Article by Disease – “Efficacy and Safety Assessment of Hypertension Management with Coveram (Perindopril/Amlodipine Fixed Combination) in Patients with Previous Angiotensin Receptor Blocker (ARB) Treatment: Arabian Gulf STRONG Study”

Article by Disease on “Cardiology


Objective: We evaluated the safety and efficacy of hypertension management with Coveram (perindopril/amlodipine combination) in patients with uncontrolled blood pressure (BP). All patients were on previous angiotensin receptor blocker (ARB) treatment.

Methods: This was a 3 country, multi-centre (7 cities), open-label, observational study in the Arabian Gulf. Patients (18 years) were recruited between October 2012 and November 2013 and followed-up for 3 months after enrolment. Outcomes included changes in BP from baseline and BP goal attainment rates as per Joint National Committee- 8 (<140/90 mmHg for diabetics and those <60 years of age and <150/90 mmHg for those 60 years of age without diabetes). Medication tolerance was also assessed from both patient and physician perspectives.

Results: Hypertensive patients (n=760; mean age: 51±10 years; 67% were males) were included. A total of 178 patients (23%) were lost to follow-up. The perindopril/amlodipine combination was associated with an overall reduction in systolic BP (SBP) (31 mmHg; p<0.001) and diastolic BP (DBP) (18 mmHg; p<0.001) from baseline. An overall BP control rate was achieved in 87% (n=507) of the participants. There were significant incremental BP reductions with dose up-titration, especially SBP (p<0.001). Those with high SBP (>180 mmHg) at baseline were associated with a mean reduction of 59 mmHg (p<0.001). The perindopril/amlodipine combination had excellent tolerance levels over the study period from both patient and physician perspectives (at 99% and 98%, respectively; p<0.001).

Conclusions: The perindopril/amlodipine combination is an effective and well tolerated anti-hypertensive option in patients on previous ARB treatment.

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“The Epidemiology of Sleep Disordered Breathing and Hypertension in Various Populations”

On World Hypertension Day, here is an article from Volume 12, Issue 1 of the journal “Current Hypertension Reviews

Author(s): Hiroyuki Sawatari, Akiko Chishaki and Shin-ich Ando

chrAbstract: Hypertension is prevalent in patients with sleep disordered breathing (SDB). Since hypertension significantly relates to cardiovascular diseases, the treatment and prevention of SDB could be targets for the prevention of cardiovascular diseases. In this article, we summarize about epidemiology of SDB and hypertension in various populations. General population based studies on the prevalence of SDB reported that 24 to 47% male and 9 to 30% female had SDB. Furthermore, the prevalence of hypertension in individuals with SDB was high, ranging from 36 to 57%. American and Korean based studies reported that the severity of SDB related to increase of blood pressure and hypertension. In the elderly, however, the severity of SDB did not relate to increase in blood pressure and hypertension, but to dipping pattern of blood pressure. With respect to children, the severity of SDB also related to increase in blood pressure, but the trend was inconstant in children with habitual snoring. In addition to the sexual differences, the severity of SDB related to hypertension in males. On the other hand, there was no relationship between the severity of SDB and hypertension in females. SDB was prevalent in the general population, regardless of race, and affected blood pressure. We should pay attention to the subjects’ individual character when we interrupt the outcome.

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World Hypertension Day 2016!

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World Hypertension Day is held on the 17th of May every year. This day is designated to the control and awareness of hypertension, or high blood pressure. Looking at the importance of this day, Bentham Science Publishers has just the right research journal for it called;

Current Hypertension Reviews


Press Release for EurekAlert! – Anti-VEGF anticancer drugs: Mind the Hypertension

The introduction of targeted therapies has revolutionized the management of cancer patients. Agents that target the vascular endothelial growth factor (VEGF), called anti-VEGF, have been administrated for the treatment of various cancer types, inhibiting the carcinogenetic procedure of angiogenesis.

Though their beneficial impact on cancer patients’ outcome, anti-VEGF drugs are accompanied with a broad spectrum of side effects. After searching the literature, we focused on the association between mainly used anti-VEGF anticancer drugs and hypertension (HTN).

Many factors are involved in the emergence of HTN in these patients such as reduced levels of nitric oxide (NO) and/or microvascular rarefaction. The incidence of HTN is high and dependent on which agent is used for treating cancer patients.

In two large meta-analyses, bevacizumab-treated patients had an incidence of developing HTN up to 24% while patients with renal cell carcinoma and gastrointestinal stromal tumors treated with sunitinib had a HTN incidence of approximately 22%. Antihypertensive therapies (i.e angiotensin-converting enzyme inhibitors, b-blockers or diuretics) have been used for the management of anti-VEGF-induced HTN.

Interestingly, the onset of HTN can be considered as a possible biomarker of clinical response to VEGF inhibition (VEGFi) treatment, seeming to be correlated with better overall survival (OS) and prolonged  progression free survival  in these patients.

Close monitoring of blood pressure (BP) levels, early BP control, proper therapeutic interventions are crucial points in the management of HTN caused by VEGFi. In severe hypertensive cases, discontinuation of anti-VEGF agents or switching to another treatment option might be required. Further research is needed for this exact entity to be elucidated and proper algorithms for HTN handling should be proposed for the optimal benefit of cancer patients.

Read the recently published research on “Anti-VEGF Anticancer Drugs: Mind the Hypertension” from the journal “Recent Advances in Cardiovascular Drug Discovery” by Dr. Zerdes Ioannis.

Dark chocolate and blood pressure


The goal of this study was to assess the effect of dark chocolate intake on cardiovascular parameters like blood pressure and heart rate values in a normotensive population.

This article is from the journal Current Drug Delivery

Hypertension; Symptoms, Causes & Prevention



For reading latest research articles related to hypertension, please visit our journal Current Hypertention Reviews



World Hypertension Day – 17 May 2015

Bentham Science Publishers contributes in creating awareness on #hypertension on World Hypertension Day 17th May 2015

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Read the latest research on hypertension in the journal Current Hypertension Reviews

Current Hypertension Reviews publishes frontier reviews, original research articles and guest edited thematic issues on all the latest advances on hypertension and its related areas e.g. nephrology, clinical care, and therapy. The journal’s aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all clinicians and researchers in the field of hypertension.

Recently Published Issue Of the Journal Current Hypertension Reviews

Current Hypertension Reviews publishes frontier reviews, original research articles and guest edited thematic issues on all the latest advances on hypertension and its related areas e.g. nephrology, clinical care, and therapy. The journal’s aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all clinicians and researchers in the field of hypertension.
Following are the articles from the journal Current Hypertension Reviews, volume 10 issue 2:
  • Author(s): Biagio R. Di Iorio


Major Article Contributions by some of the Japanese Authors of Bentham Science Publishers Journal; Current Protein & Peptide Science

7-28-2014 9-06-18 AM

Journal Title: Current Protein & Peptide Science

Article Title: Exploring New CGRP Family Peptides and their Receptors in Vertebrates

Author(s): Yoshio Takei, Maho Ogoshi and Shigenori Nobata


Vertebrates have expanded their habitats from aquatic to terrestrial environments, which has accompanied the evolution of cardiovascular and osmoregulatory hormones. Specifically, mammals have developed mechanisms to maintain high blood pressure and blood volume, while extant fishes have developed hypotensive and Na-extruding mechanisms to adapt to the marine environment where they underwent a vast diversification. The CGRP family is one of the hormone systems that decrease blood pressure and blood volume. Within the CGRP family of teleost fishes, we found that adrenomedullins (AMs) have diversified and five paralogs (AM1-5) form an independent subfamily. Based on this discovery in fishes, we found AM2 and AM5 in mammals. In mammalian species that have AM2 and/or AM5, the peptides assume greater importance in the case of pathophysiological disturbances in pressure and fluid balance such as hypertension and cardiac and renal failure. In addition, novel functions of AM peptides have been suggested by the discovery of AM2 and AM5 in mammals. Current research on the CGRP family is focused on the identification of new receptors for AM2/AM5 and the establishment of AM2 knockout mice, which will enable new developments in the basic and clinical research on this intriguing hormone family. Importantly, comparative fish studies can contribute to new developments in our understanding of the function of the AM peptides.
Article Title: Functions of Third Extracellular Loop and Helix 8 of Family B GPCRs Complexed with RAMPs and Characteristics of their Receptor Trafficking
Author(s): Kenji Kuwasako, Debbie L Hay, Sayaka Nagata, Manabu Murakami, Kazuo Kitamura and Johji Kato


At least one of three receptor activity-modifying proteins (RAMP1, RAMP2 and RAMP3) can interact with 10 G protein-coupled receptors (GPCRs; nine Family B GPCRs and a Family C GPCR). All three RAMPs interact with the calcitonin (CT) receptor (CTR), the CTR-like receptor (CLR), the vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating polypeptide (PACAP) 1 (VPAC1) and the VPAC2 receptor, which are all Family B GPCRs. Three RAMPs enable CTR to function as three heterodimeric receptors for amylin, which is a feeding suppression peptide. These RAMPs also transport the CLR to the cell surface, where they function as a CT gene-related peptide (CGRP) receptor (CLR/RAMP1 heterodimer) and two adrenomedullin (AM) receptors (CLR/RAMP2 and CLR/RAMP3 heterodimers). CGRP and AM are potent hypotensive peptides that exert powerful protective effects against multi-organ damage. We recently reported that the third extracellular loop (ECL3) of CLR governs the activation of AM, but not CGRP, signaling in the three CLR/RAMP heterodimers. Furthermore, we showed that in the presence of RAMP2, the eighth helix (helix 8) in the proximal portion of the cytoplasmic C-terminal tail of the CLR, which is thought to be present in all family B GPCRs, participates in receptor signaling. In addition, we demonstrated that overexpression of GPCR kinase (GRK) 2, GRK3 and GRK4 enhances the AM-induced internalization of the CLR/RAMP2 heterodimer. In this review, we describe these studies and consider their implications for other Family B GPCRs that can interact with RAMPs.

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Article Title: Adrenomedullin as a Potential Therapeutic Agent for Inflammatory Bowel Disease

Author(s): Shinya Ashizuka, Haruhiko Inatsu, Kyoko Inagaki-Ohara, Toshihiro Kita and Kazuo Kitamura


Adrenomedullin (AM) was originally isolated from human pheochromocytoma as a biologically active peptide with potent vasodilating action but is now known to exert a wide range of physiological effects, including cardiovascular protection, neovascularization, and apoptosis suppression. A variety of tissues, including the gastrointestinal tract, have been shown to constitutively produce AM. Pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-1, and lipopolysaccharides, induce the production and secretion of AM. Conversely, AM induces the downregulation of inflammatory cytokines in cultured cells. Furthermore, AM downregulates inflammatory processes in a variety of different colitis models, including acetic acid-induced colitis and dextran sulfate sodium-induced colitis. AM exerts antiinflammatory and antibacterial effects and stimulates mucosal regeneration for the maintenance of the colonic epithelial barrier. Here, we describe the first use of AM to treat patients with refractory ulcerative colitis. The results strongly suggest that AM has potential as a new therapeutic agent for the treatment of refractory ulcerative colitis.
Article Title: Ectodomain Structures of the CGRP and AM Receptors
Author(s): Seisuke Kusano and Shigeyuki Yokoyama


Receptor activity-modifying proteins (RAMPs) 1–3, which are classified as type I transmembrane proteins, serve as the partner proteins of several family B GPCRs for physiologically active peptides, including the calcitonin receptor- like receptor (CLR). The properties of the GPCRs are defined by the RAMP and peptide ligand combination. The CLR•RAMP1 heterodimer functions mainly as the calcitonin gene-related peptide (CGRP) receptor, while the CLR•RAMP2 and CLR•RAMP3 heterodimers primarily function as the adrenomedullin 1 and adrenomedullin 2 (AM1 and AM2) receptors, respectively. The crystal structures of the RAMP1 and RAMP2 ectodomains exhibited three-helix bundles, and those of their complexes with the N-terminal extracellular domain of CLR revealed how the two ectodomains associate to form the CGRP and AM1 receptors, respectively. On this structural framework, the various intermolecular interactions of CLR with RAMP1 and RAMP2 result in the distinct shapes of the putative ligand-binding sites, where several residues are uniquely presented. Therefore, the differences in the shapes and the presented residues of the binding sites determine the specificities of the receptors to either CGRP or AM. These structural features of the ectodomains are consistent with mutagenesis results, and are useful to further examine the binding modes of the peptide ligands to the full-length CGRP and AM1 receptors.

Article Title: Insulin Resistance-Induced Hypertension and a Role of Perivascular CGRPergic Nerves

Author(s): Shingo Takatori, Yoshito Zamami, Narumi Hashikawa-Hobara and Hiromu Kawasaki


Insulin resistance is defined as a preliminary step of type 2 diabetes mellitus with decreased insulin action evoked by continuous postprandial hyperglycemia, which is provoked by high fat and calories dieting, a lack of physical activity and obesity. In the early phase of type 2 diabetes mellitus, patients have a hyperinsulinemia to compensate deficient insulin action by increased secretion from the pancreas to maintain euglycemia. Then, pancreatic β cells progressively decrease secretion function, resulting in the development of diabetes mellitus with decreased serum insulin levels. Accumulating evidences show that insulin resistance is associated with hypertension. However, the mechanisms underlying hypertension associated with type 2 diabetes mellitus have still unknown. Therefore, to elucidate the mechanisms of insulin resistance-induced hypertension, we investigated that the effects of hyperinsulinemia or hyperglycemia on vascular responses mediated by perivascular nerves including sympathetic adrenergic nerves and calcitonin gene-related peptide (CGRP)-containing nerves (CGRPergic nerves). In this article, we show evidence that insulin resistance-induced hypertension could be resulted from increased density and function of sympathetic nerve, and decreased density and function of CGRPergic nerves. Furthermore, our findings provide a new insight into the research of therapeutic drugs for insulin resistance- induced hypertension.