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Challenges in hypertension

prevalence, definition, mechanisms and management

Zanchetti, Alberto

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doi: 10.1097/HJH.0000000000000116
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There are continuing challenges in various aspects of hypertension research and, obviously, these are reflected in the current issue of the Journal of Hypertension.

A major problem and societal challenge is the rapidly increasing prevalence of hypertension and cardiovascular morbidity and mortality in Africa. An overview of recent studies published by Commodore-Mensah et al. (pp. 464–472) shows a high prevalence of hypertension and overweight/obesity in Western Africa (Nigeria and Ghana), with minimal differences between rural and urban populations, and populations living in Africa or migrated to industrialized countries. In another study from Nigeria, Nelissen et al. (pp. 487–494) report a high prevalence of 32% organ damage among hypertensive adults with almost a quarter of grade 1 hypertensive patients having signs of organ damage. As organ damage screening is often unavailable in sub-Saharan Africa, the authors suggest antihypertensive treatment for all patients with hypertension.

There are well known challenges in blood pressure (BP) measurement and definition of hypertension. In a provocative study, Sebo et al. (pp. 509–517) evaluate the accuracy of BP measurements by primary care physicians and show that accuracy is quite low and does not improve in physicians randomized to receive training. The authors conclude that BP measurements in primary care are unreliable to diagnose hypertension. Niiranen et al. (pp. 518–524) bring forth further evidence in favour of a greater predictive effect of home BP by a prospective 11.2-year follow-up study, showing that both isolated diastolic and isolated systolic hypertensions as defined by home BP are associated with an increased incidence of cardiovascular events, with home BP providing a more accurate risk prediction than office BP.

Definition of hypertension is particularly difficult in children and adolescents, in whom a risk-based definition, like in adults, is made difficult by the low incidence of cardiovascular outcomes. Definition is commonly based on distribution-based BP reference values, and in this issue, Yip et al. (pp. 606–619) provide ambulatory BP standards for Chinese children and adolescents, with sex-related age-specific and height-specific percentiles, confirming lower values in non-overweight children, and remarking that values in Chinese children were generally higher than corresponding values for German children. In a thoughtful accompanying editorial, Chiolero (pp. 477–479) wonders whether risk-based rather than distribution-based BP reference values are needed in children like in adults, and suggests the use of intermediate outcomes (organ damage), or, alternatively, BP centile curves passing at age 18 through the adult hypertension cut-off of 140/90 mmHg.

Two other studies in this issue concern BP in children and adolescents. Islam et al. (pp. 598–605) report that microvascular (retinal) endothelial dysfunction is associated with parental hypertension, and Roberts et al. (pp. 620–626) find that in late adolescence, extreme preterm survivors have higher ambulatory BP compared with term controls and call for long-term cardiovascular surveillance for this population, whose number is increasing recently.

Definition of hypertension is nowadays associated with evaluation of total cardiovascular risk. Zambon et al. (pp. 495–508) remark that in hypertension guidelines, the level of risk is expressed in a non-uniform way, that is, each guideline expresses risk as the 10-year incidence of different types of cardiovascular outcomes. In order to avoid confusion, Zambon et al. have analysed the relationships between cardiovascular death rate and rates of other cardiovascular events in a large number of antihypertensive treatment trials and provide simple multipliers for calculating major and inclusive (Framingham) cardiovascular events from tables (such as that in the 2013 European Society of Hypertension–European Society of Cardiology) in which total cardiovascular risk is expressed as incidence of cardiovascular death. In an accompanying editorial, Banegas and Rodríguez-Artalejo (pp. 473–474) raise the issue that, although cardiovascular risk assessment is worth being used, there is insufficient evidence that it improves clinical practice and the low hypertension control generally achieved may suggest that a simpler approach, that is, the recommendation of treating every hypertensive patient with medication, may improve BP control.

For what concerns the mechanisms of hypertension and cardiovascular and renal damage, increasing emphasis is being given to the role of oxidative stress, but clinical translation of experimental evidence has been elusive. Additional experimental evidence in favour is reported in a number of studies in this issue. Wenceslau and Rossoni (pp. 542–554) have found that an ouabain inhibitor, rostafuroxin, decreases superoxide anion generation and enhance nitric oxide synthesis in mesenteric resistance arteries of deoxycorticosterone-salt hypertensive rats. McLachlan et al. (pp. 555–564) report that combination of the mitochondria-specific antioxidant, MitoQ10, with low-dose losartan significantly attenuates development of hypertension and reduces left-ventricular hypertrophy in stroke-prone spontaneously hypertensive rats. The authors suggest MitoQ10 as a potential novel therapeutic intervention in combination with current antihypertensive agents. On the clinical side, De Ciuceis et al. (pp. 565–574) have found that enalapril, but not hydrochlorothiazide, potentiates the beneficial effects of the calcium antagonist lercanidipine on retinal vascular structure and central BP, and, in parallel, enalapril, but not hydrochlorothiazide, potentiates the antioxidant properties of lercanidipine. Bang et al. (pp. 667–672) from an analysis of Losartan Intervention for Endpoint (LIFE) study patients report that a systemic inflammatory disease such as psoriasis independently predicts new-onset atrial fibrillation. In an accompanying editorial, Angeli et al. (pp. 480–483) briefly review the pathophysiological mechanisms underlying the link between hypertension and atrial fibrillation, and the role that inflammation can play in the remodelling of left ventricle and left atrium, but conclude that it is uncertain whether the link between psoriasis and atrial fibrillation is causal.

An important contribution to the debate on the therapeutic role of antioxidant agents is given by a study by Sugama et al. (pp. 534–541), who have observed that, in stroke-prone spontaneously hypertensive rats, both the antioxidant tempol and the angiotensin receptor blocker candesartan effectively reduce reactive oxygen species in the kidney, but only candesartan lowers BP and improves glomerular damage and proteinuria, whereas tempol does not decrease BP, and exacerbates proteinuria and glomerular damage. In a stimulating editorial, Rafiq and Nishiyama (pp. 475–476) review the conflicting experimental and clinical data on the effects of antioxidant therapy and conclude that current experimental evidence suggests that early antioxidant treatment may exert a beneficial action on hypertension development and cardiovascular and renal damage. However, antioxidants appear to become less effective the more advanced is the stage of hypertension, whereas the renin–angiotensin system may still play an important pathogenetic role even at later stages as suggested by the beneficial action of its blockade.

Management of hypertension still meets challenges, the most important of which is resistant hypertension. Smith et al. (pp. 635–643) have re-analysed data from the International Verapamil SR-Trandolapril Study (INVEST) and found that about 38% of the patients included in this trial (all with coronary heart disease) could be defined as resistant to treatment having achieved BP values higher than 140/90 mmHg, despite three drugs or necessitating four drugs, and that resistant hypertension was associated with poor prognosis. Salles et al. (pp. 644–651) report that in patients with resistant hypertension, two heart rate variability parameters reflecting sympathetic over-activity were independently associated with a blunted nocturnal BP fall. Finally, Borisenko et al. (pp. 681–692) have simulated the cost-effectiveness and the long-term clinical performance of baroreceptor stimulation for the treatment of resistant hypertension when compared to optimal medical treatment, and conclude Barostim may be a cost-effective treatment.

Treatment of hypertension in patients with obstructive sleep apnoea (OSA) is also challenging. Kasai et al. (pp. 673–680) bring further evidence that fluid redistribution from the legs to the neck during sleep contributes to the severity of OSA and may be relieved by intensifying diuretic therapy. In their editorial commentary, Lombardi et al. (pp. 484–486) underline that further studies should focus on the effects of an intensified diuretic treatment on 24-h and night ambulatory BP in OSA patients, as these measurements may more faithfully reflect the effect of rostral fluid volume shift during sleep.

Whether visit-to-visit BP variability should be a target of antihypertensive treatment is still debated, and an analysis of data from the Second Australian National BP Study now provides data in favour of also aiming at BP variability, by showing that in the elderly patients of this trial, visit-to-visit BP variability was a strong predictor for all types of cardiovascular events (Chowdhury et al., pp. 525–533). Treatment of hypertension during pregnancy is another issue in which experts’ opinions diverge. Al Khaja et al. (pp. 454–463) have carefully reviewed differences in the recommendations in 25 guidelines, and found a general consensus only on oral α-methyldopa and parenteral labetalol, whereas long-acting nifedipine is recommended by only a number of guidelines, and the safety of ß-blockers and diuretic is controversial and unresolved. The authors make a plea to solve these issues in view of future guidelines.

As usual, additional aspects of hypertension have been approached by studies in the current issue of the Journal. Jackson et al. (pp. 575–586), by using the centrally acting sympatholytic agent, rilmenidine, in a strain of mice with neurogenic hypertension, conclude that in this strain, hypertension is not likely to be mediated by greater neuronal activity in the rostroventrolateral medulla. Koeners et al. (pp. 587–597) report that acute neurogenic hypertension induced by intra-renal unilateral injection of phenol leads to renal vasoconstriction and increased renal hypoxia-induced factor 1α (HIF-1α): enhancing production of HIF-1α through preconditioning ameliorates renal neurogenic hypertension and renal vasoconstriction. Bouissou et al. (pp. 652–658) report that in sino-aortic denervated and chemically denervated rats, a similar increase in aortic stiffness is associated with different structural alterations.

Laukkanen et al. (pp. 659–666) report an 18.9-year follow-up of a large cohort of men whose BP had been carefully measured during and after exercise, showing SBP in the recovery phase is related to the risk of sudden cardiac death, but the relation disappears after adjusting for SBP at rest. Lonati et al. (pp. 627–634) find that the rate of false-positive tests calculating the aldosterone/renin ratio for the diagnosis of primary aldosteronism is lower when plasma renin concentration rather than activity is used. Postel-Vinay et al. (pp. 693–698) have evaluated a patient questionnaire to be completed at home before consulting in a hypertensive clinic, and found it is well accepted by patients and useful. It remains to be proved that the same approach is feasible and useful in primary care.


Conflicts of interest

There are no conflicts of interest.

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