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AIMS: The provision of high-quality education allows the European Society of Cardiology (ESC) to achieve its mission of better cardiovascular practice and provides an essential component of translating new evidence to improve outcomes. METHODS AND RESULTS: The 4th ESC Education Conference, held in Sophia Antipolis (December 2016), brought together ESC education leaders, National Directors of Training of 43 ESC countries, and representatives of the ESC Young Community. Integrating national descriptions of education and cardiology training, we discussed innovative pathways to further improve knowledge and skills across different training programmes and health care systems. We developed an ESC roadmap supporting better cardiology training and continued medical education (CME), noting: (i) The ESC provides an excellent framework for unbiased and up-to-date cardiovascular education in close cooperation with its National Societies. (ii) The ESC should support the harmonization of cardiology training, curriculum development, and professional dialogue and mentorship. (iii) ESC congresses are an essential forum to learn and discuss the latest developments in cardiovascular medicine. (iv) The ESC should create a unified, interactive educational platform for cardiology training and continued cardiovascular education combining Webinars, eLearning Courses, Clinical Cases, and other educational programmes, along with ESC Congress content, Practice Guidelines and the next ESC Textbook of Cardiovascular Medicine. (v) ESC-delivered online education should be integrated into National and regional cardiology training and CME programmes. CONCLUSION: These recommendations support the ESC to deliver excellent and comprehensive cardiovascular education for the next generation of specialists. Teamwork between international, national and local partners is essential to achieve this objective.
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Cardiologia , Educação Médica Continuada/organização & administração , Sociedades Médicas/organização & administração , Cardiologia/educação , Cardiologia/organização & administração , Europa (Continente) , Humanos , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: Recruitment challenges contribute to the paucity of palliative care research with advanced chronic heart failure patients. AIM: To describe the challenges and outline strategies of recruiting advanced chronic heart failure patients. DESIGN: A feasibility study using a pre-post uncontrolled design. SETTING: Advanced chronic heart failure patients were recruited at two nurse-led chronic heart failure disease management clinics in Ireland Results: Of 372 patients screened, 81 were approached, 38 were recruited (46.9% conversion to consent) and 25 completed the intervention. To identify the desired population, a modified version of the European Society of Cardiology definition was used together with modified New York Heart Association inclusion criteria to address inter-study site New York Heart Association classification subjectivity. These modifications substantially increased median monthly numbers of eligible patients approached (from 8 to 20) and median monthly numbers recruited (from 4 to 9). Analysis using a mortality risk calculator demonstrated that recruited patients had a median 1-year mortality risk of 22.7 and confirmed that the modified eligibility criteria successfully identified the population of interest. A statistically significant difference in New York Heart Association classification was found in recruited patients between study sites, but no statistically significant difference was found in selected clinical parameters between these patients. CONCLUSION: Clinically relevant modifications to the European Society of Cardiology definition and strategies to address New York Heart Association subjectivity may help to improve advanced chronic heart failure patient recruitment in clinical settings, thereby helping to address the paucity of palliative care research this population.
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Definição da Elegibilidade/métodos , Insuficiência Cardíaca , Cuidados Paliativos , Seleção de Pacientes , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Estudos Longitudinais , Masculino , Sujeitos da PesquisaRESUMO
BACKGROUND: Palliative care needs of patients with chronic heart failure are poorly recognised. Policy makers advise a patient-centred approach to holistically assess patients' needs and care goals. Patient-reported outcome measures are proposed to facilitate patient-centred care. AIM: To explore whether and how a palliative care-specific patient-reported outcome intervention involving the Integrated Palliative care Outcome Scale influences patients' experience of patient-centred care in nurse-led chronic heart failure disease management clinics. DESIGN: A feasibility study using a parallel mixed-methods embedded design was undertaken. The qualitative component which examined patients and nurses experience of the intervention is reported here. Semi-structured interviews were conducted and analysed using framework analysis. SETTING/PARTICIPANTS: Eligible patients attended nurse-led chronic heart failure disease management clinics in two tertiary referral centres in Ireland with New York Heart Association functional class II-IV. Nurses who led these clinics were eligible for inclusion. RESULTS: In all, 18 patients and all 4 nurses involved in the nurse-led clinics were interviewed. Three key themes were identified: identification of unmet needs, holistic assessment and patient empowerment. The intervention impacted on processes of care by enabling a shared understanding of patients' symptoms and concerns, facilitating patient-nurse communication by focusing on these unmet needs and empowering patients to become more involved in clinical discussions. CONCLUSION: This Integrated Palliative care Outcome Scale-based intervention empowered patients to become more engaged in the clinical consultation and to highlight their unmet needs. This study adds to the evidence for the mechanism of action of patient-reported outcome measures to improve patient-centred care and will help inform outcome selection for future patient-reported outcome measure research.
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Doença Crônica/enfermagem , Insuficiência Cardíaca/enfermagem , Recursos Humanos de Enfermagem Hospitalar/psicologia , Cuidados Paliativos/métodos , Satisfação do Paciente , Assistência Centrada no Paciente/métodos , Adulto , Idoso , Atitude do Pessoal de Saúde , Estudos de Viabilidade , Feminino , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Relações Enfermeiro-Paciente , Medidas de Resultados Relatados pelo Paciente , Pesquisa Qualitativa , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Alterations in the thyroid axis are frequently observed following growth hormone (GH) replacement, but uncertainty exists regarding their clinical significance. We aimed to compare fluctuations in circulating thyroid hormone levels, induced by GH, to changes in sensitive biological markers of thyroid hormone action. METHODS: This was a prospective observational clinical study. Twenty hypopituitary men were studied before and after GH replacement. Serum thyroid-stimulating hormone (TSH), thyroid hormones, and insulin-like growth factor 1 were measured. Changes in thyroid hormone concentrations were compared to alterations in resting metabolic rate and cardiac time intervals. Health-related quality of life (QOL) was assessed by disease-sensitive and generic questionnaires. RESULTS: Following GH replacement, free thyroxine concentration declined and free triiodothyronine level increased. Resting energy expenditure increased, particularly in subjects with profound hypopituitarism, including TSH deficiency (16.73 ± 1.75 kcal/kg/min vs. 17.96 ± 2.26 kcal/kg/min; P = .01). Alterations in the thyroid axis were more pronounced in subjects with a low/normal baseline respiratory quotient (RQ) who experienced a paradoxical rise in RQ (0.81 vs. 0.86; P = .01). Subjects with a high baseline RQ experienced a slight but nonsignificant fall in RQ without alteration in thyroid axis. The isovolumetric contraction time was shortened during the study; however, this did not reach statistical significance. Improvements in QOL were observed despite alterations in thyroid axis. CONCLUSION: Changes in the thyroid axis following GH replacement are associated with complex tissue-specific effects. These fluctuations may induce a hypothyroid phenotype in some tissues while appearing to improve the biological action of thyroid hormone in other organs. ABBREVIATIONS: AGHDA = Assessment of Growth Hormone Deficiency in Adulthood; CHOox = carbohydrate oxidation; ET = ejection time; fT3 = free triiodothyronine; fT4 = free thyroxine; GH = growth hormone; GHD = growth hormone deficiency; HB-RQ = high baseline respiratory quotient; HPT = hypothalamic-pituitary-thyroid; ICT = isovolumetric contraction time; IGF-1 = insulin-like growth factor 1; IRT = isovolumetric relaxation time; LB-RQ = low baseline respiratory quotient; LV = left ventricular; NHP = Nottingham Health Profile; QOL = quality of life; REE = resting energy expenditure; RQ = respiratory quotient; rT3 = reverse triiodothyronine; SF-36 = Short Form 36; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; T4 = thyroxine; TT3 = total triiodothyronine; TT4 = total thyroxine.
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Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/uso terapêutico , Hormônios Tireóideos/sangue , Adulto , Idoso , Metabolismo Energético , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica , Estudos Prospectivos , Qualidade de Vida , Hormônios Tireóideos/fisiologiaRESUMO
BACKGROUND: The goal of treating patients with coronary artery disease is to improve survival and relieve symptoms. Several studies have compared the safety and efficacy of left main coronary artery (LMCA) stenting and coronary-artery bypass grafting in case control and randomized trials. OBJECTIVE: In this study we present the long term outcome of stenting unprotected LMCA stenosis in day to day practice in unselected patients. METHODS: One hundred and fifty eight patients were prospectively recruited with symptomatic unprotected LMCA stenosis undergoing percutaneous coronary intervention (PCI). Using the euroSCORE, each patient's surgical mortality risk was estimated. Study end-points were any major adverse cardiac event (MACE) defined as cardiac death, nonfatal myocardial infarction, or target lesion revascularization at follow-up with either CABG or repeat PCI. RESULTS: The mean follow-up was 54 ± 25 months. The mean euroSCORE was 10.6 ± 13.4 (0.9-71) and the mean SYNTAX score was 39.6 ± 10.7 (10-65). The MACE rate was 11.4% at a mean follow up of 54 months. Six (3.8%) patients suffered postprocedure myocardial infarction. There were 24 (15%) deaths of which 12 were cardiac (mean euroSCORE 21.6 ± 5.5 P < 0.001). Repeat angiography was performed in 88 (55.7%) patients. Seven (4.4%) patients had in-stent restenosis; three occurred in BMS (P = 0.06). Two patients underwent revascularization with CABG and five had successful repeat PCI. CONCLUSION: In this on-going registry of high risk patients with LMCA stenosis, stenting was found to be safe and clinically effective in maintaining event-free survival.
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Estenose Coronária/terapia , Intervenção Coronária Percutânea/instrumentação , Stents , Idoso , Idoso de 80 Anos ou mais , Angiografia Coronária , Reestenose Coronária/etiologia , Estenose Coronária/diagnóstico , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
This case report demonstrates a unique case of managing complex concomitant structural cardiac issues using transcatheter techniques in a frail patient. The primary regurgitant lesion in this case caused significant right to left shunting with severely debilitating hypoxaemia for the patient, requiring high volumes of ambulatory oxygen to compensate. We would like to highlight the role of multi-modality cardiac imaging demonstrated in this case, as well as the limited surgical data and poor outcomes in advanced disease with higher peri-operative complications. Finally, it should be noted that percutaneous correction of structural lesions may provide palliative relief but carries an uncertain risk of recurrence.
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Immunomodulation by colchicine is a well-established therapy for targeting inflammatory pathways in gout, pericarditis and Behchet's disease. In more recent times, evidence has emerged demonstrating a potential role for colchicine in several cardiac conditions. This article aims to summarise the evidence behind the established guidelines for use of low-dose colchicine in pericarditis and examine the evolving evidence for its use in cardiovascular disease and most recently COVID-19.
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COVID-19 , Doenças Cardiovasculares , Pericardite , Humanos , Colchicina/uso terapêutico , Pericardite/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , RegeneraçãoRESUMO
BACKGROUND: The EU-wide, cross-sectional observational study of lipid-lowering therapy (LLT) use in secondary and primary care (DA VINCI) assessed the proportion of patients achieving low-density lipoprotein cholesterol (LDL-C) goals recommended by the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines and provided an insight into regional use of LLT in Europe, including Ireland. AIMS: This analysis focuses on data from patients in Ireland who participated in the DA VINCI study. METHODS: The DA VINCI study enrolled patients receiving LLT at primary and secondary care sites across 18 European countries between June 2017 and November 2018. The study assessed the achievement of risk-based 2016 and 2019 ESC/EAS LDL-C goals. This subgroup analysis aimed to evaluate LDL-C goal attainment in an Irish cohort of primary and secondary care patients. RESULTS: In total, 198 patients from Ireland were enrolled from three primary care and three secondary care centres. Most patients were White and male, and were receiving moderate- or high-intensity statin therapy (most frequently atorvastatin or rosuvastatin). Few patients (< 10%) were receiving combination therapy of statin and ezetimibe. Approximately 60% of patients achieved their 2016 ESC/EAC LDL-C goals while less than half the patients achieved their 2019 ESC/EAS goals. Approximately half of secondary prevention patients achieved their 2016 ESC/EAS goals and only 20% of secondary prevention patients achieved their 2019 ESC/EAS goals. CONCLUSIONS: These results highlight the disparity between dyslipidaemia management in clinical practice in Ireland and guideline recommendations. TRIAL REGISTRATION: ENCePP; EU PAS 22,075; date registered 06 February 2018.
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Aterosclerose , Cardiologia , Dislipidemias , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Masculino , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , LDL-Colesterol , Objetivos , Irlanda , Estudos Transversais , Aterosclerose/complicações , Dislipidemias/induzido quimicamente , Dislipidemias/complicações , Dislipidemias/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: Lipid disorders are now considered causal for atherosclerotic cardiovascular disease (ASCVD) which remains one of the most important contributors to morbidity and mortality in the developed world. Identification and early treatment of lipid disarrays remains the cornerstone of good clinical practice to prevent, halt and even reverse ASCVD. Guidelines for lipid management are imperative to help promote good clinical practice. Given the detail involved in comprehensive guidelines and the multiple areas of knowledge required by clinical practitioners, abbreviated, easy to understand, practical versions of guidelines are required to ensure dissemination of the most important information. The recent ESC lipid guidelines 2019 and the ESC guidelines on CVD prevention in clinical practice 2021 (1,2), provide an excellent detailed summary of all the latest evidence supporting lipid interventions that reduce ASCVD. METHOD: We therefore developed a single-page document with hyperlinks to help practitioners gain easy access to practical information on lipid management. It has been developed for future electronic use in clinical practice. CONCLUSION: It is presented here in a tabular format together with printable versions of the associated hyperlinks that provide the additional information required in decision making. It is hoped to audit the impact of this approach to help guide future ways of disseminating the latest clinical guideline updates.
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Aterosclerose , Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/prevenção & controle , LipídeosRESUMO
Myocarditis is a concerning potential consequence of COVID-19 infection, attributed to ventricular dysfunction, cardiac fibrosis, ventricular arrhythmias, cardiogenic shock, and sudden cardiac death. Recently, the Israeli Health Ministry announced that a small number of cases of myocarditis may be linked to second dose of Pfizer's BioNTech-partnered COVID-19 vaccine. The long-term impact of COVID-19 myocarditis and coronary microthrombosis which has also been described and the best therapies for these complications remain unknown. Indeed, monomorphic ventricular tachycardia and regular ventricular arrhythmias have previously been found to be more common in those recovered from myocarditis than in acute myocarditis itself. Follow-up assessment of cardiac function has been suggested for this cohort to detect and possibly prevent further cardiac events in the rehabilitation phase. Functional capacity has been shown to be a better determinant of long-term morbidity than diagnostic testing alone, but integrated approach is likely the way forward in clinical follow-up. Assessment of residual complications in the post-COVID-19 recovery phase may identify the population burden of long-term cardiac disease as a direct consequence of COVID-19.
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COVID-19 , Miocardite , Arritmias Cardíacas/diagnóstico , COVID-19/complicações , Vacinas contra COVID-19 , Estado Terminal , Humanos , Miocardite/complicações , Miocardite/diagnósticoRESUMO
Neisseria meningitidis is the leading cause of bacterial meningitis in children and young adults, with an overall mortality rate of up to 25%, but it is a rare cause of infective endocarditis. We present herein a case of N. meningitidis meningitis complicated with infective endocarditis.
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Endocardite/diagnóstico , Meningite Meningocócica/complicações , Meningite Meningocócica/diagnóstico , Neisseria meningitidis/isolamento & purificação , Adolescente , Ecocardiografia , Endocardite/microbiologia , Endocardite/patologia , Humanos , Masculino , Meningite Meningocócica/patologiaRESUMO
An 18-year-old male subject presented with recurrent strokes 3 years after percutaneous patent foramen ovale (PFO) closure with an PFO occluder device for presumed PFO-related stroke. A transesophageal echocardiogram revealed apparent device displacement during dynamic cardiac cycle. This case highlights an unusual but important delayed complication of transcatheter PFO closure. (Level of Difficulty: Intermediate.).
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 19 (COVID-19), has rapidly spread since December 2019 to become the focus of healthcare systems worldwide. Its highly contagious nature and significant mortality has led to its prioritization as a public health issue. The race to prevent and treat this disease has led to "off-label" prescribing of medications such as hydroxychloroquine, azithromycin, and Kaletra (lopinavir/ritonavir). Currently, there is no robust clinical evidence for the use of these drugs in the treatment of COVID-19, with most, if not all of these medications associated with the potential for QT interval prolongation, torsades de pointes, and resultant drug-induced sudden cardiac death. The aim of this document is to help healthcare providers mitigate the potential deleterious effects of drug-induced QTc prolongation.
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Antibacterianos/efeitos adversos , Antivirais/efeitos adversos , Azitromicina/efeitos adversos , Tratamento Farmacológico da COVID-19 , Hidroxicloroquina/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Lopinavir/efeitos adversos , Ritonavir/efeitos adversos , Torsades de Pointes/induzido quimicamente , Combinação de Medicamentos , Eletrocardiografia , Inibidores Enzimáticos/efeitos adversos , Humanos , Síndrome do QT Longo/sangue , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/prevenção & controle , Magnésio/sangue , Pandemias , Potássio/sangue , Guias de Prática Clínica como Assunto , Medição de Risco , Fatores de Risco , SARS-CoV-2RESUMO
Patients with chronic heart failure (CHF) have symptoms and concerns which are inadequately addressed. Patient-reported outcome measures (PROMs) can potentially improve the identification and management of advanced symptoms and palliative concerns. However, these have not been used in CHF. OBJECTIVES: To examine the feasibility and acceptability of using a PROM-the Integrated Palliative care Outcome Scale (IPOS)-together with heart failure nurse education and training to improve the identification and management of symptoms and concerns among patients with CHF. METHODS: A parallel, mixed methods design with an embedded qualitative component was used to examine the feasibility of recruitment, retention, intervention adherence/compliance and follow-up assessment completion (symptom burden, quality of life, psychological well-being). Patient and nurse qualitative semistructured interviews explored intervention and study design feasibility and its acceptability. RESULTS: Conversion to consent was 46.9% (372 screened, 81 approached, 38 recruited). 66% of patient participants completed the IPOS; 6% of IPOS questionnaire items were missing (non-response). Over two-thirds (65.6%) of these missing items related to three patients. No item was consistently missing; appetite was the most frequent missing item (1.4%). 92% of participants who completed the IPOS completed all follow-up assessments (1-2 days, 1-2 weeks and 4-6 weeks post-IPOS completion) with no missing data. The a priori feasibility objectives were met. Patients and nurses reported the intervention and study design feasible and acceptable. CONCLUSIONS: A palliative-specific PROM-based intervention is feasible and acceptable to both patients with CHF and nurses in nurse-led disease management clinics for the purposes of both clinical care and research.
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Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Cuidados Paliativos/normas , Medidas de Resultados Relatados pelo Paciente , Idoso , Doença Crônica , Gerenciamento Clínico , Estudos de Viabilidade , Feminino , Humanos , Masculino , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Cigarette smoking is highly pathogenic to the vasculature. In smokers, the biosynthesis of both thromboxane (Tx) A2 and prostacyclin is increased. We hypothesized that the excess in prostacyclin biosynthesis in smokers was derived from the inducible cyclooxygenase-2 (COX-2). We further hypothesized that if the overproduction of prostacyclin in smokers were restraining platelet activation, then inhibition of COX-2 would lead to an increase in the activation of platelets, with a corresponding increase in the biosynthesis of TxA2. METHODS AND RESULTS: Smokers and nonsmokers received rofecoxib 25 mg twice daily or placebo for 1 week each in random sequence. The systemic biosynthesis of TxA2 and prostacyclin was assessed by analysis of their respective urinary metabolites, 11-dehydrothromboxane B2 (Tx-M) and 2'3-donor-6-keto-PGF(1alpha) (PGI-M). Serum TxB2 was measured as an indicator of platelet COX-1 activity. Results are expressed as mean+/-SE with median and range. The elevated PGI-M in smokers (189+/-25, median 174, range 85 to 390 pg/mg creatinine) was reduced by rofecoxib to 78+/-27, median 71.5, range 50 to 135 pg/mg creatinine (P=0.002), and in nonsmokers, PGI-M at baseline (115+/-10, median 107, range 67 to 198 pg/mg creatinine) fell to 56+/-15, median 50, range 34 to 125 pg/mg creatinine (P=0.001) with rofecoxib. The increased excretion of Tx-M in smokers (284+/-26, median 252, range 200 to 569 pg/mg creatinine) was reduced by 21% to 223+/-16, median 206, range 154 to 383 pg/mg creatinine by rofecoxib (P=0.04) but was not changed in nonsmokers. Levels of serum TxB2 were not different in smokers and nonsmokers and were unaffected by rofecoxib. CONCLUSIONS: The increased prostacyclin biosynthesis in smokers is derived largely from the inducible COX-2. COX-2 also contributes to the increased biosynthesis of TxA2 in smokers, most likely from inflammatory cells.
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Ciclo-Oxigenase 2/metabolismo , Proteínas de Membrana/metabolismo , Adulto , Estudos Cross-Over , Ciclo-Oxigenase 1/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Método Duplo-Cego , Epoprostenol/biossíntese , Humanos , Lactonas/farmacologia , Masculino , Ativação Plaquetária , Prostaglandinas/urina , Valores de Referência , Fumar , Sulfonas/farmacologia , Tromboxano A2/sangueRESUMO
OBJECTIVE: Vascular calcification (VC) is inhibited by the glycoprotein osteoprotegerin (OPG). It is unclear whether treatments for type 2 diabetes are capable of promoting or inhibiting VC. The present study examined the effects of insulin and liraglutide on i) the production of OPG and ii) the emergence of VC, both in vitro in human aortic smooth muscle cells (HASMCs) and in vivo in type 2 diabetes. DESIGN/METHODS: HASMCs were exposed to insulin glargine or liraglutide, after which OPG production, alkaline phosphatase (ALP) activity and levels of Runx2, ALP and bone sialoprotein (BSP) mRNA were measured. A prospective, nonrandomised human subject study was also conducted, in which OPG levels and coronary artery calcification (CAC) were measured in a type 2 diabetes population before and 16 months after the commencement of either insulin or liraglutide treatment and in a control group that took oral hypoglycemics only. RESULTS: Exposure to insulin glargine, but not liraglutide, was associated with significantly decreased OPG production (11â913±1409âpg/10(4) cells vs 282±13âpg/10(4) cells, control vs 10ânmol/l insulin, P<0.0001), increased ALP activity (0.82±0.06 IU/10(4) cells vs 2.40±0.16âIU/10(4) cells, control vs 10ânmol/l insulin, P<0.0001) and increased osteogenic gene expression by HASMCs. In the clinical study (n=101), insulin treatment was associated with a significant reduction in OPG levels and, despite not achieving full statistical significance, a trend towards increased CAC in patients. CONCLUSION: Exogenous insulin down-regulated OPG in vitro and in vivo and promoted VC in vitro. Although neither insulin nor liraglutide significantly affected CAC in the present pilot study, these data support the establishment of randomised trials to investigate medications and VC in diabetes.
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Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Insulina de Ação Prolongada/farmacologia , Insulina de Ação Prolongada/uso terapêutico , Osteoprotegerina/sangue , Calcificação Vascular/induzido quimicamente , Idoso , Fosfatase Alcalina/metabolismo , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Vasos Coronários/patologia , Determinação de Ponto Final , Feminino , Peptídeo 1 Semelhante ao Glucagon/efeitos adversos , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Humanos , Hipoglicemiantes/efeitos adversos , Técnicas In Vitro , Insulina Glargina , Insulina de Ação Prolongada/efeitos adversos , Liraglutida , Masculino , Metformina/efeitos adversos , Metformina/farmacologia , Metformina/uso terapêutico , Pessoa de Meia-Idade , Músculo Liso Vascular/patologia , Projetos Piloto , Estudos Prospectivos , Sialoglicoproteínas/biossíntese , Sialoglicoproteínas/genéticaRESUMO
A family history of coronary artery disease (CAD), especially when the disease occurs at a young age, is a potent risk factor for CAD. DNA collection in families in which two or more siblings are affected at an early age allows identification of genetic factors for CAD by linkage analysis. We performed a genomewide scan in 1,168 individuals from 438 families, including 493 affected sibling pairs with documented onset of CAD before 51 years of age in men and before 56 years of age in women. We prospectively defined three phenotypic subsets of families: (1) acute coronary syndrome in two or more siblings; (2) absence of type 2 diabetes in all affected siblings; and (3) atherogenic dyslipidemia in any one sibling. Genotypes were analyzed for 395 microsatellite markers. Regions were defined as providing evidence for linkage if they provided parametric two-point LOD scores >1.5, together with nonparametric multipoint LOD scores >1.0. Regions on chromosomes 3q13 (multipoint LOD = 3.3; empirical P value <.001) and 5q31 (multipoint LOD = 1.4; empirical P value <.081) met these criteria in the entire data set, and regions on chromosomes 1q25, 3q13, 7p14, and 19p13 met these criteria in one or more of the subsets. Two regions, 3q13 and 1q25, met the criteria for genomewide significance. We have identified a region on chromosome 3q13 that is linked to early-onset CAD, as well as additional regions of interest that will require further analysis. These data provide initial areas of the human genome where further investigation may reveal susceptibility genes for early-onset CAD.