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From lifestyle changes to outcomes in hypertension

Zanchetti, Alberto

doi: 10.1097/HJH.0000000000001542

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

The focus of the articles published in the current issue of the Journal of Hypertension spans from studies on lifestyle changes in hypertension to studies exploring the effects of antihypertensive treatment or of risk factors on hard outcomes, such as fatal and nonfatal cardiovascular events, or intermediate outcomes, such as signs of organ damage.

Four articles report interesting investigations on lifestyle and hypertension. Pagonas et al. (pp. 2199–2206) have randomly allocated 75 hypertensive patients to a 12-week program of isometric handgrip training, sham handgrip training or aerobic exercise and measured 24-h ambulatory blood pressure (BP) in addition to office measurements and found a significant reduction of ambulatory and office BP by aerobic exercise, but not by the type of isometric exercise they used. Petersen et al. (pp. 2207–2213) report the results of a study of salt intake in North and South India, comparing data obtained in the same patients by 24-h urine collections and by spot urine samples with the use of different equations. They report a satisfactory estimate with the Tanaka, Morge and INTERSALT equations. These data are commented in an accompanying editorial by Teo (pp. 2168–2170), who remarks that in the current debate whether the amount of salt ingested by most populations is too high or just right, the debate should not be insisting that the ‘reference value’ should be 24-h urine collection, which is unfeasible in population studies, but strict methodology should be followed in the collection of the spot urine used.

Kurtz et al. (pp. 2214–2225) provide a critical review of a recent statement by the American Heart Association (AHA) on salt sensitivity and suggest greater consideration should be given to conceptual frameworks and theories for salt sensitivity beyond those emphasized in the AHA statement. Kurtz et al.'s viewpoint is supported by Alderman (p. 2175) in an accompanying commentary, underlying the results of recent research pose a serious challenge to conventional beliefs. Maritz et al. (pp. 2268–2275) report that a health profile of excessive alcohol intake, also including an urban setting, elevated plasma glucose and lower BMI, predicts large arterial stiffness independently of age and BP in black South Africans over 10 years.

A group of articles focusing on fatal and nonfatal cardiovascular outcomes includes two additional meta-analyses of BP-lowering randomized controlled trials by Thomopoulos et al. The first meta-analysis (Thomopoulos et al., pp. 2138–2149) follows a previous one by the same authors, showing that in hypertensive patients with diabetes, but not in those without diabetes, there is little or no further benefit in lowering SBP below 130 mmHg and explores the possibility that this pattern of response is common to all high–very high cardiovascular risk patients. The meta-analysis, however, provides a negative answer to the question, showing similar reductions in cardiovascular outcomes in high–very high-risk patients at a target lower than 130 mmHg as well as at higher targets. The benefits of lowering BP in high–very high risk individuals are emphasized further by the second meta-analysis by Thomopoulos et al. (pp. 2150–2160), showing that when BP-lowering treatment is given to individuals with ‘untreated’ high-normal or normal BP [with exclusion of those with a recent myocardial infarction (MI) or heart failure], a reduction of outcomes, though limited to stroke, is only found in high–very high cardiovascular risk patients (mostly with symptomatic cardiovascular disease), but not in those with low–moderate cardiovascular risk.

Elaborating data from six randomized controlled trials of antihypertensive treatment, Le et al. (pp. 2178–2184) have constructed a sudden death risk score specifically for hypertensive patients with or without cardiovascular history. The seven significant risk factors for sudden cardiac death are as follows: age, sex, SBP, serum total cholesterol, cigarette smoking, diabetes and history of MI. These data are commented by Fagard (pp. 2165–2167), who concludes that many risk scores are available for the prediction of various cardiovascular diseases or death in different populations, all having advantages and limitations. The continuous risk scores developed by Le et al. may be a useful quantitative complement for the estimation of risk of the individual hypertensive patient.

Wang et al. (pp. 2192–2198) have followed up a prospective cohort of 24 926 hypertensive patients for a mean of 6.8 years and found that proteinuria is associated with an increased incidence of MI but pointed out that the association is likely to be underestimated if baseline measurements of proteinuria are used, suggesting that measures of changes in proteinuria, particularly persistent proteinuria, are more likely to reflect the lifetime risk for MI. Shantsila et al. (pp. 2310–2314) review the West Birmingham Malignant Hypertension Registry with data collected from 1958 to 2016 and report that there has been a major improvement in 5-year survival over recent decades, with abnormal renal function at presentation still being the predictor of the worse outcome.

Adverse events are also important outcomes of antihypertensive treatment. Fitton et al. (pp. 2123–2137) have completed a systematic review of published studies on adverse outcomes to the child associated with in-utero exposure to antihypertensive medications. Increased risk of low birth weight, low size for gestational age, preterm birth and congenital defects were identified, but the systematic review demonstrates a paucity of high-quality studies. The data by Fitton et al. are commented in an accompanying editorial by Boesen (pp. 2161–2164), who underlines that, despite the efforts of the authors, there remain a number of critical questions that the current literature fails to definitively answer, and there is a further need for well designed, appropriately powered, high-quality studies to be performed in this area.

Another consistent group of articles is focused on organ damage as an outcome, with particular attention to large artery stiffness. Wohlfahrt et al. (pp. 2238–2244) provide useful reference values of cardio-ankle vascular index (CAVI) in a random sample of a white population and report current reference values derived from the Japanese population slightly overestimate CAVI in younger whites, possibly underestimating cardiovascular risk. Zaniqueli et al. (pp. 2257–2261) have measured cardio-femoral pulse wave velocity (cfPWV) in a multiethnic cohort of Brazilian children and adolescents and conclude that higher cfPWV values in blacks appear in adolescence and are independent of BP values, suggesting adolescence as the key phase for the appearance of the vascular profile of higher stiffness found in adult black individuals. By examining data in the Malmö Diet Cancer study in 1992–1996 and again in 2007–2012, Fatehali et al. (pp. 2262–2267) find that a positive family history of cardiometabolic conditions and hypertension affects arterial stiffness in offspring independently of hemodynamic factors and cardiometabolic disease in the offspring. Lu et al. (pp. 2185–2191) publish the results of a longitudinal study of the influence of lung function on vascular health from adolescence to early adulthood in a British multiethnic cohort (DASH study), finding that changes in Forced Expiratory Volume are positively and independently associated with SBP changes from adolescence to young adulthood, but vascular indices, such as aortic PWV and augmentation index, are unrelated to lung function or its change. In an accompanying editorial, Masi and Taddei (pp. 2171–2174) remark how the changes of lung function, arterial stiffness and SBP described by Lu et al. in the DASH cohort might influence the future risk of cardiovascular disease remains to be explored.

Kim et al. (pp. 2245–2256) have measured blood flow velocity waves in four cerebral vascular territories by transcranial Doppler in normal patients and reported flow waveforms entering the brain have similar pattern to central aortic pressure waveforms, and similar changes with age. The authors suggest that cerebral microvascular damage in older patients may be attributable to high pulsatile pressure tearing the delicate media and causing hemorrhage, and high pulsatile flow dislodging endothelial cells and causing thrombosis and microinfarcts.

Finally, an article by Cuspidi et al. (pp. 2303–2309) has used echocardiographically determined left ventricular (LV) mass changes as an outcome in a 10-year longitudinal study of a general population, describing a marked increase in the prevalence and severity of LV hypertrophy, correlated with BP, metabolic variables and BMI.

Other areas of hypertension research are dealt with by other articles in this issue. Two studies focus on pregnancy and preeclampsia. In a nested case–control study of mother/child pairs from the Berlin Birth Control, Putra et al. (pp. 2276–2286) have investigated epigenetic mechanisms influencing the activities of genes involved in placental hormone/hormone receptor synthesis/action during pregnancy, with effects on maternal BP. Chen et al. (pp. 2287–2294) have focused on podocalyxin, a glomerular podocyte protein that is also expressed in endothelial cells of other organs. The authors report that podocalyxin was detected in serum of normal pregnancy, with levels increasing progressively with advancing gestation, but podocalyxin serum levels were significantly elevated in preeclampsia. Within the placenta, blood vessels, but not trophoblasts, expressed podocalyxin that was also expressed in endothelial cells in all 32 human organs examined. The mechanisms of action of podocalyxin on the maternal vascular wall and podocalyxin metabolism in preeclampsia are further extensively discussed by Goulopoulou (pp. 2176–2177) in an accompanying editorial, who concludes that the role of podocalyxin in endothelial-mediated vascular functions and in vascular adaptations to pregnancy is unknown and warrants further investigation: Podocalyxin may be a biomarker for early detection of preeclampsia, but it may also be a signaling molecule that mediates maternal endothelial dysfunction. Another study with pathophysiological implications is published by Jeremic et al. (pp. 2226–2237), who have investigated the effect of ablation of Toll-like receptor 4 on aorta contractility in hyperhomocysteinemia in mice.

Two articles have direct therapeutical implications. Wang et al. (pp. 2295–2302) have studied the prevalence of morning hypertension in elderly hypertensive patients with controlled documented office BP in primary care clinics: prevalence was high and associated with short-acting antihypertensive drugs. Spannella et al. (pp. 2315–2322), by evaluating 194 consecutive patients referred to their hypertension clinic, conclude that higher plasma renin activity to plasma aldosterone concentration ratios indicate effective therapeutic blockade of the renin–angiotensin–aldosterone system, which is accompanied by lower night-time BP and pulse pressures in real-life clinical practice.

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Conflicts of interest

There are no conflicts of interest.

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