Current Hypertension Reviews (v.13, #1)

Meet Our Co-Editor by Guido Grassi (1-1).

Early Vascular Ageing (EVA): Definitions and Clinical Applicability by Pedro Guimaraes Cunha, Pierre Boutouyrie, Peter M Nilsson, Stephane Laurent (8-15).
Arterial stiffness has been accumulating evidence as an intermediate cardiovascular endpoint. It has been established as an independent risk marker for cardiovascular disease, and reflects the dissociation between chronologic and biologic age of large arteries-attributing earlier the risk that a normal vascular ageing process had installed to occur several years later. The concept of Early Vascular Ageing (EVA) is developed to establish primordial prevention, identifying individuals whose ageing path has been accelerated either by inherent features, interaction with the environment or arterial exposure to several types of insults that evolve to medial layer morphological changes. Understanding the pathophysiology of vascular ageing, its consequences and therapeutic opportunities is therefore an advantage that could be translated in time of prevention and survival free of cardiovascular disease. As the EVA construct is advancing, new features appear as interesting to better translate it into clinical practice.

Microvascular Alterations in Hypertension and Vascular Aging by Carmine Savoia, Alleggra Battistoni, Valentin Calvez, Vincezo Cesario, Giulio Montefusco, Antonio Filippini (16-23).
Hypertension and aging are characterized by vascular remodelling and stiffness as well as endothelial dysfunction. Endothelial function declines with age, since aging is associated with senescence of the endothelium due to increased rate of apoptosis and reduced regenerative capacity of the endothelium. Different phenotypes of hypertension have been described in younger and adult subjects with hypertension. In younger patients, functional and structural alterations of resistance arteries occur as the earliest vascular alterations which have prognostic significance and may contribute to stiffness of large arteries through wave reflection. In individuals above age of 50 years as well as in subjects with long-lasting elevated blood pressure, vascular changes occur predominantly in conduit arteries which become stiffer. Activation of renin-angiotensin-aldosterone and endothelin systems plays a key role in endothelial dysfunction, vascular remodelling, and aging by inducing reactive oxygen species production, and promoting inflammation and cell growth.

It is becoming increasingly clear that both microvascular network alterations and subsequent tissue perfusion defects may precede and predict the development of arterial hypertension and other cardiovascular and metabolic diseases, including diabetes and metabolic syndrome. Moreover, the subsequent functional and structural alterations in microvascular reactivity and density, as well as alterations in the macrocirculation characteristic of physiologic vascular aging, contribute to the development of target organ damage. Microvascular rarefaction appears to be an early vascular structural alteration in the setting of hypertension, as it is already present in individuals presenting with borderline hypertension and normotensive young adults with a familial predisposition to high blood pressure. The chronic increases in blood pressure that occur during senescence secondary to macrocirculatory changes induce vasoconstriction within the microcirculation, which promotes the development of tissue hypoxia and reduces both arteriolar and capillary density. This phenomenon contributes to additional increases in peripheral vascular resistance and establishes a vicious cycle that culminates in both tissue injury and target organ damage, which are equally present in senescence and hypertension. Therefore, the microcirculation may be considered an essential target for both the pharmacological and non-pharmacological treatment of arterial hypertension and other cardiovascular diseases.

Potential Role of Endothelin in Early Vascular Aging by Michelle Trindade, Wille Oigman, Mario Fritsch Neves (33-40).
Early vascular aging is a process associated with gradual alterations in the vessels, regarding their structure and function, taking a more rapid course than normal biological aging in the arteries. In the presence of cardiovascular disease, these age-associated alterations are accelerated, contributing in the appearance or the progression of cardiovascular disease, such as high blood pressure, dyslipidemia, smoking and diabetes. Endothelin-1 (ET-1) is the most abundant and important endothelin produced by vascular cells. ET-1 exerts its biological actions through the activation of two receptors: ETA and ETB. Many important functions are mediated by the activation of these receptors, such as cardiovascular remodeling, vasoconstriction, cell proliferation and differentiation, production of extracellular matrix, and water and sodium secretion control. ETA receptor seems to participate in the pathogenesis and development of diseases, such as diabetes, atherosclerosis, systemic and pulmonary hypertension, and cardiac remodeling after myocardial ischemia, whereas ETB receptor seems to prevent the overstimulation of ETA receptor, acting as a clearance receptor. Increased ET-1 system activity may contribute to vascular dysfunction in aging via multiple pathways, such as direct hemodynamic effects, vascular oxidative stress, inflammatory activity, mitogenic stimulation of the vascular smooth muscle cells and fibrotic processes. Endothelin receptor antagonists were considered to be used for the treatment of some diseases like hypertension, diabetes and chronic kidney disease. However, besides pulmonary hypertension, this class is not in clinical use because of the side effects and the availability of safer drugs for the treatment of these diseases.

Management of Hypertension in Patients with Aortic Valvular Stenosis by Kanishk Agnihotri, Vikas Singh, Sidakpal S. Panaich, Nileshkumar J Patel, Nilay Patel, Shilpkumar Arora, Dhaval Pau, Abhishek Deshmukh, Apurva O Badheka (41-45).
Aortic stenosis (AS) has an increasing prevalence with age and is commonly associated with hypertension. While it has been established that hypertension is associated with increased mortality in patients with AS, further randomized control trials addressing the use of antihypertensives specifically in patients with AS are needed. The management of hypertension in patients with AS needs a cautious approach due to complex hemodynamic and structural changes involved. Comorbidities like coronary artery disease, heart failure and arrhythmias further dictate management of hypertension in patients with AS. The aim of this article is to review the various agents used in the management of hypertension in patients with AS.

Aldosterone binds to mineralocorticoid receptors (MRs) on renal epithelial cells to regulate sodium and water reabsorption, and therefore blood pressure. Recently, the actions of aldosterone outside the kidney have been extensively investigated, with numerous reports of aldosterone having detrimental actions, including in the vasculature. Notably, elevated aldosterone levels are an independent cardiovascular risk factor, and in addition to causing an increase in blood pressure, aldosterone can have blood pressure-dependent and -independent effects commonly manifested in the vasculature in cardiovascular diseases, including oxidative stress, endothelial dysfunction, inflammation, remodeling, stiffening, and plaque formation. Receptor-dependent mechanisms mediating these actions include the MR expressed on vascular endothelial and smooth muscle cells, but also include the angiotensin II type 1 receptor, epidermal growth factor receptor and vascular endothelial growth factor receptor 1, with downstream mechanisms including NADPH oxidase, cyclooxygenase, glucose-6-phosphate dehydrogenase, poly-(ADP ribose) polymerase and placental growth factor. The beneficial actions of MR antagonism in experimental hypertension include improved endothelial function, reduced hypertrophy and remodeling, and in atherosclerosis beneficial actions include reduced plaque area, inflammation, oxidative stress and endothelial dysfunction. Aldosterone excess is detrimental and MR antagonism is beneficial in humans also. The emerging concept of the contribution of aldosterone/MR-induced immunity to vascular pathology will also be discussed.

Background: Umbilical cord blood (UCB) is in contact with all the fetal tissues and can reflect the state of fetus and UCB can be compared with maternal blood. Inflammatory, metabolic and immunological disorders during pregnancy can affect the environment in which the fetus is developing and may produce various alterations.
Objective: To analyze different biochemical parameters in maternal venous blood and new born umbilical cord blood from healthy normotensive pregnant and preeclamptic women.
Materials and Methods: Homocysteine, folate, B12, heme oxygenase-1 (HO-1), endoglin, leptin, cholinesterase, IGF-1, Apo A, lipoproteins, TSH, fT3, fT4 were analyzed in maternal sera and venous umbilical cord sera of newborns of twenty five preeclamptics (group II) and twenty five normotensive pregnant women (group I). Homocysteine, folic acid, vitamin B12, Apo A I & II, TSH, fT3, fT4 levels were estimated by competitive immunoassay using direct chemiluminiscence technology. Heme oxygenase-1 (HO-1), endoglin, leptin, cholinesterase, IGF-1 were analyzed by ELISA.
Results: Maternal and cord blood levels of homocysteine, folic acid, lipid profile (namely, total cholesterol, triglycerides, LDL-C, VLDL-C and HDL-C), TSH, heme oxygenase 1, were higher in preeclamptic women as compared to normotensive pregnant women. Endoglin levels were significantly lower in cord blood of preeclamptic mother as compared to normotensive mothers. Serum and cord blood vitamin B12, Apo A-I and Apo B l, cholinesterase, leptin levels, IGF-I were lower in preeclamptic women as compared to normotensive pregnant.
Conclusion: Findings of the present study suggest that biochemical alterations occur in mothers and fetuses and modifications of uterine environment (in terms of thyroxine and folate and vitamin B12 supplementation) can be of help.

Background: Most populations around the world consume less than the recommended levels of potassium. Long term low potassium intake could lead to decreased plasma potassium levels and induce hypokalemia. The increasing of plasma potassium levels 0,2-0,4 mmol/L by improving potassium intake decreased significantly blood pressure (BP). Assessing plasma potassium levels in healthy people related to potassium intake have not been studied.
Objective: In this study, we analysed plasma potassium levels in prehypertension (PHT) subjects to evaluate the effect of tender coconut water (TCW) as a high potassium drink on plasma potassium levels in PHT adults.
Materials and Methods: Thirthy-two female aged 25-44 years were randomly allocated to 14 days on TCW or water in a parallel randomized clinical trial. The treatment (T) group received TCW 300 ml twice daily and the control (C) group received water 300 ml twice daily too.
Results: At baseline, plasma potassium levels was 3.71A±0.41 mmol/L, and 22.58% were categorized as hypokalemia. After 14 days treatment, potassium plasma level between T and C groups were not significantly different (p=0,247). The change of plasma potassium levels in both groups showed tendency to increase but not statistically significant difference was observed (p=0.166).
Conclusion: In healthy prehypertension women, the low levels of potassium plasma may be caused by low potassium intake for long time and intervension with TCW 300 ml twice daily for 14 consecutive days has not proven yet to increase plasma potassium levels. It is necessary to give higher dose and longer time to increase potassium plasma in low potassium plasma level subjects.

Background/Objective: Intraoperative hypotension (IOH) invariably follows the induction of general anesthesia during surgical operations. The current prevailing and predominant consensus is that IOH has immense clinical benefits such as reduced bleeding, less need for blood transfusions, and shorter surgery times. Simultaneously, it is assumed that IOH is devoid of adverse renal, hepatic and neurological consequences. Emerging new evidence and our experiences suggest a strong link between IOH and postoperative acute kidney injury (AKI).
Method/Case Reports: We report on three case presentations to illustrate the impact of IOH on postoperative AKI.
Conclusion: Our recent experiences suggest and show a link between IOH and postoperative AKI. Sun et al. (2015) recently demonstrated that postoperative AKI was associated with sustained intraoperative hypotensive periods of MAP <55 and <60 mm Hg, respectively, in a graded pattern. Our experiences and new emerging Surgery-AKI literature provide an impetus for clinical trials to be set up and completed to determine whether interventions that promptly treat IOH, or better still that prevent IOH, and that are tailored to suit individual patient physiology, would reduce the risk of AKI. We posit that IOH is a neglected cause of postoperative AKI. We call for a preventative nephrology paradigm shift and the targeting of MAP ≥ 60 mm Hg and/or SBP ≥ 90 mm Hg during surgical procedures. Particularly in sub-Saharan Africa with its paucity of renal replacement therapy options to manage kidney failure, every effort to limit AKI, SORO-ESRD and exacerbation of kidney dysfunction in general, must be vigorously applied.