| 9861. |
- McGreevy, David, 1988-, et al.
(författare)
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Metabolic Response to Claudication in Peripheral Arterial Disease : a Microdialysis pilot study
- 2019
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Ingår i: Annals of Vascular Surgery. - : Elsevier. - 0890-5096 .- 1615-5947. ; 58, s. 134-141
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: In a pilot study investigate the possible use of microdialysis in the calf muscle to assess the metabolic response to intermittent claudication (IC). In addition, evaluate the simultaneous systemic inflammatory reaction.METHODS: With one microdialysis catheter in the gastrocnemic muscle and one subcutaneously in the pectoral region (as a reference), and a peripheral venous catheter, dialysate and venous blood sampling was performed before, during and after walking on a treadmill to maximal tolerable claudication (controls 10 minutes).RESULTS: A total of 9 participants were recruited, six patients with IC and three healthy controls. At baseline, IC and control subjects did not differ in metabolic findings (glucose, lactate, pyruvate, glycerol) in the gastrocnemic muscle. Subcutaneous glucose concentration was higher in controls. After physical exertion, gastrocnemic and subcutaneous glycerol, lactate and pyruvate concentrations increased in IC subjects. Plasma concentrations of Tumor Necrosis Factor--α (TNF- α), Interleucin-6 (IL-6), Interleucin-1ß (IL-1ß), Hepatocyte Growth Factor (HGF) and Vascular Endothelial Growth Factor (VEGF) were higher in IC subjects at baseline, and TNF-α, (IL-6) and Interleukin-18 (IL-18) increased after walking as did IL-6 and (IL-1ß) in controls. The muscle catheters did not show any signs of causing harm.CONCLUSIONS: Microdialysis can be used to study the ongoing metabolic response during walking and claudication. Our results suggest both an acute local and a systemic inflammatory reaction during development of claudication pain.
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| 9862. |
- McLeod, Olga, et al.
(författare)
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Genetic loci on chromosome 5 are associated with circulating levels of interleukin-5 and eosinophil count in a European population with high risk for cardiovascular disease
- 2016
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Ingår i: Cytokine. - : Elsevier BV. - 1043-4666 .- 1096-0023. ; 81, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- IL-5 is a Th2 cytokine which activates eosinophils and is suggested to have an atheroprotective role. Genetic variants in the IL5 locus have been associated with increased risk of CAD and ischemic stroke. In this study we aimed to identify genetic variants associated with IL-5 concentrations and apply a Mendelian randomisation approach to assess IL-5 levels for causal effect on intima-media thickness in a European population at high risk of coronary artery disease. We analysed SNPs within robustly associated candidate loci for immune, inflammatory, metabolic and cardiovascular traits. We identified 2 genetic loci for IL-5 levels (chromosome 5, rs56183820, BETA = 0.11, P = 6.73E(-5) and chromosome 14, rs4902762, BETA = 0.12, P= 5.76E(-6)) and one for eosinophil count (rs72797327, BETA = -0.10, P = 1.41E(-6)). Both chromosome 5 loci were in the vicinity of the IL5 gene, however the association with IL-5 levels failed to replicate in a meta-analysis of 2 independent cohorts (rs56183820, BETA = 0.04, P= 0.2763, I-2 = 24, I-2 - P = 0.2516). No significant associations were observed between SNPs associated with IL-5 levels or eosinophil count and IMT measures. Expression quantitative trait analyses indicate effects of the IL-5 and eosinophil-associated SNPs on RAD50 mRNA expression levels (rs12652920 (r2 = 0.93 with rs56183820) BETA = -0.10, P = 8.64E(-6) and rs11739623 (r2 = 0.96 with rs72797327) BETA = -0.23, P = 1.74E(-29), respectively). Our data do not support a role for IL-5 levels and eosinophil count in intima-media thickness, however SNP5 associated with IL-5 and eosinophils might influence stability of the atherosclerotic plaque via modulation of RAD50 levels.
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| 9863. |
- McLeod, Olga, et al.
(författare)
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Plasma autoantibodies against apolipoprotein B-100 peptide 210 in subclinical atherosclerosis.
- 2014
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 232:1, s. 242-248
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Tidskriftsartikel (refereegranskat)abstract
- Experimental studies have suggested that autoimmunity is involved in atherosclerosis and provided evidence that both protective and pro-atherogenic immune responses exist. This concept has received support from small clinical studies implicating autoantibodies directed against apolipoprotein B-100 (apoB-100) in human atherosclerosis. We examined circulating autoantibodies directed against native and malondialdehyde (MDA)-modified epitope p210 of apoB-100 (IgG-p210nat and IgM-p210MDA) in relation to early atherosclerosis in a large, European longitudinal cohort study of healthy high-risk individuals.
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| 9864. |
- McMahon, Colin J, et al.
(författare)
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Paediatric and adult congenital cardiology education and training in Europe.
- 2022
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Ingår i: Cardiology in the young. - 1467-1107. ; 32:12, s. 1966-1983
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Tidskriftsartikel (refereegranskat)abstract
- Limited data exist on training of European paediatric and adult congenital cardiologists.A structured and approved questionnaire was circulated to national delegates of Association for European Paediatric and Congenital Cardiology in 33 European countries.Delegates from 30 countries (91%) responded. Paediatric cardiology was not recognised as a distinct speciality by the respective ministry of Health in seven countries (23%). Twenty countries (67%) have formally accredited paediatric cardiology training programmes, seven (23%) have substantial informal (not accredited or certified) training, and three (10%) have very limited or no programme. Twenty-two countries have a curriculum. Twelve countries have a national training director. There was one paediatric cardiology centre per 2.66 million population (range 0.87-9.64 million), one cardiac surgical centre per 4.73 million population (range 1.63-10.72 million), and one training centre per 4.29 million population (range 1.63-10.72 million population). The median number of paediatric cardiology fellows per training programme was 4 (range 1-17), and duration of training was 3 years (range 2-5 years). An exit examination in paediatric cardiology was conducted in 16 countries (53%) and certification provided by 20 countries (67%). Paediatric cardiologist number is affected by gross domestic product (R2 = 0.41).Training varies markedly across European countries. Although formal fellowship programmes exist in many countries, several countries have informal training or no training. Only a minority of countries provide both exit examination and certification. Harmonisation of training and standardisation of exit examination and certification could reduce variation in training thereby promoting high-quality care by European congenital cardiologists.
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| 9865. |
- McMurray, J. J., et al.
(författare)
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Design of the Reduction of Events with Darbepoetin alfa in Heart Failure (RED-HF): a Phase III, anaemia correction, morbidity-mortality trial
- 2009
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Ingår i: European Journal of Heart Failure. - 1879-0844. ; 11:8, s. 795-801
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with heart failure (HF) and anaemia have greater functional impairment, worse symptoms, increased rates of hospital admission, and a higher risk of death, compared with non-anaemic HF patients. Whether correcting anaemia can improve outcomes is unknown. OBJECTIVE: The Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF; Clinical Trials.gov NCT 003 58215) was designed to evaluate the effect of the long-acting erythropoietin-stimulating agent darbepoetin alfa on mortality and morbidity (and quality of life) in patients with HF and anaemia. METHODS: Approximately 2600 patients with New York Heart Association class II-IV, an ejection fraction < or =40%, and a haemoglobin (Hb) consistently < or =12.0 g/dL but > or =9.0 g/dL will be enrolled. Patients are randomized 1:1 to double-blind subcutaneous administration of darbepoetin alfa or placebo. Investigators are also blinded to Hb measurements and darbepoetin alfa is dosed to achieve an Hb concentration of 13.0 g/dL (but not exceeding 14.5 g/dL) with sham adjustments of the dose of placebo. The primary endpoint is the time to death from any cause or first hospital admission for worsening HF, whichever occurs first. The study will complete when approximately 1150 subjects experience a primary endpoint.
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| 9866. |
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| 9867. |
- McMurray, John J, et al.
(författare)
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Effect of valsartan on the incidence of diabetes and cardiovascular events
- 2010
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 362:16, s. 1477-1490
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance. METHODS: In this double-blind, randomized clinical trial with a 2-by-2 factorial design, we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily) or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then followed the patients for a median of 5.0 years for the development of diabetes (6.5 years for vital status). We studied the effects of valsartan on the occurrence of three coprimary outcomes: the development of diabetes; an extended composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina; and a core composite outcome that excluded unstable angina and revascularization. RESULTS: The cumulative incidence of diabetes was 33.1% in the valsartan group, as compared with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.43) or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86 to 1.14; P=0.85). CONCLUSIONS: Among patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events. (ClinicalTrials.gov number, NCT00097786.)
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| 9868. |
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| 9869. |
- McMurray, J. J., et al.
(författare)
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Relationship of dose of background angiotensin-converting enzyme inhibitor to the benefits of candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added trial
- 2006
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Ingår i: American heart journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 151:5, s. 985-91
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Whether an angiotensin receptor blocker is of benefit when added to a full dose of angiotensin-converting enzyme (ACE) inhibitor in heart failure (HF) is uncertain. METHODS: The effect of candesartan, compared with placebo, in 2548 patients randomized in the CHARM-Added trial was analyzed according to (i) ACE inhibitor dose at baseline, (ii) ACE inhibitor dose during follow-up, and (iii) combination treatment with ACE inhibitor and beta-blocker at baseline. The main outcome was the composite of cardiovascular death or HF hospitalization. RESULTS: The benefit of candesartan was not modified by the dose of ACE inhibitor. In all patients (n = 2548), the candesartan/placebo hazard ratio (HR) for the primary outcome was 0.85 (95% CI 0.75-0.96). In patients taking a guideline recommended dose of ACE inhibitor at baseline (n = 1291), this HR was 0.79 (95% CI 0.67-0.95; interaction P value .26). In patients taking a Food and Drug Administration-designated maximum dose of ACE inhibitor (n = 529), this HR was 0.75 (95% CI 0.57-0.98; interaction P value .29). The benefit of candesartan was preserved in patients taking beta-blockers in addition to a higher dose of ACE inhibitor and in patients maintaining a high dose of ACE inhibitor throughout follow-up. CONCLUSIONS: These clinical findings support the pharmacologic evidence that ACE inhibitors and angiotensin receptor blockers have distinct mechanisms of action and show that their combined use improves outcomes in patients with HF more than an evidence-based dose of ACE inhibitor alone.
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| 9870. |
- McMurray, J. J., et al.
(författare)
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Resource utilization and costs in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme
- 2006
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 27:12, s. 1447-58
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: More treatments are needed to improve clinical outcomes in chronic heart failure (HF). It is, however, important that treatments for a condition as common as HF are affordable. We have carried out a prospective economic analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. METHODS AND RESULTS: Patients with NYHA class II-IV HF and LVEF < or =0.40 were randomized to CHARM-Alternative if intolerant of an ACE-inhibitor or to CHARM-Added if taking an ACE-inhibitor. Patients with a LVEF >0.40 were randomized in CHARM-Preserved. Each trial compared the effect of candesartan to placebo on the primary outcome of cardiovascular death or HF hospitalization. Detailed information was prospectively collected on hospital admissions, procedures/operations and drugs. A cost-consequence analysis was performed for France, Germany and the UK for CHARM-Overall and a cost-effectiveness analysis for the low LVEF trials. The cost of candesartan was substantially offset by a reduction in hospital admissions, especially for HF. In the cost-consequence analysis, candesartan was cost-saving in most scenarios for CHARM-Alternative and Added but the marginal annual net cost per patient was upto 372 euros per year in CHARM-Preserved, in which candesartan did not reduce the primary outcome significantly. In the cost-effectiveness analysis of patients with a LVEF < or = 0.40, candesartan was cost-saving in some scenarios and in the others the maximum cost per life year gained was 3881 euros. CONCLUSION: Candesartan improves functional class, reduces the risk of hospital admission, and increases survival in patients with a HF and a LVEF < or =0.40 at an acceptable cost.
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