In silico characterization of the effects of size,distribution, and modulus contrast of aortic focal softening on pulse wave propagations

Examining the change in regional stiffness of the arterial wall may prove as a reliable method for detecting various cardiovascular diseases. As suggested by Moens–Korteweg relationship, the pulse wave velocity (PWV) along the arteries has been shown to correlate to the stiffness of the arterial wall; the higher the stiffness, the higher the PWV. The current primary clinical practice of obtaining an average PWV between remote sites such as femoral and carotid arteries is not as clinically effective, since various cardiovascular diseases are shown to be accompanied by focal changes in stiffness. Therefore, methods to examine the PWVs focally are warranted. Extending on the findings of previous studies, pulse wave propagations along aortas with wall focal softening were addressed in this study using two-way coupled fluid–structure interaction (FSI) simulations of arterial pulsatile motions. Spatio-temporal maps of the wall displacement were used to evaluate the regional pulse wave propagations and velocities. In particular, soft wall inclusions of different number, size, and modulus were examined. The findings showed that the qualitative markers on the pattern of the wave propagations such as the existence of forward, reflected, and standing waves, as well as the quantitative markers such as PWV, linear coefficient of the propagating waves, and the width of the standing waves, provide a reliable tool to distinguish between the natures of the wall focal softening. Future studies are needed to include physiologically-relevant wall inhomogeneity in order to further implicate on the clinical potentials of the inverse problem for noninvasive diagnosis.     

Detection of aortic wall inclusions using regional pulse wave propagation and velocity in silico

Monitoring of the regional stiffening of the arterial wall may prove important in the diagnosis of various vascular pathologies. The pulse wave velocity (PWV) along the aortic wall has been shown to be dependent on the wall stiffness and has played a fundamental role in a range of diagnostic methods. Conventional clinical methods entail global examination of the pulse traveling between two remote sites, e.g. femoral and carotid arteries, to provide an average PWV estimate. However, the majority of vascular diseases entail regional vascular changes and therefore may not be detected by a global PWV estimate. In this paper, a fluid-structure interaction study of straight-geometry aortas of 350 mm length is described aimed at examining the effects of regional stiffness changes on the PWV. Five homogeneous aortas with increasing wall stiffness as well as two aortas with soft and hard inclusions of 5 mm length were considered. In each case, spatio-temporal maps of the wall motion were used to analyze the regional pulse wave propagation. On the homogeneous aortas, increasing PWVs were found to increase with the wall moduli ($R²=0.9988$), indicating the reliability of the model to accurately represent the wave propagation. On the inhomogeneous aortas, formation of reflected and standing waves was observed at the site of the hard and soft inclusions, respectively. Neither the hard nor the soft inclusion had a significant effect on the velocity of the traveling pulse beyond the inclusion site, which supported the hypothesis that a global measurement of the average PWV could fail to detect small, regional abnormalities.     

Effect of sildenafil on arterial stiffness and wave reflection

While sildenafil (Viagra) is widely prescribed for erectile dysfunction, its effect on arterial function is not established. The elastic properties of the aorta, as well as the magnitude and timing of wave reflection, are important factors for efficient performance of the cardiovascular system and have been identified as prognosticators of cardiovascular risk. A total of 24 subjects with coronary artery disease, of whom 14 were hypertensives, aged 69 +/- 8 years, were studied in a randomized, placebo-controlled, double-blind, cross-over design. Measurements lasted for 3 h after the sildenafil intake (50 mg, p.o.) or placebo. Aortic elastic properties were evaluated with carotid-femoral pulse wave velocity; wave reflection was evaluated with augmentation index and augmented pressure of the aortic pressure waveform. Pulse wave velocity decreased significantly (by 0.65 m/s, p = 0.005), denoting a decrease in aortic stiffness. Augmentation index and augmented pressure decreased significantly (by 4.47% absolute and by 4.01 mmHg; p < 0.001 and p = 0.001, respectively), denoting a decreased effect of wave reflection from the periphery. Aortic pulse pressure decreased significantly (by 6.74 mmHg, p < 0.05). An active effect of the drug on aortic wall appears to contribute to the decrease in pulse wave velocity, although other mechanisms such as a decrease of blood pressure and autonomic reflexes could also have contributed. The effect of sildenafil lasted throughout the study (3 h), being evident 30 min after drug intake. In conclusion, this study shows, for the first time, that sildenafil has a favorable effect on aortic stiffness and wave reflection in patients with coronary artery disease. This finding may have important implications for cardiovascular performance and exercise capacity during intercourse.     

Characterization of the Upper Limb Arterial Properties during Reactive Hyperemia

The radial artery (RA) pressure waveform is commonly used to reconstruct the central aortic pressure waveform. Because the RA pressure waveform has been used as input to this process, its features that are dependent on the local arterial properties can influence the final reconstructed aortic waveform. In this study, we determined the effects of altered upper limb pulse wave velocity (PWV) and local wave reflection parameters on RA pressure waveform augmentation (RA-AIx). Twenty healthy volunteers (10 men) between the ages of 18 and 35 years of age were recruited. Simultaneous pressure waveforms were acquired using arterial tonometers from the right carotid and the radial arteries, prior to and following tourniquet induced hyperemia. The phase velocities from the pressure wave transfer function were used to estimate the pulse wave velocity (PWV_∞), the local reflection coefficient (Γ) and an estimate of the terminal impedance of the upper limbs, PWV₀₊. The RA-AIx was represented as a linear, three-parameter model that included the input (the AIx of the carotid artery pressure waveform, CA-AIx), the Γ and PWV_∞ of the arm. Tourniquet induced hyperemia did not alter Γ but reduced PWV_∞, and PWV₀₊ and increased RA-AIx. Multiple linear regression analysis indicated that RA-AIx was increased by high levels of CA-AIx and PWV_∞ and decreased by elevated Γ. The relative weighing of CA-AIx, Γ and PWV_∞ on RA-AIx were 3:2:1, respectively. The AIx of RA is determined to an equal extent by the input and local factors. Interpretation of the AIx of the RA and the reconstructed central aortic waveform should be made in the context of this relationship. Presented in part in abstract form: June 2006 A26248 Canadian Society of Anesthesiology, Toronto, Ontario, Canada. September 2006 Proceedings of the XVII International Conference of the Cardiovascular System Dynamics Society, Vaals, The Netherlands     

Aortic diameter, wall stiffness, and wave reflection in systolic hypertension

Systolic hypertension is associated with increased pulse pressure (PP) and increased risk for adverse cardiovascular outcomes. However the pathogenesis of increased PP remains controversial. One hypothesis suggests that aortic dilatation, wall stiffening and increased pulse wave velocity result from elastin fragmentation, leading to a premature reflected pressure wave that contributes to elevated PP. An alternative hypothesis suggests that increased proximal aortic stiffness and reduced aortic diameter leads to mismatch between pressure and flow, giving rise to an increased forward pressure wave and increased PP. To evaluate these two hypotheses, we measured pulsatile hemodynamics and proximal aortic diameter directly using tonometry, ultrasound imaging, and Doppler in 167 individuals with systolic hypertension. Antihypertensive medications were withdrawn for at least 1 week before study. Patients with PP above the median (75 mm Hg) had lower aortic diameter (2.94+/-0.36 versus 3.13+/-0.28 cm, P<0.001) and higher aortic wall stiffness (elastance-wall stiffness product: 16.1+/-0.7 versus 15.7+/-0.7 ln[dyne/cm], P<0.001) with no difference in augmentation index (19.9+/-10.4 versus 17.5+/-10.0%, P=0.12). Aortic diameter and wall stiffness both increased with advancing age (P<0.001). However, an inverse relation between PP and aortic diameter remained significant (P<0.001) in models that adjusted for age, sex, height, and weight and then further adjusted for aortic wall stiffness, augmentation index, and mean arterial pressure. Among individuals with systolic hypertension, increased PP is primarily attributable to increased wall stiffness and reduced aortic diameter rather than premature wave reflection.     

Effect of caffeine on aortic elastic properties and wave reflection

OBJECTIVE: Caffeine is the most widely used pharmacologically active substance. Aortic elastic properties and arterial wave reflection are important factors for the efficient performance of the cardiovascular system, as well as prognosticators of cardiovascular risk. We investigated the effect of caffeine on aortic elastic properties and wave reflection. DESIGN: We studied the effect of caffeine (250 mg) in 20 healthy subjects according to a randomized, placebo-controlled, double-blind, cross-over design. METHODS: Aortic stiffness was evaluated with carotid-femoral pulse wave velocity and wave reflection with augmentation index of the aortic pressure waveform. RESULTS: Pulse wave velocity increased (by 0.51 m/s, 0.001) denoting an increase in aortic stiffness. Augmentation index and augmented pressure increased (by 6.8%, and by 4.4 mmHg, respectively, P <0.001 for both) denoting increased wave reflections. Concurrently, both radial and aortic systolic, diastolic and pulse pressure increased significantly. However, this increase was 20 and 9% larger for aortic systolic pressure (at 30 and 60 min, P <0.001 and P <0.05, respectively) and 56% larger for aortic pulse pressure (at 30 min, P <0.001) compared with the corresponding upper limb values. This indicates that peripheral pressure measurements are not an accurate guide for the pressor effect of caffeine in central arteries. CONCLUSIONS: Caffeine affects unfavorably aortic stiffness and enhances wave reflections. This finding has implications for the impact of caffeine consumption on cardiovascular risk.     

Die arterielle Compliance (Gefäßsteifigkeit) zur Aufdeckung einer subklinischen Atherosklerose

Cardiovascular diseases such as coronary heart disease are the leading cause for morbidity and mortality in industrial countries. Current evidence shows that stiffening of the arterial wall is one major mechanism responsible for this morbidity and mortality in cardiovascular disease. Various physiological and pathophysiological parameters influence arterial stiffening including age, gender, blood pressure, smoking, and diseases such as hypertension, diabetes, renal failure, and hypercholesterolemia. Thus, the assessment of arterial stiffness has become a widely used tool to investigate the function of the arteries in epidemiologic and clinical studies. Traditionally, arterial stiffness has been assessed by pulse wave velocity, a noninvasive parameter which has been shown to predict cardiovascular mortality. In addition, pulse wave analysis has been increasingly used to determine the augmentation index, a parameter that describes the effect of pulse wave reflection on the central aortic pressure configuration. In the present review, the pathophysiological contribution of arterial stiffening for cardiovascular morbidity and mortality is described. Details of models, indices, and techniques used to evaluate stiffness will be presented. Clinical studies investigating the predictive value of stiffness markers in defining future cardiovascular risk and survival are summarized.     

Cigar smoking has an acute detrimental effect on arterial stiffness

BACKGROUND: Despite a decline in cigarette smoking, cigar smoking is increasing, partly due to the perception that it is a "safe" alternative to cigarettes. However, cigar smoking increases cardiovascular risk, but the mechanisms involved are not fully explored. Aortic stiffness and arterial wave reflection are important factors for the efficient performance of the cardiovascular system and have been identified as prognosticators of cardiovascular risk. We investigated the acute effect of cigar smoking on aortic elastic properties and wave reflection. METHODS: We studied the effect of smoking one cigar in 12 healthy subjects according to a randomized, sham procedure-controlled, cross-over design. Aortic stiffness was evaluated with carotid-femoral pulse wave velocity and wave reflection with augmentation index of the aortic pressure waveform. RESULTS: Cigar smoking produced a significant increase in pulse wave velocity (by 0.80 m/sec, P = .001) denoting an increase in aortic stiffness. Augmentation index increased significantly (by 6.1%, P < .05) denoting an increase of wave reflections. These increases in arterial stiffness indices were evident promptly after the initiation of cigar smoking and lasted throughout the duration of the study (2 h). Concurrently, both radial and aortic systolic, and pulse pressure increased significantly throughout the study. CONCLUSIONS: The present study shows for the first time that cigar smoking increases acutely stiffness of large arteries and wave reflection, thus providing further evidence that it is not a safe alternative to cigarettes.     

Afterload reduction by hydralazine in children with a ventricular septal defect as determined by aortic input impedance

Summary Hydralazine was administered at cardiac catheterization to eight children with a ventricular septal defect (age: 2.2–8.8 years), and the extent of afterload reduction was determined using aortic input impedance and wall stress. The pulmonary to systemic blood flow ratio decreased from 2.2±0.8 to 1.8±0.4 (p<0.05) and the pulmonary systemic resistance ratio increased from 0.11±0.08 to 0.13±0.10 (p<0.05) after hydralazine administration. Hydralazine reduced mean aortic pressure and the amplitude of the late systolic peak of the aortic pressure wave. Peak flow velocity in the descending aorta increased from 62±14 to 81±24 cm/sec (p<0.05). Peripheral resistance decreased significantly from 13.3±5.9 to 6.6±3.7 10³ dyn sec/cm³ (p<0.05). The modulus of the first harmonic, indicating pulse wave reflection, decreased from 1196±575 to 815±382 dyn sec/cm³ (p<0.05). The characteristic impedance, indicating aortic stiffness, did not change. End-systolic wall stress decreased significantly from 54.4±16.7 to 34.8±10.2 g/cm² (p<0.01). Hydralazine acutely achieved afterload reduction by reducing both peripheral resistance and pulse wave reflection, and increased stroke volume.     

Independent association between glycated hemoglobin and arterial stiffness in healthy men

Aims/Introduction

Many studies have reported that high levels of glycated hemoglobin (HbA1c) are strongly associated with an increased risk of cardiovascular disease. Many researchers have not studied the association of HbA1c with various subclinical atherosclerosis phenotypes. We evaluated the impact of HbA1c on arterial stiffness and atherosclerosis in healthy Korean healthy men.

Materials and Methods

The study population included healthy adult men who participated in health check‐ups. All participants fasted for at least 8 h before taking the blood sample for fasting blood glucose, HbA1c, total cholesterol, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol and triglyceride. Arterial stiffness was measured using brachial‐ankle pulse wave velocity. Hierarchical regression analysis allowed us to determine the relationship between brachial‐ankle pulse wave velocity (baPWV) and potential risk factors for cardiovascular disease.

Results

Age and HbA1c were significantly related to baPWV, in model 1. In model 2, blood pressure was added to model 1. Systolic blood pressure was a more significant variable, which was more affected on baPWV than diastolic blood pressure. In the case of model 3, we included all variables regarding arterial stiffness. According to model 3, the most explainable variable was age, and then systolic blood pressure, body mass index and triglyceride, respectively.

Conclusions

We analyzed the associations between HbA1c, which is one of the risk factors, and arterial stiffness independently. An arterial stiffness measurement using baPWV can show the level of severity of the arteriosclerosis. When the level of stiffness has been increased, we could assume that the risk of arteriosclerosis would be increased. It can also be related to the increase of the risk of cardiovascular disease.     

Association of beta-blocker use with increased aortic wave reflection

Studies have found less cardiovascular risk reduction in patients treated with beta-blockers (BBs) compared with other agents. We compared the severity of aortic atherosclerosis, arterial stiffness, and wave reflection in patients treated and not treated with BBs. Seventy-two patients, 37 treated with BBs and 35 not treated, referred for transesophageal echocardiography were studied. Augmentation index (AI), heart-rate-corrected AI (AI-75), aortic systolic (SBP) and diastolic blood pressure, pulse wave velocity (PWV), and aortic intima-media thickness (MAIMT) were measured. There were no differences in MAIMT (2.8 ± 1.6 mm vs. 2.4 ± 1.2 mm, P = .20) and PWV (8.9 ± 2.0 m/s vs. 8.5 ± 2.6 m/s, P = .46) between the BB and non-BB groups. The BB group had higher AI (28.7 ±11.9% vs. 22.3 ± 14.1%, P = .04), AI-75 (27.7 ± 10.7% vs. 20.1± 11.0%, P = .005), aortic SBP (140 ± 21 mm Hg vs. 125 ± 21 mm Hg, P = .01), and aortic pulse pressure (62 ± 20 mm Hg vs. 47 ± 19 mm Hg, P = .01) than the non-BB group despite similar brachial blood pressure. BB use was associated with increased aortic wave reflection despite similar degree of aortic atherosclerosis.     

Non-invasive 24 hour ambulatory monitoring of aortic wave reflection and arterial stiffness by a novel oscillometric device: The first feasibility and reproducibility study

Background

Surrogates of aortic wave reflection and arterial stiffness, such as augmentation index (AIx), augmentation pressure, pulse wave velocity (PWV) and pulse pressure amplification (PPampl) are independent predictors of cardiovascular risk. A novel ambulatory, brachial cuff-based oscillometric device has been recently developed and validated, yielding 24-h assessment of the aforementioned parameters (Mobilo-O-Graph). Aim of this study was to investigate the feasibility and reproducibility of wave reflection and arterial stiffness estimation by pulse wave analysis using this device.

Methods

Thirty treated or untreated hypertensives (mean age: 53.6 ± 11.6 years, 17 men) had test–retest 24-h monitoring one week apart using the test device.

Results

Mean numbers of valid aortic readings per subject, between test and retest, were comparable. Approximately 12 aortic readings per subject (17%) were not feasible or valid. No differences were observed for any 24-h parameter between the two assessments. Bland–Altman plots showed no systemic difference, while the limits of agreement for each parameter indicated high reproducibility (AIx: − 7.2 to 8.2%, AP: − 3.7 to 4.1 mm Hg, PWV: − 0.39 to 0.41 m/s, PPampl: − 0.08 to 0.06). This was further verified by intraclass correlation coefficients which were > 0.8 for each parameter.

Conclusions

Non-invasive 24-h estimation of wave reflection and arterial stiffness indices, derived by the test device, appear to be highly reproducible. Future studies should investigate whether these measurements have additive prognostic value for cardiovascular risk stratification, beyond common brachial blood pressure measurements or single estimations of wave reflection and PWV at office settings.     

Large-artery stiffness, hypertension and cardiovascular risk in older patients

Research studies on hypertension have, so far, generally focused on vascular resistance and small arteries. The high prevalence of systolic hypertension in patients older than 50 years and the development of noninvasive Doppler and echotracking techniques have made it possible to determine large-artery stiffness with a high degree of reproducibility. Increased arterial stiffness and disturbed wave reflections are the basis for understanding reduced aortic elasticity and systolic hypertension, particularly in older people. This hemodynamic pattern results from mechanical factors and other pressure-independent risk factors, such as diabetes mellitus, renal failure, obesity and severe atherosclerosis. Distinct phenotypes of arterial stiffness and pulse pressure result from specific gene polymorphisms, such as those related to the renin-angiotensin system. The roles of arterial stiffness and wave reflections in hypertension have been elucidated by modern interpretations of the blood-pressure curve in relation to its propagation, mechanisms of systolic-blood-pressure amplification, and the pulse-pressure amplitude. New predictors of cardiovascular risk have been identified, such as increased pulse pressure and pulse-wave velocity, and disturbed wave reflections, all of which are independent predictors of cardiovascular risk that are more powerful than either systolic or diastolic blood pressure alone. Therapeutic trials are investigating ways to reduce stiffness, and thereby allow the selective reduction of systolic and pulse pressure in hypertensive patients with or without advanced renal failure. Modern pharmacologic agents need to be identified, which could reduce systolic hypertension in patients older than 50 years. Here we discuss the structural and functional factors that influence arterial stiffness, wave reflections and pulse pressure in hypertension, as well as their related roles in cardiovascular risk.     

Hemodynamics of increased pulse pressure in older women in the community-based Age, Gene/Environment Susceptibility-Reykjavik Study

Pulse pressure increases with advancing age particularly in women. As a result, women have a higher pulse pressure than men from midlife onward. Higher pulse pressure in older women as compared to men is often attributed to increased aortic wall stiffness and premature wave reflection. To evaluate this hypothesis, we measured central aortic input impedance, pulse wave velocity, and wave reflection in 408 older men and women (age range, 69 to 94 yr, mean 75 yr) participating in the community-based Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik). Women as compared to men had higher pulse pressure (75.8+/-18.7 versus 69.5+/-16.8 mm Hg, P<0.001) and smaller aortic diameters (2.74+/-0.24 versus 2.97+/-0.28 cm, P<0.001). Augmentation index (AI) was higher (11.0+/-15.9 versus 7.9+/-12.9%, P=0.032) in women whereas proximal aortic elastance-wall thickness product (Eh) did not differ (P=0.61). In a stepwise model for pulse pressure that included age and sex and offered aortic diameter, Eh, mean pressure, AI, pulse wave velocity, height, weight, and body surface area as additional covariates, higher pulse pressure was associated with increased wall stiffness, smaller aortic diameter, higher mean pressure, and increased AI (Model R(2)=0.59, P<0.001). The sex difference in pulse pressure (6.6+/-1.7 mm Hg, P<0.001) persisted after Eh entered the model (6.9+/-1.5 mm Hg, P<0.001) but not after aortic diameter entered the model (-0.4+/-1.4 mm Hg, P=0.75). Thus, reduced aortic diameter and impaired matching between diameter and flow accounts for the sex difference in pulse pressure in an unselected community-based cohort of older people.     

Correlates of aortic stiffness in elderly individuals: a subgroup of the cardiovascular health study

Background:Arterial stiffness has been associated with aging, hypertension, and diabetes; however, little data has been published examining risk factors associated with arterial stiffness in elderly individuals.Methods:Longitudinal associations were made between aortic stiffness and risk factors measured approximately 4 years earlier. Aortic pulse wave velocity (PWV), an established index of arterial stiffness, was measured in 356 participants (53.4% women, 25.3% African American), aged 70 to 96 years, from the Pittsburgh site of the Cardiovascular Health Study during 1996 to 1998.Results:Mean aortic pulse wave velocity (850 cm/sec, range 365 to 1863) did not differ by ethnicity or sex. Increased aortic stiffness was positively associated with higher systolic blood pressure (SBP), age, fasting and 2-h postload glucose, fasting and 2-h insulin, triglycerides, waist circumference, body mass index, truncal fat, decreased physical activity, heart rate, and common carotid artery wall thickness (P < .05). After controlling for age and SBP, the strongest predictors of aortic stiffness in men were heart rate (P = .001) and 2-h glucose (P = .063). In women, PWV was positively associated with heart rate (P = .018), use of antihypertensive medication (P = .035), waist circumference (P = .030), and triglycerides (P = .081), and was negatively associated with physical activity (P = .111). Results were similar when the analysis was repeated in nondiabetic individuals and in those free of clinical or subclinical cardiovascular disease in 1992 to 1993.Conclusions:In these elderly participants, aortic stiffness was positively associated with risk factors associated with the insulin resistance syndrome, increased common carotid intima–media thickness, heart rate, and decreased physical activity measured several years earlier.     

Risk factors for stiffness of the wall of the thoracic aorta in patients with mild atherosis

Previous studies have suggested that aging is associated with progressive arterial stiffness and widening of the pulse pressure, and pulse pressure has been found to be a risk factor of cardiovascular diseases. However, the effects of age, blood pressure (including pulse pressure) or atherogenic factors on thoracic aortic wall stiffness in patients with mild atherosis are unclear, so the present study used transesophageal echocardiography to examine 103 consecutive patients with various cardiovascular diseases. The extent of atherosis was evaluated in terms of intima-medial thickness (IMT), and 2 indices of wall stiffness in the aorta were calculated: elastic modulus and stiffness parameter (beta). In subjects with mild atherosis (IMT <1.0mm), age, body mass index, systolic blood pressure, pulse pressure, triglyceride level, and hypertension were factors significantly associated with high wall stiffness, and multiple logistic stepwise analysis revealed that age, pulse pressure, and triglyceride level were particularly significant.     

Arterial stiffness: Is it ready for prime time?

Recent interest in arterial stiffness as a possible new biomarker of cardiovascular (CV) disease has emerged. Arterial stiffness of the large, elastic conduit arteries is considered a risk marker of vascular aging; it leads to widened pulse pressure (PP) and the development of isolated systolic hypertension in the middle-aged and elderly population. However, increased PP is not always a good surrogate for arterial stiffening because of the frequent discrepancy between peripheral brachial and central aortic PP values caused by varying wave reflection activity. Therefore, noninvasive, easily performed methods for more direct measurement of arterial stiffness, such as pulse wave velocity (PWV) and pulse wave analysis (PWA) have been developed for clinical use. This article asks the question: How useful are PWV and PWA, when compared with traditional measurement of blood pressure components, as biomarkers of CV disease?     

Arterial stiffness and kidney function

The vascular hallmark of subjects with end-stage renal disease undergoing hemodialysis is increased aortic stiffness, a phenomenon independent of mean arterial blood pressure, wall stress, and standard cardiovascular risk factors such as plasma glucose, cholesterol, obesity, and smoking. These observations suggest that subtle links might associate arterial stiffness and kidney function in normotensive and hypertensive populations. Recently, aortic pulse wave velocity and creatinine clearance have been shown to be statistically associated in subjects with plasma creatinine < or =130 micromol/L, again independently of mean arterial blood pressure and classical cardiovascular risk factors. This association was even shown to predominate in subjects younger than age 55 years. In addition, acceleration of aortic pulse wave velocity with age was more important in these subjects than in untreated normotensive control individuals, and the phenomenon was consistently predicted by baseline plasma creatinine values. Among all antihypertensive drugs, angiotensin-converting enzyme inhibitors only were shown to exhibit a significant and independent effect on aortic stiffness. The use of these drugs was significantly associated with improvement of large aortic stiffness in subjects treated for hypertension. In conclusion, increased stiffness of central arteries is independently associated with reduced creatinine clearance in subjects with mild to severe renal insufficiency, indicating that kidney diseases may interact not only with small but also with large conduit arteries, independently of age, blood pressure level, and classical cardiovascular risk factors. Whether sodium, divalent ionic species (calcium, phosphates), and the renin-angiotensin-aldosterone system play a role in such alterations remains to be elucidated.     

Aldosterone-to-renin ratio, arterial stiffness, and the response to aldosterone antagonism in essential hypertension

BACKGROUND: Some 10% to 15% of hypertensive patients have hyperaldosteronism, an increased ambulant aldosterone-to-renin ratio. As aldosterone reduces arterial compliance, we examined the relationship between aldosterone-to-renin ratio, aortic blood pressure (BP), arterial stiffness, and the effect of spironolactone in a hypertensive population. METHODS: In 24 untreated patients (mean age 51 +/- 2 years, 10 women), we assessed arterial stiffness by augmentation index-height of the late systolic peak in the aorta, pulse pressure (Sphygmocor), and aortic pulse wave velocity (Complior). RESULTS: There were significant positive correlations between the aldosterone-to-renin ratio and aortic systolic pressure, aortic pulse pressure, and augmentation index and negative correlations with pulse pressure amplification, but none with brachial BP or pulse wave velocity. After randomization in a cross-over design to 50 mg of spironolactone or 2.5 mg of bendroflumetazide for 4 weeks with washout period of 1 month, both drugs significantly reduced brachial BP, but only spironolactone reduced (P < .001) pulse wave velocity and augmentation index, which remained significant when corrected for its greater reduction in mean BP. There were significant (P < .001) positive correlations between the ratio and decrease in aortic systolic (r = 0.78), mean (r = 0.75), diastolic BP (r = 0.66), aortic pulse pressure (r = 0.69, augmentation index (r = 0.64) and with, brachial systolic pressure (r = 0.66), brachial pulse pressure (r = 0.44, P < .05) and pulse pressure amplification (r = 0.46, P < .05). Such relationships were not found with pulse wave velocity. CONCLUSIONS: The aldosterone-to-renin ratio may have an important role in determining arterial stiffness, particularly wave reflection and aortic systolic pressure and is of predictive value for the responsiveness to spironolactone. Aldosterone antagonism has BP-independent effects on arterial stiffness.     

Aortic pulse wave velocity, elasticity, and composition in a nonhuman primate model of atherosclerosis.

Aortic pulse wave velocity was determined in Macaca fascicularis monkeys fed either atherogenic or control diets for 36 months. The foot-to-foot velocity and apparent phase velocities of the second through seventh Fourier harmonics at a given diastolic pressure in the atherosclerotic monkeys were 1.5 to 2.0 times the values for the control animals. More than 80% of the aortic intimal surface of the atherosclerotic monkeys was covered with fibrous or fatty plaque, which approximately doubled wall thickness and wall thickness to radius ratio. Angiochemical evaluations showed no difference in collagen or elastin concentration (as a fraction of lipid and mineral-free dried aorta), but the atherosclerotic aortas were 1.5 to 2.0 times that of control in collagen and elastin content (defined as the absolute quantity beneath a square centimeter of intimal surface). Total cholesterol and calcium concentrations in the atherosclerotic aortas were more than 10 times the values for the control aortas. The static circumferential distensibility of the excised atherosclerotic aortas was significantly less than control, but there was no difference in incremental (Young's) modulus of elasticity. The in vitro pressure-strain elastic modulus of the atherosclerotic aortas was more than twice that of control, which was predicted from the enhanced wave velocity. The significantly increased stiffness of the atherosclerotic arteries appeared to be due mainly to the increased wall thickness caused by the atherosclerotic plaques rather than to material changes described by Young's modulus. Extensive medial damage, however, also was present and could have had a major influence on stiffness. Atherosclerosis therefore can result in increased aortic stiffening, detectable by pulse wave velocity, even if there is no change in the overall Young's modulus of elasticity.