Current Hypertension Reviews (v.12, #3)

Meet Our Editorial Board Member by Masaki Mogi (169-169).

Angiotensins and Their Receptors in Cardiac and Vascular Injury by Sebastian Schmull, Zhenhua Wang, Liping Gao, Jingjing Lv, Jun Li, Song Xue (170-180).
The renin-angiotensin system is involved in hypertension and, thus, in cardiac and vascular injury. In general, angiotensin II is considered as the main mediator of this system but angiotensin IIderived peptides were also shown to exert effects in such diseases. Moreover, it became obvious that different cell and corresponding tissue types are characterized by their own renin-angiotensin system. This system is composed of various peptidic derivatives of the precursor angiotensinogen. Those angiotensinogen-derived peptides can be processed further by peptidases and can bind corresponding receptors. Various clinical trials were initiated considering inhibition of the renin-angiotensin system at different stages in cardiac injuries. Recently, a phase 3 trial using infused angiotensin II (LJPC-501) as treatment option in catecholamine-resistent hypotension was established (ClinicalTrials.gov identifier NCT02338843) although it might be that an influence of AngII-derived peptides is not considered. In general, more intense research on AngII-derived peptides should result in novel strategies and therapeutic options in treatment of cardiac and vascular injuries since these peptides exert actions by themselves, some may interfere with AngII-mediated effects, and some can bind different receptors as well. Consequently, they may also become new promising therapeutics in clinical settings in the future. This short review introduces all currently known angiotensins at once, their production and role related to cardiac and vascular injury, which immune cells show renin-angiotensin system components, and how immune cells containing such components might be involved in such diseases as well.

Management of Hypertension in Patients with Chronic Kidney Disease in Asia by Qi-Fang Huang, Satoshi Hoshide, Hao-Min Cheng, Sungha Park, Chang-Gyu Park, Chen-Huan Chen, Kazuomi Kario, Ji-Guang Wang, on behalf of the Characteristics On the Management of Hypertension in Asia-Morning Hypertension Discussion Group(COME Asia MHDG) (181-185).
Hypertension is both a cause and consequence of chronic kidney disease (CKD). According to the Chinese national survey in 2007-2010, the prevalence of CKD was much higher in hypertensive patients (18.9%, n=16,691) than in the overall population sample (10.8%, n=47,204). CKD in hypertension confers risks to the kidneys as well as other organs. Probably because of high dietary salt intake, Asian hypertensive patients with CKD show high prevalence of non-dipping and reversed dipping blood pressure pattern, and may have even higher risks of cardiovascular disease. Therefore, out-of-office blood pressure evaluation and comprehensive cardiovascular evaluations are required. Most of current hypertension guidelines recommend intensive antihypertensive treatment in hypertensive patients with CKD. This is probably of particular relevance for cardiovascular prevention in Asia, because stroke, as a major complication of hypertension in Asia, is more closely related to blood pressure than coronary events. Intensive blood pressure control to 130/80 mmHg is often required to prevent CKD progression and cardiovascular complications. The inhibitors of the renin-angiotensin system (RAS) are recommended as the first line antihypertensive medications in patients with a glomerular filtration rate higher than 30 ml/min/1.73 m2, which may more efficaciously prevent end-stage renal disease and cardiovascular events. Nonetheless, combination therapy of RAS inhibitors with other classes of antihypertensive drugs, such as calcium-channel blockers, diuretics, etc, is required to control blood pressure to the target.

Hypertension in the Neonatal Period: An Update by Anish Pillai, Deepak Sharma, Pratichi Kadam (186-195).
There has been a growing interest among neonatologists and paediatricians regarding identification and evaluation of hypertension in the neonatal period. Despite the emergent normative data on blood pressure values in term and preterm neonates over the last two decades, there is still controversy regarding correct definition and classification of hypertension. This article will discuss the current definitions, available normative data and etiology of neonatal hypertension. There is paucity of records in terms of efficacy of antihypertensive drugs in this specific population and management is usually experience based, causing considerable heterogeneity amongst different units. This review article will also cover the evaluation, management, outcomes and follow up of neonatal hypertension with latest advances in this field.

A Review of Hypertension Management in Atrial Fibrillation by Sidakpal S. Panaich, Nilay Patel, Kanishk Agnihotri, Shilpkumar Arora, Chirag Savani, Nileshkumar J. Patel, Samir V. Patel, Rajesh Sonani, Achint Patel, Sopan Lahewala, Vikas Singh, Badal Thakkar, Parth Bhatt, Abhishek Deshmukh, Apurva O. Badheka (196-202).
Atrial fibrillation (AF) is one of the commonest arrhythmias in clinical practice and has major healthcare and economic implications. It is a growing epidemic with prevalence all set to double to 12 million by 2050. After adjusting for other associated conditions, hypertension confers a 1.5- and 1.4-fold risk of developing AF, for men and women respectively. Furthermore, in patients with AF, the presence of hypertension has a cumulative effect on the risk of stroke. Growing evidence suggests reversal or attenuation of various structural and functional changes predisposing to AF with the use of antihypertensive medications. Randomized trials have shown major reduction in the risk of stroke and heart failure with blood pressure reduction. However, such trials are lacking in AF patients specifically. The Joint National Committee-8 guidelines have not addressed the threshold or goal BP for patients with known AF. Furthermore, “J-shaped” or “U-shaped” curves have been noted during hypertension management in patients with AF with published data demonstrating worse outcomes in patients with strict BP control to <110/60 mmhg similar to coronary artery disease. In this review, we outline the available literature on management of hypertension in patients with AF as well as the role of individual anti-hypertensive medications in reducing the incidence of AF Fig. 1.

Psychological Stress in Pathogenesis of Essential Hypertension by Alexey V. Ushakov, Vera S. Ivanchenko, Alina A. Gagarina (203-214).
The article represents literature review and provides evidence for psychological stress to play essential role in the development of arterial hypertension. The pathogenesis of hypertension is complex with a significant diversity and variability of the mechanisms involved in individual patient. In this regard, the determination of specific pathogenic pathways underlying sustained blood pressure elevation in each patient would substantially individualize therapeutic approaches, and hence increase the effectiveness of treatment. Psychological stress is proposed as a significant factor contributing to the development of hypertension. Global urbanization, sedentary lifestyle, daily stress at workplace, lack of physical activity and social support lead to increased anxiety, uncertainty, and finally to chronic mental and emotional stress. This review provides information about alterations in neuroendocrine and immune systems as the main pathogenic pathways linking psychological stress and hypertension. Endothelial dysfunction is considered not only as a consequence but also a primary factor causing prohypertensive state. Moreover, physical inactivity is discussed as one of the plausible mechanisms playing a key role in the development of hypertension in modern lifestyle conditions. Particularly the loss of connection between psychosocial strain and physical activity may underlie the deleterious effect of stress on cardiovascular and metabolic health.

High Blood Pressure Combined with Sedentary Behavior in Young People: A Systematic Review by Loreana Sanches Silveira, Daniela Sayuri Inoue, Jose Messias Rodrigues da Silva, Suziane Ungari Cayres, Diego Giulliano Destro Christofaro (215-221).
Background: High blood pressure (HBP) is a cardiovascular risk factor that can initiate in childhood and adolescence and may be associated with other risk factors such as sedentary lifestyles. Therefore, verifying if these associations occur from the earliest ages is of fundamental importance.

Objectives: to report the prevalence of HBP combined with sedentary behavior through a systematic review.

Design and Methods: The research was performed based on studies published between 2010 and 2016 in Medline, Web of Science, Excerpta Medica (EMBASE), and Scielo, using terms related to: 'sedentary behavior' OR 'screen time' AND 'high blood pressure'. In the initial search, 821 studies were found and after exclusions twelve studies were included in the review.

Results: Twelve studies addressing the relationship between sedentary behavior and HBP were found. Eighty-three percent of the studies evaluated sedentary behavior using a questionnaire (n = 10). The majority of studies analyzed in the review were conducted in North America (41.6%). Only four studies presented the prevalence of HBP related to sedentary behavior (variation 1-22.9%). In seven studies a close relationship between sedentary behavior and HBP was observed.

Conclusions: Although most studies observed a relationship between sedentary behavior and HBP, the results still need to be further explained. Based on the findings of this review, follow-up studies and objective measurements of time spent in sedentary behavior in young people could help to determine the cause-effect relationship between sedentary behavior and HBP in pediatric populations.


Laparoscopic Surgery for Pheochromocytoma and Paraganglioma Removal: A Retrospective Analysis of Anaesthetic Management by Rashmi Ramachandran, Vimi Rewari, Ankur Sharma, Rajeev Kumar, Anjan Trikha (222-227).
Introduction: Minimal invasive approaches to pheochromocytoma (PCC) and paraganglioma (PGL) removal may be complicated by the hemodynamic disturbances that are associated with the catecholamine secretion from the tumour. The anaesthetic and perioperative monitoring techniques need to be customized to handle these complications effectively. This retrospective analysis was undertaken to review the perioperative management of these patients handled by the same anaesthetic and surgical team.

Methods: Case details were collected and data analysed for the perioperative management of 29 patients who underwent laparoscopic removal of PCC and PGL. Parameters collected included details of preoperative alpha-and beta blockade, tumour size, number of hypertensive surges, dose of sodium nitroprusside (SNP) and other vasodilators used and incidence of postoperative hypotension and other complications.

Results: All patients received prazosin for pre-operative optimization. Hypertensive emergencies were seen in 4 patients during induction and endotracheal intubation and in 1 patient during pneumoperitoneum insufflation. Overall mean number of hypertensive emergencies was 3.41 (SD-2.45). The patients undergoing PGL removal had significantly more crisis compared to those undergoing unilateral PCC removal. The dose of SNP used correlated significantly with tumour size.

Conclusion: Laparoscopic surgery for PCC and PGL removal is associated with hypertensive emergencies which are amenable to usual doses of antihypertensives used intraoperatively. Surgical factors like tumour size and location affect the number of crisis and the dose of anti-hypertensives used more than the anaesthetic drugs and procedures.


Biomarkers in Preeclamptic Women with Normoglycemia and Hyperglycemia by Simmi Kharb, Prerna Panjeta, Veena S. Ghalaut, Jyoti Bala, Smiti Nanda (228-233).
The present study was planned to assess IGF-1, leptin and cholinesterase levels in maternal blood of both normoglycaemics and hyperglycaemics preeclampsia. Twenty five normotensive pregnant women at the time of delivery were selected in as group I and sub grouped according to blood glucose less than or more than 85 mg/dL as I A (<85mg/dL) and I B (>85mg/dL). Study group (group II, n=25) comprised of preeclamptic women and was further divided into group II A (<85mg/dL) and group II B (>85mg/dL). Routine biochemical investigations along with IGF-1, leptin and cholinesterase levels were analyzed in maternal and cord blood of preeclamptic and normotensive pregnant women. Serum IGF-1 levels were significantly lower in preeclamptic women and more so in those with hyperglycemia. Cord blood IGF-1 levels were nearly doubled in hyperglycemic preeclamptics as compared to normoglycemic preeclamptics. Leptin levels were higher in preeclamptic women and more in hyperglycemic preeclamptics. Cholinesterase levels were lowered in preeclamptic mothers and higher in hyperglycemics. Cord blood cholinesterase levels were reduced in preeclamptics, more so in hyperglycaemics as compared to group I. Diet recommendation, avoidance of excessive weight gain and healthy life style, exercise and nutritional interventions may be beneficial in these women.

Background: Folate, vitamin B12 and vitamin B6 are required for homocysteine metabolism and their deficiency can result in increased homocysteine concentration. Homocysteine concentrations have been found to be increased in late pregnancy toward nonpregnant values.

Objective: To study folate, vitamin B12 and homocysteine levels in cord blood and maternal blood in preeclampsia.

Materials and Methods: One hundred fifty pregnant women attending Out Patient Department of Department of Obstetrics and Gynaecology were recruited for the study. Grouped as: GROUP I (control): Fifty normotensive women with singleton pregnancy immediately after delivery; GROUP II (study): Fifty (age and gestation matched women with singleton pregnancy) women with preeclampsia immediately after delivery; GROUP III (study): Fifty normotensive pregnant women were recruited in first trimester (8-12 weeks) that were followed in second (24-28 weeks) and third trimester (32-36 weeks). Homocysteine, vitamin B12 and folic acid levels were investigated by competitive immunoassay using direct chemiluminiscence technology.

Results: Homocysteine and folic acid levels were higher in maternal blood of hypertensive pregnant women as compared to normotensive pregnant women (p<0.001, p>0.05 respectively). Vitamin B12 levels were lower in maternal blood of hypertensive pregnant women as compared to normotensive pregnant women. Levels of homocysteine were higher in cord blood of hypertensive pregnant women as compared to normotensive pregnant women (p<0.01). Levels of vitamin B12 and folic acid was lower in cord blood of preeclamptic women as compared to normotensive pregnant women (p<0.001, p<0.01 respectively). A negative correlation was found between homocysteine and folic acid levels of mothers in group II that was statistically significant.

Conclusion: Elevated homocysteine and folate and vitamin B12 deficiency during pregnancy may be a risk factor for preeclampsia and future risk of cardiovascular risk.