Aortic Wave Research Articles

ACUTE EFFECTS OF SURGICAL AORTIC VALVE REPLACEMENT ON AORTIC HEMODYNAMICS AND WAVE REFLECTIONS

Objective: Aortic hemodynamics and wave reflections are independent predictors of adverse cardiovascular events. Surgical aortic valve replacement (SAVR) is still the first choice for treatment of patients with aortic stenosis. We sought to investigate in this pilot study the effect of SAVR upon aortic vascular function and hemodynamics. Design and method: Twenty-five patients (mean age 71.0 ± 7.1 years, 11 female) with severe aortic stenosis undergoing SAVR were included. Aortic hemodynamics and wave reflections (aortic pressures, aortic augmentation index [[email protected]], augmented pressure) and subendocardial viability ratio (SEVR) were measured with Sphygmocor. Measurements were conducted prior to the surgery and at discharge. Results: There was a statistically significant decrease in aortic systolic blood pressure (SBP) (134 ± 24 vs 118 ± 17mmHg with p = 0.002, respectively). that was not apparent in peripheral SBP. Diastolic blood pressure (both peripheral and aortic) did not change significantly, while heart rate was increased after the surgery (67 ± 11 vs 88 ± 15 bpm with p < 0.001, respectively). We observed a marginally significant decrease in aortic [email protected] (29 ± 13 vs 22 ± 12% with p = 0.05, respectively) and a decrease in aortic AIx (p < 0.001, Figure) and augmented pressure (20 ± 10 vs 8 ± 7 mmHg with p < 0.001, respectively). Moreover, there was a marginally non-significant trend for an increase in SEVR (137 ± 30 vs 149 ± 35%, p = 0.095). Conclusions: Our study shows that shortly after SAVR subjects show a decrease in aortic wave reflections with a small improvement of myocardial perfusion. These findings further elucidate the short-term hemodynamic consequences of SAVR.

Aortic Pulse Pressure Does Not Adequately Index Cardiovascular Risk Factor-Related Changes in Aortic Stiffness and Forward Wave Pressure.

Through the impact of conventional risk factors on arteries, several changes in aortic function contribute to cardiovascular events. It is nevertheless uncertain whether these effects are accurately reflected by changes in central aortic pulse pressure (PPc). We, therefore, aimed to determine the extent to which relations between modifiable risk factors and aortic function translate into increases in PPc. In 1,232 black South Africans from the South West Township (SOWETO) of Johannesburg, we determined risk factors and aortic function from carotid-femoral pulse wave velocity (PWV), aortic PPc, forward wave pressures (Pf), and reflected (backward) wave pressures (Pb) (applanation tonometry and SphygmoCor software). With adjustments for alternative risk factors and distending pressure (mean arterial pressure (MAP)), diabetes mellitus (treatment or HbA1c > 6.5%, n = 151) was associated with an increased PWV (7.10 ± 2.09 vs. 6.17 ± 2.00 m/s, P < 0.0001), and Pf (26 ± 8 vs. 24 ± 8 mm Hg, P < 0.005), but neither brachial PP (46 ± 14 vs. 45 ± 13, P = 0.19), PPc (36 ± 12 vs. 35 ± 11 mm Hg, P = 0.48), nor Pb (17 ± 6 vs. 17 ± 6 mm Hg, P = 0.83). Moreover, independent of alternative risk factors and MAP, uncontrolled hypertension (office blood pressure > 140/90 mm Hg, n = 433) was associated with an increased Pf (26 ± 12 vs. 24 ± 10 mm Hg, P < 0.01), but not with changes in brachial PP (45 ± 19 vs. 44 ± 17, P = 0.75), PPc (35 ± 16 vs. 35 ± 15 mm Hg, P = 0.93), or Pb (18 ± 8 vs. 17 ± 8 mm Hg, P = 0.46). Neither brachial nor aortic PP are adequate indexes of relations between the modifiable conventional risk factors, uncontrolled hypertension or diabetes mellitus, and risk-related aortic functional changes.

Effect of organic and inorganic nitrates on cerebrovascular pulsatile power transmission in patients with heart failure and preserved ejection fraction

Objective: Increased penetration of pulsatile power to the brain has been implicated in the pathogenesis of age-related cognitive dysfunction and dementia, a common comorbidity in patients with heart failure and preserved ejection fraction (HFpEF). However, there is a lack of knowledge on the effects of organic and inorganic nitrates administration in this population on the power carried by pressure and flow waves traveling through the proximal aorta and penetrating the carotid artery into the brain microvasculature. Approach: We assessed aortic and carotid hemodynamics non-invasively in two sub-studies: (1) at baseline and after administration of 0.4 mg of sublingual nitroglycerine (an organic nitrate; n = 26); and (2) in a randomized controlled trial of placebo (PB) versus inorganic nitrate administration (beetroot-juice (BR), 12.9 mmol NO3; n = 16). Main results: Wave and hydraulic power analysis demonstrated that NTG increased total hydraulic power (from 5.68% at baseline to 8.62%, P = 0.001) and energy penetration (from 8.69% to 11.63%; P = 0.01) from the aorta to the carotid, while inorganic nitrate administration did not induce significant changes in aortic and carotid wave power (power: 5.49%PB versus 6.25%BR, P = 0.49; energy: 8.89%PB versus 10.65%BR, P = 0.27). Significance: Organic nitrates, but not inorganic nitrates, increase the amount of hydraulic energy transmitted into the carotid artery in subjects with HFpEF. These findings may have implications for the adverse effect profiles of these agents (such as the differential incidence of headaches) and for the pulsatile hemodynamic stress of the brain microvasculature in this patient population.

Development of bioimpedance sensing device for wearable monitoring of the aortic blood pressure curve

Abstract Wearable devices that monitor our vital signs have been gaining more importance with each year. Non-invasive, continuous, accurate and precise blood pressure assessment method integrated in a wearable is a multidisciplinary challenge. This work presents an electrical bioimpedance (EBI) unit for multi-frequency measurements on pulsating artery for central aortic pressure (CAP) estimation. The developed device provides low complexity in the electronics design with a frequency range between 1 kHz and 200 kHz. It is able to register the impedance of blood vessel volume change simultaneously at different locations. Experiments were carried out in vivo by using the four-electrode configuration on human thorax, axillary artery and radial artery. Preliminary results show the applicability of the proposed impedance spectroscopy system to measure blood vessel volume changes. The impedance data can be later interpreted into the aortic blood pressure wave by using a generalized transfer function. In addition, experimental test-phantom and electrode design are introduced for testing purposes of the impedance system.

Major influence of a ‘smoke and mirrors’ effect caused by wave reflection on early diastolic coronary arterial wave intensity

Coronary wave intensity analysis (WIA) is an emerging technique for assessing upstream and downstream influences on myocardial perfusion. It is thought that a dominant backward decompression wave (BDWdia ) is generated by a distal suction effect, while early-diastolic forward decompression (FDWdia ) and compression (FCWdia ) waves originate in the aorta. We show that wave reflection also makes a substantial contribution to FDWdia , FCWdia and BDWdia , as quantified by a novel method. In 18 sheep, wave reflection accounted for ∼70% of BDWdia , whereas distal suction dominated in a computer model representing a hypertensive human. Non-linear addition/subtraction of mechanistically distinct waves (e.g. wave reflection and distal suction) obfuscates the true contribution of upstream and downstream forces on measured waves (the 'smoke and mirrors' effect). The mechanisms underlying coronary WIA are more complex than previously thought and the impact of wave reflection should be considered when interpreting clinical and experimental data. Coronary arterial wave intensity analysis (WIA) is thought to provide clear insight into upstream and downstream forces on coronary flow, with a large early-diastolic surge in coronary flow accompanied by a prominent backward decompression wave (BDWdia ), as well as a forward decompression wave (FDWdia ) and forward compression wave (FCWdia ). The BDWdia is believed to arise from distal suction due to release of extravascular compression by relaxing myocardium, while FDWdia and FCWdia are thought to be transmitted from the aorta into the coronary arteries. Based on an established multi-scale computational model and high-fidelity measurements from the proximal circumflex artery (Cx) of 18 anaesthetized sheep, we present evidence that wave reflection has a major impact on each of these three waves, with a non-linear addition/subtraction of reflected waves obscuring the true influence of upstream and downstream forces through concealment and exaggeration, i.e. a 'smoke and mirrors' effect. We also describe methods, requiring additional measurement of aortic WIA, for unravelling the separate influences of wave reflection versus active upstream/downstream forces on coronary waves. Distal wave reflection accounted for ∼70% of the BDWdia in sheep, but had a lesser influence (∼25%) in the computer model representing a hypertensive human. Negative reflection of the BDWdia at the coronary-aortic junction attenuated the Cx FDWdia (by ∼40% in sheep) and augmented Cx FCWdia (∼5-fold), relative to the corresponding aortic waves. We conclude that wave reflection has a major influence on early-diastolic WIA, and thus needs to be considered when interpreting coronary WIA profiles.

Reliability of pulse waveform separation analysis responses to an orthostatic challenge.

Cardiovascular autonomic nervous system function can be assessed using an orthostatic challenge to induce arterial wave reflection. While arterial reflection is typically estimated using a central augmentation index, a superior estimation can be obtained using pulse wave separation analysis to estimate the aortic backward pressure wave (Pb). However, to be of value in a clinical or research setting, an assessment tool must be precise (reliable). Therefore, this study sought to determine the measurement precision of Pb responses to a modified tilt-table test. Twenty healthy adults (26.4 year (SD 5.2), 24.7 kg/m2 (SD 3.8), 55% female) were tested in a fasted state on three different mornings separated by a maximum of seven days. Pressure waveforms were recorded on the left arm, and aortic waveforms were generated using a generalized transfer function. Subsequently, a physiologic flow waveform was assumed to separate the aortic pressure wave into its forward and timing-independent backward (Pb) components. The criterion intra-class correlation coefficient of ≥0.75 was exceeded at baseline (0.79), following a 5-min tilt (0.75), and following a 5-min recovery from tilt (0.75). The standard error of measurement was 7%. These findings indicate that in a healthy cohort, the Pb response to an orthostatic challenge can be assessed with acceptable precision. The next step is to determine the sensitivity (validity) of this technique in identifying cardiovascular autonomic dysfunction in patient groups.

Acute effect of coffee on aortic stiffness and wave reflections in healthy individuals: differential effect according to habitual consumption

The acute effect of coffee on arterial stiffness and its dependence on habitual consumption was studied in 24 volunteers on four separate occasions during which subjects received: (a) coffee espresso, (b) decaffeinated coffee espresso, (c) caffeine alone and (d) placebo (hot water). The increase in carotid femoral pulse wave velocity (PWV), augmentation index (AIx) and augmented pressure (AP) of the aortic pressure waveform after coffee consumption was more pronounced in non-habitual (n = 13) compared to habitual drinkers (n = 11), (differences of maximal changes between groups in PWV, AIx, AP responses by 0.39 m/s, 4.5% and 1.9 mmHg, respectively, for coffee; and by 0.34 m/s, 5.3% and 2.1 mmHg, respectively, for decaffeinated coffee; all p < .05). Caffeine increased PWV, as well as AIx and AP but differences in responses between the two groups were not significant. Both caffeinated and decaffeinated coffee consumption is associated with a more potent effect on arterial stiffness in non-habitual than habitual coffee consumers, whereas caffeine induces comparable changes in both groups.

Impact of aortic rather than brachial pulsatile haemodynamics on variations in end-organ measures across the full adult blood pressure range.

To determine the extent to which the adverse effects of blood pressure (BP) are mediated by pulsatile haemodynamic changes across the normotensive as compared with the hypertensive adult brachial BP range, and whether aortic rather than brachial pulsatile changes best index these effects. In 1307 community participants, the contribution of pulsatile haemodynamics (applanation tonometry and SphygmoCor software) to variations in left ventricular mass index (LVMI) (echocardiography) (n = 920), carotid intima-media thickness (IMT) (n = 712) and estimated glomerular filtration rate (eGFR) (n = 1164) were assessed. In normotensive participants (50.5%) independent of steady-state pressure (mean arterial pressure), significant relations between aortic backward wave pressure and LVMI (partial r = 0.16, P < 0.001) or IMT (partial r = 0.15, P < 0.005) and between aortic pulse wave velocity and eGFR (partial r = -0.18, P < 0.0001) were noted, effects which in hypertensive participants were observed for LVMI and eGFR, but not IMT. With adjustments for brachial pulse pressure (PP) or SBP and confounders, aortic backward wave pressure and aortic pulse wave velocity showed independent relations with LVMI, IMT or eGFR in normotensive participants, but only with LVMI or eGFR in hypertensive participants. In normotensive participants, as compared with brachial PP or SBP, aortic backward wave pressure showed a greater slope (β-coefficient) of the relation with LVMI (0.99 ± 0.24 versus 0.47 ± 0.10 and 0.41 ± 0.09 mmHg, P < 0.05) and IMT (0.0045 ± 0.0013 versus 0.0013 ± 0.0006 and 0.0013 ± 0.0005 mmHg, P < 0.05) and a stronger association with left ventricular hypertrophy [odds ratios (95% confidence interval), 1.125 (1.059-1.195) versus 1.054 (1.027-1.082) and 1.042 (1.020-1.066), P < 0.05]. However, in hypertensive participants, only the slope of the aortic backward wave pressure-LVMI relationship was greater than that of PP-LVMI and SBP-LVMI relations. Beyond brachial BP, pulsatile haemodynamics rather than steady-state pressures account for end-organ effects more consistently across the normotensive than the hypertensive BP range. Hence, targeting aortic pulsatile haemodynamic changes may best limit BP-related cardiovascular risk within the normotensive BP range.

Gender differences of aortic wave reflection and influence of menopause on central blood pressure in patients with arterial hypertension

BackgroundEvidences suggest that central hemodynamics indexes are independent predictors of future cardiovascular events and all-cause mortality. Multiple factors have been pointed to have potential influence on central aortic function: height, heart rate, left ventricular ejection duration and blood pressure level. Data related to the influence of gender and postmenopausal status on aortic wave form reflection is scarce.MethodsIn a cross sectional study 122 hypertensive patients (52 men and 70 women) were studied. Hypertension was defined as blood pressure (BP) levels ≥140/90 mmHg or use of antihypertensive drugs. Central arterial pressure, augmentation index (AIx) and augmentation index normalized to 75bpm (Alx75) were obtained using applanation tonometry. Menopause and postmenopause history were accessed by a direct questionnaire. Post-menopause was defined as at least one year since last menstruation. Patients were paired by age, gender and menopausal status and 4 groups were compared: group 1 (young men, ≤48y), group 2 (young women, ≤48y), group 3 (older men, >48y) and group 4 (older women, >48y).ResultsHeight and weight were significantly lower in women than in men at the same age. Conversely, Alx (32.7 ± 9.8% vs. 20.1 ± 11.7%, p < 0.01), Alx75 (29.6 ± 6.7% vs. 18.3 ± 9.4%, p < 0.01) and central systolic blood pressure (136 ± 30 vs. 125 ± 23 mmHg, p = 0.03) were higher in women than men. The menopausal women had the worst indexes of aortic wave reflection.ConclusionWomen patients had both higher reflected aortic pressure wave form and central blood pressure indexes and these findings were worsened by the menopausal status.

Usefulness of Individual Shear Rate Therapy, New Treatment Option for Patients With Symptomatic Coronary Artery Disease

The aim of this study was to elucidate if patients with coronary artery disease (CAD), who fail to respond to revascularization procedures, can improve from individual shear rate therapy (ISRT). The ISRT is an adaptation of the external counterpulsation with lower individual treatment pressures based on Doppler-ultrasound measurements during counterpulsation. In contrast to the external counterpulsation therapy, the ISRT is based on the detection of the individual intra-arterial shear rate. Here we report about the first clinical trial of 31 patients with CAD who were enrolled for 30 sessions of ISRT. To determine the therapeutic effect of ISRT we measured the exercise capacity, the arterial stiffness, the aortic wave reflection, and the 24-hour blood pressure before and after 30 treatment sessions. After 6 weeks of accomplished ISRT the walking distance during the 6-minute walking test extended by 78 m (p = 0.007). The total exercise duration in the exercise stress electrocardiogram increased by 84 seconds (p = 0.012) but not the stress intensity (p = 0.086). The pulse wave velocity decreased by 1.2 m/s (p = 0.004) and demonstrated a decrease in arterial stiffness. Pulse wave analysis results demonstrated a progressive decrease in central blood pressure by 12 mmHg (p = 0.008), in pulse pressure by 9 mmHg (p = 0.005), and in augmentation pressure by 5.3 mmHg (p = 0.004). The 24-hour blood pressure decreased systolic by 15 mmHg (p <0.001) and diastolic by 8 mmHg (p = 0.033). The patients also benefited subjectively followed by New York Heart Association and Canadian Cardiovascular Society classifications. In conclusion, the ISRT is an effective treatment for patients with CAD to improve cardiac fitness, arterial stiffness, and to reduce blood pressure.

Acupuncture therapy improves vascular hemodynamics and stiffness in middle-age hypertensive individuals

Acupuncture (ACU) is becoming a more common practice among hypertensive individuals. However, the reported therapeutic effects of ACU in lowering brachial blood pressure (BP) are ambiguous. Therefore, evaluating more sensitive markers of arterial functioning might unveil the protective effects of ACU on hypertension. We examined the effects of an 8-week ACU therapy intervention on vascular hemodynamics and stiffness in middle-age hypertensive individuals. Participants were randomly assigned to either ACU (n = 23) or a control group (n = 22). Brachial and aortic BP, wave reflection (AIx) and arterial stiffness (SI) were measured before and after 8 weeks. There was a significant group x time interaction (P < 0.05) for brachial and aortic BP, AIx and SI which significantly decreased (P < 0.05) following ACU but not after control. ACU led to reductions in brachial and aortic BP, wave reflection and arterial stiffness in middle-age hypertensive individuals. ACU might be effective in the prevention and treatment of hypertension.

Preserved Cardiac Blood Supply-Workload Balance in Pediatric Patients After Aortic Arch Repair.

One of the most important problems in patients with aortic coarctation after aortic arch repair is future cardiovascular disease. We have previously reported that the enhancement of aortic pressure wave reflection in patients could be one of the causes of future cardiovascular diseases, because it results in an increase of the left ventricular workload and is disadvantageous for coronary circulation. Seventeen patients who had undergone aortic arch repair without pressure gradient in their aortic arch were enrolled. An ascending aortic pressure waveform was recorded by a pressure-sensor-mounted catheter, and a subendocardial viability ratio, which measures cardiac blood supply-workload balance, was calculated. The values were compared with those in age-matched controls. The patients' mean age was 6.8±2.8years. The mean ascending aortic systolic pressure was higher (100.4±12.9 vs. 90.2±8.9mmHg, p=0.0011) and the pulse pressure was wider (38.1±7.1 vs. 32.5±5.4mmHg, p=0.0072) in patients than in control subjects. There was no difference in the mean subendocardial viability ratio (1.01±0.25 vs. 1.01±0.24, ns), while the mean tension time index (27.4±5.6 vs. 23.0±3.3, p=0.0001) and diastolic pressure time index (28.4±11.1 vs. 23.6±8.0, p=0.0082) were higher in patients than in controls. The cardiac blood supply-workload balance was preserved in patients after aortic arch repair, despite an increase in their cardiac workload.

Reservoir pressure analysis of aortic blood pressure: an in-vivo study at five locations in humans.

The development and propagation of the aortic blood pressure wave remains poorly understood, despite its clear relevance to major organ blood flow and potential association with cardiovascular outcomes. The reservoir pressure model provides a unified description of the dual conduit and reservoir functions of the aorta. Reservoir waveform analysis resolves the aortic pressure waveform into an excess (wave related) and reservoir (compliance related) pressure. The applicability of this model to the pressure waveform as it propagates along the aorta has not been investigated in humans. We analysed invasively acquired high-fidelity aortic pressure waveforms from 40 patients undergoing clinically indicated coronary catheterization. Aortic waveforms were measured using a solid-state pressure catheter at five anatomical sites: the ascending aorta, the transverse aortic arch, the diaphragm, the level of the renal arteries, and at the aortic bifurcation. Ensemble average pressure waveforms were obtained for these sites for each patient and analysed to obtain the reservoir pressure [Pr(t)] and the excess pressure [Px(t)] at each aortic position. Systolic blood pressure increased at a rate of 2.1 mmHg per site along the aorta, whereas diastolic blood pressure was effectively constant. Maximum Pr decreased only slightly along the aorta (changing by -0.7 mmHg per site), whereas the maximum of Px increased from the proximal to distal aorta (+4.1 mmHg per site; P < 0.001). The time, relative to the start of systolic upstroke, of the occurrence of the maximum excess pressure did not vary along the aorta. Of the parameters used to derive the reservoir pressure waveform the systolic and diastolic rate constants showed divergent changes with the systolic rate constant (ks) decreasing and the diastolic rate constant (kd) increasing along the aorta. This analysis confirms the proposition that the magnitude of the calculated reservoir pressure waveform, despite known changes in aortic structure, is effectively constant throughout the aorta. A progressive increase of excess pressure accounts for the increase in pulse pressure from the proximal to distal aorta. The reservoir pressure rate constants seem to behave as arterial functional parameters. The accompanying decrease in ks and increase in kd are consistent with a progressive decrease in aortic compliance and increase in impedance. The reservoir pressure waveform therefore provides a model that might have utility in understanding the generation of central blood pressure and in specific cases might have clinical utility.

Abstract P315: Gender Differences of Aortic Wave Reflection and Influence of Menopause on Central Blood Pressure in Patients With Arterial Hypertension

Background: Evidences suggest that central hemodynamics indexes are independent predictors of future cardiovascular events and all-cause mortality. Multiple factors have been pointed to have potential influence on central aortic function: height, heart rate, left ventricular ejection duration and blood pressure level. Data related to the influence of gender and postmenopausal status on aortic wave form reflection is scarce. Methods: In a cross sectional study, 122 hypertensive patients (52 men and 70 women) were studied. Hypertension was defined as blood pressure (BP) levels ≥140/90 mmHg or use of antihypertensive drugs. Central arterial pressure, augmentation index (AIx) and augmentation index normalized to 75bpm (Alx75) were obtained using applanation tonometry. Menopause and postmenopause history were accessed by a direct questionnaire. Postmenopause was defined as at least one year since last menstruation. Patients were paired by age, gender and menopausal status and 4 groups were compared: group 1 (young men, ≤ 48y), group 2 (young women, ≤4 8y), group 3 (older men, &gt; 48y) and group 4 (older women, &gt; 48y). Results: Height and weight were significantly lower in women than in men at the same age. Conversely, Alx (32.7±9.8% vs. 20.1±11.7%, p&lt;0.01), Alx75 (29.6±6.7% vs. 18.3±9.4%, p&lt;0.01) and central systolic blood pressure (136±30 vs. 125±23 mmHg, p=0.03) were higher in women than men. The menopausal women had the worst indexes of aortic wave reflection. Conclusion: Women patients had both higher reflected aortic pressure wave form and central blood pressure indexes and these findings were worsened by the menopausal status.

PP.16.02] ASSOCIATION BETWEEN AMBULATORY BLOOD PRESSURE VALUES AND CENTRAL AORTIC PRESSURE IN LARGE POPULATION OF NORMOTENSIVE AND HYPERTENSIVE SUBJECTS

Objective: Ambulatory blood pressure monitoring (ABPM) and central aortic blood pressure (CBP) are well known predictors of cardiovascular outcome. Our aim was to examine the association of ABPM and CBP data in a large set of normotensive and hypertensive subjects and its relation with pulse wave velocity (PWV). Design and method: Study was done in a single centre and included 2108 subjects (53% female, 85% hypertensives patients, ageing 54+15years, BMI 28+5 Kg/m2) who carried out a 24 h ambulatory BP monitoring (ABPM), measurement of central BP from the aortic wave form (SphygmoCor) and carotid –femoral PWV (Complior). Results: Age, systolic blood pressure (SBP) of 24 h, daytime and nighttime, central BP, augmentation index (Aix) were correlated significantly to each other and all with PWV (R between 0.110–0.367, p < .001). Subjects were divided according to the presence of normal or abnormal values of ABPM and CBP and the correspondent PWV values were determined. Normal ABPM and CBP occurred in 16.5% (G1) and abnormal ABPM and CBP occurred in 58.9% (G4). Abnormal ABPM and normal CBP occurred in 4.1% (G2) and normal ABPM and abnormal CBP in 41.1% (G3). PWV (m/s) significantly increased (ANOVA p < 0.001) from G1 (9.1+2.1), G2 (9.3+2.5), G3 (10.3+2.7) to G4 (11.1+3.0). Sprurious hypertension (isolated systolic, ISH) occurred in 18% of subjects < 50 years. Versus systo-diastolic hypertension (HT), ISH had higher central-peripheral amplification (13+8 v 11+6, p < 0.05) but higher Aix (26+17 vs 22+14%) and PWV (10+3 v 9+2 m/s) than normotensives (both p < 0.05). Conclusions: When abnormal values of ABPM and CBP coexist target organ damage (aortic stiffness) is greater than that occurring when only one is present in the absence of the other. Isolated systolic hypertension in young and middle age associates with higher aortic stiffness and reflected waves suggesting that may not be a benign condition.

Contribution of backward and forward wave pressures to age-related increases in aortic pressure in a community sample not receiving antihypertensive therapy

Reports on the contribution of aortic forward (Pf) and backward (Pb) wave pressures to age-related increases in central aortic pulse pressure (PPc) have been confounded by the use of participants receiving antihypertensive therapy. We assessed the relative contribution of Pf and Pb to age-related increases in PPc (radial applanation tonometry and SphygmoCor software using an assumed triangular wave for wave separation analysis) in 892 community participants not receiving antihypertensive therapy. We validated our results using aortic flow waves (echocardiography) for wave separation analysis in 254 of these participants. In multivariate regression models in those aged <50 years, adjustments for both Pb and a Pf-independent measure of reflected wave function (RM = Pb/Pf), but not Pf abolished the impact of age on PPc. However, in those aged >50 years, adjustments for Pf (β-coefficient: 0.25 ± 0.06 vs. 0.74 ± 0.08; P < .0001) and Pb (0.04 ± 0.04 vs. 0.74 ± 0.08; P < .0001), but not RM markedly decreased the relationship between age and PPc. On product of coefficient mediation analysis, whether assessed in men or in women, in those participants aged <50 years, independent of several confounders and mean arterial pressure, Pb (P < .005), but not Pf contributed to age-related increases in PPc. In contrast, in those participants aged ≥50 years, independent of several confounders and mean arterial pressure, Pb (P < .005) and Pf (P < .01) contributed to age-related increases in PPc, and Pb effects were markedly diminished by adjustments for Pf (0.26 ± 0.002 vs. 0.52 ± 0.003 mm Hg per year, P < .0001 for comparison). In conclusion, independent of the effects of antihypertensive therapy, aortic backward waves contribute to age-related increases in aortic PPc across the adult lifespan, but at an older age, this effect may be attributed in part to the impact of forward on backward wave pressures.

Defects in Vascular Mechanics Due to Aging in Rats: Studies on Arterial Wave Properties from a Single Aortic Pressure Pulse.

Changes in vascular mechanics due to aging include elevated vascular impedance, diminished aorta distensibility, and an accelerated return of pulse wave reflection, which may increase the systolic workload on the heart. Classically, the accurate measurement of vascular mechanics requires the simultaneous recording of aortic pressure and flow signals. In practice, it is feasible to estimate arterial wave properties in terms of wave transit time (τw) and wave reflection index (RI) by using aortic pressure signal alone. In this study, we determined the τw and magnitudes of the forward (∣Pf∣) and backward (∣Pb∣) pressure waves in Long–Evans male rats aged 4 (n = 14), 6 (n = 17), 12 (n = 17), and 18 (n = 24) months, based on the measured aortic pressure and an assumed triangular flow (Qtri). The pulsatile pressure wave was the only signal recorded in the ascending aorta by using a high-fidelity pressure sensor. The base of the unknown Qtri was constructed using a duration, which equals to the ejection time. The timing at the peak of the triangle was derived using the fourth-order derivative of the aortic pressure waveform. In the 18-month-old rats, the ratio of τw to left ventricular ejection time (LVET) decreased, indicating a decline in the distensibility of the aorta. The increased ∣Pb∣ associated with unaltered ∣Pf∣ enhanced the RI in the older rats. The augmentation index (AI) also increased significantly with age. A significant negative correlation between the AI and τw/LVET was observed: AI = −0.7424 − 0.9026 × (τw/LVET) (r = 0.4901; P < 0.0001). By contrast, RI was positively linearly correlated with the AI as follows: AI = −0.4844 + 2.3634 × RI (r = 0.8423; P < 0.0001). Both the decreased τw/LVET and increased RI suggested that the aging process may increase the AI, thereby increasing the systolic hydraulic load on the heart. The novelty of the study is that Qtri is constructed using the measured aortic pressure wave to approximate its corresponding flow signal, and that calibration of Qtri is not essential in the analysis.

Circulating soluble receptor for advanced glycation end product: Cross-sectional associations with cardiac markers and subclinical vascular disease in older men with and without diabetes

Background and aimsThe soluble receptor for advanced glycation end products (sRAGE) has been implicated in diabetic vascular complications. We have examined the association between sRAGE and cardiac markers [NT-proBNP and cardiac troponin T (cTnT)] and subclinical vascular markers in older men with and without diabetes. MethodsWe performed a cross-sectional study of 1159 men aged 71–92 years with no history of cardiovascular disease (myocardial infarction, stroke, heart failure, coronary artery bypass graft operation or angioplasty). Prevalent diabetes included men with a doctor diagnosis of diabetes, men with fasting glucose ≥7 mmol/l or HbA1c ≥ 6.5% (N = 180). Subclinical vascular measurements included carotid intima media thickness (cIMT), arterial stiffness [pulse wave velocity (PWV)], central aortic blood pressure and arterial wave reflections [central augmentation pressure (AP) and augmentation index (AIx)]. ResultssRAGE was strongly and positively associated with renal dysfunction in men with and without diabetes. sRAGE was significantly and positively associated with NT-proBNP (but not cTnT) and AP and AIx in both groups of men after adjustment for CVD risk and metabolic risk markers, renal function and inflammation. However, no association was seen between sRAGE and central aortic blood pressure, cIMT or arterial stiffness as determined by PWV in either group. ConclusionsHigher plasma sRAGE was associated with increased NT-proBNP and markers of arterial wave reflections in men both with and without diabetes. Increased sRAGE may contribute to or be a marker of worsening cardiac dysfunction or HF. Further studies with cardiac imaging data are required to confirm this.

Arterial Stiffening With Exercise in Patients With Heart Failure and Preserved Ejection Fraction

BackgroundAortic stiffening and reduced nitric oxide (NO) availability may contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF). ObjectivesThis study compared indices of arterial stiffness at rest and during exercise in subjects with HFpEF and hypertensive control subjects to examine their relationships to cardiac hemodynamics and determine whether exertional arterial stiffening can be mitigated by inorganic nitrite. MethodsA total of 22 hypertensive control subjects and 98 HFpEF subjects underwent hemodynamic exercise testing with simultaneous expired gas analysis to measure oxygen consumption. Invasively measured radial artery pressure waveforms were converted to central aortic waveforms by transfer function to assess integrated measures of pulsatile aortic load, including arterial compliance, resistance, elastance, and wave reflection. ResultsArterial load and wave reflections in HFpEF were similar to those in control subjects at rest. During submaximal exercise, HFpEF subjects displayed reduced total arterial compliance and higher effective arterial elastance despite similar mean arterial pressures in control subjects. This was directly correlated with higher ventricular filling pressures and depressed cardiac output reserve (both p < 0.0001). With peak exercise, increased wave reflections, impaired compliance, and increased resistance and elastance were observed in subjects with HFpEF. A subset of HFpEF subjects (n = 52) received sodium nitrite or placebo therapy in a 1:1 double-blind, randomized fashion. Compared to placebo, nitrite decreased aortic wave reflections at rest and improved arterial compliance and elastance and central hemodynamics during exercise. ConclusionsAbnormal pulsatile aortic loading during exercise occurs in HFpEF independent of hypertension and is correlated with classical hemodynamic derangements that develop with stress. Inorganic nitrite mitigates arterial stiffening with exercise and improves hemodynamics, indicating that arterial stiffening with exercise is at least partially reversible. Further study is required to test effects of agents that target the NO pathway in reducing arterial stiffness in HFpEF. (Study of Exercise and Heart Function in Patients With Heart Failure and Pulmonary Vascular Disease [EXEC]; NCT01418248. Acute Effects of Inorganic Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preserved Ejection Fraction; NCT01932606. Inhaled Sodium Nitrite on Heart Failure With Preserved Ejection Fraction; NCT02262078)

Baseline values of cardiovascular and respiratory parameters predict response to acute hypoxia in young healthy men.

The majority of the available works have studied distinct hypoxic responses of respiratory and cardiovascular systems. This study examines how these systems interact while responding to hypoxia and whether baseline metrics moderate reactions to a hypoxic challenge. Central hemodynamic, aortic wave reflection, and gas exchange parameters were measured in 27 trained young men before and after 10-min normobaric isocapnic hypoxia (10 % O2). Associations were assessed by correlation and multiple regression analyses. Hypoxic changes in the parameters of pulse wave analysis such as augmentation index (-114 %, p=0.007), pulse pressure amplification (+6 %, p=0.020), time to aortic reflection wave (+21 %, p<0.001) report on the increase in arterial distensibility. Specifically, initially compliant arteries blunt the positive cardiac chronotropic response to hypoxia and facilitate the myocardial workload. The degree of blood oxygen desaturation is directly correlated with both baseline values and hypoxic responses of aortic and peripheral blood pressures. The hypoxia-induced gain in ventilation (VE), while controlling for basal VE and heart rate (HR), is inversely associated with deltaHR and deltasystolic blood pressure. The study suggests that cardiovascular and respiratory systems mutually supplement each other when responding to hypoxic challenge.