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

As of this first issue of January 2021 of The American Journal of Hypertension, we will provide a summary of the articles published in the issue. This issue brings to the reader two in depth reviews, one on immune mechanisms and kidney injury in salt-sensitive hypertension,1 and one on inflammation, immunity, and aldosterone in hypertension.2 It includes a number of original reports that go from a brief communication on the retina in malignant hypertension3 through primary aldosteronism,4 heart disease and association with metabolic and inflammatory biomarkers,5 premature mortality among Japanese in relation to stages in the 2017 ACC/AHA guideline for management of hypertension,6 uric acid and its association with blood pressure (BP) phenotypes and target organ damage,7 preeclampsia and the role of vascular endothelial growth receptor 2 on blood–brain barrier permeability,8 maternal hypertension-related genotypes and congenital heart defects,9 the rationale and design of a genotype-guided hypertension trial,10 the pancreatic microcirculation and progression of hypertension in spontaneously hypertensive rats,11 role of Trpa1 in renal ischemia-reperfusion injury with classical activation of macrophages,12 and finally, a Hypertension Rounds in which a case of late detection of pheochromocytoma in a young patient with resistant hypertension and hypertrophic cardiomyopathy is discussed.13 Among the original articles, a first brief communication by de Nattes et al.3 investigated whether the wall-to-lumen ratio of retinal arterioles measured by adaptive optics ophthalmoscopy could be correlated to wall-to-lumen ratio of kidney arterioles as determined by pathology in malignant hypertension, but failed to show a significant relationship between wall-to-lumen ratio and other relevant target organ damage.3 In the following article, Yozamp et al.4 describe a retrospective cohort study of 340 patients with primary aldosteronism who underwent adrenal venous sampling at a tertiary referral center, 116 of who also had a peripheral venous aldosterone measured hours before the procedure. Although adrenal venous sampling was performed by the same interventional radiologist using bilateral, simultaneous sampling, under unstimulated and then stimulated conditions, and each sample was obtained in triplicate, the authors found that aldosterone levels can reach circulating concentrations that are not compatible with the diagnosis of primary aldosteronism, and that adrenal venous aldosterone concentrations exhibit acute variability. They conclude that a single venous aldosterone measurement lacks precision and reproducibility in primary aldosteronism. Cauwenberghs et al.5 looked at the relation of subclinical cardiac dysfunction to metabolic and inflammatory markers in a community-based study combining high throughput biomarker profiling, multidimensional network analyses, and regression statistics to identify immune metabolic markers associated with subclinical heart dysfunction in the community. Biomarkers of insulin resistance, hyperuricemia, and chronic low-grade inflammation were associated with cardiac dysfunction, and could help improve the detection and management of cardiac dysfunction in clinical practice. Among Japanese in a national health checkup examination (n = 510,238) started in 2008, Hatano et al. report the population-attributable fraction for premature mortality due to cardiovascular disease associated with stages 1 and 2 hypertension, as defined by the 2017 American College of Cardiology/American Heart Association BP guideline.6 These authors found that the population-attributable fraction for premature mortality due to hypertension-related cardiovascular disease was associated with an increase of 4.4% of premature cardiovascular disease mortality if BP thresholds for hypertension were lowered from BP ≥ 140/90 to ≥ 130/80 mm Hg. Cai et al.7 investigated the correlation between serum uric acid (SUA) and 24-hour ambulatory BP monitoring, the association between SUA and BP phenotypes (such as controlled hypertension, white-coat uncontrolled hypertension, masked uncontrolled hypertension, and sustained uncontrolled hypertension) and that between SUA and target organ damage (TOD, including microalbuminuria, left ventricular hypertrophy, and arterial stiffness). After adjustment for covariates (age, sex, smoking, body mass index, diabetes mellitus, and estimated glomerular filtration rate), there was no association between SUA and TOD in all BP phenotypes. Accordingly, these findings did not support routine use of 24-hour ambulatory BP monitoring in treated hypertensive patients with increased SUA. Cerebral complications in preeclampsia are leading causes of maternal mortality worldwide but their pathophysiology is not well understood. Using an in vitro model of the human blood–brain barrier, Bergman et al.8 investigated the role of vascular endothelial growth factor receptor 2 (VEGFR2) in preeclampsia. They demonstrate that tyrosine phosphorylation of VEGFR2 may participate in the increased blood–brain barrier permeability in preeclampsia independently of plasma concentrations of angiogenic biomarkers. Using data from the National Birth Defects Prevention Study, Lei et al.9 evaluated whether maternal genotypes associated with maternal hypertension were also associated with congenital heart defect occurrence. These authors identified non-Hispanic White and Hispanic women with and without a pregnancy in which an isolated heart defect was found between 1999 and 2011. They genotyped 29 hypertension-related single nucleotide polymorphisms and conducted logistic regression analyses separately by race/ethnicity. A previously reported association between rs633185 and conotruncal defects was replicated. Although additional hypertension-related single nucleotide polymorphisms were also associated with congenital heart defects, the authors concluded that more work needs to be carried out to understand the relationship between genetic risk for maternal hypertension and occurrence of congenital heart defects. Because genome wide association studies have suggested that single-nucleotide polymorphisms in the 5’ end of the uromodulin gene (UMOD) affect uromodulin excretion and BP, McCallum et al.10 have proposed a genotype-blinded, multi-center trial comparing the BP response to torasemide between individuals possessing the AA genotype of the single nucleotide polymorphism rs13333226 and those possessing the G allele, since targeting loop-diuretics to individuals who are more likely to respond to this drug class could be an effective precision medicine strategy to control BP. Subjects with uncontrolled BP on ≥ 1 antihypertensive agent for ≥ 3 months would be included, and torasemide, 5 mg daily, would be taken for 16 weeks. The primary outcome would be the change in 24-h ambulatory SBP area under the curve between baseline and end of treatment. If the trial were positive, a targeted strategy with torasemide could improve BP control and help reduce the burden of uncontrolled hypertension. In a study of the pancreatic microcirculation during evolution of hypertension in spontaneously hypertensive rats, Liu et al.11 show that pancreatic microcirculation profiles are abnormal as hypertension progresses in spontaneously hypertensive rats, including a disturbed blood distribution pattern, impaired microvascular vasomotion, and reduced amplitude of endothelial oscillators. This study suggests that the pancreas may serve as a major source of degrading protease activities, and that uncontrolled proteolytic receptor cleavage could occur in hypertension, contributing to its progression. Activated macrophages can contribute to the development of renal ischemia–reperfusion injury. This study by Ma and Wang12 assessed the role of transient receptor potential ankyrin 1 (Trpa1), a regulator of macrophage activation, in ischemia–reperfusion injury–induced acute kidney injury by using the Trpa1 gene knockout (Trpa1−/−) mouse model. Trpa1 deficient mice exhibited exaggerated macrophage infiltration, renal inflammation, and injury after ischemia–reperfusion injury, suggesting a protective effect of activation of Trpa1 against ischemia–reperfusion injury–induced acute kidney injury by modulating macrophage-mediated inflammation. In the last article of this issue, Alamri et al.13 discuss in a Hypertension Rounds a case of late detection of a pheochromocytoma in a young patient that exhibited resistant hypertension associated with a hypertrophic cardiomyopathy, and whose hypertension remained uncontrolled until a pregnancy ended with preeclampsia and fetal death. Only after this event was the patient investigated for secondary hypertension, and a large adrenal tumor corresponding to a pheochromocytoma diagnosed and operated. The author declared no conflict of interest.