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Microcirculation and Macrocirculation in Hypertension: A Dangerous Cross-Link?
Laurent, S, Agabiti-Rosei, C, Bruno, RM, Rizzoni, D
Hypertension (Dallas, Tex. : 1979). 2022;(3):479-490
Abstract
Microcirculation and macrocirculation are tightly interconnected into a dangerous cross-link in hypertension. Small artery damage includes functional (vasoconstriction, impaired vasodilatation) and structural abnormalities (mostly inward eutrophic remodeling). These abnormalities are major determinants of the increase in total peripheral resistance and mean blood pressure (BP) in primary hypertension, which in the long term induces large artery stiffening. In turn, large artery stiffening increases central systolic and pulse pressures, which are further augmented by wave reflection in response to the structural alterations in small resistance arteries. Finally, transmission of high BP and flow pulsatility to small resistance arteries further induces functional and structural abnormalities, thus leading to increased total peripheral resistance and mean BP, thus perpetuating the vicious circle. Hyperpulsatility, in addition to higher mean BP, exaggerates cardiac, brain, and kidney damages and leads to cardiovascular, cerebral, and renal complications. The dangerous cross-link between micro and macrocirculation can be reversed into a virtuous one by ACE (angiotensin-converting enzyme) inhibitors, sartans, and calcium channel blockers. These three pharmacological classes are more potent than β-blockers and diuretics for reducing arterial stiffness and small artery remodeling. The same ranking was observed for their effectiveness at reducing left ventricular hypertrophy, preserving glomerular filtration rate, and preventing dementia, suggesting that they can act beyond brachial BP reduction, by breaking the micro/macrocirculation vicious circle.
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The Effect of Local Renin Angiotensin System in the Common Types of Cancer.
Almutlaq, M, Alamro, AA, Alamri, HS, Alghamdi, AA, Barhoumi, T
Frontiers in endocrinology. 2021;:736361
Abstract
The Renin Angiotensin System (RAS) is a hormonal system that is responsible for blood pressure hemostasis and electrolyte balance. It is implicated in cancer hallmarks because it is expressed locally in almost all of the body's tissues. In this review, current knowledge on the effect of local RAS in the common types of cancer such as breast, lung, liver, prostate and skin cancer is summarised. The mechanisms by which RAS components could increase or decrease cancer activity are also discussed. In addition to the former, this review explores how the administration of AT1R blockers and ACE inhibitors drugs intervene with cancer therapy and contribute to the outcomes of cancer.
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Arterial hypertension.
Brouwers, S, Sudano, I, Kokubo, Y, Sulaica, EM
Lancet (London, England). 2021;(10296):249-261
Abstract
Arterial hypertension is the most important contributor to the global burden of disease; however, disease control remains poor. Although the diagnosis of hypertension is still based on office blood pressure, confirmation with out-of-office blood pressure measurements (ie, ambulatory or home monitoring) is strongly recommended. The definition of hypertension differs throughout various guidelines, but the indications for antihypertensive therapy are relatively similar. Lifestyle adaptation is absolutely key in non-pharmacological treatment. Pharmacologically, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, calcium channel blockers, and diuretics are the first-line agents, with advice for the use of single-pill combination therapy by most guidelines. As a fourth-line agent, spironolactone should be considered. The rapidly evolving field of device-based therapy, especially renal denervation, will further broaden therapeutic options. Despite being a largely controllable condition, the actual rates of awareness, treatment, and control of hypertension are disappointingly low. Further improvements throughout the process of patient screening, diagnosis, treatment, and follow-up need to be urgently addressed.
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Nocturnal Hypertension and Heart Failure: Mechanisms, Evidence, and New Treatments.
Kario, K, Williams, B
Hypertension (Dallas, Tex. : 1979). 2021;(3):564-577
Abstract
Heart failure (HF) is a common condition with an increasing prevalence. Despite a variety of evidence-based treatments for patients with HF with reduced ejection fraction, morbidity and mortality rates remain high. Furthermore, there are currently no treatments that have yet been shown to reduce complication and death rates in patients who have HF with preserved ejection fraction. Hypertension is a common comorbidity in patients with HF, contributing to disease development and prognosis. For example, hypertension is closely associated with the development of left ventricular hypertrophy, which an important precursor of HF. In particular, nighttime blood pressure (BP) appears to be an important, modifiable risk factor. Both nighttime BP and an abnormal circadian pattern of nighttime BP dipping have been shown to predict development of HF and the occurrence of cardiovascular events, independent of office BP. Key mechanisms for this association include sodium handling/salt sensitivity and increased sympathetic activation. These pathogenic mechanisms are targeted by several new treatment options, including sodium-glucose cotransporter 2 inhibitors, angiotensin receptor neprilysin inhibitors, mineralocorticoid receptor antagonists, and renal denervation. All of these could form part of antihypertensive strategies designed to control nighttime BP and contribute to the goal of achieving perfect 24-hour BP management. Nevertheless, additional research is needed to determine the effects of reducing nighttime BP and improving the circadian BP profile on the rate of HF, other cardiovascular events, and mortality.
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5.
Blood Pressure in Childhood and Adolescence.
Hardy, ST, Urbina, EM
American journal of hypertension. 2021;(3):242-249
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Abstract
Elevated blood pressure (BP) and hypertension commonly occur in children and adolescents and increase the risk of cardiovascular disease in adulthood. The purpose of this review is to summarize recent research in pediatric hypertension including changes in defining hypertension, BP measurement techniques, hypertension epidemiology, risk factors, treatment, and BP-related target organ damage. Defining pediatric hypertension using the 2017 American Academy of Pediatrics' updated Clinical Practice Guideline resulted in a larger proportion of children being classified as having elevated BP or hypertension compared with prior guidelines. Trends in the distribution of BP among US children and adolescents suggest that BP levels and the prevalence of hypertension may have increased from 2011-2014 to 2015-2018. Factors including a family history of hypertension, obesity, minority race/ethnicity, physical inactivity, high dietary intake of sodium, and poor sleep quality are associated with an increased prevalence of elevated BP and hypertension. Evidence of a linear relationship between systolic BP and target organ damage indicates that BP levels currently considered normal could increase the risk of target organ damage in childhood. Lifestyle changes, such as adhering to the Dietary Approaches to Stop Hypertension diet, are a central component of effectively reducing BP and have been shown to reduce target organ damage. Pharmacologic treatment using angiotensin-converting enzyme inhibitors and angiotensin receptor blockers is an effective and safe method for reducing BP among children with uncontrolled BP after implementing lifestyle changes. Research gaps in the prevention, detection, classification, and treatment of hypertension in children demonstrate opportunities for future study.
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Hypertension in Diabetes: An Update of Basic Mechanisms and Clinical Disease.
Jia, G, Sowers, JR
Hypertension (Dallas, Tex. : 1979). 2021;(5):1197-1205
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Epidemiological studies have documented that insulin resistance and diabetes not only constitute metabolic abnormalities but also predispose to hypertension, vascular stiffness, and associated cardiovascular disease. Meanwhile, excessive arterial stiffness and impaired vasorelaxation, in turn, contribute to worsening insulin resistance and the development of diabetes. Molecular mechanisms promoting hypertension in diabetes include inappropriate activation of the renin-angiotensin-aldosterone system and sympathetic nervous system, mitochondria dysfunction, excessive oxidative stress, and systemic inflammation. This review highlights recent studies which have uncovered new underlying mechanisms for the increased propensity for the development of hypertension in association with diabetes. These include enhanced activation of epithelial sodium channels, alterations in extracellular vesicles and their microRNAs, abnormal gut microbiota, and increased renal sodium-glucose cotransporter activity, which collectively predispose to hypertension in association with diabetes. This review also covers socioeconomic factors and currently recommended blood pressure targets and related treatment strategies in diabetic patients with hypertension.
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Effects of the Dietary Approaches to Stop Hypertension Diet and Sodium Reduction on Blood Pressure in Persons With Diabetes.
Tseng, E, Appel, LJ, Yeh, HC, Pilla, SJ, Miller, ER, Juraschek, SP, Maruthur, NM
Hypertension (Dallas, Tex. : 1979). 2021;(2):265-274
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Abstract
Elevated blood pressure and blood pressure-related morbidity are extraordinarily common in persons with diabetes. The Dietary Approaches to Stop Hypertension dietary pattern and dietary sodium reduction are recommended as lifestyle interventions in individuals with diabetes. However, these recommendations have largely been based on studies conducted in persons without diabetes. In this review, we summarize available evidence from trials that tested the effects of these 2 dietary interventions on blood pressure in people with diabetes. Overall, of the 3 trials (total n=151) that tested the effects of the Dietary Approaches to Stop Hypertension dietary pattern in persons with diabetes, 2 trials documented that the Dietary Approaches to Stop Hypertension dietary pattern lowered blood pressure. While 16 trials (total n=445) tested the effects of sodium reduction in persons with diabetes, results were inconsistent, likely because of design limitations, for example, brief duration, small sample size, and low baseline blood pressure levels, as well as differences in the mode of intervention delivery (behavioral interventions, feeding studies, and sodium supplements). In conclusion, there is a substantial need for additional research on the blood pressure lowering effects of the Dietary Approaches to Stop Hypertension diet and sodium reduction in people with diabetes and hypertension, given the high prevalence of hypertension and the dearth of high-quality trials in this population.
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Omega-3 Polyunsaturated Fatty Acids: Versatile Roles in Blood Pressure Regulation.
Wang, H, Li, Q, Zhu, Y, Zhang, X
Antioxidants & redox signaling. 2021;(10):800-810
Abstract
Significance: Hypertension is characterized as the imbalance of vasoconstriction and vasodilatation. Hypertension is influenced by genetic variation and environmental risk factors, such as unhealthy diet. Clinical trial results suggest that increasing intake of foods rich in n-3 polyunsaturated fatty acids (PUFAs) is beneficial for hypertension. Recent Advances: We summarized recent clinical trials regarding supplementation with n-3 PUFAs to reduce blood pressure (BP) in untreated hypertensive and normotensive subjects and systematically discussed the antihypertension mechanisms of n-3 PUFAs/n-3 oxylipins, including reducing oxidative stress, altering functions of membrane-related proteins, and competing with n-6 PUFAs/n-6 oxylipins in regulating vasodilator release. Critical Issues: Previous studies considered n-3 PUFAs as single molecules with beneficial roles in hypertension. Recently, researchers have paid more attention to the metabolism of n-3 PUFAs and explored molecular mechanisms of n-3 PUFAs and oxylipins derived from n-3 PUFAs in hypertension interventions. Future Directions: Based on the metabolism of n-3 PUFAs/n-3 oxylipins and mechanisms in BP control, we suggested that supplementation of n-3 PUFAs combined with agents targeting PUFA metabolism or the related signal pathways may amplify their effects to treat hypertension and other cardiovascular diseases. Antioxid. Redox Signal. 34, 800-810.
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Insights into Salt Handling and Blood Pressure.
Ellison, DH, Welling, P
The New England journal of medicine. 2021;(21):1981-1993
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No evidence of racial disparities in blood pressure salt sensitivity when potassium intake exceeds levels recommended in the US dietary guidelines.
Kurtz, TW, DiCarlo, SE, Pravenec, M, Morris, RC
American journal of physiology. Heart and circulatory physiology. 2021;(5):H1903-H1918
Abstract
On average, black individuals are widely believed to be more sensitive than white individuals to blood pressure (BP) effects of changes in salt intake. However, few studies have directly compared the BP effects of changing salt intake in black versus white individuals. In this narrative review, we analyze those studies and note that when potassium intake substantially exceeds the recently recommended US dietary goal of 87 mmol/day, black adults do not appear more sensitive than white adults to BP effects of short-term or long-term increases in salt intake (from an intake ≤50 mmol/day up to 150 mmol/day or more). However, with lower potassium intakes, racial differences in salt sensitivity are observed. Mechanistic studies suggest that racial differences in salt sensitivity are related to differences in vascular resistance responses to changes in salt intake mediated by vasodilator and vasoconstrictor pathways. With respect to cause and prevention of racial disparities in salt sensitivity, it is noteworthy that 1) on average, black individuals consume less potassium than white individuals and 2) consuming supplemental potassium bicarbonate, or potassium rich foods can prevent racial disparities in salt sensitivity. However, the new US dietary guidelines reduced the dietary potassium goal well below the amount associated with preventing racial disparities in salt sensitivity. These observations should motivate research on the impact of the new dietary potassium guidelines on racial disparities in salt sensitivity, the risks and benefits of potassium-containing salt substitutes or supplements, and methods for increasing consumption of foods rich in nutrients that protect against salt-induced hypertension.