Aortic Wave Reflection Research Articles

Arterial stiffness and aortic hemodynamics as predictors for new or worsening cardiovascular events in childhood cancer survivors: A report from the St. Jude lifetime cohort.

e24006 Background: Survival following childhood cancer has improved due to advances in treatment and supportive care. However, survivors are at high risk of cardiovascular diseases (CVDs) later in life. Aortic artery stiffening, captured by measuring the speed and magnitude of forward and reflected pulse waves, is an independent predictor of CVD and mortality in the general population. Methods: We evaluated associations between vascular function and new or worsening CVDs [coronary artery disease (CAD), cardiomyopathy, and hypertension (HTN)] among a subset (n = 249) of St. Jude Lifetime Cohort (SJLIFE) participants who had baseline vascular function assessment and returned for a standard follow up study visit (mean age at baseline (years) ± standard deviation: 34 ± 9 years, follow-up: 39 ± 9 years). CVD conditions were graded (dichotomized as grades 0-1 and 2-4) using the Common Terminology Criteria for Adverse Events (CTCAE). Aortic stiffness, brachial and aortic blood pressure (BP), and aortic wave reflection (augmented pressure, augmentation index (AIx), AIx adjusted to a heart rate of 75 beats/min (AIx75), time and magnitude of the forward and reflected waves) were assessed using wave separation analyses. T-tests were used to test mean values between the groups with higher (2-5) and lower (0-1) grades. These tests informed the selection of identified variables for multivariate logistic models, which were adjusted for age, sex, race, body mass index, physical activity, smoking status, drinking behavior and vasoactive medications. Results: Most participants had a history of Hodgkin lymphoma (53.8%) or leukemia (20.5%) and 25.7% other diagnoses. There were 169 (67.9%) participants who had cranial/neck radiation, 167 (67.9%) received anthracyclines, and 150 (60.2%) alkylating agents. At baseline 38.2% had ≥grade 2 HTN, 9.2% cardiomyopathy, and 4% CAD. Having ≥ grade 2 CVDs was significantly associated with augmented markers of brachial and aortic BP, arterial stiffness, and wave reflection. Regression analyses revealed that AIx75 ≥ 17% was associated with an increased risk of new or worsening HTN (odds ratio (OR) 3.29, 95% confidence interval (CI) 1.03-10.48) and new or worsening cardiomyopathy (OR 4.06, 95% CI 1.02-16.16) an average of 5 years after baseline vascular testing. Conclusions: Childhood cancer survivors diagnosed with grades 2-4 CVDs at a baseline visit had elevated aortic stiffness and augmented indices of wave reflection compared to those with < grade 2 CVDs. Elevated AIx75 was associated with new or worsening HTN and cardiomyopathy five years later. Early detection and treatment of vascular dysfunction may ameliorate CVD late effects in childhood cancer survivors.

Effect of Aging and Hypertension on Ambulatory Blood Pressure, Arterial Stiffness, and Wave Reflection in Mid-life Adults

Introduction: Age-associated increases in blood pressure are partly due to increased arterial stiffness and wave reflection. How these vascular changes during aging contribute to daily fluctuations in blood pressure and hypertension remain to be elucidated. Therefore, the purpose of this study is to compare ambulatory blood pressure, arterial stiffness, and wave reflection between young healthy adults, mid-life adults without hypertension, and mid-life adults with hypertension. Methods: Twenty-five young (age: 26 ± 4 yr and body mass index [BMI]: 23.9 ± 2.5 kg/m2) and 31 mid-life adults (age: 57 ± 4 yr and BMI: 25.4 ± 2.6 kg/m2), free of obesity and major clinical diseases and non-smokers, were included. Hypertension was defined by the current use of anti-hypertension medications or offce seated blood pressure (BP) ≥ 130/80 mmHg. Young adults with hypertension were excluded. Twenty-four-hour ambulatory BP monitoring (Oscar 2™, SunTech Medical®) and assessment of aortic arterial stiffness and wave reflection (SphygmoCor XCEL, AtCor Medical) were performed in all participants. Results: Daytime, nighttime, and 24-hr systolic BP was similar between young adults (YA) and mid-life adults without hypertension (MA; n=12; P>0.9 vs. YA), while mid-life adults with hypertension (MAHTN; n=19) had higher offce, 24-hr, daytime, and nighttime systolic and diastolic BP compared to YA and MA (p<0.01 vs. YA and MA). Compared to YA, MA had higher nighttime diastolic BP (P=0.02). Aortic arterial stiffness, measured by carotid-to-femoral pulse wave velocity, was the highest in MAHTN (p<0.001 vs. YA and P=0<0.01 vs. MA), followed by MA (p<0.01 vs. YA) and YA. Aortic wave reflection, measured by augmentation index and reflection magnitude, was higher in MA and MAHTN compared to YA but was similar between MA and MAHTN (p<0.001 for MA vs. YA; p<0.001 for MAHTN vs. YA; and P>0.9 for MA vs. MAHTN). Conclusions: Our findings indicate that 1) mid-life adults with hypertension had higher ambulatory BP and arterial stiffness than mid-life adults without hypertension and young adults; 2) despite normal offce blood pressure, mid-life adults without hypertension had higher nighttime diastolic BP and arterial stiffness than young adults; and 3) regardless of hypertension, mid-life adults had higher wave reflection than young adults. These findings suggest that 1) vascular aging may present prior to the diagnosis of hypertension based on offce BP; 2) arterial stiffness, rather than wave reflection, may contribute to the development of hypertension during aging; and 3) compared to offce BP, ambulatory BP may be a more sensitive marker of age-associated increases in blood pressure. NIAAA K99/R00 AA028537 to CLH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Evening and Morning-After Aortic Wave Reflection Responses to Binge Alcohol Consumption

Binge alcohol consumption acutely increases blood pressure and disrupts sleep. Recently, sleep irregularity has been linked to increases in aortic blood pressure. Increases in aortic wave reflection (i.e., aortic augmentation index) are associated with hypertension and cardiovascular risk. The purpose of the present study was to investigate the acute and next morning effects of evening binge alcohol consumption on aortic wave reflection. We tested the hypothesis that aortic augmentation index normalized to 75 heart beats per minute (AIx@75) and aortic pulsatile load (APL) would be increased acutely after binge drinking in the evening (study 1), and also the morning-after binge drinking compared to the morning after fluid control (study 2). Participants (n=33; 52% women; age 25±1 years; BMI 27±1 kg/m2) arrived at the laboratory at 4:00pm for baseline blood pressure and SphygmoCor (CPVH, Sydney, Australia) measures, and were provided a standardized meal verified by a registered dietitian. In a randomized order, separated by one month, participants completed a binge alcohol protocol (4-5 alcoholic drink equivalents within 2 hours) or fluid control. Alcohol or fluid control doses were administered in two equal allocates at 8 and 9 pm, and participants were provided 15 min to consume during each period. Binge alcohol consisted of a 1:3 mixture of 190 proof grain ethanol and fruit juice (i.e., Orange or Cranberry Juice) based on body weight and sex (1g/kg men, 0.85g/kg women), while the fluid control was only fruit juice in equal volume. Study 1 examined blood pressure, heart rate, aortic pulse pressure, APL, and AIx@75 before the standardized meal and then thirty minutes post-consumption of each allocated beverage using repeated measures ANOVA with condition (alcohol vs. fluid control) and time (baseline, post-drink 1, and post-drink 2) as within-subjects factors. Study 2 examined the same variables as study 1, but within 15 minutes of waking the morning after binge alcohol or fluid control using paired T-tests. Means were considered significantly different when p<0.05. In study 1, fluid control decreased HR and APL after doses one and two, while HR and APL were increased after the second dose of alcohol (time x cond. p<0.001). In study 2, morning-after HR was increased with binge alcohol compared to fluid control (57±1 vs. 63±2 beats/min; p<0.001). Morning-after APL (1857±66 vs. 2060±82 a.u.; p=0.012) and AIx@75 (2.9±2.5 vs. 6.5±2.4%; p=0.042) were also elevated in the binge alcohol condition. Our results indicate binge alcohol consumption acutely increases HR and APL the evening of consumption and increases HR, APL, and AIx@75 the morning after. These findings highlight a potential key physiological contributor to the known associations between binge alcohol consumption and cardiovascular risk. NIH (AA-024892). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of At-Risk Drinking on Ambulatory Blood Pressure in Young Adults

Introduction: At-risk drinking is associated with an increased risk of cardiovascular diseases (CVD) even in young adults. However, this association is mainly based on offce blood pressure (BP) measurement. Ambulatory BP monitoring captures diurnal variation in BP and is a more sensitive CVD predictor than offce BP. Therefore, the purpose of this study is to investigate the effects of at-risk drinking on ambulatory BP in young healthy adults with normal offce BP. Method: A total of 20 healthy men and women (21-35 years), non-smokers, were included in this cross-sectional study. All participants had an offce BP lower than 130/80 mmHg. Using the US Alcohol Use Disorders Identification Test (USAUDIT), at-risk drinkers were defined as those having a total USAUDIT score higher than 7 for men (6 for women). All participants underwent 24-hour ambulatory BP monitoring (Oscar 2™, SunTech Medical®). To investigate the vascular mechanisms underlying the effects of at-risk drinking on ambulatory blood pressure, aortic arterial stiffness and wave reflection were measured as pulse wave velocity (PWV) and augmentation index (AIx) by using SphygmoCor XCEL system (AtCor Medical). Results: No differences were found in age and BMI between at-risk drinkers (n=10) vs. low-risk drinkers (n=10; mean ± SD for age: 26.7 ± 3.7 vs. 26.6 ± 4.3 years, P>0.99 and BMI: 24.5 ± 2.4 vs. 23.8 ± 2.9 kg/m2, P=0.6). At-risk drinkers had a higher total USAUDIT score (10.6 ± 2.7 vs. 1.4 ± 1.2, p<0.001). While there was no difference between at-risk drinkers and low-risk drinkers in 24-hour, daytime, and nighttime systolic and diastolic BP (P≥0.5), at-risk drinkers had a higher blood pressure morning surge compared to low-risk drinkers (systolic: 34 ± 10 vs. 22 ± 6 mmHg, P=0.014 and diastolic: 29 ± 9 vs. 15 ± 4 mmHg, P=0.002). No significant difference was found in PWV (5.7 ± 0.6 Vs. 5.5 ± 0.7 m/sec, P=0.4) and AIx (8 ± 8 Vs. 15 ± 11, P=0.1). Conclusion: Our results indicate that despite similar offce BP, young adult at-risk drinkers had higher BP morning surge, an independent risk factor for cardiovascular events, than low-risk drinkers. These findings provide implications in using USAUDIT and out-of-offce BP measurements for cardiovascular disease risk assessment. This work was supported by NIAAA AA028537 to CLH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Arterial stiffness and wave reflection responses to acute and chronic high intensity interval training in healthy older adults

Aging leads to large elastic artery stiffness which is associated with early return of wave reflection. These age-related alterations increase left ventricular afterload, predisposing older adults to cardiovascular disease. Endurance training is an effective strategy to reduce cardiovascular disease risk. We have developed a supervised home-based exercise intervention using high intensity interval training on an all-extremity non-weight-bearing ergometer (HIIT-ANE). This study aimed to test the following hypotheses in healthy older adults: 1) arterial stiffness and wave reflection would decrease in response to chronic HIIT-ANE, 2) arterial stiffness and wave reflection responses to acute HIIT-ANE would differ in the untrained compared to the trained states, and 3) arterial stiffness and aortic wave reflection responses to acute and chronic HIIT-ANE would be related. Twenty older adults (66±1 years, mean ± SE; 11 postmenopausal women and 9 men) participated in this study. Carotid-femoral pulse wave velocity (cfPWV) and augmentation index at heart rate 75 bpm (AIx@75)—indices of arterial stiffness and wave reflection, respectively—were assessed by SphygmoCor XCEL at baseline (T0), following 8 weeks of normal lifestyle (T1; control condition), and following 8 weeks of supervised home-based HIIT-ANE (T2). Acute cfPWV and AIx@75 responses to HIIT-ANE were assessed at pre-, end-of-, 1-hr post- and 24-hrs post-exercise, in the untrained and trained states. cfPWV increased after 8 weeks of normal lifestyle (T0 vs. T1: 7.9±0.3 vs. 8.2±0.3 m/s, P=0.03), but it decreased following 8 weeks of HIIT-ANE (T1 vs. T2: 8.2±0.3 vs. 7.7±0.3 m/s, P<0.001). AIx@75 decreased after 8 weeks of HIIT-ANE compared to baseline and following 8 weeks of normal lifestyle (T0 vs. T2: 23.7±1.8 vs. 17.8±1.9 %, P<0.001; T1 vs. T2: 24.9±2.2 vs. 17.8±1.9 %, P<0.001). Acute cfPWV and AIx@75 responses to HIIT-ANE were similar in the untrained and trained states ( P for condition×time interaction; cfPWV: P=0.8; AIx@75: P=0.9). cfPWV and AIx@75 responses to chronic HIIT-ANE were not significantly related with acute responses to HIIT-ANE in the untrained (cfPWV: r=0.07, P=0.8; AIx@75: r=-0.32, P=0.2) and trained states (cfPWV: r=0.10, P=0.7; AIx@75: r=-0.32, P=0.2). In conclusion, we have demonstrated that supervised home-based HIIT-ANE has beneficial vascular effects in healthy older adults. We also showed that acute vascular responses to HIIT-ANE do not change from the untrained to trained state and are not predictive of chronic vascular responses to HIIT-ANE. This work was supported by the National Institute of Aging grant AG063143. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Endothelial dysfunction influences augmented aortic hemodynamic responses to metaboreflex activation in postmenopausal women.

Postmenopausal women experience augmented aortic hemodynamic responses to isometric handgrip (IHG) exercise and metaboreflex activation post-exercise muscle ischemia (PEMI). Relationships between endothelial function brachial artery flow-mediated dilation (FMD) and aortic stiffness carotid-femoral pulse wave velocity (cfPWV) with aortic pulsatile hemodynamics during IHG and PEMI have not been determined. The relationships between aortic hemodynamic responses to PEMI were evaluated. Aortic blood pressure (BP), wave reflection, and pressure of forward (Pf) and backward (Pb) waves were measured using arterial tonometry at rest, IHG at 30% maximal force, and PEMI in 30 (15/group) postmenopausal women with low (≤ 4.5%) and normal (≥ 5.5%) FMD. Hemodynamic responses were analyzed as the change (Δ) from rest to the last minute of IHG and PEMI. Brachial and aortic systolic BP (SBP) responses to IHG were higher in the low vs normal FMD group (P < 0.05). Aortic SBP (Δ20 ± 8 vs Δ11 ± 7mmHg), pulse pressure (PP) (Δ12 ± 8 vs Δ6 ± 4mmHg), augmented pressure (AP) (Δ5 ± 3 vs Δ2 ± 2mmHg), and Pb (Δ6 ± 4 vs Δ3 ± 2mmHg) responses to PEMI were greater (P < 0.05) in women with low vs. normal FMD. FMD was negatively correlated with aortic SBP, PP, AP, and Pb (P < 0.05) responses to PEMI. cfPWV was not correlated with responses to PEMI. Endothelial dysfunction relates to augmented aortic pulsatile load during metaboreflex activation, which may increase cardiovascular risk in postmenopausal women.

Association of Arterial Stiffness With Mid- to Long-Term Home Blood Pressure Variability in the Electronic Framingham Heart Study: Cohort Study.

Short-term blood pressure variability (BPV) is associated with arterial stiffness in patients with hypertension. Few studies have examined associations between arterial stiffness and digital home BPV over a mid- to long-term time span, irrespective of underlying hypertension. This study aims to investigate if arterial stiffness traits were associated with subsequent mid- to long-term home BPV in the electronic Framingham Heart Study (eFHS). We hypothesized that higher arterial stiffness was associated with higher home BPV over up to 1-year follow-up. At a Framingham Heart Study research examination (2016-2019), participants underwent arterial tonometry to acquire measures of arterial stiffness (carotid-femoral pulse wave velocity [CFPWV]; forward pressure wave amplitude [FWA]) and wave reflection (reflection coefficient [RC]). Participants who agreed to enroll in eFHS were provided with a digital blood pressure (BP) cuff to measure home BP weekly over up to 1-year follow-up. Participants with less than 3 weeks of BP readings were excluded. Linear regression models were used to examine associations of arterial measures with average real variability (ARV) of week-to-week home systolic (SBP) and diastolic (DBP) BP adjusting for important covariates. We obtained ARV as an average of the absolute differences of consecutive home BP measurements. ARV considers not only the dispersion of the BP readings around the mean but also the order of BP readings. In addition, ARV is more sensitive to measurement-to-measurement BPV compared with traditional BPV measures. Among 857 eFHS participants (mean age 54, SD 9 years; 508/857, 59% women; mean SBP/DBP 119/76 mm Hg; 405/857, 47% hypertension), 1 SD increment in FWA was associated with 0.16 (95% CI 0.09-0.23) SD increments in ARV of home SBP and 0.08 (95% CI 0.01-0.15) SD increments in ARV of home DBP; 1 SD increment in RC was associated with 0.14 (95% CI 0.07-0.22) SD increments in ARV of home SBP and 0.11 (95% CI 0.04-0.19) SD increments in ARV of home DBP. After adjusting for important covariates, there was no significant association between CFPWV and ARV of home SBP, and similarly, no significant association existed between CFPWV and ARV of home DBP (P>.05). In eFHS, higher FWA and RC were associated with higher mid- to long-term ARV of week-to-week home SBP and DBP over 1-year follow-up in individuals across the BP spectrum. Our findings suggest that higher aortic stiffness and wave reflection are associated with higher week-to-week variation of BP in a home-based setting over a mid- to long-term time span.

Arterial Health After Preeclampsia: Role of Chronic Hypertension in the Early Vascular Aging (EVA) Study.

Preeclampsia (PE) is associated with increased cardiovascular risk. Recent data have shown worse left ventricular remodeling and diastolic function in women with PE and persistent hypertension (HTN). We performed a comprehensive arterial hemodynamic assessment to evaluate the contribution of persistent HTN on arterial health after PE. We recruited 40 women with PE history and 40 age-matched controls (6 months to 6 years postpartum). We evaluated arterial hemodynamics with validated techniques combining applanation tonometry and transthoracic echocardiography, comparing three groups: previous PE with persistent HTN (PE-HTN), previous PE with normalized blood pressure (PE-noHTN) and controls, using multivariable linear regression adjusted for age, body surface area, heart rate, diabetes, smoking history, creatinine, and gravidity. Eight (20%) of the post-PE women had persistent HTN. Mean age was 35.8 ± 3.9 years, median number of pregnancies was 2 (range 1-7), and time since last pregnancy 2.1 (range 0.5-5.7) years (not different between groups, P > 0.05). Compared to controls and to PE-noHTN, PE-HTN had higher aortic stiffness, wave reflections, pulsatile, and steady arterial load (P < 0.05 for each). Among PE-noHTN, aortic stiffness, wave reflections and steady arterial load were worse than controls (P < 0.05 for each), with smaller effect sizes. This is the most comprehensive assessment of arterial hemodynamics and first to demonstrate the contribution of persistent HTN on worse arterial health following PE. Since measures of arterial health are associated with cardiovascular events in the population, the combination of previous PE and chronic HTN may represent a higher risk subgroup who could benefit from targeted prevention strategies.

Superiority of a Representative MRI Flow Waveform over Doppler Ultrasound for Aortic Wave Reflection Assessment in Children and Adolescents With/Without a History of Heart Disease

Wave separation analysis (WSA) reveals the impact of forward- and backward-running waves on the arterial pressure pulse, but the calculations require a flow waveform. This study investigated (1) the variability of the ascending aortic flow waveform in children and adolescents with/without a childhood heart disease history (CHD); (2) the accuracy of WSA obtained with a representative flow waveform (RepFlow), compared with the triangulation method and published ultrasound-derived adult representative flow; (3) the impact of limitations in Doppler ultrasound on WSA; and (4) generalizability of results to adults with a history of CHD. Phase contrast MRI was performed in youth without (n = 45, Group 1, 10–19 years) and with CHD (n = 79, Group 2, 7–18 years), and adults with CHD history (n = 29, Group 3, 19–59 years). Segmented aortic cross-sectional area was used as a surrogate for the central pressure waveform in WSA. A subject-specific virtual Doppler ultrasound was performed on MRI data by extracting velocities from a sample volume. Time/amplitude-normalized ascending aortic flow waveforms were highly consistent amongst all groups. WSA with RepFlow therefore yielded errors < 10% in all groups for reflected wave magnitude and return time. Absolute errors were typically 1.5–3 times greater with other methods, including subject-specific (best-case/virtual) Doppler ultrasound, for which velocity profile skewing introduced waveform errors. Our data suggest that RepFlow is the optimal approach for pressure-only WSA in children and adolescents with/without CHD, as well as adults with CHD history, and may even be more accurate than subject-specific Doppler ultrasound in the ascending aorta.

Effect of aging on aortic arterial stiffness and wave reflection in healthy mid-life adults

Introduction: Aging is associated with arterial stiffening which increases pressure reflection to the heart and contributes to the development of cardiovascular disease. However, most vascular aging studies have focused on comparing young adults versus adults 65 or older, and comorbidities, such as hypertension and obesity, confounded the findings. The extent of vascular aging in healthy mid-life adults (age 50-64) is unclear. Therefore, the purpose of this study was to compare arterial stiffness and wave reflection in healthy young adults (18-35 years) and healthy mid-life adults. Methods: Twenty-six apparently healthy, nonsmoking, adults underwent assessments of arterial stiffness and wave reflection. Young adults (YA; n=15, 6 eumenorrheic women; age: 28±4 yr; systolic blood pressure [SBP]: 109±8 mmHg; body mass index [BMI]: 24.1±2.5 kg/m2; mean±SD) were compared to mid-life adults (MA; n=11, 8 postmenopausal women; age: 59±4 yr; SBP: 109±10 mmHg; BMI: 25.6±4.1 kg/m2). Using SphygmoCor XCEL (AtCor Medical), aortic arterial stiffness was measured as carotid to femoral pulse wave velocity (cfPWV) and wave reflection was measured as augmentation index normalized at heart rate of 75 (Alx75), augmented pressure (AP), backward wave pressure (Pb), and reflection magnitude (RM). Results: No significant differences between YA and MA were found in brachial and aortic SBP, diastolic blood pressure, and pulse pressure (P≥0.07). Compared to YA, MA had higher cfPWV (MA vs. YA: 6.8±0.9 m/s vs. 5.8±0.6 m/s, p=0.001), Alx75 (30±10% vs. 4±10%, p&lt;0.001), AP (13±4 mmHg vs. 4±3 mmHg, p&lt;0.001), Pb (16±2 mmHg vs. 13±2 mmHg, p=0.001), and RM (67.7±6.8% vs. 48.0±5.6%, p&lt;0.001). Conclusions: Our findings suggest that mid-life adults exhibit increased arterial stiffness and wave reflection compared to young adults. These data suggest that vascular aging may already be present in mid-life adults, despite normal peripheral blood pressure. These findings help extend our understanding of the sequence of age-related changes in vascular function throughout the lifespan. This work was supported by NIAAA K99/R00 AA028537 to CLH. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Impact of arterial stiffness on echocardiographic myocardial work indices in patients with isolated bicuspid aortic valve.

Data related to the existence of left ventricular (LV) abnormalities in normal functional bicuspid aortic valve (BAV) disease is scarce. In addition, the impact of afterload and the involved mechanisms are unclear. In this work, we study the relationship between LV function assessed with myocardial work index (MWI) and arterial stiffness in a cohort of normal functioning BAV patients. In this study, we included a total of 38 consecutive patients with isolated BAV and 44 age- and gender-matched control subjects with tricuspid aortic valve. All participants underwent transthoracic echocardiography to assess conventional parameters and global longitudinal strain (GLS). In addition, MWI was measured by the noninvasive LV pressure-strain cycle method. Aortic pulse wave velocity (PWV) and wave reflection were evaluated by applanation tonometry. The mean aortic PWV was significantly higher in BAV patients (6.4 ± 0.80, 7.02 ± 0.1.2, p=.01, respectively). LV-MWI related parameters such as global work efficiency (GWE) (96.261.69 and 97.051.27, p=.02) and global wasted work (GWW) (78.232.1 and 61.824.4, p=.01) were found significantly different between the BAV and control groups. However, global working index and global constructive working were not different between groups (1969 ± 259 and 2014 ± 278, p=.45; 2299 ± 290 and 2359 ± 345, p=.39, respectively). Multivariable ordinary least squares regression analysis revealed that BAV (ß=8.4; 95% CI: 1.5-15.3; p=.04) and PVW (ß=5.6; 95% CI: 0.7-10.5; p=.01) were significant predictors of GWV. GWW is increased and GWE is decreased in patients with BAV compared with controls, and these changes are related to arterial stiffness. The relationship between aortic PWV and GWW may help to explain the exact mechanism of subclinical myocardial dysfunction in patients with isolated BAV.

Morbid obesity is associated with hypertrophic outward remodeling and increased stiffness of small conduit arteries: An ultra-high frequency ultrasound study

Background and aimsAlthough many studies have been published on the effect of obesity on large and small arteries, there are no data in the literature regarding the effect of obesity on medium-sized arteries, and in particular of small conduit arteries. The aim of the present study was to investigate whether patients with severe obesity presented structural or functional alterations in different arterial segments. Methods and results34 patients with severe obesity (BMI≥35 kg/m2) and 34 age-and sex-matched normal weight patients were recruited as controls. Aortic stiffness (carotid-femoral pulse wave velocity) and wave reflection (augmentation index) were recorded. Ultrasound images of common carotid, radial and interdigital arteries were acquired for the assessment of wall-to-lumen ratio, wall cross-sectional area (WCSA), compliance, distensibility coefficient (DC) and Young's elastic modulus (Einc). Insulin sensitivity was calculated by oral glucose sensitivity index (OGIS). No differences between groups in carotid artery remodeling were found, while WCSA of the radial and interdigital arteries were higher in obese group than in controls. As regard the parameters of vascular elasticity, the DC of radial and interdigital arteries were lower (p = 0.025 and p = 0.001, respectively), as well as the Einc of radial arteries was higher (p = 0.021), in subject with obesity compared to controls. All these correlations were consistent after adjustment for the main covariates. Finally, in a multiple regression analysis OGIS was and independent determinant of interdigital artery DC (R2 = 0.29, p = 0.001). ConclusionsFor the first time, we describe an outward remodeling and increased stiffness in small conduit arteries in severe obesity.

Abstract 13430: Arterial Health After Preeclampsia: Role of Chronic Hypertension

Introduction: Preeclampsia (PE) is associated with an increased cardiovascular (CV) risk. Recent data have shown worse left ventricular remodeling and diastolic function in women with PE and persistent hypertension (HTN). To improve our understanding of CV risk after PE, we evaluated the contribution of persistent HTN on arterial health. Methods: We recruited 40 women with PE history and 40 age-matched women with normotensive pregnancies (6 months - 6 years post-partum). We comprehensively evaluated measures of arterial health and hemodynamics with validated technique combining applanation tonometry and transthoracic echocardiography. We compared 3 groups: previous PE with persistent HTN (PE-HTN), previous PE with normalized blood pressure (PE-noHTN) and controls. Associations of PE-HTN with arterial health measures were assessed with multivariable linear regression adjusted for age, BSA, heart rate, diabetes, smoking history, serum creatinine and parity. Results: Eight (20%) of the post-PE women had persistent HTN. Mean age was 35.8 ± 3.9 years, number of pregnancies was 2.4 ± 1.4, and time since last pregnancy was 2.6 ± 1.2 years, and not different across the 3 groups (P&lt;0.05 for each). Results of the multivariable linear regression models are summarized in the Figure, demonstrating that women with PE-HTN had significantly higher aortic stiffness, wave reflections, pulsatile and steady arterial load than controls. Among women with previous PE whose blood pressure normalized postpartum, arterial stiffness, wave reflections and steady arterial load were also worse compared to controls, albeit with smaller effect size (p&lt;0.05). Conclusions: This is the first study to demonstrate the contribution of persistent HTN on worse arterial health following PE. Since measures of arterial health are associated with CV events in the population, women with PE-HTN may represent a higher risk subgroup who could benefit from targeted primary prevention strategies.

Abstract 14300: Arterial Stiffness is Associated With Intermediate-Term Home Blood Pressure Variability: The Electronic Framingham Heart Study

Introduction: Short-term blood pressure variability (BPV) is associated with arterial stiffness in patients with hypertension. Few studies examined associations between arterial stiffness and digital home BPV over an intermediate time span. Objective: We investigated if antecedent arterial stiffness was associated with home BPV among participants in the electronic Framingham Heart Study (eFHS). We hypothesize that higher arterial stiffness predicts higher intermediate-term home BPV over one-year follow-up. Methods: At an FHS research exam (2016-2019), participants underwent arterial tonometry to acquire mean arterial pressure (MAP) and measures of arterial stiffness (carotid femoral pulse wave velocity, CFPWV; forward pressure wave amplitude, FWA) and wave reflection (reflection coefficient, RC). Participants who agreed to enroll in eFHS were provided with a digital blood pressure (BP) cuff to measure home BP weekly. Participants with &lt; 3 weeks of BP readings were excluded. Linear regression models were used to examine associations of arterial measures with home average real variability (ARV) of systolic (SBP) and diastolic (DBP) BP adjusting for covariates. We obtained ARV as an average of the absolute differences of consecutive BP measurements. ARV considers not only the dispersion of the BP readings around the mean, but also the order of BP readings. We used p&lt;0.05 for significance. Results: Among 857 eFHS participants (mean age 54 years, 59% women, mean BP 119/76, 47% hypertension, mean ARV of DBP 5.50, mean ARV of SBP 8.61), higher FWA and RC were associated with higher ARV of SBP ( Table ). Higher CFPWV was associated with lower ARV of DBP ( Table ). Conclusion: In eFHS, higher FWA and RC were associated with higher intermediate-term home BPV of SBP while higher CFPWV was associated with blunted BPV of DBP. Our findings suggest that higher aortic stiffness and wave reflection may affect day-to-day modulation of blood pressure in a home-based setting.

Prediction of Cardiovascular Events by Pulse Waveform Parameters: Analysis of CARTaGENE.

BackgroundWaveform parameters provide approximate data about aortic wave reflection. However, their association with cardiovascular events remains controversial and their role in cardiovascular prediction is unknown.Methods and ResultsWe analyzed participants aged between 40 and 69 from the population‐based CARTaGENE cohort. Baseline pulse wave analysis (central pulse pressure, augmentation index) and wave separation analysis (forward pressure, backward pressure, reflection magnitude) parameters were derived from radial artery tonometry. Associations between each parameter and major adverse atherosclerotic events (MACE; cardiovascular death, stroke, myocardial infarction) were obtained using adjusted Cox models. The incremental predictive value of each parameter compared with the 10‐year atherosclerotic cardiovascular disease score alone was assessed using hazard ratios, c‐index differences, continuous net reclassification indexes, and integrated discrimination indexes. From 17 561 eligible patients, 2315 patients had a MACE during a median follow‐up of 10.1 years. Central pulse pressure, forward pressure, and backward pressure, but not augmentation index and reflection magnitude, were significantly associated with MACE after full adjustment. All parameters except forward pressure statistically improved MACE prediction compared with the atherosclerotic cardiovascular disease score alone. The greatest prediction improvement was seen with augmentation index and reflection magnitude but remained small in magnitude. These 2 parameters enhanced predictive performance more strongly in patients with low baseline atherosclerotic cardiovascular disease scores. Up to 5.7% of individuals were reclassified into a different risk stratum by adding waveform parameters to atherosclerotic cardiovascular disease scores.ConclusionsSome waveform parameters are independently associated with MACEs in a population‐based cohort. Augmentation index and reflection magnitude slightly improve risk prediction, especially in patients at low cardiovascular risk.

Prediction of long-term outcomes by arterial stiffness and pressure wave reflections in patients with acute stroke: the Athens Stroke Registry.

Stroke patients' management might be improved by addressing the role of aortic stiffness (carotid-femoral pulse wave velocity: cfPWV) and pressure wave reflections (PWRs, augmentation index: AIx) in their pathogenesis and outcome. We tested the hypothesis that cfPWV and AIx, separately and combined, predict long-term outcomes [all-cause mortality, incidence of cardiovascular events, stroke recurrence and disability defined by modified Ranking Scale (mRS) ≥3] in patients with acute stroke, using data from the 'Athens Stroke Registry'. Data from 552 patients (70% men, age: 66.1 ± 10.4 years, 13.4% deaths from any cause, 21.2% cardiovascular events, 14.1% stroke recurrences and 20.1% poor mRS, mean follow-up 68.4 ± 41.4 months) were analyzed. The main findings were that: high aortic stiffness (cfPWV > 13 m/s) alone is an independent predictor of all-cause mortality and cardiovascular (CV) events, but not of stroke recurrence and poor functional outcome; evaluated separately from aortic stiffness, neither low nor high PWRs have any prognostic value; even after multiple adjustments, patients with both high aortic stiffness (cfPWV > 13 m/s) and low PWRs (Aix < 22%) have almost two-fold higher hazard ratio, not only for all-cause mortality and CV events but also for stroke recurrence and poor functional outcome. The present study provides evidence about the role of aortic stiffness, PWRs and their combined incremental value in the long-term survival, morbidity, and functional disability after acute stroke.

Mental Stress Pressor Response and Post‐Stress Aortic Wave Reflection

Reactivity to mental stress has been linked to cardiovascular risk, and is shown to negatively influence aortic wave reflection for up to an hour after acute mental arithmetic. It has been postulated that sympathetic catecholamine release during the stressful task drives the sustained elevation in wave reflection. In the present study we sought to determine how muscle sympathetic nerve activity (MSNA) and mean arterial pressure (MAP) reactivity influence post mental stress aortic augmentation index (AIx). Twenty‐seven volunteers (25±1 years) with resting blood pressure ≥120/80 mmHg participated in the present study. Baseline pulse wave analysis and pulse wave velocity recordings were assessed on participants after 10 minutes of supine rest. Participants were then instrumented for measurements of MSNA (microneurography), beat‐to‐beat blood pressure (finger plethysmography), and heart rate (3‐lead ECG). Subsequently MSNA, blood pressure, and heart rate were measured during a 5‐minute baseline, 5‐minute mental stress task (serial subtraction), and 5‐minute recovery. Finally, aortic wave reflection (i.e. AIx) was reassessed 10 minutes after completion of mental stress. Statistical analyses included paired t‐tests to compare MSNA, MAP, heart rate (HR), and perceived stress during baseline and mental stress. We used standard multiple regression with change in AIx as the dependent variable and changes in MSNA, MAP, and perceived stress as the independent variables. Means were considered significantly different when p&lt;0.05. The mental stress task significantly increased HR (Δ15±2 beats/minute), MAP (Δ14±1 mmHg), and perceived stress (Δ1.9±0.1 a.u.), while MSNA was not significantly increased. There was however a range of changes in MSNA from ‐13 to +20 bursts/minute. The change in MAP during mental stress was a significant predictor (ꞵ=0.47; p=0.03) of the change in AIx (post‐stress vs. baseline). Changes in MSNA and perceived stress were not predictors of mental stress‐related changes in AIx. Our results indicate that the aortic wave reflection responses to mental stress appear to be linked to the pressor response, but not sympathetic or perceived stress responses. This is novel preliminary data that suggests there may not be a direct link between sympathetic activation and aortic wave reflection following cognitive stress.

L-Citrulline supplementation attenuates aortic pulse pressure and wave reflection responses to cold stress in older adults

Augmented aortic systolic blood pressure (SBP) and wave reflection via sympathetic-mediated vasoconstriction elevates the risk for adverse cardiovascular events in older adults. L-citrulline (L-CIT) supplementation has shown to reduce aortic SBP and pulse pressure (PP) responses to cold pressor test (CPT) induced sympathoactivation in young men. The aim of this study was to elucidate the efficacy of L-CIT supplementation to attenuate aortic hemodynamic responses to CPT in older adults. Sixteen older adults were randomly assigned to placebo or L-CIT (6g/day) for 14-days in a crossover, double-blind, placebo-controlled design. Brachial SBP and aortic SBP, PP, augmented pressure (AP), augmentation index standardized at 75bpm (AIx@75), and pressure of the forward (Pf) and reflected (Pb) waves were evaluated at rest and during CPT pre- and post-intervention. Although no hemodynamic changes at rest, brachial SBP (Δ-12±18 vs. Δ4±14mmHg; P=0.008) and aortic SBP (Δ-10±14 vs. Δ4±12mmHg; P=0.005), PP (Δ-10±12 vs. Δ4±11mmHg; P=0.002), AP (Δ-4±4 vs. Δ2±7mmHg; P=0.004), AIx@75 (Δ-3.2±7.2 vs. Δ2.2±6.9%; P=0.038), Pf (Δ-6±10 vs. Δ3±9mmHg; P=0.019), and Pb (Δ-4±6 vs. Δ2±6mmHg; P=0.008) responses to the CPT were significantly attenuated following L-CIT supplementation vs. placebo. L-CIT supplementation attenuated aortic pulsatile pressure and pressure wave reflection responses to CPT in older adults, providing possible cardioprotection during cold-induced sympathoactivation in older adults.

Influence of age on arterial stiffness responses following a short period of sitting in healthy males

Background: Age-related increases in arterial stiffness including carotid-femoral pulse wave velocity (cf-PWV), aortic wave reflection via augmentation index (AIx) and reflection magnitude (RM) have been associated with future cardiovascular event risk. Chronic or prolonged inactivity has been reported to exacerbate the age-related increases in arterial stiffness. However, little is known about the impact of a short, period of inactivity on arterial stiffness with age potentially an influencing factor.

Aortic hemodynamic parameters as predictors of incident or deteriorating hypertension during carfilzomib therapy in patients with relapsed multiple myeloma

Abstract Background Carfilzomib (CFZ) improves survival in relapsed/refractory multiple myeloma but is associated with cardiovascular adverse events, among which hypertension is commonly reported. Purpose To evaluate aortic hemodynamics as possible predictors for CFZ-associated hypertension. Methods In a prospective study of 48 patients treated with Kd (CFZ 20/56 mg/m2 and dexamethasone) followed until disease progression or cycle 6 for a median of 10 months, patients underwent peripheral hemodynamic assessment, including applanation tonometry, which allows estimation of aortic blood pressure and arterial wave reflections and assessment of pulse wave velocity, which allows estimation of aortic stiffness. Hemodynamic parameters were examined at baseline and at pre-specified time points before and 24 hours after drug infusion. Results Thirteen patients (27.1%) developed hypertension or merited more intensive anti-hypertensive treatment (grade I or II: 6.25%, grade III: 20.8%). Patients with new onset or worsening hypertension had increased aortic [130±12.9 mmHg versus 115±16.7 mmHg, p=0.004] and peripheral systolic blood pressure (SBP) [145±15.7 mmHg versus 130±19.5 mmHg, p=0.001] at baseline. Patients distributed at highest tertile of baseline aortic SBP (log-rank test p=0.0001, Figure) or baseline peripheral SBP (log-rank test p=0.002) had significantly higher risk for CFZ associated hypertension as compared to those distributed at lower tertiles. After adjustment for age, gender and baseline hypertension, increased aortic [HR=8.0, 95% CIs 2.4–26.6, p=0.001] and peripheral SBP [HR=4.85, 95% CIs 1.53–15.4, p=0.007] remained significantly associated with hypertension. After adjustment for both baseline peripheral and aortic SBP in the same multivariable core model, aortic SBP was the only independent predictor of the study outcome (p=0.041). Accordingly, baseline aortic SBP was associated with higher discriminative value as compared to peripheral SBP [AUC: 0.819, 95% CIs 0.722–0.916 versus 0.724, 95% CIs 0.570–0.878, respectively]. Further adjustment for all cardiotoxicity risk factors using forced inclusion in non-parsimonious multivariable Cox regression models, revealed that increased aortic and peripheral SBP remained independent predictors of hypertensive events (p&amp;lt;0.05 for both). Conclusion Baseline aortic hemodynamics are associated with hypertension during CFZ treatment. Aortic SBP at baseline was the strongest predictor of CFZ-associated hypertensive adverse events, suggesting that an initial assessment of aortic blood pressure may facilitate discrimination of patients in need of close monitoring during treatment. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Funding from the Hellenic Foundation for Research and Innovation (HFRI) and the General Secretariat for Research and Technology (GSRT), under grant agreement No [1285].