Hypertension in adults has been extensively studied, with wide array of data about physiology, associated pathophysiology, different phenotypes, treatment, outcomes, and extensive sets of guidelines established in an attempt to facilitate practice [1,2]. Hypertension in children was also studied though not as extensively, and in the absence of solid clinical outcomes for these age groups, research mostly employed variety of surrogate outcomes, such as left ventricular mass, intima/media thickness, and the like to help realize clinical meaning of hypertension in childhood, as summarized in recent American Heart Association guidelines on hypertension in childhood . Therefore, it may appear that we have detailed sets of guidelines both for children and for adults. Nevertheless, whereas childhood hypertension lasts about a decade, that of adults spans several decades, resulting in quite a heterogeneity in age, and subsequent characteristics and quite an age-dependent variability in outcomes. Indeed, at least when it comes to outcomes in studies of hypertension, they appear to segregate among higher risk (older among other aspects) adults; thus, most randomized outcome studies in latest years involved high-risk individuals frequently older than 55 years. Thus we have guidelines based on randomized trials almost exclusively among older higher risk patients, whereas younger, standard, or low risk young adults are not well represented in the knowledge database we have about hypertension.
Most if not all the information on hypertension in young adults stems from observational studies. Of particular interest are studies on military conscripts who are examined ahead of recruitment, and yield if not population-based estimates as say in the case of Israel, with its mandatory recruitment laws , to a sample of conscripts which produce an estimate and a rare samples of blood pressure (BP) in young adults in Sweden . Such studies have the advantage of very large numbers, more than 2 million adolescents in an Israeli study and more than a million in a Swedish study. They also have disadvantages, being based on single-office BP measurement among other reasons. Such a single measurement may lend itself to effects such as white coat, or masked hypertension. This conscription setting may be more stressful than the doctor's office for many. Significantly, knowledge of BP elevation may in itself precipitate subsequently higher BP . This type of psychological influence culminates in higher stress response [6,7]. Such adrenergic response may elevate SBP by increasing cardiac output and reduce DBP by activation of the vasodilatory β2-adrenergic receptors . The combination of both effects is likely to cause increased cardiac output and lower total peripheral resistance, which may culminate in SBP more than 140 mmHg and DBP less than 90 mmHg, that is, isolated systolic hypertension (ISH). Indeed the white-coat effect on pulse pressure (PP) was greater than that on SBP, indicating the reduction of DBP at that time . If anything this type of white coat effect was found to be associated with favorable cardiovascular outcome .
It was shown decades ago with invasive hemodynamics that initially young hypertensive individuals have increased cardiac output and normal total peripheral resistance, which gradually over 10 and 20 years, change progressively to a lower cardiac output and higher total peripheral resistance .
Usually it is common to see elderly patients with ISH; it is believed secondary to aortic stiffness that occurs over the years. Observational studies have documented progressive decrease of DBP after the 6th decade of life frequently accompanied by SBP rise as part of this process .
However, ISH is not only a phenomenon of older age. As a matter of fact, there is a substantial minority of young hypertensive patients with this condition [13,14]. This brought about a controversy; some investigators found that it can be explained by brachial BP augmentation, especially, in young fit individuals [15,16]. Others found that elevated aortic stiffness expressed as increased pulse wave velocity (PWV) could explain the phenomenon and regard it as a sign that it not an innocent state, and may require treatment [17,18]. I had the clinical (unfortunately undocumented) experience that teenagers with ISH discovered in the conscription office, in whom secondary hypertension was ruled out, when seen after discharge from the 3 years long military service, with gained weight, or smoking habit, and less devotion to physical activity, turned out to be normotensive! Such an observation if substantiated could support the theory of brachial augmentation in lean athletic normotensive patients.
On this background, the new analysis of young participants of the Hypertension and Ambulatory Recording Venetia Study (HARVEST), published in the present issue of the Journal , is important. It examined 1206 never treated with newly office-diagnosed individuals with essential hypertension and subtyped them according to 24-h ambulatory BP as ISH, diastolic, or combined hypertension, followed them up closely for at least 6 months and on the average 6.9 years. Of the 206 ISH, 48% had incident office hypertension by the end of follow-up, compared with 50% of normotensive patients (more correctly should have been labeled white coat hypertensive patients), 65% of those with isolated diastolic hypertension, and 71% of those with combined systolic and diastolic hypertension P less than 0.0001. This finding somewhat confirms some of the previous studies [13,15,16]. However, the HARVEST investigators went one step further and found that those who had incident office hypertension by the end of follow-up, were those with the higher mean arterial pressure (MAP) than a threshold of 97 mmHg, which corresponds to the upper limit of what is considered normal 24-h ambulatory BP [diastolic 80 mmHg + (systolic 130 mmHg − diastolic 80 mmHg)]. They found among those with ISH only those with higher MAP, and likewise only those with diastolic hypertension and higher MAP were likely to develop office hypertension. As MAP is affected more by diastolic than by SBP (see above), this means in practice that in younger people future hypertension is predicted better by DBP than by SBP even in ISH. As PWV is influenced more by DBP , the young people destined to hypertension later because of higher PWV , and not necessarily higher PP (predictive of favorable outcome in HARVEST ), which in the older population goes along with lower DBP.
Thus, this important analysis of the HARVEST demonstrates some of the heterogeneity of ISH, which may explain in part the controversy about ISH in the young. Application of the threshold suggested by the American College of Cardiology/American Heart Association  may complicate these finding further.
Conflicts of interest
There are no conflicts of interest.
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