Pulse Wave Velocity Measurements Research Articles

MO531: The Differential Effect of Third-Generation Intravenous Iron Preparations (Ferric Carboxymaltose, Ferric Derisomaltose) on Cardiovascular Parameters in Patients With Non-Dialysis Dependent CKD and Iron Deficiency Anaemia

Abstract BACKGROUND AND AIMS Intravenous (IV) iron is commonly used to alleviate iron deficiency anaemia in patients with non-dialysis chronic kidney disease (CKD). Treatment with IV iron in patients with iron deficiency and heart failure has demonstrated an improvement in functional status and cardiac biomarkers; however, concerns remain regarding the potential pro-oxidative effect of IV iron and possible cardiovascular injury. Newer agents [such as ferric carboxymaltose (FCM) and ferric derisomaltose (FDI)] are increasingly used due to their advantage in delivering large amounts of iron effectively and safely; however, they differ as to their effect on serum phosphate and fibroblast growth factor 23, factors that have been previously shown to affect cardiac function. Given the above potential concerns, it is important to explore the comparative effect of IV iron in this population in terms of cardiac injury and vascular function. METHOD The exploratory single-centre double-blinded randomized controlled trial ‘Iron and Phosphaturia—ExplorIRON-CKD’ aimed primarily to not only assess the differential effects of FCM and FDI on levels of fibroblast growth factor 23 and phosphate, but also explore any cardiovascular effect. Non-dialysis patients with CKD and iron deficiency with/without anaemia defined as serum ferritin <200 µg/L or transferrin saturation ≤20% and serum ferritin 200–299 µg/L were recruited and randomized in a 1:1 ratio. Participants received 1000 mg at baseline and 500–1000 mg at 1 month to achieve replenishment. Measurements of NT-proBNP were taken at baseline, 1 month, 2 months and 3 months, whilst measurements of Troponin T were taken at every visit (total of eight visits). Vascular function was assessed using pulse wave velocity measurements at baseline, 1 month, 2 months and 3 months, monitoring carotid to femoral pulse wave velocity (PWVcf) and aortic augmentation index (AIx). RESULTS Twenty-six patients were recruited; 14 were randomized to receive FDI and 12 to receive FCM. All patients received at least one iron dose (1000 mg), 10 patients received two FDI doses and 11 received two FCM doses. There was a trend to an increase in NT-pro BNP (10.3%) in the combined group, with no statistical difference between the FCM and FDI groups [median for the combined population: baseline: 875.5 (3033.0) ng/L versus Visit 8: 967.0 (2976.0) ng/L] (Figure 1). Troponin T values remained constant throughout the study period in the combined and individual groups (Table 1). A decrease in both PWVcf and AIx was noted in the participants receiving IV iron irrespective of the compound used. A greater decrease was seen in the FDI group in terms of PWVcf; however, there was no statistically significant difference for the percentage change from baseline to the end of the study between the groups (FCM: −4.3 (33.6)% versus FDI: −11.9 (23.4)%; P = .60) (Figure 2). CONCLUSION Treatment of non-dialysis CKD patients with FDI or FCM was not associated with any cardiovascular safety signals. Troponin T was unaffected and there was no worsening in vascular function. Pulse wave velocity improved, as noted by the decreasing trends for PWVcf and AIx. The decrease in PWVcf was greater with FDI than FCM, but the difference was not statistically significant. A small rise in NT-proBNP was noted in the combined group, but there was no statistically significant difference between the FDI and FCM groups. These results suggest that newer IV iron compounds are not associated with any detriment in terms of vascular function and potentially no resulting cardiac insult. The study sample is small and therefore the results should be interpreted with caution; nonetheless, the evidence provided from a comparative view directs to no negative sequela.

MO768: The Association among Carotid IMT, Pulse Wave Velocity and Vascular Access Failure in Haemodialysis Patients

Abstract BACKGROUND AND AIMS Patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD) have an increased risk of cardiovascular mortality and morbidity. We aimed to compare the value of IMT with tests such as coronary CT and pulse wave velocity (PWV) as predictors of cardiovascular risk in ESRD patients undergoing maintenance dialysis and examine their association with cardiovascular disease. METHOD We reviewed the participants’ medical records, including height, body weight, smoking status, alcohol intake, medication history, aetiology of ESRD, HD vintage and blood pressure which were measured during haemodialysis. Carotid doppler was performed by a skilled sonographer who was unaware of the aims of the study and blinded to the laboratory findings. For PWV measurement, patients lie down, rest for at least 5 minutes and stop smoking and coffee for 3 h before the measurement. BaPWV is measured by recording pulse waves of both arms and ankles from the pressure signal obtained by measuring 4-extremity blood pressure. RESULTS A total of 100 patients were included, of whom 51 (50.5%) were men. The median age was 66 years (interquartile range 58–76 years). The median vintage of haemodialysis was 47.5 months (range 31.3–89.1 months). There were no significant differences between the high IMT group and the low IMT group in sex, haemodialysis vintage, ESRD aetiology and type of vascular access. However, age was significantly older in the high IMT group. IMT was significantly associated with PWV [hazard ratio (HR) 2.109; 95% confidence interval (95% CI) 1.037–4.291, P = 0.039). After adjusting for age, sex and presence of diabetes, IMT was independently associated with PWV (HR 2.110, 95% CI 1.036–4.298, P = 0.040). The risk of recurrent vascular access failure was higher in the high IMT group (HR 1.615, 95% CI 1.460–5.669, P = 0.034). CONCLUSION IMT was associated with PWV and recurrent access failure. Thus, IMT may be suggested as a potential predictor of vascular access failure.

Evaluation of Carotid Artery Atherosclerosis and Arterial Stiffness in Cardiovascular Disease Risk: An Ongoing Prospective Study From the Kailuan Cohort.

ObjectiveTo assess whether carotid artery ultrasonography and brachial-ankle pulse wave velocity (baPWV) measurement can accurately predict cardiovascular and cerebrovascular events, and all-cause mortality in patients with cardiovascular diseases (CVD).MethodsPatients from the Kailuan Study Stroke Cohort (Tangshan, China) who underwent carotid artery ultrasonography and baPWV measurement between June 2010 and June 2011 were included in this study. The effects of carotid plaque, baPWV, and their combination on cardiovascular events, including myocardial infarction (MI), cerebral ischemic stroke, cerebrovascular events, and all-cause mortality, were evaluated using Kaplan-Meier analysis and Cox proportional hazards regression.ResultsA total of 4,899 participants (59.7% males; 54.18 ± 11.52 years old) were analyzed. During a mean follow-up of 5.68 ± 0.66 years, the incidence of cardiovascular events and all-cause mortality were 4.94‰ person-years and 7.02‰ person-years, respectively; 32.8% of participants had both carotid artery atherosclerosis and increased arterial stiffness. A high baPWV alone was associated with an increased risk of CVD events [hazard ratio (HR): 2.68; 95% confidence interval (95% CI): 1.20–6.00; P = 0.007] and cerebral infarction (HR: 5.92; 95% CI: 1.76–19.93; P = 0.004), but not with MI or all-cause death. The presence of both carotid plaque and high baPWV was highly associated with an increased risk of CVD events (HR: 4.65; 95% CI: 2.06–10.45; P < 0.001) and cerebral infarction (HR: 9.21; 95% CI: 2.71–31.19; P < 0.001), but not with MI or all-cause death. Similar results were obtained by the Kaplan-Meier analyses.ConclusionThe presence of carotid plaque and high baPWV were associated with a high risk of CVD events and ischemic stroke. Moreover, the combination of carotid artery ultrasonography and baPWV measurement could predict the risk for CVD ability more accurately than a single measurement alone.

PPARγ Deacetylation: A Novel Therapeutic Strategy to Mitigate Arterial Stiffness in Obese Male Mice

BackgroundObesity has become a worldwide epidemic and is a major risk factor for the development of cardiovascular disease (CVD). Stiffening in the large arteries, such as the aorta, is a prevalent complication in obesity and frequently precedes hypertension. The mechanism by which obesity contributes to arterial stiffness remains unclear. Peroxisome proliferator‐activated receptor gamma (PPARγ) is a known vasculo‐protective factor. Post‐translational modifications of PPARγ by acetylation can regulate its function. Recently, our group identified that deacetylation of PPARγ enhances vascular endothelial function. We hypothesize that deacetylation of PPARγ protects against obesity‐related arterial stiffness.MethodsA mice model of Western diet (WD) induced obesity and our model of deacetylated PPARγ mimetic knock‐in mice with a double lysine to arginine mutation (Lys268Arg, Lys293Arg, termed 2KR mice) were utilized. Adult male C57BL/6 and 2KR mice were randomized into two dietary protocols. Control groups of C57BL/6 (n=8) and 2KR mice (n=5) received a regular chow diet (5% fat, 48.7% carbohydrates [3.2% sucrose], and 24.1% protein) for 24 weeks. WD groupsof C5 7BL/6 (n=10) and 2KR mice (n= 5) received a WD (40% fat, 43% carbohydrates [34% sucrose], and 17% protein) for 24 weeks. Metabolic profiles were assessed by using single‐mouse‐sized metabolic cages. Aortic stiffness was assessed by measuring pulse wave velocity (PWV) with high‐resolution ultrasound, the gold standard for arterial stiffness. Systolic blood pressure was measured using tail cuff plethysmography.ResultsWD‐induced obesity was confirmed by increased body weight in both WD C57BL/6 mice (36.5g vs. 28.6g controls, p&lt;0.001) and WD 2KR mice groups (44.7g vs. 29.86g controls, p&lt;0.0001). Results obtained from metabolic cages revealed reduction in food, energy and water intake, and urine and fecal output in the WD C57BL/6 and WD 2KR groups as compared to their respective controls. These results indicate that weight gain in WD‐fed mice is not explained by increased energy intake, but rather a reduced metabolic rate. As expected, the WD C57BL/6 group exhibited increased aortic stiffness (5.4 m/s vs. 4.1 m/s controls, p&lt;0.05), which was accompanied by elevated systolic blood pressure (143.8 ± 1.66 vs. 123.5 ± 4.76 mmHg controls, p&lt;0.05). Strikingly, while WD 2KR mice developed obesity, these mice did not exhibit increased aortic stiffness (4.3 m/s vs. 4/4 m/s controls, p=0.89) nor elevated systolic blood pressures (122.4 ± 3.93 mmHg vs. x 115.2 ± 4.15 mmHg controls, p=0.26), indicating that deacetylation of PPARγ protects against aortic stiffness and increases in arterial blood pressure in obesity.ConclusionsOur findings demonstrate that while deacetylation of PPARγ does not prevent the development of WD‐induced obesity, it does protect against arterial stiffness in obesity. These results indicate that PPARγ deacetylation is a potential therapeutic strategy in the prevention of obesity‐related arterial stiffness.

Ablation of Endothelial mTOR is Benign in Young Mice and Reverses Age‐Related Arterial and Metabolic Impairments in Old Mice

Systemic inhibition of mammalian target of rapamycin (mTOR) improves age‐related arterial and metabolic dysfunction. Although the mechanisms and tissues involved remain unknown, endothelial cells (ECs), key regulators of arterial and metabolic function, may be responsible for these effects. In this study, we tested the hypothesis that EC mTOR will mimic systemic mTOR inhibition. To examine this, we studied young (4‐6 mo) and old (22‐24 mo) wildtype (WT) and EC specific tamoxifen inducible mTOR knockout (KO) mice. Arterial function was determined by assessing aortic stiffness by measuring pulse wave velocity (PWV) using Doppler ultrasound in vivo as well as endothelium dependent dilation (EDD) and nitric oxide (NO) bioavailability in isolated arteries using pressure myography. Carotid artery superoxide production was measured using electric paramagnetic resonance. Two weeks after tamoxifen administration (4mg/day, 4 days, oral), we found a 60‐70% reduction in EC mTOR protein (p=0.04). EC mTOR deletion did not alter PWV and EDD in young mice (Fig 1A, 1C), suggesting that EC mTOR is not critical to arterial function in young mice. We next sought to examine whether EC mTOR deletion reverses age‐related arterial dysfunction. Aging resulted in an elevated aortic PWV, indicating higher stiffness, in WT mice and deletion of EC mTOR attenuated aortic stiffening in old mice (p˂0.001, Fig 1A, 1B). Likewise, EDD to acetylcholine (ACh) was lower in mesenteric arteries in old WT mice compared to young mice (p˂0.01, Fig 1C, 1D). However, deletion of EC mTOR markedly improved EDD in old mice (Fig 1D) resulting from an increase in NO bioavailability (31.6 ± 8.6 vs 8.4 ± 2.3; p=0.012). The superoxide scavenger, TEMPOL, increased EDD in old WT and KO mice (Fig 1E), eliminating differences between groups. Furthermore, superoxide production was lower in carotid arteries of KO compared to WT mice (Fig 1F). Collectively, these results suggest that oxidative stress promotes arterial stiffness and impairs EDD with advanced age and ablation of EC selective mTOR reverses this effect. We next examined if this improvement in vascular function resulted in an improvement in metabolic function in the aged mice. To do so, we assessed glucose (2g/kg, ip), insulin (1U/kg, ip), pyruvate (2g/kg, ip) and lipid (3mL/kg, oral) tolerance. Aged KO mice demonstrated greater glucose and lipid tolerance compared to WT littermates (Fig 2A, 2D). Insulin tolerance and glucose‐stimulated insulin secretion did not differ between groups (Fig 2B, 2C), indicating that the improvement in glucose tolerance was independent of peripheral insulin sensitivity and pancreatic beta cell function. EC mTOR deletion improved pyruvate tolerance and reduced hepatic expression of gluconeogenic genes (Fig 2E, 2F), suggesting that attenuated hepatic gluconeogenesis may underlie the enhanced glucose tolerance in the KO mice. Taken together, our findings demonstrate that although without effect on vascular function in young mice, EC specific deletion of mTOR provides beneficial effects on arterial function via reductions in oxidative stress and ameliorates metabolic dysfunction in old mice.

Enhancement of Endothelial KCa Channel Activity as a Novel Strategy to Oppose Atherosclerosis

Atherosclerosis represents a major risk factor for cardiovascular disease and is associated with endothelial dysfunction (ED), which facilitates fatty plaque formation, impairs blood flow and increases arterial stiffness. A hallmark feature of ED is decreased bioavailability of nitric oxide (NO). We have previously reported that pharmacological activation of endothelial Ca2+‐activated K+ channels (KCa2.3 and KCa3.1) can oppose ED by enhancing endothelium‐dependent vasodilation.We hypothesized that improving endothelial function will mitigate the development and/or severity of atherosclerosis in Apoe knockout (Apoe‐/‐) mice. Administration of the KCa channel activator SKA‐31 was utilized to improve endothelial function in vivo.Experimentally, male, 8‐week old Apoe‐/‐ mice on a regular chow diet were administered one of three daily treatments for 16 weeks: SKA‐31 (10 mg/kg), the KCa3.1 channel blocker senicapoc (40 mg/kg), or drug vehicle alone. Pharmacological inhibition of KCa3.1 channels is reported to reduce atherosclerosis in Apoe‐/‐ mice and was utilized as a benchmark. Drugs were formulated in miglyol and condensed milk, which was readily ingested by the mice. Cardiac function and arterial pulse wave velocity (PWV) were assessed by echocardiography under isoflurane anesthesia. Atherosclerotic lesions in the aorta were visualized by Oil‐Red‐O staining and select tissue histology was carried out using H&amp;E staining. Abdominal aortic contractility and relaxation were measured by wire myography in drug‐treated Apoe‐/‐ mice and age/sex‐matched wild‐type C57/BL6 mice.At the end of drug treatment, left ventricular (LV) ejection fraction, fractional shortening and LV posterior wall thickness were not different in Apoe‐/‐ mice treated with either SKA‐31 or senicapoc compared with vehicle. Measurements of aortic PWV showed no significant differences among the three groups, which indicated that neither drug treatment decreased aortic stiffness. Oil‐Red‐O staining of the thoracic aorta and aortic arch revealed fatty plaque formation in Apoe‐/‐ mice (i.e. 10‐12% of area) compared with WT controls (&lt; 1%), however, neither SKA‐31 nor senicapoc treatments reduced plaque formation vs. vehicle. Phenylephrine (PE)‐evoked contraction of abdominal aortic rings appeared similar in WT and vehicle/drug treated Apoe‐/‐ mice, whereas endothelium‐dependent, acetylcholine‐induced relaxation of PE‐constricted aortic rings was enhanced in aortic rings from mice treated with SKA‐31 and senicapoc vs. vehicle. Although relaxation to the smooth muscle vasodilator sodium nitroprusside was augmented in Apoe‐/‐ mice compared with WT, this response was not altered by drug treatment.While both SKA‐31 and senicapoc improved aortic endothelial function, neither drug decreased plaque formation or aortic stiffness, perhaps due to the later onset of these events in the progression of atherosclerotic pathology. We will investigate this likelihood by feeding Apoe‐/‐ mice a high fat diet to accelerate the development of plaque formation and arterial stiffness to determine the effects of both drug treatments on these later stages of atherosclerosis.

Efficacy of Hot Water Immersion versus Aerobic Exercise Training in Lowering Blood Pressure and Improving Cardiovascular Function in Adults with Untreated Hypertension

INTRODUCTIONHypertension remains among the most prevalent cardiovascular disease risk factors world‐wide. Aerobic exercise training is the current gold‐standard non‐pharmacological intervention for lowering blood pressure, yet passive heat therapy is an effective alternative means of reducing blood pressure and improving cardiovascular health for individuals that are unable or unwilling to engage in traditional exercise training. However, the effectiveness of heat therapy versus exercise training has not been compared in adults with untreated hypertension. Therefore, the purpose of this ongoing clinical trial is to compare the effectiveness of hot water immersion (HWI) versus aerobic exercise training (EX) in lowering blood pressure and improving cardiovascular function. Data presented are preliminary (mid‐point) comparisons following 15 sessions of either HWI or EX.HYPOTHESISIt was hypothesized that hot water immersion would be more effective than traditional aerobic exercise training in reducing blood pressure and improving cardiovascular function in adults with untreated hypertension.METHODSPrior to randomization, all subjects (n=6, 1F) completed resting vascular function testing, including measurements of blood pressure (automated sphygmomanometer), cardiac output (acetylene wash‐in method), and carotid‐femoral pulse wave velocity (PWV). Systemic vascular conductance (SVC) was calculated as cardiac output/mean arterial pressure (MAP). Following pre‐testing (PRE), subjects were randomized into either HWI (n=4, 1F) or EX (n=2). During HWI, subjects were immersed to the level of the sternum in 40.5°C water for 45 minutes. EX consisted of upright cycling at 60% of heart rate reserve (HRR) for 40 min, with 5 min each for warm‐up and cool‐down at 30% of HRR. Participants completed 15 sessions of either HWI or EX prior to mid‐point (MID) testing. Combined data are presented as the change from PRE as mean ± SD and were analyzed using a paired‐samples t test. Group mean data for HWI versus EX are presented as the change from PRE as means ± SD and were analyzed using an unpaired two sample t‐test.RESULTSFollowing 15 sessions of either HWI or EX, systolic blood pressure tended to be reduced (‐5±4 mmHg; p=0.10). The change in systolic blood pressure (SBP) was directionally similar between HWI and EX (∆ from PRE, HWI vs. EX; ‐3±5 vs. ‐7±7 mmHg; p=0.59), whereas the change in diastolic blood pressure (DBP) was divergent between HWI and EX (‐3±8 vs. +5±10 mmHg; p=0.43). Accordingly, changes in MAP were disparate between HWI and EX (‐3±7 vs. +2±9 mmHg; p=0.61). Cardiac output was similar between HWI and EX (‐0.09±0.71 vs. ‐0.76±1.07 L/min; p=0.53), as were changes in SVC (‐0.3±6.6 vs. ‐7.6±15.9 mL•min‐1•mmHg‐1; p=0.63). Overall, PWV was reduced by both interventions (‐0.6±0.3 m/s; p=0.01) and changes in PWV were similar between HWI and EX (‐0.6±0.4 vs. ‐0.5±0.4 m/s; p=0.72).CONCLUSIONSPreliminary data from this ongoing clinical trial suggest both hot water immersion and exercise are similarly effective in lowering systolic blood pressure and reducing arterial stiffness in people with untreated hypertension.

Effects of Exercise on Aortic Stiffness Associated with 5‐Flurouracil in Rats

Background5‐fluorouracil (5‐FU) is a chemotherapy drug that is often prescribed in treatment regimens for malignancies of the gastrointestinal tract, breast, and head/neck. However, despite its clear efficacy in cancer treatment, it is also the second most common chemotherapeutic implicated in the development of short and/or long‐term cardiotoxicity that can lead to a less efficacious cancer treatment regimen. Specifically, 5‐FU is associated with increases in arterial stiffness, leading to increased risks for developing heart failure and cardiovascular disease. Exercise, both acutely and following long‐term training, has exhibited cardiovascular health benefits and protection in healthy and disease populations, including reductions in e.g., pulse wave velocity (PWV), a clinical measure of arterial stiffness. Therefore, the purpose of this study was to investigate 5‐FU induced arterial stiffness (via PWV) and evaluate the efficacy of multiple acute bouts of exercise to mitigate arterial stiffness associated with 5‐FU. Further, we utilized reverse phase protein analysis (RPPA) to investigate mechanisms associated with 5‐FU induced arterial stiffness.MethodsMale Sprague Dawley rats aged 6‐8 months (n=26) were used in this series of experiments. All animals were first acclimated to treadmill exercise, and randomized into four groups: Control (CON, n=8), 5‐FU only (5‐FU=7), exercise (EX, n=4), and 5‐FU with exercise (5‐FUEX, n=7). All animals were surgically instrumented with catheters in the external jugular vein and tail artery. Animals received a clinically relevant dose of 5‐FU with the combination of a bolus (50mg/kg), followed immediately by a 2h continuous infusion of 5‐FU (265mg/kg) through the jugular catheter. This was done to better imitate clinical drug delivery rather than i.p injections typically used in pre‐clinical models. Baseline and 2h measurements of PWV were made from the descending to lower abdominal aorta. Both exercise groups underwent four, 20–30‐minute acute bouts of moderate intensity exercise (20m/min, 5% incline) on consecutive days, 24h apart, with the last being ~10 minutes before surgical instrumentation. RPPA analysis was performed on abdominal aorta from each animal for analysis of changes in protein expression.ResultsThere were no differences in PWV between groups at either time point (p&gt;0.05). However, a significant increase in PWV from baseline to the 2h time point was evident in the 5‐FU group alone (CON ‐1.1±4.9, 5‐FU 14.8±4.4, EX 4.6±5.7, 5‐FUEX 5.4.9±2.2%, p&lt;0.05). Preliminary RPPA analysis indicated 1.5log2fold changes in 5‐FU animals in multiple factors, several of which have been associated with increased vascular stiffness including Steroid Receptor Co‐activator (SRC‐1) and mitogen‐activated protein kinase (MAPK1/MAPK3) that will require further investigation.ConclusionThis study suggests that 5‐FU induces aortic stiffness in rats that can be attenuated with prior acute bouts of exercise. These findings provide further efficacy of exercise therapy in cancer standards of care besides its established benefits for reducing fatigue and improving quality of life in cancer patients. Lastly, the potential to mitigate cardiovascular complications of 5‐FU therapy is clinically important as it can possibly prevent early cessation or reductions of this efficacious therapy.

A study of erectile dysfunction in men 40 years of age or younger

ABSTRACT In recent years, awareness of erectile dysfunction and the demand for treatment have been increasing even among young men. We investigated the status of young patients 40 years of age or younger with erectile dysfunction. The subjects were 208 patients who visited the urology departments of Showa University Fujigaoka Hospital and affiliated hospitals with a chief complaint of erectile dysfunction. The erectile function was assessed with the Sexual Health Inventory for Men (SHIM), diary questions on sexual intercourse from the Sexual Encounter Profile, and the Erection Hardness Score, which measures the hardness of erection. The treatment was monotherapy with sildenafil (25 or 50 mg), vardenafil (10 or 20 mg), or tadalafil (10 or 20 mg) or a combination of multiple phosphodiesterase 5 (PDE5) inhibitors. To investigate the cause, blood tests including free testosterone and the Self-rating Depression Scale questionnaire were conducted, and Pulse Wave Velocity (PWV) was measured. The median age of the patients was 36 years. As for the cause of erectile dysfunction, psychogenic erectile dysfunction was observed in 141 patients, accounting for 67.7% of the patients. However, 82.1% of patients who underwent PWV measurement showed measurements suggestive of organic changes. The efficacy rates of PDE5 inhibitors were 77% for sildenafil, 73% for vardenafil, and 85% for tadalafil. This study showed that psychogenic erectile dysfunction was common in young patients, and that PDE5 inhibitors were effective for them. In addition, the study suggested the presence of organic changes as a risk factor for erectile dysfunction even in young patients. Disclosure Work supported by industry: no.

EHypertension: A prospective longitudinal multi‐omics essential hypertension cohort

eHypertension: A prospective longitudinal multi‐omics essential hypertension cohort

The Role of Urate in Cardiovascular Risk in Adolescents and Young Adults With Hypertension, Assessed by Pulse Wave Velocity.

BackgroundUrate is increasingly recognized as a cardiovascular risk factor. It has been associated with hypertension, metabolic syndrome, obesity, chronic kidney disease and diabetes. Its prognostic role is less clear. The aim of our study was to evaluate the association between serum urate and pulse wave velocity, a measure of arterial stiffness in hypertensive adolescents and young adults.Methods269 adolescents and young adults with hypertension were included in the study. From all, anthropometric, blood pressure, pulse wave velocity and serum urate measurements were made. Variables were compared between sex, participants with or without obesity and with or without elevated urate.ResultsIn multiple regression analysis for urate as dependent variable gender and diastolic pressure were found to be statistically significant. The difference between urate levels were found between boys and girls (p < 0.001), obese and non-obese (p < 0.001); however, pulse wave velocity did not differ between hyper- and eu-uricemic group (p = 0.162).ConclusionAssociations between urate, gender, diastolic blood pressure and obesity were confirmed, however, no significant associations between pulse wave velocity and urate were detected.

Pulse Wave Velocity Measurements by Magnetic Resonance Imaging in Neonates and Adolescents: Methodological Aspects and Their Clinical Implications

Pulse wave velocity (PWV) by cardiovascular magnetic resonance (CMR) lacks standardization. The aim of this study was to investigate methodological aspects of PWV measurements by CMR in neonates and adolescents. A computer phantom was created to validate the temporal resolution required for accurate PWV. Fifteen neonates and 71 adolescents underwent CMR with reference standard 3D angiography and phase-contrast flow acquisitions, and in a subset coronal overview images. Velocity and flow curves, transit time methods (time-to-foot (TTF), maximum upslope, and time-to-peak (TTP)), and baseline correction methods (no correction, automatic and manual) were investigated. In neonates, required timeframes per cardiac cycle for accurate PWV was 42 for the aortic arch and 41 for the thoracic aorta. In adolescents, corresponding values were 39 and 32. Aortic length differences by overview images and 3D angiography in adolescents were − 16–18 mm (aortic arch) and − 25–30 mm (thoracic aorta). Agreement in PWV between automatic and manual baseline correction was − 0.2 ± 0.3 m/s in neonates and 0.0 ± 0.1 m/s in adolescents. Velocity and flow-derived PWV measurements did not differ in either group (all p > 0.08). In neonates, transit time methods did not differ (all p > 0.19) but in adolescents PWV was higher for TTF (3.8 ± 0.5 m/s) and maximum upslope (3.7 ± 0.6 m/s) compared to TTP (2.7 ± 1.0 m/s; p < 0.0001). This study is a step toward standardization of PWV in neonates and adolescents using CMR. It provides required temporal resolution for phase-contrast flow acquisitions for typical heartrates in neonates and adolescents, and supports 3D angiography and time-to-foot with automatic baseline correction for accurate PWV measurements.

FEATURES OF THE CLINICAL COURSE OF NON-ST-SEGMENT ELEVATION ACUTE CORONARY SYNDROME DEPENDING ON THE INDICATOR OF THE PULSE WAVE VELOCITY

Pulse wave velocity (PWV) could be used as a predictor of the course of CVD. A carotid–femoral PWV above 10 m/s was determined in 2018 ESC/ESH Guidelines for the Management of Arterial Hypertension as factors influencing cardiovascular risk in patients with hypertension. Exactly the carotid–femoral PWV is considered the gold standard for arterial stiffness assessment in clinical practice. Usually PWV predict the long-term outcomes (in a few month or years) of the development of cardiovascular events. There are a lack of information about using PWV as prognostic marker in acute coronary syndrome.&#x0D; The aim: to study the features of the clinical course of the non-ST-segment elevation acute coronary syndrome (NSTE-ACS) depending on the carotid–femoral pulse wave velocity (PWV) and find out possibilities of using PWV as marker of intrahospital clinical outcomes.&#x0D; Materials and methods. 80 patients were recruited. All patients were hospitalized into myocardial infarction departments with a diagnosis of NSTE-ACS. Patients over 18 years of age who were hospitalized for the first 3 days after the onset of pain and signed the agreement to participate in the study were included. Exclusion criteria were the moderate or severe anemia, severe chronic renal failure, and chronic diseases in the acute or decompensated stage. The average age of patients was 64.5 [55; 72] years. Male patients are 45 persons (56.3%). Were performed standard general laboratory and instrumental examinations. Measuring of free DNA levels, and ischemic albumin were performed on 1st and 6th days of hospitalization. Also noninvasive measured of PWV. Noninvasive PWV measurements were performed after stabilization of the hemodynamic for excluding incorrect results due to its strong connection with current blood pressure. 2 groups were formed depend on the PWV above or less than 10 m/s. The analysis was performed by using non-parametric statistical methods (Mann-Whitney test, Wilcoxon T-test, Pearson's χ2 test). The results were considered statistically significant at p &lt;0.05.&#x0D; Results. Patients did not have a statistically significant difference in such parameters as gender, anamnestic data (hypertension, myocardial infarction, chronic heart failure, atrial fibrillation, and diabetes mellitus), hemodynamic parameters, ECG changes at the moment of hospitalization and laboratory parameters. There was a tendency that patients with elevated PWV were older (69 [55.3; 77.8] years vs. 63.5 [55.3; 70.8] years) (p = 0.077). Such parameters as left ventricular ejection fraction and discharge diagnosis were similar. Patients with elevated PWV had significantly more active cytolysis. This is proved by significantly higher levels of free DNA both on the first day and on the 6th day of hospitalization. In patients with normal PWV levels, free DNA decreased in dynamics, while in patients with PWV above 10 m / s this marker remained at the same level. It was also founded that patients with elevated PWV had delayed ischemia (on the 6th day of hospital stay), which was confirmed by a higher level of ischemia-modified albumin than in the group with PWV less 10 m / s.&#x0D; Conclusions. Patients with increased and normal PWV have quite similar group characteristic according typical clinical signs, results of laboratory and instrumental investigations. Due to the studying of free DNA and ischemia-modified albumin were clarified that PWV above 10 m/s is associated with delayed ischemia and longer tissue damage and could be used to predict it.

Ultrasonography evaluation on the protective effect of combination therapy of beraprost sodium and aspirin on arteries occlusion and stiffness in patients with type 2 diabetes mellitus - a prospective, randomized study

BackgroundPatients with type 2 diabetes mellitus (T2DM) are susceptible to developing symptomatic peripheral arterial disease (PAD). As a proven vasodilator and antiplatelet agent, the efficiency of Beraprost sodium (BPS) on the prevention of arteries occlusion and stiffness in T2DM patients with PAD has not yet been fully investigated.MethodsFrom July 2010 to April 2012, 64 Patients enrolled were randomly assigned to the combined therapy group (n=32), which received combination therapy with BPS (60 μg/day) and aspirin (100 mg/day), or to the control group (n=32), which only received aspirin (100 mg/day). After randomization, the patients were followed up at years 0, 1, 2, 3, 4, and 5 with the evaluation of carotid intima-media thickness (CIMT), pulse wave velocity (PWV), inner artery diameter, stenosis rate, and medial arterial calcification (MAC) of lower limb arteries via high-resolution ultrasound measurement. Adverse events were also recorded in each visit.ResultsThere was no significant change of the CIMT during the follow-up in both groups when compared to the baseline. Similar results were also observed in the PWV measurement. Significantly increases in the inner artery diameter of the dorsal pedal artery and posterior tibial artery were observed in patients with BPS and aspirin administration during the follow-up. Patients in the combined therapy group experienced marked improvement of MAC in the dorsal pedal artery and posterior tibial artery at the end of the follow-up. No significant difference in the adverse events was found between the combined therapy group and the aspirin group.ConclusionThe combined therapy of BPS and aspirin showed a protective effect on arteries occlusion and stiffness in T2DM patients with PAD, along with a significant improvement of inner artery diameter and MAC in lower limbs.Trial registrationhttp://www.chictr.org.cn, ChiCTR-TRC-10000919. Prospectively registered on 2010/06/29.

430 Time restricted feeding in diet induced obesity mouse model reduces aortic stiffness and inflammatory T cells

OBJECTIVES/GOALS: Time restricted feeding (TRF) in diet induced obesity (DIO) has several health benefits, including improved metabolic rhythms and inflammation. Our lab has shown that TRF in DIO significantly reduces renal and aortic damage. The main goal of our research is to understand how TRF impacts aortic function, organ damage, and T cell activation in DIO. METHODS/STUDY POPULATION: We will use a 20-week DIO model, where mice will be on 20 weeks of normal fat diet (ND) or high fat diet (HFD). During weeks 18-20, mice will go through TRF intervention where food is restricted to the 12-hour active period or continue ad libitum feeding. At the end of the 2-week TRF intervention or continued ad libitum feeding, aortic stiffness will be measured via pulse wave velocity measurements. We will also collect kidney, aorta, and small intestine at the end of the 20-week protocol for flow cytometric analysis of tissue T cell activation as well as histological assessments. This will allow us to determine the relationship with organ damage, organ function, and the T cell response. We will also analyze tissue and circulating levels of inflammatory T cell-derived cytokines such as interleukin-17A (IL-17A) via ELISA. RESULTS/ANTICIPATED RESULTS: DIO mice showed significantly increased aortic stiffness (measured by pulse wave velocity) compared to mice on ND. Interestingly, TRF intervention in DIO mice reduced aortic stiffness compared to DIO ad libitum. Histological assessments also showed that TRF abolished aortic and kidney fibrosis suggesting a role for the timing of feeding in regulating aortic function and organ damage from chronic HFD. We have several ongoing experiments to determine the T cell response with TRF in DIO mice. We predict that TRF in DIO mice will significantly decrease inflammatory T cells and reduce cytokine abundance in target organs. DISCUSSION/SIGNIFICANCE: Our lab has shown that TRF reduces aortic thickness and aortic and kidney fibrosis, but the driving mechanisms are unknown. We propose that TRF reduces T cell activation in DIO mice leading to reduced organ damage. Our work will provide insight on how TRF in DIO regulates the T cell response and may improve inflammation in the kidney and aorta.

Systemic Arterial Stiffness Is Associated With Structural Progression in Early Open-Angle Glaucoma.

PurposeThe purpose was to identify association between systemic arterial stiffness predicted by brachial-ankle pulse wave velocity (PWV) and initial location of structural progression in early open-angle glaucoma.MethodsPatients with early open-angle glaucoma who underwent PWV measurements were subjected to a retrospective review of medical records. A total of 160 eyes of 160 patients were subjected to analyses. Patients were categorized into three PWV groups. Structural progression was determined using event-based analysis of the Guided Progression Analysis software of Cirrus optical coherence tomography.ResultsThirty-eight patients had a PWV of 1400 cm/s or less on both the left and right sides (low PWV, 39.5% females, 53.9 ± 8.8 years old), and 46 patients showed a PWV of 1800 cm/s or more on either side (high PWV; 54.3% females, 71.3 ± 5.8 years old). The rest of the patients had an intermediate PWV (n = 76, 50.0% females, 59.8 ± 8.6 years old). Among patients who showed progression in 69.3 ± 41.5 months, macular ganglion cell–inner plexiform layer (mGCIPL) loss preceded peripapillary retinal nerve fiber layer (ppRNFL) loss in 86.7% of high PWV group (n = 15, 60.0% females, 70.0 ± 6.0 years old) in comparison with 26.7% of the low PWV group (P = 0.002). The PWV was significantly higher in patients whose structural progression was first observed at mGCIPL (1744.1 ± 347.7 cm/s) than patients whose initial location was ppRNFL (1452.0 ± 201.0 cm/s; P = 0.012). A high PWV was associated with increased likelihood of structural progression at mGCIPL (odds ratio, 7.484; 95% confidence interval, 1.212–49.196; P = 0.030) among patients who showed progression.ConclusionsPWV is a significant predictor of the location of structural progression in open-angle glaucoma. Vascular insufficiency may be an important aspect in the pathogenesis of glaucoma.

Improving the accuracy and robustness of carotid-femoral pulse wave velocity measurement using a simplified tube-load model

Arterial stiffness, as measured by pulse wave velocity, for the early non-invasive screening of cardiovascular disease is becoming ever more widely used and is an independent prognostic indicator for a variety of pathologies including arteriosclerosis. Carotid-femoral pulse wave velocity (cfPWV) is regarded as the gold standard for aortic stiffness. Existing algorithms for cfPWV estimation have been shown to have good repeatability and accuracy, however, further assessment is needed, especially when signal quality is compromised. We propose a method for calculating cfPWV based on a simplified tube-load model, which allows for the propagation and reflection of the pulse wave. In-vivo cfPWV measurements from 57 subjects and numerical cfPWV data based on a one-dimensional model were used to assess the method and its performance was compared to three other existing approaches (waveform matching, intersecting tangent, and cross-correlation). The cfPWV calculated using the simplified tube-load model had better repeatability than the other methods (Intra-group Correlation Coefficient, ICC = 0.985). The model was also more accurate than other methods (deviation, 0.13 ms−1) and was more robust when dealing with noisy signals. We conclude that the determination of cfPWV based on the proposed model can accurately and robustly evaluate arterial stiffness.

Blood pressure control, target organ protection and metabolic disorders control using a fixed combination of azilsartan medoxomil + chlorthalidone in hypertensive patients survived after severe and extremely severe COVID-19

Objective. Evaluation of the possibility of a fixed combination of azilsartan medoxomil + chlorthalidone in additional angioprotection in patients with arterial hypertension (HTN) and high pulse wave velocity (PWV) after confirmed severe or extremely severe COVID-19 (bilateral polysegmental viral pneumonia) treated by genetically engineered biological drugs, who had not previously received combined antihypertensive therapy.Design and methods. An open observational study lasting 12 weeks included 30 patients, 28–31 days after discharge from the hospital after a severe and extremely severe COVID-19, who received or had not previously received antihypertensive therapy. Patients underwent 24-hour blood pressure (BP) monitoring, applanation tonometry (augmentation index and central BP), measurement of PWV, laboratory tests before and after prescription of a fixed combination of azilsartan medoxomil + chlorthalidone.Results. At baseline, patients showed an increase in office blood pressure to 153,06/92,2 mmHg. After treatment with a fixed combination of azilsartan medoxomil + chlorthalidone, a decrease in systolic BP by 18,47% and diastolic BP by 16,24% was observed. According to ambulatory BP monitoring, the decrease in systolic BP was 19,65% and diastolic BP — 24,68%, PWV decreased by 34,4%, augmentation index — by 9,42%, central systolic BP — by 15,48% (p &lt; 0,05). At baseline, vascular age (VA) was increased to 44,96 years compared to the passport age of 35,03 years. After treatment, there was a significant decrease in VA to 38,74 years (p &lt; 0,01). In addition, the levels of C-reactive protein, fibrinogen, D-dimer, glucose, blood urea nitrogen and uric acid significantly decreased.Conclusions. The fixed combination of azilsartan medoxomil + chlorthalidone provides better control of BP. It also helps to improve vascular elasticity (augmentation index, PWV, central systolic BP, decrease in VA) and to reduce post-infectious inflammation in HTN patients after a severe coronavirus infection.

Arterial stiffness acute changes following aerobic exercise in males with and without hypertension.

While regular exercise exposure is considered the most effective therapy to reduce arterial stiffness, the effect of acute exercise training on arterial stiffness in adults with different blood pressure (BP) levels remains unclear. The authors aimed to investigate the effects of acute aerobic exercise on arterial stiffness in male with different BP levels. This cross‐sectional study utilized data for 1200 males aged 20–49 years from the Kailuan study cohort who participated in the fifth National Fitness Monitoring project. A total of 940 participants (621 in the non‐hypertensive group and 319 in the hypertensive group) aged 36.82 ± 7.76 who completed a twice‐quantitative cycle ergometer exercise and measure of brachial‐ankle pulse wave velocity (baPWV) at both the baseline and immediately after exercise were included in this study. The baPWV was decreased after acute aerobic exercise in the non‐hypertension and hypertension groups (Δ 40.29 [95% confidence interval [CI], −47.72 to −32.86] vs. Δ20.45 [95% CI, −31.32 to −9.58] cm/s). Participants without hypertension showed a greater decrease in baPWV (Δ 19.84 [95% CI, −33.83 to −5.84] cm/s) than participants with hypertension. Aerobic exercise had an acute positive effect on arterial stiffness. This study provides evidence of a greater reduction in arterial stiffness in individuals without hypertension than in those with hypertension.

The Severity of Obstructive Sleep Apnea Increases the Risk of Arteriosclerosis.

Obstructive sleep apnea (OSA) is a common disorder worldwide. It is associated with myocardial remodeling and arteriosclerosis in patients with hypertension. Our study investigated the relationship between OSA severity and arteriosclerosis and blood pressure in an Asian population. We enrolled 365 subjects from July 2018 to December 2020 at Ruijin Hospital. We recorded data from the medical history and collected blood samples from all participants. We performed 24-hour ambulatory Blood Pressure (BP) monitoring and Carotid-femoral pulse wave velocity (cf-PWV) measurements. Overnight polysomnography (PSG) was performed using Respironics Alice PDxSleepware. PSG was performed in a total of 365 subjects; mean age of 49.1 ± 12.8 years and Body Mass Index (BMI) 28.1 ± 3.8 kg/m2. The majority (89.3%) were male. The office systolic BP was significantly higher in the moderate to severe group than mild OSA group (148 ± 21 mmHg vs 139 ± 19 mmHg, p < 0.01). The subjects with moderate to severe OSA presented higher cf-PWV values than those in the mild group (10.03 ± 3.67 m/s vs 7.62 ± 1.48 m/s, p < 0.01). BMI was significantly higher in the moderate to severe than the mild OSA groups (28.3 ± 4.0 kg/m2 vs 27.5 ± 3.2 kg/m2, p < 0.05). The Pearson correlation showed that the apnea-hypopnea index (AHI) was significantly and positively correlated with cf-PWV (r = 0.217, p < 0.01), Age (r = 0.148, p < 0.01), BMI (r = 0.228, p < 0.01) and HbA1c (r = 0.172, p < 0.01). After adjusting for age, BMI, low density lipoprotein cholesterin (LDL-c), FGB, AHI, estimated Glomerular Filtration Rate (eGFR), Night BP, office diastolic BP and Day BP in Logistic regression model, AHI (OR = 1.03, 95% CI: 1.01-1.05) and office diastolic pressure (OR = 1.04, 95% CI: 1.00-1.08) and age (OR = 1.12, 95% CI: 1.06-1.19) were independent risk factors for arteriosclerosis. The severity of OSA was positively correlated with pulse wave velocity. AHI, office BP and age were independent risk factors for arteriosclerosis.