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From risk factors to treatment of hypertension

Zanchetti, Alberto

doi: 10.1097/HJH.0000000000000796

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, 20122 Milano, Italy. Tel: +39 02 50320484; e-mail:

As usual, articles in the current issue of the Journal of Hypertension cover the entire span of hypertension research, from investigation of risk factors for development of hypertension and cardiovascular disease to pathophysiological mechanisms, diagnostic approaches and aspects of antihypertensive treatment.

Using data from the prospective Suita Study, a cohort study of cardiovascular disease in Japan, Turin et al. (pp. 116–122) have investigated the lifetime risk of stroke, as the probability of disease in the residual lifetime for an index age, and report an increased lifetime risk of stroke, especially ischemic stroke, for both hypertensive men and women across all index ages. Park et al. (pp. 47–53) have analyzed data of postmenopausal women from the Korean National Health and Nutrition Examination Survey 2010–2011 and found that a history of adolescent pregnancy is significantly and independently associated with a higher risk of hypertension after menopause. Sivén et al. (pp. 54–60) have assessed the risk of progression from white-coat and masked hypertension to sustained hypertension in a nationwide unselected population sample (Finn–home study) and found individuals with white-coat or masked hypertension have a three to four-fold higher risk for developing sustained hypertension than those with normotension, suggesting they could benefit from active follow-up and lifestyle changes. Another article from Finland (Juhanoja et al., pp. 61–67) has investigated correlation between variabilities of blood pressure measured by different methods (ambulatory, home, office) and reports only weak correlations.

Another group of articles focus on a wide range of pathophysiological mechanisms of hypertension and hypertension-related organ damage. Mir et al. (pp. 68–78) have addressed the effects of a human catestatin polymorphism (rs 9658667) using humanized mouse models wherein the mouse Chga gene locus was replaced by the human ortholog -wild type and the variant versions, and suggest that this approach can also be applied in the study of other human gene polymorphisms. In a genome-wide association study in a large cohort of healthy twins, Mangino et al. (pp. 79–87) have identified one single-nucleotide polymorphism (rs 7164338) in the CIB2 gene associated with pulse wave velocity and found the same variant is associated with increased CIB2 expression in leukocytes and hypomethylation of the gene promoter. The authors suggest that reduced methylation of the CIB2 promoter may lead to increased CIB2 expression: as CIB2 is thought to regulate intracellular calcium, this may ultimately lead to slowing down the process of vascular calcification. In an accompanying commentary, Eales et al. (pp. 32–35) anticipate that applications of transcriptomics and epigenomics will become increasingly popular in the post-genome-wide association study era bringing us closer to unravelling the secrets of many associations between genes and complex cardiovascular phenotypes.

In a comprehensive review of available evidence, A. Cai et al. (pp. 3–10) summarize the pathophysiological roles of the GTP-binding protein RhoA and its main effector Rho-associated kinase (ROCK) on the cardiovascular system, and illustrate the potential benefits of controlling the RhoA/Rho-associated kinase signalling pathway. The vascular protective role of T-regulatory lymphocytes (Tregs) has been further investigated by Mian et al. (pp. 97–108), who report that Treg deficiency because of a mutation in the transcription factor forkhead box P3 (FoxP3) gene exaggerates angiotensin-induced microvascular injury by modulating innate and adaptive immune responses. These results are commented by Galán and Salaices (pp. 36–38), who underline that the study may be clinically relevant because it suggests the positive stimulation of Tregs as a therapeutic target for preventing microvascular complications associated with hypertension. The commentary also points out that the use of large animal models and human samples would be desirable.

The positive association of cystatin C with altered collagen metabolism in the heart has been investigated by Huerta et al. (pp. 130–138) in patients with heart failure with preserved ejection fraction. They report that cystatin C is increased in these patients and associated with diastolic dysfunction and altered collagen metabolism, a finding supporting the hypothesis that an excess of cystatin C may facilitate myocardial fibrosis via accumulation of osteopontin and tissue inhibitor of matrix metalloproeinases-1.

Among a group of studies with diagnostic potential, Barve et al. (pp. 88–96) report that M-mode and 2D echocardiography left ventricular mass measurements identified suggestive genetic associations, and conclude that the combined use of M-mode and 2D echocardiograms may help the study of genetic associations with left ventricular mass. Although carotid intima–media thickness is widely used to investigate atherosclerotic changes, T.Y. Cai et al. (pp. 109–115) have thought that in prepubescent children, in whom atherosclerosis is absent, investigation of the carotid extramedial thickness may provide information as to whether structural changes in the arterial adventitia may contribute to early arterial stiffening. They report a significant association between carotid extramedia thickness and stiffness of the same arterial segment in 248 healthy prepubescent children. Rohla et al. (pp. 123–129) have searched for predictors of the ambulatory blood pressure response to renal denervation and find that, out of a wide range of baseline variables, elevated ambulatory blood pressure values, BMI and the number of antihypertensive drugs used are associated with the response.

Various aspects of antihypertensive treatment have been investigated in a number of studies. Roush et al. (pp. 11–19) present a systematic review and meta-analysis of randomized comparisons of potassium-sparing diuretics exploring relative potency, dose equivalence and effects of dose doubling. Two articles explore drug interactions of antihypertensive drugs with lithium in patients with bipolar disorders (Bisogni et al., pp. 20–28) and orally administered antibiotics with amlodipine bioavailability (Kim et al., pp. 156–162). Mancia et al. (pp. 139–148) report the results of a 10-week treatment with placebo, lercanidipine monotherapy, enalapril monotherapy or a combination of the two active drugs using home blood pressure in addition to office blood pressure measurement: in this large database, randomization to the lercanidipine–enalapril combination lowered home blood pressure more effectively than the corresponding monotherapies and placebo, and this greater effect was consistent between days. Harding et al. (pp. 149–155) have analyzed pooled data from 12 Australian and New Zealand cohorts (85 593 participants followed up for a median of 15.1 years), and report that hypertension, both treated and untreated, was associated with a modest increased risk for cancer incidence and mortality: similar cancer risk in treated and untreated hypertensive patients suggest that the slightly increased cancer risk is not explained by the use of antihypertensive drugs. Despite the proved efficacy and safety of antihypertensive treatment, a recent survey of the current status of hypertension treatment in rural and urban communities in China (Li et al., pp. 39–46) confirms that more than half of hypertensive individuals were unaware of their high blood pressure, and rates of treatment and blood pressure control were very low. An accompanying commentary by He (pp. 29–31) remarks that under-diagnosis and under-treatment of hypertension is a major public health problem in China, and that prevention and treatment of hypertension could save millions of lives in China.

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Conflicts of interest

There are no conflicts of interest.

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