Decrease In Pulse Wave Velocity Research Articles

Reduction of aortic stiffness in newly diagnosed persons with HIV-infection: modifiable vascular dysfunction after antiretroviral therapy?

Abstract Background People living with HIV (PLWH) are at an increased risk of cardiovascular disease (CVD), which is underestimated by contemporary risk stratification systems[1]. Subclinical cardiovascular abnormalities may be present at the time of HIV diagnosis and serve as potential substrate for future CVD. Aortic stiffness, as measured with pulse wave velocity (PWV), is a validated predictor of CVD [2,3] and has been shown to be elevated in PLWH at the time of HIV diagnosis compared to HIV-uninfected persons[4]. Purpose To prospectively assess the influence of contemporary antiretroviral therapy (ART) on aortic stiffness in a group of newly diagnosed PLWH in a low- to middle-income setting. Methods A group of ART naïve PLWH with modest cardiovascular risk and free from known CVD, was recruited at the time of HIV diagnosis from the Western Cape Province of South Africa. Aortic stiffness was measured using carotid-femoral PWV on a commercially available device that simultaneously measured the carotid and femoral waveforms on a supine patient in a temperature-controlled room utilising established methodology[4]. The algorithmically-calculated time delay between the upstroke of the carotid and femoral wave-forms provided the transit time (TT). Carotid femoral path distance (path length) was measured using surface anatomy. PWV was calculated as direct path length divided by TT. Aortic distensibility was expressed according to the Bramwell-Hill equation as 3.57/PWV(squared)[5]. ART was initiated and PWV was re-evaluated 9 months later. Results Seventy-three participants completed follow-up and were included. The cohort was relatively young (mean age 32±7 years) with good female representation (n=33, 45%). Most received tenofovir/lamivudine/dolutegravir (n=71, 97%) Half of the group smoked cigarettes. Two participants were controlled hypertensives, and two participants had metabolic syndrome. A significant decrease in PWV (with scaling factor of 0.8) was observed at 9 months of ART (5.93 ±1.0 vs. 5.69 ±1.0 m/s; p=0.01). Aortic distensibility increased significantly as well (0.20 [IQR: 0.16 to 0.26] vs. 0.21 [IQR: 0.19 to 0.27] mmHg-1; p=0.02). Conclusion Improvement in aortic stiffness was observed in a group of newly diagnosed PLWH after 9 months of ART-initiation. This provides evidence of a modifiable component of vascular dysfunction and, in turn, cardiovascular risk with the use of contemporary ART at 9 months. It is unknown if this effect will be sustained long-term. The use of aortic stiffness (alone or in combination with other parameters) as a predictor of cardiovascular outcomes in the ART era requires further study.Abstract figureAbstract table

Effects of a medium cut-off dialyzer on inflammation and cardiac and vascular function in hemodialysis patients with heart failure.

Expanded hemodialysis (HDx) could provide clearance of larger middle-molecule uremic toxins. We compared the effect of hemodialysis with medium cut-off membranes and high-flux (HFHD) membranes regarding changes in inflammation and vascular and left ventricular function. This was a single-center, prospective, parallel-group comparative study. Patients were divided into two groups (HDx: 25 patients and HFHD: 26 patients). All measurements were performed at baseline and 12 weeks. Serum c-reactive protein, interkelukin-18, pentraxin-3, β-2 microglobulin, and brain natriuretic peptide were measured. We used pulse wave velocity and augmentation index to assess arterial stiffness and echocardiography to evaluate left and right ventricular function. We enrolled 51 patients. Although serum c-reactive protein, interkelukin-18, pentraxin 3, and β-2 microglobulin were significantly decreased in the HDx group (p = 0.02, p < 0.001, p = 0.002, and p = 0.02, respectively), there was no significant change in HFHD group at 12th week. Serum c-reactive protein and interkelukin-18were significantly lower in the HDx group compared to the HFHD group in the 12th week (p = 0.007 and p = 0.03, respectively). We observed a significant decrease in pulse wave velocity in the HDx group at the end of the study (p = 0.03). Although there was no significant change in pulse wave velocity in the HFHD group, pulse wave velocity was similar between the HDx and HFHD groups in the 12th week. We detected a significant decrease in the mean isovolumetric relaxation time in the HDx group (p = 0.006). However, there was no significant difference in isovolumetric relaxation time between the HDx and HFHD groups in the 12th week. HDx provides better clearance of middle molecular uremic toxins and inflammatory biomarkers, and it may be associated with better central hemodynamic parameters and diastolic functions.

#2570 Non-invasive blood pressure monitoring in dialysis patients using pulse wave velocity

Abstract Background and Aims Dialysis patients are at high risk of circulatory dysregulation and hypotension during treatment. Intradialytic hypotension (IDH) is a potentially life-threatening complication. The main causes are high ultrafiltration volumes and high ultrafiltration rates when patients tend to gain a lot of weight between dialysis treatments. A lack of patient compliance with regard to drinking volumes and a lack of residual diuresis are risk factors for this. Close circulatory monitoring and therapy settings to avoid absolute or relatively high UF rates to prevent IDH are frequently used. These are primarily the frequent non-invasive measurement of blood pressure using cuffs, the measurement of relative blood volume and the adjustment of ultrafiltration rates to these values. Prophylactically, the dialysis time can be extended, ultrafiltration profiles or ultrafiltration breaks can be planned, the dialysate temperature can be lowered and the composition of the dialysate can be adjusted. Despite all attempts, however, the incidence of IDH in everyday clinical practice is too high. The non-invasive measurements with cuffs are not carried out frequently enough, the measurement of the relative blood volume only covers a partial range, sudden changes in vascular tension or cardiac output are not recorded. Method The pulse wave velocity (PWV) is a well-known parameter for describing the propagation of the pressure wave after ejection of the heart beat volume in the arteries. The PWV is dependent on blood pressure, vessel wall tension and cardiac output. Changes in blood pressure can therefore be recognised by measuring the PWV. With the help of a measuring device (PESAS) for the ECG signal and peripheral pulse plethysmography, PWV can be measured non-invasively, continuously, for every heartbeat and, above all, hardly noticed by the patient. The PESAS allows the time-synchronised measurement of ECG and peripheral plethysmography curves and thus the determination of PWV. It is an experimental device. We would like to present a study showing the use of a measuring device (PESAS) in 15 prevalent dialysis patients for the detection of IDH. All study participants were examined during 3 dialysis treatments. Results The measurement of PWV in chronic dialysis patients during treatment is technically feasible. The measurement is tolerated by the patients. Changes in PWV could be detected in the patients during the course of dialysis; these were also dependent on the ultrafiltration rates. Individual patient reactions to volume withdrawal varied, with both increases and decreases in PWV being demonstrated. An acute change in PWV was usually associated with a drop in blood pressure. Continuous measurement allowed IDH events to be detected earlier than intermittent blood pressure measurement with cuffs. Sudden drops in blood pressure could be detected better and earlier with the PESAS system than by measuring the relative blood volume. Conclusion The PESAS system is suitable for monitoring dialysis patients to prevent IDH. Further adjustments and optimisation of the evaluation algorithms are necessary.

A global solution to a hyperbolic problem for blood flow modelling

The paper aims to examine the hyperbolic system of equations governing one-dimensional haemodynamics and its relevance in analysing blood flow under mechanical influences, with particular emphasis on the impact of altering the angle of the leg axis. Methods and approaches for solving hyperbolic equations have been developed in light of their properties and characteristics. The primary objective of this study was to investigate the interplay between vein pressure, pulse wave velocity, and vascular distension. The study revealed an inverse relationship between vein pressure and pulse wave velocity. A decrease in pulse wave velocity occurs when vein pressure rises, and vice versa. Both real measurements and modelling results confirmed this dependence. The pressure in the veins is between 10.8 and 13.6 kPa, and the speed of the pulse wave is between 0.061 and 0.27 kPa. The agreement between real and model data was high. The modelled venous pressure and pulse wave velocity values are close to the actual values. However, it is essential to acknowledge the limitations of this paper. These limitations include the utilisation of one-dimensional haemodynamic models, which fail to consider the three-dimensional structure of the circulatory system. Additionally, the analysis is restricted to examining changes solely in the leg axis angle. The research helps to clarify the relationship between mechanical actions and haemodynamic parameters. The findings may help research and develop new methods for identifying and treating conditions associated with the cardiovascular system.

Effects of low-pressure Valsalva maneuver on changes in cerebral arterial stiffness and pulse wave velocity.

The Valsalva maneuver (VM), commonly used to assess cardiovascular and autonomic nervous system functions, can induce changes in hemodynamic function that may affect cerebral vascular functionality, such as arterial elasticity. This study aimed to investigate the effects of low-pressure VM on cerebral arterial stiffness and cerebral vascular dynamics. Thirty-one healthy young participants (average age 21.58±1.72 years) were recruited for this study. These participants were instructed to maintain an expiratory pressure of 30-35 mmHg for 15 seconds. We measured the vasoconstriction and vasodilation diameters (VCD and VDD) of the common carotid artery (CCA), as well as systolic and diastolic blood pressures (SBP and DBP), before and after VM (PRE_VM and POST_VM). Additionally, we assessed mean arterial pressure (MAP), pulse pressure (PP), pulse wave velocity (PWV), and arterial stiffness. Our findings revealed significant increases in both the VCD and VDD of the CCA (2.15%, p = 0.039 and 4.55%, p<0.001, respectively), MAP (1.67%, p = 0.049), and DBP (1.10%, p = 0.029) following low-pressure VM. SBP showed an increasing trend, but this was not statistically significant (p = 0.108). Interestingly, we observed significant decreases in arterial stiffness and PWV in POST_VM when comparing with PRE_VM (p<0.001 and p<0.001, respectively). In conclusion, our study demonstrated the effectiveness of low-pressure VM in reducing the PWV and stiffness of the CCA. This suggests that low-pressure VM can be a simple and cost-effective method to reduce cerebrovascular stiffness in a brief interval, without the need for specific environmental conditions.

Effect of sodium-glucose co-transporter inhibitors on arterial stiffness in patients with type 2 diabetes mellitus

Abstract Introduction Selective sodium-glucose co-transporter 2 inhibitors (SGLT2i) reduce cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). In addition to glucose homeostasis the impaired arterial stiffness may participate in this morbidity and mortality. Purpose The aim of this study was to investigate the effect of administration of SGLT2i therapy on arterial stiffness parameters, including aortic pulse wave velocity (PWV) and central systolic blood pressure (SBPao), which have significant prognostic value for predicting cardiovascular events. Methods Our prospective, observational study included 40 patients with T2DM (mean age: 60.3±9.9 years, 24 males). Biochemical and arterial stiffness parameters were analysed before starting SGLT2i therapy (14 patients on dapagliflozin, 25 patients on empagliflozin, 1 patient on ertugliflozin), at 3, 6 months and an average of 3.3±1.3 years follow-up period. Arterial stiffness parameters were determined using an invasively validated oscillometric based Arteriograph (AG) method. Changes in the variables and their interrelation was analysed by repeated data ANOVA and multivariate linear regression. Results Significant decrease in PWV and HgbA1c were observed 3 months after the initiation of SGLT2i therapy (PWV: 10.68±1.35 m/s vs. 10.05±1.40 m/s and HgbA1c: 7.86±0.55 vs. 6.83±0.66 %, p&amp;lt;0,05) and this long-term effect continued during the 3.3-years follow-up period (PWV: 9.96±1.25 m/s and HgbA1c: 7.19±0.81 %, p&amp;lt;0,005, Figure 1). Pearson's correlation analysis and multivariate linear regression analysis showed no association between decreased PWV and BMI, brachial diastolic blood pressure (DBPb) while significant, but weak correlation was observed with HgbA1c and brachial systolic blood pressure (SBPb) (r=0.22-0.26, p&amp;lt;0.05, Figure 2). SBPao results showed non-significant decrease and a subsequent non-significant long-term increase comparing to baseline during the 3.3 years follow-up. Conclusion Short and long-term SGLT2i therapy in T2DM significantly improved PWV values and this effect is independent of changes in SBPao. All these findings emphasize the clinical relevance of arterial stiffness as a biomarker in the SGLT2i induced beneficial effect on the vasculature, however further clarification, long-term evaluation needed to define the role of PWV in the prediction of cardiovascular events.Figure 1Figure 2

Effects of sodium-glucose contrasporter-2 inhibitors and glucagon-like peptide-1 receptor agonists on vascular function and liver steatosis in diabetes

Abstract Background/Introduction Patients with type-2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) present increase risk of cardiovascular disease. Sodium-glucose contrasporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to significantly reduce the risk of cardiovascular complications. Purpose The aim of the study was to investigate the effect of treatment with SGLT-2i or GLP-1RA on vascular function and liver steatosis and fibrosis in patients with T2DM and NAFLD. Methods Thirty patients with T2DM and NAFLD (mean age: 57±11 years) were randomized to receive SGLT-2i (dapagliflozin; n=15) or GLP-1RA (dulaglutide; n=15). At baseline and at 6 months post-treatment, we measured: (1) Perfused boundary region (PBR) of the sublingual microvessels with a diameter 5-25μm using Sidestream Dark Field camera (Microscan, Glycocheck). Increased PBR indicates reduced glycocalyx thickness. (2) Pulse wave velocity (PWV) and augmentation index (AI) using Complior (ALAM Medical), (3) NAFLD fibrosis score (NFS), and (4) Controlled attenuation parameter (CAP) score to assess steatosis grade and liver stiffness (E) to evaluate fibrosis score using liver elastography (FibroScan, Echosens). Results At baseline, patients between the two groups had similar age, sex, HbA1c, steatosis grade, fibrosis score and markers of vascular function (p&amp;gt;0.05). Compared with baseline, all patients had reduced PBR, PWV, AI, NFS, CAP and E (p&amp;lt;0.05) after 6-month treatment. In the whole study population, the percentage reduction of markers of steatosis (NFS) correlated with the corresponding decrease in PBR (r=0.34, p=0.040) and PWV (r=0.31, p=0.043) post-treatment. Both treatments with SGLT-2i and GLP-1RA reduced markers of liver steatosis and fibrosis (Table). Conclusion Both treatments with SGLT-2i and GLP-1RA improve vascular function and reduce liver steatosis in patients with T2DM and NAFLD after 6-month treatment.Table

Effect of glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors and their combination on left atrial strain and arterial function

Abstract Funding Acknowledgements Type of funding sources: None. Background We investigated the effects of insulin, glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and their combination on left atrial function of patients with type 2 diabetes mellitus and we searched for a relation with arterial function. Patients and methods A total of 201 patients (59,5±9,1 year old, 161 male) with type 2 diabetes mellitus treated with metformin were randomized to insulin (n= 50 served as controls), liraglutide (n=51), empagliflozin (n=50) or their combination (GLP-1RA+SGLT- 2i) (n= 50) as add-on. We measured at baseline and 6 months posttreatment: (a) perfused boundary region of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness), (b) pulse wave velocity (PWV) and central systolic blood pressure, (c) global left ventricular Longitudinal strain, (d) left atrial strain. Results Six months after intervention, all patients improved left atrial reservoir strain (GLP1RA 30,7±9,3 vs 33,9±9,7%, p = 0,011/SGLT2i 30±8,3 vs 32,3±7,3%, p = 0,04/ GLP1&amp;SGLT2i 29,1±8,7 vs 31,3±8,2, p = 0,007) in comparison with controls (33±8,3% vs 32,8±7,4, p = 0,829). Also, patients treated with GLP1RA and their combination improved left atrial conduction strain (p&amp;lt;0.05). GLP-1RA or GLP-1RA+SGLT-2i provided a greater improvement in GLS compared with insulin or SGLT-2i (controls –18,5±3,9% vs − 19,1±3%, p = 0,202/GLP1RA –18,2±4,1% vs –19,1±3,5%, p = 0,03/SGLT2i –19±4,1% vs − 19,1±3,8%, p = 0,764/GLP1&amp;SGLT2i –16,7±3,9% vs –17,5±4,3%, p = 0,026). SGLT-2i or GLP-1RA and SGLT-2i showed a greater decrease of PWV (Controls 12,06±3,02 vs 11,62±2,79 m/sec, p = 0,142/ GLP1 11,54±2,91 vs 11,45±2,52 m/sec, p = 0,822/ SGLT2 11,86±2,51 vs 11,33±2,28 m/sec, p = 0,047/ GLP1&amp;SGLT2 12,01±2,46 vs 10,85±1,79 m/sec, p = 0,021) and central and brachial systolic blood pressure than insulin or GLP-1RA. At baseline, there was a correlation of LA reservoir strain with PWV (r =−0,209, p = 0,008), central SBP (r =−0,151, p = 0,030), EF (r=0,214, p = 0,004), GLS (r =−0,279, p = 0,009). At 6 months follow up, there was a correlation of LA reservoir strain with PWV (r=0,217, p = 0,003), central SBP (r =0,214, p = 0,004), EF (r=–0,221, p = 0,049), GLS (r =0,275, p = 0,014). Conclusions Treatment with GLP-1RA, SGLT-2i, and their combination for 6 months showed a greater improvement of left atrial function compared to insulin treatment in parallel with improvement arterial and myocardial function.

#5699 IS GFR DECLINE INDUCED BY SGLT-2 INHIBITOR OF CLINICAL IMPORTANCE?

Abstract Background and Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated with better cardiovascular outcome and with nephroprotection independent of diabetes status. However, the use of SGLT2i often cause an initial decline in estimated glomerular filtration rate (eGFR). This study addresses the question whether there is a relationship between vascular improvement and GFR dipping. Method We measured GFR (mGFR) and calculated GFR (eGFR) in 65 patients with T2D at baseline and after 12 weeks of treatment with either a combination of Empagliflozin (E) + Linagliptin (L) (n = 34) or Metformin (M) + Insulin (I) (n = 31). mGFR was measured using the gold standard clearance technique by infusion of inulin. In addition, pulse wave velocity (PWV) was obtained at office and under ambulatory conditions. We splitted the study cohort according to the median change of mGFR after 12 weeks and compared the baseline characteristics. Results mGFR and eGFR decreased significantly with E+L and with M+I (Ott C et. al. Cardiovasc Diabetol. 2021). However, no correlation was noticed between the change of mGFR and change of eGFR for either treatment cohorts (E+L: p = 0.404; M+I: p = 0.460). We found a significant decrease in office PWV in the E+L group only (8.2±1.6 to 7.8±1.5, p = 0.028) without any change in 24-h PWV. The change of office PWV correlated with the change of mGFR (p = 0.009) in E+L group only and remained significant after adjustment for the change of office systolic BP (p = 0.018). In addition, we observed a correlation between the change of high sensitive C reactive protein (hsCRP) and change in mGFR (p = 0.031). We identified patients with higher albumin excretion (p = 0.044), higher fasting plasma glucose (p = 0.014) and high hsCRP (p = 0.057) to have a greater decline in mGFR with E+L. Conclusion First, eGFR may not be an appropriate parameter to assess the true change in renal function after receiving E+L in a single patient. Second, after E+L medication a high decrease in mGFR goes in parallel with vascular improvement and less inflammation thereby reflecting the pleiotropic pharmacologic effects of SGLT 2 inhibitors.

Reduction of arterial stiffness in depressive individuals responding to multimodal treatment

BackgroundDepressive individuals are at higher risk for cardiovascular diseases (CVD). Thus, cardiovascular parameters such as arterial stiffness, often measured by pulse wave velocity (PWV), should be monitored. Recent research indicated that depressive individuals exhibit higher PWV, but there is little data on the changeability of PWV through multimodal treatment. This study investigated PWV in moderately to severe depressive individuals before and after undergoing treatment in dependence on responding or not responding to treatment. Methods47 participants (31 females, 16 males) underwent a PWV measurement and filled out a questionnaire surveying depressive symptom severity before and after a six-week psychiatric rehabilitation treatment including multimodal interventions. Subjects were divided in responders and non-responders, depending on their treatment success. ResultsA mixed ANCOVA analysis indicated no significant main effect of responder status, but a significant main effect of measurement time and a significant interaction between responder status and measurement time. Responders exhibited a significant decrease in PWV across time, while no significant change in PWV across time was found for non-responders. LimitationsResults are limited by the lack of a control group. The influence of medication duration or medication type was not considered in the analyses. Causality of the relationship between PWV and depression cannot be determined. ConclusionThese findings show that PWV can be positively modified in depressive individuals responding to treatment. This effect cannot solely be attributed to pharmacological interventions but rather the combination of multimodal interventions, thus highlighting the clinical relevance of multimodal treatment in depression and comorbid disorders.

PS-P15-3: PATIENTS WITH GLOMERULONEPHRITIS IN REMISSION HAVE DECREASED ARTERIAL STIFFNESS COMPARED TO CKD PATIENTS

Background: Arterial stiffness is the hallmark of the vascular aging process, in which a disruption in collagen to elastin balance in the large arteries with decreased compliance of the central vasculature leads to excess cardiovascular morbidity. Carotid- Femoral Pulse wave velocity (PWV) is the preferred non-invasive way to quantify arterial stiffness. Apart from age, blood pressure, presence of long standing hypertension, diabetes or kidney impairment, inflammation has been quoted as an harbinger of arterial stiffness. However, in a prior work of our group we found Familial Mediterrenean Fever (FMF) patients to have a decreased PWV, possibly relaed to the relapsing-remitting type of the disease and a possible ptotective role of colchicine. Objective: To compare the PWV of patients with Glomerulonephritis (GN) in clinical remission to patients with non inflammatory CKD (either eGFR &lt; 60 or uACR above 30 mg/gram), mostly related to hypertension and diabetes. Methods: We prospectively collected data on 58 patients from our Nephrology and Hypertension Center, which either had non inflammatory CKD (30 patients) or a glomerular disease in partial or complete remission (28 patients). central (aortic) blood pressure and Pulse wave velocity (PWV) were measured using validated Sphygmocor XCEL ® device. Results: In a multivariate regession analysis adjusting for age, presence of hypertension, history of diabetes and creatinine values, having glomerular disease in remission was associated with a significant decrease in PWV (B- 3.262) indicating better arterial elasticity compared to CKD patients. Conclusion: Patients with glomerulonephritis in remission have better arterial elasticity compared to CKD patients, possibly similar to the general age and blood pressure matched population. This is in accordance with our findings in FMF patients, who were adherent to colchicine treatment and in clinical remission. It is possible that prior treatment with anti-inflammatory and immunomodulatory drugs carry a beneficial effect on vascular health.

Decreased Pulse Wave Velocity in a Systemic Sclerosis Population: Preliminary Results from a Cross-Sectional Study.

Systemic Sclerosis (SSc) is an autoimmune disorder characterized by organ and tissue fibrosis in which the incidence of atherosclerosis and cardiovascular events is increased, although the exact underlying mechanism remains unclear. Arterial stiffness is a marker of vascular damage that can predict cardiovascular events; therefore, this study aimed to assess the augmentation index (AIx) and pulse wave velocity (PWV), markers of stiffness, in a Systemic Sclerosis population and to detect potentially associated variables. Fourteen female Systemic Sclerosis patients and 14 age- and sex-matched controls were enrolled. Demographic, anthropometric, sero-hematological parameters and disease characteristics were collected for each participant. Arterial stiffness was evaluated using an applanation tonometry system. No differences were found between groups, except for BMI, fasting blood glucose, red blood cells count, hemoglobin, and treatment. Patients had increased augmentation index than the controls (p = 0.008). PWV was significantly decreased in SSc patients compared with the controls (p = 0.007). PWV was correlated with age (r = 0.462; p = 0.048) and BMI (r = 0.458; p = 0.050). Finally, patients with no specific auto-antibody pattern had greater AIx than those expressing anticentromere antibodies. Our study demonstrated that SSc patients had greater AIx, but lower PWV than the controls. In addition, few variables were correlated to arterial stiffness. Further studies are necessary to validate these findings and to establish medication's role in modifying cardiovascular risk.

Effect of sodium-glucose co-transporter-2 inhibitors on arterial stiffness: A systematic review and meta-analysis of randomized controlled trials.

Arterial stiffness represents an established cardiovascular risk marker. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have significant cardio-protective effects. Herein we sought to determine the effect of SGLT-2 inhibitors on pulse wave velocity (PWV). We searched PubMed, Cochrane Library, and grey literature from inception to 7th February 2022 for randomized controlled trials (RCTs) enrolling adult subjects with or without type 2 diabetes mellitus (T2DM), assigned to a SGLT-2 inhibitor versus control and addressing their effect on PWV. We set as primary efficacy outcome the change in PWV with SGLT-2 inhibitors versus placebo or control. We pooled data from six trials in a total of 452 enrolled participants assigned either to SGLT-2 inhibitor or control. Overall, SGLT-2 inhibitor treatment compared to control resulted in a nonsignificant decrease in PWV. Exclusion of a trial utilizing cardiac magnetic resonance imaging for the assessment of PWV demonstrated that SGLT-2 inhibitors induce a significant reduction in PWV by 0.21 m/s. When we restricted our analysis to RCTs enrolling subjects with T2DM, we observed that SGLT-2 inhibitor compared to control resulted in a significant decrease in PWV by 0.17 m/s. SGLT-2 inhibitors do not decrease PWV in patients with established cardiovascular disease or cardiovascular risk factors. However, we have shown that SGLT-2 inhibitors lead to a slight, but significant decrease in PWV in patients with T2DM. The latter finding is of great value, based on the significant correlation between PWV and micro- and macro-vascular complications of T2DM.

EFFECT OF SODIUM-GLUCOSE CO-TRANSPORTER-2 INHIBITORS ON ARTERIAL STIFFNESS UNDER STATIC OR AMBULATORY CONDITIONS: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Objective: Arterial stiffness represents an emerging cardiovascular risk factor with independent prognostic implications. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are a novel drug class with significant cardio-protective effects, but largely unknown mechanism underlying this effect. Herein we sought to determine the effect of SGLT-2 inhibitors on pulse wave velocity (PWV), the “gold-standard’’ measure of arterial stiffness. Design and method: We searched PubMed, Cochrane Library and grey literature from inception to 10th October 2021 for parallel group randomized controlled trials (RCTs) enrolling adult subjects with or without type 2 diabetes mellitus (T2DM), assigned to a SGLT-2 inhibitor versus placebo or active comparator and addressing their effect on PWV under static or ambulatory conditions. We set as primary efficacy outcome the change in PWV with SGLT-2 inhibitors versus placebo or control. Results: We pooled data from 4 trials for a total of 301 enrolled participants assigned either to SGLT-2 inhibitor or control. Treatment with a SGLT-2 inhibitor compared to placebo or active control led to a significant decrease in PWV by 0.25 m/s (mean difference = -0.25, 95% CI; -0.49 to -0.01, I2 = 24%, p = 0.04). Certainty of evidence was graded as low. Conclusions: SGLT-2 inhibitors produce a slight, however statistically significant decrease in PWV in patients with established cardiovascular disease or cardiovascular risk factors, such as hypertension and T2DM.

Comparative Efficacy of Single Pill Combinations of Azilsartan Medoxomil/Chlorthalidone and Losartan/Hydrochlorothiazide in Patients with Hypertension and Heart Failure with Preserved Ejection Fraction

Aim. To study the effects of azilsartan medoxomil/chlorthalidone (AZM/CTD) and losartan/hydrochlorothiazide (LOS/HCT) combinations for NTproBNP levels, 6-minute walk test results, hydration status along with their antihypertensive efficacy according to clinical and 24-hour blood pressure in patients with hypertension and heart failure with preserved ejection fraction (HFpEF).Material and methods. An open randomized study included 56 patients with uncontrolled or untreated hypertension and HFpEF. Patients randomized to receive the AZM/CTD 40/12.5 mg/day (group 1; n=28) or LOS/HCT 100/12.5 (group 2; n=28) within 4 weeks. Patients who did not achieve the target BP &lt;140/&lt;90 mm Hg study drug dose was intensified: in the first group, an increase in the dose of AZM/CTD 40/25 mg/day, in the second group, an increase in the dose of LOS/HCT 100/25 mg/day. The observation period was 12 weeks. All patients underwent a clinical examination with an assessment of symptoms and/or signs of HF, laboratory and instrumental studies, including NT-proBNP, ambulatory blood pressure (BP) monitoring, applanation tonometry, a 6-minute walk test (6MWT), echocardiography. In order to assess the status of hydration, bioimpedance vector analysis (BIVA) was performed. HFpEF was diagnosed according to the HFA-PEFF algorithm. The results were considered statistically significant at p&lt;0.05.Results. After 12 weeks, 92% of patients in the first and 78% of patients in the second group reached the target clinical BP (р&lt;0,05). Average daily BP &lt;130/ &lt;80 mm Hg was reached by 82% of patients treated with the combination of AZM/CTD, compared with 67% treated with the combination of losartan/HCT (p&lt;0.05). After 12 weeks, patients from both groups showed a significant decrease in systolic and diastolic blood pressure, central blood pressure, and a decrease in pulse wave velocity, which was more significantly significant in the first group of patients (p&lt;0.05). During therapy in both groups of patients, a significant decrease in the level of NT-proBNP was observed: in the first group from 300 [199; 669] pg/ml to 156 [157; 448] pg/ml (p=0,003), in the second group from 298 [180; 590] pg/ml to 194 [140; 360] pg/ml (p=0,006), an increase in the distance during the 6MWT from 317 [210; 398] m to 380 [247; 455] m (p=0,006) in in the first group and an improvement in the hydration status according to the BIA data, but more significantly significant in the first group (p&lt;0.001).Conclusion. In patients with hypertension and HFpEF, therapy with the AZM/CTD combination compared with LOS/HCT is accompanied by a more pronounced antihypertensive effect in terms of ambulatory and peripheral blood pressure, central blood pressure, NTproBNP levels, increased distance in 6MWT and achievement of euvolemia status.

Vascular conditioning prevents adverse left ventricular remodelling after acute myocardial infarction: a randomised remote conditioning study

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): EU-CARDIOPROTECTION COST ACTION (European Cooperation in Science and Technology-Action) (CA16225) Background Remote ischemic conditioning (RIC) alleviates ischemia-reperfusion injury via several pathways, including micro-RNAs (miRs) expression and oxidative stress modulation. Purpose We investigated the effects of RIC on endothelial glycocalyx, arterial stiffness, LV remodelling, and the underlying mediators within the vasculature as a target for protection. Methods We block-randomised 270 patients within 48 h of STEMI post-PCI to either one or two cycles of bilateral brachial cuff inflation, and a control group without RIC. We measured: (a) the perfusion boundary region (PBR) of the sublingual arterial microvessels to assess glycocalyx integrity and (b) the carotid-femoral pulse wave velocity (PWV) at baseline (T0), following every RIC cycle (T1, T2), and 40 min after RIC onset (T3); (c) miR-144, -150, -21, -208, nitrate-nitrite (NOx) and malondialdehyde (MDA) plasma levels at baseline (T0) and 40 min after RIC onset (T3); and (d) LV volumes at baseline and after one year. Results Compared to baseline, there was a greater PBR and PWV decrease, miR-144 and NOx levels increase (p &amp;lt; 0.05) at T3 following single- than double-cycle inflation (PBR:ΔT0-T3 = 0.249 ± 0.033 vs 0.126 ± 0.034 μm, p = 0.03 and PWV:0.4 ± 0.21 vs -1.02 ± 0.24 m/s, p = 0.03). Increased miR-150,-21,-208 (p &amp;lt; 0.05) and reduced MDA was observed after both protocols. Increased miR-144 was related to PWV reduction (r = 0.763, p &amp;lt; 0.001) after the first-cycle inflation in both protocols. After one year, single-cycle RIC was associated with LV end-systolic volume reduction (LVESV) &amp;gt; 15% (odds-ratio of 3.75, p = 0.029). MiR-144 and PWV changes post-RIC were interrelated and associated with LVESV reduction at follow-up (r = 0.40 and 0.37, p &amp;lt; 0.05), in the single-cycle RIC. Conclusions RIC evokes "vascular conditioning" likely by upregulation of cardio-protective microRNAs, NOx production, and oxidative stress reduction, facilitating reverse LV remodelling.

Aortic stiffness and systemic inflammation changes predict clinical response to intravitreal anti-vascular endothelial growth factor therapy in patients with age-related macular degeneration.

Aortic stiffness and systemic inflammation are predictors of cardiovascular risk. Anti-vascular endothelial growth factor agents (anti-VEGF), injected intravitreally, can reverse the course of exudate age-related macular degeneration (AMD). We sought to investigate the association of changes in aortic stiffness and systemic inflammation with response to anti-VEGF therapy. 54 patients (mean age: 76 ± 10 years) with AMD received two consecutive monthly intravitreal injections of ranibizumab (0.5 mg). The primary outcome measure was change in carotid-femoral pulse wave velocity (PWV) from baseline to 1 month after the second injection. Secondary endpoint was the change in serum high sensitivity interleukin-6 (hsIL-6) levels. Ranibizumab caused a decrease of PWV after the first (by 0.36 ± 1.4 m/s) and the second injection (by 0.31 ± 1.4 m/s) and remained decreased 1 month after the second injection (overall P < 0.05). PWV decreased significantly in good responders (according to clinical criteria and fundus findings, P = 0.004), whereas it increased numerically in poor responders (P = 0.21) over the study period. In responders, hsIL-6 decreased after the first injection and remained decreased 1 month after the second injection (by 0.63 ± 0.35 pg/ml, overall P = 0.02). PWV (P = 0.005) and hsIL-6 (P = 0.042) were independent predictors of improvement after adjusting for age and presence of hypertension and diabetes. The decrease in PWV through the whole study period was positively correlated with the reduction in hsIL-6 (r = 0.36, P < 0.01). Intravitreal ranibizumab injections lead to a decrease in PWV and hsIL-6. Both parameters predict clinical improvement and may aid to improving treatment targeting and hence therapeutic outcome in patients with AMD.

The Left Ventricular End-Systolic Pressure Correlation with Aortic Valve Timing; a Novel Inotropic Index Description Using a Dual Pressure Catheter

Myocardial contraction is generated by ventricular pressure in early systole by the isometric force against closed valves, as ventricle is contracting without changing volume. This initial contractile phase of cardiac cycle (early systole) is followed by rapid shortening, isotonic contraction, allowing ejection of the blood against changing LV afterload. LV is coupled to the systemic arterial pressure; hence LV ejection is closely linked to the properties of the aortic valve, aorta, and its distributing arteries. Isometric relationship in the LV was characterized using the load-dependent example (naïve vs. post-dobutamine), observed mostly in case of rate of rise of LVP, LV ESP and decrease of pulse wave velocity, characteristics of LV baroinometry. Furthermore, by performing load-independent maneuver, afterload (LV ESP) was adjusting at every cardiac cycle, while an assessment of LV ESP and aortic valve timing was able to be established. By plotting decaying LV ESP against aortic valve timing, highly linear correlation of load-independent isotonic, but also an isometric contractility was captured. Steeper linear slope and time-axis intercept (IC) were identified in case of post-inotropic challenge, recapitulating changes otherwise measured during pressure-volume exam. This relationship, measured by dual-pressure catheter, could serve as novel inotropic index of functional cardiac contractility. Keywords: Left Ventricle (LV); Contractility; Inotropy; Load-Dependent and Independent; Stressed Volume; Dual Pressure Catheter. 1. Assessment of cardiac contractility using dual pressure catheter. 2. IVCO inferior vena cava occlusion, ECC excitation-contraction coupling, EF ejection fraction, TTE transthoracic echocardiography, Ea end arterial elastance, PRSW preload recruitable stroke work, IC intercept, PWV pulse wave velocity.

Abstract P151: Higher Gut Microbiota Diversity And Abundance Of Butyrogenic Species Are Associated With Lower Pulse Wave Velocity In The Baltimore Longitudinal Study Of Aging

Background: Gut microbiota, particularly butyrogenic species, may affect risk of cardiovascular disease through effects on arterial stiffness. However, studies on gut microbiota and arterial stiffness in human population studies are sparse, with no prior studies having used shotgun metagenomic sequencing to identify species. Objective: To investigate associations of gut microbiota with measures of arterial stiffness as measured by pulse wave velocity (PWV). Methods: We studied 780 adults from the Baltimore Longitudinal Study of Aging who provided feces for shotgun metagenomic microbiome sequencing and at least 1 measure of carotid-femoral PWV between 2013 and 2017. We examined associations of PWV (continuous and as quartiles) with gut microbiome features using beta-binomial and linear regression models for microbiota relative abundances; linear regression models for microbial alpha diversity (Shannon index); and PERMANOVA for microbial beta diversity (Weighted Unifrac distance). We adjusted all models for age, sex and race. We used an FDR-threshold of q &lt;0.05 for abundance models. Results: Approximately 55% of our sample were female and 65% identified as white, with a mean age of 71 years. Microbial beta diversity was significantly associated with PWV (Weighted UniFrac p=0.003, R 2 =0.01), and a 1-SD increase in (Shannon index) alpha diversity was associated with a 0.21 decrease in PWV (p=0.002). Twelve species were associated with continuous PWV, including 4 key butyrate producers in dose-response fashion (Figure). These findings persisted after further adjustment for Mediterranean diet score. Conclusion: Higher microbial diversity and abundance of key butyrogenic bacteria were associated with lower arterial stiffness in a racially diverse cohort of US adults. Some of the species associated with arterial stiffness, e.g. F. prausnitzii and other taxa in Figure, have been previously associated with lower cardiovascular disease risk. Clinical trials are needed to determine if these relationships are causal.

The effect of breastfeeding during infancy on arterial stiffness in young adults.

Breastfeeding has many benefits for health, also later in life. However, its effects on the cardiovascular system are still unclear. The aim of the present study was to evaluate the effect of exclusive breastfeeding as infants on arterial stiffness in young adults having no cardiovascular risk factors, using aortic pulse wave velocity, and brachial and aortic augmentation index. Eighty-six subjects were included in the study from similar socioeconomic status. 46 subjects who had received exclusive breastfeeding for the first 4-6 months in infancy (26 women, mean age 26.7±4 years) (group 1) and 40 subjects who had received exclusive breastfeeding for less than 3 months or had never been breast-fed (22 women, mean age: 28±3.8 years) (group 2) were recruited. Parameters of arterial stiffness (aortic pulse wave velocity, brachial and aortic augmentation index) were investigated using an arteriograph (TensioMed, Budapest, Hungary), which works on an ossilometric basis. A significant decrease in pulse wave velocity in the breast-fed group was detected compared to the non-breast-fed group (P<0.05) but no significant difference was detected for aortic and brachial augmentation index. In addition there was a significant relationship between breastfeeding duration and aortic pulse wave velocity. Breast milk intake in infancy reduces the risk of cardiovascular disease in young adults, independent of other cardiovascular risk factors. It seems that there is a negative relationship between the duration of breastfeeding and the risk reduction.