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Guidelines, organ damage, diagnostic procedures and treatment

Zanchetti, Alberto

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doi: 10.1097/HJH.0b013e328364dd74
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Guidelines, mechanisms of organ damage development, diagnostic procedures and classifications, new therapeutic approaches, all these aspects are within the scope of a journal devoted to hypertension, all these types are represented in the content of the current issue of the Journal of Hypertension.

The European Society of Hypertension-European Society of Cardiology Guidelines on the management of hypertension, published in an extensive version in the July issue, have been aimed at presenting a body of important recommendations accompanied by a critical appraisal of the available data leading to and supportive of those recommendations. This is a necessary approach to justify the recommendations and to have them shared by a larger number of experts and investigators in the area of hypertension and cardiovascular prevention. Guidelines, however, have to be implemented in medical practice, and not all practitioners and health workers involved in the management of hypertension have time and interest to read an extensive document, and only require a few pages summary to ease and support their decisions. This agile document is published in the current issue (pp. 1925–1938). Although the sponsoring scientific societies believe it will represent a widely used instrument for everyday medical practice, they also hope it will be a stimulus for doctors to peruse at least parts of the extensive document in the July issue in order to understand the critical process through which guidelines have been developed.

This issue of the Journal is also devoted to a large number of studies describing and discussing new mechanisms through which hypertension can lead to organ damage. A review by Kassan et al. (pp. 1939–1943) accompanied by an enlightening editorial commentary by Schiffrin (pp. 1944–1945) discusses immune mechanisms in hypertensive vascular dysfunction. While Kassan et al. (pp. 1939–1943) in their review concentrate on the role of T-regulatory lymphocytes to oppose the actions of T-effector lymphocytes, Schiffrin also calls attention on the evidence that the cells of the innate and adaptive immune systems talk to each other and may exert varying actions, and concludes that ‘the ability of the immune system to … exert either protective or deleterious effects is likely to … offer new surprises, discoveries, and hopefully potential novel targets for intervention … in cardiovascular disease’.

A number of articles illustrate further mechanisms associated with vascular disease. The mid-regional part of pro-adrenomedullin, a peptide hormone secreted in response to cellular strain, has been found to be positively correlated with brachial pulse pressure, carotid intima–media thickness and carotid atherosclerotic plaque score, although the cross-sectional nature of the study – as acknowledged by the authors – cannot prove the hypothesis that adrenomedullin secretion is a protective response to vascular injury (Gottsäter et al., pp. 1959–1965). The chain of events triggered by angiotensin II in inducing endothelial dysfunction has been investigated by Marampon et al. (pp. 1972–1983) by using an angiotensin-converting enzyme (ACE) inhibitor, such as zofenoprilat, in human umbilical vascular endothelial cells. They conclude that the p38-Sir T1 axis appears to modulate the cardiovascular benefit derived from ACE-inhibition and may represent a novel therapeutic target in cardiovascular prevention. Augmented calcium entry into the vascular smooth muscle cells of spontaneous hypertensive rats (SHRs) has been reported to occur mostly through nifedipine-sensitive voltage-dependent calcium channels, whereas calcium sensitization mediated by the RhoA/Rho kinase pathway is attenuated compared with normotensive animals (Behuliak et al., pp. 2025–2035). Also in an animal model, Dallatu et al. (pp. 2043–2049) provide data suggesting that the protective role exerted by physiological levels of nitric oxide (NO) may be by NO-induced inhibition of prolylhydroxylase domain containing protein (PHD) and increase of hypoxia-inducible factor-1 α (HIF-1α). However, PHD inhibition by dimethyloxallyl glycine also induced renal damage, thus challenging the dogma that PHD inhibition invariably has protective effects against vascular disease. In inbred colonies of SHRs podocyte effacement, glomerular injury, tubulo-interstitial injury and albuminuria are seen in some colonies but not in others, thus indicating an important heritability component of renal injury (Braun et al., pp. 2050–2059). Finally, Catena et al. (pp. 2077–2084) report that elevated plasma levels of fibrinogen and a prothrombothic state are associated with left ventricular diastolic dysfunction in hypertensive patients.

A considerable group of articles concern diagnostic and related therapeutic aspects of hypertension. Brant et al. (pp. 1984–1990) report that peripheral arterial tonometry, a novel noninvasive method to assess endothelial function, has acceptable reproducibility and may represent a promising method for future clinical and epidemiological studies. Ott and Schmieder (pp. 1946–1947), whose group first introduced the technique of scanning laser Doppler flowmetry in the retina about 10 years ago, comment on another interesting development of analysing the retinal vascular bed noninvasively. Through a computer-assisted program the reputable group led by Wong has been capable of analysing a newly developed parameter, retinal vascular fractal dimension (Df), as a global measure of its geometric complexity, and reports an inverse correlation between this parameter and blood pressure in uncontrolled or untreated hypertension (Sng et al., pp. 2036–2042). However, as remarked by Ott and Schmieder, whether retinal Df is the most promising and reliable parameter to detect early retinal involvement in the course of hypertension remains a question open for further investigation.

Definition of the metabolic syndrome is a highly debated issue, and a large survey in Portugal has investigated which of the various definitions of this syndrome provides the best association with uncontrolled hypertension (Cortez-Dias et al., pp. 1991–1997). Another study shows the polycystic ovary syndrome phenotype, in which components of the metabolic syndrome are often present, is associated with increased arterial stiffness (Armeni et al., pp. 1998–2004). The well known group of Devereux, on the basis of the large set of echocardiographic data from the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, presents a new four-group classification of left ventricular hypertrophy (Bang et al., pp. 2060–2068). The same group provides evidence that inclusion of basal myocardium in cardiac MRI improves agreement with echocardiographic and necropsy measurements of left ventricular mass (Simprini et al., pp. 2069–2076).

A group of articles relates to diagnostic aspects of aldosteronism and the use of drugs interfering with aldosterone synthesis or receptors in hypertension. On the basis of their large experience, Wolley et al. (pp. 2005–2009) insist on the opportunity of repeating adrenal vein sampling when neither aldosterone–cortisol ratio exceeds peripheral values. Honda et al. (pp. 2010–2017) have investigated adrenal reserve function in patients with unilateral aldosterone-producing adenoma and after unilateral adrenalectomy. The use of low-dose spironolactone in diabetic patients with resistant hypertension has been evaluated in one of the very few randomized studies, and its effectiveness and safety established (Oxlund et al., pp. 2094–2112). In a thoughtful editorial commentary, Azizi et al. (pp. 1948–1951) remark that this new study adds weight to the pathophysiological role of aldosterone in patients with resistant hypertension and diabetes, but the long-term benefit/risk ratio of mineralocorticoid receptor blockers in patients with diabetes in ‘real life’ remains to be determined. In a related article on resistant hypertension, Brambilla et al. (pp. 2018–2024) report the results of a survey carried out in Central and Eastern Europe, confirming the high prevalence of resistant hypertension, and the frequent association of this condition with obesity, renal failure, organ damage and history of cardiovascular events. Finally, Schumacher et al. (pp. 2085–2093) report results of testing a new aldosterone synthase inhibitor for the treatment of hypertension, and emphasize the need that future inhibitors improve their target selectivity by sparing the 11β-hydroxylase reaction and preferentially inhibiting one of the two other enzymatic reactions mediated by aldosterone synthase.

The October issue of the Journal is completed by two important epidemiological articles, one showing that hospitalization for hypertension clusters in families, a further confirmation of the heritability of this condition (Westerdahl et al. pp. 1952–1958). An important study of school children in North of Portugal with careful 24-h urinary sodium studies indicates that children 10–12 years old have a high salt intake well above common recommendations, and calls for an education strategy aimed at reducing daily sodium intake as an important public health target (Cotter et al., pp. 1966–1971).


Conflicts of interest

There are no conflicts of interest.

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