCARDIAL infarction treatment - Abstract
The article presents a letter to the editor in response to the article "Strategies for reducing the door-to-balloon time in acute myocardial infarction," by E. H. Bradley and colleagues in the November 30, 2006 issue.
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- 2007
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15. The OPTIMMAL trial: losartan or captopril after acute myocardial infarction.
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Chowdhary, Saqib, Townend, Jonathan N, and Optimal Trial in Myocardial Infarction with the Angiotensin II Antagonist Losartan
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ACE inhibitors , *CAPTOPRIL , *LOSARTAN , *CLINICAL trials , *COMPARATIVE studies , *RESEARCH methodology , *MEDICAL cooperation , *MYOCARDIAL infarction , *RESEARCH , *EVALUATION research , *THERAPEUTICS - Published
- 2002
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16. Coronary-Artery Calcification.
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Khogali, Saib S. and Townend, Jonathan N.
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CARDIAC calcification , *ATHEROSCLEROSIS , *MITRAL valve , *CALCIUM in the body - Abstract
Displays a clinical image of a human heart mitral valve with coronary artery calcification. Statement that, although calcification is common, little is known about the relation between atherosclerosis and vascular calcification.
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- 2002
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17. Unstable Angina Due to Spontaneous Coronary-Artery Dissection.
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Eccleshall, Simon C. and Townend, Jonathan N.
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CORONARY disease , *DISEASES in older women , *CHEST pain , *CASE studies , *HEART diseases , *MYOCARDIAL infarction , *ASPIRIN , *HEPARIN , *THERAPEUTICS , *PATIENTS - Abstract
This article discusses unstable angina caused by spontaneous coronary-artery dissection, and makes reference to a medical case wherein a 61-year-old woman was diagnosed with unstable angina. It is stated that the mechanism of spontaneous coronary-artery dissection, a rare cause of unstable angina, is unclear, but predisposing factors include inborn errors of metabolism and collagen synthesis. The patient was presented with a one-hour history of chest pain suggestive of myocardial infarction. Unstable angina was diagnosed, and treatment with aspirin, beta-blockers, and intravenous heparin and nitrates was begun. It is informed that the dissection was successfully treated by direct coronary stenting.
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- 2000
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18. Allopurinol versus usual care in UK patients with ischaemic heart disease (ALL-HEART): a multicentre, prospective, randomised, open-label, blinded-endpoint trial.
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Mackenzie, Isla S, Hawkey, Christopher J, Ford, Ian, Greenlaw, Nicola, Pigazzani, Filippo, Rogers, Amy, Struthers, Allan D, Begg, Alan G, Wei, Li, Avery, Anthony J, Taggar, Jaspal S, Walker, Andrew, Duce, Suzanne L, Barr, Rebecca J, Dumbleton, Jennifer S, Rooke, Evelien D, Townend, Jonathan N, Ritchie, Lewis D, MacDonald, Thomas M, and ALL-HEART Study Group
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RESEARCH , *STROKE , *MYOCARDIAL ischemia , *RESEARCH methodology , *MYOCARDIAL infarction , *ALLOPURINOL , *EVALUATION research , *TREATMENT effectiveness , *COMPARATIVE studies , *RANDOMIZED controlled trials , *CORONARY artery disease , *URIC acid , *GOUT , *LONGITUDINAL method - Abstract
Background: Allopurinol is a urate-lowering therapy used to treat patients with gout. Previous studies have shown that allopurinol has positive effects on several cardiovascular parameters. The ALL-HEART study aimed to determine whether allopurinol therapy improves major cardiovascular outcomes in patients with ischaemic heart disease.Methods: ALL-HEART was a multicentre, prospective, randomised, open-label, blinded-endpoint trial done in 18 regional centres in England and Scotland, with patients recruited from 424 primary care practices. Eligible patients were aged 60 years or older, with ischaemic heart disease but no history of gout. Participants were randomly assigned (1:1), using a central web-based randomisation system accessed via a web-based application or an interactive voice response system, to receive oral allopurinol up-titrated to a dose of 600 mg daily (300 mg daily in participants with moderate renal impairment at baseline) or to continue usual care. The primary outcome was the composite cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death. The hazard ratio (allopurinol vs usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis (excluding randomly assigned patients later found to have met one of the exclusion criteria). The safety analysis population included all patients in the modified intention-to-treat usual care group and those who took at least one dose of randomised medication in the allopurinol group. This study is registered with the EU Clinical Trials Register, EudraCT 2013-003559-39, and ISRCTN, ISRCTN32017426.Findings: Between Feb 7, 2014, and Oct 2, 2017, 5937 participants were enrolled and then randomly assigned to receive allopurinol or usual care. After exclusion of 216 patients after randomisation, 5721 participants (mean age 72·0 years [SD 6·8], 4321 [75·5%] males, and 5676 [99·2%] white) were included in the modified intention-to-treat population, with 2853 in the allopurinol group and 2868 in the usual care group. Mean follow-up time in the study was 4·8 years (1·5). There was no evidence of a difference between the randomised treatment groups in the rates of the primary endpoint. 314 (11·0%) participants in the allopurinol group (2·47 events per 100 patient-years) and 325 (11·3%) in the usual care group (2·37 events per 100 patient-years) had a primary endpoint (hazard ratio [HR] 1·04 [95% CI 0·89-1·21], p=0·65). 288 (10·1%) participants in the allopurinol group and 303 (10·6%) participants in the usual care group died from any cause (HR 1·02 [95% CI 0·87-1·20], p=0·77).Interpretation: In this large, randomised clinical trial in patients aged 60 years or older with ischaemic heart disease but no history of gout, there was no difference in the primary outcome of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death between participants randomised to allopurinol therapy and those randomised to usual care.Funding: UK National Institute for Health and Care Research. [ABSTRACT FROM AUTHOR]- Published
- 2022
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19. Phosphate: are we squandering a scarce commodity?
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Ferro, Charles J., Ritz, Eberhard, and Townend, Jonathan N.
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CARDIOVASCULAR diseases risk factors , *PHOSPHORUS , *PUBLIC health , *HYPERBARIC oxygenation , *KIDNEY disease risk factors - Abstract
Phosphorus is an essential element for life but is a rare element in the universe. On Earth, it occurs mostly in the form of phosphates that are widespread but predominantly at very low concentration. This relative rarity has resulted in a survival advantage, in evolutionary terms, to organisms that conserve phosphate. When phosphate is made available in excess it becomes a cause for disease, perhaps best recognized as a potential cardiovascular and renal risk factor. As a reaction to the emerging public health issue caused by phosphate additives to food items, there have been calls for a public education programme and regulation to bring about a reduction of phosphate additives to food. During the Paleoproterzoic era, an increase in the bioavailability of phosphate is thought to have contributed significantly to the oxygenation of our atmosphere and a dramatic increase in the evolution of new species. Currently, phosphate is used poorly and often wasted with phosphate fertilizers washing this scarce commodity into water bodies causing eutrophication and algal blooms. Ironically, this is leading to the extinction of hundreds of species. The unchecked exploitation of phosphate rock, which is an increasingly rare natural resource, and our dependence on it for agriculture may lead to a strange situation in which phosphate might become a commodity to be fought over whilst at the same time, health and environmental experts are likely to recommend reductions in its use. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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20. effect of admission and pre-admission serum creatinine as baseline to assess incidence and outcomes of acute kidney injury in acute medical admissions.
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Pickup, Luke, Loutradis, Charalampos, Law, Jonathan P, Arnold, Julia J, Dasgupta, Indranil, Sarafidis, Pantelis, Townend, Jonathan N, Cockwell, Paul, and Ferro, Charles J
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ACUTE kidney failure , *CREATININE , *MORTALITY , *HOSPITAL statistics , *KIDNEY diseases - Abstract
Background Acute kidney injury (AKI) in hospital-admitted patients is a common complication associated with increased mortality. The diagnosis of AKI relies on the ascertainment of peak increase in serum creatinine (SCr). This study evaluated the incidence of AKI using the increase from mean 7–365 days pre-admission (AKIpre) and admission (AKIadm) SCr levels, and examined the associations of AKI and changes in SCr levels with all-cause mortality. Methods A total of 2436 patients admitted to a tertiary hospital were recruited and followed-up for a median of 47.70 (interquartile range 18.20) months. AKI incidence and severity were defined according to the Kidney Disease: Improving Global Outcomes-AKI Guidelines. Follow-up data were collected from the Hospital Episode Statistics and Office of National Statistics. Mortality was evaluated during a short- (30 days), mid- (1 year) and long-term (4 years) period. Results No difference in the AKI rates using AKIpre and AKIadm (12.5% versus 12.2%; P = 0.695) or in the AKI severity (P = 0.261) was evident. Agreement between the two definitions was modest (Kappa-statistic = 0.596, P < 0.001). Patients with AKIpre or AKIadm had increased all-cause mortality compared with those without AKI during all follow-up periods. In fully adjusted regression analysis, AKIpre [hazard ratio (HR) = 2.226, 95% confidence interval (CI) 1.140–4.347; P = 0.027] and AKIadm (HR = 2.105, 95% CI 1.090–4.064; P = 0.027) remained associated with 30-day mortality. Results for the 1- and 4-year periods were similar. Increases of >4.00 μmol/L and >6.06% from pre-admission or >6.00 μmol/L and >17.24% from admission SCr levels presented increased mortality risk during follow-up. Conclusions Use of admission or pre-admission SCr provides similar incidence rates, but they diagnose different sets of patients. Even minor increases in SCr, below those required for the classification of AKI, were associated with increased mortality. These findings can help the clinicians to identify patients at higher risk for adverse outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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21. Screening for occult coronary artery disease in potential kidney transplant recipients: time for reappraisal?
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Ferro, Charles J, Berry, Miriam, Moody, William E, George, Sudhakar, Sharif, Adnan, and Townend, Jonathan N
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CORONARY artery disease , *KIDNEY transplantation , *MEDICAL screening , *KIDNEY diseases , *MEDICAL care standards - Abstract
Screening for occult coronary artery disease in potential kidney transplant recipients has become entrenched in current medical practice as the standard of care and is supported by national and international clinical guidelines. However, there is increasing and robust evidence that such an approach is out-dated, scientifically and conceptually flawed, ineffective, potentially directly harmful, discriminates against ethnic minorities and patients from more deprived socioeconomic backgrounds, and unfairly denies many patients access to potentially lifesaving and life-enhancing transplantation. Herein we review the available evidence in the light of recently published randomized controlled trials and major observational studies. We propose ways of moving the field forward to the overall benefit of patients with advanced kidney disease. [ABSTRACT FROM AUTHOR]
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- 2021
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22. Acute kidney injury is more common in men than women after accounting for socioeconomic status, ethnicity, alcohol intake and smoking history.
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Loutradis, Charalampos, Pickup, Luke, Law, Jonathan P., Dasgupta, Indranil, Townend, Jonathan N., Cockwell, Paul, Sharif, Adnan, Sarafidis, Pantelis, and Ferro, Charles J.
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ACUTE kidney failure , *SOCIAL accounting , *ALCOHOL , *CHRONIC kidney failure , *HOSPITAL statistics , *ETHNICITY , *SMOKING cessation - Abstract
Background: The association of several comorbidities, including diabetes mellitus, hypertension, cardiovascular disease, heart failure and chronic kidney or liver disease, with acute kidney injury (AKI) is well established. Evidence on the effect of sex and socioeconomic factors are scarce. This study was designed to examine the association of sex and socioeconomic factors with AKI and AKI-related mortality and further to evaluate the additional relationship with other possible risk factors for AKI occurrence. Methods: We included 3534 patients (1878 males with mean age 61.1 ± 17.7 and 1656 females 1656 with mean age 60.3 ± 20.0 years) admitted to Queen Elizabeth or Heartlands Hospitals, Birmingham, between October 2013 and January 2016. Patients were prospectively followed-up for a median 47.70 [IQR, 18.20] months. Study-endpoints were incidence of AKI, based on KDIGO-AKI Guidelines, and all-cause mortality. Data acquisition was automated, and information on mortality was collected from the Hospital Episode Statistics and Office of National Statistics. Socioeconomic status was evaluated with the Index of Multiple Deprivation (IMD). Results: Incidence of AKI was higher in men compared to women (11.3% vs 7.1%; P < 0.001). Model regression analysis revealed significant association of male sex with higher AKI risk (OR, 1.659; 95% CI, 1.311–2.099; P < 0.001); this association remained significant after adjustment for age, eGFR, IMD, smoking, alcohol consumption, ethnicity, existing comorbidities and treatment (OR, 1.599; 95% CI, 1.215–2.103; P = 0.001). All-cause mortality was higher in patients with compared to those without AKI. Males with AKI had higher mortality rates in the first 6-month and 1-year periods after the index AKI event. The association of male sex with mortality was independent of socioeconomic factors but was not statistically significant after adjustment for existing comorbidities. Conclusions: Men are at higher risk of AKI and this association is independent from existing risk factors for AKI. The association between male sex and AKI-related mortality was not independent from existing comorbidities. A better understanding of factors associated with AKI may help accurately identify high-risk patients. [ABSTRACT FROM AUTHOR]
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- 2021
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23. Finerenone and Chronic Kidney Disease Outcomes in Type 2 Diabetes.
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Edwards, Nicola C, Ferro, Charles J, and Townend, Jonathan N
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HETEROCYCLIC compounds , *TYPE 2 diabetes , *DISEASE complications ,CHRONIC kidney failure complications - Published
- 2021
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24. Effect of Digoxin vs Bisoprolol for Heart Rate Control in Atrial Fibrillation on Patient-Reported Quality of Life: The RATE-AF Randomized Clinical Trial.
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Kotecha, Dipak, Bunting, Karina V., Gill, Simrat K., Mehta, Samir, Stanbury, Mary, Jones, Jacqueline C., Haynes, Sandra, Calvert, Melanie J., Deeks, Jonathan J., Steeds, Richard P., Strauss, Victoria Y., Rahimi, Kazem, Camm, A. John, Griffith, Michael, Lip, Gregory Y. H., Townend, Jonathan N., Kirchhof, Paulus, and Rate Control Therapy Evaluation in Permanent Atrial Fibrillation (RATE-AF) Team
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DIGOXIN , *BISOPROLOL , *HEART beat , *ATRIAL fibrillation , *HEART failure patients , *TREATMENT effectiveness , *THERAPEUTICS research , *MYOCARDIAL depressants , *RESEARCH , *RESEARCH methodology , *EVALUATION research , *MEDICAL cooperation , *HEALTH surveys , *CARDIOVASCULAR agents , *ADRENERGIC beta blockers , *COMPARATIVE studies , *RANDOMIZED controlled trials , *QUALITY of life , *BLIND experiment , *RESEARCH funding , *STROKE volume (Cardiac output) , *STATISTICAL sampling , *HEART failure , *PHARMACODYNAMICS , *DISEASE complications - Abstract
Importance: There is little evidence to support selection of heart rate control therapy in patients with permanent atrial fibrillation, in particular those with coexisting heart failure.Objective: To compare low-dose digoxin with bisoprolol (a β-blocker).Design, Setting, and Participants: Randomized, open-label, blinded end-point clinical trial including 160 patients aged 60 years or older with permanent atrial fibrillation (defined as no plan to restore sinus rhythm) and dyspnea classified as New York Heart Association class II or higher. Patients were recruited from 3 hospitals and primary care practices in England from 2016 through 2018; last follow-up occurred in October 2019.Interventions: Digoxin (n = 80; dose range, 62.5-250 μg/d; mean dose, 161 μg/d) or bisoprolol (n = 80; dose range, 1.25-15 mg/d; mean dose, 3.2 mg/d).Main Outcomes and Measures: The primary end point was patient-reported quality of life using the 36-Item Short Form Health Survey physical component summary score (SF-36 PCS) at 6 months (higher scores are better; range, 0-100), with a minimal clinically important difference of 0.5 SD. There were 17 secondary end points (including resting heart rate, modified European Heart Rhythm Association [EHRA] symptom classification, and N-terminal pro-brain natriuretic peptide [NT-proBNP] level) at 6 months, 20 end points at 12 months, and adverse event (AE) reporting.Results: Among 160 patients (mean age, 76 [SD, 8] years; 74 [46%] women; mean baseline heart rate, 100/min [SD, 18/min]), 145 (91%) completed the trial and 150 (94%) were included in the analysis for the primary outcome. There was no significant difference in the primary outcome of normalized SF-36 PCS at 6 months (mean, 31.9 [SD, 11.7] for digoxin vs 29.7 [11.4] for bisoprolol; adjusted mean difference, 1.4 [95% CI, -1.1 to 3.8]; P = .28). Of the 17 secondary outcomes at 6 months, there were no significant between-group differences for 16 outcomes, including resting heart rate (a mean of 76.9/min [SD, 12.1/min] with digoxin vs a mean of 74.8/min [SD, 11.6/min] with bisoprolol; difference, 1.5/min [95% CI, -2.0 to 5.1/min]; P = .40). The modified EHRA class was significantly different between groups at 6 months; 53% of patients in the digoxin group reported a 2-class improvement vs 9% of patients in the bisoprolol group (adjusted odds ratio, 10.3 [95% CI, 4.0 to 26.6]; P < .001). At 12 months, 8 of 20 outcomes were significantly different (all favoring digoxin), with a median NT-proBNP level of 960 pg/mL (interquartile range, 626 to 1531 pg/mL) in the digoxin group vs 1250 pg/mL (interquartile range, 847 to 1890 pg/mL) in the bisoprolol group (ratio of geometric means, 0.77 [95% CI, 0.64 to 0.92]; P = .005). Adverse events were less common with digoxin; 20 patients (25%) in the digoxin group had at least 1 AE vs 51 patients (64%) in the bisoprolol group (P < .001). There were 29 treatment-related AEs and 16 serious AEs in the digoxin group vs 142 and 37, respectively, in the bisoprolol group.Conclusions and Relevance: Among patients with permanent atrial fibrillation and symptoms of heart failure treated with low-dose digoxin or bisoprolol, there was no statistically significant difference in quality of life at 6 months. These findings support potentially basing decisions about treatment on other end points.Trial Registration: ClinicalTrials.gov Identifier: NCT02391337 and clinicaltrialsregister.eu Identifier: 2015-005043-13. [ABSTRACT FROM AUTHOR]- Published
- 2020
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25. Coronary flow velocity reserve and inflammatory markers in living kidney donors.
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Radhakrishnan, Ashwin, Price, Anna M., Pickup, Luke C., Law, Jonathan P., McGee, Kirsty C., Fabritz, Larissa, Senior, Roxy, Steeds, Richard P., Ferro, Charles J., and Townend, Jonathan N.
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FLOW velocity , *CARDIOVASCULAR diseases risk factors , *KIDNEYS , *GLOMERULAR filtration rate , *CHRONIC kidney failure - Abstract
Coronary microvascular dysfunction is prevalent in chronic kidney disease (CKD), and may contribute to the development of myocardial dysfunction in CKD. Coronary flow velocity reserve (CFVR) is a marker of coronary microvascular function and falls with increasing CKD stage. Living kidney donors have renal function consistent with early stage CKD and concern has been raised about their cardiovascular risk. No studies to date have investigated the presence of coronary microvascular dysfunction in living kidney donors. 25 healthy controls and 23 living kidney donors were recruited and underwent assessment with transthoracic echocardiography, Doppler CFVR, myocardial contrast echocardiography and serum multiplex immunoassay panels. Doppler CFVR was significantly reduced in living kidney donors compared to controls (mean CFVR 3.4 ± 0.7 vs 3.8 ± 0.6, mean difference 0.4 95% confidence interval 0.03–0.8, p =.036). Quantitative myocardial contrast echocardiography showed a trend towards reduced coronary flow reserve in living kidney donors. Compared to controls, living kidney donors had higher serum high sensitivity C reactive peptide (hsCRP) and lower levels of uromodulin. This is the first study of CFVR in living kidney donors. We have shown that the modest drop in estimated glomerular filtration rate in living kidney donors is associated with lower values of Doppler CFVR compared to controls, suggesting that isolated reductions in renal function may lead to altered microvascular function. The increase in hsCRP and reduction in uromodulin suggests that chronic subclinical inflammation may contribute to altered microvascular function in this population. • Coronary flow velocity reserve is reduced in living kidney donors compared to controls. • Markers of inflammation are elevated in living kidney donors. • Inflammation may cause coronary microvascular dysfunction in living kidney donors. • Living kidney donors need aggressive cardiovascular risk factor management. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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26. Macrophage infiltrates in coronary plaque erosion and cardiovascular outcome in patients with acute coronary syndrome.
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Montone, Rocco A., Vetrugno, Vincenzo, Camilli, Massimiliano, Russo, Michele, Fracassi, Francesco, Khan, Sohail Q., Doshi, Sagar N., Townend, Jonathan N., Ludman, Peter F., Trani, Carlo, Niccoli, Giampaolo, and Crea, Filippo
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ACUTE coronary syndrome , *OPTICAL coherence tomography , *MYOCARDIAL infarction - Abstract
Plaque erosion (PE) is responsible for at least one-third of acute coronary syndrome (ACS), and inflammation plays a key role in plaque instability. We assessed the presence of optical coherence tomography (OCT)-defined macrophage infiltrates (MØI) at the culprit site in ACS patients with PE, evaluating their clinical and OCT correlates, along with their prognostic value. ACS patients undergoing OCT imaging and presenting PE as culprit lesion were retrospectively selected. Presence of MØI at culprit site was assessed. The incidence of major adverse cardiac events (MACEs), defined as the composite of cardiac death, recurrent myocardial infarction and target-vessel revascularization (TVR), was assessed [follow-up median (interquartile range, IQR) time 2.5 (2.03–2.58) years]. We included 153 patients [median age (IQR) 64 (53–75) years, 99 (64.7%) males]. Fifty-one (33.3%) patients presented PE with MØI and 102 (66.7%) PE without MØI. Patients having PE with MØI compared with PE patients without MØI had more vulnerable plaque features both at culprit site and at non-culprit segments. MACEs were significantly more frequent in PE with MØI patients compared with PE without MØI [11 (21.6%) vs. 6 (5.9%), p = 0.008], mainly driven by a higher risk of cardiac death and TVR. At multivariable Cox regression, PE with MØI was an independent predictor of MACEs [HR = 2.95, 95% CI (1.09–8.02), p = 0.034]. Our study demonstrates that among ACS patients with PE the presence of MØI at culprit lesion is associated with more vulnerable plaque features, along with a worse prognosis at a long-term follow-up. Image 1 • Presence of macrophage infiltrates (MØI) at erosion sites is associated with vulnerable coronary plaque features. • Presence of plaque erosion (PE) with MØI is associated with a worse prognosis at long-term follow-up. • Worse prognosis in patients with MØI was mainly driven by a higher risk of cardiac death and target-vessel revascularization (TVR). • Progression of non-culprit lesions may be involved in determining prognosis in patients with MØI. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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27. Early effects of kidney transplantation on the heart - A cardiac magnetic resonance multi-parametric study.
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Hayer, Manvir K., Radhakrishnan, Ashwin, Price, Anna M., Baig, Shanat, Liu, Boyang, Ferro, Charles J., Captur, Gabriella, Townend, Jonathan N., Moon, James C., Edwards, Nicola C., and Steeds, Richard P.
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KIDNEY transplantation , *HEART transplantation , *CARDIAC magnetic resonance imaging , *MAGNETIC resonance , *CHRONIC kidney failure - Abstract
Increased native myocardial T1 times in chronic kidney disease (CKD) may be due to diffuse interstitial myocardial fibrosis (DIF) or due to interstitial edema/inflammation. Concerns relating to nephrogenic systemic fibrosis with gadolinium-based contrast agents (GBCA) limit their use in end-stage kidney disease (ESKD) to measure extracellular volume (ECV) and characterise myocardial fibrosis. This study aimed to examine stability of myocardial T1 and T2 times before, and within 2 months after kidney transplantation; a time frame when volume status normalises but myocardial remodelling is unlikely to have occurred, and to compare these with ECV using GBCA after transplantation. Twenty-four patients with ESKD underwent serial cardiovascular magnetic resonance imaging, including T1 and T2 mapping. GBCA was administered on follow-up provided eGFR was >30 ml/min/1.73 m2. Eighteen age- and sex-matched controls were studied at one timepoint. ECV (ECV 28 ± 2% vs. 24 ± 2%, p = 0.001) and T2 times were higher in ESKD compared to controls. After transplantation, septal T1 times increased (MOLLI 985 ms ± 25 vs. 1002 ms ± 30, p = 0.014; ShMOLLI 974 ms ± 39 vs. 992 ms ± 33, p = 0.113), LV volumes reduced (LVEDvol indexed 79 ± 24 vs. 63 ± 20 ml/m2, p = 0.005) but LV mass was unchanged (LV mass index 89 g/m2 ± 38 to 83 g/m2 ± 23, p = 0.141). T2 times did not change after transplantation. Both ECV and myocardial T1 times are elevated in ESKD, supporting the theory that elevated T1 times are due to DIF, although a contribution from myocardial edema cannot be fully excluded. The lack of any fall in T1 or T2 times after transplantation suggests that myocardial T1 times are a stable measure of DIF in CKD. • ECV is elevated in ESKD suggesting the elevated myocardial T1 times observed are indicative of diffuse interstitial fibrosis. • The contribution of myocardial oedema towards elevated T1 times and ECV cannot be excluded in ESKD. • Native T1 times is a stable and reproducible biomarker of fibrosis. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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28. Double-stenting of an ostial left main-stem lesion for elastic recoil
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Ratib, Karim, Doshi, Sagar N., and Townend, Jonathan N.
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- 2005
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29. Caveolin-1 single-nucleotide polymorphism and arterial stiffness in non-dialysis chronic kidney disease.
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Chand, Sourabh, Edwards, Nicola C., Chue, Colin D., Jesky, Mark, Stringer, Stephanie, Simmonds, Matthew J., Duff, Claire E., Cockwell, Paul, Harper, Lorraine, Steeds, Richard P., Townend, Jonathan N., Ferro, Charles J., and Borrows, Richard
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KIDNEY diseases , *CAVEOLINS , *SINGLE nucleotide polymorphisms , *ARTERIOSCLEROSIS , *ARTERIAL diseases ,CARDIOVASCULAR disease related mortality - Abstract
Background. Arteriosclerosis is an independent predictor of increased cardiovascular mortality in chronic kidney disease (CKD). Histologically it is characterized by hypertrophy and fibrosis of the arterial media wall leading to increased arterial stiffness and end-organ damage. Caveolin-1 acts as an intracellular signalling pathway chaperone in human fibrotic and vascular diseases. The purpose of this study was to assess the association between caveolin-1 (CAV1) single-nucleotide polymorphism (SNP) rs4730751 and arterial stiffness as measured by arterial pulse wave velocity (PWV) in an early-stage CKD cohort and in a cohort with more severe CKD. Methods. Two prospectively maintained patient cohorts with non-dialysis CKD were studied: 144 patients in the Chronic Renal Impairment in Birmingham (CRIB) cohort and 147 patients in the Renal Impairment in Secondary Care (RIISC) cohort, with matched exclusion criteria and DNA sampling availability. At entry to each cohort database, each patient's initial arterial PWV was measured, as well as their anthropomorphic and biochemical data. CAV1 rs4730751 SNP genotyping was performed using Taqman technology. Results. The CAV1 rs4730751 SNP CC genotype was associated with lower arterial PWV in both CRIB early stage CKD patients [8.1 versus 8.6 m/s; coefficient -0.780 (-1.412, -0.149); P = 0.016] and RIISC more advanced stage CKD patients [8.7 versus 9.4 m/s; coefficient -0.695 (-1.288, -0.102); P = 0.022]; these relationships held following adjustment for other important confounders. Conclusions. This replicated study suggests potential utility of the studied CAV1 SNP as a genetic biomarker in CKD and a role for CAV1 in the development of arteriosclerosis in this setting. Further studies are warranted to further explore the basic science driving these clinical observations. [ABSTRACT FROM AUTHOR]
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- 2016
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30. Prognostic Utility of Calcium Scoring as an Adjunct to Stress Myocardial Perfusion Scintigraphy in End-Stage Renal Disease.
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Moody, William E, Lin, Erica L S, Stoodley, Matthew, McNulty, David, Thomson, Louise E, Berman, Daniel S, Edwards, Nicola C, Holloway, Benjamin, Ferro, Charles J, Townend, Jonathan N, Steeds, Richard P, and Birmingham Cardio-Renal Group
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CHRONIC kidney failure , *CORONARY disease , *DIAGNOSTIC imaging , *HEART function tests , *KIDNEY transplantation , *MYOCARDIAL infarction , *PROGNOSIS , *RESEARCH funding , *RISK assessment , *SINGLE-photon emission computed tomography , *PREDICTIVE tests , *PROPORTIONAL hazards models , *SEVERITY of illness index , *CALCINOSIS , *DIAGNOSIS ,CHRONIC kidney failure complications - Abstract
Coronary artery calcium score (CACS) is a strong predictor of adverse cardiovascular events in the general population. Recent data confirm the prognostic utility of single-photon emission computed tomographic (SPECT) imaging in end-stage renal disease, but whether performing CACS as part of hybrid imaging improves risk prediction in this population is unclear. Consecutive patients (n = 284) were identified after referral to a university hospital for cardiovascular risk stratification in assessment for renal transplantation. Participants underwent technetium-99m SPECT imaging after exercise or standard adenosine stress in those unable to achieve 85% maximal heart rate; multislice CACS was also performed (Siemens Symbia T16, Siemens, Erlangen, Germany). Subjects with known coronary artery disease (n = 88) and those who underwent early revascularization (n = 2) were excluded. The primary outcome was a composite of death or first myocardial infarction. An abnormal SPECT perfusion result was seen in 22% (43 of 194) of subjects, whereas 45% (87 of 194) had at least moderate CACS (>100 U). The frequency of abnormal perfusion (summed stress score ≥4) increased with increasing CACS severity (p = 0.049). There were a total of 15 events (8 deaths, and 7 myocardial infarctions) after a median duration of 18 months (maximum follow-up 3.4 years). Univariate analysis showed diabetes mellitus (Hazard ratio [HR] 3.30, 95% CI 1.14 to 9.54; p = 0.028), abnormal perfusion on SPECT (HR 5.32, 95% CI 1.84 to 15.35; p = 0.002), and moderate-to-severe CACS (HR 3.55, 95% CI 1.11 to 11.35; p = 0.032) were all associated with the primary outcome. In a multivariate model, abnormal perfusion on SPECT (HR 4.18, 95% CI 1.43 to 12.27; p = 0.009), but not moderate-to-severe CACS (HR 2.50, 95% CI 0.76 to 8.20; p = 0.130), independently predicted all-cause death or myocardial infarction. The prognostic value of CACS was not incremental to clinical and SPECT perfusion data (global chi-square change = 2.52, p = 0.112). In conclusion, a perfusion defect on SPECT is an independent predictor of adverse outcome in potential renal transplant candidates regardless of the CACS. The use of CACS as an adjunct to SPECT perfusion data does not provide incremental prognostic utility for the prediction of mortality and nonfatal myocardial infarction in end-stage renal disease. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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31. Diffuse Interstitial Fibrosis and Myocardial Dysfunction in Early Chronic Kidney Disease.
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Edwards, Nicola C., Moody, William E., Mengshi Yuan, Hayer, Manvir K., Ferro, Charles J., Townend, Jonathan N., and Steeds, Richard P.
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KIDNEY diseases , *HEART fibrosis , *RIGHT ventricular hypertrophy , *CARDIOVASCULAR diseases risk factors , *GLOMERULAR filtration rate , *CARDIOMYOPATHIES , *GADOLINIUM - Abstract
Early-stage chronic kidney disease (CKD) is an under-recognized highly prevalent cardiovascular (CV) risk factor. Despite a clustering of conventional atherosclerotic risk factors, it is hypothesized that nonatherosclerotic processes, including left ventricular (LV) hypertrophy and fibrosis, account for a significant excess of CV risk. This cross-sectional observational study of 129 age- (mean age 57 ± 10 years) and gender-matched subjects examined: nondiabetic CKD stages 2 to 4 (mean glomerular filtration rate 50 ± 22 ml/min/1.73 m2) with no history of CV disease, subjects who are hypertensive with normal renal function, and healthy controls. Cardiac magnetic resonance imaging was performed for assessment of LV volumes and systolic function (myocardial deformation). Diffuse myocardial fibrosis was assessed using T1 mapping for native myocardial T1 times before contrast and myocardial extracellular volume (ECV) after gadolinium administration in combination with standard late gadolinium enhancement techniques for detection of coarse fibrosis. Patients with CKD had increased native T1 times (986 ± 37 ms) and ECV (0.28 ± 0.04) compared with controls (955 ± 30 ms, 0.25 ± 0.03) and subjects who are hypertensive (956 ± 31 ms, 0.25 ± 0.02, p <0.05). Both T1 times and ECV were correlated with impaired systolic function as assessed by global longitudinal systolic strain (r = -0.22, p <0.05, and r = -0.43, p <0.01, respectively). There were no differences in LV volumes, ejection fraction, or LV mass. T1 times and ECV did not correlate with conventional CV risk factors. In conclusion, diffuse myocardial fibrosis is increased in early CKD and is associated with abnormal global longitudinal strain, an early feature of uremic cardiomyopathy and a key indicator of adverse CV prognosis. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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32. Impact of renal function on survival after transcatheter aortic valve implantation (TAVI): an analysis of the UK TAVI registry.
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Ferro, Charles J., Chue, Colin D., de Belder, Mark A., Moat, Neil, Wendler, Olaf, Trivedi, Uday, Ludman, Peter, and Townend, Jonathan N.
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HEART valve prosthesis implantation , *KIDNEY diseases , *PREOPERATIVE care , *HEMODIALYSIS , *CHRONIC kidney failure , *GLOMERULAR filtration rate ,AORTIC valve surgery - Abstract
Objective To determine the nature of the association between renal dysfunction and outcomes following transcatheter aortic valve implantation (TAVI) in all cases performed in the UK between 2007 and 2012. Methods The UK TAVI registry was established to report outcomes on all TAVI procedures performed within the UK. Data were collected prospectively on 3980 patients from 1 January 2007 until 31 December 2012. Results In total, 205 patients (5.5%) died during their admission. Moderate to advanced chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m²) was significantly associated with increased mortality, even after adjustment for risk factors (OR 1.45, 95% CI 1.03 to 2.05; p=0.04). For every 10 mL/min/1.73 m² decrease in eGFR, in-hospital mortality increased by 8.2% (95% CI 1.1% to 14.7%; p=0.03). In total 1119 patients (30.2%) died during the follow-up period (median 543 days). Moderate to advanced CKD (eGFR <45 mL/min/1.73 m²) was significantly associated with increased mortality, even after adjustment for risk factors (OR 1.36, 95% CI 1.17 to 1.58; p<0.001). For every 10 mL/min/1.73 m² decrease in eGFR, cumulative mortality increased by 4.4% (95% CI 1.2% to 7.5%; p=0.007). Preoperative kidney function and the need for preoperative dialysis treatment discriminated between patients who died and survived. However, predictive power was poor with none of the c-statistics being >0.6. Conclusions Pre-procedural renal dysfunction is associated, in a graded fashion independently of dialysis status, with worse outcomes, including mortality in patients undergoing TAVI. [ABSTRACT FROM AUTHOR]
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- 2015
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33. Endothelial Nitric Oxide Synthase Single Nucleotide Polymorphism and Left Ventricular Function in Early Chronic Kidney Disease.
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Chand, Sourabh, Chue, Colin D., Edwards, Nicola C., Hodson, James, Simmonds, Matthew J., Hamilton, Alexander, Gough, Stephen C. L., Harper, Lorraine, Steeds, Rick P., Townend, Jonathan N., Ferro, Charles J., and Borrows, Richard
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ENDOTHELIAL cells , *NITRIC-oxide synthases , *SINGLE nucleotide polymorphisms , *LEFT heart ventricle , *KIDNEY diseases , *HEART failure , *DISEASE progression - Abstract
Background: Chronic kidney disease (CKD) is associated with accelerated cardiovascular disease and heart failure. Endothelial nitric oxide synthase (eNOS) Glu298Asp single nucleotide polymorphism (SNP) genotype has been associated with a worse phenotype amongst patients with established heart failure and in patients with progression of their renal disease. The association of a cardiac functional difference in non-dialysis CKD patients with no known previous heart failure, and eNOS gene variant is investigated. Methods: 140 non-dialysis CKD patients, who had cardiac magnetic resonance (CMR) imaging and tissue doppler echocardiography as part of two clinical trials, were genotyped for eNOS Glu298Asp SNP retrospectively. Results: The median estimated glomerular filtration rate (eGFR) was 50mls/min and left ventricular ejection fraction (LVEF) was 74% with no overt diastolic dysfunction in this cohort. There were significant differences in LVEF across eNOS genotypes with GG genotype being associated with a worse LVEF compared to other genotypes (LVEF: GG 71%, TG 76%, TT 73%, p = 0.006). After multivariate analysis, (adjusting for age, eGFR, baseline mean arterial pressure, contemporary CMR heart rate, total cholesterol, high sensitive C-reactive protein, body mass index and gender) GG genotype was associated with a worse LVEF, and increased LV end-diastolic and systolic index (p = 0.004, 0.049 and 0.009 respectively). Conclusions: eNOS Glu298Asp rs1799983 polymorphism in CKD patients is associated with relevant sub-clinical cardiac remodelling as detected by CMR. This gene variant may therefore represent an important genetic biomarker, and possibly highlight pathways for intervention, in these patients who are at particular risk of worsening cardiac disease as their renal dysfunction progresses. [ABSTRACT FROM AUTHOR]
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- 2015
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34. Spironolactone to prevent cardiovascular events in early-stage chronic kidney disease (STOP-CKD): study protocol for a randomized controlled pilot trial.
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Ng, Khai P., Jain, Poorva, Heer, Gurdip, Redman, Val, Chagoury, Odette L., Dowswell, George, Greenfield, Sheila, Freemantle, Nick, Townend, Jonathan N., Gill, Paramjit S., McManus, Richard J., and Ferro, Charles J.
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SPIRONOLACTONE , *CHRONIC kidney failure , *ARTERIAL diseases , *RANDOMIZED controlled trials , *PRIMARY care , *BLOOD plasma , *PATHOLOGICAL physiology - Abstract
Background Chronic kidney disease is associated with increased arterial stiffness even in the early stages and this is thought to be a key mediator in the pathophysiology of the increased cardiovascular risk associated with this condition. The use of low-dose spironolactone has previously been shown to improve arterial stiffness and reduce left ventricular mass safely in early-stage chronic kidney disease in the context of careful monitoring at a university hospital. However, the majority of patients with chronic kidney disease are managed by their general practitioners in the community. It is not known whether similar beneficial effects can be achieved safely using spironolactone in the primary care setting. The aim of this study is to determine whether low-dose spironolactone can safely lower arterial stiffness in patients with stage 3 chronic kidney disease in the primary care setting. Methods/design STOP-CKD is a multicentre, prospective, randomized, double-blind, placebo-controlled pilot trial of 240 adult patients with stage 3 chronic kidney disease recruited from up to 20 general practices in South Birmingham, England. Participants will be randomly allocated using a secured web-based computer randomization system to receive either spironolactone 25 mg once daily or a matching inactive placebo for 40 weeks, followed by a wash-out period of 6 weeks. Investigators, outcome assessors, data analysts and participants will all be blinded to the treatment allocation. The primary endpoint is improved arterial stiffness, as measured by carotid-femoral pulse wave velocity between baseline and 40 weeks. The secondary endpoints are incidence of hyperkalaemia, change in estimated glomerular filtration rate, change in urine albumin:creatinine ratio, change in brachial blood pressure, change in pulse waveform characteristics and overall tolerability of spironolactone. An additional quality control study, aiming to compare the laboratory serum potassium results of samples processed via two methods (utilizing routine transport or centrifugation on site before rapid transport to the laboratory) for 100 participants and a qualitative research study exploring patients' and general practitioners' attitudes to research and the use of spironolactone in chronic kidney disease in the community setting will be embedded in this pilot study. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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35. Effects of age and chronic kidney disease on regional aortic distensibility: A cardiovascular magnetic resonance study.
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Chue, Colin D., Edwards, Nicola C., Ferro, Charles J., Townend, Jonathan N., and Steeds, Richard P.
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CARDIOVASCULAR disease diagnosis , *KIDNEY diseases , *CARDIAC magnetic resonance imaging , *HEALTH outcome assessment , *RANDOMIZED controlled trials - Abstract
Abstract: Background: Chronic kidney disease (CKD) is associated with increased arterial stiffness, an independent predictor of adverse cardiovascular outcome. Effects of CKD on regional aortic stiffness are unknown. This study aimed to determine the effects of CKD and ageing on regional thoracic aortic distensibility using cardiac magnetic resonance (CMR) imaging. Methods: This was a cross-sectional case control study comparing patients with stage II–IV non-diabetic CKD recruited from a university hospital with healthy controls. Aortic distensibility was measured in triplicate using CMR (1.5T) at ascending, proximal descending and distal descending thoracic aortic levels and calculated using previously validated formulae. Results: 189 patients and 40 controls were recruited. Distensibility was reduced at all three thoracic aortic levels in CKD patients compared to controls (2.8 vs. 4.1×10−3 mmHg−1; P <0.0005 for ascending aorta). The cohort was divided into tertiles of age and glomerular filtration rate (GFR); distensibility decreased with increasing age (P <0.0005) and decreasing GFR (P <0.02). In univariate analyses age (r=−0.688, P <0.0005), systolic blood pressure (r=−0.183, P =0.006) and GFR (r=0.172, P =0.009) all correlated with ascending aortic distensibility. In a multivariate regression model age and GFR were independent predictors of aortic distensibility at all three levels with 50% of the variation in ascending aortic distensibility explained (P <0.0005). Conclusions: Patients with early stage chronic kidney disease have reduced distensibility along the entire length of the thoracic aorta. This worsens with ageing and as kidney function declines, emphasizing the importance of early treatment whilst kidney function is still relatively preserved. [Copyright &y& Elsevier]
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- 2013
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36. A Longitudinal Study of Mitral Regurgitation Detected after Acute Myocardial Infarction.
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Sharma, Harish, Yuan, Mengshi, Shakeel, Iqra, Hodson, James, Radhakrishnan, Ashwin, Brown, Samuel, May, John, O'Connor, Kieran, Zia, Nawal, Doshi, Sagar N., Hothi, Sandeep S., Townend, Jonathan N., Myerson, Saul G., Ludman, Peter F., Steeds, Richard P., and Nadir, M. Adnan
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MITRAL valve insufficiency , *MYOCARDIAL infarction , *PERCUTANEOUS coronary intervention , *HEART failure , *LONGITUDINAL method - Abstract
Background: Mitral regurgitation (MR) is common following myocardial infarction (MI). However, the subsequent trajectory of MR, and its impact on long-term outcomes are not well understood. This study aimed to examine the change in MR severity and associated clinical outcomes following MI. Methods: Records of patients admitted to a single centre between 2016 and 2017 with acute MI treated by percutaneous coronary intervention (PCI) were retrospectively examined. Results: 294/1000 consecutive patients had MR on baseline (pre-discharge) transthoracic echocardiography (TTE), of whom 126 (mean age: 70.9 ± 11.4 years) had at least one follow-up TTE. At baseline, most patients had mild MR (n = 94; 75%), with n = 30 (24%) moderate and n = 2 (2%) severe MR. Significant improvement in MR was observed at the first follow-up TTE (median 9 months from baseline; interquartile range: 3–23), with 36% having reduced severity, compared to 10% having increased MR severity (p < 0.001). Predictors of worsening MR included older age (mean: 75.2 vs. 66.7 years; p = 0.003) and lower creatinine clearance (mean: 60 vs. 81 mL/min, p = 0.015). Change in MR severity was significantly associated with prognosis: 16% with improving MR reached the composite endpoint of death or heart failure hospitalisation at 5 years, versus 44% (p = 0.004) with no change, and 59% (p < 0.001) with worsening MR. Conclusions: Of patients with follow-up TTE after MI, MR severity improved from baseline in approximately one-third, was stable in around half, with the remainder having worsening MR. Patients with persistent or worsening MR had worse clinical outcomes than those with improving MR. [ABSTRACT FROM AUTHOR]
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- 2022
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37. Arterial disease in chronic kidney disease.
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Moody, William E., Edwards, Nicola C., Chue, Colin D., Ferro, Charles J., and Townend, Jonathan N.
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CHRONIC kidney failure , *ARTERIAL diseases , *ARTERIOSCLEROSIS , *ATHEROSCLEROSIS , *MYOCARDIAL infarction ,CARDIOVASCULAR disease related mortality - Abstract
End stage renal disease is associated with a very high risk of premature cardiovascular death and morbidity. Early stage chronic kidney disease (CKD) is also associated with an increased frequency of cardiovascular events and is a common but poorly recognised and undertreated risk factor. Cardiovascular disease in CKD can be attributed to two distinct but overlapping pathological processes, namely atherosclerosis and arteriosclerosis. While the risk of athero-thrombotic events such as myocardial infarction is elevated, arteriosclerosis is the predominant pathophysiological process involving fibrosis and thickening of the medial arterial layer. This results in increased arterial stiffness causing left ventricular hypertrophy and fibrosis and the exposure of vulnerable vascular beds such as the brain and kidney to high pressure fluctuations causing small vessel disease. These pathophysiological features are manifest by a high risk of lethal arrhythmia, congestive heart failure, myocardial infarction and stroke. Recent work has highlighted the importance of aldosterone and disordered bone mineral metabolism. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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38. Cytomegalovirus Seropositivity Is Associated with Increased Arterial Stiffness in Patients with Chronic Kidney Disease.
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Wall, Nadezhda A., Chue, Colin D., Edwards, Nicola C., Pankhurst, Tanya, Harper, Lorraine, Steeds, Richard P., Lauder, Sarah, Townend, Jonathan N., Moss, Paul, and Ferro, Charles J.
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CYTOMEGALOVIRUS disease diagnosis , *ARTERIAL diseases , *CHRONIC kidney failure , *CARDIOVASCULAR diseases , *BLOOD serum analysis , *ENZYME-linked immunosorbent assay , *IMMUNOGLOBULIN G , *THORACIC aorta , *PATIENTS - Abstract
Background: Patients with chronic kidney disease have an increased cardiovascular risk that is not fully explained by traditional risk factors but appears to be related to increased arterial stiffness. Cytomegalovirus (CMV) infection is associated with increased cardiovascular risk although the mechanisms for this are unknown. We examined whether CMV seropositivity was associated with increased arterial stiffness in patients with chronic kidney disease. Methodology and Principal Findings: In 215 non-diabetic patients with chronic kidney disease, CMV seropositivity was determined using an anti-CMV IgG ELISA. Pulse wave velocity was measured and aortic distensibility assessed in the ascending, proximal descending and distal descending thoracic aorta. Patients seropositive for CMV had a higher pulse wave velocity and lower aortic distensibility at all 3 levels. These differences (except for ascending aortic distensibility) persisted in a subcohort matched for age, gender and renal function, and when the whole cohort was divided into quartiles of age. In multivariable analyses, CMV seropositivity was an independent determinant of pulse wave velocity and proximal and distal descending aortic distensibility. Conclusions: In patients with chronic kidney disease, CMV seropositivity is associated with increased arterial stiffness and decreased distensibility of the proximal descending and distal aorta. These findings suggest that further research is required to examine CMV as a possible cause of arterial disease and increased cardiovascular risk in patients with CKD and may be relevant more widely for CMV seropositive patients with normal renal function. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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39. Endothelial dysfunction and cardiovascular disease in early-stage chronic kidney disease: Cause or association?
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Moody, William E., Edwards, Nicola C., Madhani, Melanie, Chue, Colin D., Steeds, Richard P., Ferro, Charles J., and Townend, Jonathan N.
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CARDIOVASCULAR diseases , *ENDOTHELIUM , *KIDNEY diseases , *GLOMERULAR filtration rate , *HYPERTENSION , *DIABETES , *DISEASE progression , *PATHOLOGICAL physiology - Abstract
Abstract: Chronic kidney disease (CKD) is strongly associated with cardiovascular disease (CVD); a graded inverse relationship between estimated glomerular filtration rate (eGFR) and cardiovascular event rates has emerged from large-scale observational studies. Chronic kidney disease is also associated with endothelial dysfunction (ED) although the precise relationship with GFR and the “threshold” at which ED begins are contentious. Abnormal endothelial function is certainly present in late-stage CKD but data in early-stage CKD appear confounded by disease states such as diabetes and hypertension which themselves promote ED. Thus, the direct effect of a reduction in GFR on endothelial function and, therefore, cardiovascular (CV) risk is far from completely established. In human studies, the precise duration of kidney impairment is seldom known and the onset of CVD often insidious, making it difficult to determine exactly when CVD first appears in the context of CKD. Kidney donors provide a near-ideal experimental model of CKD; subjects undergo an acute change from normal to modestly impaired renal function at the time of nephrectomy and lack the confounding co-morbidity that has made observational studies of CKD patients so challenging to interpret. By examining changes in endothelial function in living kidney donors before and after nephrectomy, useful insight might be gained into the pathophysiology of CVD in CKD and help determine whether targeting ED or the renal disease itself has the potential to reduce CV risk. [Copyright &y& Elsevier]
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- 2012
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40. Aortic Calcification and Femoral Bone Density Are Independently Associated with Left Ventricular Mass in Patients with Chronic Kidney Disease.
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Chue, Colin D., Wall, Nadezhda A., Crabtree, Nicola J., Zehnder, Daniel, Moody, William E., Edwards, Nicola C., Steeds, Richard P., Townend, Jonathan N., and Ferro, Charles J.
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CALCIFICATION , *AORTIC valve , *BONE density , *KIDNEY diseases , *CARDIOVASCULAR diseases risk factors - Abstract
Background: Vascular calcification and reduced bone density are prevalent in chronic kidney disease and linked to increased cardiovascular risk. The mechanism is unknown. We assessed the relationship between vascular calcification, femoral bone density and left ventricular mass in patients with stage 3 non-diabetic chronic kidney disease in a crosssectional observational study. Methodology and Principal Findings: A total of 120 patients were recruited (54% male, mean age 55±14 years, mean glomerular filtration rate 50613 ml/min/1.73 m2). Abdominal aortic calcification was assessed using lateral lumbar spine radiography and was present in 48%. Mean femoral Z-score measured using dual energy x-ray absorptiometry was 0.60±1.06. Cardiovascular magnetic resonance imaging was used to determine left ventricular mass. One patient had left ventricular hypertrophy. Subjects with aortic calcification had higher left ventricular mass compared to those without (56±16 vs. 48612 g/m2, P = 0.002), as did patients with femoral Z-scores below zero (56±15 vs. 49±13 g/m2, P = 0.01). In univariate analysis presence of aortic calcification correlated with left ventricular mass (r = 0.32, P = 0.001); mean femoral Zscore inversely correlated with left ventricular mass (r =-0.28, P = 0.004). In a multivariate regression model that included presence of aortic calcification, mean femoral Z-score, gender and 24-hour systolic blood pressure, 46% of the variability in left ventricular mass was explained (P<0.001). Conclusions: In patients with stage 3 non-diabetic chronic kidney disease, lower mean femoral Z-score and presence of aortic calcification are independently associated with increased left ventricular mass. Further research exploring the pathophysiology that underlies these relationships is warranted [ABSTRACT FROM AUTHOR]
- Published
- 2012
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41. The safety and tolerability of spironolactone in patients with mild to moderate chronic kidney disease.
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Edwards, Nicola C., Steeds, Richard P., Chue, Colin D., Stewart, Paul M., Ferro, Charles J., and Townend, Jonathan N.
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SPIRONOLACTONE , *KIDNEY diseases , *BLOOD pressure , *ANGIOTENSIN converting enzyme , *BIOMARKERS - Abstract
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Spironolactone has recently been shown to exert beneficial effects on the cardiovascular and renal systems. To date, its use in patients with chronic kidney disease has been limited due to potential risks of hyperkalaemia and declining renal dysfunction. WHAT THIS STUDY ADDS • Non-diabetic patients with early stage chronic kidney disease (CKD) on concomitant therapy with angiotensin converting enzyme (ACE) inhibition or angiotensin II receptor blockade with a serum potassium of <5.5 mmol/L and no history of hyperkalaemia who were randomized in a trial to treatment with spironolactone for 40 weeks had low rates of serious hyperkalaemia (<1%) and worsening renal function (<3%). Frequent biochemical monitoring is required for the initial 4 weeks but only routine monitoring is needed thereafter. AIM Mineralocorticoid receptor blockade (MRBs) in combination with angiotensin converting enzyme (ACE) inhibitors and angiotensin-II receptor blockade (ARBs) improve prognostic markers of cardiovascular and renal disease in early stage chronic kidney disease (CKD). Concerns relating to the safety and tolerability of MRBs in CKD may limit their use in a non clinical trial setting. METHODS In the Chronic Renal Impairment in Birmingham II study, 115 patients with non-diabetic early stage CKD (eGFR 30-89 ml/min/1.73m2) received 25 mg daily of spironolactone for 4 weeks before randomization to continuing treatment or placebo for a further 36 weeks. All patients were on ACE inhibitors and/or ARB therapy. Potassium and renal function were checked at weeks 1, 2, 4, 8, 16, 28 and 40. The incidence of hyperkalaemia, significant renal dysfunction (reduction eGFR ≥25%) and adverse effects was assessed. RESULTS After 40 weeks of treatment the incidence of serious hyperkalaemia (K+≥6.0 mmol/L) was <1%. A potassium 5.5-5.9 mmol/L occurred on ≥1 occasion over follow-up in 11 patients (nine on spironolactone) and was predicted by baseline potassium ≥5.0 mmol/L and eGFR ≤45 ml/min/1.73m2. Over follow-up, three patients experienced significant renal dysfunction but no patients withdrew due to intolerance or side effects. Changes in potassium, eGFR and systolic blood pressure were most apparent in the first 4 eeks. CONCLUSION Spironolactone was well tolerated in selected patients with early stage CKD. Strict monitoring over the first month of treatment followed by standard surveillance as for ACE inhibitors and ARBs is suggested. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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42. Serum phosphate is associated with left ventricular mass in patients with chronic kidney disease: a cardiac magnetic resonance study.
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Chue, Colin D., Edwards, Nicola C., Moody, William E., Steeds, Richard P., Townend, Jonathan N., and Ferro, Charles J.
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KIDNEY disease risk factors , *PHOSPHATES , *LEFT heart ventricle , *BLOOD serum analysis , *ARTERIAL diseases , *MAGNETIC resonance imaging - Abstract
Objective To explore the relationship between serum phosphate, arterial stiffness and left ventricular mass (LVM) in patients with early-stage chronic kidney disease (CKD). Design A cross-sectional observational study. Setting Single centre. Patients 208 patients with stage 2 to stage 4 non-diabetic CKD. Interventions Arterial stiffness was determined through measurement of aortic pulse wave velocity (PWV). Cardiac magnetic resonance was used to determine LVM. Main outcome measure Relationship between serum phosphate, aortic PWV and LVM. Results Mean age was 54±13 years, mean glomerular filtration rate was 50±15 ml/min/1.73 m², mean serum phosphate was 1.11±0.21 mmol/l and mean PWV was 8.6±2.1 m/s. When the cohort was divided into quartiles according to serum phosphate, LVM increased across quartiles (p=0.04), with no significant differences in age, kidney function, blood pressure or PWV. Serum phosphate correlated with LVM (r=0.173; p=0.01), but PWV did not (p=0.2). In a regression model containing gender, serum phosphate, office systolic blood pressure, albumin/creatinine ratio and haemoglobin, 30% of the variation in LVM was explained (p<0.0005), with serum phosphate accounting for 5% of the variance. Conclusion Serum phosphate is independently associated with LVM in patients with CKD. Interventional studies are required to determine whether this association is causative and whether reducing phosphate exposure reduces LVM in this population. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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43. Serum phosphate but not pulse wave velocity predicts decline in renal function in patients with early chronic kidney disease.
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Chue, Colin D., Edwards, Nicola C., Davis, Laura J., Steeds, Richard P., Townend, Jonathan N., and Ferro, Charles J.
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KIDNEY diseases , *KIDNEY function tests , *CARDIOVASCULAR diseases risk factors , *SERUM , *BIOMARKERS , *ARTERIAL diseases , *PHOSPHATES , *DIALYSIS (Chemistry) - Abstract
Background. The rate of decline in kidney function is a powerful predictor of cardiovascular risk in patients with chronic kidney disease (CKD). Serum phosphate and increased arterial stiffness are associated with elevated cardiovascular risk in CKD and the general population. We sought to determine whether serum phosphate and markers of arterial stiffness predict progression of renal dysfunction in patients with early CKD.Methods. Two hundred and twenty-five patients with Stage II–IV CKD were prospectively followed up at University Hospital Birmingham. Serum phosphate was measured at baseline and arterial stiffness was determined through measurement of aortic pulse wave velocity (PWV) and augmentation index (AIx). Progression of renal dysfunction was defined as the slope of estimated glomerular filtration rate (eGFR) against time. We determined the associations between possible predictors and rate of progression and also examined a combined end point of start of dialysis or ≥25% decline in eGFR.Results. Mean baseline eGFR was 43 ± 19 mL/min/1.73 m2 and serum phosphate 1.22 ± 0.27 mmol/L. Median follow-up was 924 days. Serum phosphate independently predicted a greater decline in eGFR; a 1 mmol/L increment in serum phosphate was associated with a 0.34 mL/min/month steeper decline (P = 0.02). Brachial and aortic systolic pressure independently predicted the rate of renal function decline but aortic PWV and AIx had no significant influence. Forty-one patients (18%) reached the combined end point; serum phosphate was significantly higher in this group (1.32 ± 0.36 versus 1.19 ± 0.24 mmol/L, P = 0.04) and was an independent predictor for the combined end point.Conclusions. Serum phosphate independently predicts decline in renal function in early CKD. Further studies are required to determine the mechanisms involved and to investigate the potential benefits of phosphate lowering on preserving kidney function. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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44. Effect of Spironolactone on Left Ventricular Systolic and Diastolic Function in Patients With Early Stage Chronic Kidney Disease
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Edwards, Nicola C., Ferro, Charles J., Kirkwood, Helen, Chue, Colin D., Young, Alistair A., Stewart, Paul M., Steeds, Richard P., and Townend, Jonathan N.
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SPIRONOLACTONE , *LEFT heart ventricle , *KIDNEY diseases , *CARDIOVASCULAR diseases risk factors , *ALDOSTERONE , *MINERALOCORTICOIDS , *ANGIOTENSINS , *BIOMARKERS , *INFLAMMATION - Abstract
Patients with early chronic kidney disease (CKD) have an increased risk for cardiovascular disease. Aldosterone levels are elevated and might impair ventricular function through adverse myocardial and vascular proinflammatory and fibrotic effects. In the Chronic Renal Impairment in Birmingham II (CRIB II) study, it was hypothesized that mineralocorticoid receptor blockade with spironolactone in addition to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers would improve left ventricular (LV) function and markers of inflammation, ventricular stretch, and collagen turnover in early CKD. A total of 112 patients with early CKD were randomized to spironolactone 25 mg/day or placebo for 40 weeks. Ventricular function was assessed by echocardiography and cardiac magnetic resonance imaging tagging. High-sensitivity C-reactive protein, N-terminal–pro-B-type natriuretic peptide, and aminoterminal propeptide of type III procollagen were measured. Spironolactone improved LV long-axis systolic function (Sm 8.2 ± 1.4 vs 7.7 ± 1.3 cm/s, p <0.05), torsion (7.77 ± 1.61° vs 6.77 ± 1.48°, p <0.05), and myocardial deformation (strain rate −1.14 ± 0.24 vs −1.09 ± 0.20 s−1, p <0.05) compared to placebo, without a change in the ejection fraction. Markers of LV relaxation (E/e′ ratio 7.2 ± 2.3 vs 8.5 ± 2.3, p <0.05) and suction (M-mode propagation velocity 56 ± 12 vs 50 ± 12 cm/s, p <0.05) were also improved. Spironolactone reduced N-terminal–pro-B-type natriuretic peptide (24.8 pmol/L [range 0.4 to 122.4] vs 39.4 pmol/L [range 10.8 to 102.4], p <0.01) and attenuated an increase in aminoterminal propeptide of type III procollagen observed with placebo. In conclusion, spironolactone improves markers of regional LV systolic and diastolic function in early CKD. [Copyright &y& Elsevier]
- Published
- 2010
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45. The effect of spironolactone upon corticosteroid hormone metabolism in patients with early stage chronic kidney disease.
- Author
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Hammer, Fabian, Edwards, Nicola C., Hughes, Beverly A., Steeds, Richard P., Ferro, Charles J., Townend, Jonathan N., and Stewart, Paul M.
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SPIRONOLACTONE , *CORTICOSTEROIDS , *CARDIAC patients , *KIDNEY diseases , *STEROID hormones , *ANGIOTENSINS , *PATIENTS - Abstract
Context Aldosterone has emerged as an important mediator of disease progression and mortality in patients with chronic heart and kidney disease (CKD). Despite the increasing use of mineralocorticoid receptor antagonists in these patients, little is known about the effects on corticosteroid hormone secretion and metabolism. Objective To assess corticosteroid hormone secretion and metabolism in patients with early stage CKD before and after spironolactone (Spiro). Design Randomized, double-blind, placebo-controlled interventional study. Setting Single tertiary referral centre. Patients A total of 112 patients with stable stage 2/3 CKD. Interventions Patients were randomized to receive either Spiro 25 mg once daily or placebo for 36 weeks. Main outcome measures Plasma renin activity (PRA), angiotensin II (AngII) and steroid hormones were analysed by standard assays; urinary corticosteroid hormone metabolites (5α+5β-tetrahydro-cortisol (5α+5β-THF), TH-cortisone (THE), 3α5β-TH-aldosterone (TH-Aldo), 5α+5β-TH-deoxycorticosterone (5α+5β-TH-DOC), TH-11-desoxycortisol (THS)) were analysed by gas chromatography/mass spectrometry. Results Plasma aldosterone concentration (PAC) was inversely correlated with eGFR ( r = −0·331, P < 0·001). Urinary 24-h excretion of TH-Aldo was correlated with PAC ( r = 0·214, P < 0·05) and diastolic blood pressure (BP) ( r = 0·212, P = <0·05), whereas total 24-h urinary cortisol metabolite excretion was correlated with systolic BP ( r = 0·316, P < 0·01). In addition, 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 activity (urinary 5α+5β-THF)/THE) ratio) was correlated with PRA ( r = 0·277, P < 0·01). Spiro treatment significantly reduced BP (123 ± 11/76 ± 7 vs 119 ± 11/73 ± 8 mmHg, P < 0·01) despite renin-angiotensin-aldosterone system induction, reflected by increased urinary 24-h TH-Aldo excretion (17·6 (12, 86) vs 26 (18, 80) μg/24 h, P < 0·05). By contrast, Spiro had no effect on total urinary cortisol metabolite excretion, 11β-hydroxylase, 11β-HSD type 1 and 2 activity. Conclusions Aldo and cortisol are positively associated with BP suggesting that adrenal hyperactivity may in part explain the increased cardiovascular risk in patients with early end-stage CKD. Addition of Spiro had no effect on glucocorticoid metabolism or total 24-h corticosteroid production. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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46. Prevalence and risk factors for pulmonary arterial hypertension in patients with lupus.
- Author
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Prabu, Athiveeraramapandian, Patel, Kiran, Chee-Seng Yee, Nightingale, Peter, Situnayake, Rohan D., Thickett, David R., Townend, Jonathan N., and Gordon, Caroline
- Published
- 2009
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47. Effect of Spironolactone on Left Ventricular Mass and Aortic Stiffness in Early-Stage Chronic Kidney Disease: A Randomized Controlled Trial
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Edwards, Nicola C., Steeds, Richard P., Stewart, Paul M., Ferro, Charles J., and Townend, Jonathan N.
- Subjects
- *
SPIRONOLACTONE , *PHARMACODYNAMICS , *LEFT heart ventricle , *AORTIC valve diseases , *CHRONIC kidney failure , *HEART diseases , *THERAPEUTICS , *RANDOMIZED controlled trials , *ACE inhibitors - Abstract
Objectives: We sought to determine whether the addition of spironolactone to angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) improves left ventricular mass and arterial stiffness in early-stage chronic kidney disease (CKD). Background: Chronic kidney disease is associated with a high risk of cardiovascular disease and a high prevalence of left ventricular hypertrophy and arterial stiffness that confer an adverse prognosis. It is believed that these abnormalities are in part a result of activation of the renin-angiotensin-aldosterone system. Methods: After an active run-in phase with spironolactone 25 mg once daily, 112 patients with stage 2 and 3 CKD with good blood pressure control (mean daytime ambulatory blood pressure <130/85 mm Hg) on established treatment with ACE inhibitors or ARBs were randomized to continue spironolactone or to receive a matching placebo. Left ventricular mass (cardiac magnetic resonance) and arterial stiffness (pulse wave velocity/analysis, aortic distensibility) were measured before run in and after 40 weeks of treatment. Results: Compared with placebo, the use of spironolactone resulted in significant improvements in left ventricular mass (−14 ± 13 g vs. +3 ± 11 g, p < 0.01), pulse wave velocity (−0.8 ± 1.0 m/s vs. −0.1 ± 0.9 m/s, p < 0.01), augmentation index (−5.2 ± 6.1% vs. −1.4 ± 5.9%, p < 0.05), and aortic distensibility (0.69 ± 0.86 × 10−3 mm Hg vs. 0.04 ± 1.04 × 10−3 mm Hg, p < 0.01). Conclusions: The use of spironolactone reduces left ventricular mass and improves arterial stiffness in early-stage CKD. These effects suggest that aldosterone exerts adverse cardiovascular effects in CKD and that spironolactone is worthy of further study as a treatment that could reduce adverse cardiovascular events. (Is Spironolactone Safe and Effective in the Treatment of Cardiovascular Disease in Mild Chronic Renal Failure; NCT00291720) [Copyright &y& Elsevier]
- Published
- 2009
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48. Acute aldosterone antagonism improves cardiac vagal control in humans
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Fletcher, Janine, Buch, Ashesh N., Routledge, Helen C., Chowdhary, Saqib, Coote, John H., and Townend, Jonathan N.
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ALDOSTERONE , *CARDIAC arrest , *MINERALOCORTICOIDS , *DISEASE complications - Abstract
: ObjectivesWe have examined the acute effects (<45 min) of aldosterone antagonism on heart rate variability and baroreflex sensitivity, markers of cardiac vagal control, in 13 healthy subjects.: BackgroundEvidence for the beneficial effects of aldosterone antagonists comes from studies showing increased survival rates following their addition to standard heart failure therapy. Many mechanisms have been suggested for this action, including effects upon the autonomic nervous system.: MethodsHeart rate variability and baroreflex sensitivity were examined 30 min following the administration of potassium canrenoate (intravenous) (aldosterone antagonist) or saline (control).: ResultsActive treatment reduced resting heart rate (−6 ± 1 beats/min [mean ± standard error mean]) compared to control (0 ± 1 beat/min) (p < 0.001) and increased measures of high frequency (HF) heart rate variability. Root mean square of successive RR interval differences increased by 21 ± 5 ms versus −6 ± 5 ms control (p < 0.001); HF power increased by 1,369 ± 674 ms2with aldosterone antagonism compared to −255 ± 431 ms2 following saline infusion (p < 0.01). Baroreflex sensitivity (alpha-HF) was increased after active treatment (+4 ± 2 ms/mm Hg vs. 0 ± 1 ms/mm Hg control [p < 0.05]). No changes in plasma potassium levels were observed.: ConclusionsThese results provide evidence that aldosterone antagonists acutely improve cardiac vagal control, irrespective of any diuretic effects, and may in part explain their beneficial effects in treatment of heart failure. [Copyright &y& Elsevier]
- Published
- 2004
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49. Effects of nitroglycerin treatment on cardiac autonomic control in heart failure.
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Buch, Ashesh N., Chowdhary, Saqib, Coote, John H., and Townend, Jonathan N.
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NITRIC oxide , *HEART failure , *NITROGLYCERIN , *INNERVATION of the heart , *HEART conduction system , *HEART beat , *AUTONOMIC nervous system - Abstract
There is substantial animal data suggesting that nitric oxide (NO) has an important role as a modulator of cardiac autonomic control with a net vagotonic and sympatholytic role. Recent human work would support this concept. This study investigated the effects of the NO donor glyceryl trinitrate (GTN) upon measures of cardiac vagal activity in heart failure. Twelve stable chronic heart failure patients were studied in a randomised double blind, placebo controlled crossover study to assess the effects of chronic treatment with transdermal GTN (10 mg per day) on heart rate variability (HRV) measures of cardiac vagal activity. No significant difference between GTN and placebo was observed in mean arterial blood pressure and most measures of HRV and baroreflex sensitivity (BRS). BRS measured by the alpha-LF index showed a small rise. In conclusion, chronic GTN administration does not produce a significant increase in HRV measures of cardiac vagal activity in patients with heart failure. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
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50. Impaired circumferential and longitudinal myocardial deformation in early stage chronic kidney disease: the earliest features of uremic cardiomyopathy.
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Edwards, Nicola C., Noori, Abdullah, Chue, Colin D., Moody, William E., Ferro, Charles J., Townend, Jonathan N., and Steeds, Richard
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CHRONIC kidney failure , *CONFERENCES & conventions , *MAGNETIC resonance imaging , *CARDIOMYOPATHIES , *UREMIA , *DISEASE complications , *DIAGNOSIS - Abstract
An abstract of the article "Impaired circumferential and longitudinal myocardial deformation in early stage chronic kidney disease: the earliest features of uremic cardiomyopathy," by Nicola C. Edwards and colleagues is presented.
- Published
- 2013
- Full Text
- View/download PDF
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