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The aim of this review is to analyze whether there is a need for scientific information about the beta blocker (BB) rebound phenomenon; whether such information is available; and, if it is, how detailed is the BB rebound phenomenon explained in the guidelines and papers? A narrative review is used due to the lack of valid randomized clinical trials (RCTs) on the topic, which are needed for a meta-analysis. The BB rebound phenomenon can have dangerous consequences. The discontinuation of a BB leads to a fourfold increased risk of events related to coronary artery disease in hypertensive patients; it increases in-hospital mortality in heart failure patients; it can precipitate angina pectoris attack; and it increases the risk for death and rehospitalization in patients who survive acute myocardial infarction. Consequently, being considered in the guidelines, the BB rebound phenomenon is believed to be clinically relevant (by experts in the field). This is in sharp contrast with the lack of any additional relevant information about the BB rebound phenomenon in the various important guidelines. For example, we lack a consensus about the precise definition. Moreover, data about the incidence and optimal prevention strategies are lacking for the phenomenon (which is sometimes life-threatening). The BB rebound phenomenon is an additional reason why it is very important to test the prognosis of patients following the cessation of long-term medicaments in RCTs, particularly for BBs.

Sexual health is an integral part of overall health, and an active and healthy sexual life is an essential aspect of a good life quality. Cardiovascular disease and sexual health share common risk factors (arterial hypertension, diabetes mellitus, dyslipidemia, obesity, and smoking) and common mediating mechanisms (endothelial dysfunction, subclinical inflammation, and atherosclerosis). This generated a shift of thinking about the pathophysiology and subsequently the management of sexual dysfunction. The introduction of phosphodiesterase type 5 inhibitors revolutionized the management of sexual dysfunction in men. This article will focus on erectile dysfunction and its association with arterial hypertension. This update of the position paper was created by the Working Group on Sexual Dysfunction and Arterial Hypertension of the European Society of Hypertension. This working group has been very active during the last years in promoting the familiarization of hypertension specialists and related physicians with erectile dysfunction, through numerous lectures in national and international meetings, a position paper, newsletters, guidelines, and a book specifically addressing erectile dysfunction in hypertensive patients. It was noted that erectile dysfunction precedes the development of coronary artery disease. The artery size hypothesis has been proposed as a potential explanation for this observation. This hypothesis seeks to explain the differing manifestation of the same vascular condition, based on the size of the vessels. Clinical presentations of the atherosclerotic and/or endothelium disease in the penile arteries might precede the corresponding manifestations from larger arteries. Treated hypertensive patients are more likely to have sexual dysfunction compared with untreated ones, suggesting a detrimental role of antihypertensive treatment on erectile function. The occurrence of erectile dysfunction seems to be related to undesirable effects of antihypertensive drugs on the penile tissue. Available information points toward divergent effects of antihypertensive drugs on erectile function, with diuretics and beta-blockers possessing the worst profile and angiotensin receptor blockers and nebivolol the best profile.

A considerable amount of data supports a 1.8-7.4-fold increased mortality associated with Cushing’s syndrome (CS). This is attributed to a high occurrence of several cardiovascular disease (CVD) risk factors in CS [e.g. adiposity, arterial hypertension (AHT), dyslipidaemia and type 2 diabetes mellitus (T2DM)]. Therefore, practically all patients with CS have the metabolic syndrome (MetS), which represents a high CVD risk. Characteristically, despite a relatively young average age, numerous patients with CS display a 'high' or 'very high' CVD risk (i.e. risk of a major CVD event >20% in the following 10 years). Although T2DM is listed as a condition with a high CVD risk, CS is not, despite the fact that a considerable proportion of the CS population will develop T2DM or impaired glucose tolerance. CS is also regarded as a risk factor for aortic dissection in current guidelines. This review considers the evidence supporting listing CS among high CVD risk conditions.

Very high blood pressure (BP) is a common and significant problem in the emergency department (ED), affecting 4.6% of admitted patients [1]. Hypertensive urgency (HTN-U) is a diagnosis of exclusion...

Background: The number of patients with hypertension urgencies (HTN-Us) and emergencies (HTN-Es) in the emergency department is relatively constant despite improved detection, awareness and control of arterial hypertension. Objective: This study analyses the precision of the often-used definition of HTN-E, particularly the phrase ‘with the evidence of impending or progressive hypertension-mediated organ damage (HMOD)’. We then provide a rationale for the concept of impending HMOD. MethodS: The databases PubMed, Science Direct, Springer, Oxford Press, Wiley, SAGE and Google Scholar were searched and the relevant definition has been analyzed. Results: The definition of HTN-E is suboptimal and requires a consensus on whether to include the phrase ‘impending hypertensive HMOD’ in the definition. Conclusion: A consensus on the principles of treating the ‘impending hypertensive HMOD’ does not exist, making its use inconsistent in emergency departments worldwide. In this paper, we present a rationale for the concept of ‘impending HMOD’.

Colorectal cancer (CRC) is the third most commonly diagnosed carcinoma and the fourth leading cause of carcinoma deaths worldwide. Most cases of CRC occur in people aged over 50 years, often coexisting with other chronic diseases including obesity, type 2 diabetes mellitus, and cardiovascular disease. Diabetes mellitus (DM) and cancer frequently coexist. DM is associated with an increased risk for pancreatic, gastric, liver, colorectal, breast, urinary tract, and female reproductive cancers. It is hypothesized that possible biologic links between diabetes and cancer risk could be related to hormonal (insulin resistance), inflammatory, or metabolic (hyperglycemia) characteristics of DM, as well as with some antidiabetic medications. This review summarizes the current published literature regarding the association of CRC with diabetes since there is growing evidence from recent studies that this association is not random.

Background: Aldosterone, through its actions on Mineralcorticosteroid Receptors (MR), controls fluid and electrolyte balance, but also exerts various direct deleterious actions on the vasculature. A number of aldosterone antagonists have been manufactured to reverse these effects. Objective: A comprehensive review of the underlying mechanisms of the actions of aldosterone and its antagonists in cardiovascular disease. Method: The relevant studies indexed in PubMed, Scopus and Google Scholar databases, published from 2003 to May 2018 were identified and reported. Results: Aldosterone binds to MR, activating them as intracellular transcription factors. Moreover, aldosterone, through its actions on MR, as well as on another not fully explored class of receptors, triggers several signaling pathways that produce rapid, non-genomic actions. In the vasculature, all these changes favor the establishment of inflammation and cardiovascular dysfunction, which, in turn, lead to or exacerbate various cardiovascular diseases. Mineralcorticosteroid Antagonists (MRA) are compounds that antagonize the action of aldosterone on MR. Spironolactone was the first steroidal MRA to be commercially used. It showed beneficial clinical results, but also a number of adverse effects. The next generation of steroidal MRA, exhibited lower potency but did not induce many of these adverse reactions, due to their high selectivity for MR. The third generation of MRA compromises the newly introduced non-steroidal MRA, which have a completely different chemical structure, they induce different and more drastic changes to MR, they are much more specific and currently under clinical trials. Conclusion: New MRA, which block the aldosterone induced pathways in the vasculature, hold promising results for the treatment of cardiovascular disease.

Statins represent a golden standard for treating patients with dyslipidemia. At half of the treated patients, the targeted level of LDL cholesterol is not achieved. Numerous studies which promote new medications have been published in the past several years. Therefore, the objective of this paper is to consider the new possibilities of treating dyslipidemia in terms of various dyslipidemia guidelines. Randomized clinical trials have shown that most positive effects are achieved by lowering the level of LDL cholesterol, and thus the guidelines define the target LDL value. Numerous guidelines in the field of dyslipidemia have been published, but there are some differences which will be analyzed in this review paper. Even if the target LDL cholesterol level is reached, there is still a residual lipid risk for the occurrence of cardiovascular diseases. Therefore, lipid factors, such as high level of triglycerides, low HDL cholesterol, LP(a), etc., play a very important role. Nowadays, there are numerous potent medications which are used in statin and non-statin therapies. PCSK9 inhibitors, which are in the special focus of this paper, have been tested in the past few years. The paper offers an overview of traditionally used medications, as well as new experimental medications. Moreover, the paper emphasizes the importance of non-adherence to antilipemic medications, which is an important issue which reduces the favorable effects of the treatment. Nowadays, there are drugs which, combined with statins, may reduce HDL-C level to very low values. The studies have shown inconsistent results in terms of solving the issue of residual lipid risk. Research in this field may significantly reduce lipid risk for cardiovascular events.

Beta blockers (BBs) have important side effects that contribute to low adherence and persistence. Therefore, the optimal choice of BB is an important mode to prevent BB’s side effects, leading to an increase in compliance, which can improve the outcomes in BBs' evidence-based indications, such as acute myocardial infarction, heart failure, etc. The aim of the paper is to suggest an improved method of reporting contraindications for BBs. We used a search of the following indexing databases: SCOPUS and PubMed, and web search engine Google Scholar to identify guidelines on arterial hypertension (HTN). HTN guidelines published during the last 2 decades were analyzed (from 2000 to 2020). Some of the contraindications (e.g., bradycardia, acute heart failure) are true for every BB. However, some contraindications do not belong to the whole BB class. For example, propranolol and carvedilol are contraindicated in chronic obstructive lung disease, but nebivolol and bisoprolol are not. We suggest that contraindications which are specific for some BBs (i.e., not for the whole class) ought to be listed with the exact name(s) of the individual BBs. In this way, we may decrease the number of wrong choices among BBs and consequently increase drug adherence (which is currently worse for the class of BBs than for most of the other antihypertensive drugs). To our knowledge, there is a lack of guidelines citing contraindications for individual BBs, because they vary a lot within-the-class of BBs. This is an approach to improve both basic medical education and guidelines.

The problem of high systolic blood pressure (sBP) combined with low diastolic blood pressure (dBP) requires attention because sBP is directly and continuously related to the most important criterion, i.e., all-cause mortality, whereas dBP becomes inversely related to it after the age of 50–60 years. The European Society of Cardiology and European Society of ­Hypertension (ESC/ESH) 2018 guidelines for hypertension (HTN) are helpful because they recommend a lower safety cut-off for in-treatment dBP. To prevent tissue hypoperfusion, these guidelines recommend that dBP should be ≥70 mm Hg during treatment. A patient with very elevated sBP (e.g., 220 mm Hg) and low dBP (e.g., 65 mm Hg) is difficult to treat if one strictly follows the guidelines. In this situation, the sBP is a clear indication for antihypertensive treatment, but the dBP is a relative contraindication (as it is

Background The impact of overt diabetes and poor glycemic control on the risk of cardiovascular disease is well established. Among patients with type 2 diabetes, several studies demonstrated a significant increase in coronary artery disease-related death and cardiovascular events associated with HbA1c levels of greater than 7% compared with lower levels. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a novel class of anti-diabetic drugs that lower blood glucose levels through the suppression of renal glucose reabsorption thereby promoting renal glucose excretion. Objectives To summarize data on the potential mechanisms of SGLT-2 inhibition that could exert cardiovascular benefits in patients with diabetes mellitus. Method We conducted an in-depth literature search of SGLT-2 inhibitors and potential cardiovascular benefits and mechanisms that mediate those effects. Results In diabetes, expression of the SGLT-2 genes is up-regulated and renal threshold increased, resulting in increased glucose reabsorption from glomerular filtrate, reducing urinary glucose excretion and worsening hyperglycemia. SGLT-2 inhibition should offer potential cardiovascular protection in diabetic patients via attenuating hyperglycemia, blood pressure, body weight, hyperuricemia, and diabetic nephropathy. Conclusion The initial data of SGLT-2 inhibitors suggest beneficial effects on cardiovascular risk among patients with diabetes mellitus. Several mechanisms are hypothesized to mediate the abovementioned benefits. Future randomized, controlled studies are needed in order to unveil the contribution of each mechanism to these outcomes.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) as progressive form of the disease are associated with cardiovascular risk factors including obesity, dyslipidaemia, hyperglycaemia and hypertension. When NAFLD is associated with cardiovascular disease, mortality of NAFLD patients is increased due to cardiovascular disease. Prevalence of NAFLD and NASH is high, but it seems that epidemic of the disease is under-recognized and under-appreciated. Linking pathophysiological mechanisms are complex and still not well understood. The main related pathophysiological mechanisms are lipid factors, insulin resistance, inflammation, proinflammatory cytokines, oxidative stress, pro-coagulant status, hyperglycaemia and adipokines. First-line management focuses on lifestyle modifications in both diseases. Several therapeutic interventions, insulin sensitizer agents, lipid lowering drugs, antioxidants, such as vitamin E, have been proposed. Statins appear to be safe, but their use in the treatment of NAFLD and NASH is under-appreciated. Many different agents are being investigated as future drugs for the treatment of this clinical entity. The aim of the review is to examine the extent of the epidemic and the mediating mechanisms, to critically evaluate current guideline recommendations, and to consider current and future medications for this disease.

To the editor,Impending hypertension mediated organ damage (HMOD) is included among hypertensive emergencies (HTN-Es) in numerous contemporary articles [1], books [2] and guidelines [3] but not in ...

Background:The study aim was to assess the physical activity levels as well as the intention to become physically active in patients with stable coronary heart disease (CHD) with a special focus on the association with their risk profile.Methods:Analyses are based on the cross-sectional EUROASPIRE IV surveys. Information was available on 8966 patients in EUROASPIRE III and on 7998 patients in EUROASPIRE IV. Physical activity level according to patients risk profile and their medical management was assessed, the intention to become physically active was investigated and a time trend analysis was performed.Results:A better cardiovascular risk profile as well as receiving physical activity advice or weight loss advice was associated with better physical activity levels. The physical activity status improved significantly over time, the proportion of patients reporting vigorous physical activity for at least 20 minutes ≥ 3 times/week increased from 14.1% to 20.2% (P < .001). Similarly, a significantly greater proportion of patients are in the maintenance stage (36.6% vs. 27.4%) and a smaller proportion in the precontemplation stage (43.2% vs. 52.3%).Conclusion:Although an increase was seen in the proportion of patients being adequately physical active, physical activity levels remain suboptimal in many CHD patients.

Background: Hypertension is the most prevalent major independent risk factor for developing coronary heart disease (CHD). The present analysis aimed to assess blood pressure (BP) distribution and factors associated with insufficient BP control in coronary patients from 24 countries participating in the European Society of Cardiology (ESC) EURoObservational Research Programme (EORP) EUROASPIRE IV survey. Methods: EUROASPIRE IV is a cross-sectional study conducted in 2012-2013 in patients aged 80 years or less hospitalized for CHD with a follow-up visit at a median of 16 months later. Logistic regression analysis was applied to confirm factors associated with BP control defined as less than 140/90 mmHg for nondiabetic patients and less than 140/85 mmHg for diabetic patients. Results: A total of 7998 patients (response rate, 48.7%) attended the follow-up visit. Complete data were available in 7653 participants (mean age 62.5 +/- 9.6 years). The BP goal was achieved in 57.6%. Patients failing to achieve the BP goal were older, had higher BMI, had more often a history of coronary artery bypass grafting (CABG) and reported diabetes more frequently. Logistic regression confirmed the following independent significant predictors of not achieving the BP goal: a history of diabetes [odds ratio (OR) 1.75], obesity (OR 1.70 vs. normal BMI), overweight (OR 1.28 vs. normal BMI), age at least 65 years (OR 1.53) and CABG as the index event (OR 1.26 vs. acute MI). Conclusion: EUROASPIRE IV found insufficient BP control in a large proportion of patients with stable CHD, with diabetes, increased BMI, older age and CABG as the index event being independent predictors of poor BP control.

Aims The aim of this study was to determine whether the Joint European Societies guidelines on secondary cardiovascular prevention are followed in everyday practice. Design A cross-sectional ESC-EORP survey (EUROASPIRE V) at 131 centres in 81 regions in 27 countries. Methods Patients (Results A total of 8261 patients (females 26%) were interviewed. Nineteen per cent smoked and 55% of them were persistent smokers, 38% were obese (body mass index ≥30 kg/m2), 59% were centrally obese (waist circumference: men ≥102 cm; women ≥88 cm) while 66% were physically active Conclusion A large majority of coronary patients have unhealthy lifestyles in terms of smoking, diet and sedentary behaviour, which adversely impacts major cardiovascular risk factors. A majority did not achieve their blood pressure, low-density lipoprotein cholesterol and glucose targets. Cardiovascular prevention requires modern preventive cardiology programmes delivered by interdisciplinary teams of healthcare professionals addressing all aspects of lifestyle and risk factor management, in order to reduce the risk of recurrent cardiovascular events.

The EUROASPIRE surveys (EUROpean Action on Secondary Prevention through Intervention to Reduce Events) demonstrated that most European coronary patients fail to achieve lifestyle, risk factor and therapeutic targets. Here we report on the 2-year incidence of hard cardiovascular (CV) endpoints in the EUROASPIRE IV cohort. EUROASPIRE IV (2012-2013) was a large cross-sectional study undertaken at 78 centres from selected geographical areas in 24 European countries. Patients were interviewed and examined at least 6 months following hospitalization for a coronary event or procedure. Fatal and non-fatal CV events occurring at least 1 year after this baseline screening were registered. The primary outcome in our analyses was the incidence of CV death or non-fatal myocardial infarction, stroke or heart failure. Cox regression models, stratified for country, were fitted to relate baseline characteristics to outcome. Our analyses included 7471 predominantly male patients. Overall, 222 deaths were registered of whom 58% were cardiovascular. The incidence of the primary outcome was 42 per 1000 person-years. Comorbidities were strongly and significantly associated with the primary outcome (multivariately adjusted hazard ratio HR, 95% confidence interval): severe chronic kidney disease (HR 2.36, 1.44-3.85), uncontrolled diabetes (HR 1.89, 1.50-2.38), resting heart rate ≥ 75 bpm (HR 1.74, 1.30-2.32), history of stroke (HR 1.70, 1.27-2.29), peripheral artery disease (HR 1.48, 1.09-2.01), history of heart failure (HR 1.47, 1.08-2.01) and history of acute myocardial infarction (HR 1.27, 1.05-1.53). Low education and feelings of depression were significantly associated with increased risk. Lifestyle factors such as persistent smoking, insufficient physical activity and central obesity were not significantly related to adverse outcome. Blood pressure and LDL-C levels appeared to be unrelated to cardiovascular events irrespective of treatment. In patients with stabilized CHD, comorbid conditions that may reflect the ubiquitous nature of atherosclerosis, dominate lifestyle-related and other modifiable risk factors in terms of prognosis, at least over a 2-year follow-up period.

Prehypertension is highly prevalent but also very heterogeneous entity. It was observed that some prehypertensives are more prone to progress to sustained hypertension. To identify those subjects who will mostly benefit from early interventions and treatment is scientific challenge but at the same time it is of utmost pragmatical importance. Beside determination of associated risk factors which cluster in prehypertension, it is necessary to detect the presence of subclinical target organ damages. Markers of early cardiovascular dysfunction were evaluated from childhood to elderly on different levels—from endothelial dysfunction, retinal changes, arterial stiffness to left ventricular systolic dysfunction. Pathognomonic or highly specific biomarker for risk stratification in prehypertension has not been identified so far. For clinical judgment it is important to combine several of them (i.e., albuminuria, pulse wave velocity, intima media thickness…). It is interesting to analyze markers of cardiovascular dysfunction in various aging subgroups. Based on current data electrocardiogram, microalbuminuria, left ventricle ultrasound and measurement of carotid-intima thickness could add valuable information in risk stratification of an adult and elderly prehypertensive subjects. As masked hypertension was reported to be very frequently presented, it might be prudent to recommend ambulatory blood pressure monitoring as a starting point in evaluation of prehypertensive subject with any early marker of cardiovascular dysfunction.

Background: During the past decades, the prevalence of diabetes (DM) has increased significantly, mainly as a result of continuous rise in the incidence of type 2 DM. According to World Health Organization statistics, >422 million adults globally were suffering from DM in 2014 and a continuous rise in DM prevalence is expected. Objective: The present review considers recent epidemiological data providing worldwide estimates regarding the incidence of DM. Methods: A comprehensive literature search was conducted to identify available data from epidemiological studies evaluating the current burden of DM. Results: Over the past few decades the prevalence of DM has risen significantly in nearly all countries and may be considered as a growing epidemic. Urbanization and income status are major factors which influence current rates in the prevalence studies introducing interesting differences between several population groups. Conclusion: Having recognized the global burden of DM, we now realize the urgent need for effective interventions. In order to monitor the public-health strategies and design effective future interventions we need reliable global estimates regarding the prevalence of DM.

Background: Familial Hypercholesterolaemia (FH) is an autosomal-dominant genetic disease and represents the most common genetic disorder: heterozygous 1/250 births, homozygous 1/300, 000 births. FH is characterized by high to very high low-density lipoprotein cholesterol (LDL-C), which is the main cause of increased incidence of premature atherosclerotic Cardiovascular Disease (CVD) or aortic stenosis. Objective: The aim of the review was to investigate the pathogenesis and the pathophysiology of FH. Results: The most common (60-80%) FH cause is mutations of the LDL Receptor (LDLR) protein (6 classes with a different number of receptors and functionality). Moreover, mutations in apolipoprotein B (APOB) ( Conclusion: Both homozygous and heterozygous FH are related to mutations of LDLR (mainly), APOB, PCSK9, while other rare forms exist. All aberrations lead to the impaired removal of LDL-C from the blood leading to its accumulation and subsequent CVD earlier than in the general population.

Background: This study aims to assess the cost-effectiveness of optimized guideline adherence in patients with a history of coronary heart disease. Methods: An individual-based decision tree model was developed using the SMART risk score tool which estimates the 10-year risk for recurrent vascular events in patients with manifest cardiovascular disease (CVD). Analyses were based on the EUROASPIRE IV survey. Outcomes were expressed as an incremental cost-effectiveness ratio (ICER). Results: Data from 4663 patients from 13 European countries were included in the analyses. The mean estimated 10-year risk for a recurrent vascular event decreased from 20.13% to 18.61% after optimized guideline adherence. Overall, an ICER of 52,968(sic)/QALY was calculated. The ICER lowered to 29,093(sic)/QALY when only considering high-risk patients (>= 20%) with decreasing ICERs in higher risk patients. Also, a dose-response relationship was seen with lower ICERs in older patients and in those patients with higher risk reductions. A less stringent LDL target (= 20%) instead of high-cholesterol patients lowered the ICER to 28,064(sic)/QALY. An alternative method, applying risk reductions to the CVD events instead of applying risk reductions to the risk factors lowered the ICER to 31,509(sic)/QALY. Conclusion: Depending on the method used better or worse ICERs were found. In addition, optimized guidelines adherence is more cost-effective in higher risk patients, in patients with higher risk reductions and when using a less strict LDL-C target. Current analyses advice to maximize guidelines adherence in particular patient subgroups., BACKGROUND: This study aims to assess the cost-effectiveness of optimized guideline adherence in patients with a history of coronary heart disease. METHODS: An individual-based decision tree model was developed using the SMART risk score tool which estimates the 10-year risk for recurrent vascular events in patients with manifest cardiovascular disease (CVD). Analyses were based on the EUROASPIRE IV survey. Outcomes were expressed as an incremental cost-effectiveness ratio (ICER). RESULTS: Data from 4663 patients from 13 European countries were included in the analyses. The mean estimated 10-year risk for a recurrent vascular event decreased from 20.13% to 18.61% after optimized guideline adherence. Overall, an ICER of 52,968€/QALY was calculated. The ICER lowered to 29,093€/QALY when only considering high-risk patients (≥20%) with decreasing ICERs in higher risk patients. Also, a dose-response relationship was seen with lower ICERs in older patients and in those patients with higher risk reductions. A lessstringent LDL target (

INTRODUCTION An imbalance in the Autonomic Nervous System (ANS) is a central pathophysiologic mechanism in Heart Failure (HF) and has been a principal target of treatment in these patients. Traditional pharmacologic agents do not provide specific modulation of discrete arms of the ANS, while side effects may lead to poor tolerance. Technological advances have provided a series of invasive methods that may provide a focused effect on the ANS in selected patient groups. Renal denervation, initially targeted for patients with resistant hypertension, has given positive preliminary results in terms of heart structure and function. Baroreceptor stimulation also has ongoing research with respect to its efficacy and longer term effects in HF patients. Vagal nerve stimulation and spinal cord stimulation have limited data but represent novel treatments that target the hard to reach parasympathetic system. CONCLUSION The present review overviews the pathophysiologic basis, current preclinical and clinical data and future expectations of these promising treatments.

The prevalence of resistant hypertension and existing limitations in antihypertensive drug therapy renders the interventional management of hypertension an attractive alternative. Carotid baroreceptors have been traditionally thought to be implicated only in short-term blood pressure regulation; however recent evidence suggests that the baroreceptors might play an important role even in the long-term blood pressure regulation. Electrical baroreflex stimulation appears safe and effective and might represent a useful adjunct to medical therapy in patients with resistant hypertension. This review endeavors to summarize the complex pathophysiology of blood pressure regulation, to describe the baroreflex circuit, its anatomy and physiology, to present previous data refuting a role for the baroreceptors in the long-term control of blood pressure and recent animal and human data suggesting an effective role of carotid baroreceptor activation in long-lasting blood pressure reduction. In this paper we attempt to critically evaluate existing information in this area and provide the scientific basis for carotid baroreceptor stimulation in the management of resistant hypertension.

BACKGROUND: European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) IV in primary care was a cross-sectional survey carried out by the European Society of Cardiology, EURObservational Research Programme in 2014-2015 in 71 centres from 14 European countries. The main objective was to determine whether the 2012 Joint European Societies' guidelines on cardiovascular disease (CVD) prevention in people at high CVD risk have been followed in clinical practice. METHODS: Patients without a history of atherosclerotic disease started on either blood pressure and/or lipid and/or glucose-lowering treatments were identified and interviewed at least six months after the start of medication. RESULTS: Medical notes of 6700 patients were reviewed, and 4579 patients (58.7% women; mean age 58.8 (standard deviation (SD) 11.3) years) interviewed (interview rate 68.3%). Overall, 16.6% were smokers, 39.9% were overweight (body mass index (BMI)≥25 and

Recent scientific statements and international guidelines have concluded that several aspects of diet and various elements of poor lifestyle lead to elevated blood pressure and increased global risk including stroke. Of the well-documented and modifiable risk factors, this chapter will focus on smoking, whose prevalence remains very high, salt intake – one of the most important dietary measures – and alcohol consumption, which is less well documented but particularly intriguing and provocative. In the recently published INTERSTROKE study, these were shown to be significant risk factors for ischemic and hemorrhagic stroke. Global lifestyle modifications were shown to be more beneficial than the treatment of single risk factors. Multifactorial interventions within the framework of primary and secondary prevention are required, and lifestyle changes should be part of a holistic approach aiming to reduce total cardiovascular, cerebrovascular, and renal risk. Ultimately, patient adherence to dietary and lifestyle advice and modification is crucial. Major efforts by physicians, nurses, the medical and scientific community in general and governments are needed to reduce risk and improve the health of the population. Hic Rhodus, hic salta.

Background: In order to influence every day clinical practice professional organisations issue management guidelines. Cross-sectional surveys are used to evaluate the implementation of such guidelines. The present survey investigated screening for glucose perturbations in people with coronary artery disease and compared patients with known and newly detected type 2 diabetes with those without diabetes in terms of their life-style and pharmacological risk factor management in relation to contemporary European guidelines. Methods: A total of 6187 patients (18-80 years) with coronary artery disease and known glycaemic status based on a self reported history of diabetes (previously known diabetes) or the results of an oral glucose tolerance test and HbA1c (no diabetes or newly diagnosed diabetes) were investigated in EUROASPIRE IV including patients in 24 European countries 2012-2013. The patients were interviewed and investigated in order to enable a comparison between their actual risk factor control with that recommended in current European management guidelines and the outcome in previously conducted surveys. Results: A total of 2846 (46 %) patients had no diabetes, 1158 (19 %) newly diagnosed diabetes and 2183 (35 %) previously known diabetes. The combined use of all four cardioprotective drugs in these groups was 53, 55 and 60 %, respectively. A blood pressure target of 9.0 % (>75 mmol/mol). Of the patients with diabetes 69 % reported on low physical activity. The proportion of patients participating in cardiac rehabilitation programmes was low (approximate to 40 %) and only 27 % of those with diabetes had attended diabetes schools. Compared with data from previous surveys the use of cardioprotective drugs had increased and more patients were achieving the risk factor treatment targets. Conclusions: Despite advances in patient management there is further potential to improve both the detection and management of patients with diabetes and coronary artery disease.

Erectile dysfunction (ED) is a major problem in a life of the modern men. It affects 10–25 % of middle-aged and elderly men. ED is the failure to achieve erection, ejaculation, or both. Normal erectile function requires the involvement and coordination of multiple regulatory systems and is thus subject to the influence of psychological, hormonal, neurological, vascular, and cavernosal factors. Most important risk factors are connected with penile arterial insufficiency, including atherosclerosis, hyperlipidemia, hypertension, diabetes mellitus, cigarette smoking, and pelvic irradiation. There is notice a high prevalence of ED in patients having cardiovascular disease (CAD), peripheral arterial disease, and cerebrovascular disease.

BACKGROUND AND OBJECTIVES:: It is well established by a large number of randomized controlled trials that lowering blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) by drugs are powerful means to reduce stroke incidence, but the optimal BP and LDL-C levels to be achieved are largely uncertain. Concerning BP targets, two hypotheses are being confronted: first, the lower the BP, the better the treatment outcome, and second, the hypothesis that too low BP values are accompanied by a lower benefit and even higher risk. It is also unknown whether BP lowering and LDL-C lowering have additive beneficial effects for the primary and secondary prevention of stroke, and whether these treatments can prevent cognitive decline after stroke. RESULTS:: A review of existing data from randomized controlled trials confirms that solid evidence on optimal BP and LDL-C targets is missing, possible interactions between BP and LDL-C lowering treatments have never been directly investigated, and evidence in favour of a beneficial effect of BP or LDL-C lowering on cognitive decline is, at best, very weak. CONCLUSION:: A new, large randomized controlled trial is needed to determine the optimal level of BP and LDL-C for the prevention of recurrent stroke and cognitive decline.

Left ventricular hypertrophy (LVH) is a structural remodeling of the heart developing as a response to volume and/or pressure overload. Previous studies have shown that hypertension is not an independent factor in the development of LVH and occurrence does not depend on the length and severity of hypertension, but the role played by other comorbidities such as triglycerides, age, gender, genetics, insulin resistance, obesity, physical inactivity, increased salt intake and chronic stress. LVH develops through three phases: adaptive, compensatory, and pathological phase. Contractile dysfunction is reversible in the first two phases and irreversible in the third. According to the Framingham study, LVH develops in 15-20% of patients with mild arterial hypertension, and in 50% of patients with severe hypertension. The pathophysiology of LVH includes hypertrophy of cardiomyocytes, interstitial and perivascular fibrosis, coronary microangiopathy and macroangiopathy. Individuals with LVH have 2-4 times higher risk of having adverse CV events compared to patients without LVH. (Anadolu Kardiyol Derg 2014; 14(0): 000-000)

BACKGROUND AND OBJECTIVES:: The SBP values to be achieved by antihypertensive therapy in order to maximize reduction of cardiovascular outcomes are unknown; neither is it clear whether in patients with a previous cardiovascular event, the optimal values are lower than in the low-to-moderate risk hypertensive patients, or a more cautious blood pressure (BP) reduction should be obtained. Because of the uncertainty whether 'the lower the better' or the 'J-curve' hypothesis is correct, the European Society of Hypertension and the Chinese Hypertension League have promoted a randomized trial comparing antihypertensive treatment strategies aiming at three different SBP targets in hypertensive patients with a recent stroke or transient ischaemic attack. As the optimal level of low-density lipoprotein cholesterol (LDL-C) level is also unknown in these patients, LDL-C-lowering has been included in the design. PROTOCOL DESIGN:: The European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment trial is a prospective multinational, randomized trial with a 3×2 factorial design comparing: three different SBP targets (1

ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle–brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute Candesartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : CAndesartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease—EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy Candesartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries INVEST : INternational VErapamil SR/T Trandolapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : randomized controlled trials RF : risk factor ROADMAP : Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly: Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization ### 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …

population, 1 patient (1.4%) developed hyperkalemia which resulted in a visit to the ED. Conclusions: Based on study findings, initiation of spironolactone in patients with baseline eGFR < 60 mL/min is associated with an increased incidence of hyperkalemia. Adequately powered randomized controlled studies are needed to confirm the safety of spironolactone as add-on therapy in resistant HTN and better define risk factors for spironolactone-associated hyperkalemia.