Wave Reflection Index Research Articles

A6509 The Obesity Paradox

Objectives: A clue to the “Obesity Paradox” is that patients at the upper extreme of body mass and blood pressure often have youthful arterial pressure waveforms that show optimally-timed wave reflection in the proximal aorta and left ventricle. Central obesity may compress the aorta and conduit arteries in the abdomen, thus decreasing aortic stiffness and delaying return of wave reflection to the heart. Methods: Central aortic pressure waves and indices of wave reflection on the aortic pressure wave were generated from radial tonometry and calibrated to brachial cuff pressures (SphygmoCor, AtCor Medical, Sydney, Australia). Data recorded from 101 patients attending a cardiovascular outpatient clinic at Ruijin Hospital North, Shanghai (table). Subjects were divided into 3 groups according to their Body Mass Index (BMI < = 24 normal, 24–28 overweight, > = 28 obese; for Chinese population). Results: Brachial and aortic pressure values including Systolic (SP), Diastolic (DP), Pulse Pressure (PP), and carotid-femoral pulse wave velocity did not differ significantly between normal and overweight/obese group. Aortic SP and aortic PP were lower for the overweight/obese group than normal, while aortic DP was higher. Despite no difference in standard pressure measurement, there were significant changes (p < 0.05) in indices of aortic pressure wave reflection between normal and overweight/obese groups. Augmented Pressure, Augmentation Index, and pressure amplification (calculated as aortic SP ÷ brachial SP) decreased progressively as BMI increased. Conclusion: The Obesity Paradox, presently unexplained, is likely due to reduced central pressure wave reflection in overweight and obese persons. This study is continuing; the results may explain the obesity paradox in terms of arterial wave travel and reflection.

Forward and Backward Aortic Components and Reflection Indexes in Children and Adolescents: Determinants and Role in High Pressure States.

High blood pressure states (HBP) would differ in wave components and reflections indexes, which could associate clinical and prognostic implications. The study aims: 1) to characterize the association of aortic wave components and reflection parameters (backward [Pb], forward [Pf], Pb/Pf ratio and augmentation index [AIx]) with demographic, anthropometric, hemodynamic and arterial parameters in healthy children and adolescents; 2) to generate multivariate prediction models for the associations, to contribute to understand the main determinants of Pf, Pb, Pb/Pf and AIx; 3) to identify if differences in wave reflection indexes observed in HBP could be explained by differences in the analyzed parameters. Healthy children and adolescents (n=816, females: 386; Age: 3-20 years) were studied. central aortic pressure and wave components (Pb, Pf, Pb/Pf and AIx determination with SphygmoCor [SCOR] and Mobil-o-Graph [MOG]); anthropometric assessment; regional arterial stiffness (carotid-femoral, carotid-radial pulse wave velocity [PWV] and PWV ratio); carotid intima-media thickness; carotid and femoral distensbility; cardiac output; systemic vascular resistances (SVR). Simple and multiple regression models were constructed to determine aortic wave parameters; the main explanatory variables. Normotensive and HBP groups were compared. Differences in wave reflection indexes were analyzed before and after controlling for explanatory variables. Equivalences between SphygmoCor and Mobil-O-Graph data were assessed (correlation and Bland-Altman analyses). There were systematic and proportional differences between the data obtained with SphygmoCor and Mobil-O-Graph devices. Heart rate (HR), peripheral pulse pressure, height and weight were the variables that isolated (simple associations) or combined (multiple associations), showed the major capability to explain interindividual differences in Pf, Pb, Pb/Pf and AIx. Arterial stiffness also showed explanatory capacity, being the carotid the artery with the major contribution. HBP associated higher Pf, Pb, AIx and lower Pb/Pf ratio. Those findings were observed together with higher weight, arterial stiffness and HR. After adjusting for anthropometric characteristics, HR, cardiac output and SVR, the HBP group showed greater Pf and Pb. Then, Pf and Pb characteristics associated with HBP would not be explained by anthropometric or hemodynamic factors. Evaluating wave components and reflection parameters could contribute to improve the comprehension and management of HBP states.

Increased aortic wave reflection contributes to higher systolic blood pressure in adolescents born preterm.

To evaluate the wave reflection characteristics in the aortic arch and common carotid artery of ex-preterm adolescents and assess their relationship to central blood pressure in a cohort followed prospectively since birth. Central blood pressures, pulse wave velocity, augmentation index, microvascular reactive hyperemia, arterial distensibility, compliance and stiffness index, and also aortic and carotid wave intensity were measured in 18-year-olds born extremely preterm at below 28 weeks' gestation (n = 76) and term-born controls (n = 42). Compared with controls, ex-preterm adolescents had higher central systolic (111 ± 11 vs. 105 ± 10 mmHg; P < 0.001) and diastolic blood pressures (73 ± 7 vs. 67 ± 7 mmHg; P < 0.001). Although conventional measures of arterial function and biomechanics such as pulse wave velocity and augmentation index were no different between groups, wave intensity analysis revealed elevated backward compression wave area (-0.39 ± 0.21 vs. -0.29 ± 0.17 W/m/s × 10; P = 0.03), backward compression wave pressure change (9.0 ± 3.5 vs. 6.6 ± 2.5 mmHg; P = 0.001) and reflection index (0.44 ± 0.15 vs. 0.32 ± 0.08; P < 0.001) in the aorta of ex-preterm adolescents compared with controls. These changes were less pronounced in the carotid artery. On multivariable analysis, forward and backward compression wave areas were the only biomechanical variables associated with central systolic pressure. Ex-preterm adolescents demonstrate elevated wave reflection indices in the aortic arch, which correlate with central systolic pressure. Wave intensity analysis may provide a sensitive novel marker of evolving vascular dysfunction in ex-preterm survivors.

CHANGING ARTERIAL STIFFNESS GRADIENT BY NITROGLYCERIN AND ITS RELATION TO CENTRAL PRESSURE WAVE ANALYSIS

Objective: We have previously shown that administration of nitroglycerin (NTG) reduced femoral pulse wave velocity without affecting aortic stiffness, which results in an increase in aortic-femoral (AF) PWV ratio (a measure of arterial stiffness gradient). In this study, we examined the impact of post-NTG changes of AF-PWV ratio on wave reflection using wave separation analysis. Design and method: In 20 treated hypertensive subjects with or without kidney disease, carotid-femoral (CFPWV) (aortic) and femoral-distal (FDPWV) were determined as respective measures of aortic and femoral stiffness. Aortic-femoral PWV ratio (AF PWV ratio) was used as a measure of arterial stiffness gradient. Aortic pressure waveform was obtained through generalized transfer function applied to the radial artery pressure waveform after calibration with systolic and diastolic blood pressures (SBP and DBP). Using GEE, we examined the extent of association between changes in aortic-femoral (AF) PWV ratio, and augmentation index (Aix), pressure forward (Pf), pressure backward (Pb) and reflection magnitude (RM). Results: After administration of NTG, SBP and mean BP (area under the curve) decreased (114 ± 19 vs 107 ± 15 and 89 ± 11 vs 85 ± 9 mm Hg, p < 0.01) without changes in DBP. The CFPWV remained unchanged (12.2 ± 2.2 vs 12.3 ± 2.9 m/s), whereas FDPWV decreased (8.7 ± 1.5 vs 7.2 ± 1.1 m/s, p < 0.001). Accordingly, AF PWV ratio increased (1.42 ± 0.25 vs 1.73 ± 0.41). Aix declined as expected (20.1 ± 11.9 vs 7.7 ± 12.8 %, p < 0.001). There was a slight but not statistically significant reduction in Pf (27.7 ± 10.7 vs 25.4 ± 7.9 mmHg, p = 0.068), while Pb decreased (17.2 ± 8.1 vs 13.4 ± 6.6 mmHg), resulting in a reduction in RM from 0.61 ± 0.10 to 0.51 ± 0.13 (p < 0.001). There was a significant association between the extent of changes in AF PWV ratio and changes in Aix (β = −15, p < 0.001), Pb (β = −9.5, p < 0.001) and RM (β = −0.21, p < 0.001). Conclusions: This study shows that alteration of arterial stiffness gradient with nitroglycerin is associated with changes in arterial wave reflection indices.

Effects of Acute Antioxidant Cocktail Combined with a High Sodium Meal on Arterial Stiffness and Wave Reflection

Vascular dysfunction is a non‐traditional risk factor for cardiovascular disease (CVD). Further, increased arterial stiffness and wave reflection are considered independent predictors of CVD. High dietary sodium intake has been shown to impair vascular function through an increase in oxidative stress. Therefore, the objective of this study was to investigate the acute effects of an antioxidant cocktail combined with a high sodium meal on measures of arterial stiffness and wave reflection. Twenty‐six young healthy adults (11M, 15F; 22.8 ± 0.5 years; BMI 23.1 ± 0.4 kg/m2; systolic blood pressure 116 ± 2 mmHg, diastolic blood pressure 70 ± 1 mmHg) completed two trials separated by at least 48 hours. All subjects were fasted for 4 hours and women were tested during the early follicular phase of the menstrual cycle. Carotid‐femoral pulse wave velocity (PWV) and the synthesis of a central aortic pressure waveform (by radial artery applanation tonometry and generalized transfer function) were performed. Aortic augmentation index (AIx), an index of wave reflection, was calculated from the aortic pressure waveform. Participants ingested either two doses of an antioxidant cocktail (AO; each capsule contained 500 mg vitamin C, 300 IU vitamin E, and 300 mg alpha‐lipoic acid) or a placebo (PLA; cellulose). Dose one was consumed 30 min prior and dose two was consumed with the meal. The high sodium meal (1500 mg Na+) consisted of tomato soup with added table salt. Mean arterial pressure (MAP), AIx, and PWV were measured at baseline (BSL) and 30, 60, 90, and 120 minutes after meal consumption. Baseline measurements of AIx did not differ between the two visits (P &gt; 0.05) but decreased over time in both trials (AO: BSL: 8.0 ± 1.4%, 60 min: 2.0 ± 1.3%; PLA: BSL: 6.2 ± 1.4%, 60min: −0.8 ± 1.9%; P‐time effect &lt; 0.001). PWV was not different at baseline (AO: 5.3 ± 0.1 m/s, PLA: 5.2 ± 0.1 m/s; P &gt; 0.05) nor did it change during the two trials (P &gt; 0.05). Similarly, MAP was not different at baseline (P &gt; 0.05) and it remained unchanged during the two trials (P &gt; 0.05). In conclusion, acute consumption of a high sodium meal did not impair arterial stiffness or wave reflection in young, healthy adults.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Acute Effects of Exercise Mode on Arterial Stiffness and Wave Reflection in Healthy Young Adults: A Systematic Review and Meta-Analysis.

Background: This systematic review and meta-analysis quantified the effect of acute exercise mode on arterial stiffness and wave reflection measures including carotid-femoral pulse wave velocity (cf-PWV), augmentation index (AIx), and heart rate corrected AIx (AIx75).Methods: Using standardized terms, database searches from inception until 2017 identified 45 studies. Eligible studies included acute aerobic and/or resistance exercise in healthy adults, pre- and post-intervention measurements or change values, and described their study design. Data from included studies were analyzed and reported in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA guidelines. Meta-analytical data were reported via forest plots using absolute differences with 95% confidence intervals with the random effects model accounting for between-study heterogeneity. Reporting bias was assessed via funnel plots and, individual studies were evaluated for bias using the Cochrane Collaboration's tool for assessing risk of bias. A modified PEDro Scale was applied to appraise methodological concerns inherent to included studies.Results: Acute aerobic exercise failed to change cf-PWV (mean difference: 0.00 ms−1 [95% confidence interval: −0.11, 0.11], p = 0.96), significantly reduced AIx (−4.54% [−7.05, −2.04], p = 0.0004) and significantly increased AIx75 (3.58% [0.56, 6.61], p = 0.02). Contrastingly, acute resistance exercise significantly increased cf-PWV (0.42 ms−1 [0.17, 0.66], p = 0.0008), did not change AIx (1.63% [−3.83, 7.09], p = 0.56), and significantly increased AIx75 (15.02% [8.71, 21.33], p < 0.00001). Significant heterogeneity was evident within all comparisons except cf-PWV following resistance exercise, and several methodological concerns including low applicability of exercise protocols and lack of control intervention were identified.Conclusions: Distinct arterial stiffness and wave reflection responses were identified following acute exercise with overall increases in both cf-PWV and AIx75 following resistance exercise potentially arising fromcardiovascular and non-cardiovascular factors that likely differ from those following aerobic exercise. Future studies should address identified methodological limitations to enhance interpretation and applicability of arterial stiffness and wave reflection indices to exercise and health.

Early sex differences in central arterial wave reflection are mediated by different timing of forward and reflected pressure waves.

Non-invasive assessment of central arterial pulse wave augmentation has been proved to be useful in predicting cardiovascular adverse events. Previous studies have shown that pre-pubescent girls had greater central augmentation pressure compared with height-matched boys. This study sought to investigate which factors contribute to the body height-independent sexual differences in central arterial wave reflection observed in childhood. This cross-sectional study involved 819 children and adolescents (6-18years of age) of both sexes. Phenotypes of central haemodynamic were obtained by radial applanation tonometry. Heart rate corrected augmentation index (Aix@75) was greater in girls compared with boys (2.9±10.7 vs -1.7±12.9%, P<.001) as well as the central augmented pressure (cAP; 1.3±3.3 vs 0.1±3.8mmHg, P<.001), even adjusting for age, heart rate and body height. Left ventricular ejection duration (ED) was longer (320±26 vs 314±24ms, P=.004) and time to inflection point (Tr) was shorter in girls (139±14 vs 141±21ms, P=.014). The reduction of Aix@75 with increasing body height was steeper in boys (-0.499±0.030 vs -0.428±0.036%/cm, P<.001) as well as the reduction of cAP with increasing body height (-0.108±0.010 vs -0.066±0.013mmHg/cm, P<.001). Body height-independent sexual differences observed in the pulse wave reflection indices from early adolescence were mediated by different timing of forward and reflected pressure waves.

Mechanism underlying the heart rate dependency of wave reflection in the aorta: a numerical simulation.

Arterial wave reflection has been shown to have a significant dependence on heart rate (HR). However, the underlying mechanisms inherent in the HR dependency of wave reflection have not been well established. This study aimed to investigate the potential mechanisms and role of arterial viscoelasticity using a 55-segment transmission line model of the human arterial tree combined with a fractional viscoelastic model. At varying degrees of viscoelasticity modeled as fractional order parameter α, reflection magnitude (RM), reflection index (RI), augmentation index (AIx), and a proposed novel normalized reflection coefficient (Γnorm) were estimated at different HRs from 60 to 100 beats/min with a constant mean flow of 70 ml/s. RM, RI, AIx, and Γnorm at the ascending aorta decreased linearly with increasing HR at all degrees of viscoelasticity. The means ± SD of the HR dependencies of RM, RI, AIx, and Γnorm were -0.042 ± 0.004, -0.018 ± 0.001, -1.93 ± 0.55%, and -0.037 ± 0.002 per 10 beats/min, respectively. There was a significant and nonlinear reduction in RM, RI, and Γnorm with increasing α at all HRs. In addition, HR and α have a more pronounced effect on wave reflection at the aorta than at peripheral arteries. The potential mechanism of the HR dependency of wave reflection was explained by the inverse dependency of the reflection coefficient on frequency, with the harmonics of the pulse waveform moving toward higher frequencies with increasing HR. This HR dependency can be modulated by arterial viscoelasticity. NEW & NOTEWORTHY This in silico study addressed the underlying mechanisms of how heart rate influences arterial wave reflection based on a transmission line model and elucidated the role of arterial viscoelasticity in the dependency of arterial wave reflection on heart rate. This study provides insights into wave reflection as a frequency-dependent phenomenon and demonstrates the validity of using reflection magnitude and reflection index as wave reflection indexes.

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.

Reliability of pulse waveform separation analysis: effects of posture and fasting.

Oscillometric pulse wave analysis devices enable, with relative simplicity and objectivity, the measurement of central hemodynamic parameters. The important parameters are central blood pressures and indices of arterial wave reflection, including wave separation analysis (backward pressure component Pb and reflection magnitude). This study sought to determine whether the measurement precision (between-day reliability) of Pb and reflection magnitude: exceeds the criterion for acceptable reliability; and is affected by posture (supine, seated) and fasting state. Twenty healthy adults (50% female, 27.9 years, 24.2 kg/m) were tested on six different mornings: 3 days fasted, 3 days nonfasted condition. On each occasion, participants were tested in supine and seated postures. Oscillometric pressure waveforms were recorded on the left upper arm. The criterion intra-class correlation coefficient value of 0.75 was exceeded for Pb (0.76) and reflection magnitude (0.77) when participants were assessed under the combined supine-fasted condition. The intra-class correlation coefficient was lowest for Pb in seated-nonfasted condition (0.57), and lowest for reflection magnitude in the seated-fasted condition (0.56). For Pb, the smallest detectible change that must be exceeded in order for a significant change to occur in an individual was 2.5 mmHg, and for reflection magnitude, the smallest detectable change was 8.5%. Assessments of Pb and reflection magnitude are as follows: exceed the criterion for acceptable reliability; and are most reliable when participants are fasted in a supine position. The demonstrated reliability suggests sufficient precision to detect clinically meaningful changes in reflection magnitude and Pb.

PS 14-09 CENTRAL PULSATILE HEMODYNAMICS IS ASSOCIATED WITH COGNITIVE FUNCTIONS IN HOSPITALIZED PATIENTS WITH ACUTE HEART FAILURE

Objective: Acute heart failure (AHF) is commonly precipitated by a perturbation of the central pulsatile hemodynamics, which may compromise cognitive functions due to enhanced cerebral pressure or flow pulsatility. The present study aimed to investigate the associations between central pulsatile hemodynamics and cognitive functions in hospitalized patients with AHF. Design and Method: Patients with a reduced left ventricular ejection fraction (<45%) hospitalized for AHF were enrolled. Central pulsatile hemodynamics including carotid-femoral pulse wave velocity (cf-PWV) and indices of wave reflections, including central pulse pressure (PPc), carotid augmentation index (cAI) and amplitude of reflected pressure wave (Pb), were measured. In addition, Mini-mental state examination (MMSE) and a neuropsychological test battery (NTB) were performed, including Wechsler Memory Scale visual immediate, Wechsler Memory Scale verbal immediate, Rey Auditory Verbal Learning Test (RAVLT), Wechsler Memory Digit Span, Controlled Word Association Test (COWAT) and Category Fluency Test (CFT). MMSE ≤27 or NTB total score ≤200 were defined as impaired cognitive functions in this study. Results: A total of 32 subjects (49.7 ± 11 years, 84.4% men) with a mean education of 13 ± 3 years were enrolled. Mean MMSE and total NTB score were 27.6 ± 2.2 and 177 ± 39, respectively. cf-PWV was negatively correlated with CFT (r = −0.390, P = 0.033). In contrast, cAI was negatively correlated with RAVLT, immediate and delayed memory and executive function (all P < 0.05). Twenty-five patients with impaired cognitive functions had significantly higher PPc, cAI and Pb, but similar cf-PWV, as compared to those without. After controlling for age, PPc remained predictive of impaired cognitive functions [Odds ratio and 95% confidence interval per-1 mmHg: 1.25 (1.04–1.52)]. Conclusions: Our study suggests that central pulsatile hemodynamics, excessive wave reflections in particular, is associated with impaired cognitive functions in patients hospitalized due to AHF. This finding may support a cardiac-cerebral interaction in patients with AHF.

Effects of pacing modality on noninvasive assessment of heart rate dependency of indices of large artery function.

Studies investigating the relationship between heart rate (HR) and arterial stiffness or wave reflections have commonly induced HR changes through in situ cardiac pacing. Although pacing produces consistent HR changes, hemodynamics can be different with different pacing modalities. Whether the differences affect the HR relationship with arterial stiffness or wave reflections is unknown. In the present study, 48 subjects [mean age, 78 ± 10 (SD), 9 women] with in situ cardiac pacemakers were paced at 60, 70, 80, 90, and 100 beats per min under atrial, atrioventricular, or ventricular pacing. At each paced HR, brachial cuff-based pulse wave analysis was used to determine central hemodynamic parameters, including ejection duration (ED) and augmentation index (AIx). Wave separation analysis was used to determine wave reflection magnitude (RM) and reflection index (RI). Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV). Pacing modality was found to have significant effects on the HR relationship with ED (P = 0.01), central aortic pulse pressure (P = 0.01), augmentation pressure (P < 0.0001), and magnitudes of both forward and reflected waves (P = 0.05 and P = 0.003, respectively), but not cfPWV (P = 0.57) or AIx (P = 0.38). However, at a fixed HR, significant differences in pulse pressure amplification (P < 0.001), AIx (P < 0.0001), RM (P = 0.03), and RI (P = 0.03) were observed with different pacing modalities. These results demonstrate that although the HR relationships with arterial stiffness and systolic loading as measured by cfPWV and AIx were unaffected by pacing modality, it should still be taken into account for studies in which mixed pacing modalities are present, in particular, for wave reflection studies.

Effects of acute dietary nitrate supplementation on aortic blood pressure and aortic augmentation index in young and older adults

PurposeAging is associated with elevated blood pressure (peripheral and aortic; BP) and aortic augmentation index (AIx) which may contribute to aortic BP. Although inorganic nitrate consumption reduces peripheral BP in both young and older adults, the effects of nitrate consumption on aortic BP and wave reflection in young and older adults is unknown. Therefore, we sought to characterize the effects of nitrate consumption on aortic BP and AIx in young and older adults. MethodsNoninvasive aortic pressure waveforms were synthesized from high-fidelity radial pressure waveforms via applanation tonometry before and following (60, 90, 120, 150, and 180 min) consumption of a nitrate-rich beetroot juice in 26 healthy adults (young: 25 ± 4 years, n = 14; older: 64 ± 5 years, n = 12). Aortic BP and indices of aortic wave reflection (AIx and AIx normalized for heart rate; AIx@75bpm) were calculated from the generated aortic pressure waveform. ResultsNitrate consumption increased plasma nitrite in both groups 60–180 min following beetroot consumption (P < 0.001). Nitrate consumption reduced peripheral and aortic BP in both young and older adults (P < 0.05), with the change being similar between age groups. Conversely, indices of aortic wave reflection were reduced only in young adults following nitrate consumption (range of change from baseline over time: AIx@75bpm, −4.3 to −8.8%, P < 0.05), whereas aortic AIx remained unchanged in the older adults. ConclusionsTaken together, our results suggest that acute dietary nitrate supplementation reduces peripheral and aortic BP similarly in young and older adults despite differential effects on aortic AIx between age groups.

Ambulatory (24 h) blood pressure and arterial stiffness measurement in Marfan syndrome patients: a case control feasibility and pilot study.

BackgroundThe aim of this work is the investigation of measures of ambulatory brachial and aortic blood pressure and indices of arterial stiffness and aortic wave reflection in Marfan patients.MethodsA case-control study was conducted including patients with diagnosed Marfan syndrome following Ghent2 nosology and healthy controls matched for sex, age and daytime brachial systolic blood pressure. For each subject a 24 h ambulatory blood pressure and 24 h pulse wave analysis measurement was performed.ResultsAll parameters showed a circadian pattern whereby pressure dipping was more pronounced in Marfan patients. During daytime only Marfan patients with aortic root surgery showed increased pulse wave velocity. In contrast, various nighttime measurements, wave reflection determinants and circadian patterns showed a significant difference.ConclusionsThe findings of our study provide evidence that ambulatory measurement of arterial stiffness parameters is feasible and that these determinants are significantly different in Marfan syndrome patients compared to controls in particular at nighttime. Further investigation is therefore indicated.

Effect of acute nitrate ingestion on central hemodynamic load in hypoxia

Acute hypoxia results in local vasodilation that may temporarily unload the left ventricle (LV) through nitric oxide (NO)-mediated mechanisms. Whether increasing NO levels augments LV unloading and improves ventricular-vascular coupling in hypoxia remains unknown. PurposeInvestigate the effect of acute nitrate ingestion on central hemodynamic load in hypoxia. Methods20 Healthy men (23 ± 3 yrs, BMI 24.6 ± 2.8 kg m−2) consumed 70 mL of either a) 0.45 g nitrate (NIT) or b) an inert placebo (PLA) prior to 105 min of normobaric hypoxia (11.6 ± 0.1%) in this randomized, double-blind, crossover-design study. Wave reflection index (RIX; ratio of forward to reflected wave pressure), augmentation index (AIX75) and pulse wave velocity were calculated as measures of wave reflection magnitude and aortic stiffness, respectively, from the aortic blood pressure (BP) waveform. LV wasted pressure effort (WPE) was calculated as an index of LV work due to wave reflections. Subendocardial viability ratio (SEVR) was assessed a measure of myocardial O2 supply/demand ratio. ResultsAortic diastolic BP decreased in hypoxia compared to normoxia (p < 0.05). Aortic RIX, AIX75, and LV WPE significantly decreased in hypoxia compared to normoxia (p < 0.05). Aortic systolic BP, SEVR, and PWV were unaffected by hypoxia (p > 0.05). Compared to placebo, nitrate ingestion did not significantly alter central hemodynamics in hypoxia (p > 0.05). ConclusionsAcute hypoxic exposure unloads the LV (WPE, AIX75, and RIX) without disturbing myocardial O2 supply-demand ratio (SEVR). Reductions in LV work with hypoxia are likely due to reductions in pressure from wave reflections as hypoxia had negligible effects on aortic stiffness. Nitrate ingestion did not affect the central hemodynamic response to acute systemic hypoxia.

Impact of age on aortic wave reflection responses to metaboreflex activation and its relationship with leg lean mass in post-menopausal women

Wave reflection (augmentation pressure [AP] and index [AIx]) is greater in older women than men. Resting AP is a better wave reflection index than AIx in older adults. The negative relationship between wave reflection and lean mass (LM) has been inconsistent. We investigated the impact of age and LM on aortic hemodynamic responses to metaboreflex activation in post-menopausal women. Post-menopausal women, younger and older (n=20 per group) than 60years, performed 2-min isometric handgrip at 30% of maximal force followed by 3-min post-exercise muscle ischemia (PEMI). We measured carotid–femoral pulse wave velocity (cfPWV) and femoral-ankle PWV (faPWV) at rest, and aortic systolic blood pressure (aSBP), pulse pressure (aPP), AP, AIx, and AIx-adjusted for heart rate (AIx@75) at rest and during PEMI using tonometry. Arm and leg LM were measured by DEXA. Resting cfPWV, aSBP, and aPP were higher, while AIx@75 and leg LM were lower in older than younger women. aSBP and aPP increased similarly during PEMI in both groups. Increases in AP (P<0.05), AIx (P<0.05), and AIx@75 (P<0.01) during PEMI were greater in older than younger women. From these responses, only AP during PEMI was correlated (P<0.05) positively with aSBP and aPP responses, and negatively with leg LM. Resting faPWV, but not cfPWV, was correlated (P<0.01) with AP, aSBP, and aPP during PEMI. Therefore, PEMI induces greater wave reflection responses in older than younger post-menopausal women. Our findings suggest that the increased AP response to PEMI is related to leg arterial stiffness and muscle loss in older women.

Subclinical Vascular Dysfunction Associated with Metabolic Syndrome in African Americans and Whites.

The diagnosis of metabolic syndrome (MetS) identifies individuals at risk for developing diabetes and cardiovascular disease. African Americans (AAs) have high rates of cardiovascular disease and subclinical vascular disease including arterial stiffness and microvascular dysfunction but have relatively low rates of MetS. The objective of the study was to evaluate the relationship between MetS and vascular function in a biracial cohort with the hypothesis that the diagnosis of MetS underestimates subclinical vascular disease in AAs. We measured components of MetS in a community-based cohort of 951 AAs and white subjects (aged 48.8 ± 11 y, 47% AA, 55% female). Using digital pulse amplitude tonometry, we estimated the reactive hyperemia index (RHI), a measure of microvascular endothelial function. Using applanation tonometry (Sphygmocor), central augmentation index (CAIx) and pulse wave velocity (PWV) were measured as indices of wave reflections and arterial stiffness, respectively. MetS was present in 24.0% of subjects and was associated with increased PWV (P < .001) and CAIx (P < .001) and a trend to lower RHI (P = .068) in both races. However, in subjects without MetS, AAs had lower RHI (P < .001) and higher PWV (P = .003) and CAIx (P = .002) compared with white subjects. Addition of an extra MetS criterion point for AAs with hypertension eliminated the racial differences in PWV and CAIx but not RHI. Although MetS is associated with microvascular dysfunction and increased arterial stiffness in both racial groups, AAs without MetS have greater vascular dysfunction compared with whites. Additional weighting for hypertension in AAs attenuated the racial differences in subclinical disease associated with MetS.

Pulse Waveform Analysis of Chinese Pulse Images and Its Association with Disability in Hypertension

Hypertension affects functional capacity and quality of life. Pulse wave analysis (PWA) quantifies the pulse waveform's propagation and its changes resulting from arterial remodeling. Pulse image analysis (PIA) in traditional Chinese medicine contributes to pattern differentiation and therapeutic intervention. This protocol study evaluates the relationships between the parameters of both PWA and PIA to identify patterns in patients with hypertension and the associations of those patterns with functional capacity. In this observational, cross-sectional study protocol 40 patients were subjected to clinical and laboratorial examinations to assess the risk factors for cardiovascular disease and pattern differentiation. PWA was noninvasively performed at the radial artery to estimate the pulse wave's velocity, arterial compliance, and reflection index. PIA using the “simultaneous pressing” method was performed to assess nine indicators. Handgrip strength and physical activity was assessed as functional outcomes. We hypothesized that interactions between patterns and pulse images affect the PWA parameters and that the functional outcomes are weakly associated with personal, hemodynamic and risk factors for cardiovascular disease. Performing a PIA in patients with hypertension might allow the identification of early target-organ damage, standardization of the PIA based on the PWA, and unification of the pulse diagnosis.

Impact of Aging on Aortic Wave Reflection during Lower Body Negative Pressure

Evidence suggests that increased sympathetic tone but no change of blood pressure (BP) via lower body negative pressure (LBNP) reduces indices of aortic wave reflection in young adults. The aim of this study was to examine whether aging affects central artery hemodynamics and indices of wave reflection during LBNP. In 12 young (27 ± 2 years, 5F/7M) and 10 older (70 ± 2 years 5F/5M) subjects, noninvasive aortic pressure waveforms were synthesized from high‐fidelity radial pressure waveforms via applanation tonometry before and during 10 minutes of LBNP (‐20mmHg). Aortic BP and indices of aortic wave reflection (i.e. Augmentation index; AIx) were calculated from the generated aortic pressure waveform. Aortic systolic BP decreased during LBNP in the young (110 ± 3 vs. 106 ± 3 mmHg, P&lt;0.05), but not the older adults (139 ± 3 vs. 136 ± 3 mmHg, P=0.15). Aortic diastolic BP did not change in either group (P=0.56). Since heart rate (HR) changed in the young (P&lt;0.05) but not in the older adults (P=0.33) during LBNP, we used the AIx normalized to a HR of 75bpm as an index of wave reflection. AIx@75bpm decreased in young adults (‐6 ± 3 vs. ‐13 ± 3%, P&lt;0.001), whereas no change was observed in older adults (26 ± 3 vs. 25 ± 3%, P=0.39). Our data suggest that reductions in aortic systolic blood pressure and wave reflection during lower body negative pressure are attenuated in older compared to young adults.Funded by NIH HL‐105467

Effects of Acute Dietary Nitrate Supplementation on Aortic Blood Pressure and Wave Reflection in Young and Older Adults

Inorganic nitrate supplementation reduces peripheral blood pressure (BP) in several human populations. We examined whether acute nitrate supplementation decreases central aortic pressures and indices of wave reflection in young and older adults. In 13 young (25±1 yr, 10M/3F) and 12 older (64 ± 1yr, 9M/3F) normotensive adults, noninvasive aortic pressure waveforms were synthesized from high‐fidelity radial pressure waveforms via applanation tonometry before and following (60, 90, 120, 150, and 180 min) consumption of a nitrate rich beetroot juice (BR). Aortic BP and indices of aortic wave reflection (Augmentation Index; AIx and AIx normalized for heart rate; AIx@75bpm) were calculated from the generated aortic pressure waveform. Plasma nitrite concentration increased in both groups 60‐180 min following BR (P&lt;0.001). Peripheral (Systolic: ~5mmHg; Diastolic: ~4mmHg) and aortic BP (Systolic: ~6mmHg; Diastolic: ~4mmHg) were reduced 90‐180min post BR in older (P&lt;0.05), but not young adults. Conversely, AIx (3±3 vs ‐5±3%) and AIx@75bpm (‐6±3 vs ‐15±3%) were reduced in young adults 180 min post BR (P&lt;0.05 for both). Whereas, AIx (28±3 vs 28±2%, P=1.0) and AIx@75bpm (21±3 vs 20±3%, P=0.99) did not change in the older adults. Our data suggest that acute dietary nitrate supplementation reduces central aortic BP in older adults, despite not altering indices of aortic wave reflection.Supported by ACSM Foundation