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

This issue of May 2022 of the American Journal of Hypertension begins with a review article by Bradley et al.1 on cuffless blood pressure devices. After reviewing these exciting emerging technologies, the authors conclude that despite rapid progress and device development in cuffless BP technologies, several limitations and barriers must first be addressed before these technologies can be meaningfully implemented into clinical practice. Two commentaries follow, one by P. Boutouyrie2 and another by F. Elijovich,3 which will be discussed with the original articles that they refer to. The first original article in this issue is a Brief Communication by Vidula et al.4 Matrix Gla-Protein (MGP) is an inhibitor of vascular calcification activated by vitamin K-dependent carboxylation. In vitamin K2 deficiency, dephospho-uncarboxylated MGP (dpucMGP) levels increase, which has been associated with large artery stiffening. The authors examined the association of vitamin K2 deficiency and dpucMGP with skeletal muscle mass in 155 hypertensive adults. They concluded that in hypertensive adults, dpucMGP is independently associated with lower axial muscle mass, in addition to increased large artery stiffness. The role of vitamin K supplementation in this population requires further investigation. The following article by Esposito et al. addresses the comparison of central aortic pressures obtained using a SphygmoCor device to pressures obtained using a pressure catheter.5 This study compared aortic pressures using the noninvasive SphygmoCor XCEL PWA device with pressures measured using pressure catheters during cardiac catheterization in 136 patients. These authors observed that the errors between measured and estimated aortic pressures could be reduced to <1 mmHg after using a linear-fit function derived in this study. They concluded that the SphygmoCor data must be used with the linear-fit function in order to obtain aortic pressures comparable to those found using pressure catheters. Continuous monitoring of blood pressure using a wrist-worn cuffless device was reported by Sayer et al. in the next article.6 An accurate noninvasive device that measures BP continuously could provide a more comprehensive assessment of BP. The authors attempted to determine whether the LiveOne device, a cuffless wristband that provides continuous BP measurements, is accurate in comparison to an invasive arterial line. They included 34 patients with 233 measurement periods. The correlation for SBP was 0.91 and for DBP was 0.85. The LiveOne device provided continuous, noninvasive BP measurements that were accurate in comparison to the arterial line measurements. The device is portable and unobtrusive, which may represent an advantage over currently available BP monitors, while in addition providing continuous BP measurements. Because heart failure is frequent in patients with diabetes mellitus (DM), Dillinger et al.7 investigated in 3,367 outpatients with DM without a history of cardiovascular disease whether analysis of brachial blood pressure (BP) in daily practice can identify patients with DM and high risk for subsequent heart failure, as demonstrated by brain natriuretic peptide (BNP) >50 pg/ml. They show that brachial pulse pressure is a parameter associated with high risk of incident heart failure in diabetic patients. The study was accompanied by a Commentary by Boutouyrie et al.2 who point out that mild elevations in BNP are not equivalent to heart failure, and that pulse pressure cannot be considered as the hemodynamic load that the left ventricle is exposed to. However, the paper supports the idea that arterial stiffness (and maybe microvascular dysfunction) may be contributing to heart failure, and that type 2 diabetes is a CV disease. They suggest that the study advocates for the use of assessments of vascular function, both of large and of small arteries, and of heart vessel coupling, to improve risk stratification of patients. Fu et al. studied left ventricular strain and its morphological basis during different stages of diastolic and systolic dysfunction in SHR.8 They obtained echocardiographic measurements, myocardial strain, LV+dp/dtmax and LV end diastolic pressure, and histological collagen volume fraction. These authors were able to demonstrate that myocardial fibrosis associated with hypertension develops from the inner to the outer layers of the myocardium, together with impairment of myocardial multi-directional deformation, with longitudinal strain involved at first, and LVEF declining when all directions of strain are reduced. Hanna et al.9 studied the occurrence of excessive blood pressure responses to clonidine in hospitalized patients with asymptomatic severe hypertension. They identified 200 relevant patient encounters. Only patient sex and clonidine dose of 0.3 mg were significant in multivariable models. There were 14 adverse events observed within 24h of administration of clonidine; most (nine) were acute kidney injury. There were no myocardial or cerebrovascular ischemic events. The authors concluded that a substantial minority of hospitalized patients with asymptomatic severe hypertension present precipitous BP decline with clonidine, and though BP declines more precipitously in women and those receiving higher doses (0.3 mg specifically), the response to clonidine is generally unpredictable on clinical grounds. In an associated Commentary, F. Elijovich3 mentions that the study contradicts a previously reported one, in which oral clonidine was used in an emergency room protocol to lower blood pressure in 36 patients with hypertensive urgencies. Doses were much higher (up to 0.7 mg), and no patient suffered a serious adverse event over 48 hours of follow-up. There were differences in how the dose was titrated in the latter, leading to a smooth and graded reduction of blood pressure. Moreover, in the study by Hanna et al., most patients (90%) had an uneventful course. The author suggests the study begs for a controlled trial of clonidine against a non-sympatholytic comparator drug. An Expert Consensus for the Application of Cardio-Ankle Vascular Index (CAVI) is reported in this issue by Budoff et al,10 with the purpose of providing clinicians with guidance regarding evidence in areas in which there are no clinical practice guidelines, especially for new tests, and in addition, offering practical recommendations. Zhang et al.11 describe effects of RIP2, an adaptor protein that contributes to the activation of NF-κB induced by TNF receptor-associated factor (TRAF) and NOD-dependent signaling. The authors questioned whether RIP2 is involved in the modulation of the phenotype of vascular smooth muscle cells (VSMC). RIP2 increased in VSMCs in response to PDGF-BB. Knockdown of RIP2 expression enhanced the expression of VSMC-specific differentiation genes induced by PDGF-BB and inhibited proliferation and migration of VSMCs. In addition, RIP2 knockdown promoted myocardin expression. Finally, RIP2 inhibition reduced intimal hyperplasia. The authors concluded that RIP2 plays an important role in regulation of VSMCs differentiation, migration and proliferation, and could be a novel therapeutic target for intimal hyperplasia. The effects of renin-angiotensin system inhibitors on mortality and disease severity of COVID-19 patients have been the object of many studies. Yin et al.12 performed a meta-analysis of 6 randomized controlled trials involving 1257 COVID-19 patients. ACEIs and ARBs were not associated with higher risk of mortality and disease severity in COVID-19 patients, and should not be discontinued in these patients. This is exactly what most hypertension and cardiology national and international organizations have already recommended, without much evidence at the time, from the beginning of the pandemic. In the final article of this issue, members of the World Kidney Day Joint Steering Committee have produced the article ”Kidney health for all: bridging the gap in kidney health education and literacy,” 13 reprinted also by many other journals from an original article in Kidney International. In face of the high burden of kidney disease, global disparities in kidney care, and poor outcomes of kidney failure, they recommend that by “engaging in and supporting kidney health–centered policy making, community health planning, and health literacy approaches for all, the kidney communities strive to prevent kidney diseases and enable living well with kidney disease.”

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