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Highlights of the December issue

Mancia, Giuseppea,b

doi: 10.1097/HJH.0000000000002274

aUniversità Milano-Bicocca, Milan

bPoliclinico di Monza, Monza, Italy

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

The December issue of the Journal of Hypertension starts with a review and meta-analysis on the antiproteinuric effect of mineralocorticoid receptor antagonists in chronic kidney disease, a review and meta-analysis on the risk of cardiovascular outcomes associated with prehypertension, and an article with several interesting considerations on the consequences of evolutionary human bipedalism for blood pressure (BP) homeostasis. The data provided by the meta-analysis on the effect of mineralocorticoid receptor antagonists on urinary protein excretion in chronic kidney disease (Alexandrou et al., pp. 2307–2324, 31 reports, 2767 patients) show that these drugs have a clearcut antiproteinuric effect even when administered on top of an angiotensin-converting enzyme-inhibitor or an AT1 antagonist, supporting their greater use in this clinical condition. Other factors to be considered, however, are that, as it might be expected, the antiproteinuric effect of mineralocorticoid receptor antagonists was associated with a noticeable increase in the risk of hyperkalaemia (2.6-fold compared with placebo or active control). Furthermore, and more in general, whether and to what extent a reduction of urinary protein excretion predicts renal and cardiovascular outcomes is still debated. In some studies on hypertensive diabetic or high cardiovascular risk patients (e.g. ONTARGET and TRANSCEND) this was clearly the case, whereas in other studies (ALTITUDE etc.) no such predictive ability has been reported. Han et al. (pp. 2325–2332) found that in 47 studies (for a total of almost half a million patients) both low range (SBP: 120–129 mmHg) and high range (SBP: 130–139 mmHg) prehypertension were accompanied by an increase in the risk of cardiovascular outcomes (risk ratio 1.40 and 1.81, respectively) as well as of myocardial infarction (1.43 and 1.99) and stroke (1.52 and 1.98) compared with people with normal SBP. This is confirmatory of previous studies with, however, a data dimension that further strengthens the evidence that even small BP increases have ominous cardiovascular consequences. Esler et al. (pp. 2333–2340) discuss the consequences of the human evolution to bipedalism, i.e., that bipedalism makes preservation of BP homeostasis against gravity more challenging. According to the authors bipedalism leads to a wider reflex involvement in the cardiovascular adjustment to standing, that is, a reflex modulation of sympathetic vasomotor tone not only by arterial baroreceptors but also by low pressure stretch receptors sensitive to changes in venous return and central volume located in the cardiopulmonary area. This more complex reflex involvement may favour some reflex dysregulations as well as clinical abnormalities such as orthostatic hypotension, orthostatic hypertension and a greater risk of excessive BP falls in response to the administration of BP-lowering drugs.

Five articles of the current issue of the Journal are related to the epidemiology of hypertension. Yi et al. (pp. 2345–2353) provide the interesting observation that in 244 consecutive patients with an ischemic stroke or a transient ischemic attack the magnitude of the acute BP increase was related to the subsequent patients’ outcome, that is, the occurrence of a cardiovascular or cerebrovascular event. Li et al. (pp. 2354–2360) report that in a large number (n = 10 312) of Chinese men living in rural areas the combined use of hypertriglyceridemia with the hip–waist ratio value predicts the risk of incident hypertension, this being the case also for the changes of this composite value from baseline. This is in line with observations, made years ago, on the relationship of other serum lipid components (LDL-cholesterol) with the risk of developing a BP elevation. Information is needed, however, on why in the current study no such relationship was observed in women. Jacobs et al. (pp. 2361–2370) show that in black Africans aged more than 30 years plasminogen activator inhibitor-1 (PAI-1) activity and the 4G/4G genotype increase the odds of developing peripheral and central hypertension compared with the 5G/5G genotype. As mentioned by the authors, this scores in favor of PAI-1 being a contributor of the progression to high BP rather than being a consequence of an elevated BP status. Li et al. (pp. 2371–2379) provide cross-sectional evidence that in 17 398 patients of the NHANES database studied between 2007 and 2014 the dietary content of carotenoids was inversely associated with hypertension, as defined by BP values greater than 130/80 mmHg, in line with the 2017 US hypertension guidelines. The risk of incident hypertension was clearly lower in individuals eating more than 100 μg/kg of carotenoids per day, which is the amount suggested by the authors as the daily quantity of carotenoids to eat. Pugliese et al. (pp. 2380–2388) show that in 658 mid-aged participants prevalence of masked hypertension as diagnosed by the discrepancy between office and ambulatory BP values was much greater in men than in women (60.6 vs. 37.5%), the male sex being thus a powerful predictor of this condition.

The next nine articles deal with organ damage and hemodynamic aspects (three articles), BP measurement (four articles) and pregnancy (two articles). Concerning organ damage Jung et al. (pp. 2389–2397) show that, in a small population of individuals with a mild BP elevation and low cardiovascular risk, retinal layer volumes have an inverse association with DBP, which implies that retinal neurodegeneration can be detected in very early hypertension stages and in absence of any substantial cardiovascular risk elevation. This provides further evidence in favor of the need to promote early treatment of hypertension, when risk is still close to normal and initial organ damage still reversible. This is now recommended by guidelines, in contrast with previous recommendations to wait until cardiovascular risk is high, a condition, however, in which treatment is associated with a high residual risk. Duprez et al. (pp. 2398–2403) describe a relationship between serum collagen biomarkers (ICTP and PIIINP) and renal function, an increase in the collagen biomarker concentration being associated with a decline of estimated glomerular filtration rate, possibly because of progression of renal fibrosis. Data were obtained in 2710 individuals of the Multi-Ethnic Study of Atherosclerosis who were followed for almost 10 years, which gives the observations scientific strength. Weber et al. (pp. 2404–2413) provide population-based age-specific and sex-specific values of several measures (aortic pulse wave velocity, central pulse pressure and backward wave amplitude) of pulsatile hemodynamics based on the examination of a relatively large population (n = 2721) with an age from 18 to 90 years. This can offer reference values with which to compare people with early or healthy vascular aging.

As to the articles on BP measurements, Lurbe et al. (pp. 2414–2421) focus on the differences in the distribution of office BP categories in the guidelines on children and adolescents issued by the American Academy of Pediatrics and the European Society of Hypertension. They conclude that there are differences between the guidelines which are by no means of a marginal clinical value, particularly in overweight or obese children. Differences extend to identification of white coat and masked hypertension (more frequent in the American and European guidelines, respectively) mainly because of a somewhat different approach of the two guidelines to ambulatory BP classification. Rajalingam et al. (pp. 2422–2429) compared the techniques by which central BP is measured in children and conclude that radial tonometry with a radial-to-central transfer function may be an acceptable method, although not immune for errors and inaccuracies, when peripheral BP calibration is used. Stergiou et al. (pp. 2430–2441) address the problem of BP measurements in patients with atrial fibrillation. Following a critical review of the evidence, the article confirms that atrial fibrillation reduces the accuracy of BP measurements but it also supports the view that automated monitoring devices are available by which accurate BP measurements over the 24 h can be achieved also in the presence of an arrhythmic heart. This is important because atrial fibrillation is common, particularly in the older age, and excluding these patients from the possibility to obtain reliable BP values, would represent a major limitation for cardiovascular research and clinical practice. Topouchian et al. (pp. 2442–2451) report the results of a study on 276 patients who were part of a larger group in whom the purpose was to compare the BP-lowering efficacy of initial dual vs. triple drug treatment. The current study focuses on the results obtained by use of ambulatory central BP monitoring and concludes that this is technically feasible. This adds to the scattered evidence on this issue available so far.

Finally, the articles on preeclampsia provide two interesting sets of data. Ozeki et al. (pp. 2452–2460) report that the pathophysiological features of preeclampsia are accelerated by inflammatory cytokines which are released by greater circulating concentrations of fetal cell free DNA from trophoblasts. Su et al. (pp. 2461–2469) provide information on the mechanisms that are, responsible for the prophylactic effect of aspirin administered before 16 weeks of gestation on the risk of preeclampsia. Based on the collected data, an effect of aspirin on trophoblast function and on the production of sFIt-1 (which exerts an inhibitory influence on trophoblast invasion) is involved.

The last three articles focus on treatment. Wu et al. (pp. 2470–2480) show that in a large number of individuals from the inner London population (n = 320 094) awareness, treatment and control of a BP elevation was rare, especially in black patients. The results reflect the old rule of the half which recited that in the population awareness, treatment and control of hypertension each amount to about half of the starting value. Gingles et al. (pp. 2481–2489) show that in 72 normotensive individuals with hypertension left ventricular mass reduction as assessed by NMR was less in the group treated with high doses of allopurinol than in the control group. Biomarkers of oxidative stress were greater in the treated group, justifying the suggestion that antiuricemic treatment may be associated with adverse cardiovascular effects. Shin et al. (pp. 2490–2497) show that a combination of losartan and amlodipine was accompanied by a greater on-treatment smoothness index value than the combination of losartan and hydrochlorothiazide. For the readers who have a limited familiarity with the smoothness index, this measure refers to the between-hour differences in the BP effect of treatment over the 24-h time. A greater smoothness index reflects a more stable BP control, and evidence is available that this may be associated with a more favorable effect of treatment on organ damage. An Editorial Commentary of Rizzoni (pp. 2341–2344), the investigator who first described the smoothness index, goes into the issue in depth.

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Conflicts of interest

There are no conflicts of interest.

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