From the Editor-in-Chief: Issue at a Glance

The current issue of the American Journal of Hypertension for August 2021 begins with an Editorial by Pedrosa Nunes et al.1 on COVID-19 and ROS storm: what is on the forecast for hypertension? In it the authors suggest that the pathophysiology of COVID-19 hyperinflammation involves not only a cytokine storm, and maybe a bradykinin storm as recently suggested by one of the authors of this editorial, but also an oxidative storm as a result of massive production of reactive oxygen species in response to many mediators including angiotensin II and other agents, but also a reduction in antioxidant activity. They report studies demonstrating diminishing levels in COVID-19 patients of vitamin C, thiol proteins, glutathione, γ-tocopherol, and β-carotene and as well, reduced expression of genes related to the Nrf2 pathway. An in-depth review on home blood pressure monitoring by Kazuomi Kario2 follows. Next come two commentaries, one on mortality after renal artery revascularization by Stephen Textor,3 the other on coronary atherosclerosis across the continuum of blood pressure by Whelton et al.,4 which will be commented on together with the articles they refer to. The first original contribution to this issue is by Soares Lopes et al.5 on life course socioeconomic position, intragenerational social mobility and hypertension incidence in the ELSA-Brasil study. The authors report on the effect of low socioeconomic position on BP progression over the life span. Incidence of hypertension was higher in males, the elderly, people of Black race, and those of low socioeconomic position. They conclude that socioeconomic disparities at all phases of the life course raise the incidence of hypertension. The next original paper is on time trends in comorbidity and management of hypertension and self-reported diabetes based on a 15-year (2000 – 2015) nationwide longitudinal study in China, by Li et al.6 These authors found that, not very different from findings in similar cohorts from other countries, rates of hypertension treatment and control among the 832 participants with both hypertension and self-reported type 2 diabetes had improved in recent years, but remained low. The manuscript that follows comes from Cho et al.7 on the association between nocturnal blood pressure dipping and chronic kidney disease among patients with controlled office blood pressure. An abnormal dipping profile, whether reverse-dipping, non-dipping, or extreme-dipping, was associated with decreased kidney function. The associations with abnormal dipping persisted, even among those participants with better controlled office blood pressure, <130/80 mm Hg. Sun et al.8 next describe the rationale and design of a cluster randomized trial of a village doctor-led intervention for hypertension control in China. In rural areas in China, hypertension prevalence is high and increasing, whereas control rates are low. Village doctors play an important role in the delivery of health services in rural areas. The aim of these investigators was to test how effective a village-doctor led intervention compared with usual care in its effects on blood pressure control (<130/80 mm Hg) at 18 months in a first phase, and prevention of cardiovascular events over 36 months in a second phase. N-Methyl-d-aspartate receptor (NMDAR) is one of the major types of glutamate receptors in the central nervous system. Li et al.9 report that they induced chronic bilateral blockade of the NMDAR subunit 2A (GluN2A) in the paraventricular nucleus (PVN) of the hypothalamus in 2 kidney 1-clip Goldblatt hypertensive rats. The authors used PEAQX, a specific antagonist of this NMDAR subunit. In these hypertensive rats, PEAQX lowered blood pressure by suppressing the MEK/ERK/CREB pathway. PEAQX also reduced the transcription and translation of GluN2A and altered expression levels of NMDAR subunits 1 and 2B (GluN1 and GluN2B). In addition, PEAQX reduced the levels of pro-inflammatory cytokines and reactive oxygen species in the PVN, and the level of norepinephrine in plasma of 2K1C rats. In a cohort of 933 adults from the city of Wakuya in the Miyagi Prefecture of Japan, Hashimoto et al.10 reporteds that presence of (micro)albuminuria strengthens the association between urinary sodium excretion and central pulse pressure. The correlation remained after adjusting for mean blood pressure, and was independent of age, sex, eGFR, blood lipids and presence of diabetes. It was associated with the amplitude of the forward wave but not the backward wave or the augmentation index. This occurred in particular if the subjects had chronic kidney disease. However, the mechanisms for some of these synergistic associations which could involve the renal microvasculature were not clarified, and will require further study. Yoon et al.11 investigated the association of Stage 1 hypertension defined by the ACC/AHA 2017 Guideline with asymptomatic coronary atherosclerosis in 4,666 individuals who had undergone a coronary computed tomographic angiography (CCTA). The authors evaluated the presence of coronary plaques and their characteristics, the coronary artery calcium score, and any significant coronary stenosis. They found that in Stage 1 hypertensive patients there was already significant subclinical coronary atherosclerosis. In a commentary, Whelton et al.4 suggest that while decisions to initiate treatment with antihypertensive drugs in stage 1 hypertension should be determined as part of a clinician-patient discussion, these results demonstrate that non-invasive evaluation shows significant prevalence of coronary atherosclerosis in this group of hypertensive adults. These results should allow clinicians and patients to refine their decision-making process. The impact of intravenous antihypertensives agents on outcomes among 1,784 out of 5,680 patients hospitalized patients who were prescribed these drugs was assessed by Bean-Thompson et al.12 Those who received the intravenous medication had an almost 2-day longer hospital stay compared to patients with an order for intravenous antihypertensive medication but did not receive it. In-hospital mortality was higher in the group that received the intravenous antihypertensives, although not statistically significant on multivariate analysis. Intravenous hydralazine caused the greatest reductions in blood pressure and resulted in a shorter length of stay compared to enalapril and labetalol. The authors conclude that rapid lowering of blood pressure can harm patients, and that if there is no target organ damage, physicians should lower blood pressure gradually. Zhang et al.13 assessed the association between hypertension and 10 candidate single-nucleotide polymorphisms (SNPs) in Chinese Dai people, who have a smaller gene pool than Han individuals. Whole genome sequencing was carried out on 1,193 samples from Dai people, including 488 with hypertension and 705 with normal blood pressure. Three novel genetic variants in the FAM110D, CACNA1A and NLRP12 genes were associated with susceptibility to hypertension, which according to these authors could indicate the existence of specific molecular mechanisms involved in the pathophysiology of hypertension among Dai people. Long-term mortality after renal artery stenting in 65 patients with severe atherosclerotic renal artery stenosis and high-risk clinical manifestations was reported by Dregoesc et al,14 out of 138 patients who underwent revascularization, after excluding those who had fibromuscular dysplasia, less severe stenoses, and “small” kidneys. Improved renal function and blood pressure were found in the first year after renal artery stenting. Absence of improvement in kidney function and blood pressure was independently associated with long term mortality. A commentary by SC Textor3 asks the question: “Why is there such wide variability in the observed blood pressure and renal function outcomes after stent revascularization?” The activation of the renin–angiotensin system, tissue hypoxia, mitochondrial dysfunction, microvascular rarefaction, and tissue inflammation are all proposed to play roles in poor outcomes. From a practical point of view, the author suggests that it is necessary to weigh hazards and expense of renal artery intervention versus benefit over the expected survival of each patient, and that it is reasonable to move ahead with revascularization in the case of individuals at acceptable risk.

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