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Hypertension: prognostic, diagnostic and therapeutic aspects

Zanchetti, Alberto

doi: 10.1097/HJH.0000000000001611

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

All major aspects of hypertension management, prognostic, diagnostic and therapeutic ones, are covered by articles published in the current issue of the Journal of Hypertension.

A group of 11 articles explores prognostic aspects. Marron et al. (pp. 43–53) have assessed the hypothesis that a healthy blood pressure (BP) phenotype they had developed in cohorts of familial longevity (Long Life Family Study), characterized by an age-adjusted and sex-adjusted SBP Z-score between −1.5 and −0.5, is also familial. Among 410 families, only 44 met the criteria for the healthy BP phenotype. Among the latter families, a higher proportion of offspring met the American Heart Association definition of ideal cardiovascular health (10.8 versus 3.8%), driven by BP, smoking status and BMI. In a sample of the general population of Didima, Greece, followed-up for 19 years, Ntineri et al. (pp. 69–76) found home BP predicted total mortality and cardiovascular disease as reliably as office BP. However, home SBP variability exhibited superior prognostic ability than office BP variability. Furthermore, Ntineri et al. report that not only sustained and masked, but also white-coat hypertension was associated with increased risk of death and cardiovascular disease events versus normotensive patients. In an editorial commentary, Myers (pp. 34–36) raises the point that the real cardiovascular risk associated with white-coat hypertension is still controversial, and that a small sample size and a limited number of end points during follow-up may lead to exaggerated estimates of cardiovascular risk in patients with white-coat hypertension.

Three other articles investigating prognostic aspects focus on comparing BP risk in patients with and without diabetes mellitus. Gomadam et al. (pp. 85–92) have analysed data from 17 650 participants from the National Health and Nutrition Examination Survey III and 1439 participants from the Diabetes Heart Study followed-up for a mean of 16.2 years and found that the association between SBP and cardiovascular mortality is nonlinear, but different in diabetes (U shaped) and nondiabetes, suggesting this may explain why aggressive BP lowering may have different outcomes in presence or absence of diabetes. Jiang et al. (pp. 93–100) have investigated the same problem, though with a cross-sectional approach, in 42 959 patients of the PURE China study, and report both in patients with and without diabetes risk of stroke and coronary disease events markedly increased in hypertensive patients compared with individuals with normal BP, whereas no significant difference in risk was seen between high-normal BP and normal BP groups. Always in the context of the problem of the optimal BP to be achieved by antihypertensive treatment in patients with diabetes, Ó Hartaigh et al. (pp. 101–109) have reanalysed data from the ACCORD trial, in which patients with diabetes were randomly assigned to achieve intense (<120 mmHg) or standard (<140 mmHg) BP control, by grouping them according to whether or not they achieved their respective goal. They report that, whereas in the standard treatment arm those who achieved a target less than 140 mmHg had a substantial reduction in the risk of major cardiovascular events and all-cause death, no significant risk reduction occurred in the intense treatment arm for those who achieved the target SBP less than 120 mmHg as compared with those who did not. The authors conclude suggesting that in diabetes, SBP goal should be between 120 and 140 mmHg, but not less than 120 mmHg. This post-hoc analysis of the ACCORD trial is discussed in an accompanying editorial by Ahmad and Oparil (pp. 37–40), who remark that a post-hoc analysis of a treatment-to-target study has obvious limitations, as opposed to a prespecified analysis of the comparative results of achieving two different BP goals as in the original ACCORD publication.

Other conditions influencing prognosis in hypertension are discussed by Shi et al. (pp. 54–60) and van der Sande et al. (pp. 143–150). The former authors report that early life exposure to the Chinese 1959–1961 famine exacerbated the association between hypertension and cardiovascular disease events, especially among women, those living in urban areas and those with central obesity. Van der Sande et al. (pp. 143–150) have followed up for about 7 years a cohort of 6191 hypertensive patients with clinically manifested vascular disease and observed an increased risk of cardiovascular mortality and all-cause mortality, in presence of controlled and uncontrolled apparent resistant hypertension.

Predictors of renal function loss have been studied by two groups: Leiherer et al. (pp. 110–118) report that serum uromodulin (UMOD) levels were highest when associated with a polymorphism in the UMOD coding region and were significantly associated with estimated glomerular filtration rate. Prospectively (4-year follow-up), serum uromodulin concentration was inversely associated with the development of chronic kidney disease (CKD) and significantly increased a prediction model for CKD. Mallamaci et al. (pp. 119–125) followed up 260 renal transplant patients for over 3.7 years and found daytime and night-time ambulatory SBP predict the risk of renal function loss over time, night-time SBP being the strongest predictor. The important association of night-time hypertension with organ damage is also underlined in a cross-sectional study by Tadic et al. (pp. 136–142), who describe a worse right ventricle mechanics in night-time and day-time/night-time hypertensive patients than in normotensive controls and isolated daytime hypertensive patients.

Another group of articles in the current issue of the Journal of Hypertension has diagnostic implications. Jardim et al. (pp. 61–68) present useful information on reference values for home BP by height percentiles for age and sex in a non-European population of adolescents in secondary cohorts of a Brazilian city (51.3% non-white). Cuspidi et al. (pp. 23–30) have reviewed and meta-analysed studies assessing the association of metabolic syndrome with subclinical carotid damage, finding carotid intima–media thickness is significantly higher in patients with than in those without the metabolic syndrome. They suggest ultrasound search of subclinical carotid disease may refine cardiovascular risk stratification and decision-taking strategies in patients with the metabolic syndrome. In another review in this issue of the Journal, Tsioufis et al. (pp. 16–22) summarize the evidence supporting a wider use of renal ultrasound in the diagnostic work-up of patients with newly diagnosed hypertension, not only to identify causes of secondary hypertension originating from the kidney, but also to detect renal injury signalled by increased renal resistive indices.

Salvi et al. (pp. 77–84) present data on two large cohorts of patients with the Marfan syndrome (n = 114) in whom aortic stiffness and central haemodynamics have been associated with ascending aorta diameters and fibrillin-1 genotype. Pulse wave velocity and central pulse pressure were significantly higher in Marfan syndrome patients than in matched controls, although independently of fibrillin genotype, and were associated with diameters of ascending aorta.

A third group of articles in this issue is related with aspects of hypertension management. Brunström and Carlberg publish a critical review of standardization of relative risks (RRs) and standard errors according to BP differences within trials investigating the effects of BP-lowering treatment, showing that standardization of RRs exaggerates differences between trials and makes meta-analyses highly sensitive to choice of statistical method. The implications of standardization are further discussed in an accompanying editorial by Thomopoulos and Michalopoulou (pp. 31–33), who agree with the authors that standardization to a preselected BP reduction is a problematic issue. However, when selecting to standardize to unmask some clinical aspects that crude analysis cannot explore, Thomopoulos and Michalopoulou suggest one should first investigate whether the projected comparison of the standardized RRs has a solid clinical justification and whether the outcome to standardize is linearly associated with the extent of BP reduction.

Among nonpharmacological interventions, salt reduction is known to be the most cost-effective one. Trieu et al. (pp. 188–198) report the effect of an 18-month nationwide salt reduction strategy in Samoa: though there was no change in mean population salt intake as judged from two nationally cross-sectional surveys carried out immediately before and after the intervention strategy, there were a wider awareness of the salt reduction message and some improvements in salt-related knowledge and behaviours. Gilardini et al. (pp. 199–204) report that among hypertensive patients with obstructive sleep apnoea, two-thirds have urinary normetanephrine (uNMT) above the normal limit; uNMT decreased or normalized, parallel with changes in the apnoea–hypopnea index under positive airway pressure therapy. Iwashima et al. (pp. 126–135) have investigated the impact of renal function on cardiovascular and renal outcomes after percutaneous transluminal renal angioplasty in 139 hypertensive patients with atherosclerotic renal artery stenosis followed up for 5.4 years and report that impaired renal function and, in particular, a poor response of estimated glomerular filtration rate to angioplasty are associated with worse outcome. A contribution to the debated problem of the therapeutic effectiveness of catheter renal denervation is provided by Völz et al. (pp. 151–158), who present data from the Swedish Registry for Renal Denervation showing a sustained reduction in office and ambulatory BP in patients with resistant hypertension, associated with a low complication rate. These data are commented by Mahfoud et al. (pp. 41–42), who mention the recent positive results of the sham-controlled SPYRAL-OFF-Medication study [1] in nonmedicated patients, and show the decrease in BP following renal denervation is correlated with baseline BP. Nonetheless, the authors conclude renal denervation remains an attractive, but still elusive potential technique and high-quality research is needed.

Finally, three articles focus on treatment and control of hypertension in different parts of the world. Lemogoum et al. (pp. 159–168) find that hypertension is highly prevalent in Far-North Cameroon, and awareness, treatment and control rates are low. Agyemang et al. (pp. 169–177) have investigated prevalence and management of hypertension among relatively homogeneous African migrants (Ghanaians) living in three European cities, and nonmigrants living in rural and urban Ghana: hypertension prevalence, awareness and treatment levels were generally higher in African migrants to Europe, but BP control level was lower in Ghanaian migrant men compared with their nonmigrant peers. Li et al. (pp. 178–187) report data from the first national spatial analysis of hypertension in China, showing hypertension prevalence and management are spatially patterned in China, with demographic, socioeconomic and behavioural factors, weight status, healthcare use and urbanization accounting for a significant part of the differences.

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Conflicts of interest

There are no conflicts of interest.

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1. Townsend RR, Mahfoud F, Kandzari DE, Kario K, Pocock S, Weber MA, et al. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet Published Online August 28, 2017. doi:10.1016/S0140-6736(17)32281-X
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