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Focus on clinical problems

Zanchetti, Alberto

doi: 10.1097/HJH.0000000000000427

Istituto Auxologico Italiano and Centro Interuniversitario di Fisiologia Clinica e Ipertensione, Università di Milano, Milan, Italy

Correspondence to Professor Alberto Zanchetti, Centro di Fisiologia Clinica e Ipertensione, Università di Milano, Via F. Sforza, 35, 20122 Milan, Italy.Tel: +39 02 50320484; e-mail:

Received 17 September, 2014

Revised 17 September, 2014

Accepted 17 September, 2014

The current issue of the Journal of Hypertension is particularly focused on several aspects of the clinical management of hypertension, spanning from blood pressure measurement to markers predictive of organ damage, the organ damage mechanisms, therapeutic issues especially regarding resistant hypertension and evaluation of the benefits of blood pressure lowering.

Definition of hypertension is known to be difficult in children, and the advantages of out-of-office blood pressure measurements over conventional office measurements are debated. Kollias et al. (pp. 2315–2331) provide a welcomed systematic review and meta-analysis of available studies, and conclude for a moderate but significant association between ambulatory blood pressure and asymptomatic organ damage, mostly in children with nephropathy or diabetes. Roush et al. (pp. 2332–2340) publish a systematic review and meta-analysis of cohorts of hypertensive patients with ambulatory blood pressure measurements and outcomes during follow-up, and confirm that, after adjustments, night SBP, but not clinic and daytime SBP, independently predicts cardiovascular events.

A number of studies report on predictors of organ damage. A nation-wide longitudinal study in Japan (Yano et al., pp. 2371–2377) indicates that, over a follow-up of 3 years, women with new-onset hypertension and men with high-normal blood pressure were at a higher risk of developing proteinuria. In an accompanying editorial, Carlberg (pp. 2351–2352) calls attention on the so called ‘high-normal blood pressure’, a blood pressure range that should be the most important target for prevention of hypertension. Westerdahl et al. (pp. 2378–2384) have used the very wide database in the Malmö Preventive Project to show that family history and the metabolic syndrome are important predictors for development of severe hypertension after long-term follow-up. On its turn, severe hypertension is associated with increased mortality and cardiovascular morbidity in spite of treatment. In an accompanying editorial, Waeber and Feihl (pp. 2353–2354) underline the importance of large prospective cohorts like the Malmö one, but also remark that definition of hypertension has largely changed in the past 25 years. Endothelial dysfunction is considered an initial stage of vascular damage: in a prospective study, Yang et al. (pp. 2393–2400) have found that endothelial dysfunction, as measured by impaired brachial flow-mediated dilation, is a predictor of future organ damage progression, but has little predictive value in the late stages of organ damage. Ghiadoni and Grassi (pp. 2355–2356) in their accompanying editorial remark that Yang et al.'s data bring new support to the concept of the central role of the endothelium in maintaining vascular homeostasis, but the value of testing endothelial function in cardiovascular prognosis still requires clinical trials founded on hard endpoints. In a population-based study in Malmö, Sweden, Bennet and Nilsson (pp. 2362–2370) show that the associations of body mass and HbA1c with office blood pressure are different in Middle Eastern immigrants to Sweden and native Swedes.

Organ damage is the focus of a series of studies. Muris et al. (pp. 2439–2449) have investigated skin microvascular flow motion, and found it to be impaired with ageing, high blood pressure and obesity. Li et al. (pp. 2450–2456) report that red blood cell distribution can predict early-stage renal function damage in hypertensive patients. In a South African population sample with large prevalence of obesity and hypertension investigated by Millen et al. (pp. 2457–2464), SBP has emerged as the most important correlate of left ventricular diastolic dysfunction, exceeding the role of obesity. Nonetheless, Cuspidi et al. (pp. 2359–2361), in their editorial comment, review a number of other epidemiological studies pointing to a relevant role played by obesity in diastolic dysfunction, and suggest further data will be necessary to fully clarify the relative weight of blood pressure and body weight in causing alterations in diastolic function. A blunted coronary flow reserve is described by Rimoldi et al. (pp. 2465–2471) in grade 1 and 2 hypertensive patients to be inversely related to SBP rather than left ventricular mass index. Cheng et al. (pp. 2479–2487) have studied a cohort of patients with uncontrolled hypertension, hypertensive heart disease and normal left ventricular fraction, and found that abnormalities in left ventricular mechanical systolic function can be ameliorated by intensified treatment and improved blood pressure control. On the contrary, in a subgroup of the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, Okin et al. (pp. 2472–2478) have found that persistence or development of new electrocardiographic left ventricular hypertrophy despite antihypertensive therapy was associated with an increased risk of left ventricular systolic dysfunction after 3 years follow-up.

Continuing interest in various aspects of resistant hypertension and its treatment is clearly witnessed in the current issue of the Journal. Solini et al. (pp. 2401–2410) report resistant hypertension is relatively common among individuals with type 2 diabetes, and is strongly associated with microvascular (especially renal) disease, and less clearly with macrovascular disease. Iftikhar et al. (pp. 2341–2350) have done a meta-analysis of observational studies and randomized controlled trials on the effect of continuous positive airway pressure treatment on blood pressure in patients with resistant hypertension and obstructive sleep apnoea (OSA), and report larger effect sizes than those previously reported in patients with OSA without resistant hypertension. The issue of the extent of the blood pressure-lowering effects of renal denervation in resistant hypertension continues to raise interest. Persu et al. (pp. 2422–2427) report an analysis of the European Network Coordinating research on Renal Denervation (ENCORED) database, and suggest a major overestimation of blood pressure response after denervation in extreme responders defined according to office, but not ambulatory blood pressure. Poor response was also found associated with poor renal function. The widespread opinion that a consistent proportion of cases of resistant hypertension are due to poor adherence to treatment has stimulated a cost-analysis study of therapeutic drug monitoring in order to identify nonadherent patients (Chung et al., pp. 2411–2421). Therapeutic drug monitoring is strongly supported by Kjeldsen and Os (pp. 2357–2358) in their editorial comment as an effective approach to control resistant hypertension. Persistent high salt intake is also considered a mechanism of resistance to antihypertensive treatment. Unfortunately, Okuda et al. (pp. 2385–2392), in a survey done in China, Japan, UK and USA, found that in all these countries, recommendations of reducing salt intake are very poorly followed: even for participants reporting reduced intake, 24-h urinary sodium excretion remained higher than the recommended intake. Giavarini et al. (pp. 2433–2438) reviewed a large number of cases of renal artery fibromuscular dysplasia during the past 25 years in a single centre in Paris, and described an increasing trend toward older patients with less severe disease and adequately managed by medication. Van Twist et al. (pp. 2428–2432) described an impaired vasodilatation to infusion of angiotensin-(1–7) in ‘stenotic’ kidneys, but not in the contralateral ones. Kjeldsen et al. (pp. 2488–2498) report the results of a large multinational, randomized, placebo-controlled study showing that the combination of nifedipine gastrointestinal therapeutic system (GITS) and candesartan provides statistically better blood pressure reductions and a better side-effect profile than monotherapies.

Finally, the current issue of the Journal publishes three studies (Thomopoulos et al., pp. 2285–2295, pp. 2296–2304, pp. 2305–2314) with systematic updated meta-analyses of blood pressure-lowering randomized controlled trials in patients with hypertension. In addition to providing estimation of mean effects, these meta-analyses approach some clinical relevant questions, such as the effects of blood pressure-lowering treatment at different levels of baseline untreated blood pressure, the effects of achieving different blood pressure levels and the influence of higher levels of total cardiovascular risk not only in making therapeutically induced absolute risk reduction greater but also in leaving residual risk (i.e. treatment failures) at much higher levels.

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Conflicts of interest

There are no conflicts of interest.

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