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The enigma of obesity-induced hypertension mechanisms in the youth

Kotsis, Vasiliosa; Grassi, Guidob,c

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doi: 10.1097/HJH.0000000000000829
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The purpose of cardiac output control is to maintain adequate tissues blood flow. Decreased total peripheral resistance increases cardiac output and decreases arterial pressure. When tissue blood flow falls below normal, kidneys retain water and salt, and this retention occurs until flow and blood pressure (BP) rises back to normal [1]. These physiological mechanisms are also under the control of the central and autonomic nervous system.

The hemodynamic mechanisms of SBP elevation in normal weight and overweight individuals were investigated in a large population of young adults from the Enigma Study [2] that is published in this issue of the Journal. Central BP, augmentation index, mean arterial pressure, heart rate, and pulse wave velocity were measured by pulse wave analysis. Cardiac output was assessed using a noninvasive, inert gas rebreathing technique and peripheral vascular resistance values were calculated. Study participants were stratified into tertiles of SBP and BMI and comparisons were performed between study participants in the upper and lower tertiles.

The main results of this study by Middlemiss and coworkers [2] can be summarized as follows. First, in normal-weight individuals, the increase in cardiac ouput was the predominant hemodynamic mechanism associated with the higher SBP values. The higher cardiac output in men was driven by a higher stroke volume, whereas in women it was by a higher resting heart rate. Second, in overweight individuals, cardiac output was greater in men and women in the upper SBP tertile compared with those in the lower tertile, but this trend was abolished after adjusting for body size resulting in values of cardiac index that were similar between groups. Peripheral vascular resistance values were also markedly higher in overweight men in the upper SBP tertile, but not in women. Finally, higher brachial SBP values were associated with a higher central SBP in both men and women and pulse pressure amplification did not differ between groups in either men or women. This may suggest that the elevated peripheral SBP in young adults represents a true finding and not an amplification of a normal central SBP.

Ideally, studies investigating mechanisms of obesity-induced hypertension would include measurement of the sympathetic nervous system activation by direct methods and the plasma renin–angiotensin system activity, both inducing an increase in peripheral vascular resistance as well as in volume overload caused by changes in sodium excretion. The results of the study by Middlemiss and coworkers [2] have to be interpreted with caution because there are differences in the methodology used compared with previous studies. Indeed, the recruited study participants were stratified into tertiles of SBP and BMI values, whereas comparisons were made between the upper and lower tertiles. This definition of high and low extremes in the studied population is not what is usually used in everyday clinical practice. Patients with hypertension or obesity are not defined within the 75th and 85th percentile of the population, but usually higher than the 95th percentile (average +2 SD). Furthermore, the majority of the population studied was nonobese normotensive. Moreover, cardiac output was assessed using a noninvasive, inert gas rebreathing technique, whereas invasive methods were used in previous studies. The representativeness of the real resting patient's cardiac output as reflected by the assessment based on the above-mentioned techniques may be debatable, since different stress responses exist between noninvasive and invasive methods. Moreover, noninvasive techniques should be comparable with cardiac output measured by echocardiography. Finally, cardiac output was slightly higher in overweight compared with normal-weight individuals, but differences between groups disappeared after adjustment for body size. The heart for the same body mass did the same work and cardiac index was similar despite differences in body size. Increased preload of the heart from increased volume overload is the main cause of the increased cardiac output in obesity. Differences in the population's body size (overweight versus obese) could explain the small differences in cardiac output observed in the study by Middlemiss et al.[2] compared with previous ones. Cardiac index may not be an ideal way to foresee the future of the heart in an obese individual and correction for body size may abolish the increased load of the heart over time. Obesity cardiomyopathy and heart failure are common in obese study participants even in the normotensive range [3].

Elevated peripheral vascular resistance appeared to be a primary hemodynamic abnormality associated with high SBP in overweight individuals. Peripheral vascular resistance affects organ blood flow as an expression of the effect of multiple physiological mechanisms, including the role of the sympathetic nervous system in the vessels [4–7], the effect of circulating or local vasoactive hormones such as angiotensin II, epinephrine and norepinephrine, antidiuretic hormone, atrial natriuretic peptide, and endothelin; and the actions of endothelial factors such as nitric oxide. Which of them is the most important mechanism for the increased peripheral vascular resistance and the elevation in BP in overweight and obesity is still under investigation. A new concept highlighted lately is the metabolically and hemodynamic healthy overweight and obese individuals [8,9]. In the study by Middlemiss and coworkers, peripheral vascular resistance presented the lowest values in overweight individuals with low SBP [2]. This observation suggests that protective mechanisms may occur at least in some overweight individuals, which allow them to maintain lower levels of SBP despite their larger size.

The concept of a normal central BP, which is associated with abnormal peripheral SBP because of BP amplification from central arteries to the periphery, introduced several years ago the idea of the spurious hypertension in the youth. The study by Middlemiss and coworkers [2] suggest that such a phenomenon may not exist, because higher brachial SBP was associated with higher central SBP in both young men and women. In a previous study, spurious hypertension has been associated with the white-coat effect that causes transient elevation of peripheral office BP, while central BP is normal [10]. Further studies are needed to confirm these findings, since it is important to know the clinical significance of a high peripheral SBP in young people, whether this elevation is real, and how it is going to affect the cardiovascular health status of the single individual in the long-term period.

ACKNOWLEDGEMENTS

Conflicts of interest

There are no conflicts of interest.

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