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Highlights of the issue

Mancia, Giuseppe

doi: 10.1097/HJH.0000000000001751

Università Milano-Bicocca, Milan, Italy

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

The current issue of the Journal of Hypertension provides reviews, editorial commentaries and research papers on many issues of current interest.

Despite years of research, the relationship between blood pressure and outcome in acute ischemic stroke remains unclear, preventing evidence-based recommendations to be emanated. In this issue of the Journal, the Working Group on Hypertension and the Brain of the European Society of Hypertension provide, with the contribution of invited expert neurologists, a consensus document that reviews what seems to be known (e.g. the relationship between extremely high blood pressure values and poor outcome) and what is still confusing or controversial, above all whether reducing the elevated blood pressure typical of the acute phase of a ischemic cerebrovascular event reduces subsequent brain damage and survival. Several pathophysiological and clinical aspects of this condition are critically addressed in order to clarify the desirable designs and conduction of future studies (pp. 1212–1221).

This is followed by a consensus document authored by Palatini and colleagues on a condition which has come to the attention of clinicians and investigators in the last few years (pp. 1222–1236). The article summarizes the discussion that took place in Padua after the 2016 annual meeting of the European Society of Hypertension on the pathophysiological aspects and epidemiological significance of isolated systolic hypertension in the young, and, in particular, of that subset of young individuals in whom an elevation of brachial SBP is not associated with a central blood pressure elevation. Although data on this issue have importantly grown, no unequivocal conclusions can be reached. That is not so much the case for isolated systolic hypertension of the young ‘tout court,’ which seems to be neither epidemiologically marginal nor prognostically irrelevant. It is the case, however, for isolated systolic hypertension of the young in whom central blood pressure is normal, whose clinical significance remains controversial. Collection of further evidence will remain difficult, however, because clinical events are rare in this population, making resort to data on progression of asymptomatic organ damage perhaps the only feasible approach.

The current issue of the Journal includes reviews and meta-analyses. Yannoutsos et al. (pp. 1237–1246) review the role of aortic stiffness, as measured by pulse wave velocity, in patients with diabetes and end-stage renal disease, and come to the conclusion that even in this extremely high cardiovascular risk condition, this measure retains an adverse prognostic impact with, in addition, the ability to predict the BP-lowering effect of treatment. Nephrologists may thus consider information on pulse wave velocity in end-stage renal failure, not just of research interest, but as an examination with a practical value. Roush et al. (pp. 1247–1255) show, from a meta-analysis of 12 randomized trials, that regression of left ventricular hypertrophy is similar for treatments based on blockers of the renin–angiotensin system (RAS) and for the combination of different diuretics. This may challenge the old notion that diuretics are less effective than RAS blockers against hypertension-related structural cardiac alterations. Finally, Xie et al. (pp. 1256–1265) report the results of a large (n = 143 095) meta-analysis of trials on the cardiovascular effects of different antihypertensive drugs, limited to patients with previous cardiovascular events (except heart failure). The results leave no doubt that even in these patients a blood pressure-lowering intervention is beneficial, this being the case with no significant difference between different drug classes. This expands to secondary cardiovascular prevention, the results of the meta-analyses that have addressed cardiovascular protection by antihypertensive treatment mainly in the primary cardiovascular prevention setting.

The June issue of the Journal of Hypertension also includes the following original research articles. In the blood pressure measurement area, Lindroos et al. (pp. 1276–1283) report that, cross-sectionally, left ventricular mass index correlated to a similar degree with central and brachial blood pressure, an observation that is not in line with the opinion of superior clinical value of central vs peripheral blood pressure. This is further discussed in an Editorial Commentary by Chen and Wang (pp. 1266–1268), who emphasize the limitations of cross-sectional data as well as the crucial importance of longitudinal studies to prove or disprove the central blood pressure prognostic superiority. Eguchi et al. (pp. 1284–1290) report that in more than 4000 type 2 diabetic patients, prediction of cardiovascular and renal events was better for a home SBP of 125 mmHg than for a home SBP of 135 mmHg. Although the optimal home blood pressure target to pursue with treatment remains an elusive goal, this has the merit of addressing an issue on which evidence is extremely limited, given that no trial has ever guided treatment by home (or ambulatory) rather than office blood pressure values. Finally, Tanaka et al. (pp. 1291–1298) show that in hypertensive patients, an exaggerated blood pressure response to exercise predicted, over a follow-up of 2.5 years, incident echocardiographic left ventricular hypertrophy, adding to the evidence that exercise blood pressure may have a clinical value, thereby perhaps deserving more attention than that received by guidelines.

Several other articles provide interesting observations on the epidemiology of hypertension as well as on the effects of high blood pressure on the heart. Wang et al. (pp. 1299–1305) examined in a large number of individuals (n = 84 363) the effect of blood-pressure trajectories, that is, blood pressure changes over time, on all-cause death. Compared with the group in which blood pressure was stable, the groups in which blood pressure changed showed an increased risk of mortality, including those exhibiting a blood pressure decrease from high initial values or a moderate increase within the normal range. This implies that blood pressure changes may be prognostically worse than blood pressure stability, an interesting possibility that deserves to be further addressed. Leyvraz et al. (pp. 1306–1310) showed that in children aged from about 5 to 16 years, a single elevated blood pressure value only weakly predicts future incident hypertension, and that this is particularly the case in younger and nonobese children. This does not question the existence of a ‘tracking’ phenomenon (seen also in this study) but it implies that many exceptions to the tracking rule can occur, especially when factors favouring a blood pressure rise are absent. Cuspidi et al. (pp. 1311–1317) show that in the PAMELA population, a reduced nocturnal bradycardia was associated with a greater risk of developing cardiac damage as well as cardiovascular outcomes, extending to a nondipping heart rate the adverse prognostic significance repeatedly demonstrated for a nondipping blood pressure condition.

Of interest are also the studies on the relationship between blood pressure and cardiac structure and function. The results of the ARCADUA-POL study (Dobrowolski et al., pp. 1318–1325) show that, at variance from atherosclerotic renal artery stenosis, patients with fibromuscular dysplasia do not exhibit any evidence of cardiac damage. Červenka et al. (pp. 1326–1341) describe the blood pressure lowering and antiarrhythmic effects of epoxyeicosatrienoic acids (EETS and EET-A) alone or combined, in rats with Ang-II-dependent hypertension and ischemia/reperfusion. Huang et al. (pp. 1342–1350) report on the arrhythmogenic effect (ventricular arrhythmias) of renal nerve stimulation in dogs with a recent myocardial infarction, an effect that was not seen in those with an old infarction or no cardiac disease. This may represent additional evidence that afferent renal nerve stimulation exerts a detrimental effect, adding that this may be especially the case on a background of organ damage.

Three articles address clinical and experimental aspects of hypertension in the setting of an acute stroke, and two deal with hypertension and aging. In the acute stroke area, one article (Mattaliano et al., pp. 1351–1359) shows that obstructive sleep apnea is common in patients with an acute stroke, and that this association is accompanied by greater structural alterations of the heart. Another (Brambilla et al., pp. 1360–1371) provides the first evidence that in stroke-prone hypertensive rats, the number of tissue factor-positive megakaryocytes is increased, with a greater blood concentration of platelets with a faster kinetic of thrombin generation. A third (He et al., pp. 1372–1381) reports on the effects of an immediate blood pressure reduction (about 8 mmHg of SBP) on death and major disability in patients with an acute stroke. Two weeks after the event, death was more and less common, respectively, in patients in whom initial SBP was less than 160 mmHg and greater than 180 mmHg. At the third month, however, no outcome difference between treated and untreated patients was found at any initial blood pressure value, adding to previous negative reports on the effect of BP-lowering treatment on outcomes in this condition. As regards aging, McDoom et al. (pp. 1382–1390) make the interesting observation that in an aging cohort of individuals followed in a primary care setting, new onset hypertension was lower in those with a high socioeconomic status, as quantified by income and education. Furthermore, Ji et al. (pp. 1391–1398) report that in old people, the prevalence of what is referred to as a healthy vascular aging (no incident hypertension and normal carotid–femoral pulse wave velocity), decreased from 65 to 75 years of age, but was also much more common in absence of metabolic abnormalities and cardiac or renal damage. This implies that vascular aging is not an invariably irreversible phenomenon, but that it can be favourably modified by factors that respond to therapeutic interventions. This is discussed in the related Editorial Commentary by Tadic et al. (pp. 1311–1317).

The remaining articles deal with pregnancy, primary aldosteronism and renal denervation. In female mice with induced preeclampsia (Collinot et al., pp. 1399–1406) show that methods such as Doppler ultrasonography and blood oxygenation level-dependent magnetic resonance (which avoids use of contrast medium) allow to precisely analyze fetal growth at the late stages of gestation, a finding that reinforces the rationale for their clinical use. Kline et al. (pp. 1407–1413) suggest, via a retrospective analysis of primary aldosteronism cases, that adoption of too strict diagnostic criteria for the interpretation of an excessive aldosterone concentration from one adrenal vein may result into the exclusion of a relatively high number of patients who would benefit from surgical ablation of the adrenal gland. And finally Sata et al. (pp. 1414–1422) suggest that use of a marker of arterial stiffness such as the ambulatory blood pressure derived arterial stiffness index (AASI) may predict the pressure response to renal denervation, a lower AASI being associated with a greater 24-h blood pressure fall and vice versa. As the response to renal denervation ranges from no change to a marked blood pressure reduction, predictors of what the effect of the procedure would be have been the object of many studies, unfortunately often with no conclusive results. In this context, the observation of Sata et al. may have an interest because AASI reflects arterial stiffness, which is the main pathophysiological alteration in isolated systolic hypertension, a condition repeatedly shown to poorly respond to renal denervation. AASI may thus translate into a continuous measure what isolated systolic hypertension only predicts on a yes or no basis. The related Editorial by Burnier emphasizes this aspect as well as that AASI is an easy to obtain and cheap measure that makes it suitable for use in clinical practice.

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