Pulse Wave Research Articles

Association between body shape index and arterial stiffness: results of the EVasCu study and a meta-analysis.

The aim of this study was to analyse the association between body shape index (ABSI) and arterial stiffness in healthy subjects using data from the EVasCu study. In addition, a meta-analysis was performed to compare the association between ABSI and central, peripheral and systemic arterial stiffness in the general population. The EVasCu study included 390 healthy subjects. ABSI was calculated from waist circumference, body mass index and height, and arterial stiffness was assessed with aortic pulse wave velocity (a-PWv) and cardio-ankle vascular index (CAVI). A meta-analysis of previous studies, including data from the EVasCu study, was performed to obtain pooled estimates of correlation coefficients (r) and their respective 95% confidence intervals (95% CIs) for the association between ABSI and central, peripheral and systemic arterial stiffness. In addition, pooled OR estimates and their 95% CIs were calculated. In the EVasCu study, the correlation coefficient estimate was 0.458 (p < 0.01) for the association of a-PWv and ABSI and 0.408 (p < 0.01) for the association of CAVI and ABSI. In the meta-analysis, the pooled correlation coefficient estimate was 0.22 (95% CIs: 0.16, 0.28) for central arterial stiffness and ABSI, 0.21 (95% CIs: 0.14, 0.28) for peripheral arterial stiffness and ABSI, and 0.28 (95% CI: 0.21, 0.3) for systemic arterial stiffness and ABSI. When pooled ORs were calculated, the pooled OR estimate was 2.12 (95% CIs: 1.68, 2.56) for central arterial stiffness and ABSI, 2.21 (95% CIs: 1.81, 2.60) for peripheral arterial stiffness and ABSI, and 2.99 (95% CIs: 2.14, 3.85) for systemic arterial stiffness and ABSI. Based on both the results obtained in the EVasCu study and the meta-analysis, there is a positive association between ABSI and arterial stiffness, both in healthy subjects and in participants with comorbidities. For each unit of cm/kg/m²/m increase in ABSI, the risk of arterial stiffness increased by 112% for central arterial stiffness, 121% for peripheral arterial stiffness, and 199% for systemic arterial stiffness. However, further research is needed in this field of knowledge.

Estimated aortic pulse wave velocity predicts adverse events in females with thoracic aortic aneurysms

Abstract Introduction Despite being more common in males, thoracic aortic aneurysms (TAAs) have worse prognosis in females. Females with TAA are 3x more likely to experience acute aortic syndromes, and 40% more likely to die than their male counterparts, but mechanisms underlying this paradox are incompletely understood. The estimated aortic pulse wave velocity (e-PWV) is a marker of aortic stiffness that can be used widely due to its simplicity, as it does not require specialized equipment. We have previously shown that e-PWV was independently associated with faster TAA growth,(1) and that this association was twice as strong in females than males, but the role of e-PWV as a predictor of adverse outcomes in TAA remains unknown. Purpose We sought to evaluate the sex-specific association of e-PWV with adverse outcomes in patients with TAA. Methods We performed a prospective study of 102 males and 48 females with TAA. e-PWV was calculated according to validated equations utilizing age, mean arterial pressure, and presence/absence of cardiovascular risk factors.(2) The primary outcome was a composite of acute aortic syndromes, death, or elective aortic surgery. We used a Cox proportional hazard model to determine the independent association of e-PWV with the primary outcome, adjusted for age, BSA, aneurysm size and location, hypertension, and pulse pressure. Sex-specific models were performed if the interaction of sex*e-PWV was significant (P≤0.05). Univariate logistic regression models were performed to determine the c-statistic for e-PWV in predicting adverse outcomes, and the best e-PWV cutoff for this prediction was established based on sensitivity and specificity. Kaplan-Meier curves were performed using this cut-off. Results A summary of study design and results is presented in Picture 1. Mean age was 62±12 years, 70 (47%) had degenerative etiology, baseline aneurysm size was 46.3±4.3mm, and e-PWV was 9.5±1.9 m/s (not different between sexes, P&amp;gt;0.07 for each). Mean follow-up was 4.6±2.4 years in females and 5.5±2.3 years in males, P=0.031. The primary outcome occurred in 37 (25%) participants (3 dissections, 3 intramural hematomas, 1 aortic rupture, 22 elective surgical repairs and 11 deaths - 3 of which followed surgery). The interaction term sex*e-PWV was significant (P=0.0001), so sex-specific models were performed. e-PWV independently predicted the primary outcome in females (HR for 1m/s increase in e-PWV: 3.4; 95% confidence interval (CI): 1.1-14.7, P=0.033), but not in males (HR: 0.87; 95% CI: 0.50-1.51, P=0.622). In females, e-PWV had a c-statistic of 0.860 for the detection of the primary outcome, with a best e-PWV cutoff of 11.58 m/s (73% sensitivity, 92% specificity). Kaplan-Meier curves for the primary outcome in females using this cutoff are shown in Picture 2. Conclusion e-PWV independently predicts adverse outcomes in females with TAA, highlighting a novel marker for risk stratification and therapeutic targeting.Study summaryKaplan-Meier curves

Estimated pulse wave velocity as a forefront indicator of developing metabolic syndrome

Abstract Background The predictive value of estimated pulse wave velocity (ePWV) for the development of metabolic syndrome has not been extensively explored. Purpose This study aims to fill this gap by evaluating ePWV as a potential predictor for the development of metabolic syndrome in middle-aged adults. Methods Using prospective multi-center cohort database, participants aged between 40 and 69 years without metabolic syndrome at baseline were studied (enrolled from June 2001 to January 2003 and provided follow-up information spanning up to 18 years). ePWV was calculated using specific equations based on age and blood pressure. The primary outcome was the incidence of metabolic syndrome during a median follow-up period of 15.6 years (187 months). Results Of the 6,186 participants analyzed, 2,726 (44.1%) developed metabolic syndrome during the follow-up period. ePWV values were categorized into tertiles to assess their predictive value for the development of metabolic syndrome. An ePWV cut-off of 7.407 m/s was identified as a predictor of metabolic syndrome development, with a sensitivity of 0.743 and a specificity of 0.464 (Figure 1). Participants exceeding this cut-off, especially those in the third tertile (8.77–14.63 m/s), had a notably higher risk of developing metabolic syndrome. Specifically, the third tertile exhibited a 52.8% cumulative incidence compared with 30.8% in the first tertile as illustrated by Kaplan–Meier curves (Figure 2). After adjustments, participants exceeding the ePWV cut-off had a 1.425-fold increased independent risk of developing metabolic syndrome (HR, 1.425; 95% confidence interval [CI], 1.281–1.585). Furthermore, those in the third tertile showed an even higher risk with an HR of 1.530 (95% CI, 1.330–1.761) compared to first tertile, even after adjusting for multiple variables. Conclusions ePWV is a significant predictor of the development of metabolic syndrome. This finding underscores the potential of ePWV as a cardiometabolic risk assessment tool and can thus provide useful information for primary and primordial prevention strategies.Figure 1Figure 2

Cumulative effect of lifetime smoking history on arterial stiffness and subclinical atherosclerosis in patients with arterial hypertension

Abstract Introduction Although the effect of smoking status on blood pressure (BP) changes is well known an adverse association between cumulative smoke exposure (by pack-years) and functional and structural changes in arteries of patients with high BP has not been consistently demonstrated. Aim of the study was to explore the contributions of cumulative smoke exposure to the vascular consequences of arterial hypertension. Methods Indices of vascular function and structure including carotid-femoral pulse wave velocity (PWV), augmentation index (AIx) and carotid intima media thickness (cIMT) were measured in 485 adults aged less than 60 years old without a history of cardiovascular disease. The cohort was divided into three groups according to office systolic BP (SBP) and diastolic BP (DBP): normal (SBP &amp;lt;130 and DBP &amp;lt;85 mmHg, n=242), high normal (130≤SBP&amp;lt;140 or DBP 85≤DBP&amp;lt;90mmHg, n=96), and hypertension (SBP≥140 or DBP≥90mmHg, n=147). The cohort was subdivided according to pack-years of smoking history as never smokers (0.0 pack-years), light smokers (&amp;lt;20 pack-years), moderate smokers (20-40 pack-years), and heavy smokers (&amp;gt; 40 pack-years). Results The three BP groups had similar age and metabolic parameters (body mass index, fasting blood glucose and LDL-C). Figure shows PWV, AIx and carotid IMT by smoking exposure, stratified by BP level. The lowest PWV level was observed in never smokers with normal BP; whereas heavy smokers with hypertension exhibited the highest PWV. Also of note, heavy smokers with normal BP exhibited comparable PWV to light and never smokers with hypertension. Furthermore, in smokers with more than 20 pack-years tobacco exposure, PWV was higher among patients with high normal BP compared to subjects with normal BP (all P&amp;lt;0.01). In contrast to the monotonic increases in PWV and AIx by BP and pack-years smoking history, carotid IMT was generally similar among BP groups on the basis of cumulative exposure category. This finding may indicate a plateau in subclinical atherosclerotic burden over cumulative tobacco exposure for all BP categories. Conclusion Tobacco cumulative exposure adversely modify the effect of BP on arterial stiffness. Given that most adults who smoke start before the age 18 years, efforts to promote smoking cessation should continue to target younger adults with high BP.BP, tobacco exposure-vascular changes

Serum Malondialdehyde-Modified Low-Density Lipoprotein Level May Be a Biomarker Associated with Aortic Stiffness Among Patients Undergoing Peritoneal Dialysis

Background: Serum malondialdehyde-oxidized low-density lipoprotein (MDA-oxLDL) is associated with atherosclerosis and increased risk of cardiovascular disease (CVD). Vascular calcification frequently occurs with arterial stiffness in patients on peritoneal dialysis (PD). This cross-sectional study aimed to elucidate the correlation between aortic stiffness and MDA-oxLDL levels in patients on PD. Methods: Overall, 92 patients on PD were included. The carotid–femoral pulse wave velocity (cfPWV) was evaluated using cuff-based volumetric displacement, and blood samples were obtained from all patients. Aortic stiffness was classified based on cfPWV values (&gt;10 m/s indicating aortic stiffness). Serum MDA-ox-LDL levels were quantified using commercial enzyme-linked immunosorbent assay kits. Results: In total, 33 (35.9%) patients were classified into the aortic stiffness group. Factors, including systolic blood pressure (SBP), serum triglyceride levels, C-reactive protein levels, age, weight, body mass index (BMI), waist circumference, MDA-oxLDL levels, and diabetes mellitus (DM) prevalence, were significantly higher in the aortic stiffness group. Multivariable logistic regression analysis revealed significant associations between aortic stiffness and MDA-oxLDL levels, BMI, and SBP. Furthermore, multivariable forward stepwise linear regression analysis revealed serum MDA-oxLDL levels as a significant independent predictor of cfPWV values. Conclusions: Serum MDA-oxLDL levels correlate positively with cfPWV values and may predict aortic stiffness among PD patients, highlighting its potential role in assessing CVD risk in this population.

Coronary microvascular dysfunction in patients with heart failure with reduced and mildly reduced ejection fraction: results from the PANACEA study

Abstract Aims Coronary microvascular dysfunction (CMD) is common and associated with impaired survival in patients with heart failure with preserved ejection fraction (HFpEF). In patients with heart failure with reduced ejection fraction (HFrEF) and mildly reduced ejection fraction (HFmrEF) the impact of CMD is not fully known. Purpose We aimed to investigate the prevalence of CMD and its association with phenotype, biomarkers, endothelial function and echocardiographic measurements in patients with HFrEF or HFmrEF. Method A prospective, exploratory bi-center study in patients with chronic stable heart failure, New York Heart Association (NYHA) Class II-IV, and ejection fraction (EF) &amp;lt;50% was performed. Study procedures included echocardiography, adenosine-based transthoracic Doppler echocardiography to assess coronary flow reserve (CFR), physical examination, fasting blood and urine sample, pulse wave velocity (PWV) and hemodynamic measurements. The cutoff of CFR&amp;lt;2.5 was used to diagnose CMD. A multivariable linear regression analysis with CFR as dependent variable, adjusted for age, sex, body mass index, smoking, atrial fibrillation and left ventricular mass, was performed to explore biomarkers, endothelial function, and echocardiographic measurements associated with CMD. Results Of 112 included patients, 87 (78%) were men, with a mean age of 73.3 (±7.5) years. Among patients with a successful CFR measurement (n=62), CMD was present in 40 (65%), mean age of 75.4 (±5.8) years (Table 1). Patients with CMD had higher N-terminal pro B-type natriuretic peptide (NTproBNP) and Troponin T (p&amp;lt;0.05), and more often HFrEF ( p=0.06). Patients with CMD had larger ventricles with greater left ventricular mass and larger end-diastolic volumes (p&amp;lt;0.05). In a linear regression analysis CMD was associated with higher NTproBNP, lower EF, PWV and global strain (table 2). Conclusion CMD was common and present in two thirds of patients with HFrEF or HFmrEF. Further CMD was associated with markers of more severe heart failure and systemic endothelial dysfunction indicating that CMD may be an important predictor of outcome in patients with HFrEF and HFmrEF.

Effects of SGLT-2i and GLP-1RA in vascular function parameters: the impact of the weight loss

Abstract Background Arterial stiffness and endothelial function markers flag increased cardiovascular disease risk in patients with type 2 Diabetes Mellitus (T2DM), while weight management plays a crucial role for the management of glycemic control and prevention of complications in these patients. Purpose To investigate the effects of novel antidiabetic agents on arterial stiffness and endothelial function as well as the metabolic parameters of HbA1c and Weight in T2DM patients. Patients and Methods: We enrolled 99 consecutive patients under stable antidiabetic therapy who did not reach therapeutic targets. Subjects were assessed to receive an additional antidiabetic agent to optimize glucose control; glucagon like peptide-1 receptor agonist (GLP-1RA, n=50) or sodium/glucose cotransporter-2 inhibitor (SGLT-2i, n=49). Glycosylated hemoglobin (Hba1c) and weight expressed through Body Mass Index (BMI) along with carotid-femoral pulse wave velocity (PWV) and flow-mediated dilatation (FMD), as biomarkers of arterial stiffness and endothelial function accordingly, were measured at baseline and 3 months after treatment intensification. Results There were no differences between the study groups in traditional risk factors of age and sex or baseline HbA1c, BMI, PWV, and FMD levels (ps=NS for all). In both groups PWV values displayed a statistically significant improvement from 11.2±2.5 to 9.3±2.2 m/sec (p&amp;lt;0.001) in the GLP-1RA group and from 10.7±2.4 to 8.9±2.0 m/sec (p=0.001) in the SGLT-2i group, as presented in Figure 1 through the differences in the values of PWV. FMD values were also significantly improve in both groups from baseline to follow-up; from 6.04±1.22 to 6.50±1.26% (p&amp;lt;0,001) for the GLP-1RA group and from 6.38±1.21 to 6.81±1.29% (p&amp;lt;0.001) for the SGLT-2i group. Moreover, both groups achieved better weight management goals in terms of BMI values between baseline and follow-up; from 33.6±4.9 to 31.5±4.6 kg/m2 for the GLP-1RA group (p&amp;lt;0.001) and from 31.8±5.5 to 30.5±5.6 kg/m2 for the SGLT-2i group (p&amp;lt;0.001), in addition to achieving better glycemic control in terms of HbA1c values, as seen in their paired differences: for GLP-1RA: 1.3±0.7% and for SGLT-2i: 0.8±0.5%. Interestingly, in the SGLT-2i group the magnitude of the PWV improvement was correlated with the weight loss (r=0.368, p=0.007). Conclusion These data provide evidence that the newer antidiabetic drugs, both GLP1-RA and SGLT-2i, have actions that benefit both vascular function, endothelium as well as metabolic parameters. Interestingly, in the patients receiving SGLT-2i the magnitude of the PWV improvement was correlated with the weight loss.delta PWV for SGLT-2i &amp; GLP-1RA groupsCorrelation of deltaWeight &amp; deltaPWV

Effects of sodium-glucose contrasporter-2 inhibitors and glucagon-like peptide-1 receptor agonists on arterial stiffness, coronary flow reserve and liver steatosis in diabetes

Abstract Background Patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) present an increased 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 decrease 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 cardiovascular function and liver steatosis and fibrosis in patients with T2DM and NAFLD. Methods Forty patients with T2DM and NAFLD (mean age: 58 ± 11 years) were randomized to receive SGLT-2i (dapagliflozin; n = 20) or GLP-1RA (dulaglutide; n = 20). At baseline and after 6 and 12 months of 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) using Complior (ALAM Medical), (3) coronary flow reserve (CFR) using Doppler echocardiography, (4) LV global longitudinal strain (GLS) using speckle-tracking echocardiography, (5) controlled attenuation parameter (CAP) score to assess steatosis grade and liver stiffness (E) to evaluate fibrosis score using liver elastography (FibroScan, Echosens), and (6) NAFLD fibrosis score (NFS). Results At baseline, patients between the two groups had similar age, sex, HbA1c, steatosis grade, fibrosis score and markers of cardiovascular function (p &amp;gt; 0.05). Compared with baseline, all patients had reduced PBR, PWV, CAP, E and NFS and increased CFR and GLS (p &amp;lt; 0.01) after 12-month treatment. In the whole study population, the percentage reduction of CAP and NFS was correlated with the corresponding decrease of PBR (r = 0.248 and r = 0.387), PWV (r = 0.290 and r = 0.281) and with the increase of GLS (r = -0.320 and r = -0.295) after 12-month treatment (p &amp;lt; 0.05 for all correlations). 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 cardiovascular function and reduce liver steatosis in patients with T2DM and NAFLD after 12 months.

Incremental prognostic value of combined information of arterial stiffness and the result of treadmill exercise test in patients with suspected coronary artery disease

Abstract Background The effectiveness of diagnostic tools can be enhanced by their combination. We aimed to investigate whether arterial stiffness data, obtained by brachial-ankle pulse wave velocity (baPWV) measurement, could improve prognostic value to exercise treadmill test (ETT) to predict future cardiovascular events. Methods A total of 1,788 consecutive subjects (mean age 55.8 ± 10.7 years, 59.1% men) with suspected of having coronary artery disease (CAD), who underwent ETT and baPWV on the same day were prospectively recruited. The study outcome was major adverse cardiac and cerebrovascular event (MACCE), a composite of cardiac death, non-fatal myocardial infarction, coronary revascularization and ischemic stroke. Results During a mean follow-up period of 875 days (interquartile range, 116–2,212 days), there were 88 cases of MACCE (4.9%). The elevated baPWV (≥ 1,440 cm/s) (hazard ratio [HR] 5.18; 95% confidence interval [CI] 2.68–10.0; P &amp;lt; 0.001) and positive ETT result (HR 2.81; 95% CI 1.77–4.47; P &amp;lt; 0.001) were associated with MACCE even after adjustment for potential confounders. The combination of baPWV to traditional risk factors and ETT result further stratified the subjects’ risk (low baPWV and negative ETT result vs. high baPVW and positive ETT result; HR 16.44; 95% CI 6.17–43.78; P &amp;lt; 0.001). Conclusions Arterial stiffness, assessed by baPWV, had incremental prognostic value to ETT result in patients with suspected of CAD. baPWV can serve as a useful clinical tool for risk stratification in this high-risk patient population.Kaplan-Meier survival curveMultivariable cox analysis

Treadmill exercise test as a screening tool in the development of hypertension

Abstract Background Guidelines promote screening people with high normal BP for the presence of end-organ damage because their presence is associated with a 2- to 3-fold increase in the risk of CVD. Purpose Office blood pressure measurements may be unable to detect early subclinical cardiac damage of adverse prognostic significance in subjects with high normal blood pressure. Methods 100 consecutive subjects with high normal BP [systolic BP=130-139mmHg and/or diastolic BP=85-89mmHg] were examined for early signs of hypertension-mediated organ damage (HMOD). They underwent an echocardiographic study, a negative for ischemia treadmill exercise test (Bruce protocol) where the index SBP/MET-slope [(peak SBP—resting SBP)/(peakMET-1)] was used. Arterial stiffness was evaluated based on carotid-femoral pulse wave velocity (PWV). The sympathetic drive was assessed by MSNA. Follow-up was scheduled every 6 months for 3 consecutive years, where BP measurements were assessed in the office and with ambulatory BP monitoring (ABPM). All participants offered lifestyle advice to lower their BP. The endpoint was the development of HTN either with Office BP or ABPM. Results Of 100 subjects (54±8 years, 42 males, baseline office BP: 132/82 mmHg, 24-hour BP: 122/76 mmHg), 40 developed HTN in 3 years. 34 subjects developed Hypertensive Response to Exercise (HRE) (BP &amp;gt;210mmHg in men and &amp;gt;190mmHg in women) and all of them developed HTN. The SBP/MET-slope in future hypertensives was increased in all stages till peak exercise independently of sex type (stage1: 6.7vs4.9 p=0.049, stage2: 8.4vs4.8 p=0.001, peak: 6.7vs4.9, p=0.001). Their exercise capacity was reduced (10vs11.3METs, p=0.002) as well as their maximum exercise heart rate (156vs164, p=&amp;lt;0.0001). Those with HRE had higher 24hSBP (124vs121mmHg, p=0.009), Night SBP (117vs111mmHg, p&amp;lt;0.001), Day SBP (127vs124mmHg, p=0.012) Office Pulse Pressure (51vs47mmHg, p=0.01). Additionally, they had increased PWV (8.3vs7.5m/sec, p=&amp;lt;0.0001), MSNA levels (36vs28 bursts, p=&amp;lt;0.0001), LVMI (38vs34 gr/m2.7, p=0.02), and a statistically significant deterioration of 2021 CKD-EPI eGFR (90 vs 97 mL/min/1.73 m², p=0.02). All of them correlated with development of hypertension (p=0.002), while they did not differ regarding their metabolic profile at the follow-up. Conclusion Detecting exaggerated blood pressure response and specifically an increased SBP/MET-slope in the end of second stage of Bruce protocol at treadmill exercise test is associated with increased systemic vascular resistance and early subclinical HMOD which may upgrade an individual’s cardiovascular disease (CVD) risk as they progress to HTN indicating a need for instituting a BP-lowering strategy.

Twelve-months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with type 1 diabetes mellitus

Abstract Background Individuals diagnosed with type 1 diabetes mellitus (T1DM) exhibit indications of vascular and endothelial dysfunction earlier in comparison to healthy individuals. Evidence shows that SGLT-2 inhibitors (SGLT-2i) have a beneficial impact on cardiovascular health in individuals with type 2 diabetes mellitus (T2DM). We investigated the effects of dapagliflozin on endothelial and cardiovascular function in patients with T1DM. Methods We recruited in total 40 patients with T1DM and pour glycemic control who were treated with insulin and received dapagliflozin (n=20) or intensification of insulin treatment (n=20) (control group). We measured at baseline and at twelve months post-treatment the: a) Carotid-femoral pulse wave velocity (PWV-Complior; ALAM Medical) b) Central systolic blood pressure (cSBP) c) Perfused boundary region (PBR) of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness) and d) Left ventricular global longitudinal strain (GLS) using speckle-tracking echocardiography. Results At baseline, patients among the two groups had similar age, sex, HbA1c and markers of endothelial and cardiovascular function (p&amp;gt;0.05). After 12 months of treatment, patients who received dapagliflozin displayed an improvement in PBR5–25 (−16%, p&amp;lt;0.05), in PWV (−9.3%, p&amp;lt;0.05), in cSBP (−6%, p&amp;lt;0.05) and in GLS (+4%, P&amp;lt;0.05) compared to baseline. However, no statistically significant changes in PBR5–25, in PWV, in cSBP and in GLS were observed after intensification of insulin treatment (PBR5–25: +0.4%, PWV: -1%, cSBP: −2%, GLS: −1% at 4 months, P&amp;gt;0.05), despite a similar HbA1c reduction (Table 1). Changes of PBR after one year treatment with dapagliflozin correlated with a concomitant reduction of PWV and cSBP (P&amp;lt;0.05). Conclusions Twelve months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with T1DM, independently of glycemic control.

Relationship between coronary atherosclerotic lesion and arterial stiffness in patients with coronary artery disease

Abstract Introduction Some of the previous studies demonstrated that arterial stiffness independently predicts mortality and morbidity associated with CAD. Purpose to evaluate the relationship between coronary atherosclerosis severity and arterial stiffness. Material and methods The study included 158 people aged 40 to 70 years: control group – 25 people (mean age 61,7±6,6 years; 21 men and 4 women) without cardiovascular diseases (CVD) and 133 patients (mean age 62,5±6,9 years; 80 men and 53 women) with CAD, confirmed by coronary angiography (CAG). Arterial stiffness was assessed using applanation tonometry (AT). Аssessment of the coronary calcium (CC) was performed with computer tomography (CT). Results In 133 patients with CAD, the results of AT were compared with the degree of atherosclerotic lesion according to CT and CAG data. All patients were divided into groups depending on the CC value. Group I included 19 people with a CC value of 0, group II - 55 people with a CC of up to 400, and group III - 59 patients with a CC of more than 400. With an increase in the degree of the atherosclerotic lesion, the values of peripheral and central pulse pressure (PP), augmentation index (AIx), additional augmentation index normalised for heart rate of 75 bpm (AIx@HR75) and pulse wave velocity (PWV) statistically significantly increased (Table 1). Indicators characterising augmentation of сentral PP and arterial stiffness also increased. Conclusion Increases in Pulse Pressure, Augmentation Index, and Pulse Wave Velocity reflect the worsening of atherosclerosis in coronary arteries, thereby indicating a higher risk of cardiovascular complications. Monitoring of these parameters can be crucial for early diagnosis and prevention of major adverse cardiovascular events.

Vascular adaptations following an eight-week sprint interval training intervention in healthy men.

Sprint interval training (SIT) has been shown to improve many indices of cardiovascular risk. The effect of SIT on emerging indicators of cardiovascular health, including arterial stiffness and carotid intima media thickness, remains unclear. Thus, the purpose of this study was to assess changes in augmentation index at 75 beats per minute (AIx@75), pulse wave velocity (cfPWV), and carotid intima media thickness (CIMT) at three time points of an 8-week SIT intervention. Eighteen sedentary men (age: 24.7±5.1 years, BMI: 26.7±5.8 kg/m2) participated in the study. Subjects trained 3 times a week for 8 weeks. Training consisted of 3-6 consecutive 30-second bouts of maximal intensity cycling, with 4.5 minutes of active recovery between bouts. Baseline, 4-week, and 8-week vascular assessments were performed. Training effects were analyzed using repeated measures ANOVA. Pearson correlations were used to determine the relationship between baseline values and the change scores (baseline to 8 weeks) of each vascular measure. AIx@75 (BL: -3.6±10.9%, 4W: -5.6±8.3%, 8W: -3.2±9.5%), cfPWV (BL: 5.6±1.0 m/s, 4W: 5.8±0.9 m/s, 8W: 5.6±0.7 m/s), and CIMT (BL: 0.51±0.08 mm, 4W: 0.52±0.08 mm, 8W: 0.51±0.08 mm) did not significantly change (all P>0.05). Baseline cfPWV and AIx@75 were negatively correlated to their change from baseline to 8 weeks (P<0.05). These findings demonstrate that 8 weeks of SIT is an insufficient stimulus to reduce cfPWV, AIx@75, or CIMT in a group of young, healthy men. Baseline arterial stiffness may modulate vascular adaptations to SIT.

Comparison of the predicting value for incident cardiovascular events by vascular age based on brachial-ankle pulse wave velocity or carotid-femoral pulse wave velocity

Abstract Background There is a good correlation between brachial-ankle pulse wave velocity（baPWV）and carotid-femoral pulse wave velocity (cfPWV). Whether baPWV has the same predictability for cardiovascular risk as cfPWV in calculating vascular age remains to be clarified. Purpose This study examines which vascular age calculated by baPWV or cfPWV has a stronger association with the risk of cardiovascular events. Methods This prospective cohort study included 5725 participants from a community atherosclerosis cohort in Beijing, China. Vascular age was the predicted age in a multivariable regression model, including classical cardiovascular risk factors (sex, systolic and diastolic blood pressure, glycemia, triglyceride, low density lipoprotein cholesterol, waist, body mass index, heart rate, smoking) and treatment (anti-hypertensive agents, hypoglycemic agents, lipid-lowering agents) and pulse wave velocity. Residuals between chronological age and vascular age were defined as ∆-age, and the 10th and 90th percentiles of ∆-age were used as cutoffs to define supernormal vascular aging, normal vascular aging, and early vascular aging, respectively. The major adverse cardiovascular event was a composite of myocardial infarction, stroke, and cardiovascular death. The study used Cox proportional hazards regression to examine the association between vascular age and major adverse cardiovascular events. Results During the median 3-year follow-up period, 172 endpoint events were observed. After adjusting for age and sex, ∆-age as a continuous variable calculated by baPWV was significantly and increasingly associated with cardiovascular events (every 1-year increase led to a rise of 1.04% [95% confidence interval [CI]: 1.00%-1.08%; p=0.03] in cardiovascular events risk). After adjusting for age, sex, smoking, body mass index, hypertension, diabetes, dyslipidemia, anti-hypertensive agents, lipid-lowering agents, hypoglycemic agents, family history of atherosclerotic cardiovascular disease, and estimated glomerular filtration rate, early vascular aging group calculated by baPWV had an increased risk of cardiovascular events (hazard ratio: 1.76; 95% CI: 1.19-2.62 p=0.005), compared with the normal vascular aging group. In contrast, no significant results were observed in vascular age calculated by cfPWV. Conclusion(s) Vascular age calculated by baPWV has a stronger predictive ability for cardiovascular events than that calculated by cfPWV in the Chinese population. Considering baPWV is a simple and convenient method, it is recommended for vascular age calculation.

Regular supervised exercise training improves endothelial function, early atherosclerosis, arterial stiffness and endothelial progenitor cells in PCI patients

Abstract Backgrounds A disrupted balance between endothelial injury and repair induces endothelial dysfunction and endothelial progenitor cells (EPC) augment vascular repair. So, exercise improves endothelial function through increased numbers of EPC. We investigated the effect of training on vascular health by measuring the number of circulating EPC, and assessing flow-mediated dilation (FMD), brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (IMT) in patients with percutaneous coronary intervention (PCI). Methods Fifty-nine patients who were done PCI recently were randomized to full medical treatments or additional 3 months regular supervised exercise program (4 times a week, 1 hr a day). FMD, baPWV, carotid IMT, HOMA, hs-CRP and lipid profiles were measured and circulating CD34/KDR, CD34/CD117 and CD34/CD133 EPC were quantified by flow cytometry at baselines and after 3 months. Results Finally 23 patients joined exercise program(control, N=28). There was no significant difference of baseline characteristics and medication between 2 groups. After 3 months, FMD improved significantly in exercise group (6.62% to 11.48%) compared with control group (7.61% to 8.45%) (P&amp;lt;0.001) (fig 1). Carotid IMT reduced significantly in exercise group (0.759mm to 0.707mm) compared with control group (P=0.015) (fig 2). ba-PWV reduced significantly in exercise group (1529cmm/s to 1455 cmm/s) compared with control group (P=0.016) (fig 3). Numbers of CD34/KDR, CD34/CD117 and CD34/CD133 EPCs increased significantly after exercise compared with control group (P= 0.041, 0.011, 0.022, respectively) (fig 4). We also could see to reduce waist to hip ratio in exercise group compared with control group (P&amp;lt;0.001). Conclusions Three months regular supervised exercise improved FMD, ba-PWV, carotid IMT and waist to hip ratio in PCI patients. and it augmented numbers of circulating EPCs. Our results showed that exercise contributes to additional improvement of vascular health in PCI patients with optimal medical treatments.

The incremetal predictive value of pulse wave velocity over score2 in the setting of primary cardiovascular prevention: a 6-year follow-up study

Abstract Background Arterial stiffness has been shown to be an independent additive predictor to several traditional risk factors regarding cardiovascular events. Purpose We studied in a prospective cohort whether arterial stiffness has an additive value to SCORE2 in predicting cardiovascular risk. Methods In 747 healthy subjects, we measured carotid-to-femoral pulse wave velocity (PWV), a marker of aortic stiffness. We prospectively documented the incidence of cardiovascular events (major adverse cardiovascular events [MACE]-death, stroke and myocardial infarction) during a 6-year follow-up period. Results Sixty MACE were recorded. Increased values of PWV predicted greater risk for MACE in a model including diabetes, smoking, hypertension, hyperlipidemia, sex and age (hazard ratio (HR)=1.09; 95%CI=1.03 – 1.14; p&amp;lt;0.001, Chi-square change = 8.05; p=0.004; c-statistic increased from 0.74 (0.66 – 0.81) to 0.77 (0.71 – 0.83), p=0.025). PWV was an independent and additive predictor of events when added in a model encompassing the SCORE2 and diabetes (HR=1.07; 95%CI=1.04 – 1.11; p&amp;lt;0.001, Chi-square change = 43.12; p&amp;lt;0.001, c-statistic increased from 0.73 (0.66 - 0.80) to 0.76 (0.70 - 0.82); p=0.014). Also PWV predicted significantly the occurrence of events in all subgroups of each risk factor (for smokers and non-smokers: HR=1.31 and HR=1.11 respectively; for participants with hypertension and participants without hypertension: HR=1.23 and HR=1.12 respectively; for participants with hyperlipidemia vs participants without hyperlipidemia: HR=1.19 and HR=1.12 respectively; for participants with diabetes and participants without diabetes HR=1.19 and HR=1.12 respectively) (p&amp;lt;0.05 for all subgroups). Conclusion PWV confers an additive prognostic value to SCORE2 in primary prevention.

The effect of the combined treatment with dulaglutide and dapagliflozin in arterial elasticity, cardiac function, albuminuria and endothelial thickness in type 2 diabetes mellitus after 12 months

Abstract Background The association between diabetes mellitus and diabetic nephropathy with vascular and endothelial properties is well established. Purpose In this study, we compared the effect of combined treatment with dulaglutide and dapagliflozin versus DPP-4 inhibitors on endothelial glycocalyx, arterial stiffness, myocardial function and albuminuria in patients with type 2 diabetes mellitus and albuminuria. Methods A total of 60 patients with type 2 diabetes mellitus and albuminuria were randomized to combined dulaglutide and dapagliflozin treatment (n=30) or DPP-4 inhibitors (DPP-4is, n=30). We measured at baseline and 4 and 12 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 (cSBP), (c) global left ventricular longitudinal strain (GLS) (d) urine albumin-to creatinine ratio (UACR). Results Twelve months post-treatment, the combination of dulaglutide and dapagliflozin showed a greater improvement in all indices compared to DPP-4is, despite a similar reduction in glycosylated hemoglobin. Specifically, dual therapy showed greater improvements vs DPP-4is in PBR (2,10±0,31 to 1,93±0,23 μm vs 2,11±0,31 to 2,08±0,28 μm, p&amp;lt;0,001), in UACR (326±61 to 142±47 mg/g vs 345±48 to 306±60 mg/g, p&amp;lt;0,01), and in PWV (11,77±2,37 to 10,7±2,29 m/s vs 10,64±2,44 to 10,54±2,84 m/s, p&amp;lt;0,001), while only dual therapy showed improvement in cSBP (130,21±17,23 to 123,36±18,42 mmHg). Regarding GLS, both treatments were effective, but dual therapy showed a significantly higher percentage improvement compared to DPP-4is (18,19% vs 6,01%, respectively). Conclusions Twelve-month treatment with dulaglutide and dapagliflozin showed a greater improvement in vascular markers an albuminuria than DPP-4is in patients with type 2 diabetes mellitus and albuminuria. Early initiation of combined therapy as add-on to metformin should be considered in these patients.

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

Serpina3c deficiency aggravates vascular dysfunction and VSMC dysregulation through regulating adamts4 pathway activity in obese mice

Abstract Background Obesity leads to arterial stiffness (AS), which is an independent risk factor for cardiovascular disease. Vascular smooth muscle cell (VSMC) dysfunction is a critical step in the development of AS. Adamts4 (a disintegrin and metalloproteinase with thrombospondin motifs 4) promoting the ECM remodeling can regulate VSMC differentiation. Serpina3c is a serine protease inhibitor that plays a key role in VSMC proliferation and metabolic diseases. Purpose The present study aimed to investigate the function of Serpina3c in high-fat diet (HFD)-induced AS and regulation of VSMC phenotypic switching and possible mechanisms. Methods 8-week-old male Serpina3c-/- and C57BL/6 mice were fed normal diet (ND) or HFD for 12 weeks. The adipocyte-specific Serpina3c overexpression (AAV8-Serpina3c) were constructed and injected in situ into visceral or perivascular adipose tissue (AT) of Serpina3c-/- mice fed a 12-week HFD to test in vivo effect of AT-derived Serpina3c on arterial stiffness. In vivo vascular stiffness was analyzed by obtaining pulse wave velocity (PWV) measurements. Aortic rings were dissected to assess the ex-vivo effects of Serpina3c deprivation on vascular contractile and diastolic function. Elastin van Gieson (EVG) and Hematoxylin-eosin (H&amp;E) staining were implemented to observe the pathological morphology of aortas. IP-Western analysis was performed for identifying Serpina3c-adamts4 interactions. Results The obese WT mice exhibited significantly increased PWV values, compared with ND-fed mice, which were further increased in HFD+Serpina3c-/- mice (Fig. 1A). Phenylephrine-induced vascular constriction was impaired in HFD fed mice and further deteriorated with Serpina3c deficiency (Fig. 1B). No differences were noted in the endothelial-dependent acetylcholine-mediated relaxation in HFD-fed mice. Notably, Serpina3c-/- mice exhibited poorer endothelium-independent sodium nitroprusside induced relaxation (Fig. 1C and D). The HFD+Serpina3c-/- mice showed an increased breakage of elastin fibres and medial thickness compared with the aortas of HFD+WT mice (Fig. 1E and F). Serpina3c deprivation aggravated collagen deposition and matrix metalloproteinases (MMPs, MMP2 and MMP9) accumulation. VSMC contractile gene α smooth muscle actin were upregulated and synthetic phenotype marker osteopontin were downregulated in HFD+WT mice. The effect was more pronounced in aortas with Serpina3c deficiency (Fig. 1G and H). Overexpression of serpina3c in both visceral and perivascular AT or adamts4 deprivation reversed the above phenotypes. Computer simulations and IP-Western results indicate that Serpina3c and adamts4 bind to and maintain the latter low-expression in response to obesity (Fig. 2). Conclusion Serpina3c interacts with adamts4 to maintain contractile phenotype of VSMC and suppress AS development in the context of nutrient excess. Serpina3c is a novel target for the prevention and treatment of obesity associated artery disease.Serpina3c maintains vascular functionSerpina3c interacts with adamts4

Prognostic significance of the estimated pulse wave velocity in critically ill patients with coronary heart disease

Abstract Background The estimated pulse wave velocity (ePWV) has emerged as an alternative measurement of arterial stiffness which has been suggested as a potential marker for mortality and cardiovascular risk. Nonetheless, its prognostic significance in critically ill patients with coronary heart disease (CHD) remains uncertain. Methods Patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) were grouped into quartiles according to the ePWV levels. We conducted logistic and Cox regression analyses to examine the association between ePWV and both in-hospital and 1-year all-cause mortality among critically ill patients with CHD. Additionally, we employed restricted cubic spline (RCS) analysis to explore the relationship between ePWV as a continuous variable and mortality. Results A total of 11001 patients (men: 63.6%, age: 71.94 [IQR: 62.69-81.31]) were included in this study. In-hospital mortality and 1-year mortality rates were 9.1% and 25.1%, respectively. Multivariable logistic regression models demonstrated that ePWV was independently associated with an elevated risk of in-hospital mortality (OR 1.27; 95%CI [1.14-1.41]; p&amp;lt;0.001) and 1-year mortality (OR 1.49; 95% CI [1.38-1.60]; p&amp;lt;0.001]. The restricted cubic splines regression model revealed a linear relationship between ePWV and both in-hospital and 1-year mortality (p for non-linearity = 0.098 and p for non-linearity = 0.156, respectively). Conclusion Our findings indicate a linear association between ePWV levels and short- and long-term mortality in critically ill patients with CHD.