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Highlights of the March issue

Mancia, Giuseppe

doi: 10.1097/HJH.0000000000002045
EDITOR'S CORNER
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Università Milano-Bicocca, Milan, Italy

Correspondence to Prof. Giuseppe Mancia, Università Milano-Bicocca, Piazza dei Daini, 4, 20126 Milano, Italy. Tel: +39 3474327142; e-mail: giuseppe.mancia@unimib.it

The first article of the March issue of the Journal of Hypertension provides a guidance on how to perform and report validation studies on new blood pressure (BP) measuring devices, based on a Consensus document of the Association for the Advancement of Medical Instrumentation, the European Society of Hypertension Working Group on BP measurement and the International Organization for Standardization (AAMI, ESH and ISO) (pp. 459–466). Simple but detailed recommendations are reported along with protocol steps and checklists (for investigators and reviewers) of the points that have to be addressed to make a study scientifically adequate. Because accuracy of BP measurements has a central position in the diagnosis and management of hypertension, this is a contribution of considerable importance.

The subsequent three reviews deal with the relationship between the reduction of office and ambulatory BP as obtained in antihypertensive treatment trials, the sympathetic control of vascular function and BP in pregnancy and eclampsia, and the quality of evidence supporting guidelines on the screening and management of hypertension in children and adolescents. A meta-analysis on the office/ambulatory BP relationship during antihypertensive treatment (Soranna et al., pp. 467–475) includes 52 randomized controlled trials for a total of about 9500 patients. Confirming the conclusion of a previous smaller meta-analysis, the treatment-induced reduction of office BP was found to be markedly greater than the concomitant 24-h mean BP reduction. The quantitative relationship between the two variables, however, varied according to the patients’ demographic and clinical characteristics, which means that, unlike what had been proposed in the past, no single ratio can accurately describe the two changes, and thus permit to decide which ambulatory BP fall may be appropriate for a given office BP effect of treatment. The review on the sympathetic nervous system in pregnancy (Spradley, pp. 476–487) emphasizes that preeclampsia is not only related to the placental release of vasoconstrictor factors of antiangiogenic and proinflammatory nature but also to an increase in sympathetic activity, the magnitude of which correlates with the severity of the preeclamptic condition. This does not prove the participation of a sympathetic activation to the pathogenesis of preeclampsia which, however, is not at all unlikely, given the sympathetic modulation of uteroplacental blood flow, systemic vasoconstrictor tone and BP during normal pregnancy. The article on guidelines on paediatric hypertension (Vaughn et al., pp. 488–495) reports that in this area consensus documents are predominantly based on expert opinions, and that thus more evidence-based information is an important goal to achieve by future documents. Although the absence or paucity of outcome-based long-term studies makes this problem particularly relevant for guidelines in children and adolescents, this is to a considerable extent true also for adult hypertension, as exemplified by the number of diagnostic and treatment recommendations which, in guidelines on adult hypertension, are largely based on a shared opinion among Task Force members.

Four articles of the current issue of the Journal are devoted to the factors responsible for BP variability as well as to its ability to predict outcomes. Zhao et al. (pp. 504–512) report that a 1 °C reduction of indoor temperature is accompanied by a small increase (about 0.5 mmHg) of SBP and DBP, while Vencloviene et al. (pp. 513–521) show that air temperature, atmospheric pressure, relative humidity, wind speed and other climatic factors mat lead, in spring and autumn, to sizeable BP changes, especially in the elderly. As mentioned in the Editorial of Wiley (pp. 496–497), although small, the BP effects of indoor temperature variations may not be irrelevant for the studies on the BP-lowering effects of antihypertensive treatment, particularly when these studies involve the administration of a single drug and thus deal with few mmHg changes. This may be even more the case for BP alterations due to climatic factors, which may affect in an uncontrolled fashion the group effect of treatment in geographically dispersed trials. Little is known, on the other hand, on the prognostic impact of these long-term BP alterations, although in previous studies both day-to-day and month-to-month BP variability have been associated with an adverse effect on cardiovascular and renal outcomes. In this issue of the Journal an adverse prognostic effect of BP variability for cardiovascular outcomes is further documented by two studies, one on long term and the other, at the opposite extreme, on very short-term (10 s periods) BP variations. The study on 10 s BP variations has an added element of interest because variations were referred to central rather than peripheral BP (Sluyter et al., pp. 530–537), whereas the added element of interest of the study on long-term BP variability (Stevens et al., pp. 522–529) is that, although independently related to cardiovascular risk, long-term BP variability did not substantially improve the performance of a multifactorial risk score. This scores negatively on the debated issue whether and how much addition of BP variability makes risk prediction of treated hypertensive patients more accurate than use of achieved mean BP alone. This is, however, a very important question on which further data are desirable.

Several articles focus on cardiac and vascular abnormalities in hypertension. Saeed et al. (pp. 538–545) show that, in young and middle-aged patients with an ischemic stroke, left ventricular dysfunction was common, an observation that is commented by Tadic (pp. 498–500) and that confirms the frequent association between a clinically manifest event with subclinical multiorgan abnormalities. Kuipers et al. (pp. 546–554) describe the alterations of arterial stiffness (measured by pulse wave velocity) in 772 Afro-Caribbean men aged 50+ years. An increased stiffness was common also in patients diagnosed as having grade 1 hypertension as defined by the US guidelines, that is with a SBP between 130 and 139 mmHg, confirming that in this BP category asymptomatic vascular abnormalities are not infrequent. European guidelines term patients with a BP between 130–139 mmHg SBP and 85–89 mmHg DBP as having a ‘high normal BP’ and conservatively recommend to limit antihypertensive drug use only to the presence of a cardiovascular event history. In contrast, the US guidelines recommend drug treatment when the Framingham score indicates that the 10-year risk of a cardiovascular event is more than 10%. This may be common in the elderly population and, according to the present findings, even more common in blacks because asymptomatic organ damage is usually associated with a high cardiovascular risk. Interestingly, in the subsequent two articles, greater vascular damage is reported, cross-sectionally, in African born compared with French born individuals (Safar et al., pp. 555–562) and, longitudinally, as a greater increase of arterial stiffness over an about 8-year follow-up in Americans of African vs European origin (Liang et al., pp. 563–571). A further insight into the matter is provided by the Editorial Commentary of O’Rourke et al. (pp. 501–503), which also focuses on the pathophysiological aspects of the condition termed Takotsubo cardiomyopathy. Finally, Chua et al. (pp. 572–580) describe the results of a study in which optical coherence tomographic angiography was used to measure retinal capillary density in a cohort of treated hypertensive patients. Capillary density was related to a number of factors and significantly greater in patients in whom BP was not controlled than in those in which it was controlled. This is excellent news for studies on small vessel abnormalities in hypertension and other diseases, because it confirms that these abnormalities can be adequately studied by noninvasive techniques, thereby avoiding the drawbacks of the previous approaches, that is invasiveness, barriers to data replication and collection from small numbers of patients only.

The remaining articles focus on pregnancy (Yu et al., pp. 581–589), secondary hypertension (Ohlsson et al., pp. 590–595; Kline et al., pp. 596–602; Rossi et al., pp. 603–611), and antihypertensive treatment (Prieto et al., pp. 612–628; Okin et al., pp. 636–642; Ramirez et al., pp. 629–635; Matsushita et al., pp. 643–649). An article on secondary hypertension (Kline et al., pp. 596–602) makes the interesting observation that most patients (72%) with primary aldosteronism exhibit surprisingly low aldosterone levels in the peripheral veins when sedated for performing adrenal vein aldosterone sampling. As emphasized by the authors, this challenges the concept that, in primary aldosteronism, aldosterone levels are persistently high and nonsuppressible. Aldosterone levels in the adrenal vein remain, however, the preferred method to detect primary aldosteronism, and decide in favour or against of adrenalectomy, as emphasized in a review on the diagnostic aspects of this condition by Rossi et al. (pp. 603–611) Of considerable interest are also the observations made in the articles on treatment. Okin et al. (pp. 629–635) show that, in more than 7000 hypertensive patients, the risk of intraventricular conduction delay (assessed by QRS duration) was significantly reduced (15%) by treatment with an AT1 receptor antagonist than with a beta-blocker. However, the risk of new left bundle branch block was not significantly different between the two groups, which leaves the question of the clinical relevance of the results open. Ramirez et al. (pp. 636–642) report that in type 2 diabetic patients canagliflozin reduced arterial stiffness (measured by pulse wave velocity) and that the reduction was maintained after adjusting for the concomitant BP decrease. Although adjustment procedures are only a tentative means to eliminate confounding, this supports a direct BP-independent effect of this antidiabetic agent on the structure and/or function of the vascular wall. Finally, Matsushita et al. (pp. 643–649) show that, in 2238 consecutive patients with heart failure and an ejection fraction of at least 50%, in-hospital mortality was lower if SBP was at least 140 mmHg, an additional favourable prognostic factor being treatment with beta-blockers rather than diuretics. Current European guidelines do not diversify treatment of heart failure with preserved ejection fraction according to different clinical characteristics or treatment choices, the recommendation being to reduce a high BP by whatever drug can achieve BP control. This study suggests, however, that different treatment strategies may differently affect different heart failure with preserved ejection fraction phenotypes, a stimulus to further research in this direction.

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