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Pulse wave reflection in children

Year: 2017
Type: article
Abstract: In this issue, Murakami et al.[1] detail the presence of wave reflection in the aortic system of healthy children. Identifying the components of early-life blood pressure (BP) is of critical importance as evidence builds on the role of BP in predicting future atherosclerotic cardiovascular disease (ASCVD). Classic literature has demonstrated the ability for historical BP to predict presence of atherosclerotic plaque in younger persons victim to unfortunate mortality like accident and war [2–5]. Recent data show a continuous relation between adolescent male BP separated into various indices including SBP, DBP, pulse pressure (PP), mean arterial pressure (MAP), and eventual adult ASCVD events [6]. Similar data from Native American populations show physician diagnosed hypertension in childhood as a risk factor for early mortality [7]. One study of adolescent men suggests that adolescent BP predicts future ASCVD even after adjustment for middle-aged BP, underscoring the additive utility of early-life BP [8]. Mounting evidence further demonstrates the specific role of elevated BP in preclinical atherosclerotic changes including left ventricular hypertrophy and vascular change [9,10]. Intriguing longitudinal data even suggest that normalization of elevated BP from childhood into adulthood ameliorates these preclinical atherosclerotic changes [11]. There are now multiple threads of evidence linking early-life BP to preclinical in-vivo atherosclerosis, pathological evidence of atherosclerotic plaque, actual ASCVD events and mortality, and even reversal of atherosclerotic change with attenuation in BP. Turning to physiologic classification, BP may be classified using traditional SBP and DBP per sphygmomanometer. An alternate description classifies BP by PP, an index of large artery properties, and MAP, an index of small artery function. Both combinations predict future ASCVD [12,13], but PP and MAP lend themselves to more mechanistic study of BP. For example, recent trends show that population SBP in adults is declining throughout the world despite rising obesity [14,15]. These contradictory trends could be explained by percolation of antihypertensive therapy in various parts of the globe, but similar BP trends are seen in children, and children are not being treated [16–18]. When the trend is disambiguated into PP and MAP, PP is demonstrated to rise in lockstep with obesity trends, but MAP has fallen [18]. Although the exact determinants for these trends are not clear, PP and MAP classification allows for more focused hypotheses. PP itself is determined by the dynamics of the ventricular ejection, aortic size, aortic stiffness, height, sex, age, heart rate (HR), MAP, and wave reflection [13,19–21]. Mechanistically, the ejection occurs in a time-varying fashion, engaging the distensible aorta in time-varying ways. Aortic input impedance is an index of the interaction between time-varying pulsatile flow and pressure. Different parts of the arterial tree, for example, at branch points of thicker muscular arteries, have different properties and consequent ability to accommodate the pulsatile flow, which summates into a different impedance parameter value than the proximal aorta. At points where mismatch in impedance occurs, some of the pulsatile energy is reflected back in a direction opposite to the initial ventricular ejection. Pulsatile energy thus oscillates back and forth leading to higher pulse pressure due to the convergence of waves adding to each other. The magnitude of the reflected wave is determined by factors such as the ejection pulse dynamics, the degree of impedance mismatch, and the aortic length between the ventricular outlet and the impedance mismatch locations. In adults, the role of the wave reflection is believed to be a major driver of PP in the peripheral arteries exceeding PP in the proximal aorta, in a phenomenon called PP amplification. Against this backdrop, Murakami et al. detail aortic hemodynamic data collected in 62 children. The children were aged under 15 years, both sexes, had no chronic medication use, were normal weight, and were undergoing arterial catheterization for minor left-to-right shunting. All children were sedated with midazolam, femoral arterial access was obtained, and pressure sensor mounted catheter was used to obtain aortic pressure tracings at the level of the diaphragm to index descending aorta and near the aortic valve to represent proximal aorta. With this invasive measurement, the investigators found that descending aortic PP was higher than proximal aortic PP, suggesting PP amplification as hypothesized. The degree of PP amplification appeared to be related to age or height and MAP, whereas sex, HR, and BMI (within this normal weight group) were not related. The investigators conclude that PP amplification occurs in children and increases with age. The investigators findings contrast with previous descriptions of PP amplification varying inversely with age [22]. Purported arguments for this phenomenon center around increasing aortic stiffness across adulthood, with peripheral artery impedance and arterial lengths staying the same. As aortic impedance rises, it will better match peripheral artery impedance and thereby diminish the mismatch and resultant reflection. Therefore, PP amplification would decline as a function of the diminished reflected wave. More contemporary studies offer an alternate paradigm. In a sample of the Framingham Study, in which pressure and flow were disambiguated, PP fell in young adults until about age 50 years and then rose thereafter [23]. A distinction was drawn between true PP amplification as the convergence of measured reflected and forward pressure waves in the proximal aorta, versus apparent PP amplification as the difference in PP between central and peripheral sites. Higher reflection actually corresponded to lower apparent PP amplification in adults younger than 50 years, whereas after 50 years apparent PP amplification was lower and reflection also declined. Combined with data on forward wave dynamics, the inference drawn highlights the forward wave and aortic impedance as the prime driver of PP throughout the lifecourse. In the case of children, mechanistic evidence is sparse. The author of the current study is saddled with a thorny problem: how to reconcile an increase in PP amplification with increasing age. Based on previous studies in children showing reflected waves being smaller, Murakami et al. infer that the distance traveled to reflecting sites must be the dominant driver of PP amplification in children who naturally have lower arterial stiffness [24,25]. As the slow reflected wave travels backward along the arterial tree that lengthens with age, it is likely to converge on the forward wave in the distal aorta, but in older children may arrive ‘too late’ to converge, leaving it out of phase with the forward wave. Countering this narrative are data suggesting a generally increasing trend in arterial stiffness with older age in children [24]. To their credit, the authors acknowledge the possibility that if aortic stiffness is truly increasing with age in children, the velocity of the reflected wave cannot be assumed to underbalance the lengthening of the arterial tree. As alternate explanations, Murakami et al. do consider the interaction between aortic properties and flow. If cardiac output is scaled to body size as widely maintained, and aortic properties like size or stiffness does not accommodate the increased flow in lockstep, it is possible that an imbalance between flow and accommodation can lead to increased forward pulse wave, which could be consistent with the previous observation on the dominant role of forward wave on PP amplification. Likewise, the role of MAP in younger adult PP amplification is also consistent with the observations in children as MAP is documented to be higher with age or height [18]. Unfortunately, the authors did not create a regression model to adjust for the measured MAP, probably due to sample size. Murakami et al. are to be commended on a noble attempt at defining PP amplification in children to extend observations across the lifecourse. Future work should help disentangle the complex relations among age, growth, flow, arterial properties, and resulting pressure. ACKNOWLEDGEMENTS NHLBI Career Development Award HL111335 (J.P.Z.). This work represents only the view of the author. The funding source had no role in the formulation of this work, nor was any writing assistance used. Conflicts of interest There are no conflicts of interest.
DOI: 10.1097/hjh.0000000000001357
Language: English
Field: Medicine
Open Access status: green
OpenAlex ID: W2621032828
FWCI: 0.214
Cites: 25
Cited by: 4
Related to: 10