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Therapeutic approaches, age and ethnicity in hypertension

Zanchetti, Alberto

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doi: 10.1097/HJH.0000000000001404
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A large part of the articles in the current issue of the Journal of Hypertension are devoted to therapeutic aspects of hypertension and to age and ethnicity-related problems.

Among therapeutic studies, Ashor et al. (pp. 1353–1359) have reviewed and meta-analyzed randomized controlled studies investigating whether dietary nitrate supplementation (either as inorganic nitrate or beetroot juice) can reduce SBP and DBP. They report that significant blood pressure (BP) reduction by 1–6-week dietary nitrate supplementation was only observed by clinic BP measurement and was not replicated by more accurate methods such as 24-h ambulatory or daily home monitoring. Another natural chemical product, gallic acid, which is found in plants and has been reported to have antioxidant and anti-inflammatory effects, has been tested by Jin et al. (pp. 1502–1512) in mice made hypertensive by L-NAME and showing left ventricular remodeling and fibrosis. The results here reported make the authors suggest that gallic acid may be a potential therapeutic agent for hypertension and cardiac fibrosis that may deserve clinical testing. Other experimental findings with potential clinical interest are published by Zhang et al. (pp. 1442–1456), who report that in spontaneously hypertensive rats pretreated with the AT1 blocker telmisartan adjunctive therapy with a statin, pitavastatin, significantly reduced residual albuminuria/proteinuria and enhanced nephroprotection. Possible mechanisms for this nephroprotective effect of pitavastatin have also been investigated.

In a more direct clinical study, Park et al. (pp. 1474–1480) have compared in a randomized controlled trial the BP-lowering effect of simple resting versus antihypertensive medication in patients admitted to the emergency room of a large hospital with hypertensive urgencies and found no significant difference between the two interventions during the first 2 h after admission. In another double-blind, randomized controlled trial, Mourad et al. (pp. 1481–1495) have found that a three-drug combination in a single pill (perindopril/indapamide/amlodipine) produced office, ambulatory and home SBP and DBP reductions greater than those induced by a two-drug combination (perindopril/indapamide), thus providing additional support to the current therapeutic trend to recommend multiple-agent combinations in the same pill. Another randomized, controlled trial with crossover design has been completed by Beige et al. (pp. 1496–1501) in patients with hypertension resistant to pharmacological treatment who were long-term carriers of baroreceptor-activating therapy (BAT). Temporary (4 weeks) blinded withdrawal of BAT was accompanied by significant increases of both ambulatory and office BPs, though not to preimplantation values. In an interesting case report, Barbic et al. (pp. 1513–1520) describe a male patient with autoimmune autonomic ganglionopathy with remarkable orthostatic hypotension and suggest that spectral indices of cardiovascular autonomic control may represent noninvasive, low-cost biomarkers suitable to follow-up these patients during repetitive selective immunoadsorption treatment.

The debated issue of antihypertensive treatment in the very olds has been approached by Corrao et al. (pp. 1432–1441), who have examined the large health database of the Lombardy region in Italy and found that in patients aged 85 years and more adherence with antihypertensive drug therapy reduced the risk of cardiovascular morbidity, particularly heart failure and stroke. Joas et al. (pp. 1424–1431) have studied time trends of BP among Swedish septuagenarians examined three decades apart: in these longitudinal studies, SBPs and DBPs were found considerably lower in septuagenarians born in 1930 compared with those born in 1901–1902, also when adjusting for antihypertensive treatment. The effect was especially pronounced in women. In an accompanying editorial commentary, Wiley (pp. 1366–1367) underlines that data such as those presented by Joas et al. indicate that ‘population databases or national health registries are needed that over time systematically track risk factors related to BP beyond antihypertensive treatment, such as diet, exercise, sleep and other established risk factors. Only with this additional information will we be able to understand not only that birth cohort differences exist, but why they exist and what can be done to continue moving in the direction of better population health’.

Another two articles also focus on age-related aspects of hypertension, though concerning childhood and adolescence. Sylvestre et al. (pp. 1416–1423) have identified sex-specific trajectories of SBP and DBP from early adolescence to early adulthood and assessed the magnitude of the effects of modifiable risk factors on these trajectories. Murakami et al. (pp. 1411–1415) report that pulse pressure (PP) amplification (i.e. peripheral PP is larger than central BP) is also observed in children, but the degree of amplification increases with age during childhood, contrary to the relationship in adults. In an editorial commentary, Zachariah (pp. 1363–1365) discusses the various possible mechanisms suggested by Murakami et al. to reconcile the thorny problem of an increase in PP amplification with increasing age during childhood and adolescence and concludes that future work is needed to disentangle the complex relations between age, growth, flow, arterial properties and resulting pressure. Vascular properties, though in adulthood, are the objective of two other articles in this issue. Teixeira et al. (pp. 1402–1410) show that speckle-tracking analyses of aortic arch ultrasound images is feasible and might serve as a new approach to evaluate arterial function, and Idris-Khodja et al. (pp. 1390–1401) report that inactivation of the peroxisome proliferation-activated receptor γ (PPARγ) gene in the vascular smooth muscle cells of mice exaggerates endothelin-1-induced vascular injury, supporting a protective role for PPARγ in hypertension through modulation of pro-oxidant and proinflammatory pathways.

In the past couple of years, the Journal of Hypertension has published epidemiological studies denying the claim that treatment with different antihypertensive agents is associated with increased incidence of cancer. An open problem, however, is whether hypertension per se, rather than its treatment, may be associated with increased risk of some types of cancer. The problem is likely to remain open also after the publication of two new studies in the current issue of the Journal. Hidayat et al. (pp. 1333–1344) have done an extensive search for prospective studies on the association of hypertension with renal cancer and meta-analyzed data from 18 studies involving 3 628 479 participants, concluding that each 10-mmHg increase in SBP and DBP is associated with 10 and 22% increased risk of kidney cancer. On the other hand, Yang et al. (pp. 1371–1380) in a prospective cohort study in Melbourne did not observe any associations between BP measured at baseline and breast cancer risk overall, nor by subtype.

Ethnicity is another factor influencing hypertension and its treatment, and its genetic background has actively been investigated recently. Hypertension is a major risk factor especially among African-Americans, but the two recent largest exomic analyses have been conducted in populations mostly of European ancestry. Now, Nandakumar et al. (pp. 1381–1389) publish an important study identifying a number of rare coding variants associated with BP variation in 15 914 individuals of African ancestry. In a thoughtful accompanying editorial commentary, Harrap and Charchar (pp. 1360–1362) review the recent story of genome-wide association studies and exomic analyses in BP and hypertension research and conclude that the genetic markers identified so far have little likely clinical utility because they are associated with tiny effects or are too rare to justify widespread testing. In their opinion, much more remains to be discovered and an enormous amount to be understood, before we learn whether genetics will add anything significant to the prediction of cardiovascular risk beyond simple BP measurements.

Kaze et al. (pp. 1345–1352) publish an interesting epidemiological contribution to the prevalence of hypertension in older people in Africa by doing a systematic survey and a meta-analysis of available studies and showing an overall prevalence of 55.2%, higher in urban compared with rural settings. Finally, two articles in this issue report on prevalence, awareness, treatment and control of hypertension in Middle East countries (Yusufali et al., pp. 1457–1464) and, respectively, in the Seychelles (Heiniger et al., pp. 1465–1473). In the four Middle East countries considered, prevalence of hypertension was found to be higher in rural communities, but awareness, treatment and control were significantly higher among urban dwellers. Commenting the data by Yusufali et al. on an accompanying editorial, Clement (pp. 1368–1370) underlines the poor BP control in most parts of the world despite the very good tools available to lower BP, and remark that ‘action should be taken on all possible levels and all priority should be given to such action’. Some optimism about the possible success of these actions comes from the results of the article by Heiniger et al. (pp. 1465–1473) comparing two surveys done in the Seychelles between 1989 and 2013, showing that the prevalence of high BP decreased over time, and paralleled improved detection and control of hypertension.


Conflicts of interest

There are no conflicts of interest.

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