Abstract: Aim:  To evaluate the potential impact of physicians' age on global cardiovascular (CV) risk management in the population of the Evaluation of Final Feasible Effect of Ultra Control Training and Sensitisation (EFFECTUS) study. Methods:  Involved physicians were stratified into three age groups (≤ 45, 46-55 and > 55 years), and asked to provide clinical data covering the first 10 adult outpatients, consecutively seen in May 2006. Results:  Overall 1078 physicians, among whom 219 (20%) were aged ≤ 45, 658 (61%) between 46 and 55, and 201 (19%) > 55 years, collected data of 9904 outpatients (46.5% female patients, aged 67 ± 9 years), who were distributed into three corresponding groups: 2010 (20%), 6111 (62%) and 1783 (18%), respectively. A higher prevalence of myocardial infarction and stroke was recorded by younger physicians rather than those aged > 46 years. Older physicians frequently recommended life-style changes, whereas a higher number of antihypertensive, antiplatelet, glucose and lipid-lowering prescriptions was prescribed by physicians aged ≤ 45 years. Conclusions:  This analysis of the EFFECTUS study indicates a higher prevalence of vascular diseases among outpatients who were followed by younger physicians, who prescribed a higher number of CV drugs than older physicians. These older physicians have more attitude for prescribing favourable life-style changes than younger physicians.
Abstract: The prevalence of patients with 'borderline' levels of cardiovascular risk factors has been rarely investigated, being often reported in studies evaluating abnormal values of these parameters. The BORDERLINE study represents a pilot experience to primarily identify the prevalence of 'high-normal' conditions, such as pre-hypertension, lipid and glucose levels in the upper range of normality in the setting of general practice in Italy.
Abstract: Pheochromocytoma is a neuroendocrine tumour of the adrenal gland that secretes an excessive amount of catecholamines, leading to a rapid rise and fall in blood pressure, headache, sweating and palpitations. The clinical scenario of pheochromocytoma, however, may be extremely variable and may include atypical cardiovascular manifestations, eventually leading to delays or mistakes in diagnosis. This issue is crucial since a missed diagnosis of pheochromocytoma may imply fatal consequences. This article reports a case of pheochromocytoma presenting with quite atypical cardiovascular manifestations such as transient left ventricular dysfunction and ventricular tachycardia. The pathophysiological determinants underlying uncommon clinical presentations of pheochromocytoma are also discussed. Received for publication 19 May 2011; accepted for publication 10 June 2011.
Abstract: Effective treatment of high blood pressure represents a key strategy for reducing the burden of hypertension-related cardiovascular diseases. In spite of these well-established concepts, hypertension remains poorly controlled worldwide. In addition, treated hypertensive patients often remain at higher risk compared with the normotensive population, even when a satisfactory blood pressure control is achieved, owing to a high or very high added cardiovascular risk profile. An emerging strategy to improve blood pressure control in hypertensive patients is a more extensive use of combination therapy than monotherapy in the daily clinical practice. Within the possible antihypertensive drug combinations currently available for the clinical management of hypertension, those based on the association of drugs inhibiting the renin-angiotensin system and thiazide diuretics or calcium channel-blockers have demonstrated to be effective and safe in lowering both systolic and diastolic blood pressure levels with a good tolerability profile. This article provides an overview of fixed-combination strategies, with a particular focus on the fixed-combination strategies based on olmesartan medoxomil.
Abstract: Blood pressure control is a key element in any cardiovascular prevention strategy. However, it is also one of the least frequently achieved goals in modern strategies for the clinical management of cardiovascular diseases, resulting in high impact in terms of cardiovascular morbidity and mortality. Among different factors that can be identified as the causes of poor blood pressure (BP) control in the general population of patients with hypertension, the excessive use of monotherapy, as opposed to combination therapy, is arguably one of the most significant. In this perspective, the use of combination therapies having synergic and complementary actions has been shown to reduce BP levels to increase the percentage of patients who respond to antihypertensive treatment and achieve the recommended BP targets. Moreover, recent studies have demonstrated that these strategies provide effective protection against hypertension-related organ damage, as well as a significant reduction of major cardiovascular events. While currently available evidence supports an increasingly important role of combination therapies compared with monotherapies, several other issues remain to be clarified. Among these, it has not yet been clearly established which classes of drugs should be considered for combination strategies, at what doses each component should be used, and whether combination strategies may be definitively considered as a first choice for the treatment of hypertensive patients at cardiovascular risk. Another relevant aspect concerns the choice between fixed and free combination therapies. This article discusses and analyses the different factors that may contribute to achieve effective BP control. In particular, the potential benefits and drawbacks associated with the use of fixed versus free combination therapies for hypertension treatment will be examined and discussed. The benefits of using combination strategies based on drugs that antagonize the renin-angiotensin system and dihydropyridine calcium antagonists will also be discussed, with a particular focus on amlodipine besylate combination therapies.
Abstract: The Evaluation of Final Feasible Effect of Ultra Control Training and Sensitization (EFFECTUS) study is aimed at implementing global cardiovascular (CV) risk management in Italy.
Abstract: It is still debated whether there are differences among the various antihypertensive strategies in heart failure prevention. We performed a network meta-analysis of recent trials in hypertension aimed at investigating this issue.
Abstract: The renin-angiotensin system (RAS) plays a key role in a number of pathophysiological mechanisms that are involved in the development and progression of cardiovascular and renal disease. For these reasons, pharmacological antagonism of this system, particularly the blockade of formation or the receptor antagonism of angiotensin II, has been demonstrated to be an effective and safe strategy to reduce the burden of cardiovascular disease. Among different drug classes, angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) have provided an excellent alternative to ACE inhibitors, representing a more selective and a better tolerated pharmacological approach to interfere with the RAS. Results derived from large, international, randomized clinical trials have consistently indicated that ARB-based therapeutic strategies may effectively provide cardiovascular and renal disease prevention and protection in different clinical conditions across the entire cardiovascular continuum. This article reviews the pathophysiological rationale of RAS involvement in the pathogenesis of renal diseases, focusing on the beneficial effects provided by ARBs in terms of renal protection.
Abstract: Two recently published post-monitoring follow-up studies of the United Kingdom Prospective Diabetes Study (UKPDS) have shown that although early and intensive treatment of hyperglycemia provides benefits for cardiovascular mortality that extend over time, the effects of a tight antihypertensive strategy in patients with diabetes did not seem to last during the following years. The authors concluded that blood pressure control is of crucial importance in patients with diabetes but is not protective against cardiovascular events when it is not sustained. Several lines of evidence suggest, however, that early and intensive antihypertensive treatment with some classes of drugs exerts benefits that may persist during the following years. Particularly, blockade of the renin-angiotensin-aldosterone system (RAAS) may interrupt the molecular and cellular mechanisms underlying cardiac and vascular remodeling and the maintenance of high blood pressure values. This review article critically discusses current evidence and explores the rationale for a legacy effect of RAAS blockade in hypertensive patients with diabetes.
Abstract: Prevalence of hypertension in children and adolescents has progressively and continuously increased over recent decades. Thus, early and effective control of high blood pressure may be considered an effective therapeutic approach, in order to reduce the burden of hypertension-related cardiovascular disease in future. In the past, due to the absence of prospective, long-term, randomized, controlled clinical trials performed in young hypertensive patients, lifestyle changes have been long seen as the only strategy to reduce high blood pressure levels. More recently, clinical data on the efficacy and safety of five major classes of antihypertensive drugs (including angiotensin converting enzyme inhibitors, angiotensin receptor blockers [ARBs], beta-blockers, calcium-antagonists, and diuretics) have become available. In particular, these trials demonstrated dose-dependent blood pressure reductions and a good tolerability profile of several ARBs in hypertensive children and adolescents. An overview is provided of the clinical benefits of early detection and prompt intervention of high blood pressure levels, with a closer analysis of recent clinical trials, performed with olmesartan medoxomil in young subjects with hypertension.
Abstract: BackgroundTo determine whether the administration of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) on top of standard cardiovascular (CV) therapies may reduce the incidence of new onset diabetes (NOD) in placebo-controlled clinical trials. The effects of these drugs on CV and non-CV mortality were also tested.MethodsWe performed a meta-analysis of all randomized clinical trials (11 trials, n = 84,363 patients, aged 64.2 ± 5.86 years), published until 14 March 2010, in which ACE inhibitors or ARBs were compared with placebo and NOD incidence, CV, and non-CV mortality were reported.ResultsOver an average follow-up of 4.0 ± 1.0 years, there were 1,284/15,142 (8.5%) cases of NOD in active-treated and 1,411/15,130 (9.3%) cases in placebo-treated patients in the ACE inhibitor trials, and 2,330/18,756 (12.4%) cases in active-treated and 2,669/18,800 (14.2%) cases in placebo-treated patients in the ARB trials. Overall, active therapy reduced NOD compared to placebo (odds ratio (OR) 95%, confidence interval (CI): 0.8 (0.8-0.9); P < 0.01). Both ACE inhibitors (OR 95%, CI: 0.8 (0.7-1.0); P = 0.07) and ARBs (OR 95%, CI: 0.8 (0.8-0.9); P < 0.01) reduced NOD as compared to placebo. Active treatment reduced CV mortality (OR 95%, CI: 0.9 (0.8-1.0); P < 0.01) and had a favorable impact on non-CV mortality (OR 95%, CI: 0.7 (0.9-1.0); P = 0.2) as compared to placebo.ConclusionsOur findings demonstrated that ACE inhibitors or ARBs should be preferred in patients with clinical conditions that may increase risk of NOD, since these drugs reduced NOD incidence. In addition, these drugs have favorable effects on CV and non-CV mortality in high CV risk patients.American Journal of Hypertension (2011). doi:10.1038/ajh.2011.8.
Abstract: The benefits of lowering blood pressure (BP) in hypertension, as well as in patients with diabetes, chronic renal disease or with a high cardiovascular (CV) risk profile, have been consistently demonstrated. Further clinical trials have explored the influence of BP levels in the lower range on the incidence of CV events, while some others have designed to evaluate the potential benefits obtained with an intensive antihypertensive therapy, aimed at achieving a target systolic BP levels below 120 mm Hg on major CV events among high-risk individuals with type 2 diabetes, as compared to that obtained from a standard therapy. Taken together, the results of several recent randomized clinical trials (RCTs) have challenged the currently prevailing paradigm "the lower, the better" in the hypertension management and have somehow revitalized the concept of the J-curve with respect to relations between BP levels and coronary events. In fact, detailed analyses showed an increased risk of coronary events, mostly myocardial infarction, in those patients who achieved the lowest BP levels, particularly in high-risk subsets of hypertensive patients. The same trials, however, confirmed the benefits of BP reductions even below 120 mm Hg on stroke incidence. In the present article, we revisited the main findings of some recent large clinical trials performed in hypertension and in high-risk individuals. Our conclusions highlight the importance of a closer scrutiny for coronary artery disease and suggest caution in lowering BP levels aggressively in patients with high-risk profile or diabetes.
Abstract: BACKGROUND: This study aims to evaluate left ventricular (LV) structure and function and inflammation in a paediatric population with sleep disordered breathing (SDB) and in control subjects. METHODS: Forty-nine children with SDB and 21 healthy, age-matched subjects were enrolled. The diagnosis of obstructive sleep apnoea syndrome (OSAS) was confirmed by the laboratory polysomnography, showing an obstructive apnoea/hypopnoea index of more than one per hour, according to the criteria of the American Academy of Sleep Medicine and modified for paediatric population. Fasting blood samples for the biochemical evaluation (including high-sensitivity C-reactive protein (hsCRP) were drawn in the morning, after the polysomnographic examination in all patients with SDB and in the control group. All children underwent a two-dimensional colour Doppler cardiac examination with LV mass assessment and systolic and diastolic function evaluation. RESULTS: Higher hsCRP levels were observed in subjects with OSAS than in children with primary snoring and in controls (0.8 ± 0.7 vs 0.3 ± 0.1 ng/dl, p = 0.001, and 0.4 ± 0.2 ng/dl, p = 0.01, respectively). The LV diastolic dysfunction was significantly more frequent in patients with severe OSAS and higher hsCRP levels than in control group. CONCLUSIONS: This study shows that OSAS in children is associated with higher LV mass, early LV diastolic dysfunction and a pro-inflammatory state (high CRP levels). These findings might help to explain the higher incidence of cardiovascular morbidity in patients with OSAS.
Abstract: Cardiovascular diseases represent the leading cause of morbidity and mortality, worldwide. Early detection and appropriate management of cardiovascular risk factors and disease markers in daily clinical practice may improve preventive strategies and reduce the burden of cardiovascular disease. The EFFECTUS (Evaluation of Final Feasible Effect of Control Training and Ultra Sensitisation) programme was an educational programme aimed at evaluating prevalence of major cardiovascular risk factors among outpatients, and preferences and attitudes for cardiovascular disease management among Italian physicians in their routine clinical practice. This article provides an overview of the main findings of different analyses from the EFFECTUS database, which have demonstrated a high prevalence of cardiovascular risk factors, irrespective of the clinical settings and outpatient clinics in which patients were followed. Also, findings from this database suggest that more intensive clinical data recording was paralleled by better adherence to guidelines, and that use of electronic rather than conventional support for clinical data collection and registration improved accuracy in data recording, which translated into better management of patients at risk in daily clinical practice. Received for publication 2 February 2011; accepted for publication 14 March 2011.
Abstract: In chronic heart failure (CHF), several plasma biomarkers identify subjects at risk of death over the midterm. However, their long-term predictive value in the context of other candidate predictors has never been assessed. This information may prove valuable in the management of a chronic disease with a long natural history, as CHF is today.
Abstract: BACKGROUND AND AIM: The Final Evaluation Feasible Effect of Ultra Control Training and Sensitization (EFFECTUS) is an educational program, aimed at improving global CV risk stratification and management in Italy. The present study evaluates differences on clinical approach to global CV risk among physicians involved in the EFFECTUS program and stratified in three geographical macro-areas (North, Center, South) of our Country. METHODS AND RESULTS: Physicians were asked to submit data already available in their medical records, covering the first 10 adult outpatients, consecutively seen in the month of May 2006. Overall, 1.078 physicians (27% females, aged 50 ± 7 years) collected data of 9.904 outpatients (46.5% females, aged 67 ± 9 years), among which 3.219 (32.5%) were residents in Northern, 3.652 (36.9%) in Central and 3.033 (30.6%) in Southern Italy. A significantly higher prevalence of major CV risk factors, including obesity, physical inactivity, hypertension and diabetes, was recorded in Southern than in other areas. Accordingly, Southern physicians more frequently prescribed antihypertensive, glucose and lipid lowering agents than other physicians, who paid significantly more attention to life-style changes in their clinical practice. CONCLUSIONS: This analysis of the EFFECTUS study demonstrates a high prevalence of CV risk factors in Italy, particularly in Southern areas, and indicates some important discrepancies in the clinical management of global CV risk among physcians working in different Italian regions.
Abstract: While chronic dialysis treatment has been suggested to increase pulmonary pressure values, right ventricular dysfunction (RVD) is a major cause of death in patients with end-stage renal disease. We investigated the impact of different dialysis treatments on right ventricular function.
Abstract: Arterial hypertension is a very complex disease characterized by a sustained rise in systolic and/or diastolic blood pressure (BP) levels and a significantly increased risk of developing major adverse cardiovascular and renal outcomes. Although BP-lowering treatment reduces the hypertension-related burden of disease, BP control continues to be poorly achieved worldwide. A major factor contributing to this therapeutic failure is represented by resistant (or refractory) hypertension. The diagnosis of 'resistant hypertension' is very common in clinical practice, yet it is often used to improperly define patients with difficult or challenging forms of hypertension. An incorrect use of this definition by physicians may lead to clinical behaviors that do not help to improve BP control; on the other hand, correct diagnosis of resistant hypertension may facilitate the successful treatment of hypertension. In this article, we will review and discuss the definition, pathophysiological mechanisms, diagnostic algorithms and potential new therapeutic options for treating resistant hypertension.
Abstract: Little information is available about the burden of hypertension on echo-lab activity in current practice. The aim of the present nation-wide survey in outpatient echo-labs was to investigate the prevalence rates of (1) echo examinations performed for the evaluation of hypertensive cardiac damage; (2) reports providing quantitative data on left ventricular (LV) structure and geometry; (3) LV hypertrophy (LVH) in hypertensives referred to echo labs. The study was carried out in 14 outpatient echo-labs across Italy. Prescriptions written by general practitioners were used to identify the indications for the examinations. Estimates of LVH were derived from original echo reports or were calculated from LV primary measures, when available, with Devereux's formula in a post-analysis. Echo examination was performed in 2449 subjects (1245 men and 1204 women); hypertension was the indication for echo in 745 (30.4%) cases. In this subgroup, LV mass (LVM), LVM indexed to body surface area, LVM indexed to height(2.7) and relative wall thickness ratio were reported in 58, 59, 54 and 52%, respectively. LVH was present in 53% of untreated hypertensives and, among treated patients, in 45 and 65% of those with and without blood pressure control, respectively. Our findings show that (1) hypertension accounts for approximately one-third of echo examinations performed in clinical practice; (2) a large fraction of echo reports do not provide quantitative data on LVM and LV geometry, (3) LVH is highly prevalent in hypertensives referred to echo labs for assessment of cardiac damage.
Abstract: In the past years, several risk charts have been created to increase the accuracy of cardiovascular risk stratification. The most widely used and validated algorithms do not included target organ damage as risk prediction. The aim of the present study was to evaluate whether preclinical renal damage is associated with cardiovascular diseases independently of individual risk profile assessed by risk charts.
Abstract: To evaluate the effects of treatments based on angiotensin II receptor blockers (ARBs) on the risk of myocardial infarction (MI), cardiovascular and all-cause death, as compared with conventional treatment or placebo.
Abstract: Recent hypertension guidelines have highlighted the need to achieve blood pressure control in order to effectively reduce cardiovascular and renal morbidity and mortality. However, blood pressure control remains poorly achieved in the general population, particularly in high- or very-high-risk hypertensive patients. In view of the growing need to achieve better blood pressure control and provide adequate cardiovascular and renal protection in hypertensive patients, the implementation of combination therapies--especially fixed-dose combinations--is currently recommended. A greater use of fixed-combination therapies, based on a single daily administration of two drugs, in fact, may favor better compliance and adherence to prescribed antihypertensive medications. Among the possible fixed-dose combinations, the one based on angiotensin-converting enzyme inhibitors and calcium-channel blockers, may be considered an effective, safe and well-tolerated approach and may provide a beneficial impact on cardiovascular risk. This article reviews the potential role of fixed-combination therapy in the treatment of hypertension with a specific focus on an emerging calcium-channel blocker angiotensin-converting enzyme inhibitor fixed-dose combination based on a new-generation dihiidropiridinic calcium-channel blocker (lercanidipine) and the prototype angiotensin-converting enzyme inhibitor (enalapril).
Abstract: Renal abnormalities are strongly associated with cardiac damage in essential hypertension. Detection of preclinical cardiac and renal abnormalities is a key clinical step in hypertension management. This study investigated the relationship between ECG abnormalities and microalbuminuria (MAU) in hypertensive patients without overt cardiovascular disease. This relationship, in fact, has never been extensively studied.
Abstract: Clinical evaluation of cardiovascular risk in patients with hypertension is evolving from independently assessing well-known, traditional risk factors (e.g. hypertension, hypercholesterolemia, obesity, diabetes mellitus, smoking) towards an integrated, multidisciplinary clinical approach, aimed at determining the global (or total) cardiovascular risk profile in each individual patient for planning early and effective strategies for cardiovascular prevention. A paradigmatic example is provided by hypertension, in which new clinical behaviour implies a shift from focusing only on high blood pressure levels towards a more integrated approach, aimed at identifying and reducing global cardiovascular risk, as is highlighted in the European Guidelines. This approach arises from the acknowledgement that a cluster of cardiovascular risk factors is the rule, rather than the exception in hypertension. In addition, major cardiovascular diseases often develop from a subclinical level, which can be discovered at an early stage, thus providing the opportunity promptly to intercept and treat high-risk patients early. Identification of organ damage and assessment of hypertension-related clinical conditions can further contribute to a more precise definition of an individual total cardiovascular risk profile, and to the decision on when, how and how much to treat patients with hypertension. Implementing a clinical behaviour based on global cardiovascular risk assessment will help to target global cardiovascular risk reduction, while maintaining specific therapeutic goals for individual risk factors. This synergistic approach holds the best promise for treating total cardiovascular risk and reducing the mounting global burden of cardiovascular disease associated with hypertension.
Abstract: Left ventricular diastolic dysfunction represents a frequent clinical condition and is associated with increased cardiovascular morbidity and mortality. Diastolic dysfunction is the most common cause of HF-PSF (heart failure with preserved ejection fraction). Therefore it becomes important to understand the pathophysiological mechanisms underlying diastolic dysfunction, as well as the effective therapeutic strategies able to antagonize its development and progression. Among the complex pathophysiological factors that may contribute to the development of diastolic dysfunction, the RAAS (renin-angiotensin-aldosterone system) has been shown to play a significant role. Paracrine and autocrine signals of the RAAS promote structural and functional changes in the heart largely linked to increased myocardial fibrosis. Enhanced and dysregulated activity of the RAAS also contributes to the development of volume overload and vasoconstriction with subsequent increases in left ventricular diastolic filling pressures and a higher susceptibility of developing CHF (congestive heart failure). More recently, it has also been suggested that the RAAS may play a role in triggering myocardial and vascular inflammation through the activation of different cell types and the secretion of cytokines and chemokines. RAAS-induced myocardial inflammation leads to perivascular myocardial fibrosis and to the development or progression of diastolic dysfunction. For these reasons pharmacological blockade of the RAAS has been proposed as a rational approach for the treatment of diastolic dysfunction. In fact, ACEIs (angiotensin-converting enzyme inhibitors), ARBs (angiotensin II receptor blockers) and AAs (aldosterone antagonists) have been demonstrated to delay the development and progression from pre-clinical diastolic dysfunction towards CHF, as well as to reduce the morbidity and mortality associated with this condition.
Abstract: To provide an overview of current habits, priorities, perceptions and knowledge of cardiologists with regard to hypertension and stroke prevention in outpatient practice.
Abstract: Left ventricular (LV) diastolic dysfunction (DD) associated with a preserved ejection fraction (EF) is a frequent alteration in hypertensive patients, usually considered an impairment of the diastolic phase alone. However, because systole and diastole are strictly correlated to one another, it is possible that hypertensive patients with isolated DD may also present with initial abnormalities of LV systolic properties, particularly those presenting with a more severe degree of DD. We performed a multiparametric echocardiographic assessment of LV systolic properties in patients without cardiovascular diseases, with preserved EF and different degrees of DD.
Abstract: Cardiologists play a central role in managing hypertensive patients, although recent surveys reveal a marked discrepancy between cardiologists' appreciation of their patients' risk status and the measures taken to reduce that risk. The diagnosis and the management of hypertension, in fact, must be viewed today not in isolation, but as part of a patients' global cardiovascular (CV) risk, resulting from the concomitant presence of a variety of risk factors, organ damage (left ventricular hypertrophy, carotid or peripheral atherosclerosis, microalbuminuria or impaired glomerular filtration rate), and hypertension-related clinical conditions. The choice of timing and the intensity of antihypertensive treatment should be based on blood pressure (BP)-lowering efficacy and the propensity to favourably impact patient's individual absolute CV disease risk profile. As part of this paradigm shift in CV disease prevention strategy, cardiologists can take several key steps to help improve standards of hypertension control: (i) increase the awareness of total risk management; (ii) initiate an integrated management strategy tailored to the individual patient's global CV risk (e.g. hypertension, hypercholesterolaemia, diabetes, age, smoking and gender); (iii) use any elevation in BP as a gateway to begin total risk management and (iv) utilise combination therapies (particularly fixed-dose combinations) to achieve more rapid and persistent BP control and improve patient compliance/persistence with therapy. To help improve standards of hypertension control in the cardiology setting, this review examines the concept of treating hypertension using a global risk assessment approach and proposes effective hypertensive therapy as part of global risk management in patients typically seen in cardiology practice.
Abstract: Heart failure represents a major cause of disease burden worldwide and is expected to further rise in the coming decades. Hypertension is the clinical condition most frequently associated to heart failure.
Abstract: Blood pressure reduction represents a key priority for any preventive strategy in hypertension. However, one of the issues that has been raised repeatedly over the last few years is whether blood pressure reduction is all that matters in the treatment of hypertension, or if other properties related to antihypertensive drugs may be relevant for cardiovascular and renal outcomes. In this view, a long debate has emerged in the scientific and medical community, whether the newer classes of antihypertensive agents have additional properties beyond blood pressure control and, further, are superior to traditional antihypertensive drugs. The evidence accumulated over the last 20 years have consistently demonstrated that "new" drugs are as effective as "old" drugs in terms of blood pressure-lowering effect and in several clinical trials even more effective than old drugs on major cardiovascular outcomes. In addition, they have been demonstrated to effectively antagonize the progression of the hypertensive disease, as monitored through the development of intermediate end points. Finally, in view of the need for using combination therapy to effectively achieve blood pressure control in the clinical management of hypertension, the antihypertensive combinations based on new drugs, especially those using angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers with a low-dose thiazide diuretic or those using calcium channel blockers and ACE inhibitors, are now considered more effective and safer than those using beta-blockers and low-dose thiazide diuretic, especially in view of their better metabolic profile and their better tolerability.
Abstract: The metabolic syndrome (MS) is associated with left ventricular hypertrophy (LVH). Previous evidence has shown that LVH is favoured by low levels of atrial natriuretic peptide (ANP), independently from blood pressure (BP), in hypertension. Although levels of natriuretic peptides are known to be lower in obesity, plasma ANP levels have not yet been assessed in MS. We aimed to assess the ANP levels and their relationship with left ventricular mass (LVM) in patients affected by MS.
Abstract: Previous studies have shown that metabolic syndrome (MS) is associated with an increased susceptibility to develop cardiovascular damage (CD). Experimental evidence indicates that inflammation and fibrosis could play a critical role in the development of CD in hypertension. This issue has not been clarified yet in patients with MS. The aim of our study was to investigate the relationship between markers of inflammation and fibrosis with CD in hypertensive patients with and without MS.
Abstract: Together with other modifiable cardiovascular risk factors, hypertension heavily contributes to the global burden of cardiovascular morbidity and mortality, as well as to the increase in individual absolute cardiovascular risk. Comparison of the effectiveness of different therapies in reducing the incidence of major cardiovascular events has classically required the evaluation of major 'hard' end points. In view of the long natural history of hypertension, however, it appears very useful to monitor modifications in measurable 'intermediate' end points or 'disease markers'. This approach may provide more accurate individual risk stratification and a better evaluation of the efficacy of a given treatment in preventing or modifying the course of target organ damage. This may represent a valuable and affordable strategy in clinical practice allowing the evaluation of both patient prognosis and the effectiveness of antihypertensive treatment over time.
Abstract: Cardiovascular disease represents the leading cause of morbidity and mortality in Western countries, and hypertension-related cardiovascular events affect about 37 million people per year, worldwide. In this perspective, hypertensive patients are at increased risk to experience cardiovascular events during life-long period, and treatment of high blood pressure represents one of the most effective strategies to reduce global cardiovascular risk. However, due to its multifactorial pathophysiology and its frequent association with other relevant risk factors and clinical conditions, treatment of hypertension requires an integrated approach, including life-style measures, antihypertensive drugs and other therapies. Yet, worldwide general practitioners continue to focus their attention on the management of a single risk factor, eg, blood pressure, rather than to global cardiovascular risk profile. In this view, modem strategies of cardiovascular prevention in hypertensive patients should move from a single risk factor based approach toward a more comprehensive risk evaluation in the individual patient. In other words, it is important to define the global cardiovascular risk to manage hypertensive patients at high-risk, rather than to focus on the high level of a single risk factor, for reducing cardiovascular morbidity and mortality in the general population, as well as in hypertensive population.
Abstract: Effective treatment of high blood pressure levels represents a key strategy for reducing global cardiovascular risk. Other factors, beyond blood pressure control, however, appear to be of potential relevance in reducing the risk related to hypertension. Recent clinical trials have demonstrated that those pharmacological agents that counteract the renin-angiotensin system may confer additional clinical benefits across the spectrum of cardiovascular disease, beyond their blood pressure-lowering properties. These studies are largely based on the use of an antihypertensive strategy, based on the association between angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ARBs) and low-dose thiazide diuretics or calcium channel blockers. Over the last few decades, clinical trials have also tested the potential effects of combination therapy based on the association between angiotensin-converting enzyme inhibitors or ARBs and other renin-angiotensin system-blocking agents, including mineralocorticoid receptor antagonists and, more recently, renin inhibitors. This review highlights the evidence derived from recent clinical trials, supporting a role for pharmacological strategies based on ARBs in primary and secondary prevention of cardiovascular and renal disease.
Abstract: Stroke represents the most devastating cardiovascular disease in the Western world, accounting for approximately 700,000 cases each year, including 500,000 first attacks and 200,000 recurrent episodes. High blood pressure is the most relevant modifiable risk factor for developing stroke.
Abstract: In recent years, medical practice has been influenced substantially by several factors, including the overwhelming development of evidence-based medicine, which is a consequence of the impressive, growing number of large clinical trials, the so-called "mega-trials." These clinical studies are designed mostly to investigate the effects of drugs or treatments on hard end points that cannot be tested by individual physicians in their daily clinical practice. The growing role of this epidemiologic approach to medicine, which is based mostly on the assessment of the average response or behavior of large populations rather than of individuals, is systematically replacing the former knowledge and reference points of the physician, as a substitute rather than as an aid. Taking into account the case of hypertension and particularly the renin-angiotensin system-blocking agents, this article reviews the issues and limitations of transferring evidence from mega-trials to clinical practice and suggests new strategies to make trials more effective and transferable to the case of individual patients.
Abstract: Effective treatment of high blood pressure levels represents a crucial point in reducing global cardiovascular risk, and several studies have clearly demonstrated a significant reduction in cardiovascular and renal morbidity and mortality with a more intensive blood pressure-lowering treatment. Other factors beyond blood pressure control may be important in reducing the risk related to hypertension. Pharmacologic agents blocking the renin-angiotensin system, in particular the angiotensin II-receptor blocker (ARB), a novel class of antihypertensive agents, represent an important addition to the therapeutic options for hypertension management, and recent large, international, randomized, trials have demonstrated that ARBs have clinical benefits across the spectrum of disease severity. In this article, we provide some evidence derived from these trials, supporting a role for ARBs in primary and secondary prevention of cardiovascular and renal disease, beyond blood pressure control.
Abstract: The clinical history of patients with heart failure (HF) is complicated by arterial thromboembolism. Platelet activation is reported in this population, but the underlying mechanism has not been clarified. Forty-two patients with HF scored according to New York Heart Association (NYHA) classification had higher levels of collagen-induced platelet aggregation, platelet tumor necrosis factor-alpha (TNF-alpha) receptor expression, and serum thromboxane B2 and higher circulating levels of TNF-alpha than 20 healthy subjects. Coincubation of platelets from HF patients with an inhibitor of TNF-alpha receptors significantly reduced collagen-induced platelet aggregation. In vitro study demonstrated that TNF-alpha amplified the platelet response to collagen; this effect was inhibited by TNF-alpha receptor antagonist and inhibitors of arachidonic acid metabolism. This study showed that TNF-alpha behaves as a trigger of platelet activation through stimulation of the arachidonic acid pathway.
Abstract: Several studies have demonstrated that a prolonged over-activation of neurohormonal mechanisms contributes to drive structural and functional abnormalities of the cardiovascular system and leads to poor prognosis in patients with congestive heart failure (CHF). In particular, activation of the renin-angiotensin-aldosterone system (RAAS) leads to increased levels of angiotensin II and plasma aldosterone, and promote development of arterial vasoconstriction and remodeling, sodium retention, oxidative process, and cardiac fibrosis. Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and beta-blockers may modulate this excessive over-activity and improve survival in those patients. However, high circulating and tissue levels of angiotensin II and aldosterone may persist and contribute to further progression of CHF. Many aspects of the pathophysiological role of the RAAS in CHF are still debated, and a more thorough comprehension of this fundamental system is needed. This article reviews the current knowledge on the biochemical and functional organization of the RAAS, its pathophysiological role in CHF, and the potential therapeutic implications.
Abstract: Cardiovascular disease is the leading cause of morbidity and mortality in Western countries, and hypertension-related cardiovascular events affect about 37 million people per year worldwide. In this perspective, treatment of hypertension is a reference illustrating strategies of cardiovascular prevention. Hypertensive patients are at increased risk of undergoing a cardiovascular event throughout their lives, and treatment of high blood pressure is one of the most effective strategies to reduce global cardiovascular risk. However, due to its multifactorial pathophysiology and frequent association with other important risk factors and clinical conditions such as dyslipidemia, diabetes, left ventricular dysfunction, and renal impairment, treatment of hypertension requires an integrated approach, including life-style measures, antihypertensive drugs and other therapies (statins, ASA, etc.). Nonetheless, worldwide, general practitioners continue to focus on managing a single risk factor, e.g. blood pressure, rather than on overall cardiovascular risk profiles. Another debated issue is whether it matters how blood pressure is lowered in hypertensive patients at high risk. In other words, are the latest antihypertensive drugs more effective than older blood pressure strategies in terms of reduction of cardiovascular events? The recent results of the ASCOT Study address these controversial issues and throw new light on the management of cardiovascular risk in hypertension.
Abstract: Hypertension represents the most common associated cause of heart failure, and it is frequently involved in the pathogenesis of left ventricular dysfunction and its progression towards congestive heart failure. A common pathophysiological link of hypertension to heart failure is represented by the abnormalities of the neurohormonal profile and its impact on cardiac function, systemic hemodynamics and salt/water balance. This article synthetically reviews this aspect together with a specific analysis of the significance of measurements of neurohormones for diagnosis and prognostic stratification in heart failure.
Abstract: Experimental studies have suggested that TNF alpha, a pro-inflammatory cytokine, may contribute to the deterioration of cardiovascular function through various mechanisms, including the generation of reactive oxygen species. It has not yet been demonstrated whether TNF alpha has prooxidant activity in patients with heart failure, and what the mechanism eventually resulting in this effect are. We analyzed 42 patients (38 men and 4 women, aged 26 to 74 years) with heart failure, secondary to idiopathic dilated cardiomyopathy (n=21), coronary artery disease (n=15), and valve disease (n=6), and 20 controls (18 men and 2 women, aged 49 to 67 years). Ten patients were in class I, 9 in class II, 15 in class III and 8 in class IV according to NYHA Classification. Blood samples were obtained from each patient to evaluate basal and collagen-induced platelet O(2)(-) production, and plasma TNF alpha. In vivo results showed increased platelet O(2)(-) production and plasma TNF alpha levels in NYHA class III-IV compared with that in controls or in NYHA I-II (p<0,001); platelet O(2)(-) production correlated significantly (R=0,6; p<0,01) with TNF alpha plasma levels. In vitro studies showed TNF alpha dose-dependently (5-40 pg/ml) induced platelet O(2)(-) production, and that this effect was significantly inhibited by its specific inhibitor, WP9QY (1 microM); aspirin (100 microM), AACOCF(3), a specific PLA(2) inhibitor (14 microM), and DPI, an inhibitor of NADPH oxidase, significantly inhibited TNF alpha-mediated platelet O(2)(-) production. This study suggests that in patients with heart failure, enhanced platelet O(2)(-) production is mediated by TNF alpha via activation of arachidonic acid and NADPH oxidase pathways.
