Pressure-dependence of arterial stiffness: potential clinical implications

Background: Arterial stiffness measures such as pulse wave velocity (PWV) have a known dependence on actual blood pressure, requiring consideration in cardiovascular risk assessment and management. Given the impact of ageing on arterial wall structure, the pressure-dependence of PWV may vary with age. Methods: Using a noninvasive model-based approach, combining carotid artery echo-tracking and tonometry waveforms, we obtained pressure-area curves in 23 hypertensive patients at baseline and after 3 months of antihypertensive treatment. We predicted the follow-up PWV decrease using modelled baseline curves and follow-up pressures. In addition, on the basis of these curves, we estimated PWV values for two age groups (mean ages 41 and 64 years) at predefined hypertensive (160/90 mmHg) and normotensive (120/80mmHg) pressure ranges. Results: Follow-up measurements showed a near 1 m/s decrease in carotid PWV when compared with baseline, which fully agreed with our model-prediction given the roughly 10mmHg decrease in diastolic pressure. The stiffness-blood pressure-age pattern was in close agreement with corresponding data from the 'Reference Values for Arterial Stiffness' study, linking the physical and empirical bases of our findings. Conclusion: Our study demonstrates that the innate pressure-dependence of arterial stiffness may have implications for the clinical use of arterial stiffness measurements, both in risk assessment and in treatment monitoring of individual patients. We propose a number of clinically feasible approaches to account for the blood pressure effect on PWV measurements

Large vessels as a tree of transmission lines incorporated in the CircAdapt whole-heart model:A computational tool to examine heart-vessel interaction

We developed a whole-circulation computational model by integrating a transmission line (TL) model describing vascular wave transmission into the established CircAdapt platform of whole-heart mechanics. In the present paper, we verify the numerical framework of our TL model by benchmark comparison to a previously validated pulse wave propagation (PWP) model. Additionally, we showcase the integrated CircAdapt-TL model, which now includes the heart as well as extensive arterial and venous trees with terminal impedances. We present CircAdapt-TL haemodynamics simulations of: 1) a systemic normotensive situation and 2) a systemic hypertensive situation. In the TL-PWP benchmark comparison we found good agreement regarding pressure and flow waveforms (relative errors ≤ 2.9% for pressure, and ≤ 5.6% for flow). CircAdapt-TL simulations reproduced the typically observed haemodynamic changes with hypertension, expressed by increases in mean and pulsatile blood pressures, and increased arterial pulse wave velocity. We observed a change in the timing of pressure augmentation (defined as a late-systolic boost in aortic pressure) from occurring after time of peak systolic pressure in the normotensive situation, to occurring prior to time of peak pressure in the hypertensive situation. The pressure augmentation could not be observed when the systemic circulation was lumped into a (non-linear) three-element windkessel model, instead of using our TL model. Wave intensity analysis at the carotid artery indicated earlier arrival of reflected waves with hypertension as compared to normotension, in good qualitative agreement with findings in patients. In conclusion, we successfully embedded a TL model as a vascular module into the CircAdapt platform. The integrated CircAdapt-TL model allows detailed studies on mechanistic studies on heart-vessel interaction

Do treatment-induced changes in arterial stiffness affect left ventricular structure? A meta-analysis

Background: Vascular research demonstrated that pulse wave velocity (PWV), a measure of arterial stiffness, is inherently blood pressure dependent. Considering the hypothesized pathophysiological chain of increased arterial stiffness leading to increased blood pressure load with consequent left ventricular hypertrophy (LVH) development, we conducted a systematic review of antihypertensive and lifestyle intervention studies to determine the association between, on the one hand, changes in arterial stiffness and blood pressure, and, on the other hand, changes in left ventricular mass (LVM). Methods: Using PubMed, EMBASE, Cochrane and Web of Science, we identified 23 studies, containing 2573 patients. Studies reported changes in arterial stiffness (assessed by means of PWV), SBP, DBP and LVM index (LVMI), respectively. Results: Statistically significant reductions in SBP, PWV and LVMI were reported in 16, 14 and 20 studies, respectively. Pooled analysis of studies showed that the proportion in SBP reduction did not correlate significantly to the proportion in reductions of the other two variables. On the contrary, we found a significant positive correlation (r = 0.61, P = 0.003) between arterial stiffness and reduction of LVM, expressed as a relevant reduction in LVMI of 6.9 g/m(2) per 1.0 m/s reduction in PWV. Conclusion: Our findings provide evidence that a decrease in arterial stiffness is associated with reduction of LVM. To investigate whether there exists a causal relation between LVH due to arterial stiffness increases and in turn blood pressure load increases, future studies should strive for a multiple follow-up design and use of blood pressure independent or corrected stiffness indices

Augmentation index is not a proxy for wave reflection magnitude:mechanistic analysis using a computational model

The augmentation index (AIx) is deemed to capture the deleterious effect on left ventricular (LV) work of increased wave reflection associated with stiffer arteries. However, its validity as a proxy for wave reflection magnitude has been questioned. We hypothesized that, in addition to increased wave reflection due to increased pulse wave velocity, LV myocardial shortening velocity influences AIx. Using a computational model of the circulation, we investigated the isolated and combined influences of myocardial shortening velocity vs, LV and arterial stiffness on AIx. Aortic blood pressure waveforms were characterized using AIx and the reflected wave pressure amplitude ((P) over cap (bw), obtained using wave separation analysis). Our reference simulation (normal v(s),(LV) and arterial stiffness) was characterized by an AIx of 21%. A realistic reduction in v(s),(LV) caused AIx to increase from 21 to 42%. An arterial stiffness increase, characterized by a relevant 1.0 m/s increase in carotid-femoral pulse wave velocity, caused AIx to increase from 21 to 41%. Combining the reduced v(s),(LV) and increased arterial stiffness resulted in an AIx of 54%. In a multistep parametric analysis, both v(s),(LV) and arterial stiffness were about equal determinants of AIx, whereas (P) over cap (bw) was only determined by arterial stiffness. Furthermore, the relation between increased AIx and LV stroke work was only approximate to 50% explained by an increase in arterial stiffness, the other factor being v(s),(LV). The (P) over cap (bw), on the other hand, related less ambiguously to LV stroke work. We conclude that the AIx reflects both cardiac and vascular properties and should not be considered an exclusively vascular parameter. NEW & NOTEWORTHY We used a state-of-the-art computational model to mechanistically investigate the validity of the augmentation index (AIx) as a proxy for (changes in) wave reflection. In contrary to current belief, we found that LV contraction velocity influences AIx as much as increased arterial stiffness, and increased AIx does not necessarily relate to an increase in LV stroke work. Wave reflection magnitude derived from considering pressure, as well as flow, does qualify as a determinant of LV stroke work

A constitutive modeling interpretation of the relationship among carotid artery stiffness, blood pressure, and age in hypertensive subjects

Aging has a profound influence on arterial wall structure and function. We have previously reported the relationship between pulse wave velocity, age, and blood pressure in hypertensive subjects. In the present study, we aimed for a quantitative interpretation of the observed changes in wall behavior with age using a constitutive modeling approach. We implemented a model of arterial wall biomechanics and fitted this to the group-averaged pressure-area (P-A) relationship of the "young" subgroup of our study population. Using this model as our take-off point, we assessed which parameters had to be changed to let the model describe the "old" subgroup's P-A relationship. We allowed elastin stiffness and collagen recruitment parameters to vary and adjusted residual stress parameters according to published age-related changes. We required wall stress to be homogeneously distributed over the arterial wall, and assumed wall stress normalization with age by keeping average "old" wall stress at the "young" level. Additionally, we required axial force to remain constant over the cardiac cycle. Our simulations showed a shift in pressure-load bearing from elastin to collagen, caused by a decrease in elastin stiffness and a considerable increase in collagen recruitment. Correspondingly, simulated diameter and wall thickness increased by about 20% and 17%, respectively. The latter compared well with a measured thickness increase of 21%. We conclude that the physiologically realistic changes in constitutive properties we found under physiological constraints with respect to wall stress could well explain the influence of aging in the stiffness-pressure-age pattern observed

Imaging and modeling of acute pressure-induced changes of collagen and elastin microarchitectures in pig and human resistance arteries

The impact of disease-related changes in the extracellular matrix (ECM) on the mechanical properties of human resistance arteries largely remains to be established. Resistance arteries from both pig and human parietal pericardium (PRA) display a different ECM microarchitecture compared with frequently used rodent mesenteric arteries. We hypothesized that the biaxial mechanics of PRA mirror pressure-induced changes in the ECM microarchitecture. This was tested using isolated pig PRA as a model system, integrating vital imaging, pressure myography, and mathematical modeling. Collagenase and elastase digestions were applied to evaluate the load-bearing roles of collagen and elastin, respectively. The incremental elastic modulus linearly related to the straightness of adventitial collagen fibers circumferentially and longitudinally (both R-2 &gt;= 0.99), whereas there was a nonlinear relationship to the internal elastic lamina elastin fiber branching angles. Mathematical modeling suggested a collagen recruitment strain (means +/- SE) of 1.1 +/- 0.2 circumferentially and 0.20 +/- 0.01 longitudinally, corresponding to a pressure of similar to 40 mmHg, a finding supported by the vital imaging. The integrated method was tested on human PRA to confirm its validity. These showed limited circumferential distensibility and elongation and a collagen recruitment strain of 0.8 +/- 0.1 circumferentially and 0.06 +/- 0.02 longitudinally, reached at a distending pressure below 20 mmHg. This was confirmed by vital imaging showing negligible microarchitectural changes of elastin and collagen upon pressurization. In conclusion, we show here, for the first time in resistance arteries, a quantitative relationship between pressure-induced changes in the extracellular matrix and the arterial wall mechanics. The strength of the integrated methods invites for future detailed studies of microvascular pathologies.NEW &amp; NOTEWORTHY This is the first study to quantitatively relate pressure-induced microstructural changes in resistance arteries to the mechanics of their wall. Principal findings using a pig model system were confirmed in human arteries. The combined methods provide a strong tool for future hypothesis-driven studies of microvascular pathologies.</p