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Blood pressure measurement, blood vessels and treatment of hypertension

Zanchetti, Alberto

doi: 10.1097/HJH.0000000000001667

Istituto Auxologico Italiano IRCCS, Centro Interuniversitario Fisiologia Clinica e Ipertensione, Università degli Studi di Milano, Milan, Italy

Correspondence to Professor Alberto Zanchetti, Istituto Auxologico Italiano IRCCS, Centro Interuniversitario di Fisiologia Clinica e Ipertensione, Università degli Studi di Milano, Via F. Sforza, 35, 20122 Milan, Italy. Tel: +39 2 50320484; e-mail:,

Most of the articles in the current issue of the Journal of Hypertension have investigated aspects of blood pressure (BP) measurement, blood vessel pathophysiology and antihypertensive treatment.

In the last 30 years, several organizations have developed separate protocols for the necessary clinical validation of BP-measuring devices. Recently, however, an international initiative was taken by the United States Association for the Advancement of Medical Instrumentation (AAMI), the European Society of Hypertension (ESH) and the International Organization for Standardization (ISO) experts to develop a universal standard for device validation. The Journal of Hypertension has the pleasure to publish in this issue the statement prepared by the three organizations (Stergiou et al., pp. 472–478) with the key aspects of a single standardized protocol that is intended to replace all previous standards or protocols. The new universal protocol will not deny the important contributions provided by the previous protocols, and an accompanying editorial by Stergiou et al. (pp. 479–487) remembers the important influence exerted by the ESH international protocol to improve the accuracy of BP measurement.

Articles investigating blood vessel pathophysiology cover a large part of this issue. A consensus document in two parts by the ESH Working Group on Endothelin and Endothelial Factors and the Japanese Society of Hypertension reviews endothelial factors in the pathogenesis of chronic kidney disease. The first part examines the mechanisms by which endothelial factors induce vascular remodeling and the role of different players, including endothelin-1, the renin–angiotensin–aldosterone system and their interactions, and oxidative stress (Rossi et al., pp. 451–461). The second part reviews current knowledge on the role of endothelial dysfunction in multiple disease conditions that affect the kidney, such as diabetes mellitus, preeclampsia, kidney transplantation, hyperhomocysteinemia and cancer treatment with antiangiogenic agents (Rossi et al., pp. 462–471).

Wynne et al. (pp. 510–519) publish an experimental study on the role of protein kinase Cα (PKCα) in modulating vascular contractility and, consequently, blood pressure: PKCα knockout mice had a significantly lower BP and a reduced receptor-independent relaxation response of aorta and mesenteric vessels. Ngatchou et al. (pp. 520–527) have investigated arterial stiffness in Cameroonian Pygmies (still living in rainforest with a traditional hunter–gatherer lifestyle) and urban Bantus (as well as urbanized Pygmies), and report independent association of pulse wave velocity (PWV) with age, weight, height, mean arterial pressure, total cholesterol and hip circumference. In a cross-sectional analysis of normotensive and untreated hypertensive participants in the CARTaGENE population cohort, Lepeytre et al. (pp. 495–501) find serum uric acid levels are associated with both central and peripheral steady, but not pulsatile, BP, regardless of sex. In a prospective population study (4251 Chinese individuals randomly selected, followed for 4.4 years), Lu et al. (pp. 528–536) have investigated whether brachial-ankle (ba) PWV can improve prediction of cardiovascular events over and beyond BP, and report a marginally increased prediction over mean BP, but a better prediction than pulse pressure. Brachial-ankle PWV has been measured by Tokitsu et al. (pp. 560–568) in patients with heart failure with preserved left ventricular ejection fraction and found to be helpful in improving risk stratification and predicting subsequent cardiovascular events. Quinaglia et al. (pp. 552–559) have investigated local stiffness of the ascending aorta in individuals free of overt cardiovascular disease, and found stiffness of the ascending aorta, representing the local proximal aortic function face to the left ventricle, and stiffness of the downstream aortic pathway (as assessed by carotid–femoral PWV), reflecting more advanced alterations of material properties involving the entire aorta, are independent determinants of left ventricle remodeling. Central hemodynamics has been studied by van de Velde et al. (pp. 544–551), who report myocardial preload alters central pressure augmentation through changes in the forward wave. In a large cross-sectional study Jiang et al. (pp. 569–579) show that an elevation in pulse pressure is associated with increased plasma levels of amyloid-β (Aβ 1–40) and decreased log-transformed soluble receptor for advanced glycation end products (sRAGE) among individuals not taking antihypertensive medication, thus, adding further support to the hypothesis that increased pulse pressure may be implicated in the development and progression of Alzheimer's disease.

Yang et al. (pp. 537–543) have investigated the relationship between common carotid artery diameter and target organ damage (TOD) in essential hypertension, and report carotid artery diameter is an independent risk factor for individual TOD, including left ventricular hypertrophy, PWV and urinary albumin–creatinine ratio, as well as the overall number of TODs. Carotid artery stiffness, as assessed by echotracking technique, has been found by Paini et al. (pp. 580–586) to be significantly correlated with the wall-to-lumen ratio of retinal arterioles, independently of possible confounders. The association of arterial stiffening with changes in retinal arteriole calibers has been investigated also by Kawashima-Kumagai et al. (pp. 587–593) in a large Japanese population sample of 6720 participants followed-up for 5 years: central retinal arteriolar diameter was found to be a significant inverse determinant of changes in brachial-ankle PWV, independent of possible covariates. The article by Kawashima-Kumagai et al. is accompanied by an editorial commentary by Benetos (pp. 488–489), who remarks the data suggest that individuals in their early 40s, especially those with a family history of early cardiovascular disease or those presenting modifiable risk factors, may benefit from measurements of retinal arteriole caliber as a very early sign of future systematic arteriosclerosis. However, future studies should better define the feasibility, reproducibility and cost of retinal artery measurements in real-life conditions.

Another set of articles are focused on therapeutic aspects. Marc et al. (pp. 641–650) show that compound RB150, a prodrug of the specific and selective aminopeptidase A inhibitor, EC33, whenever given orally, crosses the blood–brain barrier and lowers blood pressure also whenever administered chronically: the prolonged antihypertensive effect is associated with a significant decrease in plasma arginine–vasopressin and an increase in diuresis. In an extensive study constituting both hypertensive patients and a rat model of renovascular hypertension, Xiao et al. (pp. 651–665) investigate the contribution of hydrogen sulfide (H2S) to vascular tone, and conclude that H2S plays a protective function in renal arterial endothelium in hypertension by activating the peroxisome proliferator-activated receptor delta/endothelial nitric oxide synthase (PPARδ/eNOS) pathway, suggesting H2S may serve as an effective strategy against hypertension. These data are commented in an editorial by Chappell (pp. 493–494), who remarks that, although the study by Xiao et al. is primarily focused on the vascular actions of H2S, this molecule also exerts significant actions on the heart, as well as other cardiovascular relevant tissues such as the brain, kidney, gut microbiome and immune cells. These targets should be continued areas of investigation, particularly the extent of the nitric oxide (NO)-dependent and NO-independent actions of H2S. In another article investigating the role of NO in regulating BP and vascular tone, Rosenbaek et al. (pp. 666–679) present the results of a randomized, placebo-controlled, cross-over study of sodium nitrite (NaNO2) intravenous infusion in hypertensive patients and healthy controls: they observed an augmented BP-lowering effect in hypertensive patients, an antinatriuretic and antidiuretic effect and a decrease in the urinary excretion rate of the gamma subunit of the epithelial sodium channel (U-ENaCγ), the last effect solely in hypertensive patients. Schmieder et al. (pp. 680–689) publish the results of a randomized, sham-controlled international trial (WAVE IV) aimed at verifying the BP-lowering efficacy of externally delivered focused ultrasound for noninvasive renal denervation in 81 patients with resistant hypertension. The trial was interrupted after an interim analysis that showed no difference in antihypertensive efficacy between the treated and sham-treated group. Dorobantu et al. (pp. 690–700) analyze the current situation and the future trend regarding hypertension treatment and control in the Romanian adult population using the data from three national surveys in 2005, 2012 and 2016. An additional article with therapeutic impact investigates the ability of KCNJ5 mutations to predict the success of unilateral adrenalectomy in curing young patients with aldosterone-producing adenoma (Kitamoto et al., pp. 619–627).

Other aspects of hypertension are explored by other articles in the current issue. Liu et al. (pp. 502–509) have analyzed genes involved in Mendelian forms of low-renin hypertension in Chinese patients with early-onset hypertension, and show Liddle's syndrome is the most common form, concluding that sequencing exon 13 of both SCNN1B and SCNN1G is highly advisable in patients with early-onset and low-renin hypertension. Song et al. (pp. 594–600) report that earlier age at natural menopause is related to higher prevalence of hypertension and suggest that identification of women with earlier menopause may offer a window of opportunity to improve women's health during the postmenopausal years. A decreased sleep quality on actigraphy has been found by Oume et al. (pp. 601–607) to be associated with higher nighttime BP in a Japanese elderly women population. Using data from the 2013 and 2014 United States Nationwide Readmissions Database, Mogos et al. (pp. 608–618) show that hypertensive disorders of pregnancy are associated with increased risk of postpartum hospital readmissions and substantial medical costs, and point out preventive efforts should be done to identify women at increased risk of postpartum readmissions during initial hospitalization so that transition care intervention can be initiated. Hu et al. (pp. 628–633) have used the CHA2DS2-VASc score to evaluate the risk of ischemic stroke among patients with venous thromboembolism and the risk of venous thromboembolism among patients with ischemic stroke in the inpatient claims data of the Taiwan National Health Insurance Research Database: the performance of the score was modest, however. Faucon et al. (pp. 634–640) review 186 cases of renal infarction admitted in a tertiary center in Paris during a 15-year period: a renal artery lesion was the most frequent cause. The authors underline that extensive arterial exploration is required to identify the renal infarction mechanism and, in the case of renal artery lesion, the underlying vascular disease. In an accompanying commentary, Lengelé et al. (pp. 490–492) remark that the careful diagnostic approach followed by Faucon et al. would deserve to be applied prospectively in other centers with different patient recruitment, preferably in the context of national or international registries.

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Conflicts of interest

There are no conflicts of interest.

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