Carotid-femoral Pulse Wave Velocity Research Articles

#723 The impact of kidney function on arterial stiffness in COVID-19 survivors: an analysis from CARTESIAN Study

Abstract Background and Aims SARS-CoV-2 pandemic has been linked to an increased incidence of cardiovascular events, potentially due to accelerated vascular aging [1]. Conversely, impaired kidney function is known to contribute to the pathogenesis of heightened arterial stiffness, independent of traditional cardiovascular risk factors [2]. This study aimed to assess the impact of COVID-19 on arterial stiffness among a cohort of survivors of the first pandemic wave, with varying degrees of infection severity. The assessment was conducted at 6 ± 3 (T1) and 12 ± 3 months (T2) post-infection, with the population stratified based on kidney function. Method the CARTESIAN study, a large international multicenter cohort study, was designed to assess the long-term effects of COVID-19 on vascular aging. A total of 938 subjects were stratified into three groups based on their estimated glomerular filtration rate (eGFR) percentiles using the CKD-EPI_2021 equation: 1) >75th percentile, 2) 75th-25th percentile, and 3) <25th percentile, respectively. The same population was further categorized based on the severity of COVID-19 into three groups: 1) patients who were not hospitalized (No-Hosp), 2) subjects requiring hospitalization in a medical unit (Hosp), or 3) those in an intensive care unit (ICU). Arterial stiffness was evaluated using carotid-femoral pulse wave velocity (cf-PWV). A hierarchical repeated measures mixed model analysis was conducted to compare cf-PWV across these groups (>75th, 75th-25th, and <25th groups, respectively). Results in the cross-section analysis (T1) <25th group exhibited higher age, increased cardiovascular risk factors, and higher prevalence of severe COVID-19 compared to the >75th group. Using hierarchical linear modeling, the <25th exhibited higher cf-PWV than the >75th group, even after adjusting for both all the random and fixed variables, included the three COVID-19 group (+0.51 m/s, p = 0.013). In longitudinal analysis, globally, no substantial changes were found in the cf-PWV between T1 and T2, remained significantly higher in the <25th group compared to the >75th group (p = 0.003), in a linear mixed model adjusted for all the random and fixed variables. Interestingly, a significant interaction between eGFR groups* COVID-19 groups was found in repeated measures analysis (p = 0.039). In particular, within ICU group, we found a significant increase of cf-PWV between 6- and 12-months in <25th group, from 8.64 [7.59-9.31] to 9.41 [8.89-10.41] m/s, p = 0.021) (Fig. 1). Conclusion the findings suggest that individuals with both lower eGFR and a history of severe COVID-19 may be at a heightened risk of accelerated arterial aging. Understanding these dynamics is crucial for targeted interventions to mitigate long-term cardiovascular consequences in COVID-19 survivors with kidney disease.

#2404 Predictors of mortality in patients with chronic kidney disease stages 3-4 without heart disease

Abstract Background and Aims Cardiovascular disease is common in patients with chronic kidney disease (CKD). This may, at least in part, explain the high risk of mortality in this patient group. The aim of the present study was to identify factors associated with mortality in patients with CKD stages 3 and 4 without a diagnosis of heart disease. Method Study subjects were derived from a cohort of patients with CKD stages 3 and 4 who were recruited from our Nephrology Outpatient Clinic between February 2009 and December 2011. Ninety-one patients without a diagnosis of heart disease were included in this cross-sectional study. Mortality data were collected in April 2023. Results All-cause mortality was 28.6% (26 patients) during a mean follow-up of 11.2 ± 2.7 years. Comparison of baseline data between non-survivors and survivors showed that non-survivors were significantly older, had lower glomerular filtration rate (GFR), higher ambulatory systolic blood pressure (ASBP), less nocturnal dipping of ASBP, higher carotid–femoral pulse wave velocity (cfPWV) and higher serum levels of troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) [Tables 1 and 2]. In addition, the proportion of patients with diabetes and on treatment with beta-blockers was elevated in non-survivors [Tables 1 and 2]. There were no statistically significant differences between groups in smoking history, treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, diuretics, calcium channel blockers, alpha-blockers, statins, active vitamin D analogs, calcium-based or non-calcium-based phosphate binders. In a binary logistic regression analysis, to identify independent predictors of mortality, we included age, gender, baseline GFR, serum NT-proBNP, TnT, cfPWV, percent of nocturnal dipping of ASBP, diagnosis of diabetes, and treatment with beta-blockers. Only less nocturnal dipping of ASBP (Exp [β] value of 0.86, 95% CI 0.77–0.97, p = 0.016) and advancing age (Exp [β] value of 0.91, 95% CI 0.84–0.99, p = 0.024) significantly predicted all-cause mortality. Conclusion In patients with CKD stage 3 and 4 without a diagnosis of heart disease only older age and less nocturnal dipping of ASBP were independently associated with mortality. Although baseline levels of serum NT-proBNP and TnT were elevated in non-survivors, neither serum NT-proBNP nor TnT showed independent associations with mortality in this cohort.

Arterial Stiffness and Incident Glaucoma: A Large Population-Based Cohort Study

To investigate whether arterial stiffness, assessed oscillometrically, is associated with incident glaucoma in the Vitamin D Assessment (ViDA) Study cohort, aged 50 to 84 years. Prospective, population-based cohort study. Arterial stiffness was assessed in 4,713 participants without known glaucoma (mean ± SD age = 66 ± 8 years) from 5 April 2011 to 6 November 2012 by way of aortic PWV (aPWV), estimated carotid-femoral PWV (ePWV) and aortic PP (aPP). Incident glaucoma was identified through linkage to national prescription and hospital discharge registers. Relative risks of glaucoma for each arterial stiffness measure were estimated by Cox proportional hazards regression, over the continuum of values and by quartiles. During a mean ± SD follow-up of 10.5±0.4 years, 301 participants developed glaucoma. Arterial stiffness, as measured by aPWV (Hazard ratio (HR) per SD increase, 1.36, 95% CI 1.14-1.62) and ePWV (HR per SD increase, 1.40, 95% CI 1.14-1.71) but not aPP (HR per SD increase, 1.06, 95% CI 0.92-1.23) was associated with incident glaucoma. When arterial stiffness was analyzed as a categorical variable, the highest quartiles of aPWV (HR, 2.62, 95% CI 1.52-4.52; Ptrend = .007), ePWV (HR, 2.42, 95%CI 1.37-4.27; Ptrend = .03), and aPP (HR, 1.68, 95%CI 1.10-2.5; Ptrend = .02) were associated with the development of glaucoma. Arterial stiffness measured with a simple oscillometric device predicted the development of glaucoma and could potentially be used in clinical practice to help identify people at risk of this condition. It may also present a new therapeutic research avenue, including in respect of systemic antihypertensives.

Effect of Incorporating 1 Avocado per Day Versus Habitual Diet on Vascular Function in Adults With Abdominal Obesity: An Ancillary Study of HAT, a Randomized Controlled Trial.

Abdominal obesity is associated with endothelial dysfunction and poorer vascular health. Avocado consumption improves postprandial endothelial function; however, the longer-term effects remain unclear. It was hypothesized that the daily addition of 1 avocado to a habitual diet for 6 months would improve flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity in individuals with abdominal obesity (waist circumference ≥35 in for women, ≥40 in for men), compared with a habitual diet low in avocados. HAT (Habitual Diet and Avocado Trial) was a multicenter, randomized, controlled, parallel-arm study that investigated the health effects of adding 1 avocado per day to a habitual diet in individuals with abdominal obesity. At the Pennsylvania State University, University Park study center (n=134; age, 50 ± 13 years; women, 78%; body mass index, 32.6 ± 4.8 kg/m2), markers of vascular function were measured, including endothelial function, assessed via brachial artery flow-mediated dilation, and arterial stiffness, assessed via carotid-femoral pulse wave velocity. Between-group differences in 6-month change in flow-mediated dilation and carotid-femoral pulse wave velocity were assessed using independent t tests. Prespecified subgroup analyses were conducted using linear regression. No significant between-group differences in flow-mediated dilation (mean difference=-0.62% [95% CI, -1.70 to 0.46]) or carotid-femoral pulse wave velocity (0.25 m/s [95% CI, -0.13 to 0.63]) were observed. Results of the subgroup analyses were consistent with the primary analyses. Longer-term consumption of 1 avocado per day as part of a habitual diet did not improve measures of vascular function compared with a habitual diet low in avocados in individuals with abdominal obesity. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03528031.

Plasma Metabolome Predicts Aortic Stiffness and Future Risk of Coronary Artery Disease and Mortality After 23 Years of Follow-Up in the General Population.

Increased aortic stiffness (arteriosclerosis) is associated with early vascular aging independent of age and sex. The underlying mechanisms of early vascular aging remain largely unexplored in the general population. We aimed to investigate the plasma metabolomic profile in aortic stiffness (vascular aging) and associated risk of incident cardiovascular disease and mortality. We included 6865 individuals from 2 Swedish population-based cohorts. Untargeted plasma metabolomics was performed by liquid-chromatography mass spectrometry. Aortic stiffness was assessed directly by carotid-femoral pulse wave velocity (PWV) and indirectly by augmentation index (AIx@75). A least absolute shrinkage and selection operator (LASSO) regression model was created on plasma metabolites in order to predict aortic stiffness. Associations between metabolite-predicted aortic stiffness and risk of new-onset cardiovascular disease, cardiovascular mortality, and all-cause mortality were calculated. Metabolite-predicted aortic stiffness (PWV and AIx@75) was positively associated particularly with acylcarnitines, dimethylguanidino valeric acid, glutamate, and cystine. The plasma metabolome predicted aortic stiffness (PWV and AIx@75) with good accuracy (R2=0.27 and R2=0.39, respectively). Metabolite-predicted aortic stiffness (PWV and AIx@75) was significantly correlated with age, sex, systolic blood pressure, body mass index, and low-density lipoprotein. After 23 years of follow-up, metabolite-predicted aortic stiffness (PWV and AIx@75) was significantly associated with increased risk of new-onset coronary artery disease, cardiovascular mortality, and all-cause mortality. Aortic stiffness is associated particularly with altered metabolism of acylcarnitines, cystine, and dimethylguanidino valeric acid. These metabolic disturbances predict increased risk of new-onset coronary artery disease, cardiovascular mortality, and all-cause mortality after more than 23 years of follow-up in the general population.

Inverse association between arterial stiffness and perceived fatigue independent of disability status and BMI in multiple sclerosis.

Multiple sclerosis (MS) is an immune-mediated, neurodegenerative disease of the central nervous system. Fatigue represents one of the most prevalent and limiting symptoms of MS, and is associated with vascular dysfunction, notably increased arterial stiffness. This study examined the relationship between arterial stiffness and perceived fatigue in persons with MS. The sample of 52 persons with MS (71.2% Female; Age: 46.7 ± 12.3 yrs.) completed arterial stiffness and fatigue assessments as baseline for an exercise training intervention. Applanation tonometry measured arterial stiffness, pulsatility and waveform characteristics, and yielded the following outcomes: carotid-femoral pulse wave velocity (cfPWV), carotid pulse-pressure (cPP), and aortic augmentation pressure (AP). Perceived fatigue was measured using the Fatigue Severity Scale (FSS). The mean (SD) scores for cfPWV, cPP, and AP were 7.0 ± 1.8m/s, 35.7 ± 8.8mmHg, 8.2 ± 6.2mmHg, respectively. The mean (SD) FSS score was 4.6 ± 1.4 and indicated elevated fatigue. There were statistically significant (p < .05) inverse correlations between cfPWV (r = -.32), cPP (r = -.37) and AP (r = -.32) with FSS scores, and the correlations remained significant even after controlling for disability, body mass index, age, and sex. Our results indicate a consistent pattern of inverse relationships between arterial stiffness, pulsatility, and waveforms with fatigue independent of disability, body mass index, age, and sex in MS. This could be explained by lower sympathetic activation linking higher arterial stiffness, pulsatility and augmentation pressure with lower fatigue in persons with MS.

Vascular function and skeletal fragility: a study of tonometry, brachial hemodynamics, and bone microarchitecture.

Osteoporosis and cardiovascular disease frequently occur together in older adults; however, a causal relationship between these 2 common conditions has not been established. By the time clinical cardiovascular disease develops, it is often too late to test whether vascular dysfunction developed before or after the onset of osteoporosis. Therefore, we assessed the association of vascular function, measured by tonometry and brachial hemodynamic testing, with bone density, microarchitecture, and strength, measured by HR-pQCT, in 1391 individuals in the Framingham Heart Study. We hypothesized that decreased vascular function (pulse wave velocity, primary pressure wave, brachial pulse pressure, baseline flow amplitude, and brachial flow velocity) contributes to deficits in bone density, microarchitecture and strength, particularly in cortical bone, which is less protected from excessive blood flow pulsatility than the trabecular compartment. We found that individuals with increased carotid-femoral pulse wave velocity had lower cortical volumetric bone mineral density (tibia: -0.21 [-0.26, -0.15] standardized beta [95% CI], radius: -0.20 [-0.26, -0.15]), lower cortical thickness (tibia: -0.09 [-0.15, -0.04], radius: -0.07 [-0.12, -0.01]) and increased cortical porosity (tibia: 0.20 [0.15, 0.25], radius: 0.21 [0.15, 0.27]). However, these associations did not persist after adjustment for age, sex, height, and weight. These results suggest that vascular dysfunction with aging may not be an etiologic mechanism that contributes to the co-occurrence of osteoporosis and cardiovascular disease in older adults. Further study employing longitudinal measures of HR-pQCT parameters is needed to fully elucidate the link between vascular function and bone health.

Preliminary Study on Pulse Wave Changes in Patients with Inflammatory Arthropathies Treated with bDMARDs.

Background: Patients with inflammatory arthropathies exhibit an increased cardiovascular disease (CVD) risk as compared to the general population, which is not fully quantified by the conventional CVD risk scores. Biotechnological disease-modifying drugs (bDMARDs) have proved beneficial to reduce the overall CVD risk in these patients, although CVD remains a major cause of increased mortality. Since it has been shown that pulse wave parameters and in particular carotid-femoral pulse wave velocity (cfPWV) are predictors of CVD risk, the aim of this study was to evaluate their changes in patients with inflammatory arthropathies before and after bDMARD therapy. Methods: Pulse wave parameters were evaluated with applanation tonometry in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), and rheumatoid arthritis (RA), before and after two years of bDMARD therapy. Results: At baseline, cfPWV was significantly associated with age (p < 0.001) and, among pulse wave parameters, the subendocardial viability ratio was negatively associated with C-reactive protein (CRP) (p = 0.04) and the HAQ-disability index (p = 0.03). At baseline, PsA patients showed a higher percentage of male subjects, higher CRP, and the highest cfPWV values (p = 0.048). After two years, pulse wave parameters improved in the AS and RA groups, but not in the PsA group. Conclusions: Our data confirm that pulse wave parameters are potentially reversible after bDMARD therapy, as they improved in AS and RA patients. In PsA patients, there were no changes, which may be due to the higher percentage of male subjects and higher baseline cfPWV values.

Effect of low-volume combined aerobic and resistance high-intensity interval training on vascular health in people with type 2 diabetes: a randomised controlled trial

PurposeWe compared the effects of low-volume combined aerobic and resistance high-intensity interval training (C-HIIT), combined moderate-intensity continuous training (C-MICT) and waitlist control (CON) on vascular health after 8-weeks of supervised training, and an additional 10-months of self-directed training, in adults with type 2 diabetes (T2D).MethodsSixty-nine low active adults with T2D were randomised to 8-weeks of supervised C-HIIT (3 times/week, 78-min/week), C-MICT (current exercise guidelines, 4 times/week, 210-min/week) or CON. CON underwent usual care for 8-weeks before being re-randomised to C-HIIT or C-MICT. This was followed by 10-months of self-directed training for participants in C-HIIT and C-MICT. Vascular outcomes were evaluated at baseline, 8-weeks, and 12-months.ResultsAfter 8-weeks, supervised C-HIIT significantly improved relative flow-mediated dilation (FMD) compared with CON (mean difference [MD] 0.8% [0.1, 1.4], p = 0.025). Although not significantly different from CON, the magnitude of change in relative FMD following 8-weeks of supervised C-MICT was similar (MD 0.8% [–0.1, 1.7], p = 0.080). There were no differences in haemodynamic indices, carotid-femoral pulse wave velocity (cfPWV), or aortic reservoir pressure between groups at 8-weeks. After 12-months, there was a significant reduction in haemodynamic indices (time effect, p < 0.05) for both C-HIIT and C-MICT, with no between-group difference. The reduction in cfPWV over 12-months was significantly greater in C-MICT than C-HIIT (group × time effect, p = 0.018). There was no difference in FMD over time or between groups at 12-months.ConclusionsShort-term supervised C-HIIT and C-MICT both increased brachial artery FMD compared with CON. Long-term C-HIIT and C-MICT were beneficial for improving haemodynamic indices, but not brachial artery FMD. C-MICT was superior to C-HIIT for improving cfPWV at 12-months.Trial Registration: Australian New Zealand Clinical Trials Registry Identifier ACTRN12615000475549.

Assessing pressure wave components for aortic stiffness monitoring through spectral regression learning.

The ageing process notably induces structural changes in the arterial system, primarily manifesting as increased aortic stiffness, a precursor to cardiovascular events. While wave separation analysis is a robust tool for decomposing the components of blood pressure waveform, its relationship with cardiovascular events, such as aortic stiffening, is incompletely understood. Furthermore, its applicability has been limited due to the need for concurrent measurements of pressure and flow. Our aim in this study addresses this gap by introducing a spectral regression learning method for pressure-only wave separation analysis. Leveraging data from the Framingham Heart Study (2640 individuals, 55% women), we evaluate the accuracy of pressure-only estimates, their interchangeability with a reference method based on ultrasound-derived flow waves, and their association with carotid-femoral pulse wave velocity (PWV). Method-derived estimates are strongly correlated with the reference ones for forward wave amplitude ( ), backward wave amplitude ( ), and reflection index ( ) and moderately correlated with a time delay between forward and backward waves ( ). The proposed pressure-only method shows interchangeability with the reference method through covariate analysis. Adjusting for age, sex, body size, mean blood pressure, and heart rate, the results suggest that both pressure-only and pressure-flow evaluations of wave separation parameters yield similar model performances for predicting carotid-femoral PWV, with forward wave amplitude being the only significant factor (P < 0.001; 95% confidence interval, 0.056-0.097). We propose an interchangeable pressure-only wave separation analysis method and demonstrate its clinical applicability in capturing aortic stiffening. The proposed method provides a valuable non-invasive tool for assessing cardiovascular health.

Arterial stiffness and endothelial function in the long-term period after a coronavirus disease 2019

Aim. To assess endothelial function and arterial stiffness over time in patients after hospitalization with coronavirus disease 2019 (COVID-19) and compare them with a control group.Material and methods. A total of 53 patients over 18 years of age were hospitalized for COVID-19 in June — August 2021 was examined at two visits: the first — 10-16 months, the second — 14-23 months after discharge from the hospital. Control group included 53 patients from the ESSE-RF epidemiological study of a St. Petersburg population who did not have COVID-19, selected by sex, status of smoking, hypertension and type 2 diabetes. Endothelial function was assessed by the levels of vascular cell adhesion molecule 1 (VCAM-1) and von Willebrand factor (vWF) in plasma and the reactive hyperemia index (lnRHI) on the EndoPAT 2000 system. Carotid-femoral pulse wave velocity (cfPWV) was determined using the SphygmoCor device, while cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) — using the VaSera device.Results. The prevalence of endothelial vasomotor function disorders at the first and second visits in the active group did not differ significantly as follows: lnRHI £0,51 — 21% and 21%, cfPWV &gt;10 m/s — 17% and 14%, and SLSI &gt;9 — 28% and 34%, respectively. Plasma VCAM-1 levels were significantly higher during hospitalization than at the first and second visits — no differences were found between visits. The levels of lnRHI, vWF, cfPWV, CAVI, ABI at the first and second visits did not differ significantly. Post-COVID-19 patients differed from the control group only by a significantly higher ABI level at the second visit. According to the analysis of covariance, COVID-19 is associated with a CAVI increase at the first visit, as well as with an increase in ABI at both visits.Conclusion. The 1,5-2-year follow-up of patients after COVID-19, which required hospitalization, showed a decrease in the plasma endothelial dysfunction parameter VCAM-1. There is no changes in endothelial function and arterial stiffness over a period of time from 10-16 months to 14-23 months after hospitalization with COVID-19.

Arterial Stiffness is an early vascular complication in menopause associated with high levels of asprosin

Background: Menopause is a biological phenomenon experienced by women on average at 51 years of age. The negative impact of menopause on the health of women left without treatment is now recognized but still remains understudied. Menopause is characterized by a decline in ovarian function and estrogen levels that is associated with weight gain and an increased risk of cardiovascular events. Because cardiovascular disease clinically presents 7-10 years following menopause, research on the early onset of cardiovascular events in menopause is urgently needed. Asprosin has been recently identified as an adipokine secreted by white adipose tissue and its levels are increased in obesity. Whether asprosin production is increased in menopause remains unknown. We hypothesize that arterial stiffness is an early vascular complication and is associated with high levels of asprosin in menopause. Methods: 8-week-old female C57BL/6 mice were randomized into two experimental groups: Control Group (n=9) and Ovariectomized (OVX) Group (n=8). The OVX group received surgical ovariectomies and the Control Group underwent surgery without ovary removal. The experimental protocol spanned 22 weeks. Carotid-femoral and intracarotid pulse wave velocity (PWV) measurements, the gold standard to measure arterial stiffness, were obtained. At terminal experiments, thoracic aortas were isolated and mounted on a wire myograph for vascular reactivity studies. Acetylcholine and sodium nitroprusside concentration-response curves were used to assess endothelium-dependent and endothelium-independent relaxation, respectively. Gonadal white adipose tissue (gWAT) was collected for further asprosin measurements. Results: The OVX Group exhibited a significant reduction in uterus weight (59.87 ± 19.62 mg vs. 162.8 ± 16.37 mg controls, p&lt;0.05), validating our menopause model. At week 16, the OVX group exhibited a significant increase in carotid-femoral PWV (3.03 ± 0.09 m/s vs. 2.7 ± 0.11 m/s controls, p&lt;0.05) as well as intracarotid PWV (5.09 ± 0.35 m/s vs 2.5 ± 0.23 m/s controls, p&lt;0.05), confirming arterial stiffness. No differences in endothelium-dependent and endothelium-independent relaxation were observed between the experimental groups, indicating that the menopausal mice had not developed endothelial dysfunction at week 22. As expected, the OVX group showed a significant increase in body weight (24.7 ± 0.26 g vs. 22.2 ± 0.42 g controls, p&lt;0.05) and BMI (0.27 ± 0.002 kg/m2 vs. 0.24 ± 0.005 kg/m2 controls, p&lt;0.05), confirming obesity. The increased weight of gWAT in the OVX group (0.69 ± 0.15 g vs. 0.26 ± 0.02 g controls, p&lt;0.05) was accompanied by elevated asprosin expression (1.14-fold increase, p&lt;0.05). Conclusion: nt of endothelial dysfunction in menopause. Increased asprosin is novel and represents a potential link between adiposity and arterial stiffness in menopause. Future directions will investigate the relationship between arterial stiffness and hypertension in menopause. NIH. 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.

AMYLOID-BETA 40 ADVERSELY INFLUENCES LARGE ARTERY STIFFNESS AND CUTANEOUS MICROVASCULAR FUNCTION IN OLDER ADULTS WITH DIVERSE CARDIOVASCULAR RISK

Objective: Amyloid-beta (Aβ) peptides are considered to play a prominent role in Alzheimer's disease, but emerging experimental and clinical observations link Aβ40 with adverse extracerebral vascular manifestations and cardiovascular disease events. However, it is unclear if Aβ40 adversely influences both large artery stiffness and cutaneous microvascular function in humans. We sought to determine whether Aβ40 was associated with large artery stiffness and cutaneous microvascular function in older adults with diverse cardiovascular risk. Design and method: This cross-sectional study analysed data from 610 older adults (65.7±8.7 yrs, 242F). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (CFPWV) using a SphygmoCor device, and cutaneous microvascular function was assessed by measuring acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) responses following iontophoresis. Plasma Aβ40 concentration was measured using a human Aβ40 assay kit (Simoa Human A β40). Results: One standard deviation increase in Aβ40 was significantly associated with 0.74 (0.52, 0.96) m/s greater CFPWV in an age- and sex-adjusted model (Model-1, p&lt;0.001), which remained significant after further adjustments for conventional cardiovascular disease risk factors [Model-2, 0.46 (0.26, 0.66) m/s, p&lt;0.001]. Additionally, one standard deviation increase in Aβ40 was significantly associated with lower cutaneous acetylcholine [-27.3 (-38.9, -15.7) au] and sodium nitroprusside [-27.0 (-38.1, -15.9) au] responses in Model-1 (both p&lt;0.001). Further adjustments for conventional cardiovascular disease risk factors did not modify the inverse association [Model-2, acetylcholine response, -20.7 (-32.5, -8.8) au: sodium nitroprusside response, -21.1 (-32.3, -9.9) au: both p&lt;0.001]. Subgroup analyses found an indication of interaction effect whereby female sex influenced more on the association between Aβ40 and CFPWV, and type 2 diabetes influenced more on the association between Aβ40 and cutaneous acetylcholine responses (both p&lt;0.05). Conclusions: Aβ40 was associated with increased large artery stiffness and decreased cutaneous microvascular function in older adults with diverse cardiovascular risk. These findings suggest a potential mechanistic link between Aβ40 deposition in the systemic circulation and previously observed adverse cardiovascular disease outcomes.

ASSOCIATION BETWEEN ESTIMATED PULSE WAVE VELOCITY AND INCIDENT NONALCOHOLIC FATTY LIVER DISEASE IN KOREAN ADULTS

Objective: Nonalcoholic fatty liver disease (NAFLD) is associated with vascular dysfunction, one of the signs of which is arterial stiffness. Carotid–femoral pulse wave velocity (PWV), which is considered the gold standard measure of arterial stiffness, can be estimated using two commonly assessed clinical variables: age and blood pressure. This study aimed to evaluate the association between estimated PWV (ePWV) and the prevalence and incidence of NAFLD among Korean adults. Design and method: This study used data from the Ansan–Ansung Cohort Study, a subset of the Korean Genome and Epidemiology Study, and included 8,336 adult participants with and without NAFLD at baseline. The participants were subdivided into three tertile groups according to ePWV. Results: At baseline, the prevalence of NAFLD was 10.5, 27.5, and 35.0% in the first (lowest), second, and third (highest) tertiles of ePWV, respectively. During the 18-year follow-up period, 2,467 (42.9%) incident cases of NAFLD were identified among 5,755 participants who did not have NAFLD at baseline. After adjustment for clinically relevant variables, participants in the second (adjusted hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.12–1.40) and third (adjusted HR, 1.42; 95% CI, 1.24–1.64) tertiles of ePWV had a significantly higher risk of incident NAFLD than those in the first tertile. Conclusions: Higher ePWV independently associated with an elevated risk of NAFLD in the general population.

IMPACT OF ENDOVASCULAR ABDOMINAL AORTIC ANEURYSM REPAIR ON VENTRICULO-ARTERIAL PERFORMANCE AND LEFT ATRIAL FUNCTION: COMPARATIVE PILOT STUDY

Objective: Ventriculo-arterial (VA) coupling characterizes the interaction between myocardial contractile function and the load opposed by the arterial circulation. Clinically, measurable indicators allowing for non-invasive cardiovascular performance assessment include pulse wave velocity (PWV), left ventricular (GLS) and left atrial strain (LA strain). Endovascular repair of the aortic aneurysm is related with changes in arterial properties, yet the impact of these changes on left ventricular and atrial function remains unclear. Aim: This study aimed to compare selected parameters of cardiovascular performance between individuals post-endovascular abdominal aortic aneurysm repair and age- and sex-matched group of hypertensive individuals without aortic aneurysm. Design and method: The study group comprised 36 patients who underwent endovascular stent grafting of the abdominal aorta (mean time from surgery 21,8±8,9 months). Control group included 43 hypertensives matched for age, sex and BMI. In all subjects structured echocardiographic examination was performed, including evaluation of LA strain, left ventricular ejection fraction (EF) and GLS. Carotid-femoral PWV using SphygmoCor device was measured in all participants. Statistical analysis was conducted using SPSS statistics software. Results: The study and control groups did not differ in age (68,9±8,7 vs 67,6±6,6 years; p &gt;0.05), sex (M/F: 32/4 vs 38/5; p&gt;0.05) or BMI (28,9±4,9 vs 29,7 kg/m2; p&gt;;0.05). The study group exhibited significantly higher PWV compared to controls (10,02±1,98 vs 8.99±1,08 m/s; p&lt;0.05). Furthermore, in the study group lower left ventricular ejection fraction (54,7±9,2 vs 59,0± 5,72%; p&lt;0,01), lower absolute values of LV GLS (16,3±2,5 vs 19,0±3,2%, p=0,05) and lower LA strain (23,5±6,2 vs 29,5±10,8%; p&lt;0.01) were observed. Conclusions: This pilot study suggests that changes in arterial stiffness related to endovascular aortic aneurysm repair are associated with worse left ventricular systolic function and left atrial performance. Elucidating their etiology and dynamics necessitates further investigation through prospective studies that account for confounding factors, such as other risk factors that may influence the outcomes of the assessed parameters.

Completing a 4,486 km Multi-stage Ultramarathon Increases Arterial Stiffness and Alters Circulating Factors That Cause Endothelial Cell Dysfunction

Background: Guideline-based levels of aerobic exercise can improve vascular function, in part by decreasing arterial stiffness and oxidative stress, and increasing nitric oxide bioavailability. However, results from single-stage ultramarathons and ultra-endurance feats in modalities such as biking or triathlons suggest that excessive levels of aerobic exercise may impair vascular function. Some athletes will complete multi-day ultra-endurance events. One such example is the TransEurope FootRace (TEFR), a transcontinental ultramarathon in which participants cover 4,486 km in 64 days. However, the impact of this multi-stage ultramarathon on vascular function is unknown. Purpose: Here, we tested the hypotheses that completing the TEFR would increase arterial stiffness measured in vivo and alter circulating factors that increase reactive oxygen species (ROS) production and reduce the activation of endothelial nitric oxide synthase (eNOS) ex vivo. Methods: Data were obtained from 29 men and 1 woman (48±11 years of age) before and within 10 days of completing the TEFR. Arterial stiffness was assessed as carotid-femoral pulse wave velocity measured via MRI. Human aortic endothelial cells (HAECs) in culture were exposed to 10% subject plasma, then stained with florescent probes to detect basal ROS production (CellROX). Protein concentrations of phosphorylated(p)‐eNOS(S1177), a primary activation site of eNOS, were determined in the cultured HAECs via WES. Protein expression was normalized to total protein in the sample. P-eNOS relative to total protein was compared with total eNOS relative to total protein to determine activated eNOS. Results: Completing the TEFR caused a clinically significant 31% increase in carotid-femoral pulse wave velocity (pre-race: 610±37 cm/s, post-race: 800±99 cm/s; p=0.0374). ROS production increased by 40% in HAECs exposed to post-race plasma compared with pre-race plasma (pre-race: 1308±86 AU, post-race: 1836±131 AU; p&lt;0.0001). P-eNOS(S1177) decreased by 71% in HAECs after compared with before the race (pre-race: 0.080±0.038 AU; post-race: 0.023±0.005 AU; p=0.0047), whereas total eNOS was unchanged (pre-race: 1.646±0.328 AU, post-race 1.634±0.6533 AU, p=0.9137), suggesting a marked decrease in eNOS activation after the race. Conclusions: These findings indicate that completing a 64-day, 4,486 km ultramarathon increases arterial stiffness and changes factors in the circulation that increase ROS production and decrease eNOS activation, denoting reduced endothelial cell functioning. Performing this level of prolonged, strenuous physical exercise impairs vascular function in healthy highly trained adults. K01HL153326; SCHU 2514/1-1; SCHU 2514/1-2. 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.

CLINICAL ASSOCIATIONS AND ON-TREATMENT CHANGES OF CENTRAL SYSTOLIC BLOOD PRESSURE AND AR TERIAL STIFFNESS IN PATIENTS WITH DECOMPENSATED HEART FAILURE

Objective: Heart failure (HF) remains one of the major causes of cardiovascular mortality worldwide. The results of studies on arterial stiffness (AS) and central blood pressure (cBP) in HF are contradictory. The aim of this study was to evaluate clinical associations of cBP and parameters of AS and their on-treatment changes after 6 months of stable guideline-directed medical therapy (GDMT) in patients with acute decompensated HF (ADHF). Design and method: In 54 patients (61% males, 69.6±10 years, HTN 100%, median (med) EF 51% (IQR 38;55%), NTproBNP 623 (500;1842)pg/ml; HFrEF 37%, HFmrEF 13%, HFpEF 50%), apart from routine tests (including congestion assessment by bioimpedance vector analysis, lung ultrasound, liver density by FibroScan, and venous excess ultrasound) we assessed cBP and AS with applanation tonometry (SphygmoCor) within 3-4 days after admission and after 6 months. cSBP&gt;/=individual reference values, carotid-femoral pulse wave velocity (cfPWV)&gt;10 m/s and &gt;individual reference values, AS gradient (cfPWV/carotid-radial PWV) &gt;/=1 were considered abnormal. p&lt;0.05 was considered significant. Results: At admission and after 6 months med brachial (b)BP was 117(106;130)/70 (68;80) mmHg 116 (108;130) mmHg, bPP 47 (37;56) mmHg and 47 (39;55) mmHg (p&gt;0.05); cBP 109.5(96;120.5)/71.5 (68;80) mmHg and 106.5(95;113)/73 (65;79) mmHg (p=0.02 for cSBP), cPP 35 (25;43) mmHg and 32.5 (24;38) mmHg (p&gt;0.05), cfPWV 9.9 (6.8;13) m/s and 11.4 (8.5,14.4), m/s (p=0.04), augmentation index (AI@HR75) 20% (13;33%) and 24.5% (18;29%), (p=0.05), PP amplification 129 (120;146) mmHg and 126 (121;136) mmHg, (p=0.02), AS gradient 1.2 (0.9;1.8) and 1 (0.8;1.4) (p&gt;0.05), respectively. Elevated cSBP at admission was observed in 33%, at 6 months – in 38.1%, PWV&gt;10 m/s-in 48.1% and 61.9% respectively, cfPWV&gt;individual reference values–in 33.3% and 66.7% respectively, AS gradient&gt;/=1–in 70.3% and 95.2% respectively. There were no differences in parameters of AS and cSBP and frequencies of their elevation across EF phenotypes and no differences between groups with normal and elevated AS by characteristics of congestion. Conclusions: Patients admitted with ADHF had high frequency of CBP elevation and abnormal AS gradient. The significant increase in cSBP, cfPWV and decrease in PP amplification on stable GDMT needs further evaluation.

Effects of Perceived Social Stress on Cerebrovascular Hemodynamics in Young and Middle-Aged Adults

Depression is associated with altered cerebrovascular hemodynamics, including lower cerebral blood flow, higher cerebral pulsatility, and greater arterial stiffness. There is evidence that perceived stress may contribute to depressive symptomology, but it is unknown if stress may directly impact cerebrovascular hemodynamics. The purpose of this investigation was to examine associations among middle cerebral artery (MCA) hemodynamics, arterial stiffness, and perceived stress in young and middle-aged adults. It was hypothesized that individuals with higher reported social stress would have lower MCA mean velocity and higher MCA pulsatility and arterial stiffness. Methods: 168 adults (range 18-64 years; 40 ± 16 years; BMI 26.6 ± 4.6 kg/m2; n=88 females) underwent resting cerebrovascular measures and completed the self-reported perceived stress scale (PSS-10). Brachial blood pressure and carotid pulse pressure were assessed via oscillometric cuff and tonometry, respectively. Arterial stiffness was assessed as carotid-femoral pulse wave velocity (cfPWV) via tonometry and MCA mean velocity and pulsatility index were assessed via Transcranial Doppler. Results: The sample contained 4 adults with high (PSS score ≥27; mean, 28 ± 1), 38 adults with moderate (PSS score 14-26; mean, 17 ± 2), and 126 adults with low stress (PSS score &lt;13; mean, 8 ± 3). Self-reported perceived stress was not significantly linearly associated with MCA mean velocity (r=-0.10), MCA Pulsatility Index (r=-0.08), or arterial stiffness (r=0.05). A secondary analysis comparing adults with moderate/high stress (n=42) to adults with low stress (n=126) revealed a significantly lower MCA mean velocity among moderate/high stress adults (p&lt;0.05), however this difference was attenuated and no longer statistically significant after covarying for age. Conclusions: This data suggests that perceived stress 1) is not associated with altered cerebrovascular hemodynamics or arterial stiffness in our sample of generally healthy young and middle-aged adults, and 2) may not play a major role in altering cerebrovascular hemodynamics in the context of stress-related disorders (e.g., depression), however future research is required to directly test this hypothesis. Iowa State University College of Human Sciences Faculty Seed Grant. 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.

Central and peripheral cardiovascular responses after acute dietary nitrate supplementation in post-menopausal women

The transition to menopause is accompanied by augmented cardiovascular disease risk, partially attributed to reduced nitric oxide (NO) bioavailability. Despite a lower arterial stiffness than men, postmenopausal women are susceptible to increased aortic pulsatile hemodynamic load because of greater pressure wave reflection and vascular dysfunction. Increasing bioavailable NO with dietary nitrate has shown promise to reduce aortic (aSBP) and brachial (bSBP) systolic pressure healthy postmenopausal women. However, there are limited reports comparing hypertensive (HTN) and normotensive (NTN) postmenopausal women regarding wave separation analysis and vascular function following dietary nitrate supplementation. This study investigated if acute dietary nitrate supplementation would improve aortic hemodynamics, wave reflection characteristics, vascular stiffness, and vasodilatory function. We hypothesized that dietary nitrate would lower pulse wave velocity in hypertensives, lower aortic and brachial blood pressures and forward and backward wave magnitude and increase microvascular, but not macrovascular function in both groups. Fourteen postmenopausal women (n=7 HTN; n=7 NTN) participated in a two-day randomized crossover study design with dietary nitrate (nitrate rich, NR) or a placebo control (NP). Central and peripheral hemodynamics and carotid-femoral pulse wave velocity (cfPWV) were performed with a SphygmoCOR Excel, simultaneous resting macro- and- microvascular function was assessed using flow-mediated vasodilation (FMD) and post occlusive reactive hyperemia (PORH) using near-infrared spectroscopy. aSBP was reduced significantly following NR supplement within groups (HTN: NP 126±2 NR 120±1mmHg) and NTN group (NP 110± 1 NR 104±3mmHg p&lt;0.05). Forward pulse height HTN (NP 29±1.4 NR 26.3±1.4mmHg) NTN (NP 25.6±0.9 NR 24±2.7mmHg) and reflected pulse height HTN (NP 18.2±0.08 NR 17.2±0.4mmHg) NTN (NP 17.7±0.2 NR 15.7±1.07mmHg) were not different. cfPWV was faster in the HTN group and slowed with a NR supplement (HTN: NP 8.2±0.29 NR 7.4±0.31m/s; NTN NP 7.1±0.23 NR 6.6±0.62m/s p&lt;0.05). A significant interaction for %FMD was found (HTN: NP 7.3±0.8 NR 6.2±0.8%; NTN NP 6.6±0.7 NR 9.4±0.7%). Further, we found no difference in the NIRS derived microvascular function measurements (HTN: NP 1.9±0.2 NR 1.7±0.3%/s; NTN NP 1.6±0.1 NR 1.4±0.2%/s p&gt;0.05). These data indicate that dietary nitrate consumption led to a substantial reduction in aortic hemodynamics and reduced pulse wave velocity regardless of hypertension status. Interestingly, macrovascular, but not microvascular vasodilatory function was improved in the NTN women only. Dietary nitrate supplementation appears to have differential effects when considering HTN and NTN postmenopausal women. Supported with funds from The University of Wisconsin-La Crosse RSEL graduate grant. 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.

Home-Based Heat Therapy and Vascular Function of Adults Living with Type 2 Diabetes: Preliminary Analyses of a Randomized Controlled Trial

Background: Several studies indicate that various heat exposure interventions improve peripheral endothelial function and microvascular reactivity, as well as reduce central arterial stiffness and blood pressure in various populations. Nonetheless, few studies have considered the potential therapeutic effects of heat exposure for people living with type 2 diabetes mellitus (T2DM), who are at high cardiovascular risk. In addition, all heat therapy interventions investigated to date have been laboratory-based, which may limit long-term adherence. HYPOTHESES: This study aims is to determine the effects of a 12-week home-based heat therapy intervention on markers of vascular function in adults living with T2DM. The primary hypothesis is that heat therapy improves peripheral endothelial function relative to a sham intervention. Secondary hypotheses include improved microvascular reactivity, central arterial stiffness, and 24h blood pressure. METHODS: Thirteen adults (66 ± 10 years, 28.9 ± 6.0 kg/m2, 9 men/ 4 women) living with TD2M were randomized to 12 weeks of home-based heat therapy (n=7, lower leg immersion in 42°C water) or a thermoneutral sham intervention (n=6, lower leg immersion in 36°C water). Peripheral endothelial function (brachial artery flow-mediated dilation, FMD), microvascular reactivity (post-occlusive reactive hyperemia), arterial stiffness (carotid-femoral pulse wave velocity), and 24h blood pressure (ambulatory blood pressure monitoring), were measured before and after the intervention. RESULTS: Brachial artery FMD changed by 1.72% [95%CI, 0.06; 3.37] in response to heat therapy compared to 0.41% [-1.38; +2.20] in response to the sham intervention. Peak and total reactive hyperemia changed by 0.79 mL/min/mmHg [-0.27; 1.86] and by 1.77 mL/mmHg [0.73; 2.81], respectively, in response to heat therapy compared with 0.76 mL/min/mmHg [-0.38; 1.91] and 1.68 mL/mmHg [0.56; 2.80] in response to the sham intervention. Arterial stiffness changed by 0.55 m/s [-1.62; 2.71] in response to heat therapy compared with -1.60 m/s [-3.75; 0.57] in response to the sham intervention. The 24h-systolic and diastolic blood pressure changed by 6 mmHg [-1; +12] and 2 mmHg [-3; +7], respectively, in response to heat therapy compared with -2 mmHg [-10; +6] and -3 mmHg [-9; +3] in response to the sham intervention. CONCLUSION: These preliminary results suggest that 12 weeks of home-based lower leg hot water immersion improves brachial artery FMD in adults with T2DM. In contrast, the heat therapy intervention does not appear to improve microvascular reactivity, central arterial stiffness, or 24h blood pressure. Cardiometabolic Health Diabetes and Obesity Research Network and Diabète Quebec. 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.