Ospedale San Giuseppe

Udgivelsesdato: 2007-Jun

Table of Contents Introduction Principles New aspects Epidemiological aspects Relationship of blood pressure to cardiovascular and renal damage Definition and classification of hypertension Prevalence of hypertension Hypertension and total cardiovascular risk Assessment of total cardiovascular risk Limitations Summary of recommendations on total cardiovascular risk assessment Diagnostic evaluation Bood pressure measurement Office or clinic blood pressure Out-of-office blood pressure White-coat (or isolated office) hypertension and masked (or isolated ambulatory) hypertension Clinical indications for out-of-office blood pressure Blood pressure during exercise and laboratory stress Central blood pressure Medical history Physical examination Summary of recommendations on blood pressure measurement, history, and physical examination Laboratory investigations Genetics Searching for asymptomatic organ damage Heart Blood vessels Kidney Fundoscopy Brain Clinical value and limitations Summary of recommendations on the search for asymptomatic organ damage, cardiovascular disease, and chronic kidney disease Searching for secondary forms of hypertension Treatment approach Evidence favouring therapeutic reduction of high blood pressure When to initiate antihypertensive drug treatment Recommendations of previous Guidelines Grade 2 and 3 hypertension and high-risk grade 1 hypertension Low-to-moderate risk, grade 1 hypertension Isolated systolic hypertension in youth Grade 1 hypertension in the elderly High normal blood pressure Summary of recommendations on initiation of antihypertensive drug treatment Blood pressure treatment targets Recommendations of previous Guidelines Low-to-moderate risk hypertensive patients Hypertension in the elderly High-risk patients The ‘lower the better’ vs. the J-shaped curve hypothesis Evidence on target blood pressure from organ damage studies Clinic vs. home and ambulatory blood pressure targets Summary of recommendations on blood pressure targets in hypertensive patients Treatment strategies Lifestyle changes Salt restriction Moderation of alcohol consumption Other dietary changes Weight reduction Regular physical exercise Smoking cessation Summary of recommendations on adoption of lifestyle changes Pharmacological therapy Choice of antihypertensive drugs Monotherapy and combination therapy Summary of recommendations on treatment strategies and choice of drugs Treatment strategies in special conditions White-coat hypertension Masked hypertension Summary of recommendations on treatment strategies in white-coat and masked hypertension Elderly Summary of recommendations on antihypertensive treatment strategies in the elderly Young adults Women Oral contraceptives Hormone replacement therapy Pregnancy Long-term cardiovascular consequences in gestational hypertension Summary of recommendations on treatment strategies in hypertensive women Diabetes mellitus Summary of recommendations on treatment strategies in patients with diabetes Metabolic syndrome Summary of recommendations on treatment strategies in hypertensive patients with metabolic syndrome Obstructive sleep apnoea Diabetic and non-diabetic nephropathy Summary of recommendations on therapeutic strategies in hypertensive patients with nephropathy Chronic kidney disease stage 5D Cerebrovascular disease Acute stroke Previous stroke or transient ischaemic attack Cognitive dysfunction and white matter lesions Summary of recommendations on therapeutic strategies in hypertensive patients with cerebrovascular disease Heart disease Coronary heart disease Heart failure Atrial fibrillation Left ventricular hypertrophy Summary of recommendations on therapeutic strategies in hypertensive patients with heart disease Atherosclerosis, arteriosclerosis, and peripheral artery disease Carotid atherosclerosis Increased arterial stiffness Peripheral artery disease Summary of recommendations on therapeutic strategies in hypertensive patients with atherosclerosis, arteriosclerosis, and peripheral artery disease Sexual dysfunction Resistant hypertension Carotid baroreceptor stimulation Renal denervation Other invasive approaches Follow-up in resistant hypertension Summary of recommendations on therapeutic strategies in patients with resistant hypertension Malignant hypertension Hypertensive emergencies and urgencies Perioperative management of hypertension Renovascular hypertension Primary aldosteronism Treatment of associated risk factors Lipid-lowering agents Antiplatelet therapy Treatment of hyperglycaemia Summary of recommendations on treatment of risk factors associated with hypertension Follow-up Follow-up of hypertensive patients Follow-up of subjects with high normal blood pressure and white-coat hypertension Elevated blood pressure at control visits Continued search for asymptomatic organ damage Can antihypertensive medications be reduced or stopped? Improvement of blood pressure control in hypertension Hypertension disease management Team approach in disease management Mode of care delivery The role of information and communication technologies 53 Gaps in evidence and need for future trials Appendix 1 Appendix 2 Acknowledgments References 1. INTRODUCTION 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) follow the guidelines jointly issued by the two societies in 2003 and 2007 [1,2]. Publication of a new document 6 years after the previous one was felt to be timely because, over this period, important studies have been conducted and many new results have been published on both the diagnosis and treatment of individuals with an elevated blood pressure (BP), making refinements, modifications and expansion of the previous recommendations necessary. The 2013 ESH/ESC guidelines continue to adhere to some fundamental principles that inspired the 2003 and 2007 guidelines, namely (i) to base recommendations on properly conducted studies identified from an extensive review of the literature, (ii) to consider, as the highest priority, data from randomized, controlled trials (RCTs) and their meta-analyses, but not to disregard—particularly when dealing with diagnostic aspects—the results of observational and other studies of appropriate scientific calibre, and (iii) to grade the level of scientific evidence and the strength of recommendations on major diagnostic and treatment issues as in European guidelines on other diseases, according to ESC recommendations (Tables 1 and 2). While it was not done in the 2003 and 2007 guidelines, providing the recommendation class and the level of evidence is now regarded as important for providing interested readers with a standard approach, by which to compare the state of knowledge across different fields of medicine. It was also thought that this could more effectively alert physicians on recommendations that are based on the opinions of the experts rather than on evidence. This is not uncommon in medicine because, for a great part of daily medical practice, no good science is available and recommendations must therefore stem from common sense and personal clinical experience, both of which can be fallible. When appropriately recognized, this can avoid guidelines being perceived as prescriptive and favour the performance of studies where opinion prevails and evidence is lacking. A fourth principle, in line with its educational purpose, is to provide a large number of tables and a set of concise recommendations that could be easily and rapidly consulted by physicians in their routine practice.TABLE 1: Classes of recommendationsTABLE 2: Levels of EvidenceThe European members of the Task Force in charge of the 2013 guidelines on hypertension have been appointed by the ESH and ESC, based on their recognized expertise and absence of major conflicts of interest [their declaration of interest forms can be found on the ESC website (www.escardio.org/guidelines) and ESH website (www.eshonline.org)]. Each member was assigned a specific writing task, which was reviewed by three co-ordinators and then by two chairmen, one appointed by ESH and another by ESC. The text was finalized over approximately 18 months, during which the Task Force members met collectively several times and corresponded intensively with one another between meetings. Before publication, the document was also assessed twice by 42 European reviewers, half selected by ESH and half by ESC. It can thus be confidently stated that the recommendations issued by the 2013 ESH/ESC guidelines on hypertension largely reflect the state of the art on hypertension, as viewed by scientists and physicians in Europe. Expenses for meetings and the remaining work have been shared by ESH and ESC. 1.2 New aspects Because of new evidence on several diagnostic and therapeutic aspects of hypertension, the present guidelines differ in many respects from the previous ones [2]. Some of the most important differences are listed below: Epidemiological data on hypertension and control in Europe. of the value of home blood pressure and of its role for diagnosis and management of hypertension, to ambulatory blood pressure of the of white-coat hypertension and masked on of cardiovascular risk asymptomatic organ damage and clinical for total risk of the of asymptomatic blood and of the risk of and target in Hypertension in of antihypertensive and no drug treatment of high normal for and target systolic blood pressure in both and risk approach to for New therapeutic for target on therapeutic strategies in special recommendations on treatment of hypertension in the treatment of to resistant hypertension and new treatment Increased to New approaches to chronic management of hypertensive Relationship of blood pressure to cardiovascular and renal damage The between and and renal been in a large number of observational studies The in in the 2003 and 2007 ESH/ESC guidelines can be as Office an with the of several heart failure and peripheral artery disease as as of renal disease This is at and in The with from high to of for and for to be a of than after the of years and in elderly individuals pressure between and been to have a role This is also by the high risk by patients with an elevated and a normal or systolic hypertension A with is also by out-of-office as by and The between and and is by the of other risk Metabolic risk factors are more common when is high than when it is Definition and classification of hypertension The between and and renal the between and hypertension when based on This is more because, in the and have a practice, are both to the diagnostic approach and to the The classification is from the 2003 and 2007 ESH/ESC guidelines Hypertension is as based on the evidence from that in patients with are and The classification is in and elderly different based on are in and for data from trials are not on classification in and according to their and can be found in the on the evaluation and treatment of high in and and classification of blood pressure Prevalence of hypertension data are available on the of hypertension and the of in different European the of hypertension to be of the with a with also to be differences in the across with no changes in the to the of results and the of a of hypertension been is a good hypertension is by the most important of this A between of hypertension and for stroke been The and of stroke in have been by of European a in to European which a in from stroke Hypertension and total cardiovascular risk a hypertension guidelines on as the or the need the the ESC, ESH and European Society recommendations on of heart disease in clinical and that of be to of total (or This approach is now and been the 2003 and 2007 ESH/ESC guidelines for the management of arterial hypertension [1,2]. The is based on the that a of the hypertensive an of with the risk when and other risk factors to a total risk that is than the of its in high-risk antihypertensive treatment strategies and of of drug and as as other be different from to be in is evidence in high-risk control is more and more the combination of antihypertensive drugs with other as The therapeutic approach total risk in to in to of the management of Assessment of total cardiovascular risk of total risk is in of as with of cardiovascular disease or with elevated risk of the total risk is high or for a large number of patients with hypertension not to of the and the of at high or high risk the of to total risk, as to be to the therapeutic approach have been for total risk and limitations have been reviewed The been based on large European The the risk of from disease over years based on total and The of the for which been done for European the two of are one for high-risk and one for The of as Heart is to also for the of on total The and their can in risk assessment and management but must be in the of the knowledge and experience, with to the that total risk is associated with clinical when with other strategies not been be than in the subjects and with the risk associated with is in subjects than in individuals and from with elevated an not the diagnostic for with and with a history of the of years in and years in total risk is as the risk of from Because of its on in total risk can be in the of high with risk this to a high-risk years treatment be by of risk or by heart and A is available in the European on in Clinical which is when been to of asymptomatic in several in the which the risk that by the of risk A is to for asymptomatic where evidence for the risk of clinical is more than a guidelines for the management of hypertension and 2003 Society of Hypertension Guidelines and the 2003 and 2007 ESH/ESC have risk in different based on risk asymptomatic and of or chronic kidney disease as also done by the ESC guidelines The classification in high and high risk is in the guidelines and to the risk of as by the ESC guidelines The factors on which the is based are in Table 1: of total risk in of high and high risk according to and and of asymptomatic stage or with a high normal but a out-of-office have a risk in the hypertension with a high but normal out-of-office is no or have risk than hypertension for the than for of total risk in Limitations available for risk assessment have limitations that must be The of in of risk is on the damage is based on available limitations also be that the of total risk is to the of to that to grade in to the of risk is by or to a which treatment is It be in that to high total risk is as as the of a value to this and no at is a of on total risk It is that adults are to high-risk when have more than one major risk and a in many elderly a high total risk level being at risk to their The consequences are that most are in is and is to subjects at high risk the in the absence of their to an risk to a high and risk in with of their Summary of recommendations on total cardiovascular risk assessment cardiovascular risk The evaluation of a with hypertension (i) the diagnosis of hypertension, (ii) of secondary hypertension, and (iii) risk, and clinical This for measurement, medical history history, physical laboratory investigations and diagnostic Some of the investigations are in in specific Bood pressure measurement Office or clinic blood pressure can no be a in not or are be according to and their be in a laboratory of at the is and and be to the the of a and between which been to an risk the with the be A is by one a between with measurement, it could be to elderly patients and in other conditions in which be or it is that be 1 and 3 after of the as a reduction in of or in of 3 of been to a for and of in the with the in an isolated providing information be as a to and to by or be associated with measurement of heart heart or in several hypertension for are in Table Office blood pressure Out-of-office blood pressure The major of out-of-office is that it a large number of from the medical which a more assessment of than Out-of-office is assessed by or by A principles and for the two of in to recommendations for measurement The be to the with and in of appropriate medical of the results that the of out-of-office is good for and but for the and for more and and provide different information on the and risk and the two thus be regarded as rather than or The between with and is to Office is than ambulatory and home and the as for the of hypertension for home and ambulatory according to the ESH on are in Table have been and according to and be properly and at 6 The can be on of hypertension by and out-of-office blood pressure blood pressure aspects A number of aspects have been by the ESH on Blood is with the a on the for a period, that it information on during daily and at during the of of the the between the and from measurement by the not be than the of a the be and The is to in normal but to from exercise at the of to and and the with the at heart The is to provide information in a on and that in to the times of drug and and from clinical practice, are at during the and between be the of It be that be at the during the and The are to a and a of can be of during and be or the be The of and the of have been to are is not and be It is that not be when the is and blood pressure to the and are the most in clinical and can be from the on the of the times of and to is to in which the and differ from to It for been that from to and from to 6 with the and but other have been as from to and from 1 to 6 the of different measurement during the and the and to for it is that be for the between or to the of the to avoid of The the between and during the as the of a normal in a it is that the of a of of be as an to subjects as more have been absence of for and women been in a number of but other of an to exercise have also been the of at exercise is to arterial stiffness and and is in women than in and in than in individuals not have that an of during exercise the of hypertension in of at exercise to future hypertension is not of a number of as of of and is no on the of exercise with as after for and other as in as in hypertensive patients the results on the of exercise are not which be to the that the two of in during It is that the is a reduction of during with changes in and or not the arterial is an of at on subjects and in hypertensive patients with of an a the of normal hypertension can be an for of its with masked hypertension the other when hypertension is associated with dysfunction and of the of exercise be a during exercise a as in individuals in patients with disease or with heart failure in a exercise systolic the results the clinical of during exercise for diagnostic and in patients with exercise is as a exercise and data and an A number of stress have been to stress and a of or laboratory stress in not reflect stress and are not have and between to the are results on the of the to with future hypertension are not the is A that to stress an on future risk of elevated hypertension, ventricular atherosclerosis and clinical The results that during stress are not Central blood pressure The measurement of in hypertensive patients interest of both its value for and the of antihypertensive with The arterial pressure is a of the pressure by ventricular and a It be at the in the it the on kidney and large The of can be the as the between the and systolic as a of the for heart to the of and pressure the arterial systolic and be different from the years several and have been to systolic or pressure from pressure have been reviewed in an document studies in the that and by of and in patients with A in several the value of was or not in most studies the guidelines, previous ones the measurement of and is of great interest for in and more is their routine clinical The be in the in some of individuals at the level be to high of the pressure is normal Medical history The medical history the of the diagnosis of arterial hypertension, and and and antihypertensive be to indications of secondary of Women be Hypertension an risk of renal and heart when are a history of be in to assessment of risk, as clinical or a history of heart or heart disease, with an on stroke and transient ischaemic attack A history of the and of kidney and evidence for be A history of hypertension is an important of to hypertension and and on and medical history are in Table and medical Physical examination Physical examination to or the diagnosis of hypertension, for secondary of hypertension and risk be as in and be to the diagnosis of at one to be at both and differences between the two in in investigations of patients of the heart and renal renal on the of the and be with the and and heart be the is at heart an risk of heart the of on physical examination are in Table Physical examination for secondary hypertension, organ damage and Summary of recommendations on blood pressure history, and physical examination pressure history, and physical on Blood pressure history, and physical Laboratory investigations Laboratory investigations are at providing evidence for the of risk for secondary hypertension and for the absence or of from the most to the more on laboratory investigations are in Table Laboratory Genetics A history is a in hypertensive patients with the to between and in the of studies and been for ambulatory forms of hypertension have been as syndrome and where a the of hypertension and the treatment hypertension is a with a studies and their to a total of which are associated with systolic to risk for Searching for asymptomatic organ damage to the of asymptomatic as an stage in the of disease, and as a of risk, of organ be by appropriate It be that a large of evidence is now available on the role of asymptomatic in the risk of individuals with and high The that of of and can of is a in favour of assessment of in daily clinical more data from studies in different be It is also that the risk as the number of Heart A be part of the routine assessment of hypertensive in is by the the or been found in observational studies and clinical trials to be an of the is at in patients over years of can also be to of ventricular or which more risk and is when and ischaemic are Atrial fibrillation is a and common of in hypertensive patients of fibrillation the of by appropriate therapy not from is more than in and is to and renal risk It therefore in a more of risk and in therapy evaluation of the in hypertensive patients of and and While ventricular for or the or of is according to the Society of the between and risk is of for women and for are for of of for in which to the of or been can be in and patients in to to and avoid of It been that the is to by to the and that different for and women be by could in subjects and in ones with with and with normal an of but is the of risk Hypertension is associated with of and as dysfunction is associated with and can of heart when is normal failure with The can and heart failure and but is not to the hypertensive clinical and to recommendations it therefore be with of the of the is of hypertensive heart disease the is reduced more than the and of dysfunction is based on of and and the between and and This is an important of in a large The of and of are on and on The is to an of The value of is recognized in the hypertensive and is associated with risk, of and in hypertensive patients of can provide information and is a for the diagnosis of Left is assessed by its or been to be an of heart fibrillation and ischaemic stroke and for hypertensive heart disease for are in Table The most for in hypertension is to by that the on of and are largely largely from control with the for by the Society of and the European of are in the of for from large in different be available for in the assessment of and in patients with on and systolic can and to systolic dysfunction of hypertensive patients assessment of systolic in hypertensive heart disease not information to at in the of a normal clinical practice, be in hypertensive patients in different clinical and with different in hypertensive patients at total risk, it the risk evaluation by by in hypertensive patients with evidence of it more the hypertrophy and its and in hypertensive patients with it to It is that assessment of and be of diagnostic value in most patients with hypertension and be in hypertensive patients at the a or more on and be for assessment of and when is not and when of have therapeutic consequences are for diagnosis of in hypertensive patients with This is hypertension the of exercise and exercise a normal and an value in patients of When the exercise is or an of as stress or stress is for a of are specific for assessed artery are found with normal associated with disease The of of and on the artery been to from isolated damage A been to have an value in hypertension Blood vessels Carotid examination of the with measurement of the of been to the of both stroke and of risk factors This both for the value at the and for the value at the level of the common artery The between and is a one and a for high risk is rather a been as a of in the 2007 Guidelines the value for high risk was in the elderly patients of the and in the patients of the European on and of a can be identified by an or by a in of or of the value a value for of a and to other for and patients another risk in the A review that the value of be found in asymptomatic individuals at

: Document reviewers: Guy De Backer (ESC Review Co-ordinator) (Belgium), Anthony M. Heagerty (ESH Review Co-ordinator) (UK), Stefan Agewall (Norway), Murielle Bochud (Switzerland), Claudio Borghi (Italy), Pierre Boutouyrie (France), Jana Brguljan (Slovenia), Héctor Bueno (Spain), Enrico G. Caiani (Italy), Bo Carlberg (Sweden), Neil Chapman (UK), Renata Cifkova (Czech Republic), John G. F. Cleland (UK), Jean-Philippe Collet (France), Ioan Mircea Coman (Romania), Peter W. de Leeuw (The Netherlands), Victoria Delgado (The Netherlands), Paul Dendale (Belgium), Hans-Christoph Diener (Germany), Maria Dorobantu (Romania), Robert Fagard (Belgium), Csaba Farsang (Hungary), Marc Ferrini (France), Ian M. Graham (Ireland), Guido Grassi (Italy), Hermann Haller (Germany), F. D. Richard Hobbs (UK), Bojan Jelakovic (Croatia), Catriona Jennings (UK), Hugo A. Katus (Germany), Abraham A. Kroon (The Netherlands), Christophe Leclercq (France), Dragan Lovic (Serbia), Empar Lurbe (Spain), Athanasios J. Manolis (Greece), Theresa A. McDonagh (UK), Franz Messerli (Switzerland), Maria Lorenza Muiesan (Italy), Uwe Nixdorff (Germany), Michael Hecht Olsen (Denmark), Gianfranco Parati (Italy), Joep Perk (Sweden), Massimo Francesco Piepoli (Italy), Jorge Polonia (Portugal), Piotr Ponikowski (Poland), Dimitrios J. Richter (Greece), Stefano F. Rimoldi (Switzerland), Marco Roffi (Switzerland), Naveed Sattar (UK), Petar M. Seferovic (Serbia), Iain A. Simpson (UK), Miguel Sousa-Uva (Portugal), Alice V. Stanton (Ireland), Philippe van de Borne (Belgium), Panos Vardas (Greece), Massimo Volpe (Italy), Sven Wassmann (Germany), Stephan Windecker (Switzerland), Jose Luis Zamorano (Spain).The disclosure forms of all experts involved in the development of these Guidelines are available on the ESC website www.escardio.org/guidelines.

These practice guidelines on the management of arterial hypertension are a concise summary of the more extensive ones prepared by a Task Force jointly appointed by the European Society of Hypertension and the European Society of Cardiology. These guidelines have been prepared on the basis of the best available evidence on all issues deserving recommendations; their role must be educational and not prescriptive or coercive for the management of individual subjects who may differ widely in their personal, medical and cultural characteristics. The members of the Task Force have participated independently in the preparation of these guidelines, drawing on their academic and clinical experience and by objective examination and interpretation of all available literature. A disclosure of their potential con?ict of interest is reported on the websites of the ESH and the ESC

... ... Guidelines and position papers written under the auspices of the ESC Committee for Practice Guidelines (CPG) summarize and evaluate all available evidence on a particular issue at the time of the writing process, with the aim of assisting health professionals in selecting the best management strategies for an individual patient with a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. CPG Guidelines and position papers should help health professionals to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate. Members of this Task Force were selected by the ESC to represent professionals involved with the medical care of patients with this pathology. Selected experts in the field undertook a comprehensive review of the published evidence for management (including diagnosis, treatment, prevention and rehabilitation) of a given condition according to CPG policy. A critical evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger populations were included, where data exist.

Abbreviations ACE: angiotensin-converting enzyme; BP: blood pressure; DBP: diastolic blood pressure; eGFR: estimated glomerular filtration rate; ESC: European Society of Cardiology; ESH: European Society of Hypertension; ET: endothelin; IMT: carotid intima-media thickness; JNC: Joint National Committee; LVH: left ventricular hypertrophy; LVM: left ventricular mass; PDE-5: phosphodiesterase-5; PPAR-γ: peroxisome proliferators-activated receptor-γ; PWV: pulse wave velocity; SBP: systolic blood pressure; WHO: World Health Organization. Introduction In the 2 years since the publication of the 2007 guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) [1], research on hypertension has actively been pursued and the results of new important studies (including several large randomized trials of antihypertensive therapy) have been published. Some of these studies have reinforced the evidence on which the recommendations of the 2007 ESH/ESC guidelines were based. However, other studies have widened the information available in 2007, modifying some of the previous concepts, and suggesting that new evidence-based recommendations could be appropriate. The aim of this document of the ESH is to address a number of studies on hypertension published in the last 2 years in order to assess their contribution to our expanding knowledge of hypertension. Furthermore, some critical appraisal of the current recommendations of the ESH/ESC, as well as of other guidelines, might be a useful step toward the preparation of a third version of the European guidelines in the future. The most important conclusions are summarized in boxes. The points that will be discussed are reported in Box 1.Box. 1Assessment of subclinical organ damage for stratification of total cardiovascular risk The 2007 ESH/ESC guidelines recommend total cardiovascular risk be evaluated in each patient to decide about important aspects of treatment: the blood pressure (BP) threshold at which to commence drug administration, the target BP to be reached by treatment, the use of two-drug combinations as the initial treatment step, and the possible addition to the antihypertensive treatment regimen of lipid-lowering and antiplatelet agents [1]. Among the criteria to assess total cardiovascular risk, the European guidelines consider subclinical organ damage to be a very important component, because asymptomatic alterations of the cardiovascular system and the kidney are crucial intermediate stages in the disease continuum that links risk factors such as hypertension to cardiovascular events and death. On the basis of a number of criteria (prognostic importance, prevalence in the population, availability and cost of the assessment procedures, etc.), the 2007 European guidelines considered detection of organ damage as important for the diagnostic and prognostic evaluation of hypertensive patients. They further subdivided the different types of organ damage into (1) those that can be identified by relatively simple and cheap procedures [electrocardiogram, serum creatinine, estimated glomerular filtration rate (eGFR), and measurement of urinary protein excretion in order to detect microalbuminuria or proteinuria], which were thus regarded as suitable for routine search in the whole hypertensive population, and (2) those that require more complex procedures or instrumentations (echocardiogram, carotid ultrasonography, pulse wave velocity), which were for this reason only recommended for a more in-depth characterization of the hypertensive patient. Since then, other studies have added useful information on the importance of detecting subclinical organ damage in the hypertensive population, strengthening the recommendation to use the most easily available and the least costly procedures in the routine examination of individuals with hypertension. Heart A few recent papers have revived interest in the of the to the risk of cardiovascular In a a new of left ventricular the of left ventricular that is on and has been reported to be to cardiovascular The for and Furthermore, in the the have reported that in hypertensive with left individuals at risk of cardiovascular cardiovascular and for a very recent on the in as with left ventricular and of cardiovascular events hypertension is by risk for each evidence is available on the of as by of interest because of to more and and A has information more and hypertensive with left ventricular left ventricular left ventricular in of the left ventricular and and the risk of as large as that of with left ventricular in on population, the left ventricular and for and only in the risk with has been by other In a on a of hypertensive for with a of and cardiovascular events and with for cardiovascular risk factors Furthermore, a of hypertensive in the that cardiovascular events about more in with a or more with those with a this in the population, with a to in cardiovascular and were for a large number of and BP A in the risk more risk the The of carotid and with cardiovascular discussed in the 2007 guidelines, has been further by which have that carotid cardiovascular events of BP and and this for the at the carotid and for the at the of the carotid that by the at the and by the carotid prognostic in addition to that of prognostic of carotid has been reported in a of of the of cardiovascular which for about years has on the prognostic of arterial In the population, pulse wave with a in the risk of a cardiovascular Furthermore, of for cardiovascular events has been in for years of and wave such as BP and have been as of cardiovascular events in recent studies In in of these studies of and hypertensive only and cardiovascular for cardiovascular risk and carotid However, be that in most available the of BP pressure which the BP be considered in the of hypertensive in of further new the evidence on the prognostic of that available at the of the 2007 guidelines [1]. In the of in the with a of cardiovascular events and in the and with a in the of and cardiovascular events for cardiovascular risk and of in a of the to the of and to the different and more of the to the which only of The by the to be of and cardiovascular events in the large number of 2 in the were for the urinary protein excretion of the risk of cardiovascular events the in the risk of cardiovascular and events and evidence is available to the large of in of the prognostic of the in urinary protein as microalbuminuria In the and the microalbuminuria as important of cardiovascular the and in with microalbuminuria with those In the the of microalbuminuria with a In the a of to the with a and in the risk of cardiovascular cardiovascular and this the the to microalbuminuria The of urinary protein excretion and were of each other and the of microalbuminuria and about in for cardiovascular for cardiovascular and for of organ damage The 2007 European guidelines a number of of organ damage for which evidence of prognostic use in the could be because of of such as the cost and availability of the the and in the procedures, and in several the of of the and on the evidence available in the last 2 addition to the of organ damage in the 2007 guidelines can be the availability of more and the cost of their use about by In this the use of in a very recent in a of hypertensive cardiovascular disease has the information that are more and subclinical and in the of other of organ damage evidence these to a of importance because of the of the more and more in diagnostic procedures, disease is to more in prognostic and studies in hypertension. 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The Stroop Color and Word Test (SCWT) is a neuropsychological test extensively used to assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus attribute, well-known as the Stroop Effect. The aim of the present work is to verify the theoretical adequacy of the various scoring methods used to measure the Stroop effect. We present a systematic review of studies that have provided normative data for the SCWT. We referred to both electronic databases (i.e., PubMed, Scopus, Google Scholar) and citations. Our findings show that while several scoring methods have been reported in literature, none of the reviewed methods enables us to fully assess the Stroop effect. Furthermore, we discuss several normative scoring methods from the Italian panorama as reported in literature. We claim for an alternative scoring method which takes into consideration both speed and accuracy of the response. Finally, we underline the importance of assessing the performance in all Stroop Test conditions (word reading, color naming, named color-word).

BACKGROUND: Although the relationship between mortality and time delay to treatment has been demonstrated in patients with acute ST-segment elevation myocardial infarction (STEMI) treated by thrombolysis, the impact of time delay on prognosis in patients undergoing primary angioplasty has yet to be clarified. The aim of this report was to address the relationship between time to treatment and mortality as a continuous function and to estimate the risk of mortality for each 30-minute delay. METHODS AND RESULTS: The study population consisted of 1791 patients with STEMI treated by primary angioplasty. The relationship between ischemic time and 1-year mortality was assessed as a continuous function and plotted with a quadratic regression model. The Cox proportional hazards regression model was used to calculate relative risks (for each 30 minutes of delay), adjusted for baseline characteristics related to ischemic time. Variables related to time to treatment were age >70 years (P<0.0001), female gender (P=0.004), presence of diabetes mellitus (P=0.002), and previous revascularization (P=0.035). Patients with successful reperfusion had a significantly shorter ischemic time (P=0.006). A total of 103 patients (5.8%) had died at 1-year follow-up. After adjustment for age, gender, diabetes, and previous revascularization, each 30 minutes of delay was associated with a relative risk for 1-year mortality of 1.075 (95% CI 1.008 to 1.15; P=0.041). CONCLUSIONS: These results suggest that every minute of delay in primary angioplasty for STEMI affects 1-year mortality, even after adjustment for baseline characteristics. Therefore, all efforts should be made to shorten the total ischemic time, not only for thrombolytic therapy but also for primary angioplasty.

BACKGROUND: We investigated the long-term outcome of gene therapy for severe combined immunodeficiency (SCID) due to the lack of adenosine deaminase (ADA), a fatal disorder of purine metabolism and immunodeficiency. METHODS: We infused autologous CD34+ bone marrow cells transduced with a retroviral vector containing the ADA gene into 10 children with SCID due to ADA deficiency who lacked an HLA-identical sibling donor, after nonmyeloablative conditioning with busulfan. Enzyme-replacement therapy was not given after infusion of the cells. RESULTS: All patients are alive after a median follow-up of 4.0 years (range, 1.8 to 8.0). Transduced hematopoietic stem cells have stably engrafted and differentiated into myeloid cells containing ADA (mean range at 1 year in bone marrow lineages, 3.5 to 8.9%) and lymphoid cells (mean range in peripheral blood, 52.4 to 88.0%). Eight patients do not require enzyme-replacement therapy, their blood cells continue to express ADA, and they have no signs of defective detoxification of purine metabolites. Nine patients had immune reconstitution with increases in T-cell counts (median count at 3 years, 1.07x10(9) per liter) and normalization of T-cell function. In the five patients in whom intravenous immune globulin replacement was discontinued, antigen-specific antibody responses were elicited after exposure to vaccines or viral antigens. Effective protection against infections and improvement in physical development made a normal lifestyle possible. Serious adverse events included prolonged neutropenia (in two patients), hypertension (in one), central-venous-catheter-related infections (in two), Epstein-Barr virus reactivation (in one), and autoimmune hepatitis (in one). CONCLUSIONS: Gene therapy, combined with reduced-intensity conditioning, is a safe and effective treatment for SCID in patients with ADA deficiency. (ClinicalTrials.gov numbers, NCT00598481 and NCT00599781.)

Pulmonary hypertension (PH) frequently complicates the course of patients with various forms of chronic lung disease (CLD). CLD-associated PH (CLD-PH) is invariably associated with reduced functional ability, impaired quality of life, greater oxygen requirements and an increased risk of mortality. The aetiology of CLD-PH is complex and multifactorial, with differences in the pathogenic sequelae between the diverse forms of CLD. Haemodynamic evaluation of PH severity should be contextualised within the extent of the underlying lung disease, which is best gauged through a combination of physiological and imaging assessment. Who, when, if and how to screen for PH will be addressed in this article, as will the current state of knowledge with regard to the role of treatment with pulmonary vasoactive agents. Although such therapy cannot be endorsed given the current state of findings, future studies in this area are strongly encouraged.

Abstract Chiral π-conjugated molecules provide new materials with outstanding features for current and perspective applications, especially in the field of optoelectronic devices. In thin films, processes such as charge conduction, light absorption, and emission are governed not only by the structure of the individual molecules but also by their supramolecular structures and intermolecular interactions to a large extent. Electronic circular dichroism, ECD, and its emission counterpart, circularly polarized luminescence, CPL, provide tools for studying aggregated states and the key properties to be sought for designing innovative devices. In this review, we shall present a comprehensive coverage of chiroptical properties measured on thin films of organic π-conjugated molecules. In the first part, we shall discuss some general concepts of ECD, CPL, and other chiroptical spectroscopies, with a focus on their applications to thin film samples. In the following, we will overview the existing literature on chiral π-conjugated systems whose thin films have been characterized by ECD and/or CPL, as well other chiroptical spectroscopies. Special emphasis will be put on systems with large dissymmetry factors (gabs and glum) and on the application of ECD and CPL to derive structural information on aggregated states.

After decades of slow progress, the last years have seen a rapid acceleration of the development of adjuvanted vaccines which have lately been approved for human use. These adjuvants consist of different components, e.g. aluminium salts, emulsions such as MF59 and AS03, Toll-like receptor (TLR) agonists (CpG ormonophosphoryl lipid A (MPL) adsorbed on aluminium salts as in AS04) or combination of immunopotentiators (QS-21 and MPL in AS01). Despite their distinctive features, most of these adjuvants share some key characteristics. For example, they induce early activation (although at different levels) of innate immunity which then translates into higher antibody and cellular responses to the vaccine antigens. In addition, most of these adjuvants (e.g. MF59, AS03, AS04) clearly induce a wider breadth of adaptive responses able to confer protection against, for example, heterovariants of the influenza viruses (MF59, AS03) or against human papillomavirus strains not contained in the vaccine (AS04). Finally, the use of some of these adjuvants has contributed to significantly enhance the immune response and the efficacy and effectiveness of vaccines in the elderly who experience a waning of the immune responsiveness to infection and vaccination, as shown for MF59- or AS03-adjuvanted influenza vaccines and AS01-adjuvanted herpes zoster vaccine. These results, together with the track record of acceptable safety profiles of the adjuvanted vaccines, pave the way for the development of novel vaccines at the extremes of age and against infections with a high toll of morbidity and mortality. Here, we review the mechanisms associated with the performance of those adjuvanted vaccines in animal models and in humans through recent advances in systems vaccinology and biomarker discovery. We also provide some perspectives on remaining knowledge gaps but also on opportunities that could accelerate the development of new vaccines.

Human obesity is characterized by profound alterations in the hemodynamic and metabolic states. Whether these alterations involve sympathetic drive is controversial. In 10 young obese subjects (body mass index, 40.5 +/- 1.2 kg/m2, mean +/- SEM) with normal blood pressure and 8 age-matched lean normotensive control subjects, we measured beat-to-beat arterial blood pressure (Finapres technique), heart rate (electrocardiogram), postganglionic muscle sympathetic nerve activity (microneurography at the peroneal nerve), and venous plasma norepinephrine (high-performance liquid chromatography). The measurements were performed in baseline conditions and, with the exception of plasma norepinephrine, during baroreceptor stimulation and deactivation caused by increases and reductions of blood pressure via intravenous infusions of phenylephrine and nitroprusside. Baseline blood pressure and heart rate were similar in obese and control subjects. Plasma norepinephrine was also similar in the two groups. Muscle sympathetic nerve activity, however, was 38.6 +/- 5.1 bursts per minute in obese subjects and less than half that level in control subjects (18.7 +/- 1.3 bursts per minute), the difference being highly statistically significant (P < .02). Muscle sympathetic nerve activity and heart rate were reduced during phenylephrine infusion and increased during nitroprusside infusion, but the changes were about half as great in obese subjects as in control subjects. Thus, even in the absence of any blood pressure alteration, human obesity is characterized by a marked sympathetic activation, possibly because of an impairment of reflex sympathetic restraint. This may be involved in the high rate of hypertension and cardiovascular complications seen in obesity.

Throughout this article, the reader will notice combinations of superscripted letters and numbers (eg, "Cricoid Pressure ALS-CPR&A-007B ").These callouts are hyperlinked to evidence-based worksheets, which were used in the development of this article.An appendix of worksheets, applicable to this article, is located at the end of the text.The worksheets are available in PDF format and are open access.The topics reviewed by the International Liaison Committee on Resuscitation (ILCOR) Advanced Life Support Task Force are grouped as follows: (1) airway and ventilation, (2) supporting the circulation during cardiac arrest, (3) periarrest arrhythmias, (4) cardiac arrest in special circumstances, (5) identifying reversible causes, (6) postresuscitation care, (7) prognostication, and (8) organ donation.Defibrillation topics are discussed in Part 6.T he most important developments and recommenda- tions in advanced life support (ALS) since the 2005 ILCOR review are as follows:• The use of capnography to confirm and continually monitor tracheal tube placement and quality of cardiopulmonary resuscitation (CPR).• More precise guidance on the control of glucose in adults with sustained return of spontaneous circulation.Blood glucose values Ͼ180 mg/dL (Ͼ10 mmol/L) should be treated and hypoglycemia avoided.• Additional evidence, albeit lower level, for the benefit of therapeutic hypothermia in comatose survivors of cardiac arrest associated initially with nonshockable rhythms.• Recognition that many of the accepted predictors of poor outcome in comatose survivors of cardiac arrest are unreliable, especially if the patient has been treated with therapeutic hypothermia.There is inadequate evidence to recommend a specific approach to prognosticating poor outcome in post-cardiac arrest patients treated with therapeutic hypothermia.• The recognition that adults who progress to brain death after resuscitation from out-of-hospital cardiac arrest should be considered for organ donation.• The recommendation that implementation of a comprehensive, structured treatment protocol may improve survival after cardiac arrest.

BACKGROUND: In cross-sectional studies, ambulatory blood pressure (ABP) correlates more closely than clinic BP with the organ damage of hypertension. Whether ABP predicts development or regression of organ damage over time better than clinic BP, however, is unknown. METHODS AND RESULTS: In 206 essential hypertensive subjects with left ventricular hypertrophy (LVH), we measured clinic supine BP, 24-hour ABP, and left ventricular mass index (LVMI, echocardiography) before and after 12 months of treatment with lisinopril (20 mg UID) without or with hydrochlorothiazide (12.5 or 25 mg UID). Measurements included random-zero, clinic orthostatic, and home BP. In all, 184 subjects completed the 12-month treatment period. Before treatment, clinic supine BP was 165 +/- 15/105 +/- 5 mm Hg (systolic/diastolic), 24-hour average BP was 149 +/- 16/95 +/- 11 mm Hg, and LVMI was 158 +/- 32 g/m2. At the end of treatment, they were 139 +/- 12/87 +/- 7 mm Hg, 131 +/- 12/83 +/- 10 mm Hg, and 133 +/- 26 g/m2, respectively (P < .01 for all). Before treatment, LVMI did not correlate with clinic BP, but it showed a correlation with systolic and diastolic 24-hour average BP (r = .34/.27, P < .01). The LVMI reduction was not related to the reduction in clinic BP, but it was related to the reduction in 24-hour average BP (r = .42/.38, P < .01). Treatment-induced changes in average daytime and nighttime BPs correlated with LVMI changes as strongly as 24-hour BP changes. No substantial advantage over clinic supine BP was shown by clinic orthostatic, random-zero, and home BP. CONCLUSIONS: In hypertensive subjects with LVH, regression of LVH was predicted much more closely by treatment-induced changes in ABP than in the clinic BP. This provides the first longitudinally controlled evidence that ABP may be clinically superior to traditional BP measurements.

Star and planet formation are the complex outcomes of gravitational collapse and angular momentum transport mediated by protostellar and protoplanetary disks.In this review we focus on the role of gravitational instability in this process.We begin with a brief overview of the observational evidence for massive disks that might be subject to gravitational instability, and then highlight the diverse ways in which the instability manifests itself in protostellar and protoplanetary disks: the generation of spiral arms, small scale turbulence-like density fluctuations, and fragmentation of the disk itself.We present the analytic theory that describes the linear growth phase of the instability, supplemented with a survey of numerical simulations that aim to capture the non-linear evolution.We emphasize the role of thermodynamics and large scale infall in controlling the outcome of the instability.Despite apparent controversies in the literature, we show a remarkable level of agreement between analytic predictions and numerical results.In the next part of our review, we focus on the astrophysical consequences of the instability.We show that the disks most likely to be gravitationally unstable are young and relatively massive compared to their host star, M d /M * ≥ 0.1.They will develop quasi-stable spiral arms that process infall from the background cloud.While instability is less likely at later times, once infall becomes less important, the manifestations of the instability are more varied.In this regime, the disk thermodynamics, often regulated by stellar irradiation, dictates the development and evolution of the instability.In some cases the instability may lead to fragmentation into bound companions.These companions are more likely to be brown dwarfs or stars than planetary mass objects.Finally, we highlight open questions related to (1) the development of a turbulent cascade in thin disks, and (2) the role of mode-mode coupling in setting the maximum angular momentum transport rate in thick disks.

This is a continuity of a series of taxonomic papers where materials are examined, described and novel combinations are proposed where necessary to improve our traditional species concepts and provide updates on their classification. In addition to extensive morphological descriptions and appropriate asexual and sexual connections, DNA sequence data are also analysed from concatenated datasets (rDNA, TEF-α, RBP2 and β-Tubulin) to infer phylogenetic relationships and substantiate systematic position of taxa within appropriate ranks. Wherever new species or combinations are being proposed, we apply an integrative approach (morphological and molecular data as well as ecological features wherever applicable). Notes on 125 fungal taxa are compiled in this paper, including eight new genera, 101 new species, two new combinations, one neotype, four reference specimens, new host or distribution records for eight species and one alternative morphs. The new genera introduced in this paper are Alloarthopyrenia , Arundellina , Camarosporioides , Neomassaria , Neomassarina , Neotruncatella , Paracapsulospora and Pseudophaeosphaeria . The new species are Alfaria spartii , Alloarthopyrenia italica , Anthostomella ravenna , An . thailandica , Arthrinium paraphaeospermum , Arundellina typhae , Aspergillus koreanus , Asterina cynometrae , Bertiella ellipsoidea , Blastophorum aquaticum , Cainia globosa , Camarosporioides phragmitis , Ceramothyrium menglunense , Chaetosphaeronema achilleae , Chlamydotubeufia helicospora , Ciliochorella phanericola , Clavulinopsis aurantiaca , Colletotrichum insertae , Comoclathris italica , Coronophora myricoides , Cortinarius fulvescentoideus , Co . nymphatus , Co . pseudobulliardioides , Co . tenuifulvescens , Cunninghamella gigacellularis , Cyathus pyristriatus , Cytospora cotini , Dematiopleospora alliariae , De . cirsii , Diaporthe aseana , Di . garethjonesii , Distoseptispora multiseptata , Dis . tectonae , Dis . tectonigena , Dothiora buxi , Emericellopsis persica , Gloniopsis calami , Helicoma guttulatum , Helvella floriforma , H . oblongispora , Hermatomyces subiculosa , Juncaceicola italica , Lactarius dirkii , Lentithecium unicellulare , Le . voraginesporum , Leptosphaeria cirsii , Leptosphaeria irregularis , Leptospora galii , Le . thailandica , Lindgomyces pseudomadisonensis , Lophiotrema bambusae , Lo . fallopiae , Meliola citri-maximae , Minimelanolocus submersus , Montagnula cirsii , Mortierella fluviae , Muriphaeosphaeria ambrosiae , Neodidymelliopsis ranunculi , Neomassaria fabacearum , Neomassarina thailandica , Neomicrosphaeropsis cytisi , Neo . cytisinus , Neo . minima , Neopestalotiopsis cocoës , Neopestalotiopsis musae , Neoroussoella lenispora , Neotorula submersa , Neotruncatella endophytica , Nodulosphaeria italica , Occultibambusa aquatica , Oc . chiangraiensis , Ophiocordyceps hemisphaerica , Op . lacrimoidis , Paracapsulospora metroxyli , Pestalotiopsis sequoiae , Peziza fruticosa , Pleurotrema thailandica , Poaceicola arundinis , Polyporus mangshanensis , Pseudocoleophoma typhicola , Pseudodictyosporium thailandica , Pseudophaeosphaeria rubi , Purpureocillium sodanum , Ramariopsis atlantica , Rhodocybe griseoaurantia , Rh . indica , Rh . luteobrunnea , Russula indoalba , Ru . pseudoamoenicolor , Sporidesmium aquaticivaginatum , Sp . olivaceoconidium , Sp . pyriformatum , Stagonospora forlicesenensis , Stagonosporopsis centaureae , Terriera thailandica , Tremateia arundicola , Tr . guiyangensis , Trichomerium bambusae , Tubeufia hyalospora , Tu . roseohelicospora and Wojnowicia italica . New combinations are given for Hermatomyces mirum and Pallidocercospora thailandica . A neotype is proposed for Cortinarius fulvescens . Reference specimens are given for Aquaphila albicans , Leptospora rubella , Platychora ulmi and Meliola pseudosasae , while new host or distribution records are provided for Diaporthe eres , Di. siamensis , Di . foeniculina , Dothiorella iranica , Do. sarmentorum , Do. vidmadera , Helvella tinta and Vaginatispora fuckelii , with full taxonomic details. An asexual state is also reported for the first time in Neoacanthostigma septoconstrictum . This paper contributes to a more comprehensive update and improved identification of many ascomycetes and basiodiomycetes.

The relationship between inflammation and general health conditions in dairy cows and the link between inflammation, liver function, and fertility are poorly understood. To clarify these relationships, 120 multiparous dairy cows were followed throughout an entire lactation. Blood samples were collected during the first month of lactation for a metabolic profile, and milk yield, disease occurrence, and fertility parameters were monitored during the entire lactation. Twenty-four cows were culled, and another 19 were excluded because they had serious problems after 30 d in milk (DIM) and before the first insemination. The remaining 77 cows were pregnant at the end of lactation and were retrospectively grouped into quartiles based on liver activity index (LAI), which is based on plasma negative acute phase proteins. Cows in the lower (LO) and intermediate lower (INLO) quartiles of LAI had more severe inflammations with high concentrations of haptoglobin (0.77 and 0.61 g/L) and globulin (42.5 and 39.0 g/L), respectively, during the first week of lactation compared with cows in the upper (UP) and intermediate upper (INUP) quartiles of LAI (haptoglobin: 0.28 and 0.45 g/L, and globulin: 34.2 and 36.9 g/L, respectively). At 7 DIM, the cows in LO and INLO had greater bilirubinemia (8.7 and 10.5 vs. 6.3 microM/L in UP) and lower blood urea (3.5 and 3.7 vs. 4.1 mM in UP). The INLO group exhibited more days open (139 vs. 93) and services per pregnancy (2.68 vs. 1.65), but lower milk yield (38.3 vs. 40.8 kg/d at 28 DIM) compared with UP. The LO group did not have a significantly lower fertility status, but presented the lowest milk yield (34.1 kg/d at 28 DIM). Our data suggest that cows with lower LAI scores had a more pronounced inflammatory status during the first month of lactation, an impairment of usual hepatic functions (e.g., bilirubin clearance), and a larger negative energy balance. The same cows had poorer performance (lower milk yield and fertility) than cows with higher LAI scores. Overall data suggest that any effort to avoid the acute phase response in the transition period would be useful for optimizing the productive and reproductive performance of high-yielding dairy cows.

HERBAL MEDICINE IS THE USE OF MEDICINAL PLANTS FOR PREVENTION AND TREATMENT OF DISEASES: it ranges from traditional and popular medicines of every country to the use of standardized and tritated herbal extracts. Generally cultural rootedness enduring and widespread use in a Traditional Medical System may indicate safety, but not efficacy of treatments, especially in herbal medicine where tradition is almost completely based on remedies containing active principles at very low and ultra low concentrations, or relying on magical-energetic principles.In the age of globalization and of the so-called 'plate world', assessing the 'transferability' of treatments between different cultures is not a relevant goal for clinical research, while are the assessment of efficacy and safety that should be based on the regular patterns of mainstream clinical medicine.The other black box of herbal-based treatments is the lack of definite and complete information about the composition of extracts. Herbal derived remedies need a powerful and deep assessment of their pharmacological qualities and safety that actually can be realized by new biologic technologies like pharmacogenomic, metabolomic and microarray methology. Because of the large and growing use of natural derived substances in all over the world, it is not wise to rely also on the tradition or supposed millenarian beliefs; explanatory and pragmatic studies are useful and should be considered complementary in the acquisition of reliable data both for health caregiver and patients.

BACKGROUND: Small myocardial infarctions after percutaneous coronary intervention have been associated with higher risk of cardiac events during follow-up. Observational studies have suggested that statins may lower the risk of procedural myocardial injury. The aim of our study was to confirm this hypothesis in a randomized study. METHODS AND RESULTS: One hundred fifty-three patients with chronic stable angina without previous statin treatment were enrolled in the study. Patients scheduled for elective coronary intervention were randomized to atorvastatin (40 mg/d, n=76) or placebo (n=77) 7 days before the procedure. Creatine kinase-MB, troponin I, and myoglobin levels were measured at baseline and at 8 and 24 hours after the procedure. Detection of markers of myocardial injury above the upper normal limit was significantly lower in the statin group versus the placebo group: 12% versus 35% for creatine kinase-MB (P=0.001), 20% versus 48% for troponin I (P=0.0004), and 22% versus 51% for myoglobin (P=0.0005). Myocardial infarction by creatine kinase-MB determination was detected after coronary intervention in 5% of patients in the statin group and in 18% of those in the placebo group (P=0.025). Postprocedural peak levels of creatine kinase-MB (2.9+/-3 versus 7.5+/-18 ng/mL, P=0.007), troponin I (0.09+/-0.2 versus 0.47+/-1.3 ng/mL, P=0.0008), and myoglobin (58+/-36 versus 81+/-49 ng/mL, P=0.0002) were also significantly lower in the statin than in the placebo group. CONCLUSIONS: Pretreatment with atorvastatin 40 mg/d for 7 days significantly reduces procedural myocardial injury in elective coronary intervention. These results may influence practice patterns with regard to adjuvant pharmacological therapy before percutaneous revascularization.