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Highlights of the June issue

Mancia, Giuseppe

doi: 10.1097/HJH.0000000000002124

Università Milano-Bicocca, Milan, Italy

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

The June issue of the Journal of Hypertension includes two reviews, one meta-analysis, a consensus document and an Editorial Commentary on issues of major interest for hypertension. Vallelonga et al. (pp. 1102–1111) review the available data on supine hypertension, defined as a condition in which blood pressure (BP) is at least 140 mmHg systolic or 90 mmHg diastolic only when patients are lying, normal values being systematically measured in the orthostatic position. The authors mention that this condition can be due to antihypertensive drugs but also that its detection in untreated patients should raise the suspicion of an autonomic derangement. An important point is that, although often asymptomatic, these patients may exhibit multiple organ damage and that neither official guidelines nor evidence of long-term benefits of BP-lowering treatment are available. Treatment should thus be based on clinical wisdom, the guiding principle being to avoid antihypertensive treatment strategies that may lead to excessive orthostatic BP reductions, with thus a risk to patient's safety. Tanna et al. (pp. 1112–1118) review the debated question of the beneficial effects of a heart rate reduction in patients with coronary heart disease. Emphasis is placed on the large body of pathophysiological and clinical evidence that in these patients (as well as in hypertensive patients and the general population) an increased heart rate represents an independent risk factor for adverse outcomes, but attention is then properly directed to the limited evidence that a pharmacological reduction of heart rate by beta-blockers or ivabradine (the latter with no concomitant reduction of cardiac sympathetic drive) is accompanied by a protective effect on the heart. Although the recent European guidelines suggest that in patients with a higher heart rate (>80 beats/min) heart rate reduction may be a reasonable therapeutic goal, this represents a major gap in knowledge of current cardiovascular medicine. Webb et al. (pp. 1119–1125) provide a meta-analysis of the studies that have assessed cerebral perfusion in patients in whom BP was reduced by vasodilating agents. In 35 studies (and 57 comparisons) the BP reduction was accompanied by an increase of the cerebral pulsatility index and by no decrease of blood flow, which is in line with the notion that the brain possesses an effective blood flow autoregulation. The average BP reduction was quite small (−4.1 mmHg SBP), however, which does not allow to establish the BP value below which cerebral perfusion may fall. Evidence on the lowest BP value not to cross with treatment is especially limited in patients with cerebral vascular damage in whom cerebral blood flow autoregulation is impaired, especially in the areas surrounding the ischemic or haemorrhagic lesion. The consensus document by López-Jaramillo et al. (pp. 1126–1147) focuses on the management of hypertension in Latin American patients with diabetes and metabolic syndrome. The epidemiology of the hypertension–metabolic disease association in the Latin American continent is addressed in detail and recommendations are issued on how to therapeutically cope with this association in an environment often markedly different from those of other continents. This underlines the importance of diagnostic and treatment recommendations that take these differences into consideration, an issue that is addressed by the Editorial Commentary of Egan et al. (pp. 1148–1153) who focus on the BP targets recommended by guidelines in the United States, Canada, Europe and Australia. The potential inconveniences of lower compared with higher BP targets for treatment are discussed to make doctors aware of the risk of excessive BP reductions, in particular of reducing SBP below 120 mmHg. Emphasis is also placed on the need of further trials that can more precisely quantify the net incremental benefit of treatment strategies that lower BP more aggressively in different demographic and clinical situations. The net benefit can be calculated by the ratio between the number of outcomes spared and serious side effects, that is, those leading to treatment discontinuation and its related increase of fatal and nonfatal events.

The following seven papers deal with various aspects of the pathophysiology of vessels and heart in hypertension. Mels et al. (pp. 1157–1166) report that the profile of nonessential amino acids involved in collagen metabolism differed in black and white South-African normotensive individuals and exhibited a variable association with central BP, although limited to black individuals. Information on collagen metabolism is highly relevant to the problem of how to delay or regress the arterial stiffening that leads to systolic hypertension, an area on which research and therapeutic progress has been absent for years. Wang et al. (pp. 1167–1175) describe the predictors of the progression of large artery stiffening and carotid thickening in a Chinese cohort of adolescents followed for 12 years. The functional and structural large artery changes were related to the changing BP values but also independently predicted by heart rate. Zanoli et al. (pp. 1176–1182) show that, in a large survey of people aged 50–75 years, carotid artery stiffness was progressively greater as glomerular filtration rate decreased from 60 to 89 to less than 60 and less than 45 ml/min per 1.73 m2. This means that, in line with previous reports, advanced kidney disease is accompanied by alterations of large artery mechanical properties but, in addition, that this occurs also when renal disease is only mild. Vascular alterations (structural and functional abnormalities of the carotid artery) are also the object of the article of Salvetti et al. (pp. 1183–1190) who report that their magnitude is more marked in patients with concentric left ventricular remodelling, a cardiac abnormality that also showed an association with more severe coronary stenoses, as documented by coronary angiography. This provides an explanation of the more adverse prognostic impact of concentric vs. eccentric hypertrophy of the left ventricle consistently reported by the medical literature. Further on the heart, Bamaiyi et al. (pp. 1191–1199) and Ruppert et al. (pp. 1200–1212) provide interesting observations on the determinants and response to treatment of the diastolic dysfunction associated with hypertension. In the article of Bamaiyi et al. the alterations of diastolic dysfunction of the left ventricle seen in more than 700 individuals with a high prevalence of hypertension was, as expected, associated with structural left ventricular remodelling. However, the increase in left ventricular mass and wall thickness accounted for only a minor proportion of the diastolic function alterations, a finding that suggests that the determinants of systolic and diastolic structural and functional changes by a BP increase are, at least in part, different., On the treatment side, this is also the implication of the article of Ruppert et al. who show that the left ventricular hypertrophy and dysfunction induced in rats by pressure overload (aortic banding) was effectively reversed by unloading, no matter how long the overload had been. This was not the case, however, for the concomitant diastolic dysfunction, which did not show a regression in rats previously exposed to prolonged overload, because of the persistence of cardiac fibrosis. This implies that a time factor (hypertension of a long duration) may be involved in the inability of antihypertensive treatment to completely reverse diastolic dysfunction in patients with left ventricular hypertrophy, even when BP control is achieved. Finally, Antolini et al. (pp. 1213–1222) estimate the appropriateness of the pediatric BP classifications proposed by the recent American and European guidelines based on their ability to identify the presence of left ventricular hypertrophy. Some differences in the prevalence of hypertension between the two guidelines were observed. The main interest of the article, however, may be the use of left ventricular hypertrophy to assess the performance of the BP classifications. This is justified by the fact that, in young people, a BP elevation is by far the most important determinant of an increased left ventricle mass.

Four articles of the June issue of the Journal deal with the epidemiology of hypertension with somewhat different results. Matsumoto et al. (pp. 1223–1229) report that, in 12 279 individuals of the Physicians’ Health study free from hypertension at baseline, a long-term (about 16 years) dietary intake of fish and omega-3 fatty acids did not prevent incident hypertension, which involved more than 50% of the study participants. Somewhat in contrast, Zhou et al. (pp. 1230–1238) show that, in the large number of adults made available by the NHANES database, dietary behaviours in line with the American Heart Association recommendations (whole grains, fruits, vegetables, sodium, etc.) were associated with a much lower prevalence of hypertension, the difference between a persistent use of an ideal diet and no diet at all on the hypertension prevalence being 43%. In addition, incident hypertension was found to be markedly increased (about four times) in the individuals of the Chinese Health and Nutrition survey who exhibited an increased body weight or obesity either in childhood or in early adulthood (Hou et al., pp. 1239–1243). Thus, although the relative role of individual dietary components on the risk of new onset hypertension may still be somewhat uncertain, the favourable impact of some integrated overall low-calorie diets on the prevention of a long-term BP elevation seems beyond dispute. Rouch et al. (pp. 1244–1253) report the results of the VISAT study in which the impact of prevalent and incident hypertension on cognitive function was assessed in middle-age individuals over a long (10-year) follow-up. Compared with normotensive individuals, both prevalent and new hypertensive patients showed poorer global cognitive performances over time, which confirms the importance of high BP as a determinant of cognitive deterioration. Interestingly, the article also shows that the adverse effect of high BP on cognitive function was particularly evident in patients with untreated or uncontrolled hypertension, which provides an indirect element in favour of a beneficial influence on cognitive dysfunction of BP reduction by treatment. This is another area of great clinical importance on which evidence from randomized trials is needed.

The remaining seven articles provide information on the effects of antihypertensive treatment of nonpharmacological (three articles) and pharmacological (four articles) nature. Rorije et al. (pp. 1254–1261) describe a reduction of sublingual microvascular density in healthy individuals randomized to short-lasting (2 weeks) high-salt intake compared with low-salt intake (>12 vs. 3 g/day). An interesting aspect of the study is that this occurred in absence of BP changes, suggesting a direct negative impact of salt excess on microcirculation. Schroeder et al. (pp. 1262–1268) show that African Americans and Caucasians had a qualitatively similar haemodynamic response to maximal aerobic exercise, but that in African Americans, the extent of the exercise-dependent vasodilation was less than in Caucasians, with also little postexercise reduction of BP and arterial stiffness. This appears to extend to nonpharmacological treatment the reduced response to drug treatment often reported in black hypertensive people. Navarro-Soriano et al. (pp. 1269–1275) show that in patients with resistant hypertension and sleep apnea, a positive airway pressure reduced 24-h BP, the effect being particularly marked (−9/−7 mmHg) in patients exhibiting refractory hypertension, that is, absence of ambulatory BP control with use of five or more antihypertensive drugs. The antihypertensive effects of the positive air pressure intervention is undergoing a reevaluation, after the initial studies reporting that little or no BP reduction could be achieved.

The four articles on pharmacological treatment deal with different issues. Han et al. (pp. 1276–1284) describe the results of an analysis of a large database (Optum), which support the recent American College of Cardiology / American Heart Association recommendations to start antihypertensive treatment ‘timely’, for which the authors mean BP values within the high-normal range. In the analysed database, this led to a clear-cut reduction in the risk of myocardial infarction, stroke and death (59, 60 and 10%, respectively), suggesting that the benefit can be substantial. Kurdi et al. (pp. 1285–1293) report favourable clinical and economic consequences of switching treatment from angiotensin receptor antagonists to ACE inhibitors in the UK. The clinical advantage consisted in a greater BP reduction (mean SBP difference −2.3 mmHg) whereas the economic advantage consisted in an annual saving of 329 pounds per patient. Cooper et al. (pp. 1294–1300) report the results of a study in which type 2 diabetic patients under ACE inhibitors or angiotensin receptor antagonists were randomized to linagliptin or placebo for a 24-week treatment period. No effect of linagliptin was seen on ambulatory BP and heart rate, which excluded an interference of this antidiabetic drug with a common antihypertensive treatment. The BP effects of new antidiabetic drugs, which have shown protection against macrovascular events, is an interesting area of investigation because hypertension, and thus a need for BP-lowering intervention, involves the majority of the type 2 diabetic population. Although some drugs of the SGLT2 class, such as empagliflozin, have been shown to possess a BP-lowering influence that can help in achieving BP control, the present study excludes a similar effect for the DPP-4 inhibitor linagliptin, which, however, does not appear to interfere with the antihypertensive effect of blockers of the renin–angiotensin system either. Finally, Ando et al. (pp. 1301–1307) show that, in the large number of elderly hypertensive patients recruited for the Japanese Primary Prevention Study, low-dose aspirin did not reduce cardiovascular outcomes, but it increased substantially the risk of serious extracranial haemorrhage in moderate or more severe hypertensive patients (+153 and +114%) with, in the overall study population, also a tendency to an increased risk of haemorrhagic stroke. This is one of the most interesting reports on the effect of low-dose aspirin in hypertensive individuals since the publication of the HOT trial. It emphasizes that, when used for primary cardiovascular prevention in individuals in whom BP is elevated, the risk associated with the use of the drug should not be forgotten. This is appropriately discussed in the excellent Editorial Commentary of Desideri and Ferri (pp. 1154–1156).

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Conflicts of interest

There are no conflicts of interest.

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