Vorapaxar in the secondary prevention of atherothrombotic events.

BACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.).

La vitesse de l'onde de pouls et la pression artérielle centrale devraient-elles être mesurées chez les patients hypertendus [Not Available].

Diagnosis and treatment of arterial hypertension are essential in order to reduce the mortality and the morbidity associated with this condition. The decision to treat hypertension is often based on serial office blood pressure measurements, but new non-invasive measurements such as pulse wave velocity or central blood pressure measurement using pulse wave analysis can be useful to assess the cardiovascular risk with more precision. Indeed, pulse vawe velocity, which is a marker of arterial stiffness, is an independent risk factor for future cardiovascular events. Non-pharmacological and pharmacological therapies can affect both pulse wave velocity and central pressure. However, more studies are needed in order to determine if these measurements can be use as surrogate marker of cardiovascular disease.

Cardiologie. Quoi de neuf en 2009 [Cardiology 2009: what is new?].

The present review provides a selected choice of clinical research in the field of heart failure, electrophysiology, cardiac imaging and interventional cardiology.

Physiopathology of the embryonic heart (with special emphasis on hypoxia and reoxygenation).

The adaptative response of the developing heart to adverse intrauterine environment such as reduced O2 delivery can result in alteration of gene expression with short- and long-term consequences including adult cardiovascular diseases. The tolerance of the developing heart of acute or chronic oxygen deprivation, its capacity to recover during reperfusion and the mechanisms involved in reoxygenation injury are still under debate. Indeed, the pattern of response of the immature myocardium to hypoxia-reoxygenation differs from that of the adult. This review deals with the structural and metabolic characteristics of the embryonic heart and the functional consequences of hypoxia and reoxygenation. The relative contribution of calcium and sodium overload, pH disturbances and oxidant stress to the hypoxia-induced cardiac dysfunction is examined, as well as various cellular signaling pathways (e.g. MAP kinases) involved in cell survival or death. In the context of the recent advances in developmental cardiology and fetal cardiac surgery, a better understanding of the physiopathology of the stressed developing heart is required.

Detección Precoz de los factores de riesgo cardiovasculares en los Centros de Atención Primaria de Cataluña Central

Las enfermedades cardiovasculares son actualmente la principal causa de muerte prematura, por lo que es necesario controlar los factores que podrían reducir el riesgo cardiovascular. El presente estudio se centra en la ejecución de los protocolos de prevención cardiovascular en los Centros de Atención Primaria de Cataluña central, ya que se cree que una prevención adecuada podría reducir significativamente la mortalidad por esta enfermedad. Para lograr este objetivo, se propone utilizar una muestra poblacional de 100 individuos entre 45 y 65 años y realizar un estudio cuantitativo descriptivo. Basándose éste, en el control de las diferentes variables que afectan en poseer factores de riesgo cardiovascular: el alcohol, el tabaco, la obesidad, la inactividad física, la diabetes y el colesterol.

Lentiviral vectors efficiently transduce the EGFP gene into cardiomyocytes in vivo : immunohistology and Elisa quantification of the transgene

RESUME Les maladies cardio-vasculaires représentent la cause la plus importante de mortalité et de morbidité dans les pays occidentaux. La thérapie génique offre une nouvelle approche au traitement de ces maladies. L'expression de gènes protecteurs dans le myocarde par des technologies de transfert génique peut améliorer la fonction ventriculaire lors de l'insuffisance cardiaque ou stimuler la formation de nouveaux vaisseaux dans la maladie coronarienne. Etant donné qu'une majorité des maladies cardiaques sont des maladies chroniques, l'expression durable du gène thérapeutique introduit dans le coeur est souhaitable dans de nombreux cas. Malheureusement, l'utilité des vecteurs de transfert génique les plus utilisés en thérapie génique cardiovasculaire est limitée par une performance faible (ADN plasmidique) et une courte durée d'expression (adénovirus). Récemment, des vecteurs de transfert génique dérivés des lentivirus, une sous-famille des rétrovirus, ont retenu l'attention de la communauté scientifique en raison de leur capacité à exprimer des gènes à long terme. Contrairement aux vecteurs rétroviraux traditionnels, les vecteurs lentiviraux transduisent des gènes même dans des cellules qui ne se divisent pas, ce qui est le cas des cardiomyocytes adultes. Ces vecteurs présentent un profil de biosécurité comparable à celui des vecteurs rétroviraux traditionnels. Nous avons donc décidé de tester l'utilité des vecteurs lentiviraux pour le transfert génique dans des cardiomyocytes de rat adulte in vitro et in vivo. Plusieurs versions de vecteurs lentiviraux contenant différent promoteurs ont été construites. Ces vecteurs contenant le gène marqueur EGFP (enhanced green fluorescent protein) ont été testés dans des cardiomyocytes de rat in vitro, ainsi que dans des coeurs de rat in vivo. Le but de ces expériences était de déterminer la durée de l'expression du transgène après injection intramyocardique chez le rat. Pour ce faire, nous avons développé une technique ELISA pour détecter la protéine EGFP dans des extraits de tissu cardiaque. Les résultats ont montré que la protéine EGFP était encore présente à des niveaux significatifs jusqu'à dix semaines après l'injection de vecteurs lentiviraux, alors que l'expression transgénique obtenue avec un vecteur adénoviral traditionnel a été plus limitée dans le temps. Ces résultats démontrent la capacité des vecteurs lentiviraux à exprimer des gènes d'intérêt de manière performante et stable dans le cœur de rat adulte in vivo. SUMMARY Cardiovascular diseases are the first cause of morbidity and mortality in Western countries. Gene therapy offers a new approach to these diseases. Expression of therapeutic genes in the myocardium by gene transfer technologies can improve ventricular function in heart failure and stimulate neovascularization in coronary disease. Chronic heart diseases likely require sustained expression of the therapeutic gene within the heart itself. Unfortunately, the most commonly used vectors in cardiovascular gene therapy, i.e. plasmid DNA and recombinant adenovirus vectors, are limited by poor DNA uptake and transient transgene expression, respectively. Recently, lentivirus-derived vectors have attracted much interest because of their ability to achieve long-term transgene expression. In contrast to traditional retroviral vectors, lentiviral vectors are also able to transduce non- dividing cells, while presenting a comparable biosafety profile. Adult cardiomyocytes are terminally differentiated cells that do not divide under normal conditions. For these reasons, we have decided to evaluate the efficiency of lentiviral vectors for gene-transduction of adult cardiomyocytes both in vitro and in vivo. We constructed various types of lentiviral vectors containing various promoters. Vectors encoding EGFP as a reporter gene were tested in rat cardiomyocytes in vitro and in rat hearts in vivo. The aim of the experiments involved in this thesis work was to determine the duration of the expression of the transgene after rat intramyocardial injection using a quantitative assay. Therefore, an ELISA technique was set up to measure the EGFP protein in rat heart tissue extracts. Our results showed that the EGFP protein was still present at significant levels at ten weeks after lentiviral vector injection, whereas the duration of expression with adenoviral vectors was shorter. These results demonstrate that lentiviral vectors efficiently deliver genes and achieve sustained transgene expression in adult rat cardiomyocytes in vivo.

Short-term effects of particulate matters on pulse pressure in two general population studies.

OBJECTIVES: To explore the association of short-term exposure to particulate matter with aerodynamic diameters less than 10 μm (PM10) with pulse pressure, SBP, and DBP taking outdoor temperature into account in two large population-based studies in Switzerland. METHODS: We used data from the Bus Santé study including 5605 adults in Geneva and the CoLaus study including 6183 adults in Lausanne. PM10 and meteorological data were measured from fixed monitoring stations. We analyzed the association of short-term exposure to PM10 (on the day of examination visit and up to 7 days before) with pulse pressure, SBP, and DBP by linear regression, controlling for potential confounders and effect modifiers. RESULTS: Average PM10 levels were 22.4 μg/m in Geneva and 31.7 μg/m in Lausanne. In adjusted models, for each 10 μg/m increase in 7-day PM10 average, pulse pressure and SBP increased by 0.583 (95% confidence interval, 0.296-0.870) mmHg and 0.490 (0.056-0.925) mmHg in Geneva, and 0.183 (0.017-0.348) mmHg and 0.036 (0.042-0.561) mmHg in Lausanne, respectively. Stronger associations of pulse pressure and SBP with PM10 were observed when outdoor temperature was above 5°C. CONCLUSION: Positive associations of pulse pressure and SBP with short-term exposure to PM10 were found and replicated in the Swiss adult population. Our results suggest that even low levels of air pollution may substantially impact cardiovascular risk in the general population.

Epithelial sodium transport and its control by aldosterone: the story of our internal environment revisited.

Transcription and translation require a high concentration of potassium across the entire tree of life. The conservation of a high intracellular potassium was an absolute requirement for the evolution of life on Earth. This was achieved by the interplay of P- and V-ATPases that can set up electrochemical gradients across the cell membrane, an energetically costly process requiring the synthesis of ATP by F-ATPases. In animals, the control of an extracellular compartment was achieved by the emergence of multicellular organisms able to produce tight epithelial barriers creating a stable extracellular milieu. Finally, the adaptation to a terrestrian environment was achieved by the evolution of distinct regulatory pathways allowing salt and water conservation. In this review we emphasize the critical and dual role of Na(+)-K(+)-ATPase in the control of the ionic composition of the extracellular fluid and the renin-angiotensin-aldosterone system (RAAS) in salt and water conservation in vertebrates. The action of aldosterone on transepithelial sodium transport by activation of the epithelial sodium channel (ENaC) at the apical membrane and that of Na(+)-K(+)-ATPase at the basolateral membrane may have evolved in lungfish before the emergence of tetrapods. Finally, we discuss the implication of RAAS in the origin of the present pandemia of hypertension and its associated cardiovascular diseases.

Aspirin and statin use and the subsequent development of depression in men and women: Results from a longitudinal population-based study.

OBJECTIVE: Low-grade chronic inflammation is one potential mechanism underlying the well-established association between major depressive disorder (MDD) and increased cardiovascular morbidity. Both aspirin and statins have anti-inflammatory properties, which may contribute to their preventive effect on cardiovascular diseases. Previous studies on the potentially preventive effect of these drugs on depression have provided inconsistent results. The aim of the present paper was to assess the prospective association between regular aspirin or statin use and the incidence of MDD. METHOD: This prospective cohort study included 1631 subjects (43.6% women, mean age 51.7 years), randomly selected from the general population of an urban area. Subjects underwent a thorough physical evaluation as well as semi-structured interviews investigating DSM-IV mental disorders at baseline and follow-up (mean duration 5.2 years). Analyses were adjusted for a wide array of potential confounders. RESULTS: Our main finding was that regular aspirin or statin use at baseline did not reduce the incidence of MDD during follow-up, regardless of sex or age (hazard ratios, aspirin: 1.19; 95%CI, 0.68-2.08; and statins: 1.25; 95%CI, 0.73-2.14; respectively). LIMITATIONS: Our study is not a randomized clinical trial and could not adjust for all potential confounding factors, information on aspirin or statin use was collected only for the 6 months prior to the evaluations, and the sample was restricted to subjects between 35 and 66 years of age. CONCLUSION: Our data do not support a large scale preventive treatment of depression using aspirin or statins in subjects aged from 35 to 66 years from the community.

Thrombin-receptor antagonist vorapaxar in acute coronary syndromes

Background: Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. Methods: In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS: Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P = 0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P = 0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. Conclusions: In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.)

Disease profiles of detainees in the Canton of Vaud in Switzerland: gender and age differences in substance abuse, mental health and chronic health conditions.

BACKGROUND: Literature on the disease profile of prisoners that differentiates by age and gender remains sparse. This study aimed to describe the health of correctional inmates in terms of substance abuse problems and mental and somatic health conditions, and compare it by gender and age. METHODS: This study examined cross-sectional data from the Canton of Vaud in Switzerland on the health conditions of detainees who were in prison on January 1, 2011 or entered prison in 2011. Health conditions validated by physician examination were reported using the International Classification of Diseases (ICD) version 10. The analyses were descriptive by groups of prisoners: the entire sample (All), Men, Older adults and Women. RESULTS: A total of 1,664 individuals were included in the analysis. Men comprised 91.5 % of the sample and had a mean age of 33 years. The other 8.5 % were women and had an average age of 39. Older adults (i.e., age 50 and older) represented 7 % of the total sample. Overall, 80 % of inmates were non-Swiss citizens, but the proportion of Swiss prisoners was higher among the older adults (51 %) and women (29 %). Overall, 41 % of inmates self-reported substance abuse problems. Of those, 27 % were being treated by psychiatrists for behavioral disorders related to substance abuse. Chronic infectious diseases were found in 9 % of the prison population. In addition, 27 % of detainees suffered from serious mental health conditions. Gender and age had an influence on the disease profile of this sample: compared to the entire prison population, the older inmates were less likely to misuse illegal drugs and to suffer from communicable infections but exhibited more problems with alcohol and a higher burden of chronic health conditions. Female prisoners were more disposed to mental health problems (including drug abuse) and infectious diseases. In terms of chronic diseases, women suffered from the same conditions as men, but the diseases were more prevalent in women. CONCLUSION: It is important to understand the different disease profiles of prisoners by gender and age, as it helps identify the needs of different groups and tailor age-and gender-specific interventions.

Secondhand tobacco smoke exposure in open and semi-open settings: a systematic review

Background: Some countries have recently extended smoke-free policies to particular outdoor settings; however, there is controversy regarding whether this is scientifically and ethically justifiable. Objectives: The objective of the present study was to review research on secondhand smoke (SHS) exposure in outdoor settings. Data sources: We conducted different searches in PubMed for the period prior to September 2012. We checked the references of the identified papers, and conducted a similar search in Google Scholar. Study selection: Our search terms included combinations of"secondhand smoke,""environmental tobacco smoke,""passive smoking" OR"tobacco smoke pollution" AND"outdoors" AND"PM" (particulate matter),"PM2.5" (PM with diameter ≤ 2.5 µm),"respirable suspended particles,""particulate matter,""nicotine,""CO" (carbon monoxide),"cotinine,""marker,""biomarker" OR"airborne marker." In total, 18 articles and reports met the inclusion criteria. Results: Almost all studies used PM2.5 concentration as an SHS marker. Mean PM2.5 concentrations reported for outdoor smoking areas when smokers were present ranged from 8.32 to 124 µg/m3 at hospitality venues, and 4.60 to 17.80 µg/m3 at other locations. Mean PM2.5 concentrations in smoke-free indoor settings near outdoor smoking areas ranged from 4 to 120.51 µg/m3. SHS levels increased when smokers were present, and outdoor and indoor SHS levels were related. Most studies reported a positive association between SHS measures and smoker density, enclosure of outdoor locations, wind conditions, and proximity to smokers. Conclusions: The available evidence indicates high SHS levels at some outdoor smoking areas and at adjacent smoke-free indoor areas. Further research and standardization of methodology is needed to determine whether smoke-free legislation should be extended to outdoor settings.

Orofacial pain of cardiac origin: review literature and clinical cases

The most common types of orofacial pain originate at the dental or periodontal level or in the musculoskeletal structures. However, the patient may present pain in this region even though the source is located elsewhere in the body. One possible source of heterotopic pain is of cardiac origin. Objectives: Report two cases of orofacial pain of cardiac origin and review the clinical cases described in the literature. Study Design: Description of clinical cases and review of clinical cases. Results and conclusions: Nine cases of atypical pain of cardiac origin are recorded, which include 5 females and 4 males. In craniofacial structures, pain of cardiac origin is usually bilateral. At the craniofacial level, the most frequent location described is in the throat and jaw. Pain of cardiac origin is considered atypical due to its location, although roughly 10% of the cases of cardiac ischemia manifest primarily in craniofacial structures. Finally, the differential diagnosis of pain of odontogenic origin must be taken into account with pain of non-odontogenic origin (muscle, psychogenic, neuronal, cardiac, sinus and neurovascular pain) in order to avoid diagnostic errors in the dental practice as well as unnecessary treatments.

Phenol-Explorer 3.0: a major update of the Phenol-Explorer database to incorporate data on the effects of food processing on polyphenol content

Polyphenols are a major class of bioactive phytochemicals whose consumption may play a role in the prevention of a number of chronic diseases such as cardiovascular diseases, type II diabetes and cancers. Phenol-Explorer, launched in 2009, is the only freely available web-based database on the content of polyphenols in food and their in vivo metabolism and pharmacokinetics. Here we report the third release of the database (Phenol-Explorer 3.0), which adds data on the effects of food processing on polyphenol contents in foods. Data on >100 foods, covering 161 polyphenols or groups of polyphenols before and after processing, were collected from 129 peer-reviewed publications and entered into new tables linked to the existing relational design. The effect of processing on polyphenol content is expressed in the form of retention factor coefficients, or the proportion of a given polyphenol retained after processing, adjusted for change in water content. The result is the first database on the effects of food processing on polyphenol content and, following the model initially defined for Phenol-Explorer, all data may be traced back to original sources. The new update will allow polyphenol scientists to more accurately estimate polyphenol exposure from dietary surveys. Database URL: http://www.phenol-explorer.eu

Cardiologie [Cardiology update in 2014].

Important clinical trials and therapeutic advances in the field of cardiology have been presented in 2014. New evidences on the management of acute myocardial infarction and the duration of dual antiplatelet therapy after coronary stent implantation have been published. A new class of therapeutic agents seems to offer promising perspectives for patients with heart failure and reduced ejection fraction. The new generation of subcutaneous or MRI-compatible implantable defibrillators is a major technological breakthrough. Finally, the European Society of Cardiology published new recommendations for the management of patients with cardiovascular diseases. This selective review of the literature summarizes the most important studies in the field of interventional cardiology, rhythmology, heart failure and cardiac imaging.