Coronary magnetic resonance imaging.

Coronary magnetic resonance imaging is a powerful non-invasive technique for the combined assessment of coronary artery anatomy and function. In the present review article, challenges in coronary artery imaging are discussed and results obtained in both healthy volunteers and patients with cardiovascular disease are presented. This includes a short overview of coronary artery vessel lumen and wall imaging, contrast agents, permeability of the coronary vessel wall, high-field imaging and imaging of endothelial function.

Hypertension et diabète ADVANCE : une étude de morbidité-mortalité : nouveautés en médecine 2007 [ADVANCE: a morbidity mortality study of diabetes and hypertension]

The ADVANCE study is a morbidity-mortality double-blind trial carried out in normotensive or hypertensive patients with type 2 diabetes. The patients were randomly assigned to receive containing a fixed-combination tablet of an ACE inhibitor (perindopril) with a diuretic (indapamide) (4 mg/l,250 mg, n=5569), or placebo (n=5571), administered if needed on top of other blood pressure lowering agents. Significant reductions in the relative risk of death from cardiovascular disease (18%), total coronary events (14%), and total renal events (21%) were observed. Thus, in patients with type 2 diabetes, a drug regimen based on a fixed-dose combination of perindopril/ indapamide affords major protection against both the macro and microvascular complications. L'étude ADVANCE est un essai clinique de morbidité-mortalité réalisé en double insu chez des malades avec diabète de type 2 normo ou hypertendus. Les malades ont été alloués au hasard pour un suivi moyen de 4,3 ans à un traitement comportant soit une association fixe de l'inhibiteur de l'ECA périndopril et du diurétique indapamide (4 mg/1,250 mg, n = 5569), soit un placebo (n = 5571), ceci en plus si nécessaire d'autres médicaments antihypertenseurs. Des réductions significatives du risque relatif ont été observées sous périndopril/indapamide, en particulier de la mortalité cardiovasculaire (18%), de l'ensemble des événements coronaires (14%) et rénaux (21%). Ainsi chez le malade avec diabète de type 2, un traitement basé sur une association de périndopril et d'indapamide à doses fixes a un effet protecteur majeur contre les complications macro et microvasculaires.

Surgical menopause increases salt sensitivity of blood pressure

Salt sensitivity of blood pressure is associated with an elevated risk of developing hypertension (HTN) and is an independent risk factor for cardiovascular disease. The prevalence of HTN increases after menopause. The aim of this study was to investigate prospectively whether the loss of ovarian hormones increases the occurrence of salt sensitivity among healthy premenopausal women. We enrolled 40 normotensive, nondiabetic women (age 47.2+/-3.5), undergoing hysterectomy-oophorectomy for nonneoplastic processes and not on hormone replacement, to determine the effect of changes in sodium intake on blood pressure the day before and subsequently 4 months after surgical menopause. Salt loading was achieved using a 2-L normal saline infusion and salt depletion produced by 40 mg of intravenous furosemide. A decrease >10 mm Hg in systolic blood pressure between salt loading and salt depletion was used to define salt sensitivity. Before and after menopause, salt-sensitive women exhibited higher waist/hip and waist/thigh ratios (P<0.01). Although all of the women remained normotensive, the prevalence of salt sensitivity was significantly higher after surgical menopause (21 women; 52.5%) than before (9 women; 22.5%; P=0.01), because 12 (38.7%) salt-resistant women developed salt sensitivity after menopause. In summary, we demonstrated that the prevalence of salt sensitivity doubled as early as 4 months after surgical menopause, without an associated increase in blood pressure. Epidemiological studies indicate that development of HTN may not occur until 5 to 10 years after menopause. The loss of ovarian hormones may unmask a population of women prone to salt sensitivity who, with aging, would be at higher risk for the subsequent development of HTN and cardiovascular disease.

Prévention primaire et dépistage chez l'adulte: mise a jour 2014 [Primary prevention and screening in adults: update 2014].

Cet article propose une mise à jour des recommandations pour le bilan de santé et la prévention primaire et secondaire de nombreuses maladies cardiovasculaires et oncologiques. Les nouveautés pour le dépistage des cancers concernent essentiellement les cancers colorectal, du poumon et de la prostate. Pour la prévention des maladies cardiovasculaires, le dépistage de la sténose de l'artère carotidienne n'est toujours pas recommandé. Les preuves de la littérature sont insuffisantes pour recommander le dépistage de l'artériopathie coronarienne ou périphérique chez les patients asymptomatiques. Le partage de l'information et de la décision entre le médecin et le patient est à privilégier lorsqu'il existe une incertitude quant à l'efficacité d'une intervention. This article provides an update on the recommendations for the routine check-up and the primary and secondary prevention of cancer and cardiovascular disease. Changes for cancer screening affect mainly colorectal, lung and prostate cancers. In the area of cardiovascular disease prevention, screening for carotid artery stenosis is still not recommended. The current evidence is insufficient to recommend screening for coronary heart disease or peripheral artery disease in asymptomatic patients. Shared information and decision making between physician and patient is recommended when there is uncertainty regarding the effectiveness of an intervention.

Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study.

BACKGROUND Hypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information. METHODS A subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years) was genotyped for the LPL-HindIII (rs320), S447X (rs328), D9N (rs1801177) and N291S (rs268) polymorphisms, the APOA5-S19W (rs3135506) and -1131T/C (rs662799) variants, and the APOE polymorphism (rs429358; rs7412) using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable) and the association of variant combinations with TG levels and hypertriglyceridemia (TG > or = 1.69 mmol/L), including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption. RESULTS We found a significant lowering effect of the LPL-HindIII and S447X polymorphisms (p < 0.0001). In addition, the D9N, N291S, S19W and -1131T/C variants and the APOE-epsilon4 allele were significantly associated with an independent additive TG-raising effect (p < 0.05, p < 0.01, p < 0.001, p < 0.0001 and p < 0.001, respectively). Grouping individuals according to the presence of TG-lowering or TG-raising polymorphisms showed significant differences in TG levels (p < 0.0001), with the lowest levels exhibited by carriers of two lowering variants (10.2% reduction in TG geometric mean with respect to individuals who were homozygous for the frequent alleles of all the variants), and the highest levels in carriers of raising combinations (25.1% mean TG increase). Thus, carrying two lowering variants was protective against HTG (OR = 0.62; 95% CI, 0.39-0.98; p = 0.042) and having one single raising polymorphism (OR = 1.20; 95% CI, 1.39-2.87; p < 0.001) or more (2 or 3 raising variants; OR = 2.90; 95% CI, 1.56-5.41; p < 0.001) were associated with HTG. CONCLUSION Our results showed a significant independent additive effect on TG levels of the LPL polymorphisms HindIII, S447X, D9N and N291S; the S19W and -1131T/C variants of APOA5, and the epsilon4 allele of APOE in our study population. Moreover, some of the variant combinations studied were significantly associated with the absence or the presence of hypertriglyceridemia.

Loss of ovarian hormones increases salt-sensitivity in normotensive women

Salt sensitivity (SS) is associated with an elevated risk of developing hypertension(HTN) and is an independent risk factor for cardiovascular (CV) morbidity and mortality. Cross-sectional studies have suggested that postmenopausal women are more salt sensitive than premenopausal women. The purpose of the present study was to investigate prospectively the prevalence of SS among healthy premenopausal women and determine whether the loss of ovarian hormones increases SS.

Insulin receptor substrate-1 expression is increased in circulating leukocytes of patients with acute coronary syndrome.

The mechanisms underlying the increased risk of cardiovascular disease associated with diabetes mellitus (DM) are not fully defined. Insulin resistance in human metabolic syndrome patients is associated with decreased expression of the insulin receptor substrate-2- (Irs2-) AKT2 axis in mononuclear leukocytes (MLs). Moreover, acute coronary syndrome (ACS) has been linked through genome-wide association studies to the 2q36-q37.3 locus, which contains the Irs1 gene. Here, we investigated the expression of insulin-signaling pathway genes in MLs from patients with DM, ACS, and ACS plus DM. Quantitative real-time PCR expression studies showed no differences in the mRNA levels of Irs2, Akt2, and Akt1 among all patients. However, Irs1 mRNA expression was significantly increased in patients with ACS-diabetics and nondiabetics-compared with diabetic patients without ACS (P < .02 and P < .005, resp.). The present study reveals for the first time an association between increased Irs1 mRNA levels in MLs of patients with ACS which is not related to DM.

Blood pressure loci identified with a gene-centric array.

Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 × 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56 × 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.

Higher red blood cell distribution width is associated with a worse virologic and clinical situation in HIV-infected patients.

Background A high level of red blood cell distribution width (RDW) is a novel prognostic marker that may reflect an underlying inflammatory state. It has recently shown that when increased, it is related to cardiovascular disease, mortality, and metabolic syndrome (MetS) in the general population. Objectives To analyse the potential relation between high levels of RDW and cardiovascular risk (CVR) and MetS in HIVpatients. Patients and methods Observational, cross-sectional study of a series of HIVoutpatients attended in our Hospital. Demographic, anthropometric, clinical, and fasting lab data were recorded in all cases. CVR at 10 years was evaluated by Framingham equation, and MetS diagnosed according to the National Cholesterol Education Program criteria. Statistic program: SPSS 17.0. Results 666 patients were included, 79.3% were men, and mean age was 44.7 years. Mean CD4 count was 506 cells/ mm3 , 87.5% of the patients were on antiretroviral therapy, and 85.3% had undetectable HIV viral load. Mean RDW was 13.07% (range: 7.7-33.6%; 75th percentile 14,1%), with a prevalence of MetS of 15.7, 9.3, 18.8 and 16.6% first through fourth RDW quartile, and of patients with CVR >20% of 8.4, 4.0, 4.4 and 6.4%, respectively (p>0,05). The highest quartile of RDW (>14.1%) was associated with AIDS (OR 1.6, 95%CI 1.0-2.4; p 0.02), detectable HIV viral load (OR 1.5, 95%CI 1.01-2.4; p 0.04), and hypertension (OR 2.3, 95%CI 1.4-4.0; p 0.001). Conclusions In HIV-infected outpatients, higher RDW is related with detectable HIV viral load and with AIDS. Although it was associated with a traditional CVR factor as hypertension, we found no relation with MetS nor with higher CVR.

Validated SNPs for eGFR and their associations with albuminuria.

Albuminuria and reduced glomerular filtration rate are manifestations of chronic kidney disease (CKD) that predict end-stage renal disease, acute kidney injury, cardiovascular disease and death. We hypothesized that SNPs identified in association with the estimated glomerular filtration rate (eGFR) would also be associated with albuminuria. Within the CKDGen Consortium cohort (n= 31 580, European ancestry), we tested 16 eGFR-associated SNPs for association with the urinary albumin-to-creatinine ratio (UACR) and albuminuria [UACR >25 mg/g (women); 17 mg/g (men)]. In parallel, within the CARe Renal Consortium (n= 5569, African ancestry), we tested seven eGFR-associated SNPs for association with the UACR. We used a Bonferroni-corrected P-value of 0.003 (0.05/16) in CKDGen and 0.007 (0.05/7) in CARe. We also assessed whether the 16 eGFR SNPs were associated with the UACR in aggregate using a beta-weighted genotype score. In the CKDGen Consortium, the minor A allele of rs17319721 in the SHROOM3 gene, known to be associated with a lower eGFR, was associated with lower ln(UACR) levels (beta = -0.034, P-value = 0.0002). No additional eGFR-associated SNPs met the Bonferroni-corrected P-value threshold of 0.003 for either UACR or albuminuria. In the CARe Renal Consortium, there were no associations between SNPs and UACR with a P< 0.007. Although we found the genotype score to be associated with albuminuria (P= 0.0006), this result was driven almost entirely by the known SHROOM3 variant, rs17319721. Removal of rs17319721 resulted in a P-value 0.03, indicating a weak residual aggregate signal. No alleles, previously demonstrated to be associated with a lower eGFR, were associated with the UACR or albuminuria, suggesting that there may be distinct genetic components for these traits.

Remodelage des canaux potassiques dépendants de l'ATP lors de l'hypertrophie et de l'insuffisance cardiaque

RESUME :Introduction. Les maladies cardiovasculaires représentent la première cause de mortalité dans les pays développés et l'insuffisance cardiaque (IC) est la plus fréquente. Suite à un infarctus, le coeur des patients subit un remodelage ventriculaire pouvant évoluer vers un état d'IC. L'IC se définit comme un état dans lequel le coeur n'est plus capable d'approvisionner suffisamment les organes et cet état s'accompagne souvent de troubles du rythme cardiaque. Le remodelage ventriculaire touche de nombreux gènes codant à la fois pour les voies métaboliques et pour des canaux ioniques favorisant ainsi l'apparition des arythmies responsables de la mort subite des patients atteints d'IC. Comprendre ce passage entre remodelage et IC est crucial afin de pouvoir un jour prévenir l'IC et les complications médicales qui l'accompagnent. Nous nous sommes intéressés aux canaux potassiques dépendants de l'ATP (KATP) car ces canaux ont la capacité de coupler le métabolisme de la cellule à son activité électrique. En effet, les canaux KATP s'ouvrent quand la charge énergétique (rapport ATP/ ADP) de la cellule chute. Dans les cardiomyocytes, l'ouverture des KATP induit une hyperpolarisation de la membrane cellulaire ce qui diminue indirectement la surcharge calcique et de ce fait préserve la cellule. Les canaux KATp sont formés de 4 sous-unités Kir6.x (Kir6.1 ou Kir6.2) formant le pore du canal associées à 4 sous-unités régulatrices SUR. Les propriétés électrophysiologiques ainsi que la sensibilité pharmacologique des canaux KATP dépendent de leur composition et seuls les canaux KATP formés par la sous-unité Kirô.l sont activés par le diazoxyde.Méthodes et résultats. Nous avons d'abord montré dans un modèle in vivo d'IC chez le rat adulte que les sous-unités Kir6.1 et SUR sont surexprimées dans ces conditions pathologiques. Par ailleurs, les cardiomyocytes issus des coeurs infarcis deviennent sensibles au diazoxyde reflétant la surexpression de Kir6.1. Les potentiels d'action qui sont prolongés dans l'IC et qui sont à l'origine d'arythmies majeures sont normalisés par l'ouverture des canaux KATp induite par le diazoxyde. Ainsi, l'ouverture pharmacologique des canaux KATp contribuerait à la cardio-protection. Dans une seconde partie, nous avons déterminé quels étaient les facteurs de transcription responsables de ce changement d'expression des sous-unités formant les KATP. Dans notre modèle, nous avons pu montrer que la surexpression de Kirô.l est due aux facteurs de transcription Fox03 et FoxF2 qui est aussi responsable de la surexpression des sous-unités SUR. Dans la dernière partie de ce travail, nous avons mis au point un modèle d'IC in vitro en cultivant les cardiomyocytes de rats adultes en présence d'angiotensine II (Angll) ou de TNFa. Ce modèle expérimental nous a non seulement permis de mettre en relation l'importance de L'AnglI et du TNFa sur le remodelage des canaux KATP mais aussi de développer un modèle in vitro présentant les mêmes caractéristiques que le modèle in vivo concernant le remodelage des KATP lors de l'IC. Ce dernier modèle expérimental ouvre des perspectives afin de mieux caractériser les voies de signalisation impliquées dans le remodelage des canaux KATp lors de l'IC.Conclusion. Les canaux KATp subissent un remodelage lors de l'IC et les résultats obtenus montrent le potentiel cardio-protecteur de ces canaux.ABSTRACT :Background and aim. Cardiovascular disease is the leading cause of death in developed countries and heart failure (HF) is the most common. Following myocardial infarction, the heart of the patient undergoes ventricular remodeling which may evolve toward a state of HF. HF is defined as a state in which heart is unable to supply enough blood to organs and this state is often accompanied by cardiac arrhythmias. Ventricular remodeling involves many genes coding for both metabolic enzymes and ion channels. Changes in ion channel expression can promote arrhythmias responsible for sudden death in patients with HF. A better understanding of the transition between remodeling and HF is crucial in order to prevent the complications associated to HF We were interested in ATP-dependent potassium channels (KATp) because they couple cell metabolism to electrical activity of the cell. Indeed, KATP channels open when the energy charge (ratio of ATP / ADP) of the cell collapses. In cardiomyocytes, the opening of KATP channels induces hyper- polanzation of the cell membrane which reduces calcium overload and thereby protects the cell. KATp channels are composed by 4 Kir6.x subumts (Kir6.1 or Kir6.2) forming the pore channel associated with 4 regulatory subunits SUR. The electrophysiological properties as well as pharmacological sensitivity of KATp channels depend on their composition and only KATP channels formed by Kir6.1 subunit are activated by diazoxide.Methods and results. Firstly, using an in vivo model of HF in adult rats, we showed that Kir6.1 and SUR subunits are overexpressed in HF. In addition, cardiomyocytes from post-infarction hearts became sensitive to diazoxide reflecting the overexpression of the Kir6.1 subunit. The opening of KATP by diazoxide tended to reduce the action potential duration (APD) which is extended in HF. This increase in APD is known to be a major source of arrhythmias during HF. Therefore, the opening of KATP channels by diazoxide would be cardio-protective. Secondly, we wanted to determine which transcription factors were responsible for this KATP remodeling. In our model of HF, we showed that overexpression of Kir6.1 is due to the transcription factors Fox03 and FOXF2 which is also responsible for SUR subunits overexpression. Thirdly, we developed an in vitro model of HF by cultivation of adult rat cardiomyocytes in the presence of angiotensin II (Angll) or TNFa. This model is very interesting not only because it underlines the importance of Angll and TNFa in KATp remodeling but also because this in vitro model presents the same KATP remodeling as the in vivo model of HF. These findings show that our in vitro model of HF opens up many possibilities to investigate more precisely the signaling pathways involved in remodeling of the KATP channels in HF.Conclusion. KATP channels undergo remodeling during HF and our results show the cardio¬protective potential of KATP channels in this disease.

Association of socioeconomic status with overall and cause specific mortality in the republic of seychelles : results from a cohort study in the african region

BACKGROUND: Low socioeconomic status (SES) is consistently associated with higher mortality in high income countries. Only few studies have assessed this association in low and middle income countries, mainly because of sparse reliable mortality data. This study explores SES differences in overall and cause-specific mortality in the Seychelles, a rapidly developing small island state in the African region. METHODS: All deaths have been medically certified over more than two decades. SES and other lifestyle-related risk factors were assessed in a total of 3246 participants from three independent population-based surveys conducted in 1989, 1994 and 2004. Vital status was ascertained using linkage with vital statistics. Occupational position was the indicator of SES used in this study and was assessed with the same questions in the three surveys. RESULTS: During a mean follow-up of 15.0 years (range 0-23 years), 523 participants died (overall mortality rate 10.8 per 1000 person-years). The main causes of death were cardiovascular disease (CVD) (219 deaths) and cancer (142 deaths). Participants in the low SES group had a higher mortality risk for overall (HR = 1.80; 95% CI: 1.24-2.62), CVD (HR = 1.95; 1.04-3.65) and non-cancer/non-CVD (HR = 2.14; 1.10-4.16) mortality compared to participants in the high SES group. Cancer mortality also tended to be patterned by SES (HR = 1.44; 0.76-2.75). Major lifestyle-related risk factors (smoking, heavy drinking, obesity, diabetes, hypertension, hypercholesterolemia) explained a small proportion of the associations between low SES and all-cause, CVD, and non-cancer/non-CVD mortality. CONCLUSIONS: In this population-based study assessing social inequalities in mortality in a country of the African region, low SES (as measured by occupational position) was strongly associated with overall, CVD and non-cancer/non-CVD mortality. Our findings support the view that the burden of non-communicable diseases may disproportionally affect people with low SES in low and middle income countries.

Influencia de un programa de actividad física en niños y adolescentes obesos con apnea del sueño; protocolo de estudio.

Recent studies show an alarming increase in the rate of overweight / obesity among the infant - juvenile population. Obesity in childhood is associated with a significant number of complications, such as sleep apnea syndrome, insulin resistance and type 2 diabetes, hypertension, cardiovascular disease and some cancers. It is estimated that the prevalence of sleep apnea in children is 2-3% in the general population, while in obese adolescents, varies between 13% and 66%, according to various studies. It is associated with impairment of neurocognitive function, behavior, cardiovascular system, metabolic disorders and growth. Sleep apnea is a serious public health problem that increases when children and adolescents are overweight or obese. We hypothesize that aerobic endurance exercise can be an effective treatment for obesity and apnea at the same time. The aim of this study was to determine the influence of physical activity in children and adolescents with overweight / obesity in sleep apnea. An observational, descriptive, prospective, longitudinal study will be carried out in children with sleep apnea and obesity. The universe will be made up of 60 children and adolescents aged between 10 and 18 years, attending the endocrinology service for suffering of obesity in the Hospital Clinico San Cecilio of Granada during the period September 2012-September 2013. The smple will consist of children and adolescents that meet these characteristics and to hom their arents/tutors have authorized through the informed consent. Sleep apnea in children wil be measured by polysomnography and sleep quality questionnaire. There will also be a nutritional assessment by a food frequency questionnaire and an anthropometric assessment. Among the expected results are the lower overweight and obesity in children through the physical activity program. To reduce apnea and to improve sleep quality

Ecological correlations between food availability and mortality: more than you can eat?

Introduction: There is little information regarding the impact of diet on disease incidence and mortality in Switzerland. Objectives: We aimed at assessing the associations between food availability and disease using ecological correlations. Methods: Time-trend ecologic study for period 1970 to 2009. Food availability was measured through the FAO food balance sheets. Standardized mortality rates (SMRs) were obtained from the Swiss Federal Office of Statistics. Cancer incidence data was obtained from the WHO Health for all database and the Vaud cancer registry. Association between food availability and mortality/incidence was assessed at lags 0, 5, 10 and 15 years by Spearman correlation. Results: Alcoholic beverages and fruit availability were positively associated with SMRs from all types of cardiovascular disease, while fish availability was negatively associated. Animal products, meat and animal fats were positively associated with SMR from ischemic heart disease only. For cancers, opposite results were found whether the association used SMRs or incidence rates. For all cancers, alcoholic beverages and fruits were positively associated with SMRs but negatively associated with incidence rates. Similar findings were obtained for all other foods, with the exception of vegetables, which were weakly and negatively associated with SMRs and incidence rates. Finally, a 15 years lag time reversed the association for animal and vegetal products, weakened the association for alcohol and fruits and strengthened the association for fish. Conclusion: Ecologic associations between food availability and disease vary considerably whether mortality or incidence rates are used. Great care should be taken when interpreting the results.