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Highlights of the April issue

Mancia, Giuseppe

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doi: 10.1097/HJH.0000000000002391
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The April issue of the Journal of Hypertension includes four reviews of topics of major current interest, two of which with the addition of a meta-analysis of available studies. Quarti Trevano et al. (pp. 565–572) review the microneurographic studies on the metabolic syndrome and show that this condition is characterized by sympathetic hyperactivity. This might be predictable on the basis of the evidence that most individual components of the metabolic syndrome, that is, a blood pressure (BP) elevation, an increase of BMI and an alteration of glucose metabolism, are associated with sympathetic activation. The meta-analysis of Quarti Trevano et al., however, shows that this activation is substantial (30% increase compared with the control group) and that the BP component is the major contributor, which expands the available evidence. Han et al. (pp. 573–578) report, by a meta-analysis of 16 studies, that grade 1 hypertension as defined by the recent American College of Cardiology/American Heart Association (ACC/AHA) guidelines (130–139/80–89 mmHg) is accompanied by a significant increase in the risk of cardiovascular events. This is also predictable as the ACC/AHA grade 1 hypertension corresponds to the previous ‘high normal BP’ category, whose greater cardiovascular risk had been known since the publication of the Framingham data. Yet the meta-analysis of Han et al. is remarkable not only for its gigantic dimension (3 212 447 participants and 65 945 events) but also because it shows that, compared with lower BP values a BP between 130–139 and 85–89 mmHg (systolic/diastolic) increases the cardiovascular risk by almost 40%. This strengthens the current notion that, no matter how we call it, this BP category should prompt preventive measures through lifestyle changes and, when evidence is available, BP-lowering drug treatment. Poulter et al. (pp. 579–587) address a topic of great importance not only for hypertension but also for cardiovascular prevention in general, that is, low adherence to the prescribed treatment regimen. Emphasis is placed on the need to improve measurements of adherence in clinical practice as well as to identify the factors involved in this phenomenon, which is the major cause of poor BP control worldwide. As emphasized by the authors, hope can be placed on new electronic tools as well as on the availability of single pill combinations of two or three antihypertensive drugs as treatment simplification has been repeatedly shown to improve adherence. Finally, Cameli et al. (pp. 588–598) review the pivotal role of echocardiography for the assessment of cardiac damage in hypertension. Traditional measurements, such as left ventricular mass, relative wall thickness, and left atrial volume are duly mentioned, with the warning not to forget to look at other measurements as well, such as the aortic dimension and the aortic valve, the latter because of the frequent association of hypertension with aortic stenosis or regurgitation. The potential advantages of combining standard with advanced (speckle tracking and three-dimensional) echocardiography are also addressed.

The next five papers deal with epidemiological aspects of hypertension. Li et al. (pp. 610–617) report that visit-to-visit BP variability exhibited an association with the risk of stroke in more than 3000 patients with mild-to-moderate chronic kidney disease. The association was seen both when variability was measured by the standard deviation of the mean and when the coefficient of variation was used instead, which eliminated the problem of the confounding relationship of the standard deviation with mean BP values. The relationship of BP variability with stroke in general is discussed in the Editorial Commentary of Angeli et al. (pp. 618–624). Zhao et al. (pp. 599–602) show the association of the metabolic syndrome with an increased carotid intima--media thickness in more than 2000 children and adolescents. They also report, however, that the association was better when the factors used to diagnose metabolic syndrome were individually considered, which is in line with the long-standing criticism of the diagnostic utility of unifying these factors into a single condition. Jiang et al. (pp. 625–632) show that, in an adult Chinese cohort, hyperuricemia was not only accompanied by a greater risk of microalbuminuria but also that this effect probably played a role in the well known association between increased serum uric acid levels and the greater risk of new onset hypertension. Cuspidi et al. (pp. 633–640) provide evidence from the PAMELA study that in normotensive individuals, echocardiographic left ventricular mass index was independently associated with the 10-year risk of developing hypertension. Gaffey et al. (pp. 641–648) confirm, cross-sectionally, that in young and middle-age veterans, a posttraumatic stress disorder is associated with hypertension. They further show that this association is probably mediated, at least in part, by sleep disorders (difficulty to fall asleep, difficulty to stay asleep, distress about sleeping problems, etc.). This is in line with the often reported association of sleep quality and duration with daytime BP values, to which the study by Gaffey and coworkers provides a clinical example.

Diagnostic aspects of hypertension are addressed in the following four articles. Yamagami et al. (pp. 649–655) show that in older adults (mean age about 72 years) daytime physical activity was inversely related to night-time BP values, that is, that individuals exercising during the day exhibited a lower night-time BP. This is an observation with therapeutic implications as the superior prognostic importance of night-time (vs. daytime) BP is well known. The topic is discussed also in its general aspects in the Editorial Commentary of van den Meiracker et al. (pp. 603–604). Wohlfahrt et al. (pp. 656–662) report that in almost 2600 individuals, BP measurements by healthcare personnel (the so-called ‘attended’ condition) lead to values that were higher than those subsequently obtained in the ‘unattended’ condition, that is, when subjects were left alone and asked to activate an oscillometric BP measurement device by themselves. Interestingly, the difference was similar regardless whether, in the attended condition, BP was measured by auscultatory or oscillometric methods, an ‘attended’ SBP of 140 mmHg approximately corresponding to an ‘unattended’ SBP of 127 mmHg. Although the nonrandomized but sequential set of measurements employed by the authors might have contributed, this provides further evidence that the involvement of health personnel in BP-measuring procedures is likely to raise BP in a clearcut fashion regardless of the BP-measuring methodology. Feitosa et al. (pp. 663–670) report that in a large cohort of untreated hypertensive patients with both office and home BP measurements, white-coat hypertension was more frequently attributable to an isolated increase of only SBP or only DBP than to an elevation of both pressures. This was the case also in a similarly large cohort of treated hypertensive patients, a condition in which therapeutic control of out-of-office but not of office BP is termed as ‘white-coat uncontrolled BP’ or WUCH. Martinez-Aguayo et al. (pp. 671–678) report data obtained in healthy children, which help identifying what should be the physiological plasma aldosterone levels from the urinary Na/K ratio. This may improve the clinical detection of an abnormal function of the renin--angiotensin--aldosterone system at a young age.

Six articles of the current issue of the Journal deal with vascular or cardiac damage. Shi et al. (pp. 679–691) report that following administration of caffeine to pregnant rats, old offspring exhibited an alteration of cerebral artery functions related to the PKA/RyR/BK Ca pathway. Litwin et al. (pp. 692–700) observed a negative correlation between circulating regulatory T cells, BP elevations and arterial stiffness in children with primary hypertension. Omboni et al. (pp. 701–715) report an association of 24-h mean brachial or central BP with various measures of organ damage (left ventricular mass, carotid intima--media thickness, increased urine albumin excretion or reduction in glomerular filtration rate, and pulse wave velocity) with a marginal advantage for central compared with brachial artery BP. Leone et al. (pp. 716–722) show that in hypertensive patients with no other risk factor for aortic dilatation the proximal aorta exhibited an average increase of about 0.1 mm/year over a 5-year follow-up. No clinical or anthropometric variable predicted the rate of aortic dilatation, which was slower, however, in patients showing a low dilatation value at baseline. Peng et al. (pp. 723–730) show that in adult individuals, reservoir pressure parameters (reservoir and excess pressure) have a relationship with a measure of organ damage of prognostic significance, such as carotid intima--media thickness even when obtained by cuff BP measurements rather than by measurements such as tonometry, hardly usable in medical practice. This may open their contribution to cardiovascular risk quantification to a wider use. Pedersen Laigaard et al. (pp. 731–736) provide useful information on the outer diameter, inner diameter, and wall-to-lumen ratio of retinal arterioles in relation to BP and body composition in a population-based cohort of adolescents. BP values and indices of body mass, body fat, and hip or waist circumference all showed an association with retinal wall thickness in both male and female individuals. The importance of increasing knowledge on retinal arterioles can hardly be overemphasized, considering that this is an easy non-invasive source of information on the small vessel status in untreated and treated patients.

The final four articles deal with secondary hypertension (two articles) and treatment (two articles). Warchoł-Celińska et al. (pp. 737–744) report the results obtained by a thorough examination of the clinical characteristics of 232 patients with fibromuscular dysplasia. When compared with controls, patients with fibromuscular dysplasia exhibited smaller visceral arterial diameters as well as more frequent aneurisms of celiac and other visceral arteries. The authors conclude that this implies that fibromuscular dysplasia reflects generalized visceral artery abnormalities and that this should prompt a widespread in-depth examination of all vascular beds in these patients. Further comments and considerations on this issue are available in the Editorial Commentary of van Twist (pp. 605–607). Er et al. (pp. 745–754) report that in the Taiwan's National Health Insurance Research Database, a large number of hypertensive patients with aldosterone-producing adenomas showed a much higher prevalence of autoimmune diseases than propensity score-matched hypertensive controls. Interestingly, the incidence of autoimmune diseases was also higher in patients who had been treated with adrenalectomy or with antialdosterone agents. This provides support to the hypothesis that primary adenoma-dependent aldosteronism may be part of a generalized autoimmune disease.

The two articles on treatment address therapeutic interventions in experimental hypertension. Uijl et al. (pp. 755–764) show that in diabetic hypertensive rats, sacubitril with valsartan and valsartan alone both substantially lowered BP and albuminuria. Only the combined treatment, however, increased the urinary levels of atrial natriuretic peptide, improved glycemic control and protected podocyte integrity, with a reduction of glomerulosclerosis that indicated a nephroprotective effect independent from the BP fall. The issue is discussed in the Editorial Commentary of Berbari (pp. 608–609). Costa-Veiga et al. (pp. 765–773) show that in a rat model of chronic kidney disease, selective denervation of afferent renal fibers (by periaxonal application of capsaicin) decreased BP and normalized the preexisting renal and splanchnic sympathetic hyperactivity. This offers experimental evidence that the well known pressor and sympathetic stimulating influences of afferent renal fibers are involved in the BP depressor effects of renal denervation in hypertension.


Conflicts of interest

There are no conflicts of interest.

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