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Highlights of the September issue

Mancia, Giuseppe

doi: 10.1097/HJH.0000000000002193

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

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

The September issue of the Journal of Hypertension starts with a document authored by the investigators appointed by The Lancet about 2 years ago to critically address and propose innovative studies in areas of hypertension in need of improvement. Following a comprehensive document published in 2018 (Lancet 2018; 392:1923–1994), this group (Padwal et al., pp. 1737–1745) provides a position paper on how to improve the accuracy of office blood pressure (BP) measurements. One can hardly think of a more important aspect of hypertension to deal with for at least two major reasons. First, despite an increased (and somewhat uncritical) enthusiasm for use of out-of-office BP monitoring, office BP maintains a central position for hypertension diagnosis and treatment because of the superior amount of good epidemiological data and the evidence (not replicated by out-of-office BP-based studies) that its reduction by treatment is associated with patients’ protection. Second, there is a general agreement that the accuracy of office BP measurements leaves much to be desired and that improving the way BP is measured by health operators (better accuracy of the BP measuring devices, standardization of the environmental conditions which affects office BP, uniformity of the number and the timing of collected BP values etc.) may lead to substantial advantages, making the alternative approach recently supported by guidelines, that is, extended use of home and/or ambulatory BP monitoring, less compelling.

The following four articles provide meta-analyses of the data available on a number of debated issues. Grassi et al. (pp. 1746–1756) report on a meta-analysis of the studies that have looked at the sympathetic nerve traffic in people with heart failure. In more than 2500 patients, sympathetic nerve activity to skeletal muscle circulation was about twice as large in heart failure patients than in controls, the increase being related to various markers of the severity of hypertension. Significantly, the sympathetic activation was evident not only in untreated but also in treated heart failure patients, which suggests that currently used drugs (most of which have a sympathomoderating effect) fail to restore a normal sympathetic drive. Pinho-Gomes et al. (pp. 1757–1767) show that, in more than 91 000 heart failure patients from 37 trials, treatment with drugs that have a BP-lowering effect did result into a significant, albeit small, BP reduction. The reduction, however, did not bear any relationship with the beneficial effects of treatment on heart failure-related outcomes, which were also independent on baseline BP values. A further insight into the problem, including the substantial lack of additional side effects when heart failure treatment reduces BP, is provided by the editorial commentary of Sciarretta and Volpe (pp. 1786–1774). Salam et al. (pp. 1768–1774) show that, in more than 13 000 patients from 33 trials, initial antihypertensive treatment with a combination of two drugs lowered BP significantly more than initial standard-dose monotherapy, with an increase also in the rate of BP control. Compared with initial monotherapy, a greater BP reduction and control characterized also combinations of smaller doses of the drugs, which had the important advantage of being devoid of any greater incidence of withdrawal for adverse events. This provides support to the recent European guidelines which recommend to start treatment with dual drug combinations in most hypertensive patients. Finally, Zhang et al. (pp. 1775–1785) confirm, in 21 studies on more than 130 000 patients, that masked hypertension carries a significantly greater cardiovascular risk than normotension (+67%, 95% confidence interval 32–113%). This was the case in untreated individuals but also in people in whom a selective increase of out-of-office BP was due to full treatment effectiveness on office BP only. It should be mentioned that the extremely high number of patients included in the analysis was made possible by use of somewhat heterogeneous diagnostic criteria for masked hypertension, that is, use of ambulatory or home BP monitoring values as well as diagnosis of an out-of-office BP elevation by 24 h but also by daytime or night-time BP only. Use of stricter and more homogeneous BP criteria by future analyses will provide useful complementary data.

The next five articles address epidemiological aspects of hypertension. Miller et al. (pp. 1790–1796) provide further evidence that in the US people aged 75 years and older BP values were associated with cognitive decline, with the additional observation, however, that the association was different according to the self-reported functional status, that is, the level of daily living activities at baseline. Buhnerkempe et al. (pp. 1797–1804) provide the first representative estimate of the prevalence of refractory hypertension in the United States, based on 41 552 patients from the National Health and Nutrition Examination Survey database studied between 1999 and 2014. Although varying widely with the year of the assessment, only 6.2% of the patients classified as resistant hypertensive were found to have refractory hypertension, which implies that this condition is relatively rare. Senanayake et al. (pp. 1805–1812) report on the prevalence of hypertension in a rural area of Sri Lanka (26.3%) as well as on the marked increase of patients with a BP elevation who had an estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 m2. Lamelas et al. (pp. 1813–1821) show that, in Latin America, prevalence of hypertension is high, whereas awareness of the elevated BP status, percentage of treated patients and rate of BP control are low. Marked differences were found between different Latin American countries, which all shared, however, a relatively low use of combination treatment (36.4%), at variance from what hypertension guidelines have strongly recommended since years. Another interesting, although disappointing observation, is the very low rate of statin use (12.3%, with a 7% use in rural areas) which documents that in this continent management of cardiovascular risk factors in general is inadequate. Bischops et al. (pp. 1822–1831) show that in India a substantial fraction of the population has both raised BP and raised blood glucose. The unfavourable cardiovascular risk profile of the Indian population has been the object of several recent publications, which have also emphasized that the increased risk includes coronary disease. This makes individuals from Southern Asia different from those living in the northern part of the continent. The matter is further addressed by the Editorial Commentary of Egan (pp. 1788–1789).

The following six articles deal with BP measurements (two articles) and organ damage (four articles). Tasic et al. (pp. 1832–1837) provide results that score favourably on the intercentre reproducibility of the European Society of Hypertension-International Protocol for the validation of devices to be used in patients with large arms. This is of obvious importance because inaccuracy of BP measurements in obese individuals (with overestimation of the initial values and underestimation of the effects of treatment) is a well known problem. Salazar et al. (pp. 1838–1844) provide the interesting observation that in pregnant women masked hypertension is accompanied by an increased risk of preeclampsia which, however, disappears if office BP values are less than 125/75 mmHg. Thus, in pregnancy office BP by no means appears to be devoid of clinical importance vis-a-vis out-of-office BP, a finding that expands on the debated issue of the relative role and interaction of these pressures in different clinical conditions.

As to the articles on organ damage, Broyd et al. (pp. 1845–1852) show that, in 186 patients who underwent trans-cathether aortic valve implantation, intraoperative aortic pulse wave velocity values correlated with the risk of 1-year mortality. Deriaz et al. (pp. 1853–1860) show that, in 4141 whites followed for 5.4 years, 24-h urinary sodium and sodium/potassium ratio were associated with a decline in renal function, as quantified by eGFR reduction. This has dietary implications, which are discussed by the authors. Gonçalves et al. (pp. 1861–1870) describe the participation of tenascin-C in the cardiac dysfunction that may accompany left ventricular remodelling in rats. Vukomanovic et al. (pp. 1871–1876) provide a detailed description of the damage of the myocardial layers associated with uncomplicated type 2 diabetes. They further show a relationship between left ventricular damage and functional capacity as quantified by measures such as peak VO2, oxygen pulse and ventilation/carbon dioxide slope, which emphasizes the adverse consequences of cardiac function alterations on the ventilation/respiration processes.

The final four articles deal with treatment. Zaleski et al. (pp. 1877–1888) report on the clear-cut favourable effect of self-monitoring of the postexercise hypertension on adherence to exercise in male and female hypertensive patients. Nonpharmacological treatments are notoriously characterized by an extremely poor adherence, which makes data on adherence improvement highly relevant to hypertension management, particularly when, as was the case in this study, the improvement was not marginal. Izzo et al. (pp. 1889–1897) report that, in more than 4000 treated hypertensive patients from a ‘real life’ setting, the lowest achieved DBP value (74.1 mmHg, lowest quintile) was associated with a 49% higher risk of cardiovascular events. Somewhat at variance with this message on the risk of low BP values, in the subsequent article Kim et al. (pp. 1898–1905) showed that, in more than 1000 coronary patients who had undergone positioning of drug-eluting stents, a SBP less than 120 mmHg was more protective than a SBP more than 120 mmHg. The optimal BP target to be reached in coronary patients has long being controversial because a number of studies (INVEST trial, CLARIFY Registry etc.) have shown cardiovascular outcomes to increase progressively as SBP decreases below 130 mmHg. The critical factors can be, however, the absence or presence of myocardial revascularization because, like in the article of Kim et al. in the INVEST trial the increased risk of outcomes at lower BP values was not visible in patients in whom myocardial perfusion had been therapeutically re-established. Finally, Daemen et al. (pp. 1906–1912) show that a new renal denervation system based on endovascular ultrasounds significantly reduced office and ambulatory BP in 96 patients with resistant hypertension. At 12 months from the denervation the office and 24-h systolic reductions were 15.0 and 7.5 mmHg, respectively, which is in line with the BP-lowering effects of other denervation approaches. Except for a death unrelated to the device or the procedure, no untoward effects were observed, which is in favour of the safety of this new denervation method.

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Conflicts of interest

There are no conflicts of interest.

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