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Highlights of the October issue

Mancia, Giuseppe

doi: 10.1097/HJH.0000000000002209

Università Milano-Bicocca, Milan and Policlinico di Monza, Monza, Italy

Correspondence to Professor Giuseppe Mancia, MD, dei Daini, Università Milano-Bicocca, 4 -20126 Milano, Italy. Tel: +39 3474327142; e-mail:

The October issue of the Journal of Hypertension starts with a number of reviews and meta-analyses of the data available in the literature on topics of current interest for the diagnosis and treatment of hypertension. Cuspidi et al. (pp. 1917–1926) address a topic on which data are inconsistent, i.e., the prevalence, determinants and prognostic value of extreme dipping, that is, an excessive blood pressure (BP) reduction at night from the daytime values. The authors describe in detail the results made available by the most relevant studies, which do disagree either on the prevalence and on the demographic and clinical phenotypes associated with this condition. Disagreement also exists on whether an excessive BP reduction at night leads to a greater incidence and risk of cardiovascular outcomes, presumably because of nocturnal vital organ underperfusion. In this context, an additional contribution of Cuspidi and coworkers is a meta-analysis of four previous reports (4040 individuals, of which 322 with extreme dipping) which did not show left ventricular mass index to be different in extreme dippers vs. other nighttime BP patterns, namely dipping, nondipping and reverse dipping. By and large, the data score in favour of the authors’ conclusion that the chance that extreme dipping has adverse prognostic significance does not have adequate scientific support, and that thus, using existing data on extreme dipping to determine the optimal nighttime BP target to be pursued with treatment is not justified.

The remaining reviews and meta-analyses deal with the antihypertensive effect of isometric training, the contribution of blood glucose and BP reduction to cardiovascular outcomes in trials on antidiabetic drugs, and the relationship between thiazide or thiazide-like diuretics and the risk of skin cancer. Smart et al. (pp. 1927–1938) report the results of a meta-analysis from individuals recruited in 12 studies on the effect of isometric training. Isometric training was associated with a highly significant BP reduction (−6.2/−2.8 mmHg), the magnitude of which was perhaps greater than that reported by meta-analyses of trial mean values. Thomopoulos et al. (pp. 1939–1949) show that the reduction of blood glucose and glycated haemoglobin induced by antidiabetic drugs in trials on type 2 diabetic patients (25 trials, 174 235 individuals) only modestly reduced macrovascular outcomes while significantly and markedly increasing the risk of treatment discontinuation. Adjustment for BP differences between groups did not substantially modify the results, which thus, seem to be independent from the BP changes that may occur with some glucose-lowering drugs. Nevertheless, such adjustment may represent a useful procedure to consider because in some of these trials (the most recent ones) and with some new antidiabetic agents BP reductions were by no means trivial, raising the question of their participation in the macrovascular protective effects of the new as compared with the older drugs used to control blood glucose in diabetes. The interest of performing meta-analyses of the relationship between glucose-lowering drugs, BP lowering drugs and outcomes for different antidiabetic drug classes, for example those lowering vs. those not lowering BP, is emphasized in the editorial commentary of Gasevic and Zoungas (pp. 1959–1960). Kreutz et al. (pp. 1950–1958) focus on the association between use of thiazides and thiazide-like diuretics and an increased risk of skin cancer reported in some recent studies. The point is made that these diuretics do have photosensitizing properties and that in nine out of the 13 available observational studies, an increased risk of skin cancer (basal and squamous cell carcinoma) has indeed been found. Emphasis is given, however, to the fact that in all studies there were important methodological limitations as well as potential confounding by indication, detection bias or time window problems, which prevent any sound conclusion in one direction or another. The question should not be forgotten, however, and well designed observational studies should be strongly encouraged. Further considerations on this issue can be found in the editorial commentary of Schlaich et al. (pp. 1961–1962) who pose the interesting question whether, in the meantime, patients under thiazide or thiazide-like diuretic treatment should be warned to avoid overexposure to sun.

Two articles of the current issue of the Journal deal with BP measurements whereas six articles focus on hypertension epidemiology. Chung et al. (pp. 1966–1973) report that, in a noticeable number of patients in whom BP was measured intra-arterially, higher pulse pressure values showed a relationship with the occurrence of orthostatic hypotension, which implies a participation of an increased arterial stiffness in this phenomenon. Ntineri et al. (pp. 1974–1981) show that, in 1971 individuals, there was a considerable agreement between the diagnosis of hypertension provided by home and ambulatory BP measurements. However, in about 20% of the cases, the two types of BP measurement led to different diagnostic conclusions, because of methodological and patient-related factors. In the words of the authors, this represents an ‘appreciable minority’, which supports collection of BP data by both methods, as suggested by the recent European guidelines, which describe home and ambulatory BP measurements as complementary rather than alternative. Vigen et al. (pp. 1982–1990) show that, in a Norwegian population, single BP measurements at age 40 years was positively and independently associated with the carotid plaque burden in the later life, which emphasizes the importance of high BP for the development and progression of atherosclerosis. Li et al. (pp. 1991–1999) show, in a meta-analysis that included more than 128 000 patients from 43 studies, that in acute ischaemic stroke, women exhibit higher SBP values than men, a phenomenon that seems to be more evident with increasing age and that the authors ascribe to the greater rate of a preceding mild hypertension in the female sex. Kang et al. (pp. 2000–2006) show that, in a large (n = 4415 patients) prospective stroke registry data-base, BP variability [measured by the standard deviation (SD) of the mean BP values collected over 72 h after the stroke episode] was significantly related to 1-year poststroke mortality, its impact being greater than that of mean BP. Ma et al. (pp. 2007–2014) report that, in a Chinese population, stage 1 hypertension as defined by the 2017 ACC/AHA guidelines (systolic BP 130–139 mmHg) was associated with a noticeable increase in the risk of cardiovascular events (+43% compared with lower BP values), an observation in line with increased cardiovascular risk repeatedly described in people with a high normal BP, as was previously called the BP stratum now defined grade 1 hypertension by the US guidelines. Cifkova et al. (pp. 2015–2023) report on the data collected by EUROASPIRE IV in patients aged 80 years or less who were hospitalized for coronary disease. As in all previous EUROASPIRE surveys, BP control was found to be insufficient in a large proportion of these patients, confirming that in Europe BP control does not seem to improve substantially even in patients with a clinical condition that should favour the awareness of the BP-cardiovascular disease relationship. Li et al. (pp. 2024–2031) show that, in an old Chinese population, supine heart rate was positively related with total cardiovascular mortality. Interestingly, the relationship was not seen for heart rate measured in the sitting position, which led the authors to suggest that collecting supine heart rate values may be preferable.

Three articles address the structure and function of vital organs in hypertension. Wang et al. (pp. 2032–2040) show that in primary aldosteronism, left atrial volume and stiffness, as quantified by speckle tracking echocardiography, are altered. This provides interesting information either on the extent of organ damage in secondary hypertension (which has been studied much less than in essential hypertension) and on the perspective that new technology offers for early detection of subclinical alterations of atrial anatomy and function at high BP in general. A similar message is provided by the subsequent article of Lembo et al. (pp. 2041–2047) who describe the detection of early diastolic and longitudinal left ventricular dysfunction by 3D echocardiography in native hypertension. Ma et al. (pp. 2048–2060) focus on the factors involved in the pathogenesis of preeclampsia, providing specific evidence on the role played by BCL-2/adenovirus E1B 19KD Interacting Protein 3 (BNIP3) on decidual cells.

Finally, five articles are devoted to treatment of hypertension. In an experimental study on pigs Nargesi et al. (pp. 2061–2073) describe the existence of a sequential relationship between mitochondrial damage and loss of renal function in renovascular hypertension. In another study, Chen et al. (pp. 2074–2082) report on the improvement of renal function in renovascular hypertensive pigs, in which kidney revascularization had been preceded by exposure to extracorporeal shock wave therapy, a procedure shown to stimulate angiogenesis and reduce renal inflammation and fibrosis. Because of the disappointing functional results of restoring an elevated BP by balloon angioplasty in patients with an atherosclerotic renal artery stenosis, this has interesting clinical implications. Further clinical considerations can be found in the Editorial Commentary of van Twist (pp. 1963–1965). Qian et al. (pp. 2083–2092) show the effectiveness of renal denervation by transcatheter microwave ablations over a long segment of the renal artery, a procedure that was apparently devoid of arterial as well as collateral visceral injury. Studies on novel procedures that denervate the kidney more effectively than the older ones are published more and more frequently, with no clear evidence, however, that this leads to antihypertensive effects greater than those described in earlier studies in which less aggressive renal denervation procedures were used. However, the rationale behind the therapeutic use of renal denervation is pathophysiologically valid and this line of investigation is thus, worthwhile. Vukadinović et al. (pp. 2093–2103) report that, in a meta-analysis of 22 trials for a total of 7226 patients, peripheral oedema was, as expected, much more common in patients with amlodipine. However, when the concomitant rate of oedema in the placebo or control group was considered, the number of oedema cases for which amlodipine was responsible decreased by 37%. This implies that the tolerability profile of this calcium channel blocker is more favourable than usually perceived, a conclusion that the study of Vukadinović et al. further supports with the observation that in patients treated with low–moderate doses of amlodipine headache was less common than in placebo/control patients. Finally, Sandset et al. (pp. 2104–2109) show that in the Efficacy of Nitric Oxide in Stroke trial, different BP modifications during the interval from the acute stroke to the day 1 after the event (5% decrease to 5% increase, 5–15% decrease and >15% decrease) were associated with a progressive reduction in functional disability at 90 days (modified Rankin scale score). After the disappointing results of several recent trials, this may help in restoring some confidence in the potential benefit of BP-lowering interventions under these circumstances.

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Conflicts of interest

There are no conflicts of interest.

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