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Key Points Diagnosis of pre-eclampsia is based on new-onset hypertension and proteinuria at ≥20 weeks of gestation or, in the absence of proteinuria, hypertension together with evidence of systemic disease Genetic and environmental factors are thought to create conditions leading to defective deep placentation; the injured placenta then releases factors into the maternal circulation that induce pre-eclampsia Pre-eclampsia is characterized by multiple aetiologies and pathogenetic mechanisms, a long subclinical phase, fetal involvement, adaptive clinical manifestations and gene–environment interactions An imbalance between angiogenic and antiangiogenic factors has emerged as a central pathogenetic mechanism in pre-eclampsia An antiangiogenic state can also be observed in conditions other than pre-eclampsia, including intrauterine growth restriction, fetal death, spontaneous preterm labour and maternal floor infarction The severity and timing of the antiangiogenic state, as well as maternal susceptibility, might determine the clinical presentation of pre-eclampsia Several genetic and environmental factors have been implicated in pre-eclampsia, a rare but serious condition leading to maternal and perinatal morbidity and mortality. In the first of this two-part Review, Chaiworapongsa and colleagues discuss the pathophysiology of pre-eclampsia, including imbalance between angiogenic and antiangiogenic factors, which has emerged as the central pathogenetic mechanism. Pre-eclampsia is characterized by new-onset hypertension and proteinuria at ≥20 weeks of gestation. In the absence of proteinuria, hypertension together with evidence of systemic disease (such as thrombocytopenia or elevated levels of liver transaminases) is required for diagnosis. This multisystemic disorder targets several organs, including the kidneys, liver and brain, and is a leading cause of maternal and perinatal morbidity and mortality. Glomeruloendotheliosis is considered to be a characteristic lesion of pre-eclampsia, but can also occur in healthy pregnant women. The placenta has an essential role in development of this disorder. Pathogenetic mechanisms implicated in pre-eclampsia include defective deep placentation, oxidative and endoplasmic reticulum stress, autoantibodies to type-1 angiotensin II receptor, platelet and thrombin activation, intravascular inflammation, endothelial dysfunction and the presence of an antiangiogenic state, among which an imbalance of angiogenesis has emerged as one of the most important factors. However, this imbalance is not specific to pre-eclampsia, as it also occurs in intrauterine growth restriction, fetal death, spontaneous preterm labour and maternal floor infarction (massive perivillous fibrin deposition). The severity and timing of the angiogenic imbalance, together with maternal susceptibility, might determine the clinical presentation of pre-eclampsia. This Review discusses the diagnosis, classification, clinical manifestations and putative pathogenetic mechanisms of pre-eclampsia.

High blood pressure is one of the most important risk factors for ischaemic heart disease, stroke, other cardiovascular diseases, chronic kidney disease and dementia. Mean blood pressure and the prevalence of raised blood pressure have declined substantially in high-income regions since at least the 1970s. By contrast, blood pressure has risen in East, South and Southeast Asia, Oceania and sub-Saharan Africa. Given these trends, the prevalence of hypertension is now higher in low-income and middle-income countries than in high-income countries. In 2015, an estimated 8.5 million deaths were attributable to systolic blood pressure >115 mmHg, 88% of which were in low-income and middle-income countries. Measures such as increasing the availability and affordability of fresh fruits and vegetables, lowering the sodium content of packaged and prepared food and staples such as bread, and improving the availability of dietary salt substitutes can help lower blood pressure in the entire population. The use and effectiveness of hypertension treatment vary substantially across countries. Factors influencing this variation include a country’s financial resources, the extent of health insurance and health facilities, how frequently people interact with physicians and non-physician health personnel, whether a clear and widely adopted clinical guideline exists and the availability of medicines. Scaling up treatment coverage and improving its community effectiveness can substantially reduce the health burden of hypertension.In this Review, Zhou and colleagues summarize the current data on the global epidemiology of blood pressure and hypertension and evaluate changes over time. They also present estimates of the mortality effects of elevated blood pressure and discuss interventions that can reduce the burden of high blood pressure.

Continuous monitoring of arterial blood pressure (BP) outside of a clinical setting is crucial for preventing and diagnosing hypertension related diseases. However, current continuous BP monitoring instruments suffer from either bulky systems or poor user-device interfacial performance, hampering their applications in continuous BP monitoring. Here, we report a thin, soft, miniaturized system (TSMS) that combines a conformal piezoelectric sensor array, an active pressure adaptation unit, a signal processing module, and an advanced machine learning method, to allow real wearable, continuous wireless monitoring of ambulatory artery BP. By optimizing the materials selection, control/sampling strategy, and system integration, the TSMS exhibits improved interfacial performance while maintaining Grade A level measurement accuracy. Initial trials on 87 volunteers and clinical tracking of two hypertension individuals prove the capability of the TSMS as a reliable BP measurement product, and its feasibility and practical usability in precise BP control and personalized diagnosis schemes development. Continuous monitoring of arterial blood pressure is limited by bulky connecting systems and poor interfacial contact. Here, Li et al. report a wearable thin, soft, miniaturized system that integrates sensing, active pressure adaptation, and signal processing for improved performance and accuracy.

Current hypertension guidelines recommend using the average values of several blood pressure (BP) readings obtained both in and out of the office for the diagnosis and management of hypertension. In-office BP measurement using an upper-arm cuff constitutes the evidence-based reference method for current BP classification and treatment targets. However, out-of-office BP evaluation using 24 h ambulatory or home BP monitoring is recommended by all major medical associations for obtaining further insights into the BP profile of an individual and how it relates to their daily activities. Importantly, the highly variable nature of office and out-of-office BP readings has been widely acknowledged, including the association of BP variability with cardiovascular outcomes. However, to date, the implications of BP variability on cardiovascular outcomes have largely been ignored, with limited application in clinical practice. Novel cuffless wearable technologies might provide a detailed assessment of the 24 h BP profile and behaviour over weeks or months. These devices offer many advantages for researchers and patients compared with traditional BP monitors, but their accuracy and utility remain uncertain. In this Review, we outline and compare conventional and novel methods and techniques for assessing average BP levels and BP variability, and reflect on the utility and potential of these methods for improving the treatment and management of patients with hypertension.The most commonly available blood pressure (BP) monitoring devices are useful for capturing a snapshot BP value, but most have limited utility in measuring BP variability. In this Review, Schutte and colleagues outline the advantages and disadvantages of conventional and novel techniques to measure average BP levels and BP variability.

A Western lifestyle with high salt consumption can lead to hypertension and cardiovascular disease. High salt may additionally drive autoimmunity by inducing T helper 17 (T H 17) cells, which can also contribute to hypertension. Induction of T H 17 cells depends on gut microbiota; however, the effect of salt on the gut microbiome is unknown. Here we show that high salt intake affects the gut microbiome in mice, particularly by depleting Lactobacillus murinus . Consequently, treatment of mice with L. murinus prevented salt-induced aggravation of actively induced experimental autoimmune encephalomyelitis and salt-sensitive hypertension by modulating T H 17 cells. In line with these findings, a moderate high-salt challenge in a pilot study in humans reduced intestinal survival of Lactobacillus spp., increased T H 17 cells and increased blood pressure. Our results connect high salt intake to the gut–immune axis and highlight the gut microbiome as a potential therapeutic target to counteract salt-sensitive conditions. High salt intake changed the gut microbiome and increased T H 17 cell numbers in mice, and reduced intestinal survival of Lactobacillus species, increased the number of T H 17 cells and increased blood pressure in humans. Gut microbes worth their salt The role of the gut microbiota in human disease is becoming increasingly recognized. In this study, Dominik Müller and colleagues report that a diet high in salt alters the composition of the gut microbiota in mice, causing pronounced depletion of the commensal Lactobacillus murinus and reduced production of indole metabolites. Previous work has suggested that a high salt diet leads to the generation of pathogenic T helper 17 (T H 17) cells, which have been linked to hypertension and autoimmunity. The authors show that treatment of mice on a high salt diet with L. murinus prevents salt-induced aggravation of actively induced autoimmune encephalomyelitis and salt-sensitive hypertension, through the suppression of T H 17 cells. In a pilot study in a small number of humans, the authors also show that high-salt challenge induces an increase in blood pressure and T H 17 cells, associated with a reduction in Lactobacillus in the gut. However, future work is required to determine whether the findings for mice are translatable to humans.

The (pro)renin receptor ((P)RR) was first identified as a single-transmembrane receptor in human kidneys and initially attracted attention owing to its potential role as a regulator of the tissue renin–angiotensin system (RAS). Subsequent studies found that the (P)RR is widely distributed in organs throughout the body, including the kidneys, heart, brain, eyes, placenta and the immune system, and has multifaceted functions in vivo. The (P)RR has roles in various physiological processes, such as the cell cycle, autophagy, acid–base balance, energy metabolism, embryonic development, T cell homeostasis, water balance, blood pressure regulation, cardiac remodelling and maintenance of podocyte structure. These roles of the (P)RR are mediated by its effects on important biological systems and pathways including the tissue RAS, vacuolar H+-ATPase, Wnt, partitioning defective homologue (Par) and tyrosine phosphorylation. In addition, the (P)RR has been reported to contribute to the pathogenesis of diseases such as fibrosis, hypertension, pre-eclampsia, diabetic microangiopathy, acute kidney injury, cardiovascular disease, cancer and obesity. Current evidence suggests that the (P)RR has key roles in the normal development and maintenance of vital organs and that dysfunction of the (P)RR is associated with diseases that are characterized by a disruption of the homeostasis of physiological functions.Here, the authors discuss the multiple functions of the (pro)renin receptor in physiological processes, including blood pressure regulation, energy metabolism and autophagy, as well as its roles in the pathogenesis of diseases including fibrosis, chronic kidney disease, pre-eclampsia and cancer.

Hypertension affects two-thirds of people aged >60 years and significantly increases the risk of both vascular cognitive impairment and Alzheimer’s disease. Hypertension compromises the structural and functional integrity of the cerebral microcirculation, promoting microvascular rarefaction, cerebromicrovascular endothelial dysfunction and neurovascular uncoupling, which impair cerebral blood supply. In addition, hypertension disrupts the blood–brain barrier, promoting neuroinflammation and exacerbation of amyloid pathologies. Ageing is characterized by multifaceted homeostatic dysfunction and impaired cellular stress resilience, which exacerbate the deleterious cerebromicrovascular effects of hypertension. Neuroradiological markers of hypertension-induced cerebral small vessel disease include white matter hyperintensities, lacunar infarcts and microhaemorrhages, all of which are associated with cognitive decline. Use of pharmaceutical and lifestyle interventions that reduce blood pressure, in combination with treatments that promote microvascular health, have the potential to prevent or delay the pathogenesis of vascular cognitive impairment and Alzheimer’s disease in patients with hypertension.Hypertension and ageing have deleterious effects on the cerebral microcirculation that can lead to cognitive dysfunction. This Review discusses cerebrovascular maladaptation to hypertension and microvascular contributions to hypertension-induced cognitive impairment in ageing, as well as the role of hypertension in the pathogenesis of Alzheimer’s disease.

Preeclampsia is a hypertensive disorder of major concern in pregnancy than can lead to intrauterine growth restriction, placental abruption and stillbirth. The pathophysiology of preeclampsia is multifactorial, including not only kidney dysfunction but also endothelial dysfunction, as the maternal endothelium becomes exposed to placental factors that are released into the circulation and increase systemic levels of vasoconstrictors, oxidative stress, anti-angiogenic factors and inflammatory mediators. Importantly, inflammation can lead to insufficient placental perfusion and low birthweight in offspring. Various innate and adaptive immune cells and mediators have been implicated in the development of preeclampsia, in which oxidative stress is associated with activation of the maternal inflammatory response. Immune cells such as regulatory T cells, macrophages, natural killer cells, and neutrophils are known to have major causative roles in the pathology of preeclampsia, but the contributions of additional immune cells such as B cells, inflammatory cytokines and anti-angiotensin II type 1 receptor autoantibodies are also now recognized. Immunological interventions, therefore, have therapeutic potential in this disease. Here, we provide an overview of the immune responses that are involved in the pathogenesis of preeclampsia, including the role of innate and adaptive immune cells and mediators.Immune dysregulation contributes to the pathogenesis of preeclampsia. Here, the authors examine the role of immune cells and mediators in driving the oxidative stress and endothelial dysfunction that characterize this hypertensive disorder of pregnancy.

The past two to three decades have seen a steady increase in the prevalence of hypertension in China, largely owing to increased life expectancy and lifestyle changes (particularly among individuals aged 35–44 years). Data from the China hypertension survey conducted in 2012–2015 revealed a high prevalence of grade 3 hypertension (systolic blood pressure ≥180 mmHg and diastolic blood pressure ≥110 mmHg) in the general population, which increased with age to up to 5% among individuals aged ≥65 years. The risk profile of patients with hypertension in China has also been a subject of intense study in the past 30 years. Dietary sodium and potassium intake have remained largely the same in China in the past three decades, and salt substitution strategies seem to be effective in reducing blood pressure levels and the risk of cardiovascular events and death. However, the number of individuals with risk factors for hypertension and cardiovascular disease in general, such as physical inactivity and obesity, has increased dramatically in the same period. Moreover, even in patients diagnosed with hypertension, their disease is often poorly managed owing to a lack of patient education and poor treatment compliance. In this Review, we summarize the latest epidemiological data on hypertension in China, discuss the risk factors for hypertension that are specific to this population, and describe several ongoing nationwide hypertension control initiatives that target these risk factors, especially in the low-resource rural setting.The prevalence of hypertension in China has risen steadily in the past two to three decades. In this Review, Wang and colleagues summarize the latest epidemiological data on hypertension in China, describe the risk factors for hypertension that are relevant to this population, and provide an overview of initiatives aimed at improving awareness, treatment and control of hypertension, especially in the low-resource rural setting.

Hypertension is a global health problem, with >1.3 billion individuals with high blood pressure worldwide. In this Review, we present an inflammatory paradigm for hypertension, emphasizing the crucial roles of immune cells, cytokines and chemokines in disease initiation and progression. T cells, monocytes, macrophages, dendritic cells, B cells and natural killer cells are all implicated in hypertension. Neoantigens, the NLRP3 inflammasome and increased sympathetic outflow, as well as cytokines (including IL-6, IL-7, IL-15, IL-18 and IL-21) and a high-salt environment, can contribute to immune activation in hypertension. The activated immune cells migrate to target organs such as arteries (especially the perivascular fat and adventitia), kidneys, the heart and the brain, where they release effector cytokines that elevate blood pressure and cause vascular remodelling, renal damage, cardiac hypertrophy, cognitive impairment and dementia. IL-17 secreted by CD4+ T helper 17 cells and γδ T cells, and interferon-γ and tumour necrosis factor secreted by immunosenescent CD8+ T cells, exert crucial effector roles in hypertension, whereas IL-10 and regulatory T cells are protective. Effector mediators impair nitric oxide bioavailability, leading to endothelial dysfunction and increased vascular contractility. Inflammatory effector mediators also alter renal sodium and water balance and promote renal fibrosis. These mechanisms link hypertension with obesity, autoimmunity, periodontitis and COVID-19. A comprehensive understanding of the immune and inflammatory mechanisms of hypertension is crucial for safely and effectively translating the findings to clinical practice.In this Review, Guzik and colleagues discuss immune and inflammatory mechanisms of hypertension, including upstream regulators and downstream effectors as well as the complex interplay between the immune system, blood pressure regulation and end-organ damage, which can help to identify new targets for therapeutic interventions.