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Hypertension: HELP
Articles from Slovakia
Based on 144 articles published since 2010

These are the 144 published articles about Hypertension that originated from Slovakia during 2010-2020.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6
1 Editorial Extended consensus on blood pressure variability beyond blood pressure for management of hypertension. 2017

Singh, Ram B / Hristova, Krasimira / Bjørklund, Geir / Fedacko, Jan / Chirumbolo, Salvatore / Pella, Daniel. ·Halberg Hospital and Research Institute, Moradabad, India. · Division of Echocardiography Imaging, National Heart Hospital, Sofia, Bulgaria. · Council for Nutritional and Environmental Medicine, Mo i Rana, Norway. Electronic address: bjorklund@conem.org. · Faculty of Medicine, Pavol Jozef Šafárik University, Kosice, Slovakia. · Department of Neurological and Movement Sciences, University of Verona, Verona, Italy. ·J Am Soc Hypertens · Pubmed #28040405.

ABSTRACT: -- No abstract --

2 Editorial The 1st symposium on ECG changes in left or right ventricular hypertension or hypertrophy in conditions of pressure overload. 2014

Bacharova, Ljuba / Schocken, Douglas D / Wagner, Galen S. ·International Laser Center, Bratislava, Slovak Republic. Electronic address: bacharova@ilc.sk. · Division of Cardiology, Duke University School of Medicine, Durham, NC 27710, USA. · Duke Clinical Research Institute, Durham, NC, USA. ·J Electrocardiol · Pubmed #25042854.

ABSTRACT: -- No abstract --

3 Review Hypothalamic Inflammation at a Crossroad of Somatic Diseases. 2019

Mravec, Boris / Horvathova, Lubica / Cernackova, Alena. ·Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava, Sasinkova 2, 813 72, Bratislava, Slovakia. boris.mravec@fmed.uniba.sk. · Biomedical Research Center, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia. boris.mravec@fmed.uniba.sk. · Biomedical Research Center, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia. · Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava, Sasinkova 2, 813 72, Bratislava, Slovakia. ·Cell Mol Neurobiol · Pubmed #30377908.

ABSTRACT: Various hypothalamic nuclei function as central parts of regulators that maintain homeostasis of the organism. Recently, findings have shown that inflammation in the hypothalamus may significantly affect activity of these homeostats and consequently participate in the development of various somatic diseases such as obesity, diabetes, hypertension, and cachexia. In addition, hypothalamic inflammation may also affect aging and lifespan. Identification of the causes and mechanisms involved in the development of hypothalamic inflammation creates not only a basis for better understanding of the etiopathogenesis of somatic diseases, but for the development of new therapeutic approaches for their treatment, as well.

4 Review Biological activities of (-)-epicatechin and (-)-epicatechin-containing foods: Focus on cardiovascular and neuropsychological health. 2018

Bernatova, Iveta. ·Institute of Normal and Pathological Physiology, Center of Experimental Medicine, Slovak Academy of Sciences, Sienkiewiczova 1, 813 71 Bratislava, Slovak Republic. Electronic address: iveta.bernatova@savba.sk. ·Biotechnol Adv · Pubmed #29355598.

ABSTRACT: Recent studies have suggested that certain (-)-epicatechin-containing foods have a blood pressure-lowering capacity. The mechanisms underlying (-)-epicatechin action may help prevent oxidative damage and endothelial dysfunction, which have both been associated with hypertension and certain brain disorders. Moreover, (-)-epicatechin has been shown to modify metabolic profile, blood's rheological properties, and to cross the blood-brain barrier. Thus, (-)-epicatechin causes multiple actions that may provide unique synergy beneficial for cardiovascular and neuropsychological health. This review summarises the current knowledge on the biological actions of (-)-epicatechin, related to cardiovascular and brain functions, which may play a remarkable role in human health and longevity.

5 Review Gene therapy for hypertension. 2017

Paulis, Ludovit / Franke, Heinrich / Simko, Fedor. ·a Institute of Pathophysiology, Faculty of Medicine , Comenius University , Bratislava , Slovakia. · b Institute of Normal and Pathological Physiology , Slovak Academy of Sciences , Bratislava , Slovakia. · c 3rd Department of Internal Medicine, Faculty of Medicine , Comenius University , Bratislava , Slovak Republic. · d Institute of Experimental Endocrinology, Biomedical Research Center , Slovak Academy of Sciences , Bratislava , Slovak Republic. ·Expert Opin Biol Ther · Pubmed #28780894.

ABSTRACT: INTRODUCTION: The control of hypertension and the resulting cardiovascular events is still insufficient. Thus, the search for novel means for blood pressure (BP) reduction remains worth further clinical and research attention. The advances in vector and construct design sketch the use of gene therapy in hypertension. Areas covered: We have searched for studies using gene therapy in hypertension reporting BP outcomes. We have identified 63 experimental studies demonstrating feasible targeting of the classical and new renin-angiotensin-aldosterone system, β1-adrenergic receptor, NO-cGMP axis, endothelin, natriuretic peptides, kallikrein system, cytochrome P-450 hydroxylase, oncogenes, growth factors, interleukins, angiopoietin-1, adrenomedullin or Klotho in small rodents. Expert opinion: The usual BP reduction was by 10-30 mmHg for up to several months. Some studies reported target organ damage attenuation or even survival prolongation. However, the concept did not reach the clinical phase, in contrast to other cardiovascular conditions. Increased gene transfection efficacy necessary for a systemic treatment, personalized identification of the implied aetiology from the multifactorial background and evidence from larger mammals are required for gene therapy to compete with the broad spectrum of current therapeutic options in hypertension. Until then, in the field of hypertension, gene modulation will provide a valuable research tool.

6 Review Gut Bacteria and Hydrogen Sulfide: The New Old Players in Circulatory System Homeostasis. 2016

Tomasova, Lenka / Konopelski, Piotr / Ufnal, Marcin. ·Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw 02 091, Poland. lennytomasova@gmail.com. · Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Bratislava 845 05, Slovakia. lennytomasova@gmail.com. · Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw 02 091, Poland. piotr.konopelski@wp.pl. · Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw 02 091, Poland. mufnal@wum.edu.pl. ·Molecules · Pubmed #27869680.

ABSTRACT: Accumulating evidence suggests that gut bacteria play a role in homeostasis of the circulatory system in mammals. First, gut bacteria may affect the nervous control of the circulatory system via the sensory fibres of the enteric nervous system. Second, gut bacteria-derived metabolites may cross the gut-blood barrier and target blood vessels, the heart and other organs involved in the regulation of the circulatory system. A number of studies have shown that hydrogen sulfide (H₂S) is an important biological mediator in the circulatory system. Thus far, research has focused on the effects of H₂S enzymatically produced by cardiovascular tissues. However, some recent evidence indicates that H₂S released in the colon may also contribute to the control of arterial blood pressure. Incidentally, sulfate-reducing bacteria are ubiquitous in mammalian colon, and H₂S is just one among a number of molecules produced by the gut flora. Other gut bacteria-derived compounds that may affect the circulatory system include methane, nitric oxide, carbon monoxide, trimethylamine or indole. In this paper, we review studies that imply a role of gut microbiota and their metabolites, such as H₂S, in circulatory system homeostasis.

7 Review The role of PPARgamma in cardiovascular diseases. 2016

Kvandová, M / Majzúnová, M / Dovinová, I. ·Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic. ima.dovinova@savba.sk. ·Physiol Res · Pubmed #27775420.

ABSTRACT: The peroxisome proliferator-activated receptors (PPAR) belong to the nuclear superfamily of ligand-activated transcription factors. PPARgamma acts as a nutrient sensor that regulates several homeostatic functions. Its disruption can lead to vascular pathologies, disorders of fatty acid/lipid metabolism and insulin resistance. PPARgamma can modulate several signaling pathways connected with blood pressure regulation. Firstly, it affects the insulin signaling pathway and endothelial dysfunction by modulation of expression and/or phosphorylation of signaling molecules through the PI3K/Akt/eNOS or MAPK/ET-1 pathways. Secondly, it can modulate gene expression of the renin- angiotensin system - cascade proteins, which potentially slow down the progression of atherosclerosis and hypertension. Thirdly, it can modulate oxidative stress response either directly through PPAR or indirectly through Nrf2 activation. In this context, activation and functioning of PPARgamma is very important in the regulation of several disorders such as diabetes mellitus, hypertension and/or metabolic syndrome.

8 Review Blood pressure regulation in stress: focus on nitric oxide-dependent mechanisms. 2016

Puzserova, A / Bernatova, I. ·Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic. angelika.puzserova@savba.sk. ·Physiol Res · Pubmed #27775419.

ABSTRACT: Stress is considered a risk factor associated with the development of various civilization diseases including cardiovascular diseases, malignant tumors and mental disorders. Research investigating mechanisms involved in stress-induced hypertension have attracted much attention of physicians and researchers, however, there are still ambiguous results concerning a causal relationship between stress and long-term elevation of blood pressure (BP). Several studies have observed that mechanisms involved in the development of stress-induced hypertension include increased activity of sympathetic nervous system (SNS), glucocorticoid (GC) overload and altered endothelial function including decreased nitric oxide (NO) bioavailability. Nitric oxide is well known neurotransmitter, neuromodulator and vasodilator involved in regulation of neuroendocrine mechanisms and cardiovascular responses to stressors. Thus NO plays a crucial role in the regulation of the stress systems and thereby in the BP regulation in stress. Elevated NO synthesis, especially in the initial phase of stress, may be considered a stress-limiting mechanism, facilitating the recovery from stress to the resting levels via attenuation of both GC release and SNS activity as well as by increased NO-dependent vasorelaxation. On the other hand, reduced levels of NO were observed in the later phases of stress and in subjects with genetic predisposition to hypertension, irrespectively, in which reduced NO bioavailability may account for disruption of NO-mediated BP regulatory mechanisms and accentuated SNS and GC effects. This review summarizes current knowledge on the role of stress in development of hypertension with a special focus on the interactions among NO and other biological systems affecting blood pressure and vascular function.

9 Review The role of hydrogen sulphide in blood pressure regulation. 2016

Cacanyiova, S / Berenyiova, A / Kristek, F. ·Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic. sona.cacanyiova@savba.sk. ·Physiol Res · Pubmed #27775417.

ABSTRACT: Cardiovascular studies have confirmed that hydrogen sulphide (H(2)S) is involved in various signaling pathways in both physiological and pathological conditions, including hypertension. In contrast to nitric oxide (NO), which has a clear vasorelaxant action, H(2)S has both vasorelaxing and vasoconstricting effects on the cardiovascular system. H(2)S is an important antihypertensive agent, and the reduced production of H(2)S and the alterations in its functions are involved in the initiation of spontaneous hypertension. Moreover, cross-talk between H(2)S and NO has been reported. NO-H(2)S interactions include reactions between the molecules themselves, and each has been shown to regulate the endogenous production of the other. In addition, NO and H(2)S can interact to form a nitrosothiol/s complex, which has original properties and represents a novel nitroso-sulphide signaling pathway. Furthermore, recent results have shown that the interaction between H(2)S and NO could be involved in the endothelium-regulated compensatory mechanisms that are observed in juvenile spontaneously hypertensive rats. The present review is devoted to role of H(2)S in vascular tone regulation. We primarily focus on the mechanisms of H(2)S-NO interactions and on the role of H(2)S in blood pressure regulation in normotensive and spontaneously hypertensive rats.

10 Review The role of red blood cell deformability and Na,K-ATPase function in selected risk factors of cardiovascular diseases in humans: focus on hypertension, diabetes mellitus and hypercholesterolemia. 2016

Radosinska, J / Vrbjar, N. ·Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovak Republic; Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic. usrdnorb@savba.sk. ·Physiol Res · Pubmed #27643939.

ABSTRACT: Deformability of red blood cells (RBC) is the ability of RBC to change their shape in order to pass through narrow capillaries in circulation. Deterioration in deformability of RBC contributes to alterations in microcirculatory blood flow and delivery of oxygen to tissues. Several factors are responsible for maintenance of RBC deformability. One of them is the Na,K-ATPase known as crucial enzyme in maintenance of intracellular ionic homeostasis affecting thus regulation of cellular volume and consequently RBC deformability. Decreased deformability of RBC has been found to be the marker of adverse outcomes in cardiovascular diseases (CVD) and the presence of cardiovascular risk factors influences rheological properties of the blood. This review summarizes knowledge concerning the RBC deformability in connection with selected risk factors of CVD, including hypertension, hyperlipidemia, and diabetes mellitus, based exclusively on papers from human studies. We attempted to provide an update on important issues regarding the role of Na,K-ATPase in RBC deformability. In patients suffering from hypertension as well as diabetes mellitus the Na,K-ATPase appears to be responsible for the changes leading to alterations in RBC deformability. The triggering factor for changes of RBC deformability during hypercholesterolemia seems to be the increased content of cholesterol in erythrocyte membranes.

11 Review Protection of cardiac cell-to-cell coupling attenuate myocardial remodeling and proarrhythmia induced by hypertension. 2016

Egan Benova, T / Szeiffova Bacova, B / Viczenczova, C / Diez, E / Barancik, M / Tribulova, N. ·Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovakia. tamara.benova@savba.sk. ·Physiol Res · Pubmed #27643938.

ABSTRACT: Gap junction connexin channels are important determinants of myocardial conduction and synchronization that is crucial for coordinated heart function. One of the main risk factors for cardiovascular events that results in heart attack, congestive heart failure, stroke as well as sudden arrhythmic death is hypertension. Mislocalization and/or dysfunction of specific connexin-43 channels due to hypertension-induced myocardial remodeling have been implicated in the occurrence of life-threatening arrhythmias and heart failure in both, humans as well as experimental animals. Recent studies suggest that down-regulation of myocardial connexin-43, its abnormal distribution and/or phosphorylation might be implicated in this process. On the other hand, treatment of hypertensive animals with cardioprotective drugs (e.g. statins) or supplementation with non-pharmacological compounds, such as melatonin, omega-3 fatty acids and red palm oil protects from lethal arrhythmias. The antiarrhythmic effects are attributed to the attenuation of myocardial connexin-43 abnormalities associated with preservation of myocardial architecture and improvement of cardiac conduction. Findings uncover novel mechanisms of cardioprotective (antihypertensive and antiarrhythmic) effects of compounds that are used in clinical settings. Well-designed trials are needed to explore the antiarrhythmic potential of these compounds in patients suffering from hypertension.

12 Review Interplay of vitamin D, erythropoiesis, and the renin-angiotensin system. 2015

Santoro, Domenico / Caccamo, Daniela / Lucisano, Silvia / Buemi, Michele / Sebekova, Katerina / Teta, Daniel / De Nicola, Luca. ·Department of Clinical and Experimental Medicine, University of Messina, Via Faranda, 2-98123 Messina, Italy. · Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Italy. · Comenius University, Bratislava, Slovakia. · University Hospital (CHUV), Lausanne, Switzerland. · Second University of Naples, Naples, Italy. ·Biomed Res Int · Pubmed #26000281.

ABSTRACT: For many years deficiency of vitamin D was merely identified and assimilated to the presence of bone rickets. It is now clear that suboptimal vitamin D status may be correlated with several disorders and that the expression of 1-α-hydroxylase in tissues other than the kidney is widespread and of clinical relevance. Recently, evidence has been collected to suggest that, beyond the traditional involvement in mineral metabolism, vitamin D may interact with other kidney hormones such as renin and erythropoietin. This interaction would be responsible for some of the systemic and renal effects evoked for the therapy with vitamin D. The administration of analogues of vitamin D has been associated with an improvement of anaemia and reduction in ESA requirements. Moreover, vitamin D deficiency could contribute to an inappropriately activated or unsuppressed RAS, as a mechanism for progression of CKD and/or cardiovascular disease. Experimental data on the anti-RAS and anti-inflammatory effects treatment with active vitamin D analogues suggest a therapeutic option particularly in proteinuric CKD patients. This option should be considered for those subjects that are intolerant to anti-RAS agents or, as add-on therapy, in those already treated with anti-RAS but not reaching the safe threshold level of proteinuria.

13 Review Peripheral and central effects of melatonin on blood pressure regulation. 2014

Pechanova, Olga / Paulis, Ludovit / Simko, Fedor. ·Institute of Normal and Pathological Physiology and Centre of Excellence for Nitric Oxide Research, Slovak Academy of Sciences, Bratislava 81371, Slovak Republic. olga.pechanova@savba.sk. · Institute of Normal and Pathological Physiology and Centre of Excellence for Nitric Oxide Research, Slovak Academy of Sciences, Bratislava 81371, Slovak Republic. ludo@lfuk.sk. · Department of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava 81371, Slovak Republic. fedor.simko@fmed.uniba.sk. ·Int J Mol Sci · Pubmed #25299692.

ABSTRACT: The pineal hormone, melatonin (N-acetyl-5-methoxytryptamine), shows potent receptor-dependent and -independent actions, which participate in blood pressure regulation. The antihypertensive effect of melatonin was demonstrated in experimental and clinical hypertension. Receptor-dependent effects are mediated predominantly through MT1 and MT2 G-protein coupled receptors. The pleiotropic receptor-independent effects of melatonin with a possible impact on blood pressure involve the reactive oxygen species (ROS) scavenging nature, activation and over-expression of several antioxidant enzymes or their protection from oxidative damage and the ability to increase the efficiency of the mitochondrial electron transport chain. Besides the interaction with the vascular system, this indolamine may exert part of its antihypertensive action through its interaction with the central nervous system (CNS). The imbalance between the sympathetic and parasympathetic vegetative system is an important pathophysiological disorder and therapeutic target in hypertension. Melatonin is protective in CNS on several different levels: It reduces free radical burden, improves endothelial dysfunction, reduces inflammation and shifts the balance between the sympathetic and parasympathetic system in favor of the parasympathetic system. The increased level of serum melatonin observed in some types of hypertension may be a counter-regulatory adaptive mechanism against the sympathetic overstimulation. Since melatonin acts favorably on different levels of hypertension, including organ protection and with minimal side effects, it could become regularly involved in the struggle against this widespread cardiovascular pathology.

14 Review Endothelial dysfunction in experimental models of arterial hypertension: cause or consequence? 2014

Bernatova, Iveta. ·Centre of Excellence for Examination of Regulatory Role of Nitric Oxide in Civilization Diseases, Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Sienkiewiczova 1, 813 71 Bratislava, Slovakia. ·Biomed Res Int · Pubmed #24738065.

ABSTRACT: Hypertension is a risk factor for other cardiovascular diseases and endothelial dysfunction was found in humans as well as in various commonly employed animal experimental models of arterial hypertension. Data from the literature indicate that, in general, endothelial dysfunction would not be the cause of experimental hypertension and may rather be secondary, that is, resulting from high blood pressure (BP). The initial mechanism of endothelial dysfunction itself may be associated with a lack of endothelium-derived relaxing factors (mainly nitric oxide) and/or accentuation of various endothelium-derived constricting factors. The involvement and role of endothelium-derived factors in the development of endothelial dysfunction in individual experimental models of hypertension may vary, depending on the triggering stimulus, strain, age, and vascular bed investigated. This brief review was focused on the participation of endothelial dysfunction, individual endothelium-derived factors, and their mechanisms of action in the development of high BP in the most frequently used rodent experimental models of arterial hypertension, including nitric oxide deficient models, spontaneous (pre)hypertension, stress-induced hypertension, and selected pharmacological and diet-induced models.

15 Review Redox signaling in pathophysiology of hypertension. 2013

Majzunova, Miroslava / Dovinova, Ima / Barancik, Miroslav / Chan, Julie Y H. ·Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Sienkiewiczova 1, 813 71 Bratislava, Slovakia. Ima.Dovinova@savba.sk. ·J Biomed Sci · Pubmed #24047403.

ABSTRACT: Reactive oxygen species (ROS) are products of normal cellular metabolism and derive from various sources in different cellular compartments. Oxidative stress resultant from imbalance between ROS generation and antioxidant defense mechanisms is important in pathogenesis of cardiovascular diseases, such as hypertension, heart failure, atherosclerosis, diabetes, and cardiac hypertrophy. In this review we focus on hypertension and address sources of cellular ROS generation, mechanisms involved in regulation of radical homeostasis, superoxide dismutase isoforms in pathophysiology of hypertension; as well as radical intracellular signaling and phosphorylation processes in proteins of the affected cardiovascular tissues. Finally, we discuss the transcriptional factors involved in redox-sensitive gene transcription and antioxidant response, as well as their roles in hypertension.

16 Review Environmental noise and cardiovascular disease in adults: research in Central, Eastern and South-Eastern Europe and Newly Independent States. 2013

Argalášová-Sobotová, L'ubica / Lekaviciute, Jurgita / Jeram, Sonja / Sevcíková, L'udmila / Jurkovicová, Jana. ·Comenius University, Bratislava, Slovakia. lubica.argalasova@fmed.uniba.sk ·Noise Health · Pubmed #23412577.

ABSTRACT: The adverse effects of noise on health have been intensely explored in the past 50 years. However, the scope of research conducted in the Central and Eastern Europe, South-East Europe, and Newly Independent States is not well-known. The aim of this review was to present studies on cardiovascular effects of environmental noise in adults published since 1965 and to point out the most important issues that need to be addressed in the future. More than 100 papers on noise and health and about 20 papers on cardiovascular effects of environmental noise in adults were identified by literature search. The authors reviewed scientific international and local journals, conference proceedings, and local reports published in national languages. The major endpoints were high blood pressure, ischemic heart disease, and myocardial infarction. The target populations were adults. Experimental and exposure-assessment studies, field, empirical studies, social surveys, and epidemiological studies are presented. The major sources of environmental noise were road and air traffic. The results were presented in tables and the most relevant articles were briefly discussed. The importance of this review is that it refers to some countries that no longer exist in the same political and governmental systems. The strength of this paper is that it includes publications that were not evaluated in earlier systematic reviews. Strategies for future noise-related research on national and global level are proposed.

17 Review Experimental models of melatonin-deficient hypertension. 2013

Simko, Fedor / Reiter, Russel J / Pechanova, Olga / Paulis, Ludovit. ·Department of Pathophysiology, School of Medicine, Comenius University, Sasinkova 4, 81372 Bratislava, Slovak Republic. fedor.simko@fmed.uniba.sk ·Front Biosci (Landmark Ed) · Pubmed #23276947.

ABSTRACT: Melatonin secreted by the pineal gland plays an important role in the regulation of blood pressure (BP) and its administration reduces hypertension both in animals and humans. There are two experimental models of melatonin-deficient hypertension: one induced by pinealectomy and another by continuous 24 hour exposure to light. Both models cause melatonin deficiency and prevent darkness-mediated nocturnal melatonin secretion and are associated with increased BP and myocardial, vascular and renal dysfunction. These models also lead to neurohumoral activation of the renin-angiotensin system, sympathetic nervous system, adrenocorticotrophin-glucocorticoid axis and cause insulin resistance. Together, these alterations contribute to rise in blood pressure by vasoconstrictive or circulatory fluid volume overload. The light induced hypertension model mimics the melatonin deficiency in patients with insufficient nocturnal BP decline, in those who have night shift or who are exposed to environmental light pollution. For this reason, this model is useful in development of anti-hypertensive drugs.

18 Review Therapeutic potential of nitric oxide donors in the prevention and treatment of angiogenesis-inhibitor-induced hypertension. 2013

Kruzliak, Peter / Kovacova, Gabriela / Pechanova, Olga. ·Institute of Normal and Pathological Physiology, Centre of Excellence for Regulatory Role of Nitric Oxide in Civilization Diseases, Slovak Academy of Sciences, 813 71, Bratislava, Slovak Republic. peter.kruzliak@savba.sk ·Angiogenesis · Pubmed #23203441.

ABSTRACT: Angiogenesis is critical to tumor growth as well as to metastases. This process is tightly regulated by pro- and anti-angiogenic growth factors and their receptors. Some of these factors are highly specific for the endothelium-e.g., vascular endothelial growth factor (VEGF). A variety of drugs that target VEGF or its receptors have been developed for the treatment of different tumor types and a number of new agents is expected to be introduced within the coming years. However, clinical experience has revealed that inhibition of VEGF induces several side effects including hypertension and renal and cardiac toxicity. Angiogenesis-inhibitor-induced hypertension represents "crux medicorum" as it is often pharmacoresistant to antihypertensive therapy. We consider two most important pathomechanisms in the development of hypertension induced by angiogenesis inhibitors. The first represents direct inhibition of NO production leading to reduced vasodilatation and the second consists in increased proliferation of vascular medial cells mediated by NO deficiency and is resulting in fixation of hypertension. Based on the results of experimental and clinical studies as well as on our clinical experience, we assume that NO donors could be successfully used not only for the treatment of developed angiogenesis-inhibitor-induced hypertension but also for preventive effects. We thoroughly documented three clinical cases of cancer patients with resistant hypertension who on receiving NO donor treatment achieved target blood pressure level and a good clinical status.

19 Review L-NAME in the cardiovascular system - nitric oxide synthase activator? 2012

Kopincová, Jana / Púzserová, Angelika / Bernátová, Iveta. ·Department of Physiology, Jessenius Faculty of Medicine, Comenius University, Malá Hora 4A, 036 01 Martin, Slovak Republic. jana.kopincova@jfmed.uniba.sk ·Pharmacol Rep · Pubmed #22814004.

ABSTRACT: L-arginine analogues are widely used inhibitors of nitric oxide synthase (NOS) activity both in vitro and in vivo, with N(ω)-nitro-L-arginine methyl ester (L-NAME) being at the head. On the one hand, acute and chronic L-NAME treatment leads to changes in blood pressure and vascular reactivity due to decreased nitric oxide (NO) bioavailability. However, lower doses of L-NAME may also activate NO production via feedback regulatory mechanisms if administered for longer time. Such L-NAME-induced activation has been observed in both NOS expression and activity and revealed considerable differences in regulatory mechanisms of NO production between particular tissues depending on the amount of L-NAME. Moreover, feedback activation of NO production by L-NAME seems to be regulated diversely under conditions of hypertension. This review summarizes the mechanisms of NOS regulation in order to better understand the apparent discrepancies found in the current literature.

20 Review Key advances in antihypertensive treatment. 2012

Paulis, Ludovit / Steckelings, Ulrike M / Unger, Thomas. ·Institute of Pathophysiology, Faculty of Medicine, Comenius University, Sasinkova 4, Bratislava, Slovakia. ·Nat Rev Cardiol · Pubmed #22430830.

ABSTRACT: Although various effective treatments for hypertension are available, novel therapies to reduce elevated blood pressure, improve blood-pressure control, treat resistant hypertension, and reduce the associated cardiovascular risk factors are still required. A novel angiotensin-receptor blocker (ARB) was approved in 2011, and additional compounds are in development or being tested in clinical trials. Several of these agents have innovative mechanisms of action (an aldosterone synthase inhibitor, a natriuretic peptide agonist, a soluble epoxide hydrolase inhibitor, and an angiotensin II type 2 receptor agonist) or dual activity (a combined ARB and neutral endopeptidase inhibitor, an ARB and endothelin receptor A blocker, and an endothelin-converting enzyme and neutral endopeptidase inhibitor). In addition, several novel fixed-dose combinations of existing antihypertensive agents were approved in 2010-2011, including aliskiren double and triple combinations, and an olmesartan triple combination. Upcoming fixed-dose combinations are expected to introduce calcium-channel blockers other than amlodipine and diuretics other than hydrochlorothiazide. Finally, device-based approaches to the treatment of resistant hypertension, such as renal denervation and baroreceptor activation therapy, have shown promising results in clinical trials. However, technical improvements in the implantation procedure and devices used for baroreceptor activation therapy are required to address procedural safety concerns.

21 Review [Endothelial (dys)function in the experimental model of primary hypertension]. 2010

Púzserová, A / Kopincová, J / Bernátová, I. ·Ustav normálnej a patologickej fyziológie SAV, Centrum excelentnostipre kardiovaskulárny výskum, Bratislava. angelika.puzserova@savba.sk ·Cesk Fysiol · Pubmed #21254662.

ABSTRACT: A number of vascular diseases, including hypertension, are characterised by endothelial dysfunction caused by alterations in the production and action of the endothelium-derived relaxing (EDRFs) and/or endothelium-derived contracting (EDCFs) factors. The spontaneously hypertensive rat (SHR) is one of the most widely studied animal models for human essential hypertension. Several similarities between human primary hypertension and hypertension in the SHR have been pointed out in both the pathophysiology and the clinical course of the hypertensive disease. In human hypertension as well as in SHR, endothelium-dependent relaxation may be attenuated and this endothelial dysfunction contributes to the increased peripheral resistance. However, various results concerning endothelium-dependent relaxation, including impairment, no change and improvement have been reported in experimental hypertension. Endothelial dysfunction in hypertension has been linked to decrease in NO bioavailability, reflecting the impaired generation of NO and/or the enhanced inactivation of NO by reactive oxygen species. There is evidence that increased vascular oxidative stress is present in SHR. Thus, it has been proposed that oxidative inactivation of NO may account for the endothelial dysfunction seen in SHR. On the other hand, several studies demonstrate elevated basal NO synthesis in SHR rats which may be an adapting mechanism, preventing them from excessive blood pressure elevation. However, the role of NO in hypertension in SHR and in humans remains still controversial. We hypothesize that the vascular bed studied, the effect of age as well as methodological aspects, such as "precontraction" with different vasoconstrictors as well as antioxidants added to the solution for determination of the vasoreactivity may contribute to the discrepancies among studies. Nevertheless, the involvement of endothelial function in hypertension remains subject of debate and further research is needed to complete our knowledge on the role of NO, reactive oxygen species and other endothelial factors in the regulation of vascular and cardiac function.

22 Clinical Trial Slovak trial on cardiovascular risk reduction following national guidelines with CaDUET® (the STRONG DUET study). 2013

Fedacko, Jan / Pella, Daniel / Jarcuska, Peter / Sabol, Frantisek / Kmec, Jan / Lopuchovsky, Tomas / Merkovska, Lucia / Jedlickova, Lucia / Janicko, Martin / Sajty, Matej. ·First Department Of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Košice, Slovakia. janfedacko@hotmail.com ·Adv Ther · Pubmed #23328937.

ABSTRACT: INTRODUCTION: The efficacy and safety of single-pill amlodipine/atorvastatin for reducing blood pressure (BP), low-density lipoprotein cholesterol (LDLC), and predicted 10-year cardiovascular (CV) risk have been demonstrated in low CV risk countries. The Slovak Trial on Cardiovascular Risk Reduction Following National Guidelines with CaDUET® (amlodipine besylate/atorvastatin calcium; Pfizer, Morrisville, PA, USA; STRONG DUET) study evaluated its clinical utility in Slovakia, one of the highest CV risk regions in Europe. METHODS: This was a two-phase study involving 100 outpatient cardiologist and internist departments in Slovakia. Phase 1 assessed BP control and CV risk profiles in adults with treated hypertension, and phase 2 was an open-label, multicenter, observational study. In the phase 2 study, patients with treated but uncontrolled hypertension and three or more coronary heart disease risk factors received single-pill amlodipine/atorvastatin (5/10 or 10/10 mg) for 12 weeks. Major outcomes were the percentage of patients achieving target BP (≤140/90 mmHg) and/or LDL-C (≤3 mmol/L) and reductions in predicted 10-year CV risk. RESULTS: Of the 4,672 phase 1 patients, 80.8% had uncontrolled hypertension and 61.4% had dyslipidemia. Of the 1,406 phase 2 patients, 90.3% of patients achieved target BP at week 12, 66.3% achieved target LDL-C, and 60.7% achieved both. The mean 10-year CV risk was reduced by 49% (P < 0.0001); treatment was well-tolerated and safe. CONCLUSION: Single-pill amlodipine/atorvastatin was associated with significant improvements in BP, LDL-C target attainment, and 10-year CV risk in patients with uncontrolled hypertension in Slovakia. The treatment was well-tolerated and safe. Use of single-pill amlodipine/atorvastatin in high CV-risk countries could lead to significant improvements in CV risk management.

23 Clinical Trial Optimization of blood pressure treatment with fixed-combination perindopril/amlodipine in patients with arterial hypertension. 2012

Hatala, Robert / Pella, Daniel / Hatalová, Katarína / Šidlo, Rastislav. ·Department of Cardiology, National Cardiovascular Institute and Slovak Medical University, Bratislava, Slovakia. hatala@nusch.sk ·Clin Drug Investig · Pubmed #22877321.

ABSTRACT: BACKGROUND: Fixed-dose combination treatments using an angiotensin-converting enzyme (ACE) inhibitor, such as perindopril, plus a calcium channel blocker (CCB), such as amlodipine, have been endorsed by guidelines because they improve blood pressure control and cardiovascular outcomes in hypertensive patients, while being well tolerated and well adhered to by patients. OBJECTIVE: This study aimed to assess the blood pressure-lowering effects of fixed-combination perindopril/amlodipine in patients previously treated with an ACE inhibitor and/or a CCB. METHODS: This was a prospective, real-life, open-label, longitudinal, phase IV study conducted in 223 outpatient medical centres across Slovakia. 2132 previously treated patients whose hypertension was insufficiently controlled at baseline or who tolerated treatment poorly were included. Patients were treated for 3 months with fixed-combination perindopril/amlodipine 5 mg/5 mg, 5 mg/10 mg, 10 mg/5 mg and 10 mg/10 mg. The main outcome measure was a reduction in mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) and achievement of blood pressure targets (SBP/DBP <140/90 mmHg or <130/80 mmHg for patients with type 2 diabetes mellitus or high cardiovascular risk). RESULTS: After 3 months of treatment, mean ± SD SBP/DBP had decreased from 158.5 ± 17.5/93.6 ± 9.8 mmHg to 132.9 ± 10.6/80.7 ± 6.2 mmHg (p < 0.0001). In patients with grade 3 hypertension, mean ± SD changes from baseline in SBP/DBP were -45.4 ± 16.4/-20.0 ± 11.5 mmHg after 3 months (p < 0.0001). Blood pressure targets were reached by 74% of the overall patient population, 84% of patients with grade 1 hypertension, and 52% of difficult-to-treat patients with grade 3 hypertension. This treatment was associated with a 58% reduction in the number of patients with amlodipine-related ankle oedema compared with baseline. CONCLUSION: Fixed-combination perindopril/amlodipine was well tolerated and resulted in statistically significant and clinically meaningful decreases in blood pressure.

24 Clinical Trial HDL subfractions analysis: a new laboratory diagnostic assay for patients with cardiovascular diseases and dyslipoproteinemia. 2011

Oravec, Stanislav / Dostal, Elisabeth / Dukát, Andrej / Gavorník, Peter / Kucera, Marek / Gruber, Kristína. ·2nd Department of Internal Medicine, Comenius University, Bratislava, Slovakia. stanislavoravec@yahoo.com ·Neuro Endocrinol Lett · Pubmed #21876506.

ABSTRACT: OBJECTIVE: The HDL family forms a protective part of plasma lipoproteins. It consists of large HDL, intermediate HDL, and small HDL subclasses. The large HDL and intermediate HDL subclasses are considered anti-atherogenic parts of the HDL family. The atherogenicity of the small HDL subclass is currently the subject of much discussion. In the patient group with the diagnosis of cardiovascular disease (arterial hypertension, coronary heart disease) and in individuals with a non-atherogenic hypercholesterolemia, a type of lipoprotein profile (either a non-atherogenic phenotype A, or an atherogenic phenotype B) was identified, and a concentration of small dense LDL (sdLDL) was analyzed. The aim of this study was to identify the major representative of the HDL subclasses in the individuals with cardiovascular diseases, who had an atherogenic lipoprotein phenotype B, and in the individuals with the diagnosis of non-atherogenic hyper-betalipoproteinemia LDL1,2, who had a non-atherogenic lipoprotein phenotype A. METHODS: Identification of the specific lipoprotein phenotype and a quantitative analysis of small dense LDL was performed by an electrophoresis method on polyacrylamide gel (PAG), using the Lipoprint LDL system. For a quantitative analysis of HDL subclasses, i.e., large HDL, intermediatete HDL, and small HDL, in subjects with newly diagnosed cardiovascular diseases (arterial hypertension and coronary heart disease), and in subjects with a non-atherogenic hypercholesterolemia (hyper-betalipoproteinemia LDL1,2), we used an innovative electrophoresis method on polyacrylamide gel (PAG), the Lipoprint HDL system. With regard to lipids, total cholesterol and triglycerides in plasma were analyzed by an enzymatic CHOD PAP method. A control group consisted of a group of healthy normolipidemic volunteers without signs of clinically manifested impairment of the cardiovascular system. RESULTS: In the patient group with the diagnosis of arterial hypertension (p<0.0002) and coronary heart disease (p<0.0001), (both are classified as cardiovascular diseases), the large HDL subclass was significantly decreased and the small HDL subclass was increased (p<0.0001). The concentration of the intermediate HDL subclass did not differ from that of the control group. These results were in accordance with an atherogenic lipoprotein phenotype B in individuals with the diagnosis of cardiovascular diseases, where, using a Lipoprint LDL analysis, a high concentration of atherogenic small dense LDL (p<0.0001) was found. Thus, it seems that the small HDL subclass represents an atherogenic part of the HDL family. Conversely, an increased concentration of total HDL (p<0.0001), large HDL (p<0.005), and intermediate HDL subclasses (p<0.0001) was found in a group of subjects with a non-atherogenic hyper-betalipoproteinemia LDL1,2.The concentration of the small HDL subclass did not differ from that of the control group. In this non-atherogenic lipoprotein profile, only traces of atherogenic small dense LDL were identified. CONCLUSIONS: The advantages of this new method includes: (i) Identification of ten HDL subfractions with Lipoprint HDL analysis (large HDL1-3, intermediate HDL 4-7, and small HDL 8-10) . (ii) Discovery of a high concentration of small HDL in plasma lipoproteins in patients with cardovascular diseases with an atherogenic lipoprotein phenotype B, confirms that the atherogenic subclass of HDL family is attributable to small HDL. (iii) Presence of a low concentration of small HDL in non-atherogenic hypercholesterolemia also confirms the atherogenic characteristics of the small HDL subclass per se. (iv) Presence of small dense LDL is definitive to diagnose an atherogenic lipoprotein profile. It is valid for hyperlipidemia and for normolipidemia as well.

25 Article Pulmonary Hypertension in Adults with Congenital Heart Disease: Real-World Data from the International COMPERA-CHD Registry. 2020

Kaemmerer, Harald / Gorenflo, Matthias / Huscher, Dörte / Pittrow, David / Apitz, Christian / Baumgartner, Helmut / Berger, Felix / Bruch, Leonhard / Brunnemer, Eva / Budts, Werner / Claussen, Martin / Coghlan, Gerry / Dähnert, Ingo / D'Alto, Michele / Delcroix, Marion / Distler, Oliver / Dittrich, Sven / Dumitrescu, Daniel / Ewert, Ralf / Faehling, Martin / Germund, Ingo / Ghofrani, Hossein Ardeschir / Grohé, Christian / Grossekreymborg, Karsten / Halank, Michael / Hansmann, Georg / Harzheim, Dominik / Nemes, Attila / Havasi, Kalman / Held, Matthias / Hoeper, Marius M / Hofbeck, Michael / Hohenfrost-Schmidt, Wolfgang / Jurevičienė, Elena / Gumbienè, Lina / Kabitz, Hans-Joachim / Klose, Hans / Köhler, Thomas / Konstantinides, Stavros / Köestenberger, Martin / Kozlik-Feldmann, Rainer / Kramer, Hans-Heiner / Kropf-Sanchen, Cornelia / Lammers, Astrid / Lange, Tobias / Meyn, Philipp / Miera, Oliver / Milger-Kneidinger, Katrin / Neidenbach, Rhoia / Neurohr, Claus / Opitz, Christian / Perings, Christian / Remppis, Bjoern Andrew / Riemekasten, Gabriele / Scelsi, Laura / Scholtz, Werner / Simkova, Iveta / Skowasch, Dirk / Skride, Andris / Stähler, Gerd / Stiller, Brigitte / Tsangaris, Iraklis / Vizza, Carmine Dario / Noordegraaf, Anton Vonk / Wilkens, Heinrike / Wirtz, Hubert / Diller, Gerhard-Paul / Grünig, Ekkehard / Rosenkranz, Stephan. ·Deutsches Herzzentrum München, Klinik für Angeborene Herzfehler und Kinderkardiologie, München, Technische Universität München, 80636 Munich, Germany. · Universitätsklinikum Heidelberg, Zentrum für Kinder- und Jugendmedizin, Angelika-Lautenschläger-Klinik, 69120 Heidelberg, Germany. · Institute of Biometry and Clinical Epidemiology, and Berlin Institute of Health, Charité Universitätsmedizin, 10117 Berlin, Germany. · Medical Faculty, Institute for Clinical Pharmacology, Technical University, 01307 Dresden, Germany. · GWT-TUD GmbH, Pharmacoepidemiology, 01307 Dresden, Germany. · Universitätsklinik für Kinder- und Jugendmedizin, Sektion Pädiatrische Kardiologie, 89075 Ulm, Germany. · Universitätsklinik Münster, Klinik für Angeborene (EMAH) und Erworbene Herzfehler, 48149 Münster, Germany. · Deutsches Herzzentrum Berlin, Klinik für Angeborene Herzfehler/Kinderkardiologie, 13353 Berlin, Germany. · Unfallkrankenhaus Berlin, Klinik für Innere Medizin, 12683 Berlin, Germany. · Medizinische Universitätsklinik (Krehl-Klinik), Klinik für Kardiologie, Angiologie und Pneumologie (Innere Medizin III), 69120 Heidelberg, Germany. · UZ Leuven, Congenital and Structural Cardiology, Campus Gasthuisberg, 3000 Leuven, Belgium. · LungenClinic Grosshansdorf, Fachabteilung Pneumologie, 22927 Großhansdorf, Germany. · Royal Free Hospital, Cardiology, London NW3 2QG, UK. · Herzzentrum Leipzig GmbH, Klinik für Kinderkardiologie, 04289 Leipzig, Germany. · Ospedale Monaldi, 80131 Napoli, Italy. · Department of Respiratory Diseases, University Hospitals of Leuven, 3000 Leuven, Belgium. · Universitätsspital Zürich, Klinik für Rheumatologie, 8091 Zürich, Switzerland. · Universitätsklinikum Erlangen, Kinderkardiologie, 91054 Erlangen, Germany. · HDZ NRW, Klinik für Thorax- und Kardiovaskularchirurgie, 32545 Bad Oeynhausen, Germany. · Universitätsmedizin Greifswald, Zentrum für Innere Medizin, Klinik und Poliklinik für Innere Medizin B, 17475 Greifswald, Germany. · Klinikum Esslingen GmbH, Klinik für Kardiologie, Angiologie und Pneumologie, 73730 Esslingen a.N., Germany. · Uniklinik Köln-Herzzentrum, Klinik und Poliklinik für Kinderkardiologie, 50937 Köln, Germany. · Universitätsklinikum Gießen und Marburg GmbH, Medizinische Klinik II/V, 35392 Gießen, Germany. · Evangelische Lungenklinik Berlin, Klinik für Pneumologie, 13125 Berlin, Germany. · Kinderherzzentrum und Zentrum für Angeborene Herzfehler, Justus-Liebig Universität, Zentrum für Kinderheilkunde, Abteilung Kinderkardiologie, 35390 Giessen, Germany. · Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden, Medizinische Klinik und Poliklinik I, 01307 Dresden, Germany. · Medizinische Hochschule Hannover, Zentrum für Pulmonale Hypertonie im Kindesalter/Klinik für pädiatrische Kardiologie und Intensivmedizin, 30625 Hannover, Germany. · Waldburg Zeil Kliniken Gmbh & Co. KG, Fachkliniken Wangen, Lungenzentrum Süd-West, Klinik für Pneumologie, Beatmungsmedizin und Allergologie, 88239 Wangen im Allgäu, Germany. · 2nd Dep. of Internal Medicine and Cardiology Center Hungary, Faculty of Medicine, Szent-Györgyi Albert Clinical Center, , University of Szeged, 6725 Szeged, Hungary. · Missionsärztliche Klinik gGmbH, Abteilung für Innere Medizin, 97074 Würzburg, Germany. · Medizinische Hochschule Hannover, Abt. Pneumologie, 30625 Hannover, Germany. · Universitätsklinik für Kinder- und Jugendmedizin Tübingen, Kinderkardiologie, Pulmologie, Intensivmedizin, 72076 Tübingen, Germany. · Kardiologie-Angiologie-Pneumologie, II. Medizinische Klinik des Klinikums Coburg, 96450 Coburg, Germany. · Faculty of Medicine of Vilnius University, Referal Centre of Pulmonary Hypertension, Vilnius University Hospital Santaros klinikos, 08661 Vilnius, Lithuania. · Gemeinnützige Krankenhausbetriebsgesellschaft Konstanz mbH, Medizinische Klinik II, 78464 Konstanz, Germany. · Universitätsklinikum Hamburg Eppendorf, Studienzentrale Pneumologie, 20251 Hamburg, Germany. · Universitätsklinikum Freiburg, Medizinische Klinik, Abteilung Pneumologie, 79106 Freiburg, Germany. · Universitätsmedizin Mainz, Center for Thrombosis and Hemostasis, 55131 Mainz, Germany. · LKH - Univ. Klinikum Graz, Universitätsklinik für Kinder- und Jugendheilkunde, Abteilung für Pädiatrische Kardiologie, 8036 Graz, Austria. · Universitäres Herzzentrum Hamburg, Klinik und Poliklinik für Kinderkardiologie, 20251 Hamburg, Germany. · Universitätsklinikum Schleswig-Holstein, Klinik für angeborene Herzfehler & Kinderkardiologie (Haus 9), 24105 Kiel, Germany. · Universitätsklinikum Ulm, Klinik für Innere Medizin II/Pneumologie, 89081 Ulm, Germany. · Westfälische Wilhelms-Universität Münster, Klinik für Kinder- und Jugendmedizin - Pädiatrische Kardiologie, 48149 Münster, Germany. · Universitätsklinikum Regensburg, Medizinische Klinik und Poliklinik II, 93053 Regensburg, Germany. · Klinikum der Universität München, Medizinische Klinik und Poliklinik V, 80336 München, Germany. · Klinik Schillerhöhe, Abteilung für Pneumologie und Beatmungsmedizin, 70839 Gerlingen, Germany. · DRK Kliniken Berlin Westend, Klinik für Innere Medizin, Schwerpunkt Kardiologie, 14050 Berlin, Germany. · Klinikum Lünen, St. Marien-Hospital GmbH, 44534 Lünen, Germany. · Herz- und Gefäßzentrum Bad Bevensen, 29549 Bad Bevensen, Germany. · Clinic of Rheumatology and Clinical Immunology, University of Lübeck, University Clinic Schleswig Holstein, 23562 Lübeck, Germany. · Fondazione IRCCS Policlinico San Matteo University of Pavia, 27100 Pavia- PV Italy, Germany. · Clinic for General and Interventional Cardiology/Angiology, Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum, 32545 Bad Oeynhausen, Germany. · Dept. Cardiology and Angiology, Faculty of Medicine, Slovak Medical University and National Institute of Cardiovascular Diseases, 83348 Bratislava, Slovakia. · Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik II, Innere Medizin-Kardiologie/Pneumologie, 53127 Bonn, Germany. · Pauls Stradins Clinical University Hospital, 1002 Riga, Latvia. · Klinik Löwenstein, Medizinische Klinik I, 74245 Löwenstein, Germany. · Universitäts-Herzzentrum Freiburg - Bad Krozingen, Klinik für Angeborene Herzfehler und Pädiatrische Kardiologie, 79189 Freiburg, Germany. · 2nd Critical Care Department, Attikon University Hospital, Chaidari, 12462 Athens, Greece. · Pulmonary Hypertension Center, Dept. Clnical, Anestesiologic and Cardiovascular Sciences, University of Rome La Sapienza, 00185 Rome, Italy. · VU Medical Center Amsterdam, 1081 Amsterdam, The Netherlands. · Universitätsklinikum des Saarlandes, Innere Medizin V, 66421 Homburg, Germany. · Universitätsklinikum Leipzig, Medizinische Klinik und Poliklinik I, Abteilung für Pneumologie, 04103 Leipzig, Germany. · Thoraxklinik Heidelberg gGmbH, Zentrum für Pulmonale Hypertonie, 69126 Heidelberg, Germany. · Universitätsklinik Köln- Herzzentrum, Klinik III für Innere Medizin, 50937 Köln, Germany. ·J Clin Med · Pubmed #32414075.

ABSTRACT: INTRODUCTION: Pulmonary hypertension (PH) is a common complication in patients with congenital heart disease (CHD), aggravating the natural, post-operative, or post-interventional course of the underlying anomaly. The various CHDs differ substantially in characteristics, functionality, and clinical outcomes among each other and compared with other diseases with pulmonary hypertension. OBJECTIVE: To describe current management strategies and outcomes for adults with PH in relation to different types of CHD based on real-world data. METHODS AND RESULTS: COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) is a prospective, international PH registry comprising, at the time of data analysis, >8200 patients with various forms of PH. Here, we analyzed a subgroup of 680 patients with PH due to CHD, who were included between 2007 and 2018 in 49 specialized centers for PH and/or CHD located in 11 European countries. At enrollment, the patients´ median age was 44 years (67% female), and patients had either pre-tricuspid shunts, post-tricuspid shunts, complex CHD, congenital left heart or aortic disease, or miscellaneous other types of CHD. Upon inclusion, targeted therapies for pulmonary arterial hypertension (PAH) included endothelin receptor antagonists, PDE-5 inhibitors, prostacyclin analogues, and soluble guanylate cyclase stimulators. Eighty patients with Eisenmenger syndrome were treatment-naïve. While at inclusion the primary PAH treatment for the cohort was monotherapy (70% of patients), with 30% of the patients on combination therapy, after a median observation time of 45.3 months, the number of patients on combination therapy had increased significantly, to 50%. The use of oral anticoagulants or antiplatelets was dependent on the underlying diagnosis or comorbidities. In the entire COMPERA-CHD cohort, after follow-up and receiving targeted PAH therapy ( CONCLUSIONS: In COMPERA-CHD, the overall survival of patients with CHD associated PH was dependent on the underlying diagnosis and treatment status, but was significantly better as than that for idiopathic PAH. Nevertheless, overall survival of patients with PAH due to CHD was still markedly reduced compared with survival of patients with other types of CHD, despite an increasing number of patients on PAH-targeted combination therapy.