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Objective: Gout is the most common arthritis in adults. Despite the availability of valid therapeutic options, the management of patients with gout is still suboptimal. The Italian Society of Rheumatology (SIR) aimed to update, adapt to national contest and disseminate the 2006 EULAR recommendations for the management of gout. Methods: The multidisciplinary group of experts included rheumatologists, general practitioners, internists, geriatricians, nephrologists, cardiologists and evidence-based medicine experts. To maintain consistency with EULAR recommendations, a similar methodology was utilized by the Italian group. The original propositions were translated in Italian and priority research queries were identified through a Delphi consensus approach. A systematic search was conducted for selected queries. Efficacy and safety data on drugs reported in RCTs were combined in a meta-analysis where feasible. The strength of recommendation was measured by utilising the EULAR ordinal and visual analogue scales. Results: The original 12 propositions were translated and adapted to Italian context. Further evidences were collected about the role of diet in the non-pharmacological treatment of gout and the efficacy of oral corticosteroids and low-dose colchicine in the management of acute attacks. Statements concerning uricosuric treatments were withdrawn and replaced with a proposition focused on a new urate lowering agent, febuxostat. A research agenda was developed to identify topics still not adequately investigated concerning the management of gout. Conclusions: The SIR has developed updated recommendations for the management of gout adapted to the Italian healthcare system. Their implementation in clinical practice is expected to improve the management of patients with gout.

Atherosclerotic cardiovascular diseases remain the main cause of mortality worldwide, due to a poor control of modifiable risk factors for atherosclerosis. High levels of low-density lipoprotein cholesterol represent the most relevant actor in the development of atherosclerotic cardiovascular diseases, as well as the main target of prevention strategies. Although lipid-lowering treatments were shown to be effective for cardiovascular prevention, several barriers (e.g. clinician reluctance to prescribe an intensive treatment, poor adherence of patients to therapy, high pharmacotherapy burden of high-risk patients and the fear for adverse events potentially associated with statins) still prevent therapy optimization. Such issues will be addressed in this review article, taking into account possible strategies for their solution, through an integrated approach including both management interventions and a larger use of the available pharmacologic options.

This paper is addressed to the cardiologist, who in his or her clinical practice interacts with and treats cardiovascular risk factors associated with obesity and its complications; it may also be useful for other specialists, to whom patients with excess weight may be referred. We hope that the cardiologist will consider obesity as a preventable and treatable disease that contributes to overall cardiovascular risk, and will deploy a strong commitment to cope with this disease. To this purpose, the text is composed of 8 questions aimed to cover relevant topics for the clinical practice.

The clinical guidelines, while representing an objective reference to perform correct therapeutic choices, contain grey zones, where the recommendations are not supported by solid evidence. In the fifth National Congress Grey Zones held in Bergamo in June 2022, an attempt was made to highlight some of the main grey zones in Cardiology and, through a comparison between experts, to draw shared conclusions that can illuminate our clinical practice. This manuscript contains the statements of the symposium concerning the controversies regarding cardiovascular risk factors. The manuscript represents the organization of the meeting, with an initial revision of the present guidelines on this topic, followed by an expert presentation of pros (White) and cons (Black) related to the identified "gaps of evidence". For every issue is then reported the "response" derived from the votes of the experts and the public, the discussion and, finally, the highlights, which are intended as practical "take home messages" to be used in the everyday clinical practice. The first gap in evidence discussed is the indication for therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors for all diabetic patients at high cardiovascular risk. The second examines the possibility of using SGLT2 inhibitors in all patients with renal insufficiency, regardless of albuminuria. The last gap in evidence regards the possible use of glucagon-like peptide-1 receptor agonists as a weapon against obesity.

Coffee is the most widespread drink in the world, immediately after water. In the United States, coffee consumption amounts to 400 million cups per day and is, globally, the main source of caffeine. In view of such a high worldwide use, it is of great interest for the scientific community to understand whether or not this drink has an impact on health. In the first clinical studies aimed at investigating the effects of coffee, a possible deleterious effect on systemic blood pressure and on the incidence of cardiovascular diseases was hypothesized. These data have been interpreted on the basis of the mild increase in blood pressure that can occur immediately following the consumption of caffeine. Coffee, however, contains more than 1000 chemical components, among which are polyphenols such as chlorogenic acid and lignans, with antioxidant and anti-inflammatory properties, and substances with a vasodilating action such as vitamin E, niacin, potassium and magnesium. It is therefore likely that if, on the one hand, caffeine causes a mild increase in blood pressure, on the other hand, the countless substances contained in coffee are able to counteract this effect, actually resulting in a health benefit. The latest evidence available in the literature shows indeed how the consumption of 3-5 cups of coffee a day is not only harmless, but is even able to significantly reduce the incidence of and mortality from cardiovascular diseases, as well as mortality from all causes.

Orthostatic hypotension is a medical condition potentially debilitating and associated with a negative prognosis. It is paramount for cardiologists to recognize it, mostly for the following reasons: it is a predictive factor for cardiovascular events, it may cause syncope, and it is frequently associated with supine hypertension. Orthostatic hypotension may be secondary to neurogenic etiology (baroreflex dysfunction) or non-neurogenic etiology (dehydration or medication-related). Although laboratory tests exploring the autonomic nervous system are required for a detailed etiologic diagnosis, medical history and a sphygmomanometer can be sufficient for diagnosis. Therapeutic management of orthostatic hypotension is challenging, mostly because of the association in half of the cases with supine hypertension. Treatment should be a compromise between anti-hypotensive and anti-hypertensive measures with one overcoming the other based on the hour of the day. Non-pharmacological therapies, regarded as avoidance of precipitating factors and physical and dietary interventions, as well as chronic treatment revision, have a pivotal role.In this review we will discuss, in a pragmatic manner, about epidemiology, etiology, clinical aspects and diagnosis of orthostatic hypotension. Moreover, we will discuss about prognosis and management of orthostatic hypotension and supine hypertension.

The known interactions between the heart and the digestive system, concerning the semeiotic and the pathophysiology of coronary and non-coronary pain and the possible causal relationship between reflux pathology and the onset of atrial fibrillation, have been implemented by the most recent acquisitions on the role of intestinal microbiota in the development of atherosclerosis, hypertension and heart failure; this brief review also addresses these more innovative aspects.

Cardiovascular prevention represents a cornerstone of modern strategies to reduce the burden of cardiovascular disease. It is of key importance to prevent cardiovascular diseases and associated events, not only to reduce morbidity and mortality, but also to increase the years of wellness in the aging population and to make the growing socio-economic burden imposed by cardiovascular events more sustainable.The current approach to prevention is based on an integrated use of effective lifestyle measures and, whenever appropriate, of antihypertensive and antidiabetic drugs, lipid-lowering agents and antiplatelet drugs.Given that population characteristics, in terms of ethnicity, demography and lifestyle habits, and healthcare system organizations differ among countries, international guidelines are not always applicable to specific countries and, often, are difficult to translate into daily clinical practice.In order to afford the specific features of Italy, 10 Scientific Societies and Research Institutions, mostly involved in preventive strategies, contributed to the present Italian consensus document, which includes brief, practical recommendations to support the preventive actions within the physician community and the general practice setting.

The need for new lipid-lowering drugs is based on the clear-cut evidence that a considerable proportion of patients with dyslipidemia cannot reach the target of cardiovascular protection with the use of currently available drugs (statins, ezetimibe, fibrates). Among the new classes of drugs, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (namely alirocumab and evolocumab) provide an effective solution for patients with familial hypercholesterolemia as well as for high-risk patients who do not achieve the target or complain statin-related adverse events. The use of PCSK9 inhibitors is associated with a huge reduction in LDL-cholesterol levels (up to 30-40 mg/dl) with 1-2 monthly administrations, and their effect is integrated with that of statins and ezetimibe. The improvement of lipid profile is in the range of that observed with other new drugs such as lopitamide and mipomersen, while the tolerability profile appears definitely better. A more effective characterization of patients with dyslipidemia is the trainer of new research in the field of lipid-lowering drugs and PCSK9 inhibitors appear the more reliable product of such a promising research.

The impact of low density lipoprotein (LDL) cholesterol levels on cardiovascular risk has been extensively studied. Statins have been demonstrated to significantly reduce LDL cholesterol levels, contributing to cardiovascular risk reduction particularly in patients with high cardiovascular risk. However, low adherence to statin therapy, often due to adverse effects, has raised the need for new pharmacological approaches to combine with statin therapy in order to reach the target levels of LDL cholesterol. Ezetimibe is a selective inhibitor of Niemann-Pick C1-like 1 (NPC1L1) protein that regulates the cholesterol uptake from the small intestine into the enterocytes. Ezetimibe has been demonstrated to significantly reduce LDL cholesterol levels in combination with statins and recent trials support its role in reducing the risk of cardiovascular events.

The indications for the use of aspirin in primary cardiovascular prevention continue to be a source of intense debate, with major international guidelines providing conflicting advices. This document, written by delegates of the main Italian scientific societies dealing with cardiovascular prevention and modeled on a similar document by the European Society of Cardiology Working Group on Thrombosis, reviews the evidence in favor and against the use of aspirin therapy in primary prevention based on data cumulated so far, including recent data linking aspirin with cancer protection. While awaiting the results of several ongoing studies, this document argues for a pragmatic approach to the use of low-dose aspirin in primary cardiovascular prevention, and suggests its use in patients at high cardiovascular risk, defined as ≥2 major cardiovascular events (death, myocardial infarction, or stroke) projected per 100 person-years, who are not at increased risk of bleeding.

Acute heart failure (AHF) is a potentially life-threatening condition that may arise as a deterioration of a previous heart failure or may be the first presentation of heart failure. Several causes or precipitating factors have been listed, as well as different mechanisms have been described, thus leading to a broad spectrum of clinical presentations. Symptoms and signs of AHF have a strong clinical and prognostic significance and are kept into consideration to guide disease management. In particular, a higher clinical severity or a worse prognosis are associated with lower blood pressure levels, fluid overload, evidence of myocardial ischemia or renal impairment. Putatively, interventions addressed to restore these factors may play a role in the management of AHF.

Observational studies demonstrate that the proportion of treated hypertensive patients who attain the recommended blood pressure goals (140/90 mmHg) does not exceed 30-40%. Conversely, clinical trials have consistently shown that effective blood pressure control within the recommended targets can be achieved in 70-80% of treated hypertensive patients with different cardiovascular risk profile, especially when appropriate, effective and well tolerated combination therapies are used. In order to bridge the gap between current and optimal blood pressure control rates and to achieve a more effective cardiovascular prevention, the Italian Society of Hypertension has recently developed an interventional strategy that aims to approximate 70% of treated controlled patients by 2015. This ambitious goal can be realistically achieved by the appropriate use of modern aids and tools, also including the implementation of combination therapy, especially if this approach can be simplified into a single pill, now available in Italy. At present, 70-80% of hypertensive patients require combination therapies based on at least two classes of antihypertensive drugs to achieve the recommended blood pressure goals. It is therefore of paramount importance to implement this strategy in routine clinical practice. Among the different combination therapies, the use of combination strategies based on drugs inhibiting the renin-angiotensin system, such as angiotensin receptor blockers and angiotensin-converting enzyme inhibitors, combined with diuretics and/or calcium-channel blockers, have demonstrated to significantly reduce the rates of major cardiovascular events and discontinuations from prescribed therapies, resulting in higher antihypertensive efficacy and better tolerability than monotherapy. The present document of the Italian Society of Hypertension aims to provide main indications for implementing combination therapy in the clinical management of hypertension in order to improve blood pressure control in Italy.

Hypertension is responsible for a relevant burden of cardiovascular morbidity and mortality worldwide. Although several appropriate and integrated pharmacological strategies are available, blood pressure control still remains largely unsatisfactory. Failure to achieve effective blood pressure control in treated hypertensive patients may have a substantial impact on overall cardiovascular risk, since it significantly increases the risk of both macrovascular and microvascular complications. Hypertension is arbitrarily defined as "resistant" or "refractory" when recommended blood pressure goals (clinic blood pressure <140/90 mmHg, or <130/80 mmHg in patients with type 2 diabetes mellitus) are not achieved, despite changes in lifestyle and treatment with adequate doses of at least three antihypertensive drugs from different classes, including a diuretic. A new non-pharmacological option for the treatment of patients with resistant hypertension has recently become available. Renal sympathetic denervation is a minimally invasive procedure performed via femoral access that uses radiofrequency catheter ablation to disable renal sympathetic afferent and efferent nerves. It results in isolation of renal parenchymal and juxtaglomerular cells from the abnormal enhancement of renal adrenergic nerve activity. The present position paper of the Italian Society of Hypertension provides a diagnostic and therapeutic approach to the early identification and effective clinical management of patients with resistant hypertension, who may be candidates for renal denervation. These indications may have important implications not only from a clinical viewpoint but also from an economic perspective. The accurate identification of patients with resistant hypertension and the appropriate selection of patients eligible for this procedure may help improve blood pressure control and reduce the risk of cardiovascular and cerebrovascular complications in these patients.

Atherosclerosis is a systemic disease where atheromatous plaque is the basic lesion. A number of studies have shown that atherosclerotic lesions progress over time, when risk factors such as arterial hypertension and hyperlipidemia are present. Many clinical trials have been conducted in the last decade, both with antihypertensive and lipid-lowering drugs. These trials demonstrated that progression of atherosclerosis can be halted and even regression can be achieved. In studies with lipid-lowering drugs, the best results were achieved with a dramatic decrease in LDL cholesterol levels, obtained with statins, particularly when combined with a concomitant increase in HDL cholesterol. The treatment of hypertension provided better results on the endpoint atheromatous plaque with antihypertensive drugs belonging to the class of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or calcium antagonists. Some studies were conducted both with antihypertensive and lipid-lowering drugs, and a better control of lesion progression, together with its partial regression, was obtained. The best approach seems to be achieved with the combination of a specific intervention on lipid profile together with a targeted control of blood pressure.

Healthcare costs for heart failure are increasing. The need for a better care, however, has to be matched with a policy of cost containment. A way to improve the cost-effectiveness of heart failure care is the disease management approach, in which therapy, education and follow-up are tailored for each patient by a multidisciplinary team. Such a complex intervention can be facilitated by the use of telemedicine, which allows the remote control of considerable amounts of clinical data. In Italy, a few studies with telemedicine have been reported. A recent development in this field is represented by the ICAROS project (Integrated Care vs Conventional Intervention in Cardiac Failure Patients: Randomized Open Label Study), whose aim is to improve the clinical and psychological care of heart failure patients employing advanced wireless telecommunication technology. So far, we randomized 60 patients: 30 in usual ambulatory care, 30 in an intensive treatment group. The latter patients were instructed to use a portable computer to get in touch daily with the heart failure clinic and receive feedback instruction for the management of drug therapy and daily problems. At the first year of follow-up, the treatment group showed good compliance to drug prescriptions, and could easily handle the portable computer. The preliminary results of this ongoing study support the feasibility and appropriateness of new technologies for the management of heart failure, even in elderly patients in whom a limited expertise with these appliances could have been anticipated.

Purpose: The aim of this paper was to report a heterogeneous late-phase hepatic enhancement pattern observed after administration of a sonographic contrast agent and to present an aetiological hypothesis for the phenomenon., Materials and Methods: A total of 1,729 (1,012 women and 717 men; age range 28-82; mean age 51) patients underwent contrast-enhanced sonography of the liver. The examination was performed with a low mechanical index (MI <0.09) after injection of sulphur-hexafluoride-filled microbubbles, using different sonographic equipment and different contrast-specific algorithms., Results: Heterogeneous delayed liver enhancement was observed in six patients in the late phase (180 s), with the presence of multiple, partially confluent, hyperechoic areas peripheral to the portal vessels. The pattern appeared spontaneously between 1 and 4 h after the examination and was associated with the presence of an anomalous echogenicity in the superior mesenteric vein. No patient experienced adverse reactions., Conclusions: The phenomenon of heterogeneous hepatic enhancement may be related to gas from the intestinal microcirculation being transported to via the enteroportal circulation and becoming trapped in the hepatic sinusoids.

Since the 1950s the definition of the aggregate of metabolic disorders possibly presenting with adult obesity has evolved without reaching a unifying agreement on what metabolic syndrome is. After years of consensus on and research into identifying the extent to which certain criteria of metabolic syndrome may be predisposing factors for cardiovascular events, a reverse shift can be noticed in recent studies raising numerous points of contention about various elements that may be diagnostic for the syndrome. Of these, one of the most tenuous is probably arterial hypertension. Uncertainties have emerged regarding the arbitrariness of cut-off values, which differ according to the classification system the study applied, the methods of measurement, and the dilemma of hyperinsulinemia/insulin resistance which is present in only 50-60% of individuals with hypertension. Currently available data fail to solve these conundrums; however, some studies have correlated hypertension and dislipidemia with an increased risk of cardiovascular events. International epidemiologic data indicate that the prevalence of the syndrome varies between populations and between the sexes within the same populations, suggesting that diagnostic criteria need to take better account of ethnic group origin. Prevention of metabolic syndrome is still based on lifestyle changes; the huge risk of an imminent pandemic has called the attention of the American Heart Association to the importance of prevention and early treatment of the pediatric population--a new segment at risk of early cardiovascular events. Pharmacological therapy is directed at controlling various risk factors, particularly hypertension and metabolic disturbances. ACE inhibitors, sartans and statins are currently the drugs of first choice in treating metabolic syndrome.

Angiotensin-converting enzyme (ACE) inhibitors are widely used for the treatment of cardiovascular disease since they improve blood pressure control in patients with hypertension and prolong survival in patients with acute myocardial infarction, asymptomatic left ventricular dysfunction and congestive heart failure. Most of the information about the therapeutic role of ACE-inhibitors has been achieved during the last 20 years since the publication of some pivotal trials mostly involving the use of ACE-inhibitors like captopril and enalapril. In particular the treatment with enalapril has considerably improved the clinical outcome of patients with either mild-to-moderate (SOLVD studies) or severe (CONSENSUS trial) congestive heart failure. The benefit of ACE-inhibitors in patients with congestive heart failure has also involved a remarkable reduction in the rate of hospitalization, thus contributing to improve the pharmaco-economic approach to the disease. Most of the beneficial effect of ACE-inhibitors in clinical practice is dependent on their capacity of inhibiting the renin-angiotensin system, although some recent trials have supported a primary role for such drugs (in particular enalapril) in the prevention of atrial fibrillation. After more than 25 years from their discovery, ACE-inhibitors must be again considered among the first-line treatment in many patients with cardiovascular disease.

Ultrasonography is the most commonly used screening modality for focal liver lesions in Europe. Over the past few years, to overcome the inherent limitations of B-mode imaging and colour-Doppler ultrasound in identifying and characterising focal liver lesions, intravenous agents capable of enhancing the ultrasound signal emitted by vascular and parenchymal structures have been developed. From December 1999 to December 2001, about 400 patients with a known tumour, HCV-related chronic cirrhotic liver disease, or with an indeterminate focal liver lesion discovered incidentally were evaluated by ultrasound of the liver parenchyma both in baseline conditions and after administration of contrast material. The ultrasound contrast agents used were: SonoVue (Bracco, Milan-Italy) and Optison (Mallinckrodt, London - UK). Our experience is based on low mechanical-index contrast-enhanced imaging, which acts conservatively, performed with different commercially available algorithms, in grey-scale mode alone (B-mode). We report the morphological patterns displayed by the main benign and malignant liver lesions after the administration of second-generation ultrasound contrast material, and review the main imaging patterns able to provide effective and practical guidance in formulating a diagnosis of benignity or malignancy. Our clinical experience confirmed the literature findings that the introduction of low mechanical index methods in grey-scale imaging has allowed qualitatively better results for detecting and characterising focal liver lesions than those obtained with baseline and colour-Doppler imaging. The ease of use, substantial repeatability and predictability of the enhancement effects obtainable with low mechanical index methods are the main reasons for the success of this approach. Broadening the scope of studies to obtain controlled data and comparisons with the other imaging modalities is crucial for the definitive validation of the method.

Several epidemiological studies have already shown that hypertensive subjects are very often characterized by elevated levels of serum cholesterol, which increase the risk of cardiovascular diseases. It has been suggested that only the contemporary treatment of both cardiovascular risk factors is able to improve the individual cardiovascular risk profile even if, up to date, we still have limited results from large clinical trials regarding the impact of multiple therapeutic intervention in the prevention of cardiovascular diseases. More scientific evidences came from the results of several clinical studies that have investigate the preventive and therapeutic role of hypolipidemic drugs, especially statins, in subjects with hypercholesterolemia and high blood pressure, particularly when those diseases are associated with diabetes. Indeed, this class of hypolipidemic agent has already shown to improve the individual lipid profile and contemporary to reduce the blood pressure values in the hypertensive hypercholesterolemic subjects acting synergistically with some class of anti-hypertensive drugs.

Hormone replacement therapy (HRT) in post-menopausal or ovariectomized women reduces mortality due to cardiovascular diseases, lowers morbidity due to osteoporosis and improves vasovagal symptoms. Long-term therapy, however, increase the risk of side-effects. HRT may decrease mammographic sensitivity, markedly increasing glandular density. Enlargement of pre-existing cysts and fibroadenomas has also been reported after HRT. The correlation between HRT and breast cancer is highly controversial. We examined 650 women: 550 of them (84.6%) received HRT (157 estrogens and 393 estrogens-progestins) and 100 (15.4%) refused treatment and were thus considered as a control group. All patients underwent mammography and DEXA before HRT and, during treatment, were followed-up yearly with mammography, often combined with US, and DEXA. Fisher's test was used for data analysis (confidence interval: 95%). The statistical analysis showed a significant difference between the HRT group and the control group only for the lumbar spine. Mammographic changes (Tab. II) were shown in 150 of 550 HRT patients. Increased breast density was the most frequent finding. Benign lesions arising de novo or increasing in size and/or number were observed in 41 of 150 patients (27.3%) in the HRT group, where 3 breast carcinomas were detected, versus 1 breast cancer only in the control group. HRT had a marked positive effect on bone mineral content (BMC) at 2 years' follow-up, but it remains debated if it reduces breast cancer risk. In conclusion, our results indicate that a yearly mammography is mandatory in long-term HRT subjects and US may be also needed in particularly dense breasts.

Acute myocardial infarction, major cause of death in Western society, has been the focus of many clinical investigations over the past decade. As the result of randomized trials involving hundreds of thousands of infarct patients worldwide, the life-saving potential of several pharmacologic interventions has been validated, and the usefulness of other commonly used treatments has been disproven or brought into question. Much of the innovative therapy has been targeted toward limiting myocardial damage by eradicating the occlusive thrombus or otherwise restoring flow through the infarct-related artery, reducing oxygen demands in the injured ventricle, and altering vascular dynamics to limit the process of ventricular remodeling. Data have accumulated showing substantially lower mortality of acute myocardial infarction with simple pharmacological interventions such as intravenous thrombolytic therapy, aspirin, beta-blockers and ACE-inhibitors. In particular, ACE-inhibitors have recently proven to be effective in infarcted patients, especially in high-risk subjects with acute anterior infarction not treated with thrombolytic agents or patients with left ventricular dysfunction. ACE-inhibitors may limit the process of ventricular remodeling after a large infarction, lessening the risk of sudden death and heart failure. Intravenous heparin has a role in maintaining patency of infarct-related vessel after rt-PA, and it seems that this combination offers some benefits with respect to streptokinase plus subcutaneous heparin. Recent studies have also demonstrated the importance of lipid-lowering agents for secondary prevention after myocardial infarction. Several previously recommended therapies (routine intravenous lidocaine, calcium channel blockers, magnesium, nitrates) have not been proven to be life-saving.

The results of the large randomized trials in which antihypertensive drugs have been compared to placebo demonstrated that antihypertensive therapy reduces cardiovascular and cerebrovascular mortality and morbidity. Nowadays, however, it is not enough to lower blood pressure; the goal of the treatment should be to prevent progression of the underlying atherosclerotic disease, reduce major and minor complications and improve survival and quality of life. Furthermore, primary prevention and risk reduction in hypertensives are dependent not only on the antihypertensive effect of the chosen agent, but also on improved detection and management of the other cardiovascular risk factors. The potential ability of antihypertensive treatment to exert an effect on global cardiovascular risk profile has become one of the most important considerations in the selection of an antihypertensive treatment. Thus, in patients at risk for coronary events it seems important to choose a drug or drug combination with a documented effect on coronary events. In addition, both prevention of cardiovascular events and prevention of organ damage and organ disease have to be considered essential goals of antihypertensive therapy. The prevention of organ damage associated with hypertension has also been facilitated by the development of effective antihypertensive drugs. These agents have been shown to have a beneficial influence on organ damage in hypertensive patients through an effective, continuous, smooth control of blood pressure and through specific effects on some of the functional and structural alterations induced by hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

In this review, we evaluate the efficacy of ACE-inhibitors for the treatment of acute myocardial infarction (AMI). Our information is based on published material and personal experience derived from extensive revision of the SMILE study. All trials with a randomized experimental design, irrespective of their primary research objective, have been included. Results are presented in terms of either hemodynamic or clinical benefit. The available evidence indicates that the mortality rate of AMI patients who undergo short- and long-term treatment with ACE-inhibitors is significantly reduced. This reduction is more evident in high risk patients, such as subjects with asymptomatic left ventricular dysfunction, congestive heart failure on admission, anterior location of the infarction. ACE-inhibitors also limit the development and progression of congestive heart failure after myocardial infarction, the onset of clinical manifestations of coronary artery disease (reinfarction, need for revascularization) and the occurrence of ventricular arrhythmias, probably by means of mechanisms involving a specific effect of these compounds. In conclusion, the available data indicate that administration of ACE-inhibitors to patients with AMI is associated with significant clinical benefit.

The rationale, design, organization and outcome definitions of the Survival of Myocardial Infarction Long-term Evaluation (SMILE) study are described in detail. The recruitment of a total of 1500 patients (750 per treatment group) has been planned for this multicenter, double-blind, randomized, placebo-controlled study to investigate the effects of oral treatment with zofenopril calcium (7.5-30 mg twice a day) on the combined short-term total mortality and occurrence of severe refractory congestive heart failure in patients with acute anterior myocardial infarction (AMI). Secondary end-points of the study include recurrent myocardial infarction, angina, progression of congestive heart failure as well as long-term mortality. Patients are initially treated in hospital within 24 hours from the onset of symptoms of AMI and their active follow-up continued for 6 weeks. In addition, the patients will be passively followed for a total of 12 months from the index AMI to assess their vital status and the occurrence of congestive heart failure. The study data will be analyzed on an intention to treat basis. An international independent Policy and Safety Monitoring Board is acting as the overall supervisory body and is responsible for the ethical conduction of the trial. A Scientific Committee is responsible for the scientific aspects of the trial and for the regular review of the progress of the study. We assume that the rationale and design of the SMILE trial will provide reliable information on the ability of ACE-inhibitors to reduce the occurrence of major cardiovascular events in patients with acute myocardial infarction.

The purpose of this study was to record some clinical and psychological parameters in attempt to find out and to estimate patients with abnormal cardiovascular responses during dental therapy. On the basis of psychological questionnaires, used to value anxiety, resulted that patients who have self defined themselves anxious and therefore objectively nervous while in the dental chair, underwent cardiovascular responses significantly lower than those who were not anxious. Among the clinical parameters studied, blood pressure and the heart rate during basic conditions are not able to foresee hemodynamic responses during dental extraction. The only clinical situation able to relate to a corresponding regularity with an hemodynamic response during dental extraction, is the blood pressure determination during a provoked generic mental stress. These findings suggest that cardiovascular response during dental stress depends on the personal individual reaction of each individual.

In this study, the effects of epinephrine in the local anesthesia were valued. No significant differences were revealed to cardiovascular response when a group of patients under generic stress were given an anesthetic without epinephrine and a second group of patients underwent an anesthetic with epinephrine. In patients in which epinephrine was injected, a significant fall in diastolic blood pressure was recorded two minutes after the injection and it remained as such for ten minutes. The cardiovascular response during dental extraction has a significant result dissimilar in the two groups of patients. No significant correlation was revealed between the blood pressure and the heart rate in basic conditions and the same parameters during an extraction. There exists a significant correlation between pressure response during generic stress and pressure response during an extraction. These findings suggest that cardiovascular response during dental stress is not in relation with the use of epinephrine with an anesthetic, but rather depends on each individual reaction.

The aim of the study was to investigate renal tolerability of a flexible increasing dose-schedule of anturan (E), dependent on basal serum creatinine values. 12 male cardiovascular elderly patients (mean age: 75 years; SD: 5.5 years) suffering from mild chronic renal failure (serum creatinine between 2.00 and 4.00 mg/100 ml) entered an open study of 2-month duration. Starting dosage was 200 mg per day; daily dosage was then increased every 4 days of 200 mg, or kept constant for another 4 days, according to each patient's renal function, up to 800 mg per day. All the patients reached the maintenance dosage of 800 mg/day in 12 days, because renal function didn't worsen. Two patients were withdrawn: one at the end of the 1st month of E therapy because of exitus due to myeloma, the other one at the 24th day of E therapy for serum creatinine increase, possibly related to ongoing therapy. Creatinine clearance significantly increased, serum creatinine and uric acid significantly decreased at the end of E therapy. The other biochemical examinations didn't change and no patient complained of any undesired effect during the whole study. The obtained results seem to prove that anturan, if an incremental dose-schedule is followed at the beginning of therapy is well tolerated even in elderly azotemic patients.