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Highlights of the February issue

Mancia, Giuseppea,b

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doi: 10.1097/HJH.0000000000002764
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The February issue of the Journal of Hypertension reports the results of three systematic reviews and meta-analyses, respectively, on awareness and control of hypertension in ethnic minorities living in Europe, the effect of exercise on pulse wave velocity, and blood pressure (BP) changes in transgenders. Van der Linden et al. (pp. 202–213) show that ethnic minorities living in Europe have a high rate of hypertension-mediated complications compared with the European host populations. Their awareness of this condition varied according to their ethnicity, that is, compared with European control groups it was higher in populations with an African or Asian origin, but lower in Moroccan or Turkish populations, this being the case also for BP control in all populations studied except the Asian one. These are important observations that address an issue on which, as mentioned by the recent European guidelines (which have for the first time devoted a subsection to this problem) information is limited, despite the high and growing representation of extra European ethnicities in all countries of the Continent. Lopes et al. (pp. 214–222) show that, in 642 individuals from 14 trials, exercise training was associated with a reduction of pulse wave velocity which extended to different exercise types, including the isometric ones. This can be legitimately interpreted as a protective effect of exercise because arterial stiffness has been found to be an independent risk factor for cardiovascular disease. The question remains how much this effect is a direct one (possibly because of an exercise-dependent reduction of the stiffening influences exerted by the sympathetic nervous system on large artery walls) or it passively follows the BP-lowering effect associated with training. Connelly et al. (pp. 223–230) report that, in 1309 transgender individuals, BP did not show a significant increase, except perhaps for transgender women under sex-affirming hormone therapy. The authors emphasize, however, that the studies were heterogeneous, had frequently a limited quality and that the methods employed suffered from limitations, which suggests that conclusions should be drawn with caution.

The following studies address diagnostic issues (three studies) and specific hypertension-related problems such as those facing stroke risk (four studies), sleep apnoea (three studies) and primary aldosteronism (two studies). Bell et al. (pp. 236--242) emphasize that the new classification of BP values recommended by the 2017 American College of Cardiology/American Heart Association guidelines, that is, the grade 1 hypertension definition of a condition previously referred to as high-normal BP (130–139/85–89 mmHg, SBP/DBP), predictably increases the prevalence of those diagnosed as hypertensive compared with other guidelines. According to the authors, however, the consequences of this ‘overdiagnosis’ could be minimized by taking into account absolute cardiovascular risk when deciding whether these newly defined hypertensive individuals should be given antihypertensive drugs. Olbers et al. (pp. 243--249) show that, in patients with atrial fibrillation, restoration of sinus rhythm was accompanied by an increase of ambulatory BP values, a phenomenon that has never been duly emphasized by previous studies but that it needs attention and possibly retitration of antihypertensive treatment, given the relationship between BP and cerebrovascular or cardiac risk in patients with permanent or paroxysmal atrial fibrillation. Nolde et al. (pp. 250–258) show that nocturnal hypertension is a common hypertension phenotype, adding that its occurrence is associated with an increase of central BP and of pulse wave velocity. Uemera et al. (pp. 259–265) describe the relatively high incidence (about 19%) of cerebral microbleeds in coronary patients receiving antithrombotic treatment who were followed for about 3 years. This calls for a greater diagnostic attention to the structural status of the brain in patients with coronary heart disease who are given anticoagulant drugs, a conclusion further supported by the study evidence that in patients with microbleeds the risk of adverse cardiac and cerebral vascular events was increased. Tsivgoulis et al. (pp. 266–272) describe the results of a post-hoc analysis of the CLOTBUST-ER trial which show that patients with acute ischaemic stroke treated with tissue plasminogen activator exhibited, in the following 24 h, BP peaks to values above 185/105 mmHg, the number of which showed an inverse relationship with the odds of clinical recovery. Ouyang et al. (pp. 273–279) provide post-hoc evidence from the HeadPoST trial that, in more than 11 083 patients with an acute stroke, patients with BP values below 120/70 mmHg exhibited a worse functional outcome compared to higher BP values. In the words of the authors exacerbation of cerebral ischaemia by organ underperfusion was the most likely explanation because the worse functional outcome survived adjustment for potential confounders. Although in post-hoc analyses confounding and reverse causality can never be completely excluded, this finds support also from the evidence that in acute stroke the brain loses its blood flow autoregulation, becoming more prone to the adverse effects of excessive BP reductions. Brain or more in general vital organ underperfusion can be also the explanation of the results of the following article (Minhas et al., pp. 280--285) which shows that in more than 1300 patients with an acute ischaemic stroke intensive BP lowering was associated with an increased mortality. Thomas et al. (pp. 286--291) report that, in patients with refractory hypertension, sleep apnoea is particularly common and that this appears to be more evident in men than in women. Svedmyr et al. (pp. 292--301) show that, in a large cohort of patients (n = 5818) with obstructive sleep apnoea, poor BP control was, as it might be expected, frequent (66% of the patients) and that the best control was obtained in patients in whom the treatment regimen consisted of a beta-blocker/diuretic combination. These interesting results are commented by the Editorial of Manolis et al. (pp. 231--233). Navarro-Soriano et al. (pp. 302--309) show that in patients with resistant hypertension and obstructive sleep apnoea, reduction of ambulatory BP was favoured by frequent use of positive airway pressure which led to lower BP values despite a reduced use of antihypertensive drugs. After some negative studies and opinions on the BP-lowering efficacy of this procedure, positive evidence is growing, and positive airway pressure can be legitimately regarded as one of the device-based treatment to be considered for the treatment of drug-resistant hypertension after its origin from obstructive sleep apnoea has been documented. The limitation is, however, that positive airway pressure is unpleasant to the patient which can make long-term adherence to its repeated applications low. Further considerations can be found in the Editorial Commentary of Pengo et al. (pp. 234--235). Ma et al. (pp. 310--317) show that in patients with primary aldosteronism postsurgery clinical data show only minor differences between those who were operated on the basis of diagnostic computed tomography or on elevated aldosterone values in adrenal vein samples, with just a marginal difference in favour of the latter group. Salvetti et al. (pp. 318--324) describe an impairment of the production and utilization of energy in the myocardium of patients with primary aldosteronism compared with those with essential hypertension, an observation which may explain, together with other factors, why in primary aldosteronism cardiovascular events are more common than in essential hypertension.

The last five articles address a variety of issues related to antihypertensive treatment. Kim et al. (pp. 325--332) provide some interesting observations on the effect of guiding antihypertensive treatment by ambulatory vs. office BP in patients with advanced chronic kidney disease, that is, with an estimated glomerular filtration rate below 40 ml/min. The risk of renal events was not significantly different between the two groups, and indeed in absolute numbers it was less in the office BP-guided than in the ambulatory BP-guided treatment. Thus, guiding treatment by ambulatory BP did not protect patients more effectively than guiding treatment by the time-honoured clinically measured BP values. It should be noticed that the number of renal events was too small to make the results conclusive. However, the paper has the merit of calling attention to an issue of primary importance on which no properly designed studies have so far been conducted. That is, whether, compared with conventionally measured BP, use of out-of-office BP does not only improve the diagnosis of hypertension and the quantification of cardiovascular risk but it also increases the benefit of BP-lowering interventions. Maloberti et al. (pp. 333--340) show that, in more than 17 000 individuals from a large number of Italian observation studies, those under treatment with diuretics who had a serum uric acid above the median of the entire cohort (4.8 mg/dl) exhibited a greater risk of cardiovascular events, cardiovascular mortality and all-cause mortality than those below the median value. Thus, even treatment-dependent increases of serum uric acid appear to be associated with an increased risk, an effect which can be seen also at relatively low serum uric acid levels. Edwards et al. (pp. 341--348) show the BP-lowering effect (ambulatory BP) of high intensity training in a large patients’ cohort and de la Sierra et al. (pp. 349--355) report a greater reduction of 24-h BP variability in patients treated with calcium channel blockers or diuretics compared with beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor 1 blockers. The authors discuss the possibility to consider a reduction of 24-h BP variability as an additional target for treatment, given the evidence that 24-h BP variability is an independent cardiovascular risk factor. There is, however, no evidence that reduction of 24-h BP variability is associated with a cardiovascular benefit independently of a reduction of BP mean. Furthermore, data are limited on the normality value and reproducibility of this measure. Yao et al. (pp. 356--366) show that, in patients with heart failure and a left ventricular ejection fraction of at least 40%, the BP values recorded at the hospital admission and discharge influenced the relationship between BP at discharge from hospital and the subsequent outcomes (cardiovascular death and heart transplantation). In patients defined as initially hypertensive (SBP ≥ 130 mmHg) outcome was worse if discharge SBP was more than 145 mmHg, which was not the case in patients without hypertension.

As in the issues of the Journal published in the past few months, the February issue includes scientific contributions on the Covid-19 disease. Lahens et al. (pp. 367--375) describe the effect of stopping vs. continuing blockers of the renin–angiotensin–aldosterone system on the outcome of 347 retrospectively analyzed hospitalized Covid-19 patients. The study, however, also calls attention to the confounding potential of this approach because of the chance that treatment discontinuation is preferentially adopted in patients in whom the infection appears to be more severe. This emphasizes once more the need for any conclusion on the drugs to be used during a Covid-19 infection to be based on trials in which confounding by indication is avoided by patient randomization to the drug of interest or the control group. Mancusi et al. (pp. 376--380) report that, in a large number of hospitalized Italian patients, healing of Covid-19 (two consecutive negative swaps) was predicted in a multivariable analysis by age, absence of chronic disease and absence of heart failure. Interestingly, treatment with renin–angiotensin blockers was not a predictor in line with the results of observational studies that pretreatment with these drugs does not modify the severity of this disease.


Conflicts of interest

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