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1.
Artículo en Inglés | MEDLINE | ID: mdl-32675281

RESUMEN

BACKGROUND AND OBJECTIVES: Elevated BP is an important risk factor for cardiovascular disease, with a prevalence of over 80% in patients undergoing maintenance dialysis. We assessed the comparative BP-lowering efficacy and the safety of BP-lowering drugs in patients undergoing maintenance dialysis. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: We performed a frequentist random effects network meta-analysis of randomized, controlled trials evaluating BP-lowering agents in adult patients undergoing maintenance dialysis. Electronic databases (CENTRAL, MEDLINE, and Embase) were systematically searched (up to August 2018) for relevant trials. The main outcome was systolic BP reduction. RESULTS: Forty trials (4283 participants) met our inclusion criteria. Angiotensin-converting enzyme inhibitors, ß-blockers, calcium-channel blockers, and aldosterone antagonists lowered systolic BP to a greater extent than placebo, with effect sizes ranging from -10.8 mm Hg (95% confidence interval, -14.8 to -6.7 mm Hg) for the aldosterone antagonists to -4.3 mm Hg (95% confidence interval, -7.2 to -1.5 mm Hg) for angiotensin-converting enzyme inhibitors. Aldosterone antagonists and ß-blockers were superior to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium-channel blockers, and renin inhibitors at lowering systolic BP. Compared with angiotensin-converting enzyme inhibitors, aldosterone antagonists and ß-blockers lowered systolic BP by 6.4 mm Hg (95% confidence interval, -11.4 to -1.4 mm Hg) and 4.4 mm Hg (95% confidence interval, -7.4 to -1.3 mm Hg), respectively. Systolic BP reduction was not different with angiotensin receptor blockers, α-blockers, and calcium-channel blockers compared with angiotensin-converting enzyme inhibitors. Renin inhibitors were less effective. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone antagonists incurred risks of drug discontinuation due to adverse events and hypotension. CONCLUSIONS: BP-lowering agents significantly reduced systolic BP in patients undergoing maintenance dialysis. ß-Blockers and aldosterone antagonists may confer larger reductions, although treatment with aldosterone antagonists may be limited by adverse events.

2.
Artículo en Español | PAHO-IRIS | ID: phr-51862

RESUMEN

[RESUMEN]. La Comisión Lancet de Hipertensión determinó que una medida clave para responder a la carga mundial que representa la hipertensión arterial era mejorar la calidad de las mediciones de la presión arterial, mediante la utilización de dispositivos cuya exactitud haya sido validada. En la actualidad existen 3000 dispositivos comercializados, pero muchos no tienen datos publicados sobre pruebas de exactitud conformes a las normas científicas establecidas. La falta de regulación o su ineficiencia, que permiten la autorización de dispositivos para uso comercial sin una validación oficial, posibilitan este problema. Además, han surgido tecnologías nuevas de medición de la presión arterial (por ejemplo, los sensores sin brazalete) sobre las cuales no existe unanimidad en la comunidad científica con respecto a las normas de exactitud de la medición. En conjunto, estos aspectos contribuyen a la disponibilidad generalizada de tensiómetros de consultorio o domiciliarios que ofrecen una exactitud limitada o incierta, que llevan a diagnósticos, manejo y farmacoterapia inapropiados de la hipertensión a escala mundial. Los problemas más importantes relacionados con la exactitud de los dispositivos de medición de la presión arterial se pueden resolver mediante el requisito regulatorio de una validación independiente obligatoria de los dispositivos, en consonancia con la norma ISO universalmente aceptada. Esta es una recomendación básica y constituye una necesidad internacional acuciante. Otras recomendaciones clave son la elaboración de normas de validación específicas para las tecnologías nuevas de medición de la presión arterial y la publicación en línea de listas de los dispositivos nuevos exactos que están a la disposición de los usuarios y los profesionales de salud. Las recomendaciones están en consonancia con las políticas de la Organización Mundial de la Salud sobre los dispositivos médicos y la atención universal de la salud. El cumplimiento de las recomendaciones aumentará la disponibilidad mundial de dispositivos de medición de la presión arterial que sean exactos y tendrá como efecto un mejor diagnóstico y tratamiento, reduciendo así la carga mundial de la hipertensión.


[ABSTRACT]. The Lancet Commission on Hypertension identified that a key action to address the worldwide burden of high blood pressure (BP) was to improve the quality of BP measurements by using BP devices that have been validated for accuracy. Currently, there are over 3 000 commercially available BP devices, but many do not have published data on accuracy testing according to established scientific standards. This problem is enabled through weak or absent regulations that allow clearance of devices for commercial use without formal validation. In addition, new BP technologies have emerged (e.g. cuffless sensors) for which there is no scientific consensus regarding BP measurement accuracy standards. Altogether, these issues contribute to the widespread availability of clinic and home BP devices with limited or uncertain accuracy, leading to inappropriate hypertension diagnosis, management and drug treatment on a global scale. The most significant problems relating to the accuracy of BP devices can be resolved by the regulatory requirement for mandatory independent validation of BP devices according to the universally-accepted International Organization for Standardization Standard. This is a primary recommendation for which there is an urgent international need. Other key recommendations are development of validation standards specifically for new BP technologies and online lists of accurate devices that are accessible to consumers and health professionals. Recommendations are aligned with WHO policies on medical devices and universal healthcare. Adherence to recommendations would increase the global availability of accurate BP devices and result in better diagnosis and treatment of hypertension, thus decreasing the worldwide burden from high BP.


[RESUMO]. A Comissão Lancet sobre Hipertensão Arterial identificou que uma iniciativa central para enfrentar a carga mundial da hipertensão arterial seria a melhoria na qualidade da mensuração da pressão arterial pelo uso aparelhos de pressão arterial validados quanto à acurácia. Atualmente, existem mais de 3 000 aparelhos de pressão arterial disponíveis comercialmente; entretanto, muitos não têm dados publicados sobre testes de acurácia realizados de acordo com padrões científicos estabelecidos. Este problema resulta de regulamentação fraca ou inexistente, o que permite a aprovação para uso comercial de dispositivos sem validação formal. Além disso, surgiram novas tecnologias de mensuração da pressão arterial (por exemplo, sensores sem algemas) sem consenso científico quanto aos padrões de acurácia. No conjunto, essas questões contribuem para a oferta generalizada de dispositivos de pressão arterial clínica e domiciliar com acurácia limitada ou incerta, levando a diagnóstico, gerenciamento e tratamento inadequados da hipertensão em escala global. Os problemas mais significativos relacionados com a acurácia dos dispositivos de pressão arterial podem ser resolvidos por regulamentação que imponha a obrigatoriedade de validação independente dos aparelhos de pressão arterial, de acordo com a norma universalmente aceita pela Organização Internacional de Normalização. Esta é uma recomendação fundamental para a qual existe uma necessidade internacional urgente. Outras recomendações essenciais incluem o desenvolvimento de padrões de validação especificamente para novas tecnologias de mensuração da pressão arterial e listas on-line de aparelhos com acurácia adequada que sejam acessíveis aos consumidores e profissionais de saúde. As recomendações estão alinhadas com as políticas da Organização Mundial da Saúde (OMS) sobre dispositivos médicos e atenção universal à saúde. A adesão às recomendações aumentaria a oferta global de dispositivos de pressão arterial com acurácia adequada e resultaria em melhor diagnóstico e tratamento da hipertensão arterial, diminuindo assim a carga mundial dessa doença.


Asunto(s)
Salud Global , Tecnología Biomédica , Estándares de Referencia , Equipo para Diagnóstico , Salud Global , Tecnología Biomédica , Estándares de Referencia , Equipo para Diagnóstico , Salud Global , Tecnología Biomédica , Estándares de Referencia , Equipo para Diagnóstico
3.
J Hypertens ; 38(7): 1235-1243, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31990898

RESUMEN

: Blood pressure (BP) exhibits seasonal variation with lower levels at higher environmental temperatures and higher at lower temperatures. This is a global phenomenon affecting both sexes, all age groups, normotensive individuals, and hypertensive patients. In treated hypertensive patients it may result in excessive BP decline in summer, or rise in winter, possibly deserving treatment modification. This Consensus Statement by the European Society of Hypertension Working Group on BP Monitoring and Cardiovascular Variability provides a review of the evidence on the seasonal BP variation regarding its epidemiology, pathophysiology, relevance, magnitude, and the findings using different measurement methods. Consensus recommendations are provided for health professionals on how to evaluate the seasonal BP changes in treated hypertensive patients and when treatment modification might be justified. (i) In treated hypertensive patients symptoms appearing with temperature rise and suggesting overtreatment must be investigated for possible excessive BP drop due to seasonal variation. On the other hand, a BP rise during cold weather, might be due to seasonal variation. (ii) The seasonal BP changes should be confirmed by repeated office measurements; preferably with home or ambulatory BP monitoring. Other reasons for BP change must be excluded. (iii) Similar issues might appear in people traveling from cold to hot places, or the reverse. (iv) BP levels below the recommended treatment goal should be considered for possible down-titration, particularly if there are symptoms suggesting overtreatment. SBP less than 110 mmHg requires consideration for treatment down-titration, even in asymptomatic patients. Further research is needed on the optimal management of the seasonal BP changes.

4.
Am Heart J ; 220: 264-272, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31923768

RESUMEN

BACKGROUND: Bereavement is associated with an increased risk of cardiovascular disease; however, no reports exist of interventions to reduce risk. In a randomized, double-blind, placebo-controlled trial of 85 recently bereaved participants, we determined whether ß-blocker (metoprolol 25 mg) and aspirin (100 mg) reduce cardiovascular risk markers and anxiety, without adversely affecting bereavement intensity. METHODS: Participants were spouses (n = 73) or parents (n = 12) of deceased from 5 hospitals in Sydney, Australia, 55 females, 30 males, aged 66.1 ±â€¯9.4 years. After assessment within 2 weeks of bereavement, subjects were randomized to 6 weeks of daily treatment or placebo, and the effect evaluated using ANCOVA, adjusted for baseline values (primary analysis). RESULTS: Participants on metoprolol and aspirin had lower levels of home systolic pressure (P = .03), 24-hour average heart rate (P < .001) and anxiety (P = .01) platelet response to arachidonic acid (P < .001) and depression symptoms (P = .046) than placebo with no difference in standard deviation of NN intervals index (SDNNi), von Willebrand Factor antigen, platelet-granulocyte aggregates or bereavement intensity. No significant adverse safety impact was observed. CONCLUSIONS: In early bereavement, low dose metoprolol and aspirin for 6 weeks reduces physiological and psychological surrogate measures of cardiovascular risk. Although further research is needed, results suggest a potential preventive benefit of this approach during heightened cardiovascular risk associated with early bereavement.


Asunto(s)
Antagonistas de Receptores Adrenérgicos beta 1/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Aspirina/uso terapéutico , Aflicción , Enfermedades Cardiovasculares/prevención & control , Metoprolol/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Ansiedad/tratamiento farmacológico , Ácido Araquidónico/farmacología , Plaquetas/efectos de los fármacos , Depresión/tratamiento farmacológico , Método Doble Ciego , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Administración del Tratamiento Farmacológico , Persona de Mediana Edad , Placebos , Estudios Prospectivos , Sístole/efectos de los fármacos
5.
Rev. panam. salud pública ; 44: e21, 2020. tab
Artículo en Español | LILACS-Express | ID: biblio-1101778

RESUMEN

resumen está disponible en el texto completo


ABSTRACT The Lancet Commission on Hypertension identified that a key action to address the worldwide burden of high blood pressure (BP) was to improve the quality of BP measurements by using BP devices that have been validated for accuracy. Currently, there are over 3 000 commercially available BP devices, but many do not have published data on accuracy testing according to established scientific standards. This problem is enabled through weak or absent regulations that allow clearance of devices for commercial use without formal validation. In addition, new BP technologies have emerged (e.g. cuffless sensors) for which there is no scientific consensus regarding BP measurement accuracy standards. Altogether, these issues contribute to the widespread availability of clinic and home BP devices with limited or uncertain accuracy, leading to inappropriate hypertension diagnosis, management and drug treatment on a global scale. The most significant problems relating to the accuracy of BP devices can be resolved by the regulatory requirement for mandatory independent validation of BP devices according to the universally-accepted International Organization for Standardization Standard. This is a primary recommendation for which there is an urgent international need. Other key recommendations are development of validation standards specifically for new BP technologies and online lists of accurate devices that are accessible to consumers and health professionals. Recommendations are aligned with WHO policies on medical devices and universal healthcare. Adherence to recommendations would increase the global availability of accurate BP devices and result in better diagnosis and treatment of hypertension, thus decreasing the worldwide burden from high BP.


RESUMO A Comissão Lancet sobre Hipertensão Arterial identificou que uma iniciativa central para enfrentar a carga mundial da hipertensão arterial seria a melhoria na qualidade da mensuração da pressão arterial pelo uso aparelhos de pressão arterial validados quanto à acurácia. Atualmente, existem mais de 3 000 aparelhos de pressão arterial disponíveis comercialmente; entretanto, muitos não têm dados publicados sobre testes de acurácia realizados de acordo com padrões científicos estabelecidos. Este problema resulta de regulamentação fraca ou inexistente, o que permite a aprovação para uso comercial de dispositivos sem validação formal. Além disso, surgiram novas tecnologias de mensuração da pressão arterial (por exemplo, sensores sem algemas) sem consenso científico quanto aos padrões de acurácia. No conjunto, essas questões contribuem para a oferta generalizada de dispositivos de pressão arterial clínica e domiciliar com acurácia limitada ou incerta, levando a diagnóstico, gerenciamento e tratamento inadequados da hipertensão em escala global. Os problemas mais significativos relacionados com a acurácia dos dispositivos de pressão arterial podem ser resolvidos por regulamentação que imponha a obrigatoriedade de validação independente dos aparelhos de pressão arterial, de acordo com a norma universalmente aceita pela Organização Internacional de Normalização. Esta é uma recomendação fundamental para a qual existe uma necessidade internacional urgente. Outras recomendações essenciais incluem o desenvolvimento de padrões de validação especificamente para novas tecnologias de mensuração da pressão arterial e listas on-line de aparelhos com acurácia adequada que sejam acessíveis aos consumidores e profissionais de saúde. As recomendações estão alinhadas com as políticas da Organização Mundial da Saúde (OMS) sobre dispositivos médicos e atenção universal à saúde. A adesão às recomendações aumentaria a oferta global de dispositivos de pressão arterial com acurácia adequada e resultaria em melhor diagnóstico e tratamento da hipertensão arterial, diminuindo assim a carga mundial dessa doença.

6.
J Hypertens ; 38(1): 21-29, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31790375

RESUMEN

: The Lancet Commission on Hypertension identified that a key action to address the worldwide burden of high blood pressure (BP) was to improve the quality of BP measurements by using BP devices that have been validated for accuracy. Currently, there are over 3000 commercially available BP devices, but many do not have published data on accuracy testing according to established scientific standards. This problem is enabled through weak or absent regulations that allow clearance of devices for commercial use without formal validation. In addition, new BP technologies have emerged (e.g. cuffless sensors) for which there is no scientific consensus regarding BP measurement accuracy standards. Altogether, these issues contribute to the widespread availability of clinic and home BP devices with limited or uncertain accuracy, leading to inappropriate hypertension diagnosis, management and drug treatment on a global scale. The most significant problems relating to the accuracy of BP devices can be resolved by the regulatory requirement for mandatory independent validation of BP devices according to the universally-accepted International Organisation for Standardization Standard. This is a primary recommendation for which there is an urgent international need. Other key recommendations are development of validation standards specifically for new BP technologies and online lists of accurate devices that are accessible to consumers and health professionals. Recommendations are aligned with WHO policies on medical devices and universal healthcare. Adherence to recommendations would increase the global availability of accurate BP devices and result in better diagnosis and treatment of hypertension, thus decreasing the worldwide burden from high BP.

7.
J Hypertens ; 37(11): 2159-2167, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31145176

RESUMEN

OBJECTIVES: Excess pressure and reservoir pressure are related to various clinical outcomes in cardiovascular diseases, but whether there are sex differences in healthy individuals remains uncertain. We compared phenotypes of excess pressure and reservoir pressure between healthy men and women. METHODS: Different features of noninvasively recorded radial and reconstructed aortic pressure waveforms were measured in 435 healthy adults (257 women, 59%). In addition to SBP and DBP, we compared values of maximal excess pressure and reservoir pressure (RPMAX), excess pressure and reservoir pressure time integrals, respectively, as well as relative contributions of excess pressure (EPREL) and reservoir pressure to total blood pressure time integral, respectively, between men and women divided in two age categories, below 51 (82 women and 66 men) and greater than or equal to 51 years old (175 women and 112 men), corresponding to average age of menopause for women and acceleration of vascular ageing for all. RESULTS: In both age categories, compared with men, women had significantly lower peripheral and aortic SBP and DBP. Analysis of covariance adjusted for BMI revealed that women who were greater than or equal to 51 years old had significantly higher excess pressure time integral, RPMAX, reservoir pressure time integral, EPREL, and relative contributions of reservoir pressure than men in the same age category. In the younger age category below 51 years old, EPREL and RPMAX were also significantly higher in women than men. CONCLUSION: Our study shows that healthy women have lower peripheral and aortic SBP and DBP compared with healthy men; however, their excess and reservoir pressures are higher, particularly after 51 years of age.

8.
Vitam Horm ; 109: 133-149, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30678853

RESUMEN

Encouraging changes in the steroid hormone receptor field from initially questioning the role of non-genomic actions of steroid hormones to acceptance of the concept that the acute, membrane-centric actions are linked and/or regulate the nuclear actions. The focus of this chapter is how the non-genomic effects are linked to the longer lasting, genomic actions of aldosterone. By non-genomic we refer to the rapid actions that occur within minutes do not require transcription or translation and occur in both classical MR target organs (kidney and colon) and non-epithelial tissues (blood vessels, heart, and adipose). The mechanism of rapid non-genomic actions of aldosterone varies between tissues. As a result, this chapter is viewed through the lens of how the non-genomic and genomic actions of aldosterone are linked in cardiovascular disease. Specifically, regulation of sodium flux in the myocardium has an important role in pathogenesis of cardiac arrhythmia. Since there are now recognized gender differences in cardiovascular disease, we also include preliminary studies to investigate the interaction of sex steroid hormones with the ligand binding pocket of the mineralocorticoid receptor. Overall, we aim to showcase how the non-genomic effects of aldosterone potentially modulate the genomic effects and represent additional targets for intervention.


Asunto(s)
Aldosterona/metabolismo , Transducción de Señal/fisiología , Animales , Femenino , Hormonas Esteroides Gonadales/metabolismo , Humanos , Masculino , Receptores Acoplados a Proteínas G , Receptores de Mineralocorticoides/metabolismo , Factores Sexuales
10.
Mol Endocrinol ; 29(8): 1144-55, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26121234

RESUMEN

Aldosterone (Aldo) activates both genomic and nongenomic signaling pathways in the cardiovascular system. Activation of genomic signaling pathways contributes to the adverse cardiac actions of Aldo during reperfusion injury; however, the extent nongenomic signaling pathways contribute has been difficult to identify due to lack of a specific ligand that activates only nongenomic signaling pathways. Using a pegylated aldosterone analog, aldosterone-3-carboxymethoxylamine-TFP ester conjugated to methoxypegylated amine (Aldo-PEG), we are able for the first time to distinguish between nongenomic and genomic cardiac actions of Aldo. We confirm Aldo-PEG activates phosphorylation of ERK1/2 in rat cardiomyocyte H9c2 cells similar to Aldo and G protein-coupled receptor 30 (GPR30 or GPER) agonist G1. GPER antagonist, G36, but not mineralocorticoid receptor (MR) antagonist spironolactone, prevented ERK1/2 phosphorylation by Aldo, Aldo-PEG, and G1. The selective nongenomic actions of Aldo-PEG are confirmed, with Aldo-PEG increasing superoxide production in H9c2 cells to similar levels as Aldo but having no effect on subcellular localization of MR. Striatin serves as a scaffold for GPER and MR, with GPER antagonist G36, but not spironolactone, restoring MR-striatin complexes. Aldo-PEG had no effect on MR-dependent transcriptional activation, whereas Aldo increased transcript levels of serum-regulated kinase 1 and plasminogen activator inhibitor-1. Using our ex vivo experimental rat model of myocardial infarction, we found aggravated infarct size and apoptosis by Aldo but not Aldo-PEG. Our studies confirm that in the heart, activation of nongenomic signaling pathways alone are not sufficient to trigger the deleterious effects of aldosterone during myocardial reperfusion injury.


Asunto(s)
Aldosterona/farmacología , Daño por Reperfusión/metabolismo , Aminas/química , Animales , Proteínas de Unión a Calmodulina/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Antagonistas de Receptores de Mineralocorticoides/farmacología , Daño por Reperfusión Miocárdica , Proteínas del Tejido Nervioso/metabolismo , Fosforilación , Ratas , Ratas Sprague-Dawley , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Mineralocorticoides/metabolismo , Transducción de Señal , Espironolactona/farmacología , Superóxidos/metabolismo , Activación Transcripcional
11.
Future Cardiol ; 10(6): 677-8, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25495807

RESUMEN

The International Conference on Clinical & Experimental Cardiology was held in San Antonio (TX, USA) on 14-16 April 2014. This was the fourth meeting and had the theme 'Novel Perspectives on Clinical Cardiology and Cardiac Surgery' with sessions in heart disease, congenital heart disease, cardiac therapeutic agents, biophysics and systems biology, current research, and interventional cardiology, providing an interactive forum for discussion of science and clinical practices. Presentations by delegates from Africa, Saudi Arabia, India, China, Japan, Australia, Europe, South America, in addition to Canada and the USA, provided an opportunity for collaboration but also an appreciation of the challenges for treatment in remote locations as well as distance between health facilities.


Asunto(s)
Fibrilación Atrial/epidemiología , Enfermedad de la Arteria Coronaria/epidemiología , Estrés Oxidativo/fisiología , Inhibidores de Serina Proteinasa/uso terapéutico , Serpinas/uso terapéutico , Humanos , Inflamación/complicaciones
12.
Steroids ; 91: 32-7, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25173820

RESUMEN

Ischemic heart disease (IHD) continues to be the most common cause of death globally, although mortality rates are decreasing with significant advances in treatment. Higher prevalence of co-morbidities in women only partly explains the lack of decrease in mortality rates in younger women due to. Until recently there has been gender bias in pre-clinical studies and many clinical trials, resulting in a significant gap in knowledge whether there are differential responses to therapy for women, particularly younger women. There is increasing evidence that there are significant gender-specific differences in the outcome of post-infarction remodelling, prevalence of hypertension and sudden cardiac death. These differences indicate that cardiac tissue in females displays significant physiological and biochemical differences compared to males. However, the mechanisms mediating these differences, and how they change with age, are poorly understood. Circulating levels and physiological effects of aldosterone vary across the menstrual cycle suggesting female steroid sex hormones may not only regulate production of, but also responses to, aldosterone in pre-menopausal women. This modified tissue response may foster a homeostatic environment where higher levels of aldosterone are tolerated without adverse cardiac effect. Moreover, there is limited data on the direct regulation of this signalling axis by androgens in female animals/subjects. This review explores the relationship between gender and the effects of aldosterone in cardiovascular disease (CVD), an issue of significant need that may lead to changes in best practice to optimise clinical care and improve outcomes for females with CVD.


Asunto(s)
Aldosterona/fisiología , Corazón/fisiología , Caracteres Sexuales , Aldosterona/sangre , Aldosterona/farmacología , Animales , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Genoma , Hormonas Esteroides Gonadales/metabolismo , Corazón/efectos de los fármacos , Humanos , Masculino
13.
Endocrinology ; 155(2): 568-75, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24424037

RESUMEN

Age-specific incidence of ischemic heart disease in men is higher than in women, although women die more frequently without previous symptoms; the molecular mechanism(s) are poorly understood. Most studies focus on protection by estrogen, with less attention on androgen receptor-mediated androgen actions. Our aim was to determine the role of androgens in the sex differences in cardiac damage during myocardial infarction. Mature age-matched male and female Sprague Dawley rats, intact or surgically gonadectomized (Gx), received testosterone (T) or 17ß-estradiol (E2) via subdermal SILASTIC (Dow Corning Corp.) implants; a subset of male rats received dihydrotestosterone. After 21 days, animals were anesthetized, and hearts were excised and subjected to ex vivo regional ischemia-reperfusion (I-R). Hearts from intact males had larger infarcts than those from females following I-R; Gx produced the opposite effect, confirming a role for sex steroids. In Gx males, androgens (dihydrotestosterone, T) and E2 aggravated I-R-induced cardiac damage, whereas in Gx females, T had no effect and E2 reduced infarct area. Increased circulating T levels up-regulated androgen receptor and receptor for advanced glycation end products, which resulted in enhanced apoptosis aggravating cardiac damage in both males and females. In conclusion, our study demonstrates, for the first time, that sex steroids regulate autophagy during myocardial infarction and shows that a novel mechanism of action for androgens during I-R is down-regulation of antiapoptotic protein Bcl-xL (B cell lymphoma-extra large), a key controller for cross talk between autophagy and apoptosis, shifting the balance toward apoptosis and leading to aggravated cardiac damage.


Asunto(s)
Andrógenos/farmacología , Apoptosis/efectos de los fármacos , Infarto del Miocardio/metabolismo , Miocardio/metabolismo , Caracteres Sexuales , Animales , Dihidrotestosterona/farmacología , Regulación hacia Abajo/efectos de los fármacos , Estradiol/farmacología , Estrógenos/farmacología , Femenino , Masculino , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Miocardio/patología , Ratas , Ratas Sprague-Dawley , Índice de Severidad de la Enfermedad , Testosterona/farmacología
14.
Clin Exp Pharmacol Physiol ; 41(1): 54-7, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24111529

RESUMEN

1. Although two population-based studies have demonstrated the prognostic value of day-to-day home blood pressure (BP) variability, data are still limited. 2. Thresholds of normality, target levels for treatment and optimal number and times of home measurement needed for better assessment of day-to-day home BP variability also remain to be investigated. 3. Although further prospective studies are required, home BP is a strong and modifiable risk factor, and patient compliance should be encouraged.


Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial/métodos , Hipertensión/terapia , Presión Sanguínea/fisiología , Manejo de Caso , Humanos , Pronóstico , Resultado del Tratamiento
16.
Cardiovasc Diabetol ; 12: 139, 2013 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-24083804

RESUMEN

UNLABELLED: Development of a cardiomyopathy in diabetes mellitus is independent of traditional risk factors, with no clinical trials targeting specific therapeutic interventions. Myocardial fibrosis is one of the key mechanisms and aldosterone is a key mediator of myocardial fibrosis. We propose that aldosterone antagonism will improve cardiac function. We aim to evaluate the efficacy of selective aldosterone receptor antagonism with eplerenone added to optimal medical treatment in improving cardiac structure and function in diabetic cardiomyopathy. We will randomize 130 patients with type 2 diabetes mellitus, stable metabolic control and impaired left ventricular (LV) systolic or diastolic function, to either eplerenone (target dose 50mg) or matching placebo, in addition to optimal medical therapy for 12 months. The primary endpoints are changes in LV systolic and diastolic function, measured by echocardiographic 2-dimensional speckle tracking strain and strain rate and tissue Doppler imaging. The secondary endpoints include changes in echocardiographic markers and plasma biomarkers of collagen turnover; left atrial dimensions and function, incidence of atrial fibrillation and changes in exercise capacity and dyspnea score. The present study will assess whether specific aldosterone antagonism with eplerenone in addition to standard therapy will prevent progression or reverse cardiac dysfunction in diabetic cardiomyopathy using sensitive, robust and quantifiable echocardiographic measures that allow early detection of change. The study may offer a new direction in the management of this condition. TRIAL REGISTRATION: ACTRN12610001063000.


Asunto(s)
Fármacos Cardiovasculares/uso terapéutico , Cardiomiopatías Diabéticas/tratamiento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Proyectos de Investigación , Espironolactona/análogos & derivados , Función Ventricular Izquierda/efectos de los fármacos , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Protocolos Clínicos , Colágeno/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Cardiomiopatías Diabéticas/diagnóstico , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/fisiopatología , Diástole , Método Doble Ciego , Quimioterapia Combinada , Ecocardiografía Doppler , Eplerenona , Fibrosis , Humanos , Miocardio/metabolismo , Miocardio/patología , Nueva Gales del Sur , Estudios Prospectivos , Recuperación de la Función , Espironolactona/uso terapéutico , Sístole , Factores de Tiempo , Resultado del Tratamiento
17.
Am J Respir Crit Care Med ; 187(8): 879-87, 2013 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-23413266

RESUMEN

RATIONALE: Continuous positive airway pressure (CPAP) and mandibular advancement device (MAD) therapy are commonly used to treat obstructive sleep apnea (OSA). Differences in efficacy and compliance of these treatments are likely to influence improvements in health outcomes. OBJECTIVES: To compare health effects after 1 month of optimal CPAP and MAD therapy in OSA. METHODS: In this randomized crossover trial, we compared the effects of 1 month each of CPAP and MAD treatment on cardiovascular and neurobehavioral outcomes. MEASUREMENTS AND MAIN RESULTS: Cardiovascular (24-h blood pressure, arterial stiffness), neurobehavioral (subjective sleepiness, driving simulator performance), and quality of life (Functional Outcomes of Sleep Questionnaire, Short Form-36) were compared between treatments. Our primary outcome was 24-hour mean arterial pressure. A total of 126 patients with moderate-severe OSA (apnea hypopnea index [AHI], 25.6 [SD 12.3]) were randomly assigned to a treatment order and 108 completed the trial with both devices. CPAP was more efficacious than MAD in reducing AHI (CPAP AHI, 4.5 ± 6.6/h; MAD AHI, 11.1 ± 12.1/h; P < 0.01) but reported compliance was higher on MAD (MAD, 6.50 ± 1.3 h per night vs. CPAP, 5.20 ± 2 h per night; P < 0.00001). The 24-hour mean arterial pressure was not inferior on treatment with MAD compared with CPAP (CPAP-MAD difference, 0.2 mm Hg [95% confidence interval, -0.7 to 1.1]); however, overall, neither treatment improved blood pressure. In contrast, sleepiness, driving simulator performance, and disease-specific quality of life improved on both treatments by similar amounts, although MAD was superior to CPAP for improving four general quality-of-life domains. CONCLUSIONS: Important health outcomes were similar after 1 month of optimal MAD and CPAP treatment in patients with moderate-severe OSA. The results may be explained by greater efficacy of CPAP being offset by inferior compliance relative to MAD, resulting in similar effectiveness. Clinical trial registered with https://www.anzctr.org.au (ACTRN 12607000289415).


Asunto(s)
Conducción de Automóvil , Presión de las Vías Aéreas Positiva Contínua/estadística & datos numéricos , Avance Mandibular/estadística & datos numéricos , Calidad de Vida , Apnea Obstructiva del Sueño/terapia , Adulto , Anciano , Monitoreo Ambulatorio de la Presión Arterial/instrumentación , Simulación por Computador , Presión de las Vías Aéreas Positiva Contínua/instrumentación , Presión de las Vías Aéreas Positiva Contínua/métodos , Estudios Cruzados , Fatiga/etiología , Fatiga/fisiopatología , Femenino , Humanos , Hipertensión/etiología , Hipertensión/fisiopatología , Masculino , Avance Mandibular/instrumentación , Avance Mandibular/métodos , Persona de Mediana Edad , Nueva Gales del Sur , Cooperación del Paciente/estadística & datos numéricos , Polisomnografía/instrumentación , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/fisiopatología , Resultado del Tratamiento , Rigidez Vascular/fisiología , Adulto Joven
18.
Hypertension ; 59(6): 1164-9, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22508833

RESUMEN

Low-dose mineralocorticoid receptor antagonists reduce morbidity and mortality in patients with heart failure and myocardial infarction, despite normal plasma aldosterone levels. Since apoptosis plays an important role in heart failure and postinfarction left ventricular remodeling, we examined whether low-dose mineralocorticoid receptor antagonists modulate cardiomyocyte death by regulating the apoptosis repressor protein apoptosis repressor with caspase recruitment domain to lessen the extent of apoptosis. Hearts from adult male Sprague-Dawley rats were subjected to regional ischemia followed by reperfusion ex vivo, with mineralocorticoid receptor antagonists added to perfusates before ischemia. Low-dose spironolactone (10 nmol/L) or eplerenone (100 nmol/L) significantly reduced infarct size. Spironolactone also prevented cleavage of the apoptotic chromatin condensation inducer in the nucleus and of the inhibitor of caspase-activated DNAse induced by ischemia-reperfusion, thereby abolishing chromatin condensation and internucleosomal cleavage. Ischemia-reperfusion-induced activation of caspases 2, 3, and 9, but not caspase 8, was prevented by spironolactone, suggesting targeted regulation of the intrinsic pathway. Low-dose spironolactone and eplerenone prevented loss of the apoptosis repressor with the caspase recruitment domain and reduced myocyte death. In H9c2 cells, mineralocorticoid receptor activation by aldosterone resulted in apoptosis repressor with caspase recruitment domain degradation and enhanced apoptosis; these actions were prevented by coadministration of spironolactone. Using a triple lysine mutant we identified that aldosterone enhances posttranscriptional degradation of the apoptosis repressor with a caspase recruitment domain via the ubiquitin-proteasomal pathway. Our data demonstrate that low-dose mineralocorticoid receptor antagonists reduce infarct size and apoptosis in the reperfused myocardium by preventing the apoptosis repressor with caspase recruitment domain degradation.


Asunto(s)
Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Musculares/metabolismo , Infarto del Miocardio/prevención & control , Espironolactona/farmacología , Animales , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/genética , Caspasa 2/metabolismo , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Línea Celular , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Eplerenona , Immunoblotting , Técnicas In Vitro , Masculino , Antagonistas de Receptores de Mineralocorticoides/farmacología , Proteínas Musculares/genética , Infarto del Miocardio/genética , Infarto del Miocardio/metabolismo , Proteolisis/efectos de los fármacos , Interferencia de ARN , Ratas , Ratas Sprague-Dawley , Receptores de Mineralocorticoides/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Espironolactona/análogos & derivados
19.
Curr Hypertens Rep ; 14(2): 125-9, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22311652

RESUMEN

Numerous studies have now shown that sustained elevation of aldosterone levels induces cardiovascular damage independent from its effects on regulation of renal sodium and blood pressure. Increased aldosterone and cortisol levels in patients with heart failure independently predict the risk of mortality. Over the past decade, there has been increased interest in identifying the role of the receptor for aldosterone, the mineralocorticoid receptor (MR), following the results from the large clinical heart failure trials that showed low doses of MR antagonists reduced morbidity and mortality in heart failure and myocardial infarction, even though plasma levels of aldosterone were in the physiologic range. The mechanism for this cardioprotective action remains to be defined, although changes in the redox state have been shown to play a key role in MR-mediated cardiac damage. This review will highlight some of these studies and provide an update on the action of aldosterone in heart disease.


Asunto(s)
Arritmias Cardíacas/genética , Insuficiencia Cardíaca/genética , Hiperaldosteronismo/genética , Hipertensión/genética , Humanos , Hidrocortisona/sangre , Receptores de Mineralocorticoides/genética , Sodio en la Dieta
20.
J Hypertens ; 30(2): 253-66, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22179076

RESUMEN

OBJECTIVE: Although most national guidelines for the diagnosis and management of hypertension emphasize that the initiation and modification of blood pressure (BP)-lowering treatment should be related to absolute cardiovascular disease (CVD) risk, there is only limited information on how to incorporate ambulatory BP (ABP) monitoring into this framework. The objective of this initiative is to provide ABP equivalents for BP cut-points for treatment initiation and targets to be included into guidelines. METHODS: A critical analysis of the best available evidence from clinical trials and observational studies was undertaken to develop a new consensus statement for ABP monitoring. RESULTS: ABP monitoring has an important place in defining abnormal patterns of BP, particularly white-coat hypertension (including in pregnancy), episodic hypertension, masked hypertension, labile BP and nocturnal or morning hypertension. This consensus statement provides a framework for appropriate inclusion of ABP equivalents for low, moderate and high CVD risk patients. The wider use of ABP monitoring, although justified, is limited by its availability and cost due to the lack of medical subsidy in Australia. However, cost-benefit analysis does suggest a cost-saving in reduced numbers of inappropriate antihypertensive treatments. CONCLUSION: Although clinic measurement of BP will continue to be useful for screening and management of suspected and true hypertension, ABP monitoring provides considerable added value toward accurate diagnosis and the provision of optimal care in uncomplicated hypertension, as well as for patients with moderate or severe CVD risk.


Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial , Guías de Práctica Clínica como Asunto , Australia , Medicina Basada en la Evidencia , Humanos
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