Complementary roles of mechanotransduction and inflammation in vascular homeostasis

Arteries are exposed to relentless pulsatile haemodynamic loads, but via mechanical homeostasis they tend to maintain near optimal structure, properties and function over long periods in maturity in health. Numerous insults can compromise such homeostatic tendencies, however, resulting in maladaptations or disease. Chronic inflammation can be counted among the detrimental insults experienced by arteries, yet inflammation can also play important homeostatic roles. In this paper, we present a new theoretical model of complementary mechanobiological and immunobiological control of vascular geometry and composition, and thus properties and function. We motivate and illustrate the model using data for aortic remodelling in a common mouse model of induced hypertension. Predictions match the available data well, noting a need for increased data for further parameter refinement. The overall approach and conclusions are general, however, and help to unify two previously disparate literatures, thus leading to deeper insight into the separate and overlapping roles of mechanobiology and immunobiology in vascular health and disease

Physiological basis for longitudinal motion of the arterial wall

As opposed to arterial distension in the radial plane, longitudinal wall motion (LWM) is a multiphasic and bidirectional displacement of the arterial wall in the anterograde (i.e., in the direction of blood flow) and retrograde (i.e., opposing direction of blood flow) directions. While initially disregarded as imaging artifact, LWM has been consistently reported in ultrasound investigations in the last decade and is reproducible beat-to-beat, albeit with large inter-individual variability across healthy and diseased populations. Emerging literature has sought to examine the mechanistic control of LWM to explain the shape and variability of the motion pattern but lacks considerations for key foundational vascular principles at the level of the arterial wall ultrastructure. The purpose of this review is to summarize the potential factors that underpin the causes and control of arterial LWM, spanning considerations from the arterial extracellular matrix to systems-level integrative theories. First, an overview of LWM and relevant aspects wall composition will be discussed, including major features of the multiphasic pattern, arterial wall extracellular components, tunica fiber orientations, and arterial longitudinal pre-stretch. Second, current theories on the systems-level physiological mechanisms driving LWM will be discussed in the context of available evidence including experimental human research, porcine studies, and mathematical models. Throughout, we discuss implications of these observations with suggestions for future priority research areas

Adults With Type 2 Diabetes Mellitus Exhibit a Greater Exercise-Induced Increase in Arterial Stiffness and Vessel Hemodynamics

Individuals with type 2 diabetes mellitus (T2DM) have a greater blood pressure (BP) response to acute maximal exercise compared to those without T2DM; however, whether they exhibit a different arterial stiffness response to maximal exercise has yet to be explored. Adults with (n=66) and without T2DM (n=61) underwent an arterial stress test: at rest and immediately postexercise, carotid-femoral pulse wave velocity, the gold standard measure of arterial stiffness, brachial BP, heart rate, and other hemodynamic measurements were assessed. Linear regression models were used to evaluate between-group differences at rest, and the response to exercise (postexercise value), adjusting for covariates including BP and heart rate when relevant, and the corresponding baseline value of each parameter. All participants (mean +/- SD: age 59.3 +/- 10.6 years; body mass index 31.2 +/- 3.9 kg/m(2)) had hypertension (mean BP 130 +/- 14/80 +/- 9 mm Hg). At rest, participants with T2DM had significantly higher carotid-femoral pulse wave velocity (10.3 +/- 2.7 versus 9.1 +/- 1.9 m/s), heart rate (69 +/- 11 versus 66 +/- 10 beats/min), and lower diastolic BP (79 +/- 9 versus 83 +/- 9 mm Hg), but systolic BP (129 +/- 15 versus 131 +/- 13 mm Hg) was similar. In response to exercise, participants with T2DM showed greater increases in carotid-femoral pulse wave velocity (1.6 [95% CI, 0.4-2.9 m/s]) and systolic BP (9 [95% CI, 1-17 mm Hg]) than participants without T2DM. A greater proportion of participants with T2DM had a hypertensive response to exercise compared to participants without T2DM (n=23, 35% versus n=11, 18%; P=0.033). By incorporating exercise as a vascular stressor, we provide evidence of a greater increase in arterial stiffness in individuals with T2DM, independently of resting arterial stiffness, and the BP postexercise.</p

Arterial stiffness index beta and cardio-ankle vascular index inherently depend on blood pressure but can be readily corrected

Objectives: Arterial stiffness index beta and cardio-ankle vascular index (CAVI) are widely accepted to quantify the intrinsic exponent (beta(0)) of the blood pressure (BP)-diameter relationship. CAVI and b assume an exponential relationship between pressure (P) and diameter (d). We aim to demonstrate that, under this assumption, beta and CAVI as currently implemented are inherently BP-dependent and to provide corrected, BP-independent forms of CAVI and beta.Methods and results: In P = P(ref)e(beta 0[(d/dref)-1)], usually reference pressure (P-ref) and reference diameter (d(ref)) are substituted with DBP and diastolic diameter to accommodate measurements. Consequently, the resulting exponent is not equal to the pressure-independent beta(0). CAVI does not only suffer from this 'reference pressure' effect, but also from the linear approximation of (dP=dd). For example, assuming beta(0) = 7, an increase of SBP/DBP from 110/70 to 170/120mmHg increased beta by 8.1% and CAVI by 14.3%. We derived corrected forms of b and of CAVI (CAVI(0)) that indeed did not change with BP and represent the pressure-independent beta(0). To substantiate the BP effect on CAVI in a typical follow-up study, we realistically simulated patients (n = 161) before and following BP-lowering 'treatment' (assuming no follow-up change in intrinsic beta(0) and therefore in actual P-d relationship). Lowering BP from 160 +/- 14/111 +/- 11 to 120 +/- 15/79 +/- 11 mmHg (p &lt;0.001) resulted in a significant CAVI decrease (from 8.1 +/- 2.0 to 7.7 +/- 2.1, p = 0.008); CAVI(0) did not change (9.8 +/- 2.4 and 9.9 +/- 2.6, p = 0.499).Conclusion: beta and CAVI as currently implemented are inherently BP-dependent, potentially leading to erroneous conclusions in arterial stiffness trials. BP-independent forms are presented to readily overcome this problem.</p

Pediatric reference values for arterial stiffness parameters cardio-ankle vascular index and CAVI0

The process of arteriosclerosis begins early in life, and cardiovascular risk factors identified in childhood tend to persist into adulthood. Cardio-ankle vascular index (CAVI), a recent parameter of arterial stiffness, is considered an independent predictor of cardiovascular risk. However, there are no studies reporting sex- and age-specific physiological values of CAVI in childhood. We aimed to establish reference values for CAVI and its blood pressure-corrected variant (CAVI0) in 500 healthy children and adolescents aged 7 to 19 years and to study potential relationships with anthropometric indices. Sex- and age-specific distributions of CAVI and CAVI0 values in healthy children and adolescents are presented. Boys aged 15-19 years had lower CAVI than girls, which could result from CAVI's slight blood pressure dependence. CAVI0 did not show such sex difference. Body roundness index-a novel parameter to quantify abdominal fat-was a strong anthropometric predictor of both CAVI and CAVI0. This is the first study providing pediatric age- and sex-specific reference values for arterial stiffness parameters CAVI and CAVI0. The presented data can contribute to the understanding of the evolution of these indices during childhood and adolescence. Under specific conditions, CAVI0 may offer more robust information about arterial stiffness than standard CAVI

Percutaneous Device Closure of Congenital Isolated Ventricular Septal Defects:A Single-Center Retrospective Database Study Amongst 412 Cases

To identify suitable cases and reduce failure/complication rates for percutaneous ventricular septal defect (VSD) closure, we aimed to (1) study causes of device failure and (2) compare outcomes with different VSD types and devices in a high-volume single center with limited resources. Retrospective data of 412 elective percutaneous VSD closure of isolated congenital VSDs between 2003 and 2017 were analyzed. Out of 412, 363 were successfully implanted, in 30 device implantation failed, and in 19 the procedure was abandoned. Outcome was assessed using echocardiography, electrocardiography, and catheterization data (before procedure, immediately after and during follow-up). Logistic regression analyses were performed to assess effects of age, VSD type, and device type and size on procedural outcome. Median [interquartile range] age and body surface area were 6.6 [4.1-10.9] years and 0.7 [0.5-1.0] m(2), respectively. Device failure was not associated with age (p = 0.08), type of VSD (p = 0.5), device type (p = 0.2), or device size (p = 0.1). Device failure occurred in 7.6% of patients. As device type is not related to failure rate and device failure and complication risk was not associated with age, it is justifiable to use financially beneficial ductal devices in VSD position and to consider closure of VSD with device in clinically indicated children

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

Age-Specific Acute Changes in Carotid-Femoral Pulse Wave Velocity With Head-up Tilt

BACKGROUND: Aortic stiffness as measured by carotid-femoral pulse wave velocity (cfPWV) is known to depend on blood pressure (BP), and this dependency may change with age. Therefore, the hydrostatic BP gradient resulting from a change in body posture may elicit a cfPWV change that is age-dependent. We aimed to analyze the relationship between BP gradient-induced by head-up body tilting-and related changes in cfPWV in individuals of varying age. METHODS: cfPWV and other hemodynamic parameters were measured in 30 healthy individuals at a head-up tilt of 0° (supine), 30°, and 60°. At each angle, the PWV gradient and resulting cfPWV were also estimated (predicted) by assuming a global nonlinear, exponential, pressure-diameter relationship characterized by a constant β0, and taking into account that (diastolic) foot-to-foot cfPWV acutely depends on diastolic BP. RESULTS: cfPWV significantly increased upon body tilting (8.0 ± 2.0 m/s supine, 9.1 ± 2.6 m/s at 30°, 9.5 ± 3.2 m/s at 60°, P for trend <0.01); a positive trend was also observed for heart rate (HR; P < 0.01). When the observed, tilt-induced cfPWV change measured by applanation tonometry was compared with that predicted from the estimated BP hydrostatic gradient, the difference in observed-vs.-predicted PWV change increased nonlinearly as a function of age (R2 for quadratic trend = 0.38, P < 0.01, P vs. linear = 0.04). This result was unaffected by HR tilt-related variations (R2 for quadratic trend = 0.37, P < 0.01, P vs. linear = 0.04). CONCLUSIONS: Under a hydrostatic pressure gradient, the pulse wave traveling along the aorta undergoes an age-related, nonlinear PWV increase exceeding the increase predicted from BP dependency