Aortic Stiffness Research Articles

Ascending Aortic Stiffness Analysis Using Tissue Doppler Imaging for the Diagnosis of Coronary Artery Stenosis in Suspected Stable Angina: A Retrospective Study

Background: Coronary artery disease (CAD) and arterial stiffening may coexist. Stable angina pectoris (SAP) is one of the common types of CAD. However, the association between SAP and aortic stiffness metrics remains poorly understood. Tissue Doppler imaging (TDI) measurement of ascending aorta motion velocity may be used to employed to assess the elastic properties of the great arteries. We hypothesized that non-CAD individuals may exhibit higher. TDI velocities in the ascending aorta. Aim: To explore the correlation between ascending aortic stiffness and SAP using parameters derived from two-dimensional and TDI echocardiography of the ascending aorta. Methods: This study comprised 118 patients with clinically suspected SAP. Two-dimensional echocardiography, TDI, electrocardiogram (ECG), and coronary angiography (CAG) were performed on all patients. Patients with coronary lumen area stenosis ≥70% were categorized as having significant CAD (CAD Group n=57) and were compared with patients without significant CAD (non-CAD Group n=61). Using TDI, aortic systolic velocity (SAo), early diastolic velocity (EAo), and late diastolic velocity (AAo) were measured from the anterior wall of the ascending aorta 3 cm above the aortic cusps in the parasternal long-axis view. Aortic stiffness index (β), aortic distensibility (D), and pressure-strain elastic modulus (Ep) were calculated from aortic diameters measured by two-dimensional M-mode echocardiography and blood pressure obtained by sphygmomanometry. Results: SAo was significantly higher in the non-CAD group (11.70 ±1.53 cm/s vs.12.80 ±2.21 cm/s, p < 0.05). EAo and AAo velocities of ascending aorta were similar in control and CAD groups. Based on the receiver operating characteristic curve (ROC curve) for diagnosing non-CAD, the optimal cut-off value of SAo was ≥13.35 cm/s (sensitivity, 85.96%; specificity, 40.98%; area under curve (AUC)=0.64; P<0.05). There was a significant correlation between SAo velocity and β (r=−0.34, P<0.05), D (r=0.32, P<0.05) and Ep (r =−0.29, P<0.05). Conclusions: Arterial stiffness is lower in patients without significant CAD. Measuring SAo of the anterior ascending aorta using TDI echocardiography has good sensitivity but poor specificity in patients without significant coronary artery stenosis in SAP.

EFFECT OF ANTI–PCSK9 ANTIBODIES ON ARTERY STRUCTURE AND FUNCTION: THE NIGUARDA HOSPITAL COHORT

Abstract Background PCSK9 inhibitors antibodies (PCSK9–i) are a valid option to reduce LDL cholesterol in patients who failed to reach therapeutic target with maximized lipid–lowering therapies or in patient with statins intolerances. These antibodies reduce the frequency of new cardiovascular events, however if this effect is due only to LDL reduction or also to an improvement in arterial function and structure is yet to be proved. Our study aim was to evaluate aortic stiffness (Pulse Wave Velocity – PWV), carotid’s Intima–Media Thickness (IMT) and endothelial function (brachial Flow Mediated Dilatation – FMD) in patients treated with Alirocumab and Evolocumab. Methods This is a monocentric prospective longitudinal study on patients who received PCSK9–i administrations at the Niguarda Hospital’s cardiovascular rehabilitation and prevention unit. They underwent 3 evaluations of PWV, FMD and IMT (T0 the same day of the first injection, T1 after 6 months and T2 after 12 months of therapy). Results 39 patients concluded the 12 months period. The group average age is 66.8 ± 7.6 years, most of them were male (64.1%). LDL cholesterol average levels were significantly reduced by the therapy (128.3 ± 27.7 vs 44.7 ± 29.3 mg/dL, p<0.001), however, there were no significant changes in PWV (10.2 ± 3.0 vs 10.6 ± 2.5 m/s, p=0.404), FMD (8.6 ± 7.0 vs 8.9 ± 7.4 %, p=0.560) and IMT (768.7 ± 175.4 vs 733.5 ± 147.2 µm, p=0.270) values. Conclusions It was not possible to prove a significant effect of PCSK9–i on vascular properties, however, the stability of these indexes may suggest a deceleration of the atherosclerotic disease which it could have worsen in this population, especially considering the risk factors of our patients.

Should aortic stiffness parameters be used in MIS-C patient follow-up?

We evaluated the short- and long-term effects of multisystem inflammatory syndrome in children (MIS-C) on their cardiovascular system. The study population consisted of 38 MIS-C patients and 55 control patients. Standard echocardiographic measurements and aortic stiffness parameters were compared between the two groups at different time points. During the standard echocardiographic examination at the time of diagnosis, mitral valve insufficiency was detected in 42% of the cases, left ventricular systolic dysfunction in 36%, aortic valve insufficiency in 3%, tricuspid valve insufficiency in 13%, and coronary artery dilatation in 31%. The ejection fraction, pulse pressure of the experimental group were significantly lower than the control group (p < 0.01, p = 0.045, respectively). When aortic stiffness parameters were compared, it was seen that the parameters increased in the experimental group and the difference was significant for aortic distensibility. (p = 0.105, p = 0.029 respectively). When comparing the experimental group's results at diagnosis and at the sixth month, there was a decrease in aortic stiffness parameters at the sixth month compared to the time of diagnosis, but the difference wasn't significant (p = 0.514, p = 0.334). However, no statistically significant difference was detected when comparing the aortic distensibility results of the experimental group with the control group at the sixth month (p = 0.667). Our results showed that many pathological echocardiographic findings detected at diagnosis in MIS-C patients returned to normal within six months. Therefore, we believe that the cardiovascular follow-up period of MIS-C cases should be at least six months.

Pediatric Primary Raynaud's Phenomenon: A Comprehensive Cardiovascular Analysis.

Our aim in this study is to evaluate the cardiovascular findings of pediatric patients with primary Raynaud's phenomenon (RP) and to determine if there are any pathological findings. Our study included 42 pediatric patients aged between 7 and 18 who were diagnosed with primary RP and did not have any additional underlying structural vascular disease or secondary rheumatological conditions. The control group consisted of 30 healthy volunteers aged 7-18years, matched by age and sex, without any additional diseases. We evaluated demographic, clinical, and laboratory findings, echocardiographic and capillaroscopic features, as well as carotid intima-media thickness. Compared to the control group, pediatric patients with primary RP showed increased A wave velocity and E/E' ratio parameters in the left ventricle, indicating diastolic dysfunction of the heart. The isovolumetric relaxation time (IVRT) was prolonged in both the left and right ventricles, and the E/A ratio decreased in the left ventricle. The myocardial performance index (MPI), indicating both systolic and diastolic dysfunction, increased in both ventricles. Additionally, the aortic stiffness index, aortic elastic modulus (Ep), and left carotid intima-media thickness (CIMT) significantly increased, while distensibility decreased in pediatric patients with primary RP compared to the control group. The cardiovascular evaluation of pediatric patients with primary RP revealed that diastolic dysfunction is likely present in both the left and right heart. Additionally, based on the aorta and carotid intima measurements, it is suggested that pediatric patients with primary RP are at risk for developing atherosclerosis.

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.

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.

High altitude sojourn elicits divergent effects in aortic and carotid stiffness in healthy-young adults

High altitude exposure challenges the cardiovascular system to compensate for barometric pressure-mediated reductions in arterial oxygen content. Reductions in oxygen content elicit simultaneous increases in sympathetic nervous system activity and vasodilation that may have competing effects on changes in large artery stiffness. The objective of this study was to examine changes in aortic and carotid stiffness during high altitude sojourn in healthy, young adults. We hypothesized that short-term high-altitude sojourn would increase both aortic and carotid stiffness. 17 Generally healthy adults (23±4 yrs, 25.0±3.0 BMI, n=9 females) underwent vascular assessments in the supine position at 1400 m and after an 8-day incremental ascent to 4300 m. Aortic stiffness and carotid β-stiffness were derived from carotid-femoral pulse wave velocity (cfPWV) via applanation tonometry and right common carotid artery ultrasonography, with blood pressure assessed via oscillometry. Ascent from 1400 m to 4300 m resulted in decreased arterial oxygen saturation (-11±4 %, p&lt;0.001) and carotid β-stiffness (-4.48±2.73 au, p&lt;0.001), and increased cfPWV, (+54.98±78.10 cm/s, p=0.01) and mean arterial pressure (+4±7 mmHg, p=0.02). Changes in cfPWV, arterial oxygen saturation, and blood pressure were moderately to strongly correlated (r=-0.425-0.503, p=0.09-0.04). Our data suggest that short term exposure to high altitude has differential effects on carotid versus aortic stiffness despite increases in mean blood pressure. Increases in aortic stiffness appear related to hypoxia-induced reductions in arterial oxygen saturation and concomitant increases in blood pressure, while reductions in carotid stiffness may stem, in-part, from compensatory carotid artery dilation necessary to increase cerebral blood flow at high altitude. Additional research is necessary to further understand mechanisms underlying differential changes in large artery stiffness during high altitude sojourn. 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.

OxLDL/LOX-1 Mediated Sex, Age, and Cell Dependent Alterations in Mouse Thoracic Aortic Vascular Reactivity, Stiffness, and Remodeling

Elevated oxidized low-density lipoprotein (oxLDL) is a risk factor and component that worsens cardiovascular disease states. OxLDL can elicit its detrimental action, via lectin-like oxLDL receptor 1 (LOX-1) and has been shown to disrupt vascular function. In this study, we determined whether oxLDL, via LOX-1, alters aortic vascular reactivity and determined if sex differences exist. Thoracic aortic endothelium-intact or -denuded ring segments were isolated from intact C57BL/6J female and male mice and incubated with oxLDL ex vivo (50ug/dL; 2h). Using wire myography, cumulative concentration-response curves to phenylephrine (PE) were generated to determine contractile responses. From these curves, the EC50 was determined and used to contract rings to assess acetylcholine (ACh) dependent relaxation. Calculated aortic stiffness and remodeling, as well as mRNA expression of vasoactive and pro-inflammatory mediators were assessed. BI-0115 (10μM; selective LOX-1 inhibitor) was used to determine LOX-1 dependence. In this study, we investigated the effects of oxidized low-density lipoprotein (oxLDL) via the LOX-1 receptor on murine thoracic aortic vasoreactivity, stiffness, and remodeling across age and sex. Our results demonstrate a differential sex, age, endothelial cell, and LOX-1 dependent alterations to the effcacy of PE-induced contractile responses and ACh-mediated vasorelaxation in the thoracic aortic rings following oxLDL exposure. Additionally, we observed a distinct sex and age effect on thoracic aortic stiffness following exposure to oxLDL. There was also a sex effect on calculated vessel diameter, as well as an age effect on oxLDL-mediated inward remodeling that was LOX-1 dependent. We also observed an oxLDL and age dependent increase in LOX-1, IL-6, endothelin-1 (ET-1), and ET-1 receptor alpha and beta mRNA expression. Thus, LOX-1 inhibition and the resulting attenuation of oxLDL/endothelial-mediated alterations in aortic function suggests that there are differential sex differences in the role of oxLDL/LOX-1 in the thoracic aorta of male and female mice. In conclusion, acute exposure to oxLDL led to altered vasoreactivity, endothelial dysfunction, and changes in aortic stiffness and remodeling. These effects were in-part age, sex, endothelial, and LOX-1 dependent. This study reveals potential complex interactions in oxLDL/LOX-1-mediated vascular responses that could serve as potential therapeutic intervention for vascular diseases such as atherosclerosis. University of Arizona Valley Research Partnership Grant VRP37 P2 (RJG), American Heart Association 19AIREA34480018 (RJG), UA VRP Grant VRP55 P1a (TSW). 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.

Intermittent oral supplementation with fisetin improves arterial function in doxorubicin chemotherapy-treated mice by suppressing cellular senescence

Introduction. Arterial dysfunction (endothelial dysfunction and aortic stiffening) is a key antecedent to the development of cardiovascular diseases. Cellular senescence, a state of nearly irreversible cell cycle arrest, develops in arteries following doxorubicin (Doxo) chemotherapy treatment and induces arterial dysfunction. Fisetin is a natural senolytic (senescent cell clearing compound) that improves arterial function in old mice. However, it is unknown if fisetin supplementation can decrease cellular senescence to reverse Doxo-induced arterial dysfunction. Purpose. To determine if fisetin supplementation can improve arterial function following Doxo treatment by decreasing cellular senescence. Methods &amp; Results. Cell culture. Human aortic endothelial cells were treated with fisetin for 48 hr (0.25, 0.5, 1 uM) following Doxo-induced cellular senescence (200 nm Doxo for 48 hr). 1 uM fisetin lowered senescence burden (senescence-associated β-galactosidase staining) by ~50% ( P = 0.0003). Animals. Young adult (4 mo) male/female p16-3MR mice received Doxo (10 mg/kg) or sham (saline) intraperitoneally. Four weeks later (established time-point of Doxo-induced arterial dysfunction), animals were treated daily with vehicle (V; 10% EtOH, 30% PEG400, 60% Phosal 50 PG) or fisetin (F; 100 mg/kg) via oral gavage using an intermittent 1 week on - 2 weeks off - 1 week on dosing paradigm, yielding 4 groups (Sham-V; Sham-F; Doxo-V; Doxo-F). Data from Sham-V and Sham-F groups were similar for all outcomes. Data are combined due to no sex differences. Endothelial function. Endothelial function (carotid artery endothelium dependent dilation [EDD] to acetylcholine [ACh]) and nitric oxide (NO)-mediated EDD (± L-NAME) were measured following fisetin (or vehicle) supplementation. Doxo-V mice had lower peak EDD relative to Sham-V (73 ± 2 v. 89 ± 2 %; P = 0.003), and this difference was ameliorated in Doxo-F animals (88 ± 3 %). Likewise, Doxo-V mice had lower NO-mediated EDD compared to Sham-V (39 ± 7% v. 55 ± 8%, P = 0.047), and this difference was ameliorated in Doxo-F mice (66 ± 7%). Incubation of carotid arteries ex vivo with ganciclovir (GCV) to clear p16+ senescent cells in p16-3MR mice normalized peak EDD (Sham-V, 93 ± 1; Doxo-V, 93 ± 2; Doxo-F, 91 ± 2%), suggesting that reducing cellular senescence is the mechanism by which fisetin supplementation improved endothelial function. Aortic stiffness. The Doxo-induced increase in aortic stiffness (aortic pulse wave velocity [PWV]) (Doxo-V, 426 ± 20 vs. Sham-V, 332 ± 5 cm/sec; P &lt; 0.0001) was reversed following fisetin supplementation in Doxo-F mice (pre-fisetin: 426 ± 10 v. post-fisetin: 345 ± 5 cm/sec; P = 0.001). The differences in PWV were associated with corresponding differences in ex vivo aortic intrinsic mechanical wall stiffness (Doxo-V, 5991 ± 362 v. Doxo-F, 3996 ± 415 vs. Sham-V, 4813 ± 133 kPa; P = 0.010). Ex vivo incubation of aorta rings with GCV for 48h ameliorated group differences in aortic intrinsic mechanical wall stiffness, suggesting a causal role for suppression of cellular senescence in the response. Conclusion: Intermittent fisetin supplementation may be a novel strategy to favorably modulate cellular senescence, a key cellular signaling pathway mediating arterial dysfunction with Doxo chemotherapy. R21 AG078408 &amp; K99 HL159241. 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.

Estudio de la asociación de marcadores de rigidez arterial central y periférica con la función renal en pacientes con hipertensión arterial, diabetes mellitus y enfermedad renal crónica

Rationale and objectivesIncreased aortic or central arterial stiffness (CAS) is a major factor in cardiovascular morbidity and mortality in patients with vascular risk factors. Decreased glomerular filtration rate (GFR) and increased urinary albumin excretion (uALB) are associated with lethal and non-lethal cardiovascular events. The pathophysiological mechanisms of this association are not fully defined.The aim of this study was: 1.- To analyze the CAS, comparing several markers, in subjects with arterial hypertension (HTN), diabetes mellitus (DM), chronic kidney disease (CKD) and their combination. 2.- To study the possible association of CAS with renal dysfunction (decrease in GFR and increase in uALB). Material and methodsA total of 286 subjects were included, divided into several groups: Control (n: 38); HTN (n:51); DM without CKD (n:26); CKD without DM (n:77); CKD with DM (n:94). Several indices obtained by applanation tonometry were used to determine the CAS: carotid-femoral pulse velocity (VPc-f); central pulse pressure (cPP); augmentation index standardized to a cardiac frequency of 75 l/min (IA75); peripheral / aortic arterial stiffness gradient (ASGp-a). As a marker of peripheral arterial stiffness, the carotid-radial pulse velocity (PVc-r) was determined. The ASGp-a was calculated from the PVc-r /PVc-f ratio. The subendocardial viability index (iBuckberg) was obtained from the aortic pulse wave.Multiple regression, binary logistic regression, and multinomial regression were used to study the association between arterial stiffness markers and renal function. ResultsThe adjusted values of the PVc-f [(median (interquartile range) (m/sec)] were significantly higher in subjects with DM [(9 (1.2)], CKD [(9.4 (0.7)] and DM with CKD [(10.9 (0.7)] than in the control group [(8.2 (1.3)] and group with HTN [(8.3 (0.9)], (p:0.001). Patients with DM with CKD had higher PVc-f values than all other groups (p: 0.001). The ASGp-a of the patients was significantly lower than that of the controls, and the group with DM with CKD had significantly lower values than the other groups. The cPP in the DM with CKD group was significantly higher than in the other groups. All patients had an AI75 higher than the control group.When all aortic stiffness markers were introduced together in the regression, PV c-f was the only one that, after multivariate adjustment, was independently and inversely associated with GFR (β; –4, p:0.001) and predicted the presence of GFR decrease (< 60mL/min/1.73 m2), [(OR (95%CI): 1.50 (1.17-1.92; p:0.001]. The PVc-f was the only index directly associated with albuminuria (β: 0.15, p: 0.02) and predicted the existence of abnormal albuminuria (> 30mg/g), [(OR; 1.66 (1.25-2.20), p:0.001)]. The PVc-f was also associated with the iBuckberg (β: -2.73, p: 0.01).Multinomial regression confirmed that PVc-f is a significant determinant of GFR and uALB. On the other hand, the increase in PVc-f and the presence of DM contribute significantly to the magnitude of albuminuria. ConclusionsAortic stiffness increases in the presence of vascular risk factors such as hypertension, DM and CKD. This increase is greater when DM and CKD coexist. Increased aortic stiffness is inversely associated with GFR and directly with uALB, and is predictive of decreased GFR and abnormal uALB. The VPc-f is the parameter of aortic stiffness that is most consistently associated with renal dysfunction. Increased aortic stiffness could be one of the pathomechanisms linking renal dysfunction to cardiovascular events.

The bottlenose dolphin (Tursiops truncatus): A novel model for studying healthy vascular aging

Aging is the primary non-modifiable risk factor for the development of cardiovascular diseases (CVD). CVD are often preceded by arterial dysfunction, including endothelial dysfunction and aortic stiffening. Our preliminary results suggest that the circulating milieu is associated with differences in arterial function in young and mid-life/older (ML/O) adults. Moreover, incubation of mouse arteries with serum from young and ML/O adult humans can directly transfer arterial aging phenotypes for endothelial function and aortic stiffness. These results suggest that age-related changes in the circulating milieu are an underlying mechanism of age-related arterial dysfunction. Dolphins are mammals that have evolutionary adapted to diving, with constant cycles of tissue hypoxia/reoxygenation and disturbed shear stress -- exposures which cause arterial dysfunction in humans. Dolphins also have long lifespans and are relatively free of CVD. Taken together, dolphins may be a unique model of healthy vascular aging, with possible applications to clinical medicine. PURPOSE: To determine if the serum of bottlenose dolphins ( Tursiops truncatus) induces the same arterial aging phenotypes as the serum of age-equivalent humans. Methods: Common carotid arteries and aorta rings from young (Y; 5 mo) and old (O; 25 mo) wildtype female (F) and male (M) C57BL/6N mice were exposed ex vivo for 24 and 48h, respectively, to 5% sex-matched adult dolphin serum. Dolphin serum of Y (17 ± 4 years; n = 16: 5F / 11 M) and ML/O (29 ± 2 years; n = 4: 1F/3M) adults was obtained from the National Marine Mammal Tissue Bank. Endothelial function was assessed as carotid artery endothelium-dependent dilation (EDD) in response to increasing doses of acetylcholine. Aortic stiffness was measured as elastic modulus, a measure of intrinsic mechanical wall stiffness. Dolphin serum-mediated responses in mouse arteries were compared with that of adult human serum data (Y, 24 ± 1 years, n=10: 5F/5M; ML/O, 67 ± 3 years, n=10: 5F/5M). Differences were assessed via 2-way ANOVAs; within species post hoc analyses conducted between age groups. Results: Endothelial Function. Peak EDD in Y mouse carotid arteries was lower following exposure to serum from ML/O adult humans (ML/O, 78 ± 2 v. Y, 92 ± 2%; P &lt; 0.001) and higher in O mouse carotid arteries after exposure to Y adult serum (92 ± 2 vs. 73 ± 5%, P = 0.001). In contrast, EDD was similarly high across all groups following dolphin serum exposure (³ 93% peak EDD), independent of the age of the serum donor or the mouse arteries (Y v. ML/O serum donor in Y arteries, P = 0.773; in O mouse arteries, P = 0.942). Aortic Stiffness. Stiffness in Y aortic rings was ~60% higher following exposure to ML/O adult human serum (P = 0.001 v. Y adult serum). In O mouse aortic rings, stiffness was 25% lower after exposure to Y adult serum (P = 0.044 v. ML/O adult serum). In contrast, stiffness was similar across all groups following dolphin serum exposure, independent of age of the serum donor or the arteries (Y v. ML/O serum donor in Y aortic rings, P = 0.974; in O aortic rings P = 0.157). CONCLUSIONS: The circulating milieu of bottlenose dolphins may be geroprotective, which could serve as a model to investigate mechanisms and potential therapies for preventing adverse vascular aging and promoting CV health and longevity in humans. FUNDING: R21 AG078408 &amp; MSCA-IF-2019:892267. 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.

Liver-specific Bmal1 deletion in mice leads to increased aortic stiffness and altered vascular remodeling

Circadian rhythms have an important role in cardiovascular physiology. Circadian clock genes are critical for vascular homeostasis. Global loss of the circadian clock gene Bmal1 increases aortic stiffness with impaired vascular function and blood pressure rhythm in mice. We previously found that hepatocyte-specific Bmal1 deletion (HBK) in the liver changes perivascular adipose tissue-mediated vascular function in young adult mice, indicating that liver circadian clock disruption distally affects function in another tissue and potential cross-talk between the liver and vasculature. We hypothesized that liver-specific Bmal1 deletion leads to aortic stiffness and pathological vascular remodeling. Studies were performed in 4- to 6- month old male HBK and flox control mice. Aortic stiffness, measured by pulse wave velocity, was significantly elevated in HBK mice compared to flox control mice (Flox: 1.84 ± 0.1 m/s; HBK: 2.9 ± 0.2 m/s; n = 5, p &lt; 0.01). Systolic blood pressure (tail-cuff) in the light phase was similar in both flox control and HBK mice (Flox: 101 ± 1 mm Hg; HBK: 103 ± 2 mm Hg; n = 3-5, p = 0.35). Aortas and plasma were collected at ZT2 for histological analysis and metabolite measurements. MetaMorph software analysis of Masson’s Trichrome-stained aortic sections revealed significantly increased aortic wall fibrosis in HBK mice (% fibrosis per area, Flox 17.0% ± 3.3%, HBK 27.4% ± 2.1%, p=0.03). The medial cell number in H&amp;E stained-aortic sections was increased in HBK mice compared to flox control mice (Flox: 534.6 ± 31.9; HBK: 1069 ± 90.1; p &lt; 0.01). TUNEL stained apoptotic cells were also counted and more apoptotic cells were observed in young HBK mice aortas compared to flox controls (Flox: 224.4 ± 56.1; HBK: 408.4 ± 20.8; p = 0.02). Aortic wall thickness was not different in young adult HBK mice compared to flox control mice. Aortic levels of the lipid peroxidation marker vascular 4-hydroxynonenal (4-HNE), a measure of oxidative stress, were similar between flox control and HBK mice. In plasma, the oxidative stress marker, 8-hydroxy-2’-deoxyguanosine (8-OHdG), a DNA damage product, and plasminogen activator inhibitor-1 (PAI-1) were not different between genotypes. In conclusion, our findings indicate that liver circadian clock disruption increases aortic stiffness and fibrosis with higher cell numbers as well as aortic apoptosis. These data suggest that altered vascular remodeling in HBK mice may contribute to aortic stiffness resulting in cardiovascular disease. Funded by P01HL136267 to JSP, R21AA026906 to SMB, and AHA 856877 to PP. 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.

Abstract 2144: Smooth Muscle Cell Specific Beclin-1 Deficiency Promotes Aging-accelerated Aortic Stiffness In Mice

Background and Objective: Aortic stiffness, a hallmark of aging, is a significant riskfactor for cardiovascular diseases like hypertension and atherosclerosis. Vascularsmooth muscle cells (SMCs) play a crucial role in maintaining aortic structural integrity,and increased SMC stiffness contributes to age-accelerated aortic stiffness.Autophagy, a self-regulatory cellular process, declines with aging, predisposingindividuals to age-related diseases. Reduced levels of Beclin-1, a key autophagyinduction gene, have been observed in aging-associated diseases. However, thecontribution of SMC-derived Beclin-1 in aortic stiffness progression remains unknown.This study examined the contribution of SMC-derived Beclin-1 to aortic stiffnessdevelopment in mice. Methods and Results: Ultrasound measurements revealed increased aortic stiffnessin 60-week-old aged mice, characterized by elevated pulse-wave velocity (PWV) andreduced aortic distensibility and radial strain compared to 8-week-old young mice.Western blot and immunohistochemistry analyses showed a decline of aortic Beclin-1in the SMC-rich aortic medial layer of aged mice. To investigate the role of SMC-Beclin-1 in aortic stiffness, mice with inducible SMC-Beclin-1 deletion were generated bybreeding Acta2-CreERT2 hemizygous mice with Beclin-1 floxed mice. Baselinemeasurements at 8 weeks showed no PWV difference between Beclin-1 x Acta2-CreERT2 (Cre+) and non-Cre littermates (Cre-). However, following tamoxifen-induced Cre recombination, SMC-Beclin-1 deficiency significantly accelerated PWVby 18 weeks (Cre-: 2.4 ± 0.1 vs Cre+: 4.1 ± 0.2 m/s; P&lt;0.001), accompanied byreduced aortic distensibility (Cre-:115.4 ± 3.2 vs Cre+: 93.1 ± 3.4; P&lt;0.001) and radialstrain(Cre-:20.3 ± 0.7 vs Cre+:15.8 ± 0.7; P&lt;0.001). Histological analyses indicatedthat Beclin-1 deficiency increased collagen deposition in aortic media and adventitia.RNA Sequencing and Western blot analyses identified extracellular matrix regulatingGalectin-3 and S100A4 as novel targets of Beclin-1, selectively upregulated in SMC-Beclin-1 deficient aorta. Conclusion: These findings suggest that SMC-derived Beclin-1 plays a critical rolein suppressing aging-accelerated aortic stiffness in mice.

Lactobacillus plantarum 299v administration prevents high-sodium diet-induced glycocalyx degradation and arterial dysfunction

A central feature of cardiovascular disease (CVD) is arterial dysfunction (i.e., elevated systolic blood pressure [BP], aortic stiffening, and endothelial dysfunction), which may be initiated by a degraded endothelial glycocalyx. The glycocalyx is a negatively charged structure bound to the vascular endothelium that appears to play a critical role in cardiovascular health, particularly by buffering sodium in blood, although excessive sodium degrades the glycocalyx. In the United States, a high-sodium (HS) diet is consumed by ~90% of the population with average sodium intake ~2.3x greater than recommended by the American Heart Association. We have previously shown that HS diet induces glycocalyx degradation and arterial dysfunction in outbred, genetically diverse UM-HET3 mice. Others have shown that HS diet lowers Lactobacillus abundance in mouse gut microbiome. However, it is unknown whether maintaining Lactobacillus would prevent HS diet-induced glycocalyx degradation and arterial dysfunction. To test this concept, male and female UM-HET3 mice (n=21-35/group) were randomized into a low-sodium (LS) diet (1% NaCl), HS diet (4% NaCl), or HS diet with Lactobacillus plantarum 299v (Lp299v) administration (60 million CFU/ml in drinking water) for 12 weeks. Glycocalyx barrier function was determined by assessing perfused boundary region (PBR), which represents red blood cell penetration into the glycocalyx. At week 12, we observed higher PBR in HS mice (2.36±0.04 μm) compared to LS and HS+Lp299v mice (2.09±0.03 and 2.20±0.04 μm, respectively; p&lt;0.05), indicating a worse glycocalyx barrier function in HS mice. PBR was similar between LS and HS+Lp299v mice (P&gt;0.05), indicating a preserved glycocalyx barrier function in HS+Lp299v mice. Systolic BP was higher in HS (127±1 mmHg) compared to LS and HS+Lp299v mice (113±1 and 118±1 mmHg, respectively; p&lt;0.05). Aortic stiffness, determined by aortic pulse wave velocity (PWV), was also higher in HS (345±5 cm/s) compared to LS and HS+Lp299v mice (268±5 and 300±3 cm/s, respectively; p&lt;0.05). However, systolic BP and aortic PWV were higher in HS+Lp299v compared to LS mice (p&lt;0.05). Ex vivo endothelial function, determined by the maximal vasodilatory response to acetylcholine in the carotid artery, was lower in HS (83.9±1.3%) compared to LS and HS+Lp299v mice (89.8±1.3 and 90.1±1.0%, respectively; p&lt;0.05). Endothelial function was similar between LS and HS+Lp299v mice (P&gt;0.05). In summary, Lp299v administration prevents HS diet-induced glycocalyx degradation and endothelial dysfunction, while mitigating HS diet-induced elevations in systolic BP and aortic stiffness. These findings suggest that Lp299v administration may be a novel strategy to lower the risk of CVD in humans that consume a HS diet. This study was funded in part by a grant from the National Institutes of Health (R00 AT010017). 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.

The Circulating Milieu Mediates Arterial Dysfunction with Aging: Protection by Habitual Aerobic Exercise

Age-related arterial dysfunction (aortic stiffening and endothelial dysfunction) is the key antecedent to cardiovascular diseases. Habitual aerobic exercise largely mitigates arterial dysfunction in mid-life/older (ML/O) adults; however, the mechanisms by which this occurs remain to be fully elucidated. The circulating milieu (bioactive factors in the bloodstream) shifts towards a pro-inflammatory/oxidative state with advancing age but is preserved with habitual aerobic exercise. However, it is unclear if the circulating milieu directly contributes to age-related arterial dysfunction and if habitual aerobic exercise preserves arterial function with aging, in part, by favorably modulating the circulating milieu. PURPOSE: To determine the influence of aging and habitual aerobic exercise on circulating milieu-mediated aortic stiffening and endothelial function. METHODS: Human serum was collected from healthy young (18-29 yr) and ML/O (50+ yr) men and women. Aerobic exercise status was determined by leisure-time physical activity (&gt;60 h/wk). Aortic rings (~1 mm) and common carotid arteries were obtained from young adult (3-4 mo), intervention naïve male and female C57BL/6N mice to assess aortic stiffness and endothelial function, respectively. Arteries were exposed ex vivofor 24-48 hours to 5% sex-matched human serum from one of the following groups: young sedentary (n=9; 4F), ML/O sedentary (n=14; 7F) or ML/O habitually aerobic exercise trained (n=8; 4F). Aortic stiffness was measured as elastic modulus (a measure of intrinsic mechanical wall stiffness). Endothelial function was assessed as endothelium-dependent dilation (EDD) and endothelium-independent dilation (EID) as peak response to acetylcholine and the nitric oxide (NO) donor sodium nitroprusside, respectively. Differences were determined via one-way ANOVA. RESULTS: Aortic Stiffness. Aortic elastic modulus was higher in aorta rings incubated with ML/O sedentary serum compared to young sedentary serum (ML/O sedentary, 4912 ± 588 v. Young sedentary, 3019 ± 522 kPa; p=0.020). Compared with ML/O sedentary serum, aorta rings incubated with ML/O trained serum had lower elastic modulus (2237 ± 426 kPa, p=0.002) which was not different to aorta rings incubated with young sedentary serum (p=0.369). Endothelial Function. Peak EDD was lower in carotid arteries incubated with ML/O sedentary v. young sedentary serum (79 ± 3% v. 92 ± 2%, p=0.001). Compared with ML/O sedentary serum, incubation with ML/O trained serum evoked higher peak EDD (93 ± 1%; p=0.001) that was similar to that produced by Young sedentary serum (p=0.866). There were no group differences in peak EID (p=0.228) suggesting that circulating milieu-induced differences were endothelium-specific and were not attributable to changes in smooth muscle sensitivity to NO. CONCLUSION: These findings suggest that the circulating milieu is a key mechanism by which aging induces arterial dysfunction and by which habitual aerobic exercise training preserves arterial function with aging. F31 HL165885, R21 AG078408, K99 HL159241, K99/R00 HL151818. 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 cell HDAC1 mediates aortic stiffness in diet-induced obese mice

Histone deacetylase 1 (HDAC1) is an important regulator of cell differentiation and is associated with progression of cardiovascular disease (CVD). Our lab previously showed that over-expression of HDAC1 in cultured endothelial cells reduces NO production. Other investigators have shown increased HDAC1 protein in models of CVD. However, there is a gap in knowledge of whether endothelial-specific HDAC1 mediates vascular dysfunction in models of CVD. Diet induced obesity (DIO) is a leading risk factor for CVD, thus our studies are focused on a chronic high fat feeding mouse model. Our studies utilize a mouse model of DIO where mice are fed a normal diet (ND, 10% fat) or high fat diet (DIO, 45% fat) beginning at 8 weeks of age for 20 weeks. Previously, we showed that this model of DIO in male mice significantly increases aortic stiffness (measured by pulse wave velocity, PWV) and increases aortic thickness compared to ND (PWV: unpaired T test, n=9-12, normal diet (ND) vs DIO, p=&lt;0.0001; Aortic Thickness: unpaired T test, n=6, ND vs DIO, p=0.005). We hypothesized that endothelial-specific HDAC1 mediates aortic dysfunction in a mouse model of DIO. We generated inducible endothelial-Scl-Cre-ER-HDAC1 knockout (KO) mice (iEC-HDAC1KO), which specifically deletes HDAC1 in endothelial cells after tamoxifen injection, and the flox control mice (iEC-HDAC1flox), which does not delete HDAC1 after tamoxifen injection. We assessed aortic stiffness of iEC-HDAC1 KO and iEC-HDAC1flox in ND and DIO mice. We treated with tamoxifen for 5 days when ND mice were 20 weeks old and measured PWV 2 weeks later. Interestingly, iEC-HDAC1KO mice had significantly reduced PWV compared to iEC-HDAC1flox mice on ND (unpaired T test; n=4-5, p=0.009). At week 18 of the DIO protocol, mice were given daily tamoxifen injections for 5 days. After week 20 of the DIO protocol, iEC-HDAC1KO DIO mice had significantly reduced PWV compared to iEC-HDAC1flox DIO mice (unpaired T test; n=4-5; p=0.008). These data indicate that endothelial-specific HDAC1 mediates vascular stiffness and remodeling in high fat fed mice. Further investigation is needed to understand the relationship of endothelial HDAC1 and NO in the context of DIO and aortic health. Funding: R01 DK134562, F31HL167626. 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.

Age and Handgrip Strength Induce Differences in Micro- and Macro-Vascular Responses

Purpose: Handgrip (HG) strength is a potent predictor of cardiovascular disease (CVD) and all-cause mortality. Advances in technology have provided novel assessments of peripheral microvascular and macrovascular health and function. These advances include measurements of skeletal muscle tissue oxygenation (StO2, %) with near-infrared spectroscopy (NIRS) during vascular occlusion tests (VOT) as well as carotid-femoral pulse-wave velocity (cfPWV), which is the current gold-standard to measure aortic stiffness. Although NIRS-VOT and cfPWV have been shown to change across the lifespan, it is unknown if these variables are sensitive to group differences as defined by HG strength. Therefore, our purpose was to examine mean differences in NIRS-VOT parameters and cfPWV between groups of low and high HG strength. We hypothesized that individuals with lower HG strength would exhibit lower vascular function. Methods: 67 adults were separated into age groups: young (19 – 40 yr), midlife (41 – 64 yr), and older (≥65 yr). Groups were divided into low and high strength at the median for HG strength, and quasi-balanced based on biological sex. This resulted in six participant groups (e.g., midlife low strength). The VOT included 3 min of rest, 5 min of ischemia, and 3 min of reperfusion to determine indices of reactive hyperemia. Indices included the initial (i.e., first 10 s) rate of re-saturation (upslope) and the maximal StO2 (StO2max) percent following ischemia. Aortic stiffness was defined as cfPWV using the time difference between the appearance of the carotid and femoral pulses. Separate 2×3 between factor (HG by Age Group) ANOVAs were conducted for each outcome. A p≤0.05 was considered significant, and data were presented as mean ± SD. Results: For upslope, there was a significant interaction (p=0.042, ηp2=0.078), and follow-up analyses revealed for young and midlife adults the high HG group exhibited greater upslopes than the low strength group (young: 2.24±0.9 vs. 1.64±0.7 and midlife: 2.21±0.9 vs. 1.59±0.7%∙s−1). There was no significant interaction (p=0.360) for StO2max, but there was a significant main effect (p&lt;0.001) of Age such that it progressively decreased across the lifespan (83.9 ± 2.0 &gt; 80.7 ± 2.3 &gt; 77.3 ± 2.8%). Similarly, cfPWV exhibited a significant main effect (p&lt;0.001; ηp2 =0.429) of Age indicating aortic stiffness worsened with age, independent of HG strength. Conclusions: These results indicated that upslope was sensitive to group differences in HG strength, but only in the young and midlife age groups. For StO2max and cfPWV, age differences appeared to elicit a stronger effect than HG strength. The current findings suggested that HG strength may be most reflective of a specific portion of the vascular tree, while the initial rate of re-saturation and StO2max may be influenced by different mechanisms associated with reactive hyperemia. Notably, the participants in this study were relatively healthy based on being free of any chronic disease. Future work is necessary to determine the predictive power of NIRS-VOT parameters for future onset of CVD. We would like to thank the American Physiology Society for support and the University of South Alabama for allowing us to use its facilities. We would also like to thank all of the participants who agreed to adhere to the protocol and procedures of this study. 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.

O-GlcNAcylation regulates angiotensin II-dependent induction of thrombospondin 1

O-Linked attachment of β-N-acetylglucosamine (O-GlcNAc) on serine and threonine residues of nuclear, cytoplasmic, and mitochondrial proteins is a highly dynamic and ubiquitous post-translational modification that plays an important role in altering the function, activity, subcellular localization, and stability of target proteins. It has been proposed that physiologically, O-GlcNAcylation serves primarily to modulate cellular signaling and transcription regulatory pathways in response to nutrients and stress. However, in the vascular physiology literature, O-GlcNAc has predominantly been shown to be detrimental. Our preliminary data has shown that O-GlcNAcylation can cause aortic stiffness, however, the mechanisms underlying this phenotype remain to be elucidated. The predominant mechanisms by which O-GlcNAcylation contributes to alterations in proteostasis include competition with other post-translational modifications as well as regulation of gene expression. Thrombospondin-1 (TSP1) is a multifunctional matrix glycoprotein that impacts extracellular function (ECM) and cell adhesion, migration, proliferation, and cell-cell interaction. Therefore, we hypothesized that TSP1 could be an important downstream mediator of O-GlcNAcylation in aortic vascular smooth muscle cells (VSMCs). To test this hypothesis, primary VSMCs from the thoracic aorta were isolated from 12-week-old female Wistar rats and submitted to angiotensin (ANG) II treatment (100 nM, 3h). Some cells were also treated in the presence of ANG II type 1 (AT1)-receptor antagonist losartan (10−5 M, 30 min). ANG II was chosen because it is a physiological stressor known to cause arterial stiffening. O-GlcNAcylation (RL2 antibody), O-GlcNAcase (OGA), and TSP1 protein amounts were analyzed by Western blot, and the results were expressed in arbitrary units (AU) and mean ±standard error mean. Unpaired Student's test T was used and p&lt;0.05 was considered statistically significant. Genetic and pharmacological inhibition of O-GlcNAc was achieved through OGT silencing and inhibition with a shRNA (FunGene6) and OSMI-4 (10−5 M, 30 min), respectively. As hypothesized, ANG II significantly increased O-GlcNAc in aortic VSMC (0.3±0.03 vs 0.5±0.03 AU n=8, p&lt;0.05) which was inhibited by losartan (0.1±0.02). Moreover, ANG II significantly decreased OGA expression (0.16±0.04 vs 1.16±0.19 AU n=4, p&lt;0.05), the enzyme responsible for removing O-GlcNAc motifs, supporting the observed increase in O-GlcNAc expression. Importantly, ANG II also increased TSP1 protein expression (0.2±0.04 vs 2.0±0.4 n=4, p&lt;0.05), however, shRNA (0.7±0.05) for OGT and OSMI-4 (0.06±0.08) prevented this increase. Overall, these data indicate that Ang II-AT1R signaling can cause O-GlcNAcylation and that TSP1 could be an important downstream mediator of O-GlcNAc-mediated aortic stiffness. National Institutes of Health (R00HL151889, P20GM109091-Pilot Project, and P20GM103641-Pilot Project). University of South Carolina Offce of Research ASPIRE Award (180950-23-64136). American Heart Association Postdoctoral Fellow (916031). 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.

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&gt;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&lt;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&lt;0.001 vs. YA and P=0&lt;0.01 vs. MA), followed by MA (p&lt;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&lt;0.001 for MA vs. YA; p&lt;0.001 for MAHTN vs. YA; and P&gt;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.

PERIPHERAL ARTERIAL STIFFNESS PREDICTS INDEPENDENTLY FUNCTIONAL OUTCOME AFTER ISCHEMIC STROKE

Objective: Aortic stiffness is a strong predictor of morbidity in various clinical conditions, including ischemic stroke. However, the prognostic significance of the peripheral arterial stiffness, defined as radial -carotid pulse wave velocity - for functional outcome in ischemic stroke remains unknown. Design and method: We enrolled 189 patients (126 males, age 62.9±11.9 years, mean±SD) with acute ischemic stroke (NIHSS score at admission 6.4±5.1 points). Radial-carotid pulse wave velocity (CR PWV), peripheral blood pressure (BP) and heart rate (HR) were measured (SphygmoCor®) within several (6±2) days after stroke onset. Functional outcome was evaluated 90 days after stroke using the modified Rankin Scale (mRS) with an mRS score of 0 to 1 considered as an excellent outcome. Results: In univariate analysis, age, severity of stroke, heart rate, previous stroke, predicted stroke functional outcome. By contrast, CR PWV had no significant predictive value for stroke outcome (8.91±1.66 vs 8.56±1.50 m/s; p=0.14). In a multivariate analysis, the predictive value of CR PWV was significantly associated with functional outcome (OR, 1.34; 95% CI, 1.77–1.01; p=0.04) after adjustment for covariates, with higher values of CR PWV being associated with better prognosis. Conclusions: We found that the CR PWV in patients in the subacute phase of ischemic stroke is associated with functional outcome independently of traditional neurologic and hemodynamic factors. This PWV index might be useful in clinical practice, including therapeutic decisions, but needs broader studies in patient populations of stroke subtypes.