Un estudio indica que una variación del cromosoma 9 genera el riesgo de padecer ELA

Determinadas variaciones genéticas en el cromosoma 9 podrían desempeñar un papel en el desarrollo de la esclerosis lateral amiotrófica (ELA) y en la demencia frontotemporal, según dos estudios diferentes que se publican en la edición 'on line' de 'The Lancet Neurology', junto con evidencias de que una región de este cromosoma está vinculada a un mayor riesgo de ELA en múltiples poblaciones.
Entre el 5 y el 10 por ciento de los casos de ELA (también conocida como Enfermedad de Lou Gehrig') son hereditarias. Hasta ahora, unos cuantos genes han sido vinculados a la ELA, pero éstos explican sólo un pequeño número de casos familiares. La causa de los casos esporádicos de ELA más comunes sigue siendo desconocida.
Varios estudios recientes de asociación del genoma completo (GWAS, por sus siglas en inglés) han identificado un conjunto de genes susceptibles, pero la replicación de estas asociaciones no ha tenido éxito en estudios independientes. En 2006, el vínculo entre los casos hereditarios de ELA y el cromosoma 9 fue identificado, por primera vez, en familias de Escandinavia. Sin embargo, posteriores investigaciones no revelaron a ninguna variante genética culpable de la aparición de la enfermedad.

En el primer estudio, el investigador de los Institutos Nacionales de Salud de Estados Unidos Bryan Traynor y varios científicos internacionales realizaron un GWAS para identificar factores de riesgo genéticos para la ELA en la población de Finlandia. En concreto, analizaron 318.167 variaciones del ADN conocidas como polimorfismos de un solo nucleótido o SNP en el genoma de 405 pacientes con ELA (93 casos familiares y 312 esporádicos) y en 497 pacientes de control.

Descubrieron dos variaciones genéticas que contribuyen a aumentar el riesgo de ELA. Una fue identificada en el gen SOD1, previamente asociado con el riesgo de ELA --en el cromosoma 21q (rs13048019)-- y otra en el cromosoma 9p (rs3849942). Una u otra de estas variaciones fue localizada en más del 70 por ciento de los pacientes con un historial familiar de ELA, lo que explica una proporción importante de casos de ELA familiar en Finlandia.

Además, los autores definieron un grupo de 42 SNPs en el cromosoma 9p (compartido por el 44 por ciento de los pacientes con ELA familiar y por el 19 por ciento de los casos de ELA esporádicos) que fue vinculado a un significativo incremento del riesgo de ELA entre la población finlandesa. El haplotipo compartido sugiere también un posible 'efecto fundador' para el cromosoma 9p localizado en Finlandia. Los autores concluyen diciendo que el cromosoma 9p21 es "la mayor causa de ELA familiar entre la población finlandesa".

European Society of Cardiology guidelines for Myocardial Revascularisation

The European Society of Cardiology (ESC) today announces the release of new Clinical Practice Guidelines covering Myocardial Revascularisation. These guidelines were developed following pioneering and extensive co-operation between the ESC and the European Association of Cardio-Thoracic Surgeons (EACTS). Myocardial Revascularisation – simply, the restoration of adequate blood and oxygen supplies to the heart – is the collective term for the response to the symptoms of coronary artery disease (CAD), including heart attacks and angina. The new guidelines will be presented at the ESC Congress in Stockholm on 29 August during the Clinical Practice Guidelines session in lecture room Stockholm, Zone K, starting at 0845hrs.
These guidelines reflect the fact that there are many options available to physicians to treat the many forms of CAD, both acute and non-acute. These include surgery, stent implantation and drug therapies, and the options cross traditional boundaries of medicine such as cardiology and surgery. “Our intention in writing these guidelines was to give patient-centred recommendations that lead to the most appropriate treatment regime for the different types of CAD,” said Doctor William Wijns of the ESC and Co-Chair of the Task Force. “We also wanted to provide reference materials based on best practice but not conditioned by the skill and preferences of individual physicians. The major challenge faced by physicians is not how to treat the CAD patient, but which of the many treatment options to select.”
The Task Force was made up of 24 experts, drawn equally from surgeons, interventional cardiologists and general cardiologists, and representing the ESC and the EACTS. The new guidelines are noteworthy for three main reasons:
They are an example of strong co-operation between the ESC and the EACTS, and have proved to very successful in meeting the objectives.
The content addresses the full extent of CAD, and of associated diseases, which was previously covered in separate guidelines, or not at all.
The guidelines introduce the concept of Heart Teams, essentially a grouping from across disciplines ensuring – when practical – that the patient is fully informed and takes part in the key decisions. The heart team should include one of each of the following specialists; interventional cardiologist, clinical cardiologist, and cardiac surgeon.
The guidelines encompass the full extent of CAD treatment and expected outcomes, including managing stable and unstable angina, myocardial infarction, diabetes-related symptoms and associated renal failure. Recommendations are made on all treatment options, from the technical aspects of stent implantation to the use of imaging technologies, and from risk management to follow-up activities.
The establishment of Heart Teams is a vital recommendation for medical teams everywhere, and formalises the make-up of the multi-discipline team responsible for patient care following CAD treatment. Co-Chair, Professor Philippe Kolh of the EACTS explains, “It is important that physicians offer patients the opportunity to influence the response to their condition. Clearly, for acute cases, such flexibility can be difficult to accommodate, but for the 30 percent of patients with stable conditions, it is an important factor. Immediate but less durable treatments such as a stent implantation may not be the right choice for some patients. Depending on their lifestyle and responsibilities, some may prefer to elect for a surgical procedure that offers a longer-term result.”


The complete guidelines document can be downloaded from the ESC website at http://www.escardio.org/guidelines-surveys/esc-guidelines.

Iron Deficiency in Heart Failure

Iron plays a key role in human homeostasis. It is essential for growth and survival, and is a vital ingredient in numerous processes including erythropoiesis, oxygen transport and storage, oxidative metabolism in the skeletal and heart muscle, synthesis and degradation of lipids, carbohydrates, DNA and RNA. Important though it is, iron metabolism must be precisely controlled because iron is insoluble and excess levels can be toxic.Iron deficiency is a relatively common nutritional disorder that affects more than one third of the general population, and is often associated with chronic diseases such as inflammatory bowel disease, Parkinson’s disease, rheumatoid diseases and renal failure. Until recently, there has been little interest in the linkage between iron deficiency and the natural course of chronic heart failure (CHF) syndrome. Traditionally iron deficiency has been linked with a presence of anaemia in CHF, and its reported prevalence varies from 20 percent to 70 percent. Recent research carried out at the Military Hospital, Medical University of Wroclaw has now demonstrated that iron deficiency must be viewed in a much broader clinical context, as it also affects at least one-third of non-anaemic CHF patients. The research was led by Doctor Piotr Ponikowski, who said, “Iron deficiency appears to be independent of the severity of CHF symptoms, and occurs irrespective of anaemia. It also seems to be associated with exercise intolerance and leads to a reduced quality of life. Our research shows that it probably constitutes an ominous sign of a poor outcome, independently of the other well-established prognosticators. In light of its high prevalence and clinical consequences, iron deficiency may well be perceived as an attractive therapeutic target in CHF.”Several earlier reports have already shown that, in iron deficient CHF patients, iron repletion can safely improve functional capacity, exercise tolerance and quality of life. Cardiologists should become more aware of the importance of iron deficiency in CHF patients, and be able to evaluate iron status using a combination of simple, clinically relevant parameters of iron metabolism. More studies are needed to evaluate whether correction of iron deficiency in CHF would translate into clinical benefits.

La nutrigenética será clave para un mejor rendimiento del deportista

El catedrático de Nutrición de la Universidad de Navarra, Alfredo Martínez, ha asegurado que la nutrigenética "mejorará el rendimiento de los deportistas y cambiará su forma de competir", ya que, "podrán prever su mejor momento de forma y recuperarse más fácilmente gracias a la alimentación". Así lo ha expuesto el investigador y profesor de Nutrición durante el curso de verano 'Nutrición, alimentos funcionales y actividad física en la promoción de la salud', impartido en la Universidad del País Vasco (UPV), y en la que se refirió a los beneficios de la nutrición basada en los genes.

Según ha informado la Universidad de Navarra en un comunicado, el experto señaló que "una buena combinación de deporte y alimentación mantiene la salud, aumenta el rendimiento y acelera la recuperación". Sin embargo, advirtió de que "no todas las actividades son iguales, tienen la misma intensidad, duración o frecuencia". "Los individuos también nos diferenciamos, en edad, sexo y el estado nutricional previo. Por eso hay muchos aspectos que deben considerarse para una correcta planificación, incluyendo la herencia genética", defendió.

Respecto a los alimentos más convenientes para practicar deporte, destacó que existe consenso en la importancia de los hidratos de carbono como fuente primaria de energía, "aunque hay quien piensa que los niveles de glucógeno no influyen en los resultados deportivos, en muchas disciplinas sí lo hacen". "Un maratoniano, por ejemplo, lo primero que gasta son sus reservas de glucógeno, antes de utilizar otra mezcla de combustible", añadió.

En el caso de las proteínas, el catedrático de Nutrición de la Universidad de Navarra señaló que su valor se complementa con el entrenamiento. "Por ejemplo, Rafael Nadal tiene mucho más desarrollado el brazo izquierdo -es zurdo-, pero las proteínas las toma para los dos brazos. Lo que ocurre es que toma un buen aporte de proteínas y el ejercicio -la hormesis- hace que le sirvan para aumentar la fuerza de la extremidad que más usa", explicó.

Por su parte, los lípidos, explicó el experto, "resultan esenciales para la vida y para el deporte, por sus funciones reguladores, estructurales y energéticas". En su opinión, decir que la grasa "sólo sirve como fuente de energía para ejercicios intensos y prolongados o con bajo nivel de glucógeno resulta por tanto falso, puesto que la usamos en todo momento dentro de la mezcla de nutrientes que nos sirve como combustible".

Angiotensin II antagonists in paroxysmal atrial fibrillation: Results from the ANTIPAF trial

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting about 7 million people in Europe. It is a progressive chronic disease in which episodes become more frequent and long-lasting over time. Conventional anti-arrhythmic therapy aims at halting progression and reducing symptoms, but the use of most anti-arrhythmic drugs is compromised by severe side effects, such as pro-arrhythmia or extra-cardiac organ toxicity.
A number of meta-analyses have shown that angiotensin II antagonists (or ARBs) may have the potential to reduce recurrence of AF, with an almost placebo-like tolerability. However, the available evidence from meta-analyses is heterogeneous with respect to the patient populations under investigation, the specific study designs, and the methods used to detect recurrent AF.
The ANTIPAF (ANgiotensin II anTagonists In Paroxysmal Atrial Fibrillation) trial was the first trial to prospectively evaluate the principal hypothesis that the angiotensin II receptor antagonist olmesartan suppresses episodes of paroxysmal AF. The primary endpoint of the trial was the percentage of days with documented episodes of paroxysmal AF throughout 12 months of follow-up. Secondary endpoints included the time to first occurrence of a documented relapse of AF, quality of life, time to first AF recurrence, time to persistent AF, and the number of hospitalisations.
Patients were stratified according to presence of beta-blocker therapy and randomised to placebo or olmesartan (40 mg/day). Concomitant therapy with ARBs, ACE inhibitors, and anti-arrhythmic drugs was prohibited. Patients were followed using daily trans-telephonic ECG recordings (at least one 1-minute ECG/day) independent of symptoms - and were encouraged to submit further tele-ECGs in any case of AF-related symptoms. Follow-up visits were scheduled after 3, 6, 9 and 12 months, which included long-term ECGs, transthoracic echocardiography, laboratory markers, and assessment of quality of life.
425 patients (at least 18 years old) with documented episodes of paroxysmal AF were included from 37 centres in Germany. A total of 87,818 tele-ECGs were analysed during follow-up (44,888 ECGs in the placebo group and 42,930 ECGs in the olmesartan group). Thus, a mean of 207 tele-ECGs were recorded per patient with an average of 1.12 tele-ECGs per patient and day of follow-up.
The study demonstrated no significant difference in the burden of AF (primary endpoint) between both treatment groups. Further secondary outcome parameters such as quality of life, time to first AF recurrence, time to persistent AF, and the number of hospitalisations were also similar between groups. However, the time to prescription of recovery medication (amiodarone) was longer in patients treated with olmesartan than in those receiving placebo.
Commenting on the study results, principal investigator Professor Andreas Götte from St. Vincenz Hospital, Paderborn, Germany, said: "In patients with AF and concomitant structural heart disease such as hypertensive heart disease or systolic heart failure, ARBs are effective adjunct therapies while being highly tolerable. ANTIPAF provides pivotal evidence, however, that ARBs do not reduce the number of AF episodes in patients with paroxysmal AF and without structural heart disease."

* The ANTIPAF study was conducted by the German Competence Network on Atrial Fibrillation (AFNET), an interdisciplinary national research network funded by the German Federal Ministry of Education and Research.

AVERROES trial terminated early: apixaban associated with "important" relative risk reduction for stroke and systemic embolism in AF

The phase 3 AVERROES (Apixaban Versus Acetylsalicylic acid (ASA) to Prevent Strokes) trial, designed to show the superiority of apixaban over aspirin for the prevention of stroke or systemic embolism in high-risk atrial fibrillation patients unsuitable for treatment with a vitamin K antagonist (warfarin), was terminated early following a recommendation from the Data Monitoring Committee. Final study visits took place between 1 July and 15 August this year. A predefined interim analysis had shown clear evidence of a clinically important reduction in stroke and systematic embolism and an acceptable safety profile for apixaban compared to aspirin. The principal investigator, Dr Stuart Connolly from Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada, and the study's sponsors accepted the recommendation to terminate the trial.
AVERROES was a double-blind randomised trial which recruited 5600 patients with atrial fibrillation (mean age 70 years) demonstrated or expected to be unsuitable for treatment with a vitamin K antagonist (because of difficulty in controlling treatment effect, increased risk of haemorrhage, patient refusal to take warfarin or intermediate stroke risk). So far, aspirin is the only effective treatment for stroke prevention in patients unsuitable for warfarin.
Apixaban, a Factor Xa inhibitor, has already been investigated for the prevention of deep vein thrombosis, following orthopaedic surgery, and after acute coronary syndrome - but not so far in patients with atrial fibrillation. The AVERROES trial compared the effects of apixaban and aspirin in these patients. Another trial, ARISTOTLE (not yet completed) is studying apixaban against warfarin in patients suitable for warfarin.
The AVERROES study was performed at 520 sites worldwide and recruitment was completed in December 2009. The primary endpoint was a composite of stroke or systemic embolism, while the primary safety endpoint was major haemorrhage. Secondary and tertiary endpoints were a composite of stroke, systemic embolism, myocardial infarction or vascular death, and total death.
At the interim analysis results showed that the annual rate of stroke or systemic embolism (the primary outcome) was 3.9% per year on aspirin and 1.7% per year on apixaban (HR 0.45, p<0.001). The rate of major haemorrhage was 1.4% per year on aspirin and 1.6% per year on apixaban (HR 1.18, p=0.33). The rate of haemorrhagic stroke was 0.2% per year in both treatment groups and there was no evidence of hepatic toxicity or other major adverse events.
Commenting on the results, Dr Connolly said: "The results of AVERROES are truly impressive. The reduction in stroke and systemic embolism is very important and the increased risk of haemorrhage is small. It appears that apixaban will be an excellent treatment for the many patients with atrial fibrillation who are unsuitable for warfarin. These findings will reduce the burden of stroke in society.”

* Atrial fibrillation is a common heart rhythm disorder in which the upper chamber of the heart beats improperly. Patients with AF are at increased risk of stroke because of the formation of blood clots in the upper chamber. The standard therapy for the prevention of stroke and other embolic events in AF is warfarin.

Nurses can significantly reduce the risk of recurrent complications in heart patients: results from the RESPONSE trial

A six-month outpatient prevention programme conducted by nurses has resulted in significant and sustained improvements in the control of cardiovascular risk factors, including high cholesterol or high blood pressure, in patients hospitalised for a heart attack or impending heart attack.
The programme, applied in addition to standard medical care, led to the improved adherence to current guidelines on prevention, including lifestyle and compliance with drug treatment. The nurses were able to increase the proportion of patients with good control of risk factors by 40% (defined as at least seven out of nine risk factors on target) and to reduce the calculated risk of dying in the next 10 years by about 17%.
RESPONSE (Randomised Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists) was an 11-centre randomised study designed to quantify the impact of a nurse-co-ordinated outpatient risk management programme on the risk of future clinical events in patients with symptomatic coronary artery disease. The primary endpoint was patient evaluation according to the SCORE risk score at 12 months, with secondary endpoints assessed according to the Framingham risk score and individual risk factors at 12 months follow-up (including lipid profile, glucose, blood pressure, weight, waist circumference, physical activity, healthy diet, alcohol consumption).
In explaining the background to the trial, principal investigator Professor Ron Peters from the Academic Medical Center, Amsterdam, said: "Patients with coronary artery disease are at high risk of recurrent complications and death. Preventive care can effectively reduce this risk, and guidelines have been issued by the American Heart Association/American College of Cardiology and the European Society of Cardiology which target common risk factors for heart disease such as high blood pressure, smoking, and high cholesterol.
"Together, these risk factors are associated with the development of coronary artery disease, which remains the world's leading cause of death. At present, a considerable gap exists between these guidelines and their application in clinical practice. It is widely believed, both by patients and doctors, that the preventive aspect of treatment is given insufficient priority and that new approaches are needed to realise the full benefits of prevention. A short coaching programme by a nurse, on top of usual care, is such a new approach already found promising in primary care."
The RESPONSE trial, which evaluated an outpatient nursing programme in 11 hospital centres in the Netherlands, included 754 patients hospitalised for an acute coronary complication (MI or impending MI). They were randomised to either usual care alone or usual care plus a six-month nursing intervention that included four extra visits to the outpatient clinic. Nurses gave advice on healthy lifestyle (food choices, physical exercise, non-smoking, weight control), and monitored major risk factors, such as blood pressure, cholesterol and sugar levels, and use of preventive medication. The nurses pursued specific targets as defined by the guidelines, and if necessary drug treatment was adjusted in collaboration with treating physicians.
The primary measurement of the study was performed at 12 months, which was six months after the last visit to the nurse. Results showed a significant improvement in risk factor prevalence at the end of the programme, with no loss of effect at 12 months.
Overall, at 12 months after the start of the programme, 35% of patients in the nursing group and 25% of patients in the control group were classified as having good control of risk factors (defined as at least seven out of nine factors on target). This reflects an increase of 40%. Of the risk factors targeted by the intervention, body weight was the least successful. There was no change in weight or waist circumference between baseline and 12 months, with no difference between the two study groups. "This may indicate that weight loss is not a realistic target in the first year after a coronary event," said Professor Peters, "when priority needs to be given to several other risk factors. It remains to be seen if later attempts might be more successful."
When the risk of death over the next ten years was calculated according to the SCORE risk function, the nurses were able to reduce this risk by 17%.
Professor Peters noted that these results were achieved against a background of medical care that was better than expected, with risk factor levels in the study population more favourable than those reported in the literature - and with excellent adherence to medication in both groups. This high level of care in the control group, he added, may have been influenced by participation in the trial.
"The nurse programme was practical and well attended by the patients," he said. "More than 93% of patients attended all visits to the nurse. These findings are very encouraging and support the initiation of prevention programmes by nurses to help patients reduce their risk of future complications."