Forward Pressure Wave Research Articles

Clinical Associations of Vascular Stiffness, Microvascular Dysfunction, and Prevalent Cardiovascular Disease in a Black Cohort: The Jackson Heart Study.

BackgroundMeasures of vascular dysfunction are related to adverse cardiovascular disease (CVD) outcomes in non‐Hispanic, White populations; however, data from Black individuals are limited. We aimed to investigate the associations between novel hemodynamic measures and prevalent CVD in a sample of Black individuals.Methods and ResultsAmong older Black participants of the Jackson Heart Study, we assessed noninvasive vascular hemodynamic measures using arterial tonometry and Doppler ultrasound. We assessed 5 measures of aortic stiffness and wave reflection (carotid‐femoral pulse wave velocity, pulse wave velocity ratio, forward pressure wave amplitude, central pulse pressure, and augmentation index), and 2 measures of microvascular function (baseline and hyperemic brachial flow velocity). Using multivariable logistic regression models, we examined the relations between vascular hemodynamic measures and prevalent CVD. In models adjusted for traditional CVD risk factors, higher carotid‐femoral pulse wave velocity (odds ratio [OR],1.25; 95% CI, 1.01–1.55; P=0.04), lower augmentation index (OR, 0.84; 95% CI, 0.70–0.99; P=0.05), and lower hyperemic brachial flow velocity (OR, 0.77; 95% CI, 0.65–0.90; P=0.001) were associated with higher odds of CVD. After further adjustment for hypertension treatment, lower augmentation index (OR, 0.84; 95% CI, 0.70–0.99; P=0.04) and hyperemic brachial flow velocity (OR, 0.79; 95% CI, 0.67–0.94; P=0.006), but not carotid‐femoral pulse wave velocity (OR, 1.23; 95% CI, 0.99–1.051; P=0.06), were associated with higher odds of CVD.ConclusionsIn a sample of older Black individuals, more severe microvascular damage and aortic stiffness were associated with prevalent CVD. Further research on hemodynamic mechanisms that contribute to cardiovascular risk among older Black individuals is merited.

Distinct Contribution of Systemic Blood Flow to Hypertension in an African Population Across the Adult Lifespan

Although hypertension in groups of African ancestry is volume-dependent, the relative impact of systemic flow (stroke volume, peak aortic flow [Q]) versus vascular mechanisms (systemic vascular resistance, aortic characteristic impedance [Zc], total arterial compliance) components of arterial load has not been evaluated across the adult age range. In participants of African ancestry (n=824, age=16-99 years, 68.3% female), using central arterial pressure and aortic velocity and diameter measurements in the outflow tract, we determined the hemodynamic correlates of age-related increases in blood pressure. Strong independent positive relations between age and stroke volume or peak aortic Q were noted (P<0.0001), effects associated with ventricular end diastolic volume and aldosterone-to-renin ratios. Age-related increases in mean arterial pressure were associated with stroke volume and not systemic vascular resistance. Although age-Q relations began from early adulthood, initially an inverse association between age and aortic Zc (P<0.0001) driven by increments in aortic root diameter (P<0.0001) prevented an enhanced systolic blood pressure and pulse pressure. When Zc began to positively relate to age (P<0.0001), age-Q relations translated into increases in forward wave pressures and hence systolic blood pressure and pulse pressure. Age relations with pulse pressure were as strongly determined by Q as by Zc or total arterial compliance (0.027±0.001 versus 0.028±0.001 and 0.032±0.003 mm Hg per yearly increase in pulse pressure produced by Q, Zc, and total arterial compliance; P<0.0001). Uncontrolled hypertension (confirmed with 24-hour blood pressure) was determined more by Q, Zc, and total arterial compliance than by increases in systemic vascular resistance (P<0.0005 for comparison). In conclusion, relationships between age and systemic blood flow contribute markedly to hypertension in groups of African origins.

4392 Comparative Analysis of Vascular Hemodynamics in a Young Biracial Cohort

OBJECTIVES/GOALS: We investigated hemodynamic measures in young black and white adults below the age of 50 years to identify mechanisms that may predispose blacks to more CVE. METHODS/STUDY POPULATION: We recruited 276 young blacks and white adults in Jackson, MS (mean age: 33 ± 9 years; 70% women; 57% Black;). Participants had clinical and vascular tonometry parameters obtained. Vascular measures included carotid femoral pulse wave velocity, central and peripheral pulse pressure (CPP and PPP), characteristic impedance (Zc), augmentation index, and forward pressure wave. Race-specific characteristic means and proportions were tested using Student’s T- or Chi-square tests. After further sex stratification, significant variation in characteristics among sex within race were tested using nested ANOVA. RESULTS/ANTICIPATED RESULTS: Characteristics of the study group stratified by race were found to be similar. Vascular measures stratified by race revealed blacks to have significantly higher Zc (p = 0.03) and PPP (p = 0.03) than whites. DISCUSSION/SIGNIFICANCE OF IMPACT: In this study of vascular hemodynamics in young black and white participants we found differences in Zc and PPP. Findings suggest that differing relations between proximal aortic diameter and wall stiffness may contribute to the racial disparity in CVE in adults. This finding could offer an explanation to the beneficial effects of treatment modalities that target aortic stiffness in blacks.

Marked Arterial Functional Changes in Patients With Arterial Vascular Events Across the Early Adult Lifespan.

The age at which arteriosclerosis begins to contribute to events is uncertain. We determined, across the adult lifespan, the extent to which arteriosclerosis-related changes in arterial function occur in those with precipitous arterial events (stroke and critical limb ischemia). Approaches and Results: In 1082 black South Africans (356 with either critical limb ischemia [n=238] or stroke [n=118; 35.4% premature], and 726 age, sex, and ethnicity-matched randomly selected controls), arterial function was evaluated from applanation tonometry and velocity and diameter measurements in the outflow tract. Compared with age- and sex-matched controls, over 10-year increments in age from 20 to 60years, multivariate-adjusted (including steady-state pressures) aortic pulse wave velocity, characteristic impedance (Zc), forward wave pressures (Pf), and early systolic pulse pressure amplification were consistently altered in those with arterial events. Increases in Zc were accounted for by aortic stiffness (no differences in aortic diameter) and Pf by changes in Zc and not aortic flow or wave re-reflection. Multivariate-adjusted pulse wave velocity (7.48±0.30 versus 5.82±0.15 m/s, P<0.0001), Zc (P<0.0005), and Pf (P<0.0001) were higher and early systolic pulse pressure amplification lower (P<0.0001) in those with precipitous events than in controls. In comparison to age- and sex-matched controls, independent of risk factors, pulse wave velocity, and Zc (P<0.005 and <0.05) were more closely associated with premature events than events in older persons and Pf and early systolic pulse pressure amplification were at least as closely associated with premature events as events in older persons. Arteriosclerosis-related changes in arterial function are consistently associated with arterial events beyond risk factors from as early as 20 years of age.

Assessment of Pulsatile Load During Lower Body Aerobic Exercise in Young and Older Adults

Increased wave reflection magnitude (RM) and early return of reflected pressure waves augment pulsatile load, waste left ventricular effort, and are associated with cardiovascular events. Acute lower body aerobic exercise (AE) decreases RM and reflected wave transit time (RWTT) in young adults (YA). Due to age‐related changes in arterial structure and function, older adults (OA) experience an elevated RM and earlier RWTT at rest compared to YA. However, it is unknown how AE influences RM and RWTT in OA, and whether OA respond differently than YA.PURPOSEThe purpose of this study was to test the hypotheses that 1) RM and RWTT would be reduced during AE and 2) the reduction in RM would be attenuated in OA while the reduction in RWTT would be augmented in OA compared to YA.METHODSRadial artery pressure waveforms and aortic blood flow velocities were acquired at baseline and during light, moderate, and vigorous intensity AE on a supine cycle via applanation tonometry and echocardiography, respectively, in 20 YA (25±5 yrs) and 20 OA (66±4 yrs). Central pressure waveforms were synthesized from radial waves using a generalized transfer function. Pressure‐flow relations were analyzed offline to perform wave separation analysis. This provided a comprehensive assessment of ventricular‐arterial interactions for the determination of the relative amplitude and timing of forward (Pf) and backward (Pb) pressure waves, yielding RM (Pb/Pf) and RWTT.RESULTSAs expected, baseline RM was greater in OA (YA: 40±6 vs. OA: 49±6%, p&lt;0.05) and RWTT was shorter in OA compared to YA (YA: 191±20 vs. OA: 140±18 ms, p&lt;0.05). RM was decreased during all intensities of AE. However, the reduction in RM from baseline was different between YA and OA during light intensity AE (ΔYA: −12±8 vs. ΔOA: −17±7, p&lt;0.05), trended toward being different during moderate AE (ΔYA: −12±10 vs. ΔOA: −18±7%, p=0.06), and was not different during vigorous AE (ΔYA: −15±6 vs. ΔOA: −18±6%, p&gt;0.05). RWTT decreased during all intensities of AE. The reduction in RWTT from baseline was attenuated in OA compared to YA during light (ΔYA: −39±18 vs. ΔOA: −9±13ms, p&lt;0.05), moderate (ΔYA: −51±18 vs. ΔOA: −11±17ms, p&lt;0.05), and vigorous intensity AE (ΔYA: −57±25 vs. ΔOA: −19±17ms, p&lt;0.05).CONCLUSIONRM decreased during AE, however, differences in ΔRM between YA and OA were exercise intensity dependent. Our results suggest a greater decrease in RM in OA compared to YA during light‐moderate intensity AE. Contrary to our hypothesis, there was an attenuated reduction in RWTT in OA compared to YA during all intensities of AE, which may be due to the OA reaching the floor in RWTT.Support or Funding InformationACSM Foundation Doctoral Student Research Grant and NIH grant P20 GM 113125

Increased Aortic Characteristic Impedance Explains Relations Between Urinary Na+/K+ and Pulse or Systolic Blood Pressure.

Alterations in sodium (Na+) relative to potassium (K+) intake increase systolic blood pressure, effects in-part attributed to enhanced pulsatile loads (pulse pressure) beyond steady-state pressures (mean arterial pressure). Whether this effect is through reversible changes (increases in blood volume and hence aortic flow [Q] or wave reflection [Pb]), or potentially irreversible structural changes in the proximal aorta, is unknown. In 581 black South Africans, we determined 24-hour urinary Na+ and K+ excretion and aortic function from central aortic pressure (radial pulse wave analysis [SphygmoCor software]), velocity, and diameter measurements. Proximal aortic function was assessed from characteristic impedance (Zc). Beyond mean arterial pressure and additional confounders, urinary Na+/K+ was independently associated with Zc (P<0.005) but not peak aortic Q (P=0.30) or alternative aspects of Q or ejection volume. Although age was strongly associated with proximal aortic diameter, no independent relations between urinary Na+/K+ and aortic diameter were noted (P=0.17). Relations between urinary Na+/K+ and Zc translated into independent relations with early systolic compression wave pressures (QxZc [PQxZc]) and aortic forward wave pressures but not Pb. Moreover, neither reflected wave magnitude (P=0.92) nor aortic pulse wave velocity were independently associated with urinary Na+/K+. In product of coefficient mediation analysis, the independent relations between urinary Na+/K+ and peak aortic or brachial pulse pressure or systolic blood pressure were accounted for by Zc and PQxZc. In conclusion, abnormalities in Na+/K+ intake determine pulse pressure or systolic blood pressure beyond mean arterial pressure mainly through potentially irreversible impacts on proximal aortic impedance rather than readily modifiable increases in aortic flow (blood volume) or wave reflection.

The compound stream event of March 20-25, 2011 as measured by the STEREO B spacecraft

The interaction of interplanetary coronal mass ejections (ICME) with each other and with co-rotating interaction regions (CIR) changes their configuration, dynamics, magnetic field and plasma characteristics and can make space weather forecasting difficult. During the period of March 20–25, 2011, the Solar Terrestrial Relation Observatory (STEREO B) encountered a compound stream containing several interacting structures. Our analysis suggests that the stream consists of two ICMEs followed by an embedded ICME/CIR. The sudden appearance of the third ICME within the fast wind side of the CIR causes the proton temperature(T_{p} ) to drop suddenly to its lowest level in about 1.2 hours, from 3.89 times 10^{5} K to 1.07 times 10^{4} K (by a factor of ≈36). The fast wind which follows the CIR influences not only the third ICME’s temperature but also its proton beta (upbeta_{mathrm{p}}). In addition, the third ICME impacts the CIR through expansion and deceleration. A forward pressure wave penetrates ICME1. It’s source is either the second ICME, the merged third ICME and CIR, or it may be a remnant shock. The compression causes an increase of the T_{p} and upbeta_{mathrm{p}} of the second and part of the first ICME. Despite the signatures of four large-scale interacting structures within the compound stream, it is difficult to reconcile the in-situ sequence with other remote sensing observations of ejecta close to the Sun because of the large system of coronal expanding loops above the active region. Compound streams therefore remain difficult to interpret, and further understanding of the subject will depend on the future study of similar events.

P1528 Prognostic impact of pulmonary arterial wave reflection in heart failure

Abstract Background Pulmonary hypertension (PH) is prevalent and is associated with adverse outcomes in heart failure. The pathophysiology of PH is heterogeneous, including pre-capillary PH and combined pre- and post-capillary PH. The latter PH has been reported in experimental studies to cause wave reflection in pulmonary circulation, putting additional burden on right ventricle. This study tested the hypothesis that separating wave reflection would enhance risk stratification in heart failure. Methods This study included 152 patients with clinical stable heart failure associated with PH who were referred to echocardiography for hemodynamic assessment (age = 72 ± 13 years old, ejection fraction = 49 ± 21%). Pulmonary arterial wave reflection was characterised by separating PA pressure waveform into forward (Pf) and backward pressure (Pb) waves, based on the concept of wave intensity. PA pressure waveform was estimated from continuous Doppler tracing of tricuspid regurgitation. Flow velocity was measured by pulse Doppler at right ventricular outflow tract. Outcome data was obtained by reviewing medical charts. The endpoint was hospitalization for worsening heart failure (WHF). Results Figure A compares PA pressure waveforms (total and separated waves) obtained from 2 patients with and without WHF event. The patient with event had higher total pressure associated with late peak than the patient without event. Pb appeared later than Pf; it was markedly higher in the patient with event than the patient without event, although Pf was similar between both patients. Kaplan-Meier analysis demonstrated a significant separation of survival curves stratified by Pb (chi-square = 25.1, p &amp;lt; 0.001, figure B). During follow-up period of 1.5 ± 1.8 years, 65 patients (43%) experienced the endpoint. Sequential Cox analysis revealed that PASP remained significant after adjusted for left ventricular ejection fraction and E/e’ (hazard ratio = 1.017, p = 0.019). Pb also remained significant after the same adjustment (hazard ratio = 1.066, p = 0.003); the addition of Pb to a baseline model resulted in greater increase in predictive power than the addition of PASP (model chi-square: from 27.4 (baseline), to 37.6 (p = 0.004) for Pb, to 31.6 (p = 0.027) for PASP, figure C) Conclusions Pressure wave reflection in pulmonary artery is associated with early decompensation in heart failure. Abstract P1528 Figure.

Arterial Stiffness Gradient, Systemic Reflection Coefficient, and Pulsatile Pressure Wave Transmission in Essential Hypertension.

Arterial stiffness and impedance gradients are known to influence pressure wave propagation and macrovascular-microvascular interactions. We studied the association between the carotid-femoral arterial stiffness gradient and the systemic reflection coefficient (N=393); of this population, 246 also underwent assessment of forward/backward pressure wave propagation and microvascular pulsatile pressure transmission (MPPT). Hemodynamic parameters were measured noninvasively. From peripheral vascular resistance and characteristic impedance, we estimated the systemic reflection coefficient and MPPT on peripheral and cardiac microcirculation in age-matched, sex-matched and body mass index-matched individuals with (n=147) or without (n=98) hypertension. The arterial stiffness gradient, systemic reflection coefficient, and correlations between the arterial stiffness gradient and age or blood pressure were similar in both populations. MPPT was higher in hypertension (P<0.0001), and the subendocardial viability (Buckberg) index lower (P<0.0001). In both populations, the systemic reflection coefficient and arterial stiffness gradient were significantly associated with changes in MPPT and the subendocardial viability index. Despite similar systemic reflection coefficients, the carotid reflected pressure and MPPT were higher in hypertension. Maintaining the systemic reflection coefficient within normal ranges was, therefore, insufficient to compensate for higher carotid forward pressure waves which, in hypertension, were associated with increased aortic stiffness (P<0.0001) and higher stroke volume (P=0.0365). Independently of cardiovascular risk, hypertension-induced changes have a weighted effect on MPPT, although insufficient to compensate for increased forward pressure waves. In hypertension, elevated aortic stiffness negatively affects the arterial stiffness gradient and systemic reflection coefficient but positively affects forward pressure.

Extracorporeal Life Support Enhances the Forward Pressure Wave to Cause a Mismatch between Cardiac Oxygen Demand and Supply

Extracorporeal life support (ECLS) is a world-famous life-saving method. Until now, changes in arterial wave properties due to ECLS have remained unexamined. In this study, we determined the effects of ECLS on arterial wave properties and ventricular/arterial coupling in male Wistar rats with the measured aortic pressure alone. Ascending aortic pressure signals were measured before ECLS and at 30, 60, and 90 min after weaned off. The aortic pressure signal then calculated by fourth-order derivative to obtain an assumed triangular flow wave. The ratio of mean systolic pressure to mean diastolic pressure (Pms/Pmd), a parameter for evaluating the matching condition between myocardial oxygen demand and supply, was significantly higher after ECLS. The magnitude of forward pressure (|Pf|) augmented by ECLS prevailed over the backward pressure (|Pb|), leading to a decline in wave reflection factor. Pms/Pmd was positively linearly correlated with |Pf| (Pms/Pmd = 0.9177 + 0.0078 × |Pf|, r = 0.8677; P < 0.0001). These findings suggest that |Pf| was a predominant factor responsible for the mismatch between the myocardial oxygen demand and supply in rats after ECLS phase of experiment.

Altered Wave Reflection in Patients with Duchenne Muscular Dystrophy (DMD)

Cardiovascular complications are progressive in Duchenne Muscular Dystrophy (DMD) with cardiomyopathy/heart failure characterized as the leading cause of death in these young patients. Increased wave reflection augments pulsatile load on the heart and is known to be predictive of new onset heart failure in adults. Patients with DMD may have higher wave reflection as measured by augmentation index (AIx) but this has yet to be comprehensively studied in these patients. Given the incidence of dilated cardiomyopathy in DMD, a better understanding of the pulsatile load and ventricular‐arterial interactions could provide valuable insight into disease progression and management.PURPOSEThus, the purpose of this study was to characterize wave reflectance and pulsatile load with wave separation and wave intensity analyses in a group of patients with DMD compared to typically‐developing controls.METHODSAssessments were performed on 23 boys (10 DMD and 13 typically‐developing controls (CON)) between the ages of 8 and 18 years. A brachial artery oscillometric‐cuff device was used to record brachial artery pressure waveforms that were calibrated and synthesized to central pressure waves using a generalized transfer function. Pulse wave analysis (PWA) was performed to determine central blood pressures and AIx. Wave separation analysis was also used to determine the relative contributions of forward (Pf) and backward (Pb) pressure waves and reflection magnitude (RM=Pb/Pf).RESULTSPatients with DMD had a significantly higher augmentation index (AI) as measured by PWA (DMD: 21.2 ± 5 vs CON: 0.9 ± 2 %, p&lt;0.05) but no difference in central pulse pressure (DMD: 34 ± 3 vs CON: 30 ± 1 mmHg). There was also no difference in Pf between groups (DMD: 27 ± 2 vs CON: 26 ± 2 mmHg). However, both Pb (DMD: 14.0 ± 1 vs CON: 11.7 ± 1 mmHg, p&lt;0.05) and RM (DMD: 52.0 ± 1 vs CON: 43.5 ± 2 %, p&lt;0.05) were significantly elevated in the children with DMD.CONCLUSIONThese preliminary data suggest that patients with DMD have higher wave reflection, which may indicate increased arterial stiffness and increased pulsatile load on the heart.Support or Funding InformationGrant support: NIH P20GM113125This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Sex Differences in Aortic Hemodynamics Following Acute Exercise: Wave Separation Analysis.

The importance of sex differences in the control of blood pressure responses to exercise is controversial. It is unknown whether the potential sex differences are a result of magnitude differences in forward or reflected pressure waves. The purpose of this study was to investigate sex differences in BP following acute exercise using wave separation analysis. Sixty-eight adults (36 females) participated in the study. Aerobic capacity was measured during a graded cycle ergometry test. Central pulse wave analysis was derived from the radial pulse using applanation tonometry and separated into forward and reflected pressure waves before, and 15 min and 30 min after maximum aerobic exercise. Both males and females exhibited significantly decreased brachial SBP (p<0.05) following acute exercise. However, only males exhibited a significant decrease in forward wave pressure (p<0.05). Reflected wave pressure was decreased following exercise in both sex (p<0.05) with no sex difference. Males and females differ in blood pressure control following maximal exercise. Results show that males rely on both central and peripheral hemodynamic modifications, whereas females mostly rely on peripheral modifications. The preferential peripheral adaptations in females may provide insight regarding mechanisms of blood pressure control and the disproportionate development of hypertension in young men compared to women.

Long- and short-term air pollution exposure and measures of arterial stiffness in the Framingham Heart Study

BackgroundStudies of air pollution exposure and arterial stiffness have reported inconsistent results and large studies employing the reference standard of arterial stiffness, carotid-femoral pulse-wave velocity (CFPWV), have not been conducted. AimTo study long-term exposure to ambient fine particles (PM2.5), proximity to roadway, and short-term air pollution exposures in relation to multiple measures of arterial stiffness in the Framingham Heart Study. MethodsWe assessed central arterial stiffness using CFPWV, forward pressure wave amplitude, mean arterial pressure and augmentation index. We investigated long-and short-term air pollution exposure associations with arterial stiffness with linear regressions using long-term residential PM2.5 (2003 average from a spatiotemporal model using satellite data) and proximity to roadway in addition to short-term averages of PM2.5, black carbon, particle number, sulfate, nitrogen oxides, and ozone from stationary monitors. ResultsWe examined 5842 participants (mean age 51 ± 16, 54% women). Living closer to a major roadway was associated with higher arterial stiffness (0.11 m/s higher CFPWV [95% CI: 0.01, 0.22] living <50 m vs 400 ≤ 1000 m). We did not observe association between arterial stiffness measures and long-term PM2.5 or short-term levels of PM2.5, particle number, sulfate or ozone. Higher levels of black carbon and nitrogen oxides in the previous days were unexpectedly associated with lower arterial stiffness. ConclusionsLong-term exposure to PM2.5 was not associated with arterial stiffness but positive associations with living close to a major road may suggest that pollutant mixtures very nearby major roads, rather than PM2.5, may affect arterial stiffness. Furthermore, short-term air pollution exposures were not associated with higher arterial stiffness.

Is It the Forward Wave Pressure That Matters?

Is It the Forward Wave Pressure That Matters?

The Effect of Lower Body Aerobic Exercise on Forward and Backward Pressure Wave Amplitude

The Effect of Lower Body Aerobic Exercise on Forward and Backward Pressure Wave Amplitude

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.

Myocardial preload alters central pressure augmentation through changes in the forward wave.

Augmentation index (AIx) is often used to quantify the contribution of wave reflection to central pulse pressure. Recent studies have challenged this view by showing how contractility-induced changes in the forward pressure wave can markedly impact AIx. We hypothesized that changes in preload will also affect AIx through changes in the forward wave and studied this in two experiments. Noninvasively obtained aortic pressure was used to study central haemodynamics and wave morphology. In the first experiment, we examined the effects of head-up tilt with and without unilateral thigh cuff in 12 young healthy volunteers (mean age 26 years, 50% men). In the second experiment, we examined the effects of active standing in 31 middle-aged patients (mean age 57 years, 65% men) before and after phlebotomy. Head-up tilt or active standing significantly decreased AIx [-17.7 ± 10.4 percentage point (pp) in the young population, -4.7 ± 12.3 pp in the middle-aged population, both P < 0.05]. The fall in AIx was associated with increases in HR, diastolic pressure and systemic vascular resistance and a decrease in stroke volume (all P < 0.05). Inflation of a unilateral thigh cuff reduced the decrease in AIx by 10.7 pp, whereas 500 ml of blood loss augmented the fall in AIx by 5.9 pp (both P < 0.05). The changes in AIx were related to a preload-induced change in forward pressure wave shape (earlier peaking and steeper downstroke). Next to inotropic and chronotropic effects, preload emerges as another myocardial factor that obscures the relation between wave reflection and AIx.

Disease severity impacts the relationship of apelin with arterial function in patients with rheumatoid arthritis.

Apelin can improve arterial function by enhancing the expression of endothelial nitric oxide synthase but this effect depends markedly on endothelial integrity. We hypothesized that inflammation influences the potential impact of apelin on arterial function in rheumatoid arthritis (RA). We assessed the associations of apelin concentrations with arterial stiffness (pulse wave velocity), wave reflection (augmentation index, reflected wave pressure, and reflection magnitude), and pressure pulsatility (central systolic pressure (CSP), central pulse pressure (CPP), peripheral pulse pressure (PPP), pulse pressure amplification (PPamp), and forward wave pressure (Pf)) among 170 RA patients without cardiovascular disease. In multivariable regression models, apelin concentrations were not independently associated with arterial function measures (p ≥ 0.15) in all patients. Inflammation markers were not consistently associated with apelin levels but joint deformity counts, Disease Activity Score in 28 joints (DAS28), and erythrocyte sedimentation rate (ESR) impacted apelin-pressure pulsatility relations (interaction p ≤ 0.05). In stratified analysis, apelin was associated with CSP (partial r = - 0.33, p = 0.01), CPP (partial r = - 0.26, p = 0.04), PPamp (partial r = 0.27, p = 0.03), and Pf (partial r = - 0.33, p = 0.01) in patients without but not with joint deformities; apelin was related to CSP (partial r = - 0.24, p = 0.05) in those with a DAS28 joint < 2.8 (median value) (partial r = - 0.24, p = 0.05) but not ≥ 2.8, and to CSP (partial r = - 0.36, p = 0.003) in those with an erythrocyte sedimentation rate < 13mm/h (median value) but not ≥ 13mm/h. Apelin is associated with reduced pressure pulsatility in RA patients without but not with a high inflammatory burden. A loss of apelin protective effects on arterial function may contribute to the link between RA severity and cardiovascular risk.

Metabolic Predictors of Change in Vascular Function: Prospective Associations From a Community-Based Cohort.

Vascular function varies with age because of physiological and pathological factors. We examined relations of longitudinal change in vascular function with change in metabolic traits. Longitudinal changes in vascular function and metabolic traits were examined in 5779 participants (mean age, 49.8±14.5 years; 54% women) who attended sequential examinations of the Framingham Offspring, Third Generation, and Omni-1 and Omni-2 cohorts. Multivariable regression analysis related changes in vascular measures (dependent variables), including carotid-femoral pulse wave velocity (CFPWV), forward pressure wave amplitude, characteristic impedance, central pulse pressure, and mean arterial pressure (MAP), with change in body mass index, fasting total:high-density lipoprotein cholesterol ratio, serum triglycerides, and blood glucose. Analyses accounted for baseline value of each vascular and metabolic measure, MAP change, and multiple comparisons. On follow-up (mean, 5.9±0.6 years), aortic stiffness (CFPWV, 0.2±1.6 m/s), and pressure pulsatility (forward pressure wave, 1.2±12.4 mm Hg; characteristic impedance, 23±73 dyne×sec/cm5; central pulse pressure, 2.6±14.7 mm Hg; all P<0.0001) increased, whereas MAP fell (-3±10 mm Hg; P<0.0001). Worsening of each metabolic trait was associated with increases in CFPWV and MAP (P<0.0001 for all associations) and an increase in MAP was associated with an increase in CFPWV. Overall, worsening metabolic traits were associated with worsening aortic stiffness and MAP. Opposite net change in aortic stiffness and MAP suggests that factors other than distending pressure contributed to the observed increase in aortic stiffness. Change in metabolic traits explained a greater proportion of the change in CFPWV and MAP than baseline metabolic values.

PP.03.08] THE HAEMODYNAMIC MECHANISM OF THE AGE-RELATED INCREASE IN PULSE PRESSURE IN WOMEN

Objective: An age-related increase in pulse pressure is the major cause of morbidity and mortality in the ageing population and is more marked in women than in men. The haemodynamic determinants of increased pulse pressure remain incompletely understood. The aim of this study is was to examine the contribution of ventricular dynamics, large artery stiffness, and pressure wave reflection to central pulse pressure. Design and method: A total of 2162 women aged 18 to 91 years (mean ± SD, age 57 ± 13 years) from the Twins UK cohort were studied. Non-invasive aortic flow velocity and blood pressure were measured by Doppler sonography and carotid tonometry system respectively. Carotid-femoral PWV was measured using the SphygmoCor system. Reflection index (the ratio of the peak of the backward pressure wave over that of the forward pressure wave) was computed from the pressure and flow waves. Results: Central pulse pressure increased with age, from 29.5 ± 0.46 mmHg for those aged below 40 years to 52.6 ± 0.85 mmHg for those over 70 years (means ± SE, P < 0.001). PWV increased approximately 13.2% per decade. Maximum flow velocity tended to increase (from 1.11 ± 0.01 to 1.16 ± 0.01 m/s over the 5 decades, P < 0.01), and ejection volume at the time of peak pulse pressure increased from 63.3 ± 1.41 to 72.3 ± 1.92 ml (P < 0.001) but reflection index decreased from 0.28 ± 0.01 to 0.25 ± 0.01 (P < 0.001). Conclusions: These results suggest that the age-related increase in central pulse pressure is driven mainly by an increase in arterial stiffening and increased ventricular ejection.