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Diagnostic and therapeutic approaches to hypertension

Zanchetti, Alberto

doi: 10.1097/HJH.0000000000001465

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

Correspondence to 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:;

The focus of the current issue of the Journal of Hypertension is on diagnostic and therapeutic approaches, but, as usual, also other aspects of hypertension research are discussed.

The September issue opens with a Consensus article (pp. 1727–1741), jointly prepared by the European Association of Cardiovascular Imaging, the European Society of Cardiology (ESC) Council on Hypertension and the European Society of Hypertension (ESH), extensively dealing with noninvasive cardiovascular imaging for evaluating subclinical target-organ damage in hypertension. European hypertension guidelines jointly prepared by ESH and ESC in 2003, 2007 and 2013 have always underlined the importance of quantitatively assessing organ damage to help classifying cardiovascular risk, staging progression of cardiovascular disease and being able to target and control the effects of treatment on the pathological consequences of hypertension. The noninvasive nature of most of the available methodologies, particularly those based on cardiac and vascular ultrasounds, and the spreading of facilities and technical expertise in their clinical use are undoubtedly making noninvasive cardiovascular imaging more and more important in the diagnosis and follow-up of many hypertensive patients.

Other articles in this issue are relevant for the diagnostic and prognostic work-up of the hypertensive patient. The recent interest for the assessment of blood pressure (BP) variability in addition to the measurement of average prevailing BP values has resulted in two articles published in this issue. Vogiatzakis et al. (pp. 1750–1757) have reviewed and meta-analyzed all studies that have measured short-term (24 h) SBP and DBP variability following renal denervation in patients with treatment-resistant hypertension, and report a significant reduction in short-term variability, independent of the extent of BP reduction, an observation consistent with the known effect of renal denervation on sympathetic activation. In an accompanying editorial, Hering and Grassi (pp. 1780–1781) comment that despite robust evidence linking increased BP variability to adverse cardiovascular outcomes, the therapeutic management of patients with variable BP remains empirical and based on improvement of medication adherence and use of long-acting drugs. Sumida et al. (pp. 1816–1824) have investigated another BP variability parameter, visit-to-visit SBP variability, in patients with chronic kidney disease in the year preceding transition to dialysis and found high predialysis SBP variability predicted higher all-cause and infection-related mortality during the dialysis period. Importantly, higher predialysis SBP variability was associated with a number of modifiable clinical factors, such as higher SBP, use of erythropoietin-stimulating agents, inadequate cardiovascular medication adherence, and catheter use, and the authors suggest further studies should be done to test whether modification of predialysis SBP variability can improve survival in patients with end-stage renal disease.

Three articles have studied characteristics of the arterial wall with potential pathophysiological and diagnostic implications. In individuals undergoing clinically indicated cardiac angiography, X. Peng et al. (pp. 1825–1831) have investigated arterial reservoir characteristics through the large arteries of the upper limb, reporting that whereas reservoir pressure is relatively constant, excess pressure is highly related to BP amplification. Johansen et al. (pp. 1832–1840) in a 7.8 years of follow-up of individuals from a Danish population-based study, have found that dysglycemia at baseline is associated with future aortic stiffness. In a series of 1052 untreated Chinese patients with hypertension, Cheng et al. (pp. 1841–1848) report arterial stiffness independently increases with serum parathyroid hormone, but BP remains the main driver of arterial stiffening.

The supposed role of galectin-3 in mediating aldosterone-induced myocardial fibrosis has been investigated by van den Berg et al. (pp. 1849–1856), who report, however, that plasma galectin-3 concentrations are not elevated in patients with primary aldosteronism when compared with patients with essential hypertension and do not decrease after adrenalectomy.

Another consistent group of articles are related to problems of antihypertensive treatment. Among them, two are devoted to the elusive problem of treatment adherence. Kurdi et al. (pp. 1881–1890) have completed a retrospective cohort study of 176 835 patients with primary hypertension identified in the UK Clinical Practice Research Datalink and report that an index of treatment adherence (proportion of days covered by treatment) was associated with increasing age, using renin–angiotensin blockers and being a preexisting user of antihypertensive drugs. Higher deprivation, multiple comorbidities and switching of antihypertensive drugs were associated with lower adherence. Happier news comes from a study by Hamdidouche et al. (pp. 1891–1898), who, by directly measuring antihypertensive drugs and their metabolites in urine, find a good adherence to antihypertensive drugs in patients attending the out-patient clinics of a university hospital, thus suggesting that a suitable organization of care and good physician–patient relationships may be of considerable improvement.

The debated problem whether the antihypertensive effect may persist in a number of patients after treatment withdrawal has been systematically reviewed by van der Wardt et al. (pp. 1742–1749), who report that 38% of patients remain normotensive 6 months after cessation of antihypertensive therapy, the proportion decreasing to 26% after 2 years or longer. The authors suggest prescribers should consider offering patients with well controlled hypertension the possibility of treatment withdrawal, provided that BP is regularly monitored subsequently. This controversial problem is discussed by Jennings (pp. 1778–1779) in an accompanying editorial: in the absence of a well powered randomized outcome study, the systematic review by van der Wardt et al. appears to add significantly to the body of evidence. However, until data from an appropriate randomized study is available, Jennings remarks that any decision to stop therapy in people with good BP control over many years will require a contract between the doctor and the patient, the former carefully monitoring the patient's BP at frequent intervals, the latter continuing nondrug measures helping to keep BP under control.

Two other articles with therapeutic impact are two reviews focusing on vasodilator beta-blockers. Giles et al. (pp. 1758–1767) summarize preclinical and clinical data of a single-pill combination of the vasodilator beta-blocker, nebivolol, with the angiotensin receptor blocker, valsartan, showing a greater BP reduction by the combination than by component monotherapies. In addition, the two drug combinations prevented valsartan-induced increases in plasma renin and produced a greater reduction in plasma aldosterone. The review by Kwon et al. (pp. 1768–1777) deals with the renal effects of five different vasodilator beta-blockers: vasodilator beta-blockers were found not to affect glomerular filtration rates or serum creatinine levels and to decrease proteinuria. Vasodilator beta-blockers decreased renal vascular resistance significantly more than nonvasodilator beta-blockers, but proteinuria reduction was similar.

Two additional articles have therapeutic implications: Wang et al. (pp. 1899–1908) have shown that in the rat sodium butyrate suppresses angiotensin-II-induced hypertension by a mechanism involving the intrarenal renin–angiotensin system, and Bahadoran et al. (pp. 1909–1916) report evidence in favor of cardioprotective properties of allium vegetables.

Renal pathophysiology and epidemiology are two other areas approached by articles in the current issue of the Journal. Rubattu et al. (pp. 1857–1871) provide evidence that a differential expression of the mitochondrial anion transporter, uncoupling protein-2, associates with a different degree of renal damage in two congenic lines of spontaneously hypertensive rats stroke prone, through modulation of mitochondrial function, inflammation and oxidative stress, and Zhu et al. (pp. 1872–1880) report that miR-429 is an important upstream mediator of renal adaptation to high salt intake and salt sensitivity of BP.

Two epidemiological articles present data from the Strong Heart Study on American Indians. H. Peng et al. (pp. 1787–1793) find that a higher level of plasma plasminogen activator inhibitor-1 is significantly associated with incident hypertension, and Haring et al. (pp. 1794–1800) report that red meat consumption over a 4-year period was related to cardiovascular target organ damage. In an accompanying editorial, Banegas and Rodríguez-Artalejo (pp. 1782–1784) remark that although there are still aspects of red meat consumption that should be investigated in future studies, the available evidence indicates that a prudent, low red meat diet may help preventing preclinical and also symptomatic cardiovascular disease.

Another interesting epidemiological article deals with BP among Australian Aboriginal children, and reports BP is frequently elevated among urban children, the stronger predictors of BP being caregiver BP and child BMI (Larkins et al., pp. 1801–1807). Data from more than 100 000 participants in the Japan Arteriosclerosis Longitudinal Study have been used by Asayama et al. (pp. 1808–1815) to provide information on BP, heart rate and double product in Japan, reporting insufficient BP control even in Japan, the world country where the average life expectancy is the longest. Commenting this article, Elgendy and Pepine (pp. 1785–1786) conclude that although the mortality for cardiovascular disease and hypertension has been decreasing over the past few decades, optimal BP control remains an important factor that deserves better control as well as new approaches.

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Conflicts of interest

There are no conflicts of interest.

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