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Investigation clues for prognosis, diagnosis and therapeutic strategies

Zanchetti, Alberto

doi: 10.1097/HJH.0000000000000022

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

Hypertension research is traditionally interested in searching for clues that may help in predicting blood pressure trajectories, hypertension onset, cardiovascular and renal dysfunctions, and, finally, events. These clues are used for prognosis, diagnosis, or developing therapeutic strategies, although these clues often result from association studies, which cannot have the same strength as those obtained in prospective studies. A number of papers published in the current issue of the Journal of Hypertension belong to this type of investigation, some being prospective, some retrospective, some association studies.

Genetic research naturally ambitions to prediction. Diastolic dysfunction and so-called diastolic heart failure are a common consequence of hypertension, but their molecular mechanisms are incompletely understood. In a thorough review of available evidence from animal experiments, Deng (pp. 2329–2336) concludes that different genes in combinations must be involved in the physiological mechanisms ameliorating or reversing diastolic dysfunction. Since not all quantitative trait loci that influence blood pressure can affect diastolic function, it is not blood pressure reduction itself that restores diastolic function, but rather specific genes. By analysing data from the United Kingdom Twin Cohort, Menni et al. (pp. 2356–2361) have investigated whether not only long-term average blood pressure but also long-term visit-to-visit blood pressure variability (an emerging new cardiovascular risk predictor) is a heritable trait, and find that blood pressure variability does not show any additive genetic variance except after stratification by age, suggesting that blood pressure variability in younger and older age groups may reflect different pathological phenotypes. Endothelial dysfunction and arterial stiffness are early vascular alterations in hypertension, linked to oxidative stress and inflammation. However, Ghiadoni et al. (pp. 2362–2369) report that polymorphisms of the P2X7 receptors (known to respond to extracellular ATP and to modulate inflammatory responses and cell growth) are not associated with altered endothelial function or arterial stiffness in untreated newly diagnosed hypertensive individuals.

Lifestyles are important predictors of hypertension and cardiovascular disease. Although moderate alcohol consumption has sometimes been claimed not to be a risk factor, a prospective study of a large cohort of coal mine workers in North China finds that long-term alcohol intake, even in light to moderate quantity, increases the risk of incident hypertension (Peng et al., pp. 2342–2347). On the other hand, cardiorespiratory fitness is reported by Kawano et al. (pp. 2370–2379) to attenuate the age-dependent increase in wall viscosity of a central artery, such as the common carotid. Along the same line, lower carotid artery stiffness in endurance-trained adults has been found by Tarumi et al. (pp. 2400–2409) to be associated with better neuropsychological outcome and greater occipito-parietal cerebral perfusion, thus supporting the notion that vascular aging is associated with cognitive decline, and raising hopes that habitual aerobic exercise may be an effective lifestyle strategy to reduce central arterial stiffness and related cognitive impairment. These interesting data are commented by Izzard (pp. 2337–2338), who remarks that the functional consequence of cerebral arterial growth is unclear, but notes that alterations in cerebral arterial structure may limit the ability of the cerebral circulation to increase flow if the normal pressure to a cerebral vascular territory is reduced. The pathological significance of changes of arterial wall properties is also the objective of another paper. Stea et al. (pp. 2418–2424) report that pulse wave reflection is positively correlated with renal insufficiency, thus denying the hypothesis that peripheral wave reflection may have a protective role for the microcirculation of a low-resistance vascular bed, such as that of the kidney.

Obviously, blood pressure itself is an important predictor of organ damage. In a further analysis of the Ohasama study – an important prospective study of a Japanese population – Kanno et al. (pp. 2410–2417) have found that night-time blood pressure is a better predictor of chronic kidney disease than daytime blood pressure, thus extending to kidney damage what was previously known for cardiovascular damage. Cuspidi and Grassi (pp. 2339–2341) in an editorial commentary remark that this observation supports the value of ambulatory blood pressure for assessing the risk of chronic kidney disease in the general population. By a sophisticated method (three-dimensional echocardiography speckle tracking analysis), Tadic et al. (pp. 2438–2446) report that left-ventricular and left-atrial mechanics are impaired to a greater extent in non-dippers than in dippers untreated hypertensive patients, thus adding further evidence to the usefulness of night blood pressure monitoring. In a prospective cohort of pregnant women followed up from the first trimester of pregnancy to childbirth, Martell-Claros et al. (pp. 2380–2385) find that a SBP at least 120 mmHg and a uric acid serum concentration above 3.15 mg/dl during the first trimester are consistent predictors of gestational hypertension. On the contrary, De Luca et al., analysing a large cohort of myocardial infarction patients undergoing primary angioplasty, have found that hypertension did not influence infarct size (pp. 2433–2437).

Ethnic African descent is also known to be associated with increased prevalence of cerebrovascular disease, but evidence on the risk factors responsible is conflicting. Shibata et al. (pp. 2391–2399) have compared prevalence of brain infarcts and severe white matter hyperintensities on cerebral MRI in a community-based sample of men and women of African Caribbean and European descent. Apart from confirming a higher prevalence of both types of cerebrovascular lesions, the authors find this excess is related to elevated clinic and ambulatory blood pressure, and to hyperglycaemia. Cardiovascular risk is reported to be frequently elevated among hypertensive individuals in Mozambico: in a representative sample of Mozambicans aged 40–64 years, the prevalence of hypertension (SBP/DBP ≥140/90 mmHg) was 40%, and about a half of the hypertensive patients were found to have a risk of major cardiovascular events equal to or greater than 20% in 10 years (Damasceno et al., pp. 2348–2355).

Two articles in this issue are devoted to the problem of resistant hypertension. In a large therapeutic study conducted in China (Ma et al., pp. 2386–2390), over 50 000 hypertensive patients were treated according to a five-step drug treatment programme, and the rate of uncontrolled hypertension was very low (1.9%) and may have been even lower if the final step would have been prolonged beyond 2 weeks. The low prevalence of resistant hypertension in a large cohort involved in an intervention study makes it likely that the higher prevalence reported in observational studies is largely due to high level of non-adherence to treatment recommendations. This is supported by another paper published in this issue, documenting non-adherence to treatment by drug serum analysis (Strauch et al., pp. 2455–2461).

Other papers in this issue report the results of interesting diagnostic and therapeutic studies. Eeftinck-Schattenkerk et al. (pp. 2447–2454) report that two beta-blockers, nebivolol and metoprolol, have equivalent effects in reducing aortic wave augmentation and central blood pressure when combined with hydrochlorothiazide. Kwakernaak et al. (pp. 2425–2432) have found that in patients with chronic renal disease, sodium restriction associated with blockade of the renin–angiotensin system increases circulating levels of the anti-inflammatory and anti-fibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP). This rise is suggested to contribute to increase the cardio-renal protection exerted by renin–angiotensin system blockade during sodium restriction.

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Conflicts of interest

There are no conflicts of interest.

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