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From inflammation to renal denervation in hypertension research

Zanchetti, Alberto

doi: 10.1097/HJH.0000000000001148

Istituto Auxologico Italiano IRCCS and Centro Interuniversitario di Fisiologia Clinica e Ipertensione, University of Milan, Milan, Italy

Correspondence to Prof Alberto Zanchetti, Istituto Auxologico Italiano IRCCS and Centro Interuniversitario di Fisiologia Clinica e Ipertensione, Università degli Studi di Milano, Via F. Sforza, 35, 20122 Milano, Italy. Tel: +39 02 50320484; e-mail:;

As usual, the present issue of the Journal of Hypertension spans from basic problems, such as the role of microinflammation, to therapeutic problems, such as the effects of renal denervation.

The number of articles on resistant hypertension and renal denervation is particularly high, witnessing the continuing interest in this therapeutic procedure. The issue is opened by a summary of a Joint Position Paper prepared by the Cardiovascular and Interventional Radiological Society of Europe and the European Society of Hypertension (ESH) (pp. 2303–2304), in which experts of the two scientific societies review the available evidence, particularly after publication of the SYMPLICITY HTN-3 randomized trial. The document, which can be read in extensive form on the websites of the two Societies, concludes that there is still interest in the therapeutic potentialities of renal denervation, but high-quality research is needed before its widespread adoption. The new contributions on renal denervation published in the current issue of the journal include a study by Ott et al. (pp. 2475–2479) showing a significant reduction of both office and 24-h blood pressure (BP) in a group of patients with moderate resistant hypertension, in whom satisfactory adherence to treatment had been controlled by toxicological analysis; a publication of data from the Global SYMPLICITY Registry showing renal denervation reduces both BP and heart rate (HR), the two responses being mutually independent (Böhm et al., pp. 2480–2486); an experimental study by Chen et al. (pp. 2465–2474) finding that in high fat diet-fed rats renal denervation, in addition to reducing BP, markedly decreases hepatic glucose production and suggesting renal denervation potentiates hepatic insulin sensitivity. An additional article on resistant hypertension (Mendes et al., pp. 2458–2464) reports that plasma copeptin, a surrogate marker for vasopressin secretion, is significantly higher in patients with resistant hypertension than in patients with controlled BP.

There are, of course, many other articles in this issue of direct clinical interest. Roush et al. (pp. 2305–2317) publish a systematic review of recent meta-analyses of trials on antihypertensive therapy and evaluate their quality. Tomlinson et al. (pp. 2330–2332) comment on the ESH document on management of the hypertensive patient with elevated HR, recently published in the Journal of Hypertension[1], and report the opinions experts from the Asia-Pacific region expressed on this important topic during a Consensus Conference in Mumbai, India. The Asia-Pacific forum also recommended that resting HR should be considered independent risk factor for cardiovascular events, and pharmacotherapy should be considered in high-risk hypertensive patients with elevated HR. As their European colleagues, also experts from the Asia-Pacific region, acknowledge that further studies are required to determine the optimum HR to be achieved and the HR threshold at which treatment should be started.

Two articles concern stroke, its lifetime risk and prediction of outcomes. From the data of the Chinese Multi-Provincial Cohort Study (21 953 participants followed up for 18 years), Wang et al. (pp. 2434–2440) developed a lifetime stroke model and calculated that for individuals aged 35–40 years lifetime stroke risk was 18.0 (men) and 14.7% (women). For people with all risk factors optimal, lifetime risk was 8–10 times lower than in those with two or more high-risk factors. These interesting data are commented in an accompanying editorial by Coca and Sierra (pp. 2333–2334), who remark that the epidemiological data by Wang et al. are supported by the results of the recent HOPE-3 study showing cardiovascular morbidity and mortality, including stroke, could be significantly reduced by combining antihypertensive and cholesterol lowering therapies in individuals with grade 1 hypertension and low–moderate cardiovascular risk. The other article on stroke (Rojek et al., pp. 2441–2448) demonstrates that the combination of left ventricular dysfunction and increased arterial stiffness identifies patients with the poorest poststroke prognosis. Perlini et al. (pp. 2335–2336), commenting these data in their editorial, remark that the cross-talk between heart and large vessels appears crucial, not only in determining the risk of an event, but also in modulating its short-term and long-term sequelae.

Another article with potential clinical application is published by Alexandre et al. (pp. 2449–2457), who have carried out a prospective follow-up of patients undergoing coronary artery bypass graft (CABG) to determine the role of plasma aldosterone in the incidence of atrial fibrillation in the 30 days after surgery. They have developed a preoperative ‘Aldoscore’, which may be helpful in the management of post-CABG patients.

In a group of epidemiological articles, Yan et al. (pp. 2337–2343) shed light on secular trends of body-size measurements and prevalence of hypertension among Chinese children and adolescents in the past few decades, reporting hypertension prevalence in Chinese children increased 0.19% per year, which is consistent with the obesity trend. Camacho et al. (pp. 2344–2352) find that social disparities explain differences in hypertensive prevalence, detection and control in Colombia, and Zack et al. (pp. 2353–2364), in a screening survey of community-dwelling adults in Dar es Salaam, Tanzania find that major risk factors for hypertension are overweight, obesity, inadequate physical activity and limited access to quality medical care.

Exercise-related problems have been investigated in other articles in this issue of the Journal. Demmer et al. (pp. 2365–2375) have examined the evolution of relationships between measures of muscle strength and endurance with individual cardiometabolic risk factors from childhood to late adolescence in a prospective population-based cohort in Western Australia. By running a randomized crossover trial in inactive obese adults with type-2 diabetes mellitus, Dempsey et al. (pp. 2376–2382) find that interrupting prolonged sitting with brief bouts of light walking or simple resistance activities reduces BP and plasma noradrenaline with simple resistance activities being more effective. In “sedentary” spontaneously hypertensive rats (SHR), Maida et al. (pp. 2383–2392) have observed that amlodipine was more effective in promoting beneficial autonomic cardiovascular adaptations, whereas enalapril achieved better autonomic results only when combined with aerobic physical training.

As mentioned at the beginning of this article, several mechanistic articles are also included in this issue of the journal. Brie et al. (pp. 2318–2329) have conducted a systematic review and meta-analysis of randomized controlled trials on the impact of pentoxifylline on BP and various inflammatory markers, finding no significant effect on BP, but a significant reduction of TNF-α and C-reactive protein, but not of IL-6. Lane-Cordova et al. (pp. 2402–2409) report that BP and endothelial responses to an inflammatory stimulus are influenced by age, but not by age-associated inflammation, whereas Greve et al. (pp. 2410–2417) show that elevated estimated arterial age is associated with the metabolic syndrome and low-grade inflammation. Another mechanistic study by Karamat et al. (pp. 2418–2426) provides evidence in SHR on the BP lowering effect (including vasodilatation and a diuretic effect) of creatine kinase inhibition, suggesting that modulation of the creatine kinase system may be a potential novel approach to the treatment of hypertension.

Two articles investigate mechanisms of BP changes during night and sleep. Tabara et al. (pp. 2393–2401) have investigated the possible role of B-type natriuretic peptide (BNP), a marker of body fluid retention, in opposing the physiological dipping of BP at night, finding higher BNP in hypertensive patients whose BP rises, rather than dipping, at night. Svedmyr et al. (pp. 2427–2433) report that arterial stiffness, measured during sleep as finger pulse wave form reflection (pulse propagation time), is influenced by sleep stage and sleep apnea in normotensive but not in hypertensive patients.

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Conflicts of interest

There are no conflicts of interest.

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1. Palatini P, Agabiti Rosei E, Casiglia E, Julius S, Kjeldsen SE, Mancia G, et al. Management of the hypertensive patient with elevated heart rate; statement of the Second Consensus Conference endorsed by the European Society of Hypertension. J Hypertens 2016; 34:813–821.
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