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Prediction and prevention of hypertension-related events

Zanchetti, Alberto

doi: 10.1097/HJH.0000000000000885

aIstituto Auxologico Italiano

bCentro Interuniversitario di Fisiologia Clinica e Ipertensione, Università degli Studi di Milano, Milan, Italy

Correspondence to Professor Alberto Zanchetti, Direzione Scientifica, Istituto Auxologico Italiano, Via L. Ariosto, 13, 20145 Milano, Italy. Tel: +39 02 61911.2237; e-mail:

Prediction and prevention of disease are two strictly related aspects of medicine, prevention being difficult to achieve without the ability to predict individuals at risk, and prediction being a vain and even threatening activity when means to prevent are not available. This is not the case of hypertension, an area in which studies on factors predicting development of hypertension and related cardiovascular disease, and studies on means to prevent and treat hypertension and reduce associated cardiovascular events have gone, so to say, hand-in-hand and paved the way to the success of hypertension research and therapy. This valuable approach to research is continuing, as witnessed by a number of articles devoted to prediction and prevention of hypertension-related events in the current issue of the Journal of Hypertension.

Cavka et al. (pp. 676–684) report that 7-day high salt intake, although not raising blood pressure in healthy adults, reduces brachial artery endothelial function and switches the mediator of vasodilation in the subcutaneous fat microcirculation to a nonnitric-dependent mechanism. A mechanism of vascular wall damage is commonly believed to be endothelial insulin resistance, but Roussel et al. (pp. 685–691) in a large cohort of men and women free of diabetes, hypertension and dyslipidemia of the European Relationship between Insulin Sensitivity and Cardiovascular Risk (RISK) cohort show that low insulin secretion also does play a role, intima-media thickness in the common carotid artery being negatively correlated with insulin secretion indices, independently of insulin sensitivity. Abdominal obesity, another well known condition associated with hypertension development, was found by Vogt et al. (pp. 637–645) to strengthen the relationship between serum 25-hydroxyvitamin D and SBP in participants of the US National Health and Nutrition Survey 2001–2006. Similarly, Tadic et al. (pp. 772–780) report that blood pressure variability and echocardiographic left ventricular deformation are significantly affected by obesity in untreated hypertensive patients. The relationship of blood pressure variability with aortic function and structure has been investigated by Isabelle et al. (pp. 666–675) in spontaneously hypertensive rats treated with a nitric oxide synthase inhibitor. The authors report rapid and simultaneous increases in blood pressure, blood pressure variability, pulse wave velocity and structural alterations in the aortic wall. On their turn, Cauwenberghs et al. (pp. 762–771) in the large cohort of the European Project on Genes in Hypertension study also show the importance that arterial stiffness plays as a mediator of left ventricular systolic and diastolic dysfunction. These interesting data are commented by Avolio and Butlin (pp. 634–636), who underline the association between cardiac and arterial indices reverses at old age, and comment that this reversal may predispose to heart failure.

The risk of developing prehypertension or hypertension 1 year after a pregnancy accompanied by a pregnancy-associated hypertensive disorder has been investigated by Black et al. (pp. 728–735) in the large cohort of Kaiser Permanente Bellflower Medical Center (Pasadena, California, USA). The authors report a significantly increased risk of prehypertension and hypertension among women with hypertensive disorder in pregnancy, and highlight the need for large prospective studies on possible benefits of postpartum screening and follow-up of these women. Studies on the molecular mechanisms of preeclampsia are actively going on with the intention to detect early markers of this condition for therapeutic intervention. Two such studies are published in this issue of the Journal of Hypertension. Tong et al. (pp. 710–718) suggest that a novel estrogen receptor, G-protein coupled receptor 30, is a critical regulator of trophoblast cell invasion, and as such may be a potential therapeutic target for preeclampsia. Wang et al. (pp. 719–727) report that WNT4 and WNT5 are relevant to normal decidualization in women, and thus trophoblast invasion and implantation, and suggest their deficiency may be involved in the development of preeclampsia.

Prediction of hypertension-related morbidity and mortality is the focus of four articles. Briasoulis et al. (pp. 593–599) present the results of a meta-analysis of 14 observational studies on 29 100 participants followed up for 8 years, approaching the debated problem of the cardiovascular risk of so-called white-coat hypertension. They conclude that cardiovascular morbidity and mortality (but not all-cause mortality and stroke) appear to be slightly higher in white-coat hypertension compared with normotension, but quite lower than the risks associated with sustained hypertension. In an accompanying editorial, Mancia (pp. 623–626) comments that deciding whether in white-coat hypertensive patients physicians should start antihypertensive drugs remains a most difficult task, and a properly designed trial would be desirable.

Meccariello et al. (pp. 646–653) report the results of a prospective 3-year study of a cohort of hypertensive patients seen by general practitioners, and conclude that presence of microalbuminuria is accompanied by increased risk of cardiovascular events only in essential hypertensive patients with a previous history of cardiovascular events. The authors, therefore, suggest that assessment of microalbuminuria should be considered as useful in secondary prevention. In a commentary, Schlaich (pp. 627–628) comments that, aside from its clinical importance, this study is an example of the capacity and quality of research that can be achieved in a general practitioner setting.

In patients with chronic kidney disease, Yoshitomi et al. (pp. 753–761) find that higher plasma B-type natriuretic peptide concentrations are associated with greater renal function decline, independent of cardiac structure and function, and suggest that B-type natriuretic peptide may be a useful biomarker for exploring factors associated with kidney disease progression.

According to a prospective study by Weidung et al. (pp. 745–752) in people older than 85 years, the association of SBP with mortality appears to be influenced by cognitive impairment: very old individuals with severe reduction of the Mini-Mental State Examination score have an increased mortality risk both at low and high blood pressure levels. In view of these findings, Coca and Camafort (pp. 632–633) caution against a too enthusiastic extension of the results of the SPRINT study to old patients with cognitive impairment.

Among articles focusing on the effects of blood pressure-lowering treatment, Thomopoulos et al. (pp. 613–622) update their previous meta-analysis of randomized trials comparing more with less-intensive antihypertensive treatment by including data from a few recent trials, mostly from SPRINT, and show that more intense blood pressure lowering can significantly reduce not only nonfatal but also fatal cardiovascular events. Their additional updating of a meta-analysis of the effects of a standardized blood pressure reduction across different cutoffs of SBP finds that risk of all cardiovascular outcomes can be significantly reduced even across the systolic cutoff of 130 mmHg, although absolute risk reduction is smaller than that of a similar blood pressure lowering across higher systolic cutoffs. In an interesting further analysis of the ADVANCE trial, the trial investigators (Hirakawa et al., pp. 781–787) have studied the associations of discontinuation of randomized medications on major outcomes, and found that discontinuation was associated with increased risks of combined macrovascular and microvascular events, macrovascular events, microvascular events and all-cause mortality. As these associations were similar in both the active and the placebo-treated group, the authors suggest that discontinuation of study medication is a potent risk marker of high-risk patients. The risk of discontinuation of placebo treatment also strengthens the concept that being included in a randomized trial is in itself protective, probably because of the added and expert medical attention given to the enrolled patients. Unfortunately, it is well known that in medical practice, treatment discontinuation is high and even attendance to follow-up visits is poor. Therefore, growing attention is being paid to promoting self-management of individuals with hypertension. Digital interventions with this aim in view have been reviewed and meta-analyzed by McLean et al. (pp. 600–612). These techniques are promising and deserve their effects are tested on morbid events. Other articles on antihypertensive treatment in this issue of the Journal of Hypertension include a pooled analysis of three separate randomized placebo-controlled trials comparing the effects of azilsartan medoxomil, olmesartan, valsartan and placebo on 24-h ambulatory blood pressure of patients with hypertension and either prediabetes or type-2 diabetes mellitus (White et al., pp. 788–797), and a randomized controlled study comparing the blood pressure-lowering effects of a chlorthalidone/amiloride combination and losartan (Fuchs et al., pp. 798–806).

Other articles in the present issue of the Journal of Hypertension deal with other interesting aspects of hypertension. Te Riet et al. (pp. 654–665) have studied homozygous fibulin-4 R/R mice developing aortic aneurysms and left ventricular dilation, and found a positive survival effect of losartan but not of aliskiren, a difference the authors suggest may be caused by a protective effect of angiotensin type 2 receptor stimulation. Heumann et al. (pp. 692–703) report that sympathetic denervation enhances L-type Ca2+-channel-dependent signalling in renal but not in mesenteric arteries of the rat. The authors suggest this effect may be partly explained by the decreased vascular smooth muscle potential in denervated renal arteries. In untreated hypertensive patients, Missouris et al. (pp. 704–709) find that urinary norepinephrine excretion is increased in proportion to the severity of the blood pressure rise and this also occurs in patients taking a long-acting dihydropyridine calcium antagonist or a β-blocker. In their accompanying editorial commentary, Jordan and Grassi (pp. 629–631) comment that the study by Missouris et al. (pp. 704–709) underscores the importance of the sympathetic system in hypertension and reminds us that a widely available biochemical measurement can be used to gauge sympathetic activity. They also suggest that most device-based approaches to the treatment of hypertension (such as renal denervation and baroreflex stimulation) target the sympathetic nervous system, and a simple screening like urinary catecholamines might be useful in identifying resistant hypertensive patients potentially suitable to favourably respond to these interventions.

Finally, Przewoźny et al. (pp. 736–744) report the interesting association of hypertension with dysfunction of both the peripheral and central auditory system.

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Conflicts of interest

There are no conflicts of interest.

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