Increase In Arterial Stiffness Research Articles

#1514 Elevated FGF23 increases systolic, and diastolic blood pressure, and pulse pressure in non-dialysis CKD patients

Abstract Background and Aims Arterial stiffness is associated with high blood pressure. Elevated fibroblast growth factor 23 (FGF23) has been shown to produce changes in the phenotype of vascular smooth muscle cells that may cause an increase in arterial stiffness and an impairment of vascular function. Thus, we aimed to evaluate whether, in g5 non-dialysis CKD patients, higher concentration FGF23 is associated with elevated systolic (SBP), diastolic blood pressure (DBP), and pulse pressure (PP). Method We included 159 g5 non-dialysis CKD patients. Generalized additive models analyzed the association between intact FGF23, SBP, DBP, and PP. The body composition measurement was used to evaluate overhydration (OH). Given the potential non-linear relationship between iFGF23, with the other variables, iFGF23 was categorized into tertiles (T1 ≤ 389 pg/ml, T2 = 389—517 pg/ml, and T3 = >517 pg/ml). Results The mean age was 65.2 ± 14.7 years. 46% (n = 73) were female. The mean values of SBP and DBP were 158.8 ± 21.3 mmHg, and 87.2 ± 12.3 mmHg respectively, and the PP was 76.6 ± 20 mmHg. The median concentration of iFGF23 was 468.3 (268.8—904.9) pg/ml. It was observed a positive correlation between iFGF23 tertiles and SBP (p < 0.001), DBP (<0.01), PP (p = 0.02), and OH (p < 0.01) (Fig. 1). Multivariate generalized additive models showed an independent association of iFGF23 with SBP (Beta 5.16, CI 34-68), DBP (Beta 38.7, CI 24-53), and PP (Beta 36.3, CI 22.2-50.4). This association was not influenced by OH (%). Residual diuresis did not attenuate the association of iFGF23 with SBP, DBP, and PP. Conclusion Elevated FGF23 was associated with higher SBP, DBP, and PP in g5 non-dialysis CKD patients. This association was not modified by OH and residual diuresis.

Factors associated with change in arterial stiffness in patients with rheumatoid arthritis: the JointHeart study

Background Rheumatoid arthritis (RA) predominantly affects women and is associated with hypertension and arterial stiffness. We explored factors associated with change in arterial stiffness in patients with RA treated with disease-modifying antirheumatic drug (DMARD) therapy. Methods Seventy-seven outpatients with RA (age 55 ± 11, 69% women), with indication for treatment with biological or targeted synthetic DMARDs, were included. Pulse wave velocity (PWV), augmentation pressure (AP), augmentation index (AIx) and Disease Activity Score in 28 joints (DAS28) were measured at baseline and after a mean of 22 months of follow-up. Results At follow-up, 83% used DMARDs and 73% had achieved remission or low disease activity. DAS28 decreased from 3.8 ± 1.3 to 2.8 ± 1.2 (p < 0.001). Mean PWV increased from 7.8 ± 1.6 m/s at baseline to 8.5 ± 1.8 m/s at follow-up (p < 0.001), while AP and AIx were stable. Increase in PWV during follow-up was associated with increase in systolic blood pressure (BP), diabetes, higher DAS28 and body mass index (BMI) at baseline, independent of achieved remission/low disease activity and use of DMARDs at follow-up. In multivariable analyses at follow-up, female sex was associated with higher AP and AIx, but with lower PWV, after adjusting for possible confounders. Conclusion In patients with RA, higher disease activity, BMI and diabetes at baseline, together with increase in office systolic BP were associated with an increase in arterial stiffness during follow-up, despite DMARD therapy. This highlights the need for management of cardiovascular risk factors in addition to reducing the inflammatory load in patients with RA to preserve arterial function.

Age and Sex Differences in the Contribution of Mean Arterial Pressure to Pulse Pressure Before Middle Age.

A lower ability to buffer pulse pressure (PP) in the face of increasing mean arterial pressure (MAP) may underlie the disproportionate increase in systolic blood pressure (SBP) in women from young adulthood through middle-aged relative to men. To evaluate the contribution of MAP to the change in PP and pressure wave contour in men and women from young adulthood to middle age. Central pressure waveform was obtained from radial artery applanation tonometry in 312 hypertensive patients between 16 to 49 years (134 women, mean age 35 ± 9 years), 185 of whom were on antihypertensive treatment. Higher MAP levels (≥ 100 mmHg) were significantly associated with higher brachial and central SBP (P < 0.001), PP (P < 0.001), incident wave (P = 0.005), AP (P < 0.001), and PWV (P < 0.001) compared to lower MAP levels. The relationship between MAP and brachial PP (P < 0.001), central PP (P < 0.001), incident wave (P < 0.001), and AP (P < 0.01), but not PWV, strengthens with age. The age-related increase in the contribution of MAP to brachial PP (P < 0.001), central PP (P < 0.001), and incident wave (P < 0.001) was more prominent in women than in men beginning in the fourth decade. In multiple regression analyses, MAP remained a significantly stronger predictor of central PP and incident wave in women than in men, independent of age, heart rate, and antihypertensive treatment. In turn, age remained a significantly stronger predictor of central PP and incident wave in women than in men, independent of MAP, heart rate, and antihypertensive treatment. Women of reproductive age showed a steeper increase in PP with increasing MAP, despite comparable increases in arterial stiffness in both sexes. The difference was driven by a greater contribution of MAP to the forward component of the pressure wave in women.

Increases in Central Arterial Stiffness and Reductions in Diastolic Velocity in the Large Cerebral Arteries are Associated with Age-Related Decline in Cerebral Blood Flow

Background: Advanced aging is characterized by a reduction in cerebral blood flow (CBF) and an increase in central arterial stiffness. Increased central arterial stiffness results in reduced Windkessel effects and augmented pulsatile arterial blood pressure and CBF. These changes are detrimental to small cerebral blood vessels because of increases in biomechanical stresses associated with the augmented pulsatile arterial blood pressure and CBF. Purpose: To examine the associations of central arterial stiffness with cerebral hemodynamics and age-related reductions in CBF. Methods: 171 healthy subjects (20-81 yrs, 63% F) underwent color-coded duplex ultrasonography of the left and right internal carotid (ICA) and vertebral artery (VA) to characterize individual artery blood flow (BF), velocity, pulsatility, and CBF. Structural Magnetic Resonance Imaging (MRI) was used to measure total brain tissue volume (TBV). Carotid β-stiffness and carotid-femoral pulse wave velocity (cfPWV) were measured via applanation tonometry to assess central artery stiffness. Data: Age was negatively associated with global CBF (r = -0.425, p &lt; 0.001), and positively with cfPWV (r = 0.701, p &lt; 0.001), and carotid β-stiffness (r = 0.660, p &lt; 0.001). Arterial stiffness was negative associated with ICA diastolic velocity (r = -0.280, p &lt; 0.001; r = -0.259, p &lt; 0.001) and VA diastolic velocity (r = -0.280, p &lt; 0.001; r = -0.248, p = 0.001) controlling for sex, body mass index (BMI), education, and TBV. Carotid β-stiffness moderated indirect effect between age and CBF through ICA diastolic velocity (index of moderated-mediation -0.47 ± 0.13, [-0.74,-0.23]. cfPWV did not moderate the indirect effect between age and CBF through ICA diastolic velocity (index of moderated-mediation -0.36 ± 0.18, [-0.69, 0.03]. The indirect effect of age on CBF through VA diastolic velocity was not moderated by cfPWV (0.03 ± 0.09, [-0.13, 0.23]) or carotid β-stiffness (-0.17 ± 0.09, [-0.33, 0.01]). Conclusions: Age-related decline in CBF is mediated by the decreases in ICA blood flow diastolic velocity, and this relationship was moderated by carotid β-stiffness. This data suggests that increases in central arterial stiffness and reductions in CBF diastolic velocity in the large cerebral arteries likely plays an important role in age-related decline in CBF. This study was supported by NIH R01HL102457-01 and NIH R01AG033106-01. 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.

Loss of nitric oxide bioavailability promotes arterial stiffening in a tissue transglutaminase-dependent manner

Although arterial stiffening undeniably contributes to cardiovascular disease, the cellular and molecular mechanisms leading to increased arterial stiffness are not well understood. Increased arterial stiffness in disease states such as obesity and type 2 diabetes typically coexists with indices of endothelial dysfunction including diminished nitric oxide (NO) bioavailability. In fact, it is commonly assumed that endothelial dysfunction precedes, and causally contributes to, arterial stiffening; yet the molecular underpinnings for this causal relationship remain elusive. We and others previously showed that activation of tissue transglutaminase (TG2), a crosslinking enzyme that also works as a G-protein and cellular scaffold, promotes cytoskeletal actin polymerization and stiffening of vascular smooth muscle cells (VSMC), thus contributing to whole-artery stiffening. It is also reported that NO is an endogenous inhibitor of TG2. Accordingly, herein, we tested the hypothesis that increased exposure of VSMC to NO suppresses TG2 activity and actin polymerization. Conversely, we hypothesized that loss of NO bioavailability promotes arterial stiffening, and that this effect is mediated by TG2 activity and downstream activation of LIM kinase (LIMK), an enzyme that modulates fibrillar (F)-actin severing via cofilin phosphorylation. All differences reported herein are significant at P&lt;0.05. In support of our hypotheses, we show that treatment of cultured human aortic VSMC with the NO donor S-nitrosoglutathione (200μM for 2 hours) reduces TG2 activity (N-epsilon gamma glutamyl Lysine presence) and F-actin formation (phalloidin staining) induced by TG2 activation (dithiothreitol, 200μM). Furthermore, we show that exposure of mouse isolated mesenteric arteries to the NO synthase inhibitor L-NAME (300μM for 18 hours) causes an increase in arterial stiffness ( i.e., increased incremental modulus of elasticity) as determined using pressure myography and videomicroscopy. Of note, L-NAME-induced arterial stiffening is prevented when arteries are co-treated with a TG2 inhibitor (cystamine, 1mM) or LIMK inhibitor (LIMKi, 1μM). Taken together, these findings support the notion that NO is a key downregulator of TG2 activity and demonstrate that reduced NO bioavailability promotes arterial stiffening in a VSMC TG2-LIMK-F-actin dependent manner. As such, this work provides insight into plausible molecular mechanisms by which endothelial dysfunction leads to arterial stiffening. R01HL153264 (to LAML and JP), and MU Research Excellence Program (REP) postdoctoral fellowship (to FIRP). 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.

Mechanistic insights into cardiovascular effects of ultrafine particle exposure: A longitudinal panel study

BackgroundUltrafine particle (UFP) has been linked with higher risks of cardiovascular diseases; however, the biological mechanisms remain to be fully elucidated. ObjectivesThis study aims to investigate the cardiovascular responses to short-term UFP exposure and the biological pathways involved. MethodsA longitudinal panel study was conducted among 32 healthy, non-smoking young adults in Shanghai, China, who were engaged in five rounds of follow-ups between December 2020 and November 2021. Individual exposures were calculated based on the indoor and outdoor real-time measurements. Blood pressure, arterial stiffness, targeted biomarkers, and untargeted proteomics and metabolomics were examined during each follow-up. Linear mixed-effect models were applied to analyze the exposure and health data. The differential proteins and metabolites were used for pathway enrichment analyses. ResultsShort-term UFP exposure was associated with significant increases in blood pressure and arterial stiffness. For example, systolic blood pressure increased by 2.10 % (95 % confidence interval: 0.63 %, 3.59 %) corresponding to each interquartile increase in UFP concentrations at lag 0–3 h, while pulse wave velocity increased by 2.26 % (95 % confidence interval: 0.52 %, 4.04 %) at lag 7–12 h. In addition, dozens of molecular biomarkers altered significantly. These effects were generally present within 24 h after UFP exposure, and were robust to the adjustment of co-pollutants. Molecular changes detected in proteomics and metabolomics analyses were mainly involved in systemic inflammation, oxidative stress, endothelial dysfunction, coagulation, and disturbance in lipid transport and metabolism. DiscussionThis study provides novel and compelling evidence on the detrimental subclinical cardiovascular effects in response to short-term UFP exposure. The multi-omics profiling further offers holistic insights into the underlying biological pathways.

Deletion of Sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunction.

Sigmar1 is a ubiquitously expressed, multifunctional protein known for its cardioprotective roles in cardiovascular diseases. While accumulating evidence indicate a critical role of Sigmar1 in cardiac biology, its physiological function in the vasculature remains unknown. In this study, we characterized the expression of Sigmar1 in the vascular wall and assessed its physiological function in the vascular system using global Sigmar1 knockout (Sigmar1-/-) mice. We determined the expression of Sigmar1 in the vascular tissue using immunostaining and biochemical experiments in both human and mouse blood vessels. Deletion of Sigmar1 globally in mice (Sigmar1-/-) led to blood vessel wall reorganizations characterized by nuclei disarray of vascular smooth muscle cells, altered organizations of elastic lamina, and higher collagen fibers deposition in and around the arteries compared to wildtype littermate controls (Wt). Vascular function was assessed in mice using non-invasive time-transit method of aortic stiffness measurement and flow-mediated dilation (FMD) of the left femoral artery. Sigmar1-/- mice showed a notable increase in arterial stiffness in the abdominal aorta and failed to increase the vessel diameter in response to reactive-hyperemia compared to Wt. This was consistent with reduced plasma and tissue nitric-oxide bioavailability (NOx) and decreased phosphorylation of endothelial nitric oxide synthase (eNOS) in the aorta of Sigmar1-/- mice. Ultrastructural analysis by transmission electron microscopy (TEM) of aorta sections showed accumulation of elongated shaped mitochondria in both vascular smooth muscle and endothelial cells of Sigmar1-/- mice. In accordance, decreased mitochondrial respirometry parameters were found in ex-vivo aortic rings from Sigmar1 deficient mice compared to Wt controls. These data indicate a potential role of Sigmar1 in maintaining vascular homeostasis.

Possible Mechanisms for Adverse Cardiac Events Caused by Exercise-Induced Hypertension in Long-Distance Middle-Aged Runners: A Review.

Sudden cardiac death (SCD) is rare among athletes. However, hypertrophic cardiomyopathy is the leading cause of SCD among those <35 years of age. Meanwhile, coronary artery disease (CAD) is the primary SCD cause among those ≥35 years of age. CAD-induced plaque ruptures are believed to be a significant cause of cardiovascular diseases in middle-aged individuals who participate in extreme long-distance running activities such as marathons. A total of 1970 articles related to EIH were identified using search terms. Out of these, 1946 studies were excluded for reasons such as arterial hypertension, exercise-induced pulmonary hypertension, the absence of exercise stress testing (EST), and a lack of relevance to EIH. The study analyzed 24 studies related to both long-distance runners with exercise-induced hypertension (EIH) and the general public. Among these, 11 studies were quasi-experimentally designed studies used in randomized controlled trials (RCTs) on long-distance runners with EIH. Additionally, 12 studies utilized cohort designs, and one study with a quasi-experimental design was conducted among the general population. Recent studies suggest that an imbalance between oxygen demand and supply due to ventricular hypertrophy may be the actual cause of cardiovascular disease, regardless of CAD. Exercising excessively over an extended period can reduce endothelial function and increase arterial stiffness, which in turn increases afterload and leads to an excessive increase in blood pressure during exercise. Exercise-induced hypertension (EIH), which increases the morbidity rate of resting hypertension and is a risk factor for cardio-cerebro-vascular diseases, is more prevalent in middle-aged long-distance runners than in runners from other age groups, and it increases the prevalence of critical arrhythmias, such as atrial fibrillation or ventricular arrhythmias. EIH is associated with angiotensin II activity, and angiotensin II receptor blockers show promising effects in middle-aged runners. Further, guidelines for preventing excessive participation in races and restricting exercise intensity and frequency would be useful. This review identifies EIH as a potential risk factor for cardiovascular diseases and describes how EIH induces SCD.

Influence of MAFLD and NAFLD on arterial stiffness: A longitudinal cohort study

Background and aimsThis cohort study investigated associations of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction–associated fatty liver disease (MAFLD) with risk of increase in arterial stiffness (AS), measured as brachial-ankle pulse wave velocity (baPWV). Methods and resultsParticipants who had health examinations between 2006 and 2019 were analyzed for fatty liver and increased baPWV using liver ultrasonography and automatic volume plethysmography device. Participants were classified based on presence of MAFLD or NAFLD and further divided into subgroups: no fatty liver disease (reference), NAFLD-only, MAFLD-only, and both NAFLD and MAFLD. Subgroups were additionally stratified by sex. Cox proportional hazard model was utilized to analyze the risk of developing baPWV ≥1400 cm/s in participants without baseline elevation of the baPWV. The NAFLD and MAFLD groups exhibited higher risks of increased baPWV (NAFLD: adjusted hazard ratio (aHR), 1.35 [95% CI, 1.29–1.42]; MAFLD: aHR, 1.37 [95% CI, 1.31–1.43]) compared to group without the conditions. Incidence of NAFLD or MAFLD were higher in men than in women but aHR of developing the increase in AS was higher in women. In subgroup analysis, the MAFLD-only group presented the strongest associations with increase in AS (aHR, 1.53 [95% CI, 1.43–1.64]), with the trend more pronounced in women than in men (Women, aHR, 1.63 [95% CI, 1.08–2.46]; Men, aHR 1.45 [95% CI, 1.35–1.56]). ConclusionsBoth NAFLD and MAFLD are significantly associated with elevated AS. These associations tended to be stronger in MAFLD than in NAFLD, in women than in men.

Wireless Photoplethysmography (PPG) Measurement with Pulse Wave Velocity (PWV) Method for Arterial Stiffness Evaluation

Indications of symptoms of cardiovascular disease can be seen from the level of elasticity of the arteries. The Pulse Wave Velocity (PWV) method using PPG signal analysis is used to determine the level of arterial stiffness based on the time difference between pulse waves of Photoplethysmography (PPG) signal measurements. PWV measurements use a non-invasive technique using pulse sensors on the fingers and toes, the measurement data is sent wirelessly using the ESP-NOW protocol. Analysis of the measured PPG signal is used as an approach to calculating the PWV value. Realization and testing can be used to measure the pulse in BPM and classify the index of arterial stiffness using the PWV method. The results of testing on 15 test volunteers from 3 age groups showed the results of an arterial stiffness index with indications of normal, stiff and very stiff arteries. The PWV value for the 20 year old group was 4.30-6.77 cm/s, normal arterial conditions. The age group of 30-40 years has a PWV value ranging from 5.11-8.77 cm/s, normal arterial conditions. The age group of 50-60 years had PWV values in the range of 10.69-18.43 cm/s, stiff and very stiff arterial conditions. Increasing age linearly affects the increase in PWV value. An increased PWV value may indicate an increase in arterial stiffness.

Regular Intermittent Aerobic Exercise Reduces Arterial Stiffness Associated with Postprandial Hyperglycemia in Middle-Aged and Older Individuals

Hardening of arterial walls associated with elevated postprandial blood glucose levels increases the risk of cardiovascular disease; however, the impact of intermittent aerobic training on reducing arterial stiffness is unknown. The aim of this study was to examine the chronic effects of intermittent aerobic exercise on arterial stiffness during hyperglycemia in middle-aged adults: 30 healthy middle-aged adults were randomly assigned to an 8-week intermittent aerobic training group (n = 15, jogging or running, 30 min/run, 3 times/week, 65% reserve heart rate) and a control group (n = 15, no training). Pulse wave velocity (PWV) of carotid-femoral (cf) and brachial-ankle (ba), heart rate, blood pressure, and blood glucose was measured before a 75 g oral glucose tolerance test (OGTT) and 30, 60, and 90 min after the test, before the exercise intervention, and 4 and 8 weeks after intervention. The baPWV and blood glucose levels before the intervention were elevated at 30, 60, and 90 min in both groups compared to levels before the 75 g OGTT (p &lt; 0.01). The baPWV and blood glucose levels after 4 and 8 weeks of intervention were unchanged in the training group compared to that before the 75 g OGTT, but increased at 30, 60, and 90 min in the control group compared to that before the 75 g OGTT (p &lt; 0.01). The baPWV and blood glucose levels at 30 and 60 min after the 75 g OGTT after 4 and 8 weeks of intervention were lower in the training group than in the control group (p &lt; 0.01). These results indicate that intermittent aerobic exercise training may reduce the acute increase in arterial stiffness after hyperglycemia.

Dihydrotestosterone induces arterial stiffening in female mice

BackgroundAndrogens are important sex hormones in both men and women and are supplemented when endogenous levels are low, for gender transitioning, or to increase libido. Androgens also circulate at higher levels in women with polycystic ovarian syndrome, a condition that increases the risk for cardiovascular diseases including hypertension and arterial stiffness. Since our previous work shows an important role for the G protein-coupled estrogen receptor (GPER) in arterial stiffness, we hypothesized that other hormones including androgens may impact arterial stiffness in female mice via downregulation of GPER.MethodsThe impact of the non-aromatizable androgen dihydrotestosterone (DHT), the glucocorticoid dexamethasone, and the progestin medroxyprogesterone acetate (all 100 nM for 24 h) on GPER and ERα expression was assessed in cultured vascular smooth muscle cells using droplet digital PCR (ddPCR). To assess the in vivo impact of the DHT-induced downregulation of GPER, female ovary-intact C57Bl/6 mice at 15–16 weeks of age were treated with silastic capsules containing DHT for 4 weeks, one with a dosage expected to mimic human male DHT levels and another to double the expected human concentration (n = 8–9/group).ResultsIn cultured vascular smooth muscle cells, GPER mRNA was decreased by DHT (P = 0.001) but was not impacted by dexamethasone or medroxyprogesterone. In contrast, ERα expression in cultured cells was significantly suppressed by all three hormones (P < 0.0001). In control mice or mice treated with a single or double dose of DHT, a dose-dependent increase in body weight was observed (control 22 ± 2 g, single dose 24 ± 2 g, double dose 26 ± 2 g; P = 0.0002). Intracarotid stiffness measured via pulse wave velocity showed a more than two-fold increase in both DHT-treated groups (control 1.9 ± 0.3 m/s, single dose 4.3 ± 0.8 m/s, double dose 4.8 ± 1.0 m/s). This increase in arterial stiffness occurred independent of changes in blood pressure (P = 0.59). Histological analysis of aortic sections using Masson’s trichrome showed a significant decrease in collagen between the control group (24 ± 5%) and the double dose group (17 ± 3%, P = 0.007), despite no changes in aortic wall thickness or smooth muscle content. Lastly, ddPCR showed that in vivo DHT treatment decreased aortic expression of both GPER (control 20 ± 5, single dose 10.5 ± 5.6, double dose 10 ± 4 copies/ng; P = 0.001) and ERα (control 54 ± 2, single dose 24 ± 13, and double dose 23 ± 12 copies/ng; P = 0.003).ConclusionsThese findings indicate that androgen promotes arterial stiffening and cardiovascular damage in female mice and is associated with decreased estrogen receptor expression. These data are important for transgender men, women using testosterone for fitness or reduced libido, as well as patients with polycystic ovarian syndrome.

Impact of arterial stiffness on cerebrovascular function: a review of evidence from humans and preclincal models.

With advancing age, the cerebral vasculature becomes dysfunctional, and this dysfunction is associated with cognitive decline. However, the initiating cause of these age-related cerebrovascular impairments remains incompletely understood. A characteristic feature of the aging vasculature is the increase in stiffness of the large elastic arteries. This increase in arterial stiffness is associated with elevated pulse pressure and blood flow pulsatility in the cerebral vasculature. Evidence from both humans and rodents supports that increases in large elastic artery stiffness are associated with cerebrovascular impairments. These impacts on cerebrovascular function are wide-ranging and include reductions in global and regional cerebral blood flow, cerebral small vessel disease, endothelial cell dysfunction, and impaired perivascular clearance. Furthermore, recent findings suggest that the relationship between arterial stiffness and cerebrovascular function may be influenced by genetics, specifically APOE and NOTCH genotypes. Given the strength of the evidence that age-related increases in arterial stiffness have deleterious impacts on the brain, interventions that target arterial stiffness are needed. The purpose of this review is to summarize the evidence from human and rodent studies, supporting the role of increased arterial stiffness in age-related cerebrovascular impairments.

Arterial stiffness assessment in obese black South African patients.

Increased arterial stiffness is a determinant of cardiovascular mortality and an independent marker of cardiovascular disease. The objective of this study was to asses arterial elasticity by determination of pulse-wave velocity (PWV) and augmentation index (Aix) in obese black patients. PWV and Aix were assessed non-invasively using the AtCor SphygmoCor® system (AtCor Medical, Inc, Sydney, Australia). The study participants were divided into four groups; healthy volunteers (HV) (n = 29), patients with concomitant diseases but normal body mass index (Nd) (n = 23), obese patients without concomitant diseases (OB) (n = 29) and obese patients with concomitant diseases (OBd) ( n = 29). The difference in the mean levels of PWV was statistically significant in the obese group with and without concomitant disease. The PWV in the OB group (7.9 ± 2.9 m/s) and in the OBd group (9.2 ± 4.4 m/s) was, respectively, 19.7 and 33.3% higher than in the HV group (6.6 ± 2.1 m/s). PWV was directly correlated with age, glycated haemoglobin level, aortic systolic blood pressure and heart rate. The risk of cardiovascular diseases in the obese patient without additional diseases was increased by 50.7%. The presence of concomitant diseases (type 2 diabetes mellitus and hypertension) in addition to obesity increased arterial stiffness by a further 11.4% and therefore also increased the risk of cardiovascular diseases by a further 35.1%. Aix was increased in the OBd and Nd groups by 8.2 and 16.5%, respectively, however the increase was not statistically significant. Aix was directly correlated with age, heart rate and aortic systolic blood pressure. The obese black patients had a higher PWV, indicating increase in arterial stiffness and therefore a higher risk for cardiovascular disease. In addition, aging, increased blood pressure and type 2 diabetes mellitus contributed further to arterial stiffening in these obese patients.

Association of carotid wall shear stress measured by vector flow mapping technique with ba-PWV: a pilot study.

Arterial stiffness is an important tissue biomarker of the progression of atherosclerotic diseases. Brachial-ankle pulse wave velocity (ba-PWV) is a gold standard of arterial stiffness measurement widely used in Asia. Changes in vascular wall shear stress (WSS) lead to artery wall remodeling, which could give rise to an increase in arterial stiffness. The study aimed to explore the association between ba-PWV and common carotid artery (CCA) WSS measured by a newly invented vascular vector flow mapping (VFM) technique. We included 94 subjects free of apparent cardiovascular disease (CVD) and divided them into a subclinical atherosclerosis (SA) group (N = 47) and non subclinical atherosclerosis (NSA) group (N = 47). CCA WSS was measured using the VFM technique. Bivariate correlations between CCA WSS and other factors were assessed with Pearson's, Spearman's, or Kendall's coefficient of correlation, as appropriate. Partial correlation analysis was conducted to examine the influence of age and sex. Multiple linear stepwise regression was used for the analysis of independent determinants of CCA WSS. Receiver operating characteristic (ROC) analysis was performed to find the association between CCA WSS and 10-year CVD risk. The overall subjects had a mean age of 47.9 ± 11.2 years, and males accounted for 52.1%. Average systolic CCA WSS was significantly correlated with ba-PWV (r = -0.618, p < 0.001) in the SA group. Multiple linear stepwise regression analysis confirmed that ba-PWV was an independent determinant of average systolic CCA WSS (β = -0.361, p = 0.003). The area under the curve (AUC) of average systolic CCA WSS for 10-year CVD risk ≥10% was 0.848 (p < 0.001) in the SA group. Average systolic CCA WSS was significantly correlated with ba-PWV and was associated with 10-year CVD risk ≥10% in the SA group. Therefore, CCA WSS measured by the VFM technique could be used for monitoring and screening subjects with potential CVD risks.

Increase of Arterial Stiffness in Patients with Polycythemia Vera

Introduction: Preventing thrombotic adverse events (TAEs) is crucial in Polycythemia Vera (PV), as it is the leading cause of death. A targeted approach is required to achieve this, aiming to lower hematocrit (HCT) blood levels and manage thrombocytosis through cytoreductive therapy and anti-platelet treatments. The reasons behind the higher incidence of TAEs in PV are partially known. A novel perspective considers that increased blood vessel content may result in a stiffer aorta, which is clinically measurable with the Pulse Wave Velocity (PWV). The stiffer aorta, a proxy of arterial aging, has been recognized as a significant independent contributor to TAEs. Objectives: This study aimed to investigate the impact of hematological parameters on arterial stiffness in PV patients Methods: Clinical and laboratory information was collected for each patient. Aorta PWV (PWV) was estimated using the SphygmoCor System (AtCor Medical Pty Ltd., Head Office, West Ryde, Australia). The patients were observed and measured twice with a minimum interval of six months between sessions. Results: We evaluated patients with a diagnosis of PV according to WHO 2016 classification, attending from November 2021 to March 2023, the Hematology Unit of the Businco Hospital in Cagliari, Italy. The study involved 26 patients aged 27 to 77 years old. Among them, 58% were female. The median follow-up between diagnosis and PWV evaluation was 7±3 years. The median Hemoglobin (Hb) level was 13.9±1.7 g/dl, with an HCT level of 44.1±4.6 %. Leucocytes and platelets at evaluation time were 9.1±4.2×10 3/μL and 395±227 ×10 3/μL, respectively. Fourteen (53.8%) patients reported a high-risk thrombotic score at diagnosis, and 65.3% had at least one comorbidity. Two (7.7%) patients had diabetes. Moreover, 15.4% showed dyslipidemia, while 38.5% had arterial hypertension. The median body mass index (BMI) was 24.8 ± 3.6 Kg/m2, and the median waist circumference was 94.4 ±13.4 cm. Characteristics of patients were resumed in Table 1. A significant correlation with a high level of PWV was found with age (r:0.54, p=0.004), systolic and diastolic blood pressure (r:0.55, p=0.004 and r:0.44, p=0.025 respectively), heart rate (r:0.47, p=0.02), Hb (r:0.50, p=0.009), and use of hydroxycarbamide (r:0.42, p=0.03). Even after adjusting for age, waist circumference, BMI, and hypertension, the hemoglobin level still significantly correlated with PWV (β0.64 ± 0.27, p&amp;lt;0.05). No associations were found with hematocrit levels (β0.09 ± 0.12, p=0.42). When comparing patients treated only with phlebotomy versus those treated with hydroxycarbamide, PWV was significantly higher (stiffer artery) in the second group (8.9 ± 1.8 vs 11.2 ± 3.2, p&amp;lt; 0.05, respectively). Still, the difference lost significance when accounting for age and blood pressure levels. Conclusion: In PV, Hb levels showed a significant positive correlation with arterial stiffness, indexed as PWV, regardless of PV-specific treatment. The stiffer artery may contribute to the higher TAEs in PV patients. Reducing Hb levels in PV patients also seems beneficial for arterial aging. Further studies are necessary to determine the possible role of PWV in defining and preventing thrombotic events.

Abstract 17170: Association of Plasma Homocysteine Levels in Cancer Survivors - Data From Framingham Heart Study Offspring Cohort

Introduction: Cancer survivors experience a high prevalence of vascular remodeling from their anti-cancer therapies, which can lead to arterial stiffness. High plasma homocysteine (Hcy) is associated with increased cardiovascular disease risk via its role in decreasing nitric oxide bioavailability and impairing vascular function. However, there is limited work on its role in cancer survivorship. We, therefore, hypothesized that survivors of breast, gastrointestinal, and prostate cancer with elevated plasma Hcy values have higher arterial stiffness and lower endothelial function compared to those with low plasma Hcy. Methods: We evaluated cardiovascular disease-free cancer survivors in the Framingham Heart Study Offspring Cohort (n=196, 66±8 years old, 55.1% women, 26.4±1.2 years from cancer diagnosis, Range: [23.8 - 29.6 years]) with plasma Hcy measurements. The cohort median plasma Hcy was used to define low (&lt;8.16 μmol/L) and high Hcy (≥8.16 μmol/L) groups. Arterial stiffness was assessed via carotid-femoral pulse wave velocity (cfPWV). Peripheral vascular endothelial function was assessed via endothelium-dependent brachial artery flow-mediated dilation (FMD). Differences in cfPWV, FMD, and cardiovascular risk factors were assessed via independent sample t-test or chi-square test. Differences in cfPWV and FMD were further assessed via one-way ANCOVA with age, sex, and cardiovascular medications included as covariates. Results: cfPWV was significantly higher in the high Hcy (9.9±1.5m/s) vs. low Hcy group (8.5±1.9m/s, p=0.005); however, there were no differences in FMD between groups (2.4±1.7 vs. 2.7±2.0%, p=0.42). After controlling for our covariates, cfPWV was still significantly higher in the high Hcy group (Mean[95% CI]): (9.8[9.0-10.61]) compared to the low Hcy group (8.5[8-9.1]) (p=0.015). Conclusions: Our findings suggest an association between elevated Hcy and an increase in arterial stiffness in cancer survivors. This supports the potential adverse consequences of vascular stiffening following cancer diagnosis and treatment which could have long-term cardiovascular health implications.

Abstract 13719: Minimal and Delayed Age-Related Increase of Arterial Stiffness Among Tsimane Forager-Horticulturalists

Background: Tsimane forager-farmers of the Bolivian Amazon exhibit a distinct trajectory of vascular aging, characterized by low age-related increases in BP, the lowest levels of coronary calcification ever reported, and robust VO 2 max. However, the prevalence of arterial stiffness (ArSt) in this population and its association with age and other cardiovascular risk factors are unknown. Methods: Large artery elasticity (LAE) and small artery elasticity (SAE) were measured among 491 Tsimane adults (mean age 55.3±13.0 y, 55% female) using HDI CR-2000 (Eagan, MN). Carotid-femoral pulse wave velocity (cfPWV) was assessed among 89 Tsimane (mean age 53.1±15.7 y, 54% female) using the foot-to-foot method with ECG and carotid/femoral pulse wave data. Results: Compared to previous studies from diverse urban populations, Tsimane show lower indices of ArSt: higher LAE (mean 22.79±12.21 ml/mmHg·10) and SAE (mean 7.57±4.04 ml/mmHg·100), and lower cfPWV (mean 6.34±2.1 m/s). LAE and SAE are 73% and 57% higher for Tsimane men, and 70% and 86% higher for Tsimane women, compared to age-matched US MESA adults. Tsimane demonstrate lower LAE and SAE with age, while higher cfPWV was only evident among Tsimane over 70 years (β=2.26±0.71, P =0.001; reference &lt;40 y). Hypertension is rare in this population, but was associated with having higher ArSt. Conclusion: Tsimane forager-farmers have substantially lower levels of ArSt and fewer age-related differences in ArSt compared to more urbanized and sedentary populations. The minimal and delayed age-related increase of arterial stiffness might contribute to the very low observed levels of coronary atherosclerosis and dementia in the Tsimane.

Clinical efficacy of a fixed-dose combination of amlodipine/indapamide/perindopril in patients with hypertension and multiple risk factors

Aim. To evaluate the antihypertensive and organ protective efficacy of the triple fixed-dose combination of amlodipine/indapamide/perindopril in patients with hypertension (HTN) who did not achieve target blood pressure (BP) on previous antihypertensive therapy (AHT).Material and methods. The study included 47 patients with HTN and multiple risk factors who did not achieve target blood pressure during previous AHT. They were prescribed triple fixed-dose combination of amlodipine/indapamide/perindopril with preliminary prescription of amlodipine, indapamide and perindopril in the free-dose combination. At baseline and after 3 months of AHT, 24-hour ambulatory blood pressure monitoring (ABPM), echocardiography and arterial stiffness were analyzed.Results. Initially, in patients included in the study, the main ABPM parameters were increased, while non dipper and reduced dipper (66% of patients) patterns prevailed. The results of echocardiography indicated left ventricular (LV) hypertrophy (LVH) by left ventricular mass index (LVMI), left ventricular posterior wall thickness (LVPWT), interventricular septum (IVS) and its diastolic dysfunction by E/A, while an increase in CAVI and biological vascular age reflected an increase in arterial stiffness. After 3 months of AHT, significant (p£0,05) ABPM changes and a predominance of the dipper-type 24-hour BP pattern were recorded in more than half of the patients (53%). A decrease in LVMI, LVPWT and IVS by 7%, 12% and 8%, respectively (p£0,05), while an E/A increase by 12% reflected LVH regression and LV diastolic function improvement. A decrease in arterial stiffness was evidenced by a decrease (p£0,05) in CAVI by an average of 10% and biological vascular age by 4 years.Conclusion. Triple fixed-dose therapy of amlodipine/indapamide/perindopril after 3-month treatment made it possible to achieve target blood pressure in 78% of patients, improved ABPM parameters and ensured pronounced cardioand vasoprotective effects, reflected in LVH regression, improvement of LV diastolic function and reduction of arterial stiffness.

Cross-Sectional Relationship Between Atrial Conduction Delay and Arterial Stiffness in Patients with Obstructive Sleep Apnea.

Prolonged P-wave duration (PWD), which indicates atrial conduction delay, is a potent precursor of atrial fibrillation (AF) that may be induced by obstructive sleep apnea (OSA). The cardio-ankle vascular index (CAVI), which is an arterial stiffness parameter, is elevated in patients with OSA; moreover, an increased CAVI is associated with atrial conduction delay through left atrium enlargement in association with left ventricular diastolic dysfunction. We aimed to examine the relationship between the CAVI and PWD in patients with OSA. We included patients with a sinus rhythm who underwent overnight polysomnography. We measured the PWD and CAVI on standard 12-lead electrocardiograms; further, we analyzed the relationship between PWD and CAVI. We analyzed data from 300 participants (men, 89.0%; mean age, 52.3 ± 13.1 years; and body mass index, 26.2 ± 3.9 kg/m2). The mean PWD was 104.4 ± 10.4 ms while the mean CAVI was 7.5 ± 1.5. PWD was significantly correlated with CAVI (r = 0.478, p < 0.001); additionally, PWD and CAVI were directly associated with OSA severity (p = 0.002 and p = 0.002, respectively). Multivariate regression analysis revealed an independent significant correlation of PWD and CAVI with OSA severity. In patients with OSA, an increase in arterial stiffness is associated with atrial conduction delay.