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Highlights of the August issue

Mancia, Giuseppe

doi: 10.1097/HJH.0000000000001822
Editor's Corner

Università Milano-Bicocca, Milan, Italy

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

The August issue of the Journal of Hypertension includes original research articles and meta-analyses on the epidemiological and treatment aspects of this condition as well as on its association with organ damage.

The ‘epidemiological’ articles cover a wide range of issues. Benitez-Camps et al. (pp. 1656–1662) show that administration of paracetamol at the dose of 3 g/day leads to an about 4 mmHg increase in 24 h mean systolic BP. Data were obtained in a relatively small number of patients (n = 46) according, however, to a cross-over design (randomized paracetamol and control periods in all individuals), which minimized the risk of chance results and justified the conclusion that this commonly used drug is associated with a nonmarginal pressor effect, considering that a 4 mmHg increase in ambulatory systolic BP roughly corresponds to 6 or 7 mmHg increase in office systolic BP. Hou et al. (pp. 1663–1670) report that in a large (n = 1254) cohort of children and adolescents, pulse and mean arterial pressure independently predicted adult carotid intima–media thickness, once more emphasizing the importance of early-life BP for the future development of vascular damage and, indirectly, the need of early intervention for prevention of later disease. Buendia et al. (pp. 1671–1679) analyze data from several large studies (184 178 subjects) showing that a higher dairy intake (cheese, milk and especially yogurt) is associated with a reduced risk of high BP in the middle age, the reduction rising from 8% to up to 30% when the increase of dairy consumption was combined with the DASH diet. Years after the controversial reports on the relationship between calcium and BP, this provides evidence on the favourable effect of calcium-rich food on the risk of developing hypertension, adding, more in general, to the already abundant evidence that, over the lifetime, the risk of a BP elevation can be effectively counteracted by dietary means. Finally, Mehata et al. (pp. 1680–1688) provide large up-to-date evidence on the prevalence of hypertension in a part of the world in which healthcare-related data are not easy to be collected, Nepal. In 13 598 participants in the study, hypertension prevalence was 18%, a figure that compares favourably with that reported from other Asian countries. However, only 38% of the hypertensive individuals were aware of their condition, and only 18% were taking antihypertensive medications, with a rate of BP control of 52%, namely, only about 9% of the overall hypertensive population. After the comprehensive data provided by the PURE study, this confirms that in nonindustrialized countries, BP control can be extremely poor, a phenomenon responsible for the persistence of hypertension as the first cause of death worldwide.

Organ damage in hypertension is addressed by the following five articles. Sekoba et al. (pp. 1689–1696) report that masked hypertension (diagnosed by a normal office and a high ambulatory BP) involved more than 16% of a cohort of black and white individuals aged 20 to 30 years, and exhibited a significant association with an increased echocardiographic left ventricular mass index, after adjustment for multiple confounding variables. This is in line with the results of several other studies that found a greater prevalence of left ventricular hypertrophy in subjects with a selective elevation of ambulatory BP, adding to the available evidence that because cardiac organ damage is already detectable at a relatively young age, masked hypertension can lead to an early development of this abnormality. Lembo et al. (pp. 1697–1704) show that, compared with the classical two-dimensional echocardiography, three-dimensional echocardiography may detect left ventricular abnormalities such as a concentric remodelling in a greater number of subjects (37 vs. 24%, P = 0.03), thereby offering a more accurate assessment of myocardial dysfunction in hypertension. As discussed in the accompanying Editorial (pp. 1648–1650) by Cuspidi and Tadic, this is of practical interest, because in hypertensive patients myocardial dysfunction has an adverse prognostic significance that makes its regression by appropriate treatments a desirable goal. Spoto et al. (pp. 1705–1711) describe a polymorphism of the Sirt-1 gene (a mediator of the response to oxidative stress and inflammation) associated with concentric remodelling of the left ventricle in two cohorts of patients with chronic kidney damage. Thus evidence continues to grow that genetic factors are importantly involved in the determination of left ventricular structural abnormalities in different diseases. Whether this will lead to the use of genetic profiling to identify patients with a greater risk of developing organ damage remains an important but unfortunately remote goal. Perez-Hernandez et al. (pp. 1712–1718) found that diabetic and nondiabetic patients with microalbuminuria or macroalbuminuria exhibit an increased urinary level of nephrin, aquaporin, podocalyxin, that is, proteins which have been associated with a podocyte damage of the kidney that may favour the loss of proteins from the glomerulus. This also suggests that measuring the urine concentration of podocyte-related proteins may provide a marker of early glomerular injury. Finally, Viazzi et al. (pp. 1719–1728) report that in hypertensive type 2 diabetic patients, a persistent 4-year albuminuria was accompanied by a marked increase in the risk of progression of renal damage (assessed as a greater than 30% loss of estimated glomerular filtration rate or the development of stage 3 kidney disease) compared with a persistently normal albuminuria, adding to the evidence that changes in urinary protein excretion during treatment predict the risk of renal outcomes. Because a relationship between treatment-induced changes in urinary protein excretion and renal (or cardiovascular) outcomes has not been found in all studies, this will not put an end to the continuing debate on whether the antiproteinuric effect of treatment can be a proxy of the treatment ability to prevent ‘hard’ clinical events. It seems appropriate to emphasize, however, that the results of Viazzi and colleagues are based on 12 611 patients in whom glomerular filtration rate was estimated over a 1-year baseline and at regular visits during the 4-year follow-up, a remarkable collection of relevant data that strengthens the article conclusions.

The remaining articles of the August issue deal with secondary hypertension and various aspects of antihypertensive treatment. Van Twist et al. (pp. 1729–1735) make the interesting observation that unifocal fibromuscular dysplasia may have more severe consequences for renal hemodynamics and function (renal blood flow and renin secretion) than multifocal fibromuscular dysplasia, advancing the hypothesis that 1) the pathophysiological mechanisms that operate in these two subtypes of renovascular hypertension differ and 2) this may account, at least in part, for the different effects of treatment. Ferreira et al. (pp. 1736–1742) found that, as in hypertensive patients, in patients with a previous myocardial infarction and a persistent systolic dysfunction or heart failure, an increased visit-to-visit BP variability was associated with a worse prognosis. They further found, however, that this was the case also when visit-to-visit BP variability was low, giving the variability–outcome relationship a U-shaped appearance. The increased risk of outcome at low visit-to-visit BP variability values may suggest that, ‘fixed’ rather than variable BP values between visits might result from the existence of serious clinical conditions that limit the ability of BP to vary in response to environmental and other stimuli. That is, that visit-to-visit BP variability might sometimes be not the cause but the effect of an existing disease, making the results the expression of a reverse causality phenomenon. Lefferts et al. (pp. 1743–1752) describe the effects of aerobic exercise (30-min cycling) on arterial stiffness and the carotid or middle cerebral artery pulsatility index and report that no difference can be seen between normotensive and hypertensive individuals. As pointed out by both the authors and by the accompanying Editorial Commentary (pp. 1651–1653) the hemodynamic effects of exercise are complex and still far from a detailed description. This is highly desirable also to identify the variables that might suitably address the still unresolved problem of whether and how much exercise-based data improve the diagnosis of hypertension as well as its prognostic assessment. Schwartz et al. (pp. 1753–1761) provide further evidence on the pros and cons of self-management of hypertension. The pros appear to be that the self-management strategy does reduce BP whereas the cons are that about one-third of the patients did not complete the required training sessions, did not follow the prescribed treatment algorithms or dropped out from the program. Thus, self-management of hypertension requires, to be effective, training, attention and monitoring. In other words, this interesting therapeutic approach is exposed to the same problems (low adherence and inertia) of the traditional treatment approaches. This is also discussed in the Editorial Commentary of Omboni (pp. 1654–1655). Finally, an original article and a meta-analysis address resistant hypertension. The original article (Wallbach et al., pp. 1762–1769) reports on the 1-year effects of the a new baroreceptor activation device (Barostim neo) in 42 patients with resistant hypertension. The initially high systolic BP (169 mmHg) was clearly reduced after a 6-month baroreceptor stimulation (148 mmHg), and the reduction did not show any attenuation after the stimulation was extended to 1 year (145 mmHg). This, and the few reported side effects, make use of this new device promising 1. For both baroreceptor stimulation and renal denervation, however, a research priority remains the documentation that the BP reduction is associated with a reduction in the risk of cardiovascular and renal events, which are markedly increased in patients unable to reach BP control with multiple antihypertensive drug treatment. In this setting, promising data are provided by a meta-analysis of Kordalis and co-workers (pp. 1614–1621) who show that, in 698 patients from 17 studies, renal denervation led to regression of left ventricular mass as assessed by echocardiography or nuclear magnetic resonance. Although the relationship between treatment-induced improvement of organ damage and the risk of subsequent outcomes remains a debated issue, this scores in favour of the protective effect of invasive treatment procedures in resistant hypertension, supporting the planning and conduction of future outcome-based studies.

Finally, the August issue of the Journal of Hypertension includes two large meta-analyses from Thomopoulos and co-workers (pp. 1622–1636 and pp. 1637–1647) that continue the series published in the Journal by the same authors over the last few years. Both meta-analyses focus on the effect of antihypertensive drug treatment in patients younger and older than 65 years, with results that leave no doubt that the protective effect of BP-lowering interventions is independent on age and extends to patients older than 80 years and younger than 55 years. The data also indicate that in older people treatment should start at systolic values of 140–159 mmHg, aim at a target BP of less than 140/80 mmHg and make use of the drug classes recommended for preferred use by the most accredited international guidelines (thiazides or thiazide-like diuretics, blockers of the renin–angiotensin system, calcium channel blockers and beta-blockers) because for all of them administration is accompanied by a reduced incidence of events compared with placebo. This provides further support to the notion that the benefits of antihypertensive treatment originate from BP lowering ‘per se’ rather than from the type of treatment employed, and that controlling BP with whatever drugs are effective is thus the primary treatment goal. A new finding of these meta-analyses, however, is that use of beta-blockers is as protective as that of other drugs in younger people whereas in older people the protective effect of these drugs is somewhat less marked. The readers of the previous meta-analyses will have appreciated that the driving force behind them was Alberto Zanchetti, Emeritus Professor of Medicine at the University of Milan, Italy, who passed away while these last two articles were under review. Alberto Zanchetti has been for 23 years the Editor-in-Chief of the Journal of Hypertension to the success of which he has immensely contributed with his wide scientific culture, experience and dedication. An obituary reporting his life achievements has been published in the July issue of the Journal.

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Conflicts of interest

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