Altered Dependence of Aortic Pulse Wave Velocity on Transmural Pressure in Hypertension Revealing Structural Change in the Aortic Wall

Abstract

Stiffening of the aorta, a ubiquitous feature of cardiovascular ageing, imposing adverse loading on the left ventricle and generating high pulse pressure, predisposes to cardiovascular events independent of traditional risk factors.1,2 The determinants of aortic stiffening are, however, poorly understood. Aortic pulse wave velocity (aPWV, the measure of aortic stiffening with most prognostic impact) is only weakly, if at all, associated with traditional risk factors for cardiovascular disease other than age and blood pressure.3,4 By contrast, aPWV is closely associated with concurrent levels of blood pressure 5 implicating hypertension in the etiology of aortic stiffening. However, it is unclear whether the relation of aPWV to blood pressure is simply because of the aorta becoming stiffer as it is stretched by a higher transmural distending pressure (TMP, usually equal to intra-aortic blood pressure) 6 or whether it results from a structural change in the aortic wall associated with and contributing to a sustained elevation in blood pressure (ie, hypertension). Previous attempts to address this question by obtaining indirect estimates of isobaric stiffness have yielded conflicting results. 7-10However, isobaric stiffness does seem to be of prognostic significance. 11 In the present study, we have exploited a novel technique to modulate TMP independent of blood pressure by controlled variation of intrathoracic pressure (ITP) around the adventitial surface of the aorta. We used this to examine the relation of aPWV to TMP in normotensive and hypertensive subjects, reasoning that if aPWV in hypertension is because of a higher TMP, then aPWV in hypertensive subjects would equal that in normotensive subjects when measured at the same TMP. We then used a theoretical model to examine whether aPWV-TMP relationships may be explained by recruitment of collagen fibers in an elastin/collagen matrix when the aorta is distended by increased TMP.Abstract-Aortic pulse wave velocity (aPWV), a major prognostic indicator of cardiovascular events, may be augmented in hypertension as a result of the aorta being stretched by a higher distending blood pressure or by a structural change. We used a novel technique to modulate intrathoracic pressure and thus aortic transmural pressure (TMP) to examine the variation of intrathoracic aPWV with TMP in hypertensive (n=20; mean±SD age, 52.1±15.3 years; blood pressure, 159.6±21.2/92.0±15.9 mm Hg) and normotensive (n=20; age, 55.5±11.1 years; blood pressure, 124.5±11.9/72.6±9.1 mm Hg) subjects. aPWV was measured using dual Doppler probes to insonate the right brachiocephalic artery and aorta at the level of the diaphragm. Resting aPWV was greater in hypertensive compared with normotensive subjects (897±50 cm/s versus 784±43 cm/s; P<0.05). aPWV was equal in hypertensive and normotensive subjects when measured at a TMP of 96 mm Hg. However, dependence of aPWV on TMP in normotensive subjects was greater than that in hypertensive subjects (9.6±1.6 versus 3.8±0.7 cm/s per mm Hg increase in TMP, respe...

Toward Ubiquitous Blood Pressure Monitoring via Pulse Transit Time: Theory and Practice

“…Except for blood density, these parameters are all subject-specific. Experimental data indeed confirm the dependency of the calibration curve on the subject [50]. Hence, a calibration curve that is tailored to each subject would be optimal.…”

Constitutive interpretation of arterial stiffness in clinical studies: a methodological review

“…Taken together, most studies use PWV as an arterial stiffness measure and correct for blood pressure dependence by statistically adjusting for mean arterial pressure. By using, rather than correcting for it, three studies explicitly addressed the pressure dependence to assess underlying ultrastructural changes at the ECM level (42,64,125). Because these studies had a focus on the constitution of the ECM, these three papers are further discussed below.…”

“…This approach was pioneered by our laboratory at carotid level (47,48,147) and recently extended to the proximal aorta (56). In their elegant study, Gaddum et al (42) actively modified transmural pressure over a considerable range (by Valsalva and Mueller maneuvers in patients with hypertension and matched controls) to quantify the pressure dependence of PWV (measured over the arch-diaphragm trajectory by Doppler transit time). They found pressure dependence to be markedly greater in the 2 Distensibility was calculated as follows: distensibility ϭ ⌬d…”

“…Furthermore, they showed (isobaric) PWV to be equal between both groups at 8 m/s and a transmural pressure of ϳ95 mmHg. Using a nonlinear two-constituent model, Gaddum et al (42) tentatively interpreted their measured findings as resulting from changes in elastin/collagen content in combination with a decrease in elastin elastic modulus. Justifiably, the investigators evaluated the validity of their modeling approach by observing that the data in the hypertensive group was well represented by a simpler model (i.e., with fewer parameters; also see Local minima and overfitting).…”

Clinical Diagnostic Biomarkers from the Personalization of Computational Models of Cardiac Physiology

“…Furthermore, in many cases the extracted information is also valuable for informing the parameterization of fully predictive biophysically based models and/or defining boundary conditions. Specific examples include the calculation of pressure gradients from imaged fluid motion (Lamata, Pitcher, et al 2014), the determination of patterns of electrical activation from high temporal resolution cardiac motion maps (Rappaport et al 2007), the estimation of vessel wall stiffness from velocity of pressure pulse wave transmission (Gaddum et al 2015), and the computation of the fractional flow reserve without the need for catheterised measurements (Min et al 2012;Morris et al 2013).…”