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Arterial hypertension is a major cause of cardiovascular morbidity and mortality and the most common cause of comorbidity in heart failure (HF) with preserved ejection fraction (HFpEF). As an adjunct to medication, healthy lifestyle modifications with emphasis on regular exercise are strongly recommended by both the hypertension and the HF guidelines of the European Society of Cardiology. Several long-term studies have shown that exercise is associated with a reduction in all-cause mortality, a favorable cardiac and metabolic risk profile, mental health, and other non-cardiovascular benefits, as well as an improvement in overall quality of life. However, the instructions for the prescriptive or recommended exercise in hypertensive patients and, more specifically, in those with HFpEF are not well defined. Moreover, the evidence is based on observational or small randomized studies, while well-designed clinical trials are lacking. Despite the proven benefit and the guidelines' recommendations, exercise programs and cardiac rehabilitation in patients with hypertensive heart disease and HFpEF are grossly underutilized. This position statement provides a general framework for exercise and exercise-based rehabilitation in patients with hypertension and HFpEF, guides clinicians’ rehabilitation strategies, and facilitates clinical practice. It has been endorsed by the Working Group of Arterial Hypertension of the Hellenic Society of Cardiology and is focused on the Health Care System in Greece.

This study aimed to assess the reliability of opportunistic screening programs in estimating the prevalence, treatment, and control rate of hypertension in the general population. Two recent epidemiological surveys obtained data on hypertension in the adult general population in Greece. The EMENO (2013–2016) applied a multi-stage stratified random sampling method to collect nationwide data. The MMM (2019) collected data through opportunistic (voluntary) screening in five large cities. Hypertension was defined as blood pressure (BP) ≥ 140/90 mmHg (single occasion; average of 2nd–3rd measurement; electronic devices) and/or use of antihypertensive drugs. Data from a total of 10,426 adults were analyzed (EMENO 4,699; MMM 5,727). Mean age (SD) was 49.2 (18.6)/52.7 (16.6) years (EMENO/MMM, p< 0.001), men 48.6/46.5% (p< 0.05) and body mass index 28.2 (5.7)/27.1 (5.0) kg/m2(p< 0.001). The prevalence of hypertension in ΕΜΕΝΟ/MMM was 39.6/41.6% (p< 0.05) and was higher in men (42.7/50.9%, p< 0.001) than in women (36.5/33.6%, p< 0.05). Among hypertensive subjects, unaware were 31.8/21.3% (EMENO/MMM, p< 0.001), aware untreated 2.7/5.6% (p< 0.001), treated uncontrolled 35.1/24.8% (p< 0.001), and treated controlled 30.5/48.3% (p< 0.001). In conclusion, the prevalence of hypertension was similar with random sampling (EMENO) and opportunistic screening (MMM). However, opportunistic screening underestimated the prevalence of undiagnosed hypertension and overestimated the rate of hypertension treatment and control. Thus, random sampling national epidemiological studies are necessary for assessing the epidemiology of hypertension. Screening programs are useful for increasing awareness of hypertension in the general population, yet the generalization of such findings should be interpreted with caution.

AbstractAortic valve stenosis is a degenerative disease affecting increasing number of individuals and characterised by thickening, calcification and fibrosis of the valve resulting in restricted valve motion. Degeneration of the aortic valve is no longer considered a passive deposition of calcium, but an active process that involves certain mechanisms, that is endothelial dysfunction, inflammation, increased oxidative stress, calcification, bone formation, lipid deposition, extracellular matrix (ECM) remodelling and neoangiogenesis. Accumulating evidence indicates an important role for neoangiogenesis (i.e. formation of new vessels) in the pathogenesis of aortic valve stenosis. The normal aortic valve is generally an avascular tissue supplied with oxygen and nutrients viadiffusion from the circulating blood. In contrast, presence of intrinsic micro-vasculature has been demonstrated in stenotic and calcified valves. Importantly, presence and density of neovessels have been associated with inflammation, calcification and bone formation. It remains unclear whether neoangiogenesis is a compensatory mechanism aiming to counteract hypoxia and increased metabolic demands of the thickened tissue or represents an active contributor to disease progression. Data extracted mainly from animal studies are supportive of a direct detrimental effect of neoangiogenesis, however, robust evidence from human studies is lacking. Thus, there is inadequate knowledge to assess whether neoangiogenesis could serve as a future therapeutic target for a disease that no effective medical therapy exists. In this review, we present basic aspects of anatomy and structure of the normal and stenotic aortic valve and we focus on the role of valve vasculature in the natural course of valve calcification and stenosis.

Hypertension remains a major public health issue with inadequate control worldwide. The May Measurement Month (MMM) initiative by the International Society of Hypertension was implemented in Greece in 2019 aiming to raise hypertension awareness and control. Adult volunteers (≥18 years) were recruited through opportunistic screening in five urban areas. Information on medical history and triplicate sitting blood pressure (BP) measurements were obtained using validated automated upper-arm devices. Hypertension was defined as systolic BP ≥140 mmHg and/or diastolic ≥90 mmHg, and/or self-reported use of drugs for hypertension. A total of 5727 were analysed [mean age 52.7 (SD 16.6) years, men 46.5%, 88.3% had BP measurement in the last 18 months]. The prevalence of hypertension was (41.6%) and was higher in men and in older individuals. Among individuals with hypertension, 78.7% were diagnosed, 73.1% treated, and 48.3% controlled. Awareness, treatment, and control of hypertension were higher in women and in older individuals. Hypertensives had a higher body mass index (BMI) and were more likely to have diabetes, myocardial infarction and stroke, and less likely to smoke than normotensives (all P< 0.001). Among treated hypertensives, 65.1% were on monotherapy, and with increasing number of antihypertensive drugs the BP levels were higher and hypertension control rates lower. The prevalence of hypertension in Greece is high, with considerable potential for improving awareness, treatment, and control. Screening programmes, such as MMM, need to be widely implemented at the population level, together with training programmes for healthcare professionals aiming to optimise management and control.

The COVID-19 pandemic had an adverse impact on several cardiovascular risk factors. This study investigated the prevalence, awareness and treatment of hypertension in Greece before and after the pandemic. Data were collected in the context of the May Measurement Month (MMM) global survey initiated by the International Society of Hypertension.

The blood–brain barrier (BBB) constitutes the complex anatomic and physiologic interface between the intravascular compartment and the central nervous system, and its integrity is paramount for the maintenance of the very sensitive homeostasis of the central nervous system. Arterial hypertension is a leading cause of morbidity and mortality. The BBB has been shown to be disrupted in essential hypertension. BBB integrity is important for central autonomic control and this may be implicated in the pathophysiology of hypertension. On the other hand, evidence from experimental studies indicates that BBB disruption can be present in both hypertensive disease and dementia syndromes, suggesting a possibly key position of loss of BBB integrity in the pathophysiological pathways linking arterial hypertension with cognitive decline. Although much still remains to be elucidated with respect to the exact underlying mechanisms, the discovery of novel pathological pathways has changed our understanding of adult dementia and central nervous system disease overall, pointing out—in parallel—new potential therapeutic targets. The aim of this review is to summarize current scientific knowledge relevant to the pathophysiologic pathways that are involved in the disruption of the BBB function and potentially mediate hypertension-induced cognitive impairment. In parallel, we underline the differential cognition-preserving effect of several antihypertensive agents of similar blood pressure-lowering capacity, highlighting the presence of previously under-recognized BBB-protective actions of these drugs.

Evidence suggests a crucial role for vaccines in cardiovascular disease, mediated not only by disease prevention but also by immunomodulatory effects. This review attempts to briefly present the effects of pathogens and vaccines on the cardiovascular system and potential mechanisms for the development of vaccines against cardiovascular diseases per se. Current epidemiological evidence regarding vaccine effectiveness in different categories of heart disease is discussed, as well as current international guidelines’ recommendations. In summary, cardiologists should strive to promote vaccination against specific pathogens with proven beneficial effects on cardiovascular diseases.

In recent years, the Angiotensin-(1-7)/Mas receptor [Ang-(1-7)/Mas] sub-branch of the Renin-Angiotensin System (RAS) in the brain, and Angiotensin Type 2 Receptors (AT2R), have attracted scientific interest, as there is evidence that they constitute an essential pathway in cardiovascular regulation, in health and in disease. By acting centrally, the Ang-(1-7)/Mas axis - that has been termed ‘the axis of good’- can exert blood pressure-lowering effects, while also favourably altering baroreflex sensitivity and noradrenergic neurotransmission. Thus, research has focused on the possible neuro- and cardioprotective effects of this pathway in the setting of cardiovascular disease, ultimately aiming to evaluate the potential for development of novel therapeutic strategies based on its modulation. We summarize the available evidence from experimental studies in this context, aiming to assess current limits of scientific knowledge relevant to this newly-described ‘player’ in haemodynamic regulation, that may become a potential therapeutic target.

Arterial hypertension is a progressive cardiovascular syndrome arising from complex and interrelated etiologies. The human microbiome refers to the community of microorganisms that live in or on the human body. They influence human physiology by interfering in several processes such as providing nutrients and vitamins in Phase I and Phase II drug metabolism. The human gut microbiota is represented mainly by Firmicutes and Bacteroidetes and to a lesser degree by Actinobacteria and Proteobacteria, with each individual harbouring at least 160 such species. Gut microbiota contributes to blood pressure homeostasis and the pathogenesis of arterial hypertension through production, modification, and degradation of a variety of microbial-derived bioactive metabolites. Animal studies and to a lesser degree human research has unmasked relative mechanisms, mainly through the effect of certain microbiome metabolites and their receptors, outlining this relationship. Interventions to utilize these pathways, with probiotics, prebiotics, antibiotics and fecal microbiome transplantation have shown promising results. Personalized microbiome-based disease prediction and treatment responsiveness seem futuristic. Undoubtedly, a long way of experimental and clinical research should be pursued to elucidate this novel, intriguing and very promising horizon.

Preeclampsia (PE) continues to represent a worldwide problem and challenge for both clinicians and laboratory-based doctors. Despite many efforts, the knowledge acquired regarding its pathogenesis and pathophysiology does not allow us to treat it efficiently. It is not possible to arrest its progressive nature, and the available therapies are limited to symptomatic treatment. Furthermore, both the diagnosis and prognosis are frequently uncertain, whilst the ability to predict its occurrence is very limited. MicroRNAs are small non-coding RNAs discovered two decades ago, and present great interest given their ability to regulate almost every aspect of the cell function. A lot of evidence regarding the role of miRNAs in pre-eclampsia has been accumulated in the last 10 years. Differentially expressed miRNAs are characteristic of both mild and severe PE. In many cases they target signaling pathway-related genes that result in altered processes which are directly involved in PE. Immune system, angiogenesis and trophoblast proliferation and invasion, all fundamental aspects of placentation, are controlled in various degrees by miRNAs which are up- or downregulated. Finally, miRNAs represent a potential therapeutic target and a diagnostic tool.

Smoking during pregnancy is a risk factor associated with adverse pregnancy outcomes. Despite the fact that these outcomes are well known, a considerable proportion of pregnant women continue to smoke during this critical period. This paper evaluates critically smoking cessation interventions targeting pregnant women. We describe the findings of key published studies, review papers and expert statements to report the efficacy and safety of strategies for smoking cessation in pregnancy, including counselling and pharmacotherapy. Counselling appears to improve quit rates but mainly when used in combination with pharmacological therapy. Pharmacotherapy is recommended for women who are heavy smokers and are unable to quit smoking on their own. Nicotine replacement therapy is a reasonable first-line drug option. It is recommended that women who are pregnant, or planning to become pregnant, should be informed of potential risks for the foetus before considering smoking cessation therapy with bupropion or varenicline. Pregnant women view electronic nicotine delivery systems as being safer than combustible cigarettes, and this indeed may be the case; however, further evidence is required to assess their effectiveness as a smoking cessation aid and their safety for the mother and the child. Postpartum relapse is a significant problem, with approximately one out of two quitters relapsing in the first 2 months after delivery. These women should be considered ‘at risk’ and provided with ongoing support.

Arterial hypertension is a disease that still affects a major part of the population worldwide, and leads to fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. From the CDC statistical analysis, as regarding to United States, 1 of every 3 adults has high blood pressure, and only about half (54%) of them have it under control. Furthermore, all that leads to a nation cost about $46 billion each year. Efforts to find new ways to regulate arterial hypertension are therefore imperative. In our days, a lot of references have been made to the use of a new therapeutic combination, that of azilsartan – an innovative ARB, in combination with chlorthalidone. In fact, it is a combination now prescribed in a number of countries. A significant number of trials shows both azilsartan vs popular antihypertensive drugs, as well as chlorthalidone vs chlorothiazide, to present a better antihypertensive effect. This effect is even greater when the two substances are combined. In this article, we will try to present the latest findings concerning the efficacy, safety and clinical utility of this combination, as well as its adverse events, in comparison with other widely used therapeutic options.

Background: Diabetes mellitus type 2 (T2DM) often co-exists with hypertension, and this aggregation of co-morbidities amplifies the risk for future cardiovascular events. Therefore, it appears crucial to understand the essence of choosing oral and non-insulin injectable anti-diabetic drugs (ADs) with a favorable hemodynamic impact that could partially attenuate the increased baseline cardiovascular risk. Objective: We sought to evaluate the effect of ADs on blood pressure (BP) indices and to assess the potential role of certain ADs towards hypertension treatment. Method: We performed a systematic review of the literature searching MEDLINE via Pubmed for all human studies implementing ADs, either individually or in combinations. Results: Metformin was found to reduce BP in small cohorts but failed to confirm its beneficial effect in a metaanalysis of 41 studies. Thiazolidinediones are associated with BP lowering but are contraindicated in patients with heart failure. Sulfonylureas, on the other hand, may increase BP, while a-glucosidase inhibitors, DPP-4 inhibitors, and SGLT2 inhibitors activate favorable pathophysiologic mechanisms serving as potential BP lowering agents. Relevant BP reduction was established for GLP-1 Ras in most clinical trials. Conclusion: The favorable hemodynamic impact of certain classes of ADs might provide synergistic or incremental therapeutic benefits in high-risk patients suffering from both T2DM and hypertension. Additional randomized trials designed under the hypothesis of the emerging beneficial hemodynamic effect of ADs are expected to provide more robust evidence and to guide the optimization of combined treatment strategies in this challenging group of patients.

Sirtuins (SIRTs) are a class of nicotine adenine dinucleotide (NAD+)-dependent proteins which participate in numerous molecular pathways involved in various age-related human diseases, such as type II diabetes, cardiovascular (CV) diseases and cancer. They have a major role in apoptosis, inflammation, oxidative stress and metabolism regulation, traits that have a great impact on CV physiology and pathology. Their unique profile of NAD+ energy dependency makes them an appealing target for human intervention in cellular and metabolic processes. This review focuses on the recent advances of SIRTs research aiming to shed light on the emerging roles of SIRTs in the pathophysiology of CV and metabolic diseases.

Age-related macular degeneration (AMD) is one of the main causes of vision loss, especially in the elderly. The involvement of essential hypertension in its pathogenesis has been well covered in the literature since it was first recognized. Hemodynamic abnormalities appear to contribute to AMD, with the renin–angiotensin system playing a significant role. Many studies have demonstrated that high blood pressure is associated with lower choroidal blood flow and disturbed vascular homeostasis in these patients. In addition, AMD is characterized by abnormal neovascularization, to which angiotensin II and growth factors make a large contribution. Most epidemiological studies have found essential hypertension to be a risk factor for AMD. However, although all agree that the strongest predisposing factors are age and smoking, overall there is some inconsistency regarding the exact role of hypertension in its pathogenesis. In particular, there are no data in the literature to support the view that antihypertensive medication and the successful management of hypertension have a positive effect on the clinical outcome of AMD. This reinforces the data indicating that the cause of AMD is multifactorial and suggests that, although essential hypertension probably plays a role, in itself it is unlikely to be a major contributor to the future occurrence of AMD.

Hepatitis C virus (HCV) is well known for being the leading cause of hepatocellular carcinoma and cirrhosis, contributing to a devastating array of metabolic dysfunctions associated with hepatic failure. However, the cardiac manifestations of HCV and chronic hepatitis C (CHC) are being explored, thus illuminating the connection between HCV infection and cardiac disease. Although not all studies agree, the evidence in favor of CHC promoting major risk factors for cardiovascular disease such as hypertension, insulin resistance, diabetes mellitus, and atherosclerosis is compelling. Similarly, properly warranted attention is being guided towards CHC as an independent risk factor for the development of atherosclerotic heart disease and cardiomyopathy. This review provides a synopsis on the relationship between (HCV) infection and cardiac disease, emphasizing on some of the key possible mechanisms and population derived data.

The introduction of therapies that inhibit tumor angiogenesis and particularly target to vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) (VEGF inhibitors/VEGFi) have revolutionized the treatment of various cancer types. Although their clinical benefit can be optimal for cancer-affected patients, the safety of these targeted agents is of special concern especially for longer-term adjuvant or maintenance treatment. Importantly, VEGFi therapy has been significantly associated with hypertension (HTN) as an adverse effect and therefore the control of blood pressure (BP) after the administration of these drugs remains a challenging matter to be faced. The aim of this review is to summarize studies which investigate the association of VEGFi agents with HTN manifestation and the possible risks associated with this complication. Additionally, given that the optimal management of HTN caused by VEGFi remains obscure, this review will focus on prevention strategies including BP monitoring plans and propose potential therapeutic approaches.

Canagliflozin-with the patent number WO2011142478A1- belongs to a novel class of antidiabetic drugs known as SGLT2 inhibitors, which has been approved by FDA in March 2013. This medication acts through the inhibition of glucose reabsorption in the kidney resulting in glucosuria and thus lowering of glucose blood levels. There are several phase III clinical ongoing trials involving this new class of medications. So far promising results have been shown. This review article summarizes current knowledge regarding the novel SGLT2 inhibitor canagliflozin and its future perspectives in the treatment of type 2 diabetes mellitus.

Depression is a common mental health issue worldwide leading to disability, functional decline and increased mortality. Novel antidepressants have been developed during the last decades in order to treat depression syndromes. Some evidence suggests that major depression has been associated with the development of congestive heart failure and with adverse outcomes in patients with coronary heart disease. The purpose of the present article is to review the impact of novel antidepressant patent drugs on cardiovascular disease and arterial hypertension.

Obesity is a major public health concern associated with increased morbidity and mortality. Its prevalence is rising worldwide mainly due to modern lifestyle habits. Several mechanisms like inflammation, endothelial dysfunction, increased sympathetic tone, high leptin and insulin concentrations as well as enhanced thrombogenesis are implicated to the emergence and progress of cardiovascular disease. Although, changes in the lifestyle remain the cornerstone of antiobesity treatment, alone do not always provide the desired weight loss. Often, the addition of pharmacotherapy or bariatric surgery is considered the treating option for patients meeting eligibility criteria. Although, bariatric surgery is limited to patients with a high body mass index due to the risks of the procedures, the effects of anti-obesity medication on cardiovascular outcome are still unclear. Several anti-obesity drugs have been abandoned because of serious adverse events. Qsymia is a combination of phentermine and topiramate used for obesity treatment. Administration of this drug reduces body weight and has favorable effects in various metabolic and anthropometric parameters. However, there are concerns regarding cardiovascular safety of this drug. In this review, we are going to present the history of current antiobesity medication focusing on the combination of phentermine and topiramate and recent patents.

Hypertension is a disorder of the heart and vessels that affects almost a billion individuals worldwide and is considered the most important preventable factor for premature death. Overall, 95 of all cases are deemed as primary or essential hypertension, where no cause can be identified. Essential hypertension has a complex pathophysiology, involving derailment of endocrine and sympathetic mechanisms, still not completely understood. The kallikrein–kinin system comprises a collection of autacoid peptides such as bradykinin that exert multiple physiologic actions and are of strategic importance for the regulation of blood pressure. Scientific research suggests that its impairment contributes toward the development of hypertension and hypertension-induced end-organ damage.

The beneficial properties of melatonin have captured the attention of clinicians during the past decades. It is a ubiquitous molecule with a remarkable functional role in many diseases such as cancer, depression, neurological diseases, immunodiseases, tinnitus, septic shock, diabetes, insomnia, and osteoporosis. Of special interest in this regard is its role in the cardiovascular system, especially in hypertension. Blood pressure and the cardiovascular system as a whole exhibits a circadian rhythm. Melatonin, the major circadian hormone, has been examined as a potent antihypertensive tool for the past few years of research. The mechanisms related to its hypotensive action are mainly mediated by its receptors melatonin type 1 and melatonin type 2. Melatonin acts as an antioxidant and anti-inflammatory factor, reduces the levels of catecholamines and promotes vasodilatation of peripheral blood vessels by enhancing the production of nitric oxide. Studies on a larger scale should be conducted in humans to ensure its future use in hypertension.

The need for novel antihypertensive therapies represents a continuous challenge. LCZ696 is a first-in-class angiotensin receptor neprilysin inhibitor that has been shown to enhance endogenous natriuretic peptide (NP) actions on neurohormonal activation. This effect seems to be additive to that of the renin–angiotensin–aldosterone system (RAAS) suppression, as impressively suggested in the PARADIGM HF study. LCZ696 has been shown to be effective in reducing blood pressure in several small studies; however, its effectiveness and safety remain to be proved in larger studies. This review summarizes the role of RAAS and NP system in the pathophysiology of hypertension and reviews the current data on the antihypertensive effects of LCZ696.