Preliminary estimates and forecasts of the population prevalence of self reported of hypertension, of ischaemic heart disease and stroke in the Republic of Ireland from 2005 - 2015

Ireland and Northern Ireland’s Population Health Observatory (INIsPHO) recently published estimates of the population prevalence of diabetes in 2005 and forecasts to 2010 and 2015 for the island of Ireland, at the national and sub-national levels. These estimates are based the PBS Model developed by York and Humber Public Health Observatory (YHPHO), Brent NHS Trust and the School of Health and Related Research (ScHARR).The Department of Health and Children (DoHC) has requested additional estimates and forecasts for hypertension.This paper outlines the results from preliminary work from the initial steps towards a more systematic approach to monitoring the prevalence of other chronic diseases on the island.

Replacement therapy for iron deficiency improves exercise capacity and quality of life in patients with cyanotic congenital heart disease and/or the Eisenmenger syndrome

La teràpia suplementària de ferro millora la capacitat d’exercici i la qualitat de vida en malalts amb una cardiopatia congènita cianòtica i/ o síndrome d’Eisenmenger El dèficit de ferro és una troballa comú en la cardiopatia congènita cianòtica, i pot ser la causa d’una reducció en la capacitat d’exercici. Actualment, està indicada la reposició dels dipòsits de ferro en aquest grup de malalts, éssent les evidències científiques escasses. En el present treball investiguem la seguretat i eficàcia del tractament amb ferro en malalts amb una cardiopatia congènita cianòtica. Per tal motiu, vint-i-cinc malalts amb una cardiopatia congenita cianòtica i dèficit de ferro van ser inclosos de forma prospectiva entre Agost del 2008 i Gener del 2009. El tractament utilitzat fou fumarat ferròs oral, fins a una dosi màxima de 200 mg tres vegades al dia. En l’anàlisi basal i als tres mesos de seguiment es va utilitzar el test de qualitat de vida “CAMPHOR”, el test de la marxa dels 6 minuts i la prova d’esforç amb consum d’oxigen. L’edat mitja fou 39.9+/-10.9 anys, 80% dones. Catorze malalts tenien la síndrome d’Eisenmenger, sis una malaltia cianòtica complexa i cinc circulació de Fontan. Cap d’ells va haver d'interrompre el tractament degut a efectes adversos. Després de tres mesos de tractament, l’hemoglobina (19.0+/-2.9g/dL a 20.4+/-2.7g/dL, p&0.001), ferritina (13.3+/-4.7mug/L a 54.1+/-24.2mug/L, p&0.001) i saturació de transferrina (17.8+/-9.6% a 34.8+/-23.4%, p&0.001) van augmentar significativament. També hi va haver una millora significativa en la puntuació del test de qualitat de vida (20.7+/-10.9 a 16.2+/-10.4, p=0.001) i el test de la marxa (371.7+/-84.7m a 402.8.0+/-74.9m, p=0.001). No es van evidenciar canvis significatius en els valors de consum d’oxigen (40.7+/-9.2% a 43.8+/-12.4%, p=0.15). En definitiva, la teràpia suplementària amb ferro en els malats amb una cardiopatia congènita cianòtica i dèficit de ferro és segura i millora la qualitat de vida i la capacitat funcional. En aquest grup de malalts, per tant, és aconsellable identificar el dèficit de ferro i restaurar-ne els seus dipòsits.

Gender differences in HIV progression to AIDS and death in industrialized countries: slower disease progression following HIV seroconversion in women.

To evaluate sex differences in human immunodeficiency virus (HIV) disease progression before (pre-1997) and after (1997-2006) introduction of highly active antiretroviral therapy, the authors used data from a collaboration of 23 HIV seroconverter cohort studies from Europe, Australia, and Canada restricted to the 6,923 seroconverters infected through injecting drug use and sex between men and women. Within a competing risk framework, they used Cox proportional hazards models allowing for late entry to evaluate sex differences in time from HIV seroconversion to death, to acquired immunodeficiency syndrome (AIDS), and to each first AIDS-defining disease and death without AIDS. While no significant sex differences were found before 1997, from 1997 onward, women had a lower risk of AIDS (adjusted cumulative relative risk (aCRR) = 0.76, 95% confidence interval (CI): 0.63, 0.90) and death (adjusted hazard ratio = 0.68, 95% CI: 0.56, 0.82) than men did. Compared with men, women also had lower risks of AIDS dementia complex (aCRR = 0.23, 95% CI: 0.07, 0.74), tuberculosis (aCRR = 0.60, 95% CI: 0.39, 0.92), Kaposi's sarcoma (aCRR = 0.27, 95% CI: 0.07, 0.99), lymphomas (aCRR = 0.47, 95% CI: 0.23, 0.96), and death without AIDS (aCRR = 0.74, 95% CI: 0.56, 0.98). Sex differences in HIV disease progression have become larger and statistically significant in the era of highly active antiretroviral therapy, supporting a stronger impact of health interventions among women.

Magnetic resonance stress tagging in ischemic heart disease.

High-dose dobutamine magnetic resonance stress testing has been shown to be superior to dobutamine stress echocardiography for diagnosis of coronary artery disease (CAD). We determined the feasibility of quantitative myocardial tagging during low- and high-dose dobutamine stress and tested the ability of global systolic and diastolic quantitative parameters to identify patients with significant CAD. Twenty-five patients suspected of having significant CAD were examined with a standard high-dose dobutamine/atropine stress magnetic resonance protocol (1.5-T scanner, Philips). All patients underwent invasive coronary angiography as the standard of reference for the presence (n = 13) or absence (n = 12) of significant CAD. During low-dose dobutamine stress, systolic (circumferential shortening, systolic rotation, and systolic rotation velocity) and diastolic (velocity of circumferential lengthening and diastolic rotation velocity) parameters changed significantly in patients without CAD (all P < 0.05 vs. rest) but not in patients with CAD. Identification of patients without and with CAD during low-dose stress was possible using the diastolic parameter of "time to peak untwist." At high-dose stress, none of the global systolic or diastolic parameters showed the potential to identify the presence of significant CAD. With myocardial tagging, a quantitative analysis of systolic and diastolic function was feasible during low- and high-dose dobutamine stress. In our study, the diastolic parameter of time to peak untwist as assessed during low-dose dobutamine stress was the most promising global parameter for identification of patients with significant CAD. Thus quantitative myocardial tagging may become a tool that reduces the need for high-dose dobutamine stress.

The London health inequalities forecast: A briefing on inequalities in life expectancy and deaths from cancers, heart disease and stroke in London

This briefing considers the national health inequalities targets which must be met by 2010. The targets include those set for heart disease and stroke, cancers and life expectancy.

Severity of chronic experimental Chagas' heart disease parallels tumour necrosis factor and nitric oxide levels in the serum: models of mild and severe disease

Heart tissue inflammation, progressive fibrosis and electrocardiographic alterations occur in approximately 30% of patients infected by Trypanosoma cruzi, 10-30 years after infection. Further, plasma levels of tumour necrosis factor (TNF) and nitric oxide (NO) are associated with the degree of heart dysfunction in chronic chagasic cardiomyopathy (CCC). Thus, our aim was to establish experimental models that mimic a range of parasitological, pathological and cardiac alterations described in patients with chronic Chagas’ heart disease and evaluate whether heart disease severity was associated with increased TNF and NO levels in the serum. Our results show that C3H/He mice chronically infected with the Colombian T. cruzi strain have more severe cardiac parasitism and inflammation than C57BL/6 mice. In addition, connexin 43 disorganisation and fibronectin deposition in the heart tissue, increased levels of creatine kinase cardiac MB isoenzyme activity in the serum and more severe electrical abnormalities were observed in T. cruzi-infected C3H/He mice compared to C57BL/6 mice. Therefore, T. cruzi-infected C3H/He and C57BL/6 mice represent severe and mild models of CCC, respectively. Moreover, the CCC severity paralleled the TNF and NO levels in the serum. Therefore, these models are appropriate for studying the pathophysiology and biomarkers of CCC progression, as well as for testing therapeutic agents for patients with Chagas’ heart disease.

From diabetes to heart disease : studies on dyslipidemia-induced B-cell dysfunction, immunomodulation in heart transplantation, and cardiac stem cell therapy

Diabetes is a growing epidemic with devastating human, social and economic impact. It is associated with significant changes in plasma concentrations of lipoproteins. We tested the hypothesis that lipoproteins modulate the function and survival of insulin-secreting cells. We first detected the presence of several receptors that participate in the binding and processing of plasma lipoproteins and confirmed the internalization of fluorescent LDL and HDL particles in insulin-secreting β-cells. Purified human VLDL and LDL particles reduced insulin mRNA levels and β-cell proliferation, and induced a dose-dependent increase in the rate of apoptosis. In mice lacking the LDL receptor, islets showed a dramatic decrease in LDL uptake and were partially resistant to apoptosis caused by LDL. VLDL-induced apoptosis of β-cells involved caspase-3 cleavage and reduction in levels of the c-Jun N-terminal (JNK) Interacting Protein-1 (IB1/JIP-1). In contrast, the pro-apoptotic signaling of lipoproteins was antagonized by HDL particles or by a small peptide inhibitor of JNK. The protective effects of HDL were mediated, in part, by inhibition of caspase-3 cleavage and activation of the protein kinase Akt/PKB. Heart disease is a major cause of morbidity and mortality among patients with diabetes. When heart failure is refractory to medical therapy and cannot be improved by electrical resynchronization, percutaneous angioplasty or coronary graft bypass surgery, heart transplantation remains a "last resort" therapy. Nevertheless, it is limited by the side effects of immunosuppressive drugs and chronic rejection. Localized expression of immunomodulatory genes in the donor organ can create a state of immune privilege within the graft, and was performed in rodent hearts by infecting cells with an adenovirus encoding indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme in the catabolism of tryptophane. Other strategies are based on genetic manipulation of dendritic cells (DCs) with immunosuppressive genes and in vitro exposure of DCs to agents that prevent their maturation by inflammatory cytokines. Finally, we used 5-bromo-2'-deoxyuridine, which is incorporated into DNA and diluted with cell division, to identify long-term label retaining cells in the adult rodent heart. The majority of these cells were positive for the stem cell antigen-1 (Sca-1) and negative for the endothelial precursor marker CD31. They formed cardiospheres in vitro and showed differentiation potential into mesenchymal cell lineages. When cultured in cardiomyogenic differentiation medium, they expressed cardiac-specific genes. Taken together, these data provide evidence of slow-cycling stem cells in the rodent heart. Chronic shortage of donor organs opens the way to cardiac stem cell therapy in humans, although the long way from animal experimentation to routine therapy in patients may still take several years. - Du diabète de type 2 à la maladie coronarienne : trois études sur les dysfonctions de la cellule sécrétrice d'insuline induites par les dyslipidémies, l'immunomodulation dans la transplantation cardiaque, et la thérapie par des cellules souches myocardiques. Le diabète de type 2 a pris les dimensions d'une épidémie, avec des conséquences sociales et économiques dont nous n'avons pas encore pris toute la mesure. La maladie s'accompagne souvent d'une dyslipidémie caractérisée par une hypertriglycéridémie, des taux abaissés de cholestérol HDL, et des concentrations de cholestérol LDL à la limite supérieure de ce qui est considéré comme acceptable. L'hypothèse à la base de cette étude est qu'une modification des taux plasmatiques de lipoprotéines pourrait avoir une influence directe sur la cellule β sécrétrice d'insuline en modifiant sa fonction, sa durée de vie et son taux de régénération. Dans un premier temps, nous avons mis en évidence, sur la cellule β, la présence de plusieurs récepteurs impliqués dans la captation des lipoprotéines. Nous avons confirmé la fonctionnalité de ces récepteurs en suivant l'internalisation de LDL et de HDL marqués. En présence de VLDL ou de LDL humains, nous avons observé une diminution de la transcription du gène de l'insuline, une prolifération cellulaire réduite, et une augmentation de l'apoptose, toutes fonctions de la dose et du temps d'exposition. L'apoptose induite par les VLDL passe par une activation de la caspase-3 et une réduction du taux de la protéine IB1/JIP-1 (Islet Brain1/JNK Interacting Protein 1), dont une mutation est associée à une forme monogénique de diabète de type 2. Par opposition, les HDL, ainsi que des peptides inhibiteurs de JNK, sont capables de contrer la cascade pro-apoptotique déclenchée, respectivement, par les LDL et les VLDL. Ces effets protecteurs comprennent l'inhibition du clivage de la caspase-3 et l'activation de la protéine kinase Akt/PKB. En conclusion, les lipoprotéines sont des éléments clés de la survie de la cellule β, et pourraient contribuer au dysfonctionnement observé dans le pancréas endocrine au cours du développement du diabète. La maladie cardiaque, et plus particulièrement la maladie coronarienne, est une cause majeure de morbidité et de mortalité chez les patients atteints de diabète. Plusieurs stratégies sont utilisées quotidiennement pour pallier les atteintes cardiaques: traitements médicamenteux, électromécaniques par resynchronisation électrique, ou communément appelés « interventionnels » lorsqu'ils font appel à l'angioplastie percutanée. La revascularisation du myocarde par des pontages coronariens donne également de très bons résultats dans certaines situations. Il existe toutefois des cas où plus aucune de ces approches n'est suffisante. La transplantation cardiaque est alors la thérapie de choix pour un nombre restreint de patients. La thérapie génique, en permettant l'expression locale de gènes immunomodulateurs dans l'organe greffé, permet de diminuer les réactions de rejet inhérentes à toute transplantation (à l'exception de celles réalisées entre deux jumeaux homozygotes). Nous avons appliqué chez des rongeurs cette stratégie en infectant le coeur greffé avec un adénovirus codant pour l'enzyme indoleamine 2,3-dioxygénase (IDO), une enzyme clé dans le catabolisme du tryptophane. Nous avons procédé de manière identique in vitro en surexprimant IDO dans les cellules dendritiques, dont le rôle est de présenter les antigènes aux lymphocytes Τ du receveur. Des expériences similaires ont été réalisées en traitant les cellules dendritiques avec des substances capables de prévenir, en partie du moins, leur maturation par des agents pro-inflammatoires. Finalement, nous avons exploré une stratégie utilisée couramment en hématologie, mais qui n'en est encore qu'à ses débuts au niveau cardiaque : la thérapie par des cellules souches. En traitant des rongeurs avec un marqueur qui s'incorpore dans l'ADN nucléaire, le 5-bromo- 2'-deoxyuridine, nous avons identifié une population cellulaire se divisant rarement, positive en grande partie pour l'antigène embryonnaire Sca-1 et négative pour le marqueur endothélial CD31. En culture, ces cellules forment des cardiosphères et sont capables de se différencier dans les principaux types tissulaires mésenchymateux. Dans un milieu de differentiation adéquat, ces cellules expriment des gènes cardiomyocytaires. En résumé, ces données confirment la présence chez le rongeur d'une population résidente de précurseurs myocardiques. En addenda, on trouvera deux publications relatives à la cellule β productrice d'insuline. Le premier article démontre le rôle essentiel joué par la complexine dans l'insulino-sécrétion, tandis que le second souligne l'importance de la protéine IB1/JIP-1 dans la protection contre l'apoptose de la cellule β induite par certaines cytokines.

Mirror image atrial dilatation in adult patients with atrial fibrillation and congenital heart disease.

BACKGROUND: Atrial fibrillation (AF) is largely regarded to be initiated from left atrial (LA) dilatation, with subsequent dilatation of the right atrium (RA) in those who progress to chronic AF. We hypothesized that in adult patients with right-sided congenital heart disease (CHD) and AF, RA dilatation will predominate with subsequent dilatation of the left atrium, as a mirror image. METHODS: Adult patients with diagnosis of right-sided, ASD or left-sided CHD who had undergone an echocardiographic study and electrocardiographic recording in 2007 were included. RA and LA area were measured from the apical view. AF was diagnosed from a 12-lead electrocardiogram or Holter recording. A multivariate logistic regression model was used to identify predictors of AF and linear regression models were performed to measure relationship between RA and LA area and AF. RESULTS: A total of 291 patients were included in the study. Multivariate analysis showed that age (p=0.0001), RA (p=0.025) and LA area (p=0.0016) were significantly related to AF. In patients with pure left-sided pathologies, there was progressive and predominant LA dilatation that paralleled the development of AF from none to paroxysmal to chronic AF. In patients with pure right-sided pathologies, there was a mirror image of progressive and predominant RA dilatation with the development of AF. CONCLUSION: We observed a mirror image atrial dilatation in patients with right sided disease and AF. This may provide novel mechanistic insight as to the origin of AF in these patients and deserves further studying in the form of targeted electrophysiological studies.

Congenital heart disease affects local gyrification in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11.2DS) is a common genetic condition associated with cognitive and learning impairments. In this study, we applied a three-dimensional method for quantifying gyrification at thousands of points over the cortical surface to imaging data from 44 children, adolescents, and young adults with 22q11.2DS (17 males, 27 females; mean age 17y 2mo [SD 9y 1mo], range 6-37y), and 53 healthy participants (21 males, 32 females; mean age 15y 4mo [SD 8y 6mo]; range 6-40y). Several clusters of reduced gyrification were observed, further substantiating the pattern of cerebral alterations presented by children with the syndrome. Comparisons within 22q11.2DS demonstrated an effect of congenital heart disease (CHD) on cortical gyrification, with reduced gyrification at the parieto-temporo-occipital junction in patients with CHD, as compared with patients without CHD. Reductions in gyrification can resemble mild polymicrogyria, suggesting early abnormal neuronal proliferation or migration and providing support for an effect of hemodynamic factors on brain development in 22q11.2DS. The results also shed light on the pathophysiology of acquired brain injury in other populations with CHD.

Douteurs thoraciques en médecine ambulatoire. Sans oublier les patients qui n'ont "rien au coeur" [Thoracic pain in primary care. Don't forget the patients without heart disease].

Thoracic pain in primary care. Don't forget the patients without heart disease Thoracic pain is a frequent medical complaint. Diagnostic and therapeutic guidelines have been developed and evaluated mostly in emergency and hospital settings. The primary care practitioner, as the emergency room doctor, has to identify quickly any severe condition needing urgent and highly specialized treatment. But in primary care, the process is not finished then! A patient with no vital and urgent problem still needs a diagnosis, information and adequate treatment. This review goes over the presentation of thoracic pain, the differential diagnoses and the challenge of treating such patients in ambulatory care.

Importance of the right ventricle in valvular heart disease.

The importance of the right ventricle as a determinant of clinical symptoms, exercise capacity, peri-operative survival and postoperative outcome has been underestimated for a long time. Right ventricular ejection fraction has been used as a measure of right ventricular function but has been found to be dependent on loading conditions, ventricular interaction as well as on myocardial structure. Altered left ventricular function in patients with valvular disease influences right ventricular performance mainly by changes in afterload but also by ventricular interaction. Right ventricular function and regional wall motion can be determined with right ventricular angiography, radionuclide ventriculography, two-dimensional echocardiography or magnetic resonance imaging. However, the complex structure of the right ventricle and its pronounced translational movements render quantification difficult. True regional wall motion analysis is, however, possible with myocardial tagging based on magnetic resonance techniques. With this technique a baso-apical shear motion of the right ventricle was observed which was enhanced in patients with aortic stenosis.

Regional cortical volumes and congenital heart disease: a MRI study in 22q11.2 deletion syndrome.

Children with congenital heart disease (CHD) who survive surgery often present impaired neurodevelopment and qualitative brain anomalies. However, the impact of CHD on total or regional brain volumes only received little attention. We address this question in a sample of patients with 22q11.2 deletion syndrome (22q11DS), a neurogenetic condition frequently associated with CHD. Sixty-one children, adolescents, and young adults with confirmed 22q11.2 deletion were included, as well as 80 healthy participants matched for age and gender. Subsequent subdivision of the patients group according to CHD yielded a subgroup of 27 patients with normal cardiac status and a subgroup of 26 patients who underwent cardiac surgery during their first years of life (eight patients with unclear status were excluded). Regional cortical volumes were extracted using an automated method and the association between regional cortical volumes, and CHD was examined within a three-condition fixed factor. Robust protection against type I error used Bonferroni correction. Smaller total cerebral volumes were observed in patients with CHD compared to both patients without CHD and controls. The pattern of bilateral regional reductions associated with CHD encompassed the superior parietal region, the precuneus, the fusiform gyrus, and the anterior cingulate cortex. Within patients, a significant reduction in the left parahippocampal, the right middle temporal, and the left superior frontal gyri was associated with CHD. The present results of global and regional volumetric reductions suggest a role for disturbed hemodynamic in the pathophysiology of brain alterations in patients with neurodevelopmental disease and cardiac malformations.