Revista Societatii de Medicina Interna
PROIECTE EUROPENE DE CERCETARE
Proiectul BLOODOMICS a descoperit un nou receptor trombocitar, de tip succinat
Activitatea trombocitară creşte în prezenţa succinatului
Claudia Laslo
claudia.laslo@yahoo.com
Bolile cardiovasculare reprezintă ucigaşul numărul 1 în UE, prin infarctele de miocard (IFM) şi prin accidentele vasculare cerebrale (AVC). La fiecare 3 secunde, un cetăţean european face un IFM, 10% din aceste evenimente fiind mortale. Bolile cardiovasculare presupun o cheltuială anuală de 230 euro/cetăţean şi 169 miliarde de euro, în UE.
De ce unii oameni sunt predispuşi mai mult decât alţii la evenimente vasculare ischemice? De ce persoane aparent sănătoase, tinere şi active devin victime ale cheagurilor de sânge? Se pare că răspunsul stă în modul de reacţie, mai lent sau mai rapid, a trombocitelor în procesele în care sunt implicate: formarea cheagurilor de sânge, inclusiv a celor care conduc la IFM şi AVC, împiedicarea sângerării în cazul rănirii unui vas de sânge. Acest comportament diferit este programat la nivel de celulă şi este încă necunoscut oamenilor de ştiinţă. Proiectul BLOODOMICS îşi propune să descopere markerii genetici implicaţi în formarea trombilor în arterele coronare şi să proiecteze medicamente antitrombotice noi, mult mai eficiente în prevenirea şi tratarea acestor evenimente.
Se cunosc deja facorii de risc implicaţi în accidentele vasculare sistemice: fumatul, consumul de alimente grase, sedentarismul şi hipertensiunea arterială. Alături de aceştia se situează şi factorii de risc genetici, care se moştenesc. În acest caz, vorbim despre rezultatul unor variaţii ale mai multor gene, despre care se cunoaşte foarte puţin. Proiectul BLOODOMICS îşi propune să studieze ADN-ul din inimile a 10 000 de pacienţi cardiovasculari şi 10 000 de oameni sănătoşi, pentru a explica de ce trombocitele reactionează diferit în momentul în care sunt activate. Cercetătorii au descoperit deja un receptor plachetar tip succinat, necunoscut până acum, numit SUCNR1. Acesta este o proteină G cuplată cu un receptor printr-o grupare succinat, aspect ce se gândeşte a fi parte dintr-o cale nouă, cu relevanţă fiziologică, de activare a trombocitelor. De altfel, s-a demonstrat că, în prezenţa unor concentraţii fiziologice de succinat, are loc potenţarea efectului unor doze mici de agonişti trombocitari.
“Descoperirea proeiectului BLOODOMICS este foarte importantă, deoarece ne ajută să înţelegem legătura dintre trombocite şi formarea cheagului de sânge”, a afirmat dr. Willem Ouwehand, coordonatorul proiectului BLOODOMICS şi directorul de cercetare şi planificare al Fundaţiei Europene de Genetică Cardiovasculară (ECGF), care a mai adaugat: “Acum încercăm să înţelegem impactul acestui receptor şi a altor astfel de receptori noi în apariţia şi evoluţia bolilor cardiovasculare, cu scopul de a le preveni şi de a le trata mai bine în viitor.”
Vaccin antigripal cu aplicare intranazală
(Proiectul FLUVACC)
Gripa rămâne o ameninţare de temut pentru omenire, prin uşurinţa cu care virusurile gripale se pot modifica genetic şi se pot combina cu cele care provin de la alte specii. Astfel, acestea îşi pot schimba virulenţa şi se pot transmite rapid de la o persoană la alta, determinând foarte rapid o pandemie serioasă. Noua gripă A H1N1 (aşa numita “gripă porcină”) ne-a readus în atenţie potenţialul crescut al gripei de a deveni un duşman redutabil şi fără frontiere al vieţii noastre. Deocamdată, singura armă împotriva gripei este vaccinul, care însă trebuie să îndeplinească anumite condiţii: să fie eficient, să se producă rapid, să se administreze cât mai uşor şi să nu producă reacţii adverse.
Până la acest moment, pe piaţa vaccinurilor antigripale domină preparatele injectabile cu virus inactivat, chiar dacă, cele mai eficiente din punctul de vedere al răspunsului imun, în timp, rămân vaccinurile cu virusuri vii atenuate. Totuşi, vaccinurile vii atenuate existente până în prezent, deşi considerate fără riscuri majore, pot determina unele complicaţii la copiii mici, persoanele în vârstă, precum şi la cele cu diferite tipuri de imunodeficienţe. În plus, acestea nu se pot administra la oamenii alergici la ou, deoarece astfel de vaccinuri utilizează proteine virale produse pe ouă de găină. Un alt incovenient al vaccinurilor convenţionale vii atenuate este că producţia lor este limitată de mediul de producţie (numărul de ouă de gaină disponibile) şi deci ar fi dificil să se obţină un număr foarte mare de vaccinuri într-un timp foarte scurt, aşa cum ar fi necesar în caz de pandemie.
Noul vaccin aflat în cercetare, FLUVACC, încearcă să depăşească toate aceste neajunsuri, venind în întâmpinarea unei viitoare posibile pandemii gripale agresive.
FLUVACC este un vaccin viu atenuat, obţinut prin inginerie genetică şi conţine întreg virusul gripal, mai puţin gena reponsabilă de patogenicitatea virală, respectiv factorul NS1. Astfel, acesta induce un răspuns imun puternic, dar nu este capabil să declanşeze boala. Vaccinul se va putea utiliza împotriva oricărui tip de virus gripal şi poate induce un răspuns de neutralizare nu numai împotriva variantelor omoloage virale, dar şi împotriva celor heteroloage.
FLUVACC aduce o altă noutate prin modul de administrare. Acesta se aplică intranazal, cu un dispozitiv tip spay, ceea ce înseamnă o cale de administrare mai uşoară, fără durere şi care stimulează raspunsul imun direct de la locul de intrare a virusului, conferindu-i astfel o mai mare eficienţă.
Producţia acestui vaccin se face pe culturi de celule de mamifer, ceea ce înseamnă un proces eficient, rapid şi care poate conduce în scurt timp la obţinerea unui număr foarte mare de doze. FLUVACC sau vaccinul antigripal intranazal cu deficienţă de replicare poate fi folosit practic împotriva oricărui tip de virus gripal, oricât de virulent ar fi, inclusiv împotriva virusului gripei aviare care s-a dovedit a fi letal pentru ouăle de găină fertilizate, utilizate în metoda convenţională.
Cercetatorii afirmă că producerea acestui nou vaccin antigripal se poate realiza în aproximativ două săptămani şi în cantităţi foarte mari. Deocamdată, studiile clinice pe voluntari confirmă avantajele precizate de oamenii de ştiinţă, urmând ca acestea să se confirme, folosind loturi mai numeroase.
Clasă nouă de medicamente lansate în lupta impotriva pandemiei actuale de tuberculoză: benzothiazinonele
(Proiectul NM4TB)
Tuberculoza este una dintre cele mai vechi boli ale omenirii, unii cercetatori conferindu-i o viaţă de aproximativ 6.000 de ani. La ora actuală, o treime din populaţia globului este infectată cu bacilul Koch. La fiecare 15 secunde cineva moare din cauza TB şi se preconizează că în următorii zece ani, 30 de milioane de oameni işi vor pierde viaţa din cauza acestei infecţii microbiene.
Tratamentul actual este învechit, durează foarte mult şi, în multe cazuri, şi-a pierdut eficienţa. Ca urmare, în ultimii 15 ani şi-au făcut apariţia tulpini rezistente şi extrem de rezistente de Mycobacterium tuberculosis, fapt accentuat şi de intersectarea TB cu infecţia HIV/SIDA şi cu răspândirea sărăciei. În aceste condiţii, cercetătorii europeni îşi îndreaptă atenţia asupra dezvoltării unor tehnologii noi de abordare a bacteriei Mycobacterium tuberculosis.
Proiectul european NM4TB a descoperit câteva ţinte noi asupra cărora să se acţioneze şi care sunt în principal enzime implicate în biogeneza pereţilor celulari, în sinteza acizilor nucleici, precum şi căi metabolice centrale.
Oamenii de ştiinţă au dezvoltat deja o nouă clasă de componente candidat pentru medicamente, care să combată nu numai TB, ci şi TB multidrog rezistentă (MDR-TB) şi TB cu rezistenţă extinsă la medicamentele actuale (XDR-TB). Este vorba despre benzothiazinone (BTZ) care acţionează, de exemplu, prin impiedicarea bacteriei TB să-şi construiască proprii pereţi celulari. Deci, ţinta acestor compuşi este maşinăria de construire a pereţilor celulari ai bacteriei tuberculoase. Cel mai avansat component este BTZ043, care este extrem de eficient, omorând bacilul Koch atât în vitro cât şi în plămânii şi splinele şoriceilor de laborator infectaţi. Acesta reprezintă un candidat important în terapiile combinate viitoare pentru MDR-TB şi XDR-TB.
Ne putem apăra de epidemiile virale viitoare?
(Proiectul VIZIER: Viral Enzymes Involved in Replication)
Virusurile ARN reprezintă cauze majore de mortalitate umană şi au trei caracteristici de bază: se înmulţesc rapid, suferă mutatii genetice, nu există încă un tratament specific şi eficient împotriva acestora.
Virusurile ARN includ mai mult de 350 de agenţi patogeni majori pentru om şi pe cei mai mulţi factori care determină izbucnirile şi reizbucnirile unor boli infecţioase virale, ca de exemplu: gastroenteritele (>1 milion de decese annual), rujeola (>45 de milioane de cazuri şi > 0,5 decese anual), gripa (>100 de milioane de cazuri anual), febra Denga (300 mlilioane de cazuri anual), enterovirozele şi encefalitele (câteva milioane de cazuri de meningită anual), hepatitele cu virus C (>150 milioane de persoane infectate). De asemenea, epidemia SARS ne-a demonstrat dramatic cât de sus se pot ridica sumele ce se cheltuiesc în epidemii declanţate de virusuri.
Strategiile de luptă împotriva virusurilor ARN au în vedere proiectarea unor medicamente antivirale, bazată pe o mai bună cunoaştere a acestor virusuri, prin caracterizarea lor genomică şi structurală. Este ceea ce îşi propune şi proiectul VIZIER, şi anume să lege caracterizarea ştiinţifică a acestor virusuri cu design-ul de noi medicamente. Până acum au fost studiate, în acest context, 170 de virusuri ARN dintr-un total de 300. S-au identificat peste 95 de structuri cristaline de enzime virale drept ţinte de acţiune şi s-au gândit noi inhibitori enzimatici corespunzători. Dintre aceştial s-au dezvoltat şase componenţi cu spectru larg, care s-au experimentat cu rezultate bune pe animale şi care reprezintă candidaţi de bază pentru medicamentele antivirale viitoare. Mai sunt aşteptaţi încă trei.
Acestă initiaţivă a cercetarii europene va duce la caracterizarea mult mai rapidă a unei potenţiale ţinte virale şi la proiectarea în timp scurt a unor medicamente specifice .
Sursa: Congresul Mondial al Jurnalistilor de Stiinta, Londra, 2009
Hypertension – a global risk factor for cardiovascular disease possible to treat
by Peter Nilsson and Krzysztof Narkiewicz
High blood pressure as a risk factor.
Elevated blood pressure is a common phenomenon in Western populations. Normally blood pressure must be tightly regulated according to physiological needs, for example when climbing out of bed in the morning. Everybody can experience a transient rise in blood pressure during stressful conditions or after exposure to high noise etc. If, however, the blood pressure is constantly elevated above 140/90 mmHg at different times of measurement, most often in the sitting position after a few minutes of rest, this is regarded as high blood pressure (hypertension) - one of the most common risk factors known for risk of cardiovascular disease manifestations (e.g. myocardial infarction, congestive heart failure and stroke) but also for some sorts of cognitive impairment (dementia), renal disease and peripheral arterial disease with risk of losing limbs after surgery for peripheral disease.
Hypertension is common in most populations and associated with obesity and a sedentary life stile including too much intake of sodium and alcohol in some people. If a positive family history of hypertension and cardiovascular disease add to this situation, the risk of hypertension and its complications in an individual is even more increased.
If somebody is diagnosed with hypertension, the next step is to consider all other relevant risk factors for cardiovascular disease that might be present, such as smoking, high levels of cholesterol and glucose (diabetes) as well as increased psychosocial stress exposure. If long-standing, hypertension might also impact on the development and malfunction of some organs, most often related to the eyes (retinal changes in the eye fundus), the heart (enlargement of the muscular wall of the left side of the heart) and the kidneys (impaired function associated with increased protein secretion). In addition, the arteries leading the blood flow from the heart to the periphery might get stiffer in a process that resembles early ageing of the vascular tree.
It is of great importance not to overlook an elevated blood pressure, but to have it measured repeatedly in order to calculate a mean blood pressure. If moderately elevated, lifestyle improvement is of great importance (weight control, appropriate diet, smoking cessation and increased physical activity) in the first place, but if the blood pressure is very high antihypertensive drug treatment should be commenced without delay. In most cases an early period of lifestyle improvement is soon followed by an appropriate drug treatment, often in combination therapy when lower dosage of complementary drugs can be effectively used in combination. This will lead to increased synergy of beneficial effects and control of elevated blood pressure, but also to less side effects as these are mostly associated with increased dosage of pharmaceutical drugs.
For a normal healthy person it is recommended to have the blood pressure measured every 3-5 years to avoid a silent increase in blood pressure. For other subjects, e.g. with obesity, a positive family history, or with concomitant disease such as cardiovascular disease or diabetes, it is recommended that blood pressure is measured at least annually.
Some people get disappointed or even depressed when they are notified that their blood pressure is elevated and in need of control and treatment, maybe for life, but on the other hand will find relief when taught that there are many positive things to do in order to improve the situation and decrease the risk. Of great importance is that nurses can screen for high blood pressure in pregnant women in order to avoid hypertension in pregnancy, a harmful condition both for the mother and her child. Other risk groups suitable for screening by nurses or physicians include abdominally obese subjects or subjects from families with a heavy burden of cardiovascular disease, most notably stroke.
Hypertension management in Europe - getting better but not optimal
Hypertension remains the leading cause of mortality and the third largest cause of disability worldwide, but also in Europe. About one billion people suffer from hypertension which accounts for about seven million deaths per year. The problem is rapidly worsening and this happens at a time when a large number of very well-tolerated and inexpensive antihypertensive drugs have become available. We know that influence on the heart, brain, kidneys and other tissues can be detected early and that hypertension can be successfully treated before established disease breaks out.
The failure to control hypertension takes an unacceptable toll on patients, families and society. In addition to the personal cost, to the individual patient, uncontrolled hypertension creates huge, avoidable economic burdens when viewed in terms of the general population. In addition, the effects of hypertension contribute to significant indirect economic stresses, including increased welfare benefits, demands' on social care, lost income and productivity. Across the European Union, the estimated cost of cardiovascular disease is in the neighbourhood of 169 billion: Euro annually, with healthcare accounting for 62% of this amount.
Previous studies in Western Europe have shown that hypertension remains uncontrolled in the majority of patients. The recent "BP-CARE" study has shown that blood pressure control rate is similarly low in Central and Eastern European countries, i.e. in a geographic area characterized by a high prevalence of coronary and cerebrovascular disease (stroke). Blood pressure control was even more unsatisfactory in very high cardiovascular risk patients. However, blood pressure control was significantly better in patients followed by specialists than by general practitioners.
Any patient with blood pressure of 140/90 mmHg or greater can be characterized as a "challenging patient" and therefore at significant risk. There are six major challenges related to hypertension management:
1. Inadequate primary prevention including obesity due to poor diet and lack of exercise.
2. Faulty awareness of risk and underestimation of the numbers of 'challenging patients'.
3. Urgent need for simpler treatment regimens to encourage patient compliance.
4. More aggressive physician follow-up and motivating patients.
5. Insufficient patient empowerment to promote better patient compliance with treatment regimens.
6. Unsupportive healthcare systems.
Potential solutions include:
7. Driving awareness of the dangers including (a) creating publicity opportunities for physicians to "get the message across"; (b) peer-to-peer discussions throughout the health community to disseminate latest research evidence/best practice;
8. Getting serious about patient education;
9. Making better use of a multidisciplinary team, and in particular involving nurses and pharmacists in "the message" to the patient;
10. Encouraging patients: to become more "accountable" by teaching patients how to self-monitor their blood pressure at home;
11. Simplifying treatment by (a) promoting treatment guidelines to assist physicians´ prescriptions, and (b) promoting fixed-dose combinations to simplify treatment regimens;
12. Encouraging: (a) community/national level campaigns to improve healthcare policies/structures; (b) effective public education initiatives; and (c) clinician improvement of professional education for younger colleagues.
The European Society of Hypertension (ESH) is making continuous efforts to manage the burden of hypertension in Europe by stimulating scientific exchange related to knowledge about hypertension, and supporting and building organisations committed to work for the control of hypertension. For some years now, ESH has been striving to streamline and bolster the ability of doctors for this battle by identifying hypertension specialists in European countries and standardizing their skills to the highest level through what it calls the Hypertension Specialist Initiative. The idea was simple: Establish criteria for eligibility as a Hypertension Specialist of ESH for doctors interested in this program, and proceed to certify each candidate through a standardized vetting which involves the cooperation between ESH and individual National Hypertension Societies. Under this program, over eight hundred Hypertension Specialists of the ESH have been certificated by receiving an ESH Clinical Hypertension Specialist Diploma.
Now that the clinician has been and will continue to be trained, the next step is deployment throughout Europe in the most effective way. ESH has recently launched a new initiative to create a unique Pan-European network of Hypertension Excellence Centres. The main purpose of this network is to provide a stable and organised European platform for the advancement of hypertension prevention and control. By marshalling an array of forces into a vast united front and positioning this strength through a network scattered across the continent, these ESH Centres of Excellence provide the highest level of both inpatient and outpatient hypertension care, including surgical and vascular interventions, and assessment of global cardiovascular risk.
As of June, 2009, the ESH Scientific Council has approved 86 centres representing 21 European countries. All ESH Hypertension Excellence Centres have in-house access to multi-disciplinary services and have high number of hypertension-related hospitalisations and outpatient visits per year.
The specific tasks for each Hypertension Excellence Centres are:
o To provide the best possible clinical management of patients with high blood pressure;
o To set standards in the diagnostics and treatment of hypertension in regions of service;
o To evaluate and improve blood pressure control for primary care, specialists and hypertension centres in regions of service;
o To offer continuing medical education opportunities focusing on teaching primary-care physicians in the region of service;
o To carry out research (experimental/clinical/epidemiology) represented by papers in peer-reviewed international as well as in local scientific journals;
o To co-operate with other ESH Hypertension Excellence Centres to increase the understanding concerning the importance of hypertension as a major health risk in Europe;
o To co-operate with the ESH Scientific Council to elaborate new hypertension control strategies in Europe.
We hope that our new initiative will support the need for establishing hypertension as a clearly-defined medical specialty with official approval in the EU region.
In summary, inadequate blood pressure control is a problem that reaches down to the individuals who suffer from it, and all the way up to include our societal institutions. Patients must become better informed, doctors must be more aggressive and our healthcare system must be supportive. It is fully possible to stop the deleterious complications of hypertension in risk patients - but the first step will always remain: know your own blood pressure!
Peter M Nilsson, Professor Krzysztof Narkiewicz, Professor
Malmö, Sweden Gdànsk, Poland
June 16, 2009 (Milan, Italy) -The European Society of Hypertension (ESH)
June 16, 2009 (Milan, Italy) — The European Society of Hypertension (ESH) is set to stir up the field of BP guidelines later this year, when it publishes an update to its 2007 recommendations. During a special session at the European Meeting on Hypertension 2009 here yesterday, Dr Giuseppe Mancia (University of Milan Bicocca, Monza, Italy), outlined the main changes and said the complete new guidelines will be published in the October 2009 issue of the Journal of Hypertension.
Key among the changes will be the recommendation of a lower threshold level--around 120 mm Hg systolic and 70 mm Hg diastolic--below which it could be dangerous to reduce blood pressure in high-risk individuals, representing the so-called J-curve phenomenon, Mancia said. And rather than emphasizing which antihypertensives should be used first-line, second-line, etc, the new guidelines will instead advise tailoring therapy to individual patient circumstances, he explained.
Also new will be the first European guidelines on the management of high blood pressure in children and adolescents, which will be published in the September 2009 issue of the Journal of Hypertension, Dr Empar Lurbe (University of Valencia, Spain) told meeting attendees. Of key importance among these recommendations will be the indications for future research, she said. "Currently, in Europe, we don't have reference data on adolescents and children, we have to rely on data from the US," so it's imperative that baseline values based on the European pediatric population are established. Other important future endeavors include the development of accurate nonmercury sphygmomanometers for pediatric use and drug trials in this "therapeutic orphan" patient population, she said.
Doctors are also eagerly awaiting new American guidelines on hypertension--the eighth edition of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8) is expected later this year--but many are unsure exactly what to expect.
J-Curve: A Narrow Window of Optimum BP for High-Risk Individuals
Mancia told the meeting that the decision to update the 2007 European hypertension guidelines was taken "because, since then, there have been a number of trials published that could change the recommendations, or in other instances, new data have reinforced the recommendations made."
There are also other situations where "difficult and controversial conclusions" have created confusion, he explained, adding that although the new guidelines document "is still under refinement, the committee agrees on the principles and the issues, which is why I can present it today."
In terms of hypertension treatment thresholds and goals, these will remain pretty much the same as in 2007, he said, with a treatment threshold of 140/90 mm Hg or greater for general hypertension, and a therapy goal of <140/90 mm Hg for this population. For high-risk individuals, the treatment threshold is 130/85 or greater and the treatment goal should be <130/80 mm Hg, although he acknowledged that "the more aggressive goal in high-risk individuals is not supported by outcomes trials, so further hard evidence is needed."
But with the decision to include a lower threshold below which BP should not be lowered in high-risk individuals, this means the window of optimum BP will be narrow in high-risk individuals.
Explaining the new decision, Mancia said: "In 2007, apart from HOT, all the trials were retrospective, but we knew there must be a BP below which perfusion of vital organs is compromised. Now, a number of studies--including INVEST, ONTARGET, VALUE and TNT--have been remarkably consistent" in showing that there is indeed a floor for high-risk individuals below which BP should not be lowered "in order to avoid harm," he noted. "If BP approaches 120/70 in high-risk individuals, a J-curve appears, and this should generate concern," he said.
Treat the Elderly; Tailor Treatment to Specific Patients
Another important change since 2007 will be the recommendation for the very elderly, those aged over 80, in whom the benefits of lowering blood pressure had previously been "inconclusive," Mancia explained.
"Now things have changed with the HYVET data, which showed major benefit, suggesting that we prolong the life of these very old people if we control their BP when BP is elevated," although the trial does have some limitations, he commented.
In terms of choice of drug therapy for hypertension, in 2007 there were five drug classes listed as suitable for initiation of therapy--diuretics, ACE inhibitors, calcium-channel blockers (CCBs), angiotensin receptor blockers (ARBs), and beta blockers.
"Since then, a number of important trials have added new evidence in favor of the protective effects of ACE inhibitors, ARBs, and CCBs and have reinforced the position of these drugs as options to treat hypertension and other conditions such as heart failure and renal disease."
One of the controversies with regard to drug choice has been the debate about the use of beta blockers, he said, with the UK NICE and the British Society of Hypertension removing them from first-, second-, and even third-line choice of treatment in 2006.
"In 2007, the [ESH] committee felt this was not an appropriate decision, as beta blockers were usually employed together with diuretics in virtually all trials, so it was difficult to discriminate what was the favorable or unfavorable role of one drug class or another," he noted. And although there have been negative trials with beta blockers--LIFE and ASCOT--there have also been positive ones, such as HAPPHY, IPPPSH, STOP, INVEST, and UKPDS, he noted.
The totality of evidence now shows different conclusions for different patient populations, he said. "For example, for stroke prevention, beta blockers are inferior to calcium antagonists, but for congestive heart failure prevention, beta blockers are superior to calcium antagonists and similar to other drugs," he noted.
In fact, reducing the emphasis on the step-by-step approach to treatment in general--not recommending particular antihypertensives as first-line, second-line therapy--is another central tenet of the new guidelines, Mancia noted.
"Classifying agents as first choice, second choice, third choice, etc, betrays reference to an average patient who hardly exists in clinical practice," he said, adding: "It is much better to indicate which drug might be preferred in which patient under which circumstance. All drugs have advantages and disadvantages, and we have to try to see in which conditions the advantages of a drug come out."
But Combination Therapy Remains Choice for High-Risk Individuals
But the new guidance will again stress the importance of using combination therapy first-line in high-risk individuals, as advised in 2007, he said, although new data in the intervening two years are helping to refine these recommendations, he noted.
"In 2007, we took a strong stance in favor of combination treatment. This has been shown again--trials such as ACCOMPLISH, ADVANCE, HYVET, ASCOT and ONTARGET are changing the picture. We have to lower BP rather quickly [in these patients] to try to prevent a catastrophe," and more recently, studies have shown there is less discontinuation of treatment in this patient population if treatment is started with combination therapy, Mancia said.
"The evidence is now in favor of giving such patients a blocker of the renin-angiotensin system (RAS)--such as an ACE inhibitor or ARB--with a calcium-channel blocker or diuretic." However, he stressed: "This does not mean that other combinations cannot be used or are not useful."
Another issue that was debated was whether the use of an ACE-inhibitor/ARB combination "should be banned," on the basis of the ONTARGET findings, he noted. But he indicated this would likely not be the case, "because this remains an effective treatment to lower proteinuria compared with single blockade of the RAS system, and this is regarded by nephrologists to be important whenever proteinuria is not reduced sufficiently by one agent.
"But, of course, the data from ONTARGET cannot be forgotten," he stressed, "which means dose titration must be cautious, with frequent monitoring of renal function and BP and close attention to environmental circumstances that might reduce bodily fluids."
PROIECTE EUROPENE DE CERCETARE
Proiectul BLOODOMICS a descoperit un nou receptor trombocitar, de tip succinat
Activitatea trombocitară creşte în prezenţa succinatului
Claudia Laslo
claudia.laslo@yahoo.com
Bolile cardiovasculare reprezintă ucigaşul numărul 1 în UE, prin infarctele de miocard (IFM) şi prin accidentele vasculare cerebrale (AVC). La fiecare 3 secunde, un cetăţean european face un IFM, 10% din aceste evenimente fiind mortale. Bolile cardiovasculare presupun o cheltuială anuală de 230 euro/cetăţean şi 169 miliarde de euro, în UE.
De ce unii oameni sunt predispuşi mai mult decât alţii la evenimente vasculare ischemice? De ce persoane aparent sănătoase, tinere şi active devin victime ale cheagurilor de sânge? Se pare că răspunsul stă în modul de reacţie, mai lent sau mai rapid, a trombocitelor în procesele în care sunt implicate: formarea cheagurilor de sânge, inclusiv a celor care conduc la IFM şi AVC, împiedicarea sângerării în cazul rănirii unui vas de sânge. Acest comportament diferit este programat la nivel de celulă şi este încă necunoscut oamenilor de ştiinţă. Proiectul BLOODOMICS îşi propune să descopere markerii genetici implicaţi în formarea trombilor în arterele coronare şi să proiecteze medicamente antitrombotice noi, mult mai eficiente în prevenirea şi tratarea acestor evenimente.
Se cunosc deja facorii de risc implicaţi în accidentele vasculare sistemice: fumatul, consumul de alimente grase, sedentarismul şi hipertensiunea arterială. Alături de aceştia se situează şi factorii de risc genetici, care se moştenesc. În acest caz, vorbim despre rezultatul unor variaţii ale mai multor gene, despre care se cunoaşte foarte puţin. Proiectul BLOODOMICS îşi propune să studieze ADN-ul din inimile a 10 000 de pacienţi cardiovasculari şi 10 000 de oameni sănătoşi, pentru a explica de ce trombocitele reactionează diferit în momentul în care sunt activate. Cercetătorii au descoperit deja un receptor plachetar tip succinat, necunoscut până acum, numit SUCNR1. Acesta este o proteină G cuplată cu un receptor printr-o grupare succinat, aspect ce se gândeşte a fi parte dintr-o cale nouă, cu relevanţă fiziologică, de activare a trombocitelor. De altfel, s-a demonstrat că, în prezenţa unor concentraţii fiziologice de succinat, are loc potenţarea efectului unor doze mici de agonişti trombocitari.
“Descoperirea proeiectului BLOODOMICS este foarte importantă, deoarece ne ajută să înţelegem legătura dintre trombocite şi formarea cheagului de sânge”, a afirmat dr. Willem Ouwehand, coordonatorul proiectului BLOODOMICS şi directorul de cercetare şi planificare al Fundaţiei Europene de Genetică Cardiovasculară (ECGF), care a mai adaugat: “Acum încercăm să înţelegem impactul acestui receptor şi a altor astfel de receptori noi în apariţia şi evoluţia bolilor cardiovasculare, cu scopul de a le preveni şi de a le trata mai bine în viitor.”
Vaccin antigripal cu aplicare intranazală
(Proiectul FLUVACC)
Gripa rămâne o ameninţare de temut pentru omenire, prin uşurinţa cu care virusurile gripale se pot modifica genetic şi se pot combina cu cele care provin de la alte specii. Astfel, acestea îşi pot schimba virulenţa şi se pot transmite rapid de la o persoană la alta, determinând foarte rapid o pandemie serioasă. Noua gripă A H1N1 (aşa numita “gripă porcină”) ne-a readus în atenţie potenţialul crescut al gripei de a deveni un duşman redutabil şi fără frontiere al vieţii noastre. Deocamdată, singura armă împotriva gripei este vaccinul, care însă trebuie să îndeplinească anumite condiţii: să fie eficient, să se producă rapid, să se administreze cât mai uşor şi să nu producă reacţii adverse.
Până la acest moment, pe piaţa vaccinurilor antigripale domină preparatele injectabile cu virus inactivat, chiar dacă, cele mai eficiente din punctul de vedere al răspunsului imun, în timp, rămân vaccinurile cu virusuri vii atenuate. Totuşi, vaccinurile vii atenuate existente până în prezent, deşi considerate fără riscuri majore, pot determina unele complicaţii la copiii mici, persoanele în vârstă, precum şi la cele cu diferite tipuri de imunodeficienţe. În plus, acestea nu se pot administra la oamenii alergici la ou, deoarece astfel de vaccinuri utilizează proteine virale produse pe ouă de găină. Un alt incovenient al vaccinurilor convenţionale vii atenuate este că producţia lor este limitată de mediul de producţie (numărul de ouă de gaină disponibile) şi deci ar fi dificil să se obţină un număr foarte mare de vaccinuri într-un timp foarte scurt, aşa cum ar fi necesar în caz de pandemie.
Noul vaccin aflat în cercetare, FLUVACC, încearcă să depăşească toate aceste neajunsuri, venind în întâmpinarea unei viitoare posibile pandemii gripale agresive.
FLUVACC este un vaccin viu atenuat, obţinut prin inginerie genetică şi conţine întreg virusul gripal, mai puţin gena reponsabilă de patogenicitatea virală, respectiv factorul NS1. Astfel, acesta induce un răspuns imun puternic, dar nu este capabil să declanşeze boala. Vaccinul se va putea utiliza împotriva oricărui tip de virus gripal şi poate induce un răspuns de neutralizare nu numai împotriva variantelor omoloage virale, dar şi împotriva celor heteroloage.
FLUVACC aduce o altă noutate prin modul de administrare. Acesta se aplică intranazal, cu un dispozitiv tip spay, ceea ce înseamnă o cale de administrare mai uşoară, fără durere şi care stimulează raspunsul imun direct de la locul de intrare a virusului, conferindu-i astfel o mai mare eficienţă.
Producţia acestui vaccin se face pe culturi de celule de mamifer, ceea ce înseamnă un proces eficient, rapid şi care poate conduce în scurt timp la obţinerea unui număr foarte mare de doze. FLUVACC sau vaccinul antigripal intranazal cu deficienţă de replicare poate fi folosit practic împotriva oricărui tip de virus gripal, oricât de virulent ar fi, inclusiv împotriva virusului gripei aviare care s-a dovedit a fi letal pentru ouăle de găină fertilizate, utilizate în metoda convenţională.
Cercetatorii afirmă că producerea acestui nou vaccin antigripal se poate realiza în aproximativ două săptămani şi în cantităţi foarte mari. Deocamdată, studiile clinice pe voluntari confirmă avantajele precizate de oamenii de ştiinţă, urmând ca acestea să se confirme, folosind loturi mai numeroase.
Clasă nouă de medicamente lansate în lupta impotriva pandemiei actuale de tuberculoză: benzothiazinonele
(Proiectul NM4TB)
Tuberculoza este una dintre cele mai vechi boli ale omenirii, unii cercetatori conferindu-i o viaţă de aproximativ 6.000 de ani. La ora actuală, o treime din populaţia globului este infectată cu bacilul Koch. La fiecare 15 secunde cineva moare din cauza TB şi se preconizează că în următorii zece ani, 30 de milioane de oameni işi vor pierde viaţa din cauza acestei infecţii microbiene.
Tratamentul actual este învechit, durează foarte mult şi, în multe cazuri, şi-a pierdut eficienţa. Ca urmare, în ultimii 15 ani şi-au făcut apariţia tulpini rezistente şi extrem de rezistente de Mycobacterium tuberculosis, fapt accentuat şi de intersectarea TB cu infecţia HIV/SIDA şi cu răspândirea sărăciei. În aceste condiţii, cercetătorii europeni îşi îndreaptă atenţia asupra dezvoltării unor tehnologii noi de abordare a bacteriei Mycobacterium tuberculosis.
Proiectul european NM4TB a descoperit câteva ţinte noi asupra cărora să se acţioneze şi care sunt în principal enzime implicate în biogeneza pereţilor celulari, în sinteza acizilor nucleici, precum şi căi metabolice centrale.
Oamenii de ştiinţă au dezvoltat deja o nouă clasă de componente candidat pentru medicamente, care să combată nu numai TB, ci şi TB multidrog rezistentă (MDR-TB) şi TB cu rezistenţă extinsă la medicamentele actuale (XDR-TB). Este vorba despre benzothiazinone (BTZ) care acţionează, de exemplu, prin impiedicarea bacteriei TB să-şi construiască proprii pereţi celulari. Deci, ţinta acestor compuşi este maşinăria de construire a pereţilor celulari ai bacteriei tuberculoase. Cel mai avansat component este BTZ043, care este extrem de eficient, omorând bacilul Koch atât în vitro cât şi în plămânii şi splinele şoriceilor de laborator infectaţi. Acesta reprezintă un candidat important în terapiile combinate viitoare pentru MDR-TB şi XDR-TB.
Ne putem apăra de epidemiile virale viitoare?
(Proiectul VIZIER: Viral Enzymes Involved in Replication)
Virusurile ARN reprezintă cauze majore de mortalitate umană şi au trei caracteristici de bază: se înmulţesc rapid, suferă mutatii genetice, nu există încă un tratament specific şi eficient împotriva acestora.
Virusurile ARN includ mai mult de 350 de agenţi patogeni majori pentru om şi pe cei mai mulţi factori care determină izbucnirile şi reizbucnirile unor boli infecţioase virale, ca de exemplu: gastroenteritele (>1 milion de decese annual), rujeola (>45 de milioane de cazuri şi > 0,5 decese anual), gripa (>100 de milioane de cazuri anual), febra Denga (300 mlilioane de cazuri anual), enterovirozele şi encefalitele (câteva milioane de cazuri de meningită anual), hepatitele cu virus C (>150 milioane de persoane infectate). De asemenea, epidemia SARS ne-a demonstrat dramatic cât de sus se pot ridica sumele ce se cheltuiesc în epidemii declanţate de virusuri.
Strategiile de luptă împotriva virusurilor ARN au în vedere proiectarea unor medicamente antivirale, bazată pe o mai bună cunoaştere a acestor virusuri, prin caracterizarea lor genomică şi structurală. Este ceea ce îşi propune şi proiectul VIZIER, şi anume să lege caracterizarea ştiinţifică a acestor virusuri cu design-ul de noi medicamente. Până acum au fost studiate, în acest context, 170 de virusuri ARN dintr-un total de 300. S-au identificat peste 95 de structuri cristaline de enzime virale drept ţinte de acţiune şi s-au gândit noi inhibitori enzimatici corespunzători. Dintre aceştial s-au dezvoltat şase componenţi cu spectru larg, care s-au experimentat cu rezultate bune pe animale şi care reprezintă candidaţi de bază pentru medicamentele antivirale viitoare. Mai sunt aşteptaţi încă trei.
Acestă initiaţivă a cercetarii europene va duce la caracterizarea mult mai rapidă a unei potenţiale ţinte virale şi la proiectarea în timp scurt a unor medicamente specifice .
Sursa: Congresul Mondial al Jurnalistilor de Stiinta, Londra, 2009
Hypertension – a global risk factor for cardiovascular disease possible to treat
by Peter Nilsson and Krzysztof Narkiewicz
High blood pressure as a risk factor.
Elevated blood pressure is a common phenomenon in Western populations. Normally blood pressure must be tightly regulated according to physiological needs, for example when climbing out of bed in the morning. Everybody can experience a transient rise in blood pressure during stressful conditions or after exposure to high noise etc. If, however, the blood pressure is constantly elevated above 140/90 mmHg at different times of measurement, most often in the sitting position after a few minutes of rest, this is regarded as high blood pressure (hypertension) - one of the most common risk factors known for risk of cardiovascular disease manifestations (e.g. myocardial infarction, congestive heart failure and stroke) but also for some sorts of cognitive impairment (dementia), renal disease and peripheral arterial disease with risk of losing limbs after surgery for peripheral disease.
Hypertension is common in most populations and associated with obesity and a sedentary life stile including too much intake of sodium and alcohol in some people. If a positive family history of hypertension and cardiovascular disease add to this situation, the risk of hypertension and its complications in an individual is even more increased.
If somebody is diagnosed with hypertension, the next step is to consider all other relevant risk factors for cardiovascular disease that might be present, such as smoking, high levels of cholesterol and glucose (diabetes) as well as increased psychosocial stress exposure. If long-standing, hypertension might also impact on the development and malfunction of some organs, most often related to the eyes (retinal changes in the eye fundus), the heart (enlargement of the muscular wall of the left side of the heart) and the kidneys (impaired function associated with increased protein secretion). In addition, the arteries leading the blood flow from the heart to the periphery might get stiffer in a process that resembles early ageing of the vascular tree.
It is of great importance not to overlook an elevated blood pressure, but to have it measured repeatedly in order to calculate a mean blood pressure. If moderately elevated, lifestyle improvement is of great importance (weight control, appropriate diet, smoking cessation and increased physical activity) in the first place, but if the blood pressure is very high antihypertensive drug treatment should be commenced without delay. In most cases an early period of lifestyle improvement is soon followed by an appropriate drug treatment, often in combination therapy when lower dosage of complementary drugs can be effectively used in combination. This will lead to increased synergy of beneficial effects and control of elevated blood pressure, but also to less side effects as these are mostly associated with increased dosage of pharmaceutical drugs.
For a normal healthy person it is recommended to have the blood pressure measured every 3-5 years to avoid a silent increase in blood pressure. For other subjects, e.g. with obesity, a positive family history, or with concomitant disease such as cardiovascular disease or diabetes, it is recommended that blood pressure is measured at least annually.
Some people get disappointed or even depressed when they are notified that their blood pressure is elevated and in need of control and treatment, maybe for life, but on the other hand will find relief when taught that there are many positive things to do in order to improve the situation and decrease the risk. Of great importance is that nurses can screen for high blood pressure in pregnant women in order to avoid hypertension in pregnancy, a harmful condition both for the mother and her child. Other risk groups suitable for screening by nurses or physicians include abdominally obese subjects or subjects from families with a heavy burden of cardiovascular disease, most notably stroke.
Hypertension management in Europe - getting better but not optimal
Hypertension remains the leading cause of mortality and the third largest cause of disability worldwide, but also in Europe. About one billion people suffer from hypertension which accounts for about seven million deaths per year. The problem is rapidly worsening and this happens at a time when a large number of very well-tolerated and inexpensive antihypertensive drugs have become available. We know that influence on the heart, brain, kidneys and other tissues can be detected early and that hypertension can be successfully treated before established disease breaks out.
The failure to control hypertension takes an unacceptable toll on patients, families and society. In addition to the personal cost, to the individual patient, uncontrolled hypertension creates huge, avoidable economic burdens when viewed in terms of the general population. In addition, the effects of hypertension contribute to significant indirect economic stresses, including increased welfare benefits, demands' on social care, lost income and productivity. Across the European Union, the estimated cost of cardiovascular disease is in the neighbourhood of 169 billion: Euro annually, with healthcare accounting for 62% of this amount.
Previous studies in Western Europe have shown that hypertension remains uncontrolled in the majority of patients. The recent "BP-CARE" study has shown that blood pressure control rate is similarly low in Central and Eastern European countries, i.e. in a geographic area characterized by a high prevalence of coronary and cerebrovascular disease (stroke). Blood pressure control was even more unsatisfactory in very high cardiovascular risk patients. However, blood pressure control was significantly better in patients followed by specialists than by general practitioners.
Any patient with blood pressure of 140/90 mmHg or greater can be characterized as a "challenging patient" and therefore at significant risk. There are six major challenges related to hypertension management:
1. Inadequate primary prevention including obesity due to poor diet and lack of exercise.
2. Faulty awareness of risk and underestimation of the numbers of 'challenging patients'.
3. Urgent need for simpler treatment regimens to encourage patient compliance.
4. More aggressive physician follow-up and motivating patients.
5. Insufficient patient empowerment to promote better patient compliance with treatment regimens.
6. Unsupportive healthcare systems.
Potential solutions include:
7. Driving awareness of the dangers including (a) creating publicity opportunities for physicians to "get the message across"; (b) peer-to-peer discussions throughout the health community to disseminate latest research evidence/best practice;
8. Getting serious about patient education;
9. Making better use of a multidisciplinary team, and in particular involving nurses and pharmacists in "the message" to the patient;
10. Encouraging patients: to become more "accountable" by teaching patients how to self-monitor their blood pressure at home;
11. Simplifying treatment by (a) promoting treatment guidelines to assist physicians´ prescriptions, and (b) promoting fixed-dose combinations to simplify treatment regimens;
12. Encouraging: (a) community/national level campaigns to improve healthcare policies/structures; (b) effective public education initiatives; and (c) clinician improvement of professional education for younger colleagues.
The European Society of Hypertension (ESH) is making continuous efforts to manage the burden of hypertension in Europe by stimulating scientific exchange related to knowledge about hypertension, and supporting and building organisations committed to work for the control of hypertension. For some years now, ESH has been striving to streamline and bolster the ability of doctors for this battle by identifying hypertension specialists in European countries and standardizing their skills to the highest level through what it calls the Hypertension Specialist Initiative. The idea was simple: Establish criteria for eligibility as a Hypertension Specialist of ESH for doctors interested in this program, and proceed to certify each candidate through a standardized vetting which involves the cooperation between ESH and individual National Hypertension Societies. Under this program, over eight hundred Hypertension Specialists of the ESH have been certificated by receiving an ESH Clinical Hypertension Specialist Diploma.
Now that the clinician has been and will continue to be trained, the next step is deployment throughout Europe in the most effective way. ESH has recently launched a new initiative to create a unique Pan-European network of Hypertension Excellence Centres. The main purpose of this network is to provide a stable and organised European platform for the advancement of hypertension prevention and control. By marshalling an array of forces into a vast united front and positioning this strength through a network scattered across the continent, these ESH Centres of Excellence provide the highest level of both inpatient and outpatient hypertension care, including surgical and vascular interventions, and assessment of global cardiovascular risk.
As of June, 2009, the ESH Scientific Council has approved 86 centres representing 21 European countries. All ESH Hypertension Excellence Centres have in-house access to multi-disciplinary services and have high number of hypertension-related hospitalisations and outpatient visits per year.
The specific tasks for each Hypertension Excellence Centres are:
o To provide the best possible clinical management of patients with high blood pressure;
o To set standards in the diagnostics and treatment of hypertension in regions of service;
o To evaluate and improve blood pressure control for primary care, specialists and hypertension centres in regions of service;
o To offer continuing medical education opportunities focusing on teaching primary-care physicians in the region of service;
o To carry out research (experimental/clinical/epidemiology) represented by papers in peer-reviewed international as well as in local scientific journals;
o To co-operate with other ESH Hypertension Excellence Centres to increase the understanding concerning the importance of hypertension as a major health risk in Europe;
o To co-operate with the ESH Scientific Council to elaborate new hypertension control strategies in Europe.
We hope that our new initiative will support the need for establishing hypertension as a clearly-defined medical specialty with official approval in the EU region.
In summary, inadequate blood pressure control is a problem that reaches down to the individuals who suffer from it, and all the way up to include our societal institutions. Patients must become better informed, doctors must be more aggressive and our healthcare system must be supportive. It is fully possible to stop the deleterious complications of hypertension in risk patients - but the first step will always remain: know your own blood pressure!
Peter M Nilsson, Professor Krzysztof Narkiewicz, Professor
Malmö, Sweden Gdànsk, Poland
June 16, 2009 (Milan, Italy) -The European Society of Hypertension (ESH)
Elevated blood pressure is a common phenomenon in Western populations. Normally blood pressure must be tightly regulated according to physiological needs, for example when climbing out of bed in the morning. Everybody can experience a transient rise in blood pressure during stressful conditions or after exposure to high noise etc. If, however, the blood pressure is constantly elevated above 140/90 mmHg at different times of measurement, most often in the sitting position after a few minutes of rest, this is regarded as high blood pressure (hypertension) - one of the most common risk factors known for risk of cardiovascular disease manifestations (e.g. myocardial infarction, congestive heart failure and stroke) but also for some sorts of cognitive impairment (dementia), renal disease and peripheral arterial disease with risk of losing limbs after surgery for peripheral disease.
Hypertension is common in most populations and associated with obesity and a sedentary life stile including too much intake of sodium and alcohol in some people. If a positive family history of hypertension and cardiovascular disease add to this situation, the risk of hypertension and its complications in an individual is even more increased.
If somebody is diagnosed with hypertension, the next step is to consider all other relevant risk factors for cardiovascular disease that might be present, such as smoking, high levels of cholesterol and glucose (diabetes) as well as increased psychosocial stress exposure. If long-standing, hypertension might also impact on the development and malfunction of some organs, most often related to the eyes (retinal changes in the eye fundus), the heart (enlargement of the muscular wall of the left side of the heart) and the kidneys (impaired function associated with increased protein secretion). In addition, the arteries leading the blood flow from the heart to the periphery might get stiffer in a process that resembles early ageing of the vascular tree.
It is of great importance not to overlook an elevated blood pressure, but to have it measured repeatedly in order to calculate a mean blood pressure. If moderately elevated, lifestyle improvement is of great importance (weight control, appropriate diet, smoking cessation and increased physical activity) in the first place, but if the blood pressure is very high antihypertensive drug treatment should be commenced without delay. In most cases an early period of lifestyle improvement is soon followed by an appropriate drug treatment, often in combination therapy when lower dosage of complementary drugs can be effectively used in combination. This will lead to increased synergy of beneficial effects and control of elevated blood pressure, but also to less side effects as these are mostly associated with increased dosage of pharmaceutical drugs.
For a normal healthy person it is recommended to have the blood pressure measured every 3-5 years to avoid a silent increase in blood pressure. For other subjects, e.g. with obesity, a positive family history, or with concomitant disease such as cardiovascular disease or diabetes, it is recommended that blood pressure is measured at least annually.
Some people get disappointed or even depressed when they are notified that their blood pressure is elevated and in need of control and treatment, maybe for life, but on the other hand will find relief when taught that there are many positive things to do in order to improve the situation and decrease the risk. Of great importance is that nurses can screen for high blood pressure in pregnant women in order to avoid hypertension in pregnancy, a harmful condition both for the mother and her child. Other risk groups suitable for screening by nurses or physicians include abdominally obese subjects or subjects from families with a heavy burden of cardiovascular disease, most notably stroke.
Hypertension management in Europe - getting better but not optimal
Hypertension remains the leading cause of mortality and the third largest cause of disability worldwide, but also in Europe. About one billion people suffer from hypertension which accounts for about seven million deaths per year. The problem is rapidly worsening and this happens at a time when a large number of very well-tolerated and inexpensive antihypertensive drugs have become available. We know that influence on the heart, brain, kidneys and other tissues can be detected early and that hypertension can be successfully treated before established disease breaks out.
The failure to control hypertension takes an unacceptable toll on patients, families and society. In addition to the personal cost, to the individual patient, uncontrolled hypertension creates huge, avoidable economic burdens when viewed in terms of the general population. In addition, the effects of hypertension contribute to significant indirect economic stresses, including increased welfare benefits, demands' on social care, lost income and productivity. Across the European Union, the estimated cost of cardiovascular disease is in the neighbourhood of 169 billion: Euro annually, with healthcare accounting for 62% of this amount.
Previous studies in Western Europe have shown that hypertension remains uncontrolled in the majority of patients. The recent "BP-CARE" study has shown that blood pressure control rate is similarly low in Central and Eastern European countries, i.e. in a geographic area characterized by a high prevalence of coronary and cerebrovascular disease (stroke). Blood pressure control was even more unsatisfactory in very high cardiovascular risk patients. However, blood pressure control was significantly better in patients followed by specialists than by general practitioners.
Any patient with blood pressure of 140/90 mmHg or greater can be characterized as a "challenging patient" and therefore at significant risk. There are six major challenges related to hypertension management:
1. Inadequate primary prevention including obesity due to poor diet and lack of exercise.
2. Faulty awareness of risk and underestimation of the numbers of 'challenging patients'.
3. Urgent need for simpler treatment regimens to encourage patient compliance.
4. More aggressive physician follow-up and motivating patients.
5. Insufficient patient empowerment to promote better patient compliance with treatment regimens.
6. Unsupportive healthcare systems.
Potential solutions include:
7. Driving awareness of the dangers including (a) creating publicity opportunities for physicians to "get the message across"; (b) peer-to-peer discussions throughout the health community to disseminate latest research evidence/best practice;
8. Getting serious about patient education;
9. Making better use of a multidisciplinary team, and in particular involving nurses and pharmacists in "the message" to the patient;
10. Encouraging patients: to become more "accountable" by teaching patients how to self-monitor their blood pressure at home;
11. Simplifying treatment by (a) promoting treatment guidelines to assist physicians´ prescriptions, and (b) promoting fixed-dose combinations to simplify treatment regimens;
12. Encouraging: (a) community/national level campaigns to improve healthcare policies/structures; (b) effective public education initiatives; and (c) clinician improvement of professional education for younger colleagues.
The European Society of Hypertension (ESH) is making continuous efforts to manage the burden of hypertension in Europe by stimulating scientific exchange related to knowledge about hypertension, and supporting and building organisations committed to work for the control of hypertension. For some years now, ESH has been striving to streamline and bolster the ability of doctors for this battle by identifying hypertension specialists in European countries and standardizing their skills to the highest level through what it calls the Hypertension Specialist Initiative. The idea was simple: Establish criteria for eligibility as a Hypertension Specialist of ESH for doctors interested in this program, and proceed to certify each candidate through a standardized vetting which involves the cooperation between ESH and individual National Hypertension Societies. Under this program, over eight hundred Hypertension Specialists of the ESH have been certificated by receiving an ESH Clinical Hypertension Specialist Diploma.
Now that the clinician has been and will continue to be trained, the next step is deployment throughout Europe in the most effective way. ESH has recently launched a new initiative to create a unique Pan-European network of Hypertension Excellence Centres. The main purpose of this network is to provide a stable and organised European platform for the advancement of hypertension prevention and control. By marshalling an array of forces into a vast united front and positioning this strength through a network scattered across the continent, these ESH Centres of Excellence provide the highest level of both inpatient and outpatient hypertension care, including surgical and vascular interventions, and assessment of global cardiovascular risk.
As of June, 2009, the ESH Scientific Council has approved 86 centres representing 21 European countries. All ESH Hypertension Excellence Centres have in-house access to multi-disciplinary services and have high number of hypertension-related hospitalisations and outpatient visits per year.
The specific tasks for each Hypertension Excellence Centres are:
o To provide the best possible clinical management of patients with high blood pressure;
o To set standards in the diagnostics and treatment of hypertension in regions of service;
o To evaluate and improve blood pressure control for primary care, specialists and hypertension centres in regions of service;
o To offer continuing medical education opportunities focusing on teaching primary-care physicians in the region of service;
o To carry out research (experimental/clinical/epidemiology) represented by papers in peer-reviewed international as well as in local scientific journals;
o To co-operate with other ESH Hypertension Excellence Centres to increase the understanding concerning the importance of hypertension as a major health risk in Europe;
o To co-operate with the ESH Scientific Council to elaborate new hypertension control strategies in Europe.
We hope that our new initiative will support the need for establishing hypertension as a clearly-defined medical specialty with official approval in the EU region.
In summary, inadequate blood pressure control is a problem that reaches down to the individuals who suffer from it, and all the way up to include our societal institutions. Patients must become better informed, doctors must be more aggressive and our healthcare system must be supportive. It is fully possible to stop the deleterious complications of hypertension in risk patients - but the first step will always remain: know your own blood pressure!
Peter M Nilsson, Professor Krzysztof Narkiewicz, Professor
Malmö, Sweden Gdànsk, Poland
June 16, 2009 (Milan, Italy) -The European Society of Hypertension (ESH)
June 16, 2009 (Milan, Italy) — The European Society of Hypertension (ESH) is set to stir up the field of BP guidelines later this year, when it publishes an update to its 2007 recommendations. During a special session at the European Meeting on Hypertension 2009 here yesterday, Dr Giuseppe Mancia (University of Milan Bicocca, Monza, Italy), outlined the main changes and said the complete new guidelines will be published in the October 2009 issue of the Journal of Hypertension.
Key among the changes will be the recommendation of a lower threshold level--around 120 mm Hg systolic and 70 mm Hg diastolic--below which it could be dangerous to reduce blood pressure in high-risk individuals, representing the so-called J-curve phenomenon, Mancia said. And rather than emphasizing which antihypertensives should be used first-line, second-line, etc, the new guidelines will instead advise tailoring therapy to individual patient circumstances, he explained.
Also new will be the first European guidelines on the management of high blood pressure in children and adolescents, which will be published in the September 2009 issue of the Journal of Hypertension, Dr Empar Lurbe (University of Valencia, Spain) told meeting attendees. Of key importance among these recommendations will be the indications for future research, she said. "Currently, in Europe, we don't have reference data on adolescents and children, we have to rely on data from the US," so it's imperative that baseline values based on the European pediatric population are established. Other important future endeavors include the development of accurate nonmercury sphygmomanometers for pediatric use and drug trials in this "therapeutic orphan" patient population, she said.
Doctors are also eagerly awaiting new American guidelines on hypertension--the eighth edition of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8) is expected later this year--but many are unsure exactly what to expect.
J-Curve: A Narrow Window of Optimum BP for High-Risk Individuals
Mancia told the meeting that the decision to update the 2007 European hypertension guidelines was taken "because, since then, there have been a number of trials published that could change the recommendations, or in other instances, new data have reinforced the recommendations made."
There are also other situations where "difficult and controversial conclusions" have created confusion, he explained, adding that although the new guidelines document "is still under refinement, the committee agrees on the principles and the issues, which is why I can present it today."
In terms of hypertension treatment thresholds and goals, these will remain pretty much the same as in 2007, he said, with a treatment threshold of 140/90 mm Hg or greater for general hypertension, and a therapy goal of <140/90 mm Hg for this population. For high-risk individuals, the treatment threshold is 130/85 or greater and the treatment goal should be <130/80 mm Hg, although he acknowledged that "the more aggressive goal in high-risk individuals is not supported by outcomes trials, so further hard evidence is needed."
But with the decision to include a lower threshold below which BP should not be lowered in high-risk individuals, this means the window of optimum BP will be narrow in high-risk individuals.
Explaining the new decision, Mancia said: "In 2007, apart from HOT, all the trials were retrospective, but we knew there must be a BP below which perfusion of vital organs is compromised. Now, a number of studies--including INVEST, ONTARGET, VALUE and TNT--have been remarkably consistent" in showing that there is indeed a floor for high-risk individuals below which BP should not be lowered "in order to avoid harm," he noted. "If BP approaches 120/70 in high-risk individuals, a J-curve appears, and this should generate concern," he said.
Treat the Elderly; Tailor Treatment to Specific Patients
Another important change since 2007 will be the recommendation for the very elderly, those aged over 80, in whom the benefits of lowering blood pressure had previously been "inconclusive," Mancia explained.
"Now things have changed with the HYVET data, which showed major benefit, suggesting that we prolong the life of these very old people if we control their BP when BP is elevated," although the trial does have some limitations, he commented.
In terms of choice of drug therapy for hypertension, in 2007 there were five drug classes listed as suitable for initiation of therapy--diuretics, ACE inhibitors, calcium-channel blockers (CCBs), angiotensin receptor blockers (ARBs), and beta blockers.
"Since then, a number of important trials have added new evidence in favor of the protective effects of ACE inhibitors, ARBs, and CCBs and have reinforced the position of these drugs as options to treat hypertension and other conditions such as heart failure and renal disease."
One of the controversies with regard to drug choice has been the debate about the use of beta blockers, he said, with the UK NICE and the British Society of Hypertension removing them from first-, second-, and even third-line choice of treatment in 2006.
"In 2007, the [ESH] committee felt this was not an appropriate decision, as beta blockers were usually employed together with diuretics in virtually all trials, so it was difficult to discriminate what was the favorable or unfavorable role of one drug class or another," he noted. And although there have been negative trials with beta blockers--LIFE and ASCOT--there have also been positive ones, such as HAPPHY, IPPPSH, STOP, INVEST, and UKPDS, he noted.
The totality of evidence now shows different conclusions for different patient populations, he said. "For example, for stroke prevention, beta blockers are inferior to calcium antagonists, but for congestive heart failure prevention, beta blockers are superior to calcium antagonists and similar to other drugs," he noted.
In fact, reducing the emphasis on the step-by-step approach to treatment in general--not recommending particular antihypertensives as first-line, second-line therapy--is another central tenet of the new guidelines, Mancia noted.
"Classifying agents as first choice, second choice, third choice, etc, betrays reference to an average patient who hardly exists in clinical practice," he said, adding: "It is much better to indicate which drug might be preferred in which patient under which circumstance. All drugs have advantages and disadvantages, and we have to try to see in which conditions the advantages of a drug come out."
But Combination Therapy Remains Choice for High-Risk Individuals
But the new guidance will again stress the importance of using combination therapy first-line in high-risk individuals, as advised in 2007, he said, although new data in the intervening two years are helping to refine these recommendations, he noted.
"In 2007, we took a strong stance in favor of combination treatment. This has been shown again--trials such as ACCOMPLISH, ADVANCE, HYVET, ASCOT and ONTARGET are changing the picture. We have to lower BP rather quickly [in these patients] to try to prevent a catastrophe," and more recently, studies have shown there is less discontinuation of treatment in this patient population if treatment is started with combination therapy, Mancia said.
"The evidence is now in favor of giving such patients a blocker of the renin-angiotensin system (RAS)--such as an ACE inhibitor or ARB--with a calcium-channel blocker or diuretic." However, he stressed: "This does not mean that other combinations cannot be used or are not useful."
Another issue that was debated was whether the use of an ACE-inhibitor/ARB combination "should be banned," on the basis of the ONTARGET findings, he noted. But he indicated this would likely not be the case, "because this remains an effective treatment to lower proteinuria compared with single blockade of the RAS system, and this is regarded by nephrologists to be important whenever proteinuria is not reduced sufficiently by one agent.
"But, of course, the data from ONTARGET cannot be forgotten," he stressed, "which means dose titration must be cautious, with frequent monitoring of renal function and BP and close attention to environmental circumstances that might reduce bodily fluids."
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office@srmi.ro
Tel: 021.315.65.11
Editorial Secretary
Dr. Roxana Pioaru
roxana.pioaru@srmi.ro
Secretariat organizatoric
Email: office@srmi.ro
Str. C-tin Noica, nr.134, Interfon 1, sector 6, Bucuresti
Tel : 021-3156511
Fax :021-3156537
Departament Comercial
Mihaela Dragomir
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Str. C-tin Noica, nr.134, Interfon 1, sector 6, Bucuresti
Tel : +40 753 359 693