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, Milano 20122, Italy. Tel: +39 02 503 204 84; e-mails: email@example.comfirstname.lastname@example.org
Received 5 February, 2013
Accepted 5 February, 2013
As usual, articles published in this issue of the Journal of Hypertension bring new contributions to several currently debated problems concerning understanding and management of hypertension.
An important editorial by O’Rourke and Adji (pp. 649–654) calls attention to the long neglected ‘isolated systolic hypertension’ in youth, remarking that guidelines have focused only on ‘isolated systolic hypertension’ of the elderly and underlined the very strong available evidence of outcome reduction by lowering blood pressure in this condition, thus causing some misunderstanding if recommendations for treatment are extended from the elderly to the young. O’Rourke and Adji clarify that different haemodynamic patterns are responsible for the two types of isolated systolic hypertension. In youth, at variance with old age, central blood pressure is not raised, and in an accompanying commentary (pp. 655–658) another authority in the field, Michel Safar, concludes that the dilemma ‘to treat or not to treat’ the young individual with isolated systolic hypertension should be solved, at present, in a negative way, unless organ damage is present. Isolated systolic hypertension in youth seems to be a clinical condition in which measurement of central blood pressure is really useful for a correct diagnosis. The possible usefulness of central blood pressure measurement for monitoring the results of antihypertensive treatment is debated in another paper (Park et al., pp. 813–819), comparing two different β-blockers, bisoprolol and atenolol: both reduced central blood pressure to the same extent despite the higher β1-receptor selectivity of bisoprolol. As in this study also atenolol significantly reduced central pulse pressure, the issue whether different β-blockers are differently effective on central blood pressure remains open.
Another problem central to the management of hypertension is the risk represented even by transient blood pressure elevations. After a remarkably long-term follow-up, mothers with a history of hypertensive pregnancy were found to have impaired vascular function and metabolic status as compared with mothers with a normal pregnancy (Collén et al., pp. 758–765), suggesting that even a remote alteration of blood pressure regulatory mechanisms may have influences on cardiovascular health. In a French community-based study, elderly individuals with isolated elevation of office (white-coat hypertension) or home blood pressure (masked hypertension) had an increased risk of sustained hypertension (both office and home) 1 year later (Cacciolati et al., pp. 680–689). Because of the current debate on the predictive value of blood pressure variability, Xu et al. (pp. 690–697) have analyzed 24-h ambulatory blood pressure variability in two large cohorts of twins and found this variability is predominantly determined by unique environmental factors in youth with a minor genetic component. Whether this also applies to other types of blood pressure variabilities remains to be investigated.
The role of the sympathetic system in blood pressure control has long been a favourite objective of hypertension research. An article by Hering et al. (pp. 739–746) brings new evidence on the elusive relationships between changes in sympathetic activity and blood pressure: the effect of slow breathing on muscle sympathetic activity appears to relate more to office than ambulatory blood pressure. This finding is in line with other previously reported observations with other manoeuvres, such as continuous positive airway pressure in sleep apnoea or renal denervation in resistant hypertension, which certainly reduce sympathetic activity but whose blood pressure effects have been so far more clearly shown by office than ambulatory measurements. Whether sympathetic activity is predominantly associated with the amplitude of the white-coat effect is obviously a question worth being investigated promptly. Along the same line of evidence, a careful analysis of US population data by Vozoris (pp. 663–671) shows that a condition presumably associated with high sympathetic activity, insomnia with short sleep time, is associated with increased odds of subjective definition of hypertension, but not with objective hypertension measures.
In the same area of sympathetic regulation of blood pressure control, an interaction between renal innervation and a brain Gαi2-subunit protein-gated pathway has been described in rats (Wainford et al., pp. 747–757), thus strengthening available evidence on sympathetic (efferent as well as afferent) control of renal function.
Exercise is another manoeuvre known to influence neural control of the circulation, and widely recommended by all guidelines as a life-style measure to lower blood pressure. However, the effects of endurance training are less well known, and individual studies investigating the effect of this type of exercise on ambulatory blood pressure have remained nonconclusive. A systematic review and meta-analysis by Cornelissen et al. (pp. 639–648) shows that aerobic endurance exercise significantly decreases day-time, but not night-time, blood pressure. Accordingly, in a large group of young professional football players, studied by Berge et al. (pp. 672–679), prevalence of hypertension was found to be low, but when blood pressure was elevated it was associated with reduced arterial compliance and increased left ventricular mass.
Organ damage associated with hypertension is given due attention in this issue of the Journal. Michael Mulvany's group, the group that first developed methods for measuring structural changes of small resistance arteries in hypertensive patients, publishes the results of a 15-year follow-up study showing that on-treatment alterations of small artery structure identify individuals still at increased cardiovascular risk despite long-term blood pressure normalization. This suggests that monitoring these structural changes may help predicting treatment results (Buus et al., pp. 791–797). Measurement of carotid intima–media thickness is also known to help classifying cardiovascular risk. Den Ruijter et al. (pp. 782–790) now provide calculations that the procedure is cost-effective over a period of 10 years, and even more over a 30-year period. Another vascular bed in which quantitative measures of structure and function have become available is the retinal vascular bed, and Ritt et al. (pp. 775–781) call attention to the finding that haemoglobin concentration is an independent determinant of retinal vascular function, possibly through a NO scavenging effects of haemoglobin. As commented by Avolio and Grassi (pp. 661–662), blood haemoglobin content would need to be taken into account when measuring retinal blood flow. Two articles deal with microalbuminuria: Konno et al. (pp. 798–804) have studied predictors of microalbuminuria in a population study in Japan, underlining the role of DBP even in the high-normal range, and Hellemons et al. (pp. 805–812) in a case–control study identify high-sensitivity troponin-T as an independent marker predicting the transition from normalbuminuria to microalbuminuria and from microalbuminuria to macroalbuminuria.
In this issue of the Journal a number of pathophysiological articles focus on the renin–angiotensin system. Activation of AT2 receptors, a problem that has long been debated, has been investigated by Schalekamp and Danser (pp. 705–712), who have calculated that the threshold concentration of angiotensin II needed for response is much higher for AT2 than for AT1 receptors, and that plasma angiotensin II rather than tissue angiotensin II is the agonist of AT2 receptors. The renin inhibitor aliskiren has been found to accumulate in the murine kidney, but neither renin nor (pro)renin receptor-bound protein appear to be major players in this process (Lange et al., pp. 713–719). An editorial commentary by Rahman et al. (pp. 659–660) points out that these findings suggest that hyperkalemia and hypotension observed in the ALTITUDE study may not simply be explained by the assumption that aliskiren accumulates in the kidney by binding to increased renin in response to concomitant ACE inhibitor or angiotensin receptor blocker treatment. Local mechanical stimulation has been found to activate the AT1 receptor in the porcine coronary artery as a mechanism leading to endothelial dysfunction (Lu et al., pp. 720–729), and in obese mice the role of angiotensin II in endothelial dysfunction is demonstrated by attenuation of this dysfunction by infusion of angiotensin 1–7 (Beyer et al., pp. 730–738).
Finally, a group of articles more directly explores therapeutically relevant problems. McDonough et al. (pp. 698–704) have conducted a pharmacogenomic research in a large number of patients included in two clinical trials to detect genetic predictors of the blood pressure response by hydrochlorothiazide. Fenofibrate was found to reduce blood pressure only in salt-sensitive individuals, whereas the reduction in triglycerides occurred independently of salt sensitivity (Gilbert et al., pp. 820–829). In a large cohort of patients defined with uncontrolled hypertension despite the use of at least four antihypertensive agents, analysis of these drugs or their metabolites in urine revealed that 53% of the patients had complete or partial nonadherence to therapy (Jung et al., pp. 766–774). Finally, the debated issue of the target blood pressure has been approached by Zygmuntowicz et al. (pp. 830–839) in terms of health-related quality of life. They report that blood pressure values associated with optimal quality of life are generally within the guidelines-recommended levels, but values increase with the number of antihypertensive drugs prescribed. This may further support the suggestion provided by two articles previously published in the Journal of Hypertension (2012; 30: 2202–2210, 2213–2222) that the need of more complex therapy may be an index of more severe disease and higher cardiovascular risk.
Conflicts of interest
There are no conflicts of interest.
© 2013 Lippincott Williams & Wilkins, Inc.