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

This issue of April 2022 of the American Journal of Hypertension begins with a review by B.I. Levy and J.-J. Mourad1 on renin-angiotensin blockers and cardiac protection, from basics to clinical trials. The authors discuss the effects of inhibition of angiotensin converting enzyme and the role of the subtypes of angiotensin receptors, and in the context of their effects and results of clinical trials draw conclusions on the clinical application of blockers of the renin-angiotensin system in different cardiovascular conditions. A commentary by M.F. Elias and C.J. Brown comes next, on homocysteine lowering for management of treatment-resistant hypertension.2 The authors present some evidence suggesting that there are benefits of using folate and some of the B vitamins to lower blood pressure in patients with difficult to control hypertension. Two reviewer commentaries follow, one by L. Gomes-Pereira and J.E. da Silva-Santos,3 and another by Rizzoni et al.,4 which will be discussed with the original articles that they refer to. The first original article in this issue is by Vecchiola et al.,5 who demonstrate in a cross-sectional study of 202 individuals that PAI-1 and adiponectin are associated with metabolic syndrome components in a general population. In a Commentary by L. Gomes-Pereira and J.E. da Silva-Santos,3 these authors highlight some limitations of the study by Vecchiola et al., such as the sample size that could limit the conclusions, but point out that the strength of this study is the demonstration, through receiver operating characteristic analysis, that PAI-1 and adiponectin values can be both sensitive and specific enough to identify the development of the metabolic syndrome. The following article is by Muntner et al.,6 who analyzed the US National Health and Nutrition Examination Survey 2011–2018 data (n = 21,581). They found normal BP in 57.8% of adults under 44 years of age, and decreasing prevalence of normal BP up to 5.0% at ≥75 years. Normal BP was more common among those with moderate and no alcohol consumption, those doing ≥150 minutes of physical activity per week, those who were not obese, and had a high Dietary Approaches to Stop Hypertension score. US adults ≥65 years with normal BP were less likely to have diabetes, albuminuria, atherosclerotic cardiovascular disease, and heart failure. Thus, the authors concluded that among US adults ≥65 years, normal BP was associated with a healthy lifestyle and a lower prevalence of adverse health conditions. Satoh et al.7 investigated prediction models for new-onset home morning hypertension among 978 participants without home hypertension in the general population of Ohasama, Japan. Participants were divided into a derivation and a validation cohort and results assessed after the 5- or 10-year follow-up. Sex, age, body mass index, smoking, office systolic blood pressure (SBP), and home SBP at baseline were selected as significant risk factors for new-onset home hypertension in the derivation cohort. The full model revealed good ability to predict the 5- and 10-year home morning hypertension risk in the validation cohort. Although the model without home SBP was acceptable, the low C-statistic implies that home BP needs to be measured to predict home morning hypertension in a precise manner. The Trial of Nonpharmacologic Interventions in the Elderly (TONE) demonstrated the efficacy of weight loss and sodium reduction to reduce hypertension medication in older adults. Juraschek et al.8 evaluated adverse effects of hypertension medication withdrawal in the 975 participants. Drug withdrawal increased SBP compared to baseline. There were 113 adverse events mainly during drug withdrawal. Weight loss and sodium reduction decreased effects of drug withdrawal on BP and reduced orthostatic symptoms, but did not affect adverse events. Sodium reduction alone increased the risk of adverse events mainly during drug withdrawal. In older adults, antihypertensive drug withdrawal may increase the risk of symptomatic adverse events. These results underline the need for caution when withdrawing antihypertensive medications in older adults. Gavrilin et al.9 studied 7 newly diagnosed moderate to severe obstructive sleep apnea OSA before and 12 weeks after intensive treatment with continuous positive airway pressure (CPAP), compared to 7 weight- and age-matched controls. Small arteries were isolated from gluteal biopsies and gene expression was assessed. They found that angiotensin receptor type 1 and NOX4 were up-regulated and dimethylarginine dimethylaminohydrolase (DDAH 1) was down-regulated. Endothelial nitric oxide synthase was unchanged, although nitric oxide availability as measured through brachial artery flow-mediated dilation was reduced. Endothelin, hypoxia inducible factor-1 alpha, nuclear factor kappa B, interleukin-8, and interleukin-6 were also altered. The authors concluded that CPAP has effects on microcirculatory endothelial dysfunction. Their findings could support a role of renin–angiotensin activation and endothelial oxidative stress in OSA affecting availability of nitric oxide. In a Commentary on this article, Rizzoni et al.4 underline some of the limitations of the study, including the small number of subjects studied, and the fact that whole vessels were homogenized to investigate gene expression making it difficult to specifically attribute changes found to the endothelium. Furthermore, the authors of the Commentary point out that the potential beneficial effects of CPAP observed at a molecular level should be taken cautiously, considering the lack of benefit on cardiovascular risk found in recent trials, although quality of life of OSA patients was indeed improved. Anjos et al.10 performed a systematic review and meta-analysis to evaluate the use of optical coherence tomography angiography (OCTA) to investigate the retinal microvascular network in hypertensive patients and found 9 studies that could be included. The authors report that microvascular rarefaction of the macula was been found in hypertensive patients with a reduction of foveal and parafoveal vascular density, and an increase of the foveal avascular zone area. They conclude that OCTA could be useful for the assessment and follow-up of hypertensive patients. In the final article of this issue, Sam et al.11 evaluated six clinical prediction models that have been developed to help select patients who would most likely benefit from adrenal venous sampling (AVS) in order to establish their performance for primary aldosteronism (PA) subtyping, using a validation cohort of 342 subjects who underwent AVS. The prediction models evaluated did not accurately predict AVS lateralization in this cohort of PA subjects, leading the authors to conclude that these models cannot be used to decide carrying out AVS.

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