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Blood vessels and the kidney in hypertension

Zanchetti, Alberto

doi: 10.1097/HJH.0000000000001592

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

Correspondence to Prof. Alberto Zanchetti, Istituto Auxologico Italiano IRCCS and Centro Interuniversitario di Fisiologia Clinica e Ipertensione, Università degli Studi di Milano, Via F. Sforza, 35, 20122 Milano, Italy. Tel: +39 02 50320484; e-mail:,

Received 11 September, 2017

Accepted 11 September, 2017

Studies on blood vessels and the kidney in hypertension make up the largest part of the current issue of the Journal of Hypertension and deserve a special mention.

A group of articles investigate diagnostic and pathophysiological aspects of arterial stiffness. In a number of young male individuals, Schroeder et al. (pp. 2454–2461) have found that arterial stiffness, measured as pulse wave velocity (PWV), cardio-ankle vascular index and carotid beta-stiffness index, increases with an increasingly upright body position and conclude carotid beta-stiffness index needs to be calibrated accounting for hydrostatic effects of gravity if measured in a sitting position. In a group of overweight–obese hypertensive patients, Barone-Gibbs et al. (pp. 2411–2418) report that interrupting prolonged sitting during deskwork with intermittent standing slightly, but significantly decreased carotid-ankle PWV. Osman et al. (pp. 2436–2442) have investigated PWV and augmentation index (AIx) in a number of healthy women in the third trimester of pregnancy at four different time points over a 24-h period and found that PWV and AIx were not significantly different at the four times of the day, concluding that these measurements do not need to be undertaken at a specific time period of the day. In 1307 community participants, Hodson et al. (pp. 2443–2453) report that, beyond baseline blood pressure (BP), pulsatile hemodynamics rather than steady-state pressures account for end-organ effects more consistently across the normotensive than the hypertensive BP range, and suggest that targeting aortic pulsatile hemodynamic changes may best limit BP-related cardiovascular risk within the normotensive BP range. In 3055 participants of the Malmö Diet and Cancer study 2007–2012, carotid–femoral PWV was not associated with prevalent dementia and did not predict incident dementia (Nilsson et al., pp. 2462–2467). Finally, Nie et al. (pp. 2419–2435) have investigated in mice whether α-solanine, a glycoalkaloid known to have antitumor activity in different cancers, reverses experimental pulmonary arterial hypertension by activating the tumor suppressor-axis inhibitor protein 2. Their results indicate that an inhibitory effect on pulmonary artery smooth muscle cell proliferation and pulmonary artery endothelial cell angiogenic action in vivo and in vitro may be responsible for α-solanine-mediated beneficial effects on small pulmonary arteries and that α-solanine-induced apoptosis and anti-inflammatory action may also contribute to the mitigation of pulmonary artery remodeling. In an accompanying editorial, Cheng et al. (pp. 2377–2379) find the results presented by Nie et al. open an exciting new direction in the therapeutic control of experimental pulmonary artery hypertension by α-solanine, but further studies are necessary to shed light on how α-solanine-mediated antipulmonary artery smooth muscle cell proliferation and apoptosis as well as antipulmonary artery endothelial cell tubulogenesis contribute to the reversal of pulmonary artery remodeling and pulmonary angiogenesis.

Another large part of articles focus on the kidney. Nilsson et al. (pp. 2493–2500) have investigated renal function (estimated glomerular filtration rate, eGFR) in Iraqi-born immigrants residing in Sweden and native Swedes, and report there are differences across ethnicities in renal function and its association with BP. Chatzikyrkou et al. (pp. 2501–2509) have investigated predictors for the development of microalbuminuria in patients randomized in the ROADMAP trial and find predictors were the classical cardiovascular risk factors. Furthermore, microalbuminuria development was associated with baseline urinary albumin-to-creatinine ratio (UACR) but not eGFR, whereas eGFR decrease after introduction of olmesartan was dependent on baseline eGFR but not on baseline UACR. A related article by Catena et al. (pp. 2510–2516) shows that in nondiabetic, treatment-naïve patients with hypertension, low-grade albuminuria is independently associated with elevated plasma aldosterone, suggesting a contribution of aldosterone to the early glomerular changes occurring in hypertensive nephropathy. Karpetas et al. (pp. 2517–2526) present data from an extensive study in hemodialysis patients, showing that BP variability is increased in intradialytic day 2 compared to day 1, suggesting this could be an additional mechanism involved in the increased mortality of hemodialysis patients. Another important article concerning renal disease opens this issue, namely a call to optimize hypertension management in renal transplantation, hypertension being an often-neglected complication of renal transplantation (Halimi et al., pp. 2335–2338). The appeal is signed by a number of well known European nephrologists on behalf of the European Renal and Cardiovascular Medicine and the Transplant DESCARTES Working Group of the European Renal Association – European Dialysis and Transplant Association, the Working Group ‘Hypertension and the Kidney’ of the European Society of Hypertension, the EKITA committee of the European Society of Organ Transplantation, and the FCRIN INI-CRCT Cardiovascular and Renal Clinical Trials. Finally, another article with more indirect relation to the kidney is a review and meta-analysis by Cuspidi et al. (pp. 2339–2345) on the association of echocardiographic left ventricular (LV) hypertrophy with renovascular hypertension: a very relevant information of this meta-analysis is that renal artery revascularization is followed by a significant decrease in LV mass index.

As usual, other areas of hypertension research are also represented in the current issue of the Journal.

Two epidemiological articles are a review and meta-analysis of studies investigating the association between exposure to noise and risk of hypertension and a study of hypertension among US-born and foreign-born non-Hispanic blacks. The meta-analysis by Fu et al. (pp. 2358–2366) shows there is a positive dose–response association between exposure to noise and hypertension, and supports the concept that exposure to noise may be a risk factor for hypertension. By using NHANES 2003–2014 data, Brown et al. (pp. 2380–2387) have found that foreign-born versus US-born non-Hispanic blacks have substantially lower prevalence of hypertension. These observations are commented by Spence (pp. 2369–2371) in an accompanying editorial: he remarks that the article by Brown et al. seems to support the African Diaspora hypothesis, with natural selection for salt and water retention conferring a survival advantage during the conditions of heat and privation on the slave ships during the Atlantic crossing. On the practical clinical side, Spence suggests that it is possible now to improve BP control in blacks by employing physiologically individualized therapy based on aldosterone/renin phenotyping.

Two articles are focused on problems related to BP measurement. De la Sierra et al. (pp. 2388–2394), analyzing a huge number of data (115 708 untreated or treated hypertensive patients) from the Spanish Ambulatory BP Monitoring Registry, report that prevalence of white-coat hypertension is dependent on definition criteria: only diagnostic criteria which consider the normality of all ambulatory periods identifies subjects with cardiovascular risk similar to that of normotensive patients. These data are discussed in an accompanying editorial by Muntner and Shimbo (pp. 2372–2373), who remark that, given the growing consensus for using out-of-office BP measurements as part of the diagnosis of hypertension, additional research including the conduct of randomized trials is needed to identify the correct criteria for screening and delaying treatment for white-coat hypertension. Until such data are available, it may be prudent, as suggested by De la Sierra et al., to require awake, sleep and 24-h BP to be in the normotensive range when making the diagnosis of white-coat hypertension. The debated question whether the association between higher BP and stroke is attenuated or inverted among older adults with impaired functional capacity has been investigated by Murakami et al. (pp. 2395–2401) in community-dwelling elderly adults: they find that higher home, but not office, BP was associated with increased risk of stroke even among those with impaired physical function. In an accompanying editorial, Bursztyn and Grassi (pp. 2374–2376) discuss these observations in the context of the existing discrepancies between many randomized and observational studies on the effects of BP lowering in the frail elderly hypertensive.

Winkler et al. (pp. 2402–2410) have investigated whether acute hypoxia in laboratory conditions influences the BP response to exercise and report that, in their large group of normotensive and hypertensive patients, acute hypoxia did not exacerbate the exercise-induced increase in SBP. Significantly, the authors also report that, based on questionnaires filled-out at high altitude, hypertensive patients were not more prone than normotensive patients to develop severe acute mountain sickness.

Two articles are dealing with preeclampsia and one on primary aldosteronism. Van der Graaf et al. (pp. 2468–2478) have observed an increased responsiveness to angiotensin II following experimental eclampsia in rats, and also describe an increased BP responsiveness to angiotensin II in formerly preeclamptic women. Raman et al. (pp. 2479–2485) report that MRI total gray matter volumes were smaller in women with a history of preeclampsia and late-life hypertension. Zhang et al. (pp. 2486–2492) present data on the use of a modified prediction score to identify unilateral primary aldosteronism.

Finally, a group of articles focus on problems with therapeutic relevance. Durand et al. (pp. 2346–2357) have completed a review and meta-analysis of studies of medication adherence among patients with so-called treatment-resistant hypertension, concluding that medication nonadherence is a significant problem. Calhoun and Grassi (pp. 2367–2368) in an accompanying editorial comment that effective management of resistant hypertension firstly requires reliable confirmation of true treatment resistance based on accurate BP measurements, exclusion of a prominent white-coat effect, determination of adequate medication adherence and, then, optimization of treatment. Seravalle et al. (pp. 2532–2536) present 43-month follow-up data on a group of heart failure patients who had undergone baroreflex activation therapy (BAT) and provide evidence that BAT in heart failure with reduced ejection fraction not only improves the hemodynamic and clinical profile but also exerts sympathoinhibitory effects leading to an almost complete restoration of physiological levels of sympathetic neural function. Oosterhuis et al. (pp. 2537–2547) report experimental evidence that extravascular renal denervation ameliorates juvenile hypertension and renal damage resulting from experimental hyperleptinemia in rats. Finally, Nash et al. (pp. 2527–2531) report that Facebook advertising was successful in helping to increase recruitment of middle-to-older-aged participants into a BP clinical trial.

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Conflicts of interest

There are no conflicts of interest.

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