Pulse Wave Velocity Research Articles

Arterial stiffness characterization of patients with different ACS-causing plaque morphologies quantified by optical coherence tomography

Abstract Background Optical coherence tomography (OCT) has refined acute coronary syndrome (ACS)-management by enabling in-depth characterization of culprit lesions. Differentiating between plaques with ruptured (RFC) and intact fibrous cap (IFC) has shaped clinical decision making. However, the systemic vascular changes associated with different plaque morphologies remain unexplored. Purpose To investigate arterial stiffness among different ACS-causing plaque morphologies (RFC vs. IFC) and its prognostic value post-ACS. Methods We conducted a secondary analysis of a prospective registry study, including patients who underwent OCT-characterization of the ACS-causing culprit lesion and received arterial stiffness assessment 90 days post-index event. The association between arterial stiffness parameters, such as pulse wave velocity (PWV), aortic pulse pressure (APP), heart rate-corrected augmentation index (AIx@75) and plaque morphologies was assessed using logistic regression, adjusted for age, sex, hypertension, presence of diabetes mellitus, smoking status, LDL-C and discharge medications (ACE-inhibitors/ARBs, beta blockers, calcium-channel blockers and diuretics). A multiparameter model additionally included intima-media-thickness and all arterial stiffness metrics. Cox regression, further adjusted for stroke history, prior percutaneous coronary intervention or stable coronary artery disease and Killip class, evaluated the link between arterial stiffness parameters and major adverse cardiovascular events plus (MACE+). Results In total, 110 patients with arterial stiffness and OCT data were included. Of these, 78 (70.9%) patients had RFC- and 32 (29.1%) IFC-ACS. The median age was 61.5 years and 80.0% of patients were male. Patients with RFC- had significantly higher PWV (8.35 vs. 7.50 m/s, p=0.015) compared to IFC-ACS. Both groups received similar regimens of antihypertensive, diuretic and lipid-lowering pharmacological therapy at discharge (p>0.1). After multivariable adjustment, increased PWV (4th Quartile [Q4] vs. 1st Quartile [Q1] Adjusted Hazard Ratio [aHR]: 1.38 [95% Confidence Interval (CI) 1.02-1.88], p=0.043) was associated with RFC- while high APP was significantly associated with IFC-ACS as the underlying plaque morphology (Q4 vs. Q1 aHR: 0.65 [95% CI 0.48-0.87], p=0.005) (Figure 1). Furthermore, per one-unit increment in APP we observed a 10% increase in risk for MACE+ in patients with RFC-ACS (aHR: 1.10 [95% CI 1.02-1.19], p=0.016) but not IFC-ACS (aHR: 0.95 [95% CI 0.82-1.11], p=0.54). No risk modification with increases in PWV and AIx@75 were observed, regardless of underlying plaque pathology (p>0.05). Conclusion There are distinct differences in arterial stiffness between patients with RFC- and IFC-ACS. These results underscore the value of a patient-specific approach that integrates invasive and non-invasive vascular characterization for identifying high-risk individuals and guiding therapy to enhance clinical outcomes.

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 > 0.05). Compared with baseline, all patients had reduced PBR, PWV, CAP, E and NFS and increased CFR and GLS (p < 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 < 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.

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<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<0.001, Chi-square change = 43.12; p<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<0.05 for all subgroups). Conclusion PWV confers an additive prognostic value to SCORE2 in primary prevention.

Undiagnosed impaired glucose tolerance/diabetes mellitus and relationship with aortic stiffness in patients with acute coronary syndromes

Abstract Background Patients admitted with an acute coronary syndrome (ACS) often have unknown cardiovascular risk factors, such as impaired glucose tolerance (IGT) or diabetes mellitus (DM). Detecting these conditions is crucial to intensify appropriate therapies. Increased aortic stiffness, assessed by aortic pulse wave velocity (PWV), is associated with higher mortality in patients at high cardiovascular risk. Purpose Estimating the prevalence of IGT and DM and their relationship with increased aortic stiffness in patients admitted with an ACS. Methods Seventy-five consecutive patients admitted for ACS (21% women, mean age 63.6±11.1 ys), with fasting plasma glucose (PG) and glycated hemoglobin (HbA1c) not diagnostic for diabetes mellitus, underwent a fully standardized oral glucose tolerance test. All patients were also evaluated with the Arteriograph device, which applies a brachial cuff-based oscillometric method for the estimation of aortic PWV and arterial pulse waveform features. The automated vascular studies and OGTTs were performed after patient stabilization, at least 96 hours after admission. Results Forty-one patients (55% of the total study population) showed an abnormal OGTT response: 14 patients had a 2-h PG-OGTT ≥ 200 mg/dL, uncovering a diagnosis of DM, and 27 patients had a 2-h PG-OGTT ≥ 140 mg/dL, uncovering a diagnosis of IGT. Patients with DM showed no differences in terms of age, cardiovascular risk factors, Framingham risk score, C-reactive protein values, whereas a significant difference was observed in the number of diseased coronary vessels (2.2±0.8 vs 1.6±0.9, p=0.016) and PWV values (10.0±1.3 vs 8.8±1.6 m/s, p=0.028). Similarly, when considering all patients with an abnormal OGTT, a significant difference was observed in PWV values compared to patients with a normal OGTT (9.5±1.5 vs 8.4±1.7 m/s, p=0.032), as well as in estimated glomerular filtration rate (78±18 vs 83±23 mL/min/1.73mq, p=0.05), and peak troponin values (3698±2905 vs 2124±2561 ng/ml, p=0.02). At follow-up (mean time 51.7 months), no patients had died, but 5 patients had a new major cardiovascular event. Aortic pulse wave velocity values were different between patients with and without events (10.6±2.3 vs 8.6±1.4 m/s, p=0.024), and PWV was a significant predictor of events at univariate regression analysis (hazard ratio 1.93; 95 confidence intervals 1.01-3.69, p=0.047). Conclusions An unknown diagnosis of DM and/or IGT is very frequent in patients with ACS. Undiagnosed dysglycemic conditions are linked to a higher prevalence of coronary multivessel disease and increased aortic stiffness, which is also predictive of future cardiovascular events. A systematic screening with OGTT may help identifying patients at even higher cardiovascular risk, and tailoring secondary prevention strategies through personalized aggressive therapeutic interventions.

Carotid-Femoral pulse wave velocity progression in hypertensive patients is associated with subsequent cardiovascular outcomes

Abstract Background Arterial stiffness (Pulse Wave Velocity - PWV) is associated with CV events and mortality. However, little is known on the relationship of its progression (ΔPWV) over time with CV outcomes. Purpose The aim of our study was to evaluate the relationship between PWV progression and all-cause mortality and CV events in hypertensive subjects. Methods We enrolled 402 consecutive hypertensive outpatients. At baseline anamnestic, clinical, BP, laboratory data and PWV were assessed. We performed a PWV follow-up examination at a median time of 3.7±0.5 years. Patients were subsequently followed for a median time of 10.1 (IQR 9.5 -10.5) years recording all-cause mortality and CV events. Results At baseline the mean age was 53.2±13.0 years, SBP and DBP were 141.8±17.5 and 86.8±10.5 mmHg and PWV was 8.5±1.9 m/s. Despite an improvement in BP control (- 9.2±19.5 and -8.0±12.3 for SBP and DBP respectively), at follow-up the population showed a PWV increase (ΔPWV +0.6±1.9 m/s). Progressors (ΔPWV ≥ 0.5 m/s, 204 patients, 50.7%) had a significantly lower survival probability and higher cumulative incidence of composite events, while no differences were seen for CV events (unadjusted analysis). At cox multivariable analysis neither ΔPWV ≥ 0.5 m/s (progressors) nor ΔPWV (as a spline function) were associated with CV events and with all-cause mortality. However, the association with survival probability and cumulative incidence of CV events, as a composite outcome, was significant (HR = 2.32, 95% CI: 1.33 – 4.04, p=0.003). Conclusions In conclusion, our study shows that PWV progression of at least 0.5 m/s is frequent in hypertensive patients and that it is associated with a significantly higher risk of developing CV events or dying (composite outcome).

Empaglifozin modifies the arterial stiffness in type-2 diabetic patients: a preliminary report.

Abstract Background Sodium-glucose cotransporter-2 (SGLT2) inhibitors demonstrated beneficial effects on cardiovascular and renal events in patients with type 2 diabetes mellitus. The mechanisms underlying these effects are not fully elucidated. Aim of this study was to investigate whether empagliflozin is able to modify the arterial stiffness in type 2 diabetic patients. Methods Pulse wave velocity (PWV) and other parameters of arterial stiffness were assessed before and after adding empagliflozin to a traditional antidiabetic treatment in 16 consecutive T2DM outpatients folowed for 3 months. Arterial stiffness were evaluted using SphygmoCor ECEL measuring the pulse waveform of the arterial pulse moving from tha descending aorta to the femoral artery (PWV). Data obtained from the diabetic population has been compared to 16 T2DM outpatients not treated with SGLT2 inhibitors. Results In the two groups differences according gender distribution or duration of diabetes mellitus did not emerge. However the empagliflozin group was younger compared to controls (64.1±8.68 vs 74.45±8.13, P < 0.05). Empagliflozin treatment significantly decreased HbA1c after 12 weeks of treatment (7.9±0.78 vs 7.04±1.09%, P < 0.008.). After 12 weeks’ treatment, empagliflozin significantly improved PWV compared to controls not treated with SGLT2-i (ΔPWVV -0.68±1.1 vs 0.89±1,6 p <0.004, P = 0.0065 with age and HbA1c as covariates). Moreover body weight significantly decreased in the empagliflozin group (86.75±16.16 vs 81.71±16.5 kg, p =0.001) compared to controls (in whom remained unchanged) as long as BMI (30.48±5.4 versus 28.75±5.66 kg/m2, P < 0.002) compared to controls (in whom remained unchanged). Estimated glomerular filtration rate (eGFR) remained unchanged in the two groups during the study whereas urine Albumin to Creatinine ratio significantly improved using empagliflozin (17.8±46.8 vs 12.2±35.7 mg/mmol, P = 0.049). Conclusion In this ‘real clinical practice’ experience, the potential effect of empagliflozin treatment on arterial stiffness in T2DM patients was extensively investigated. Arterial stiffness was significantly decreased adding empaglifozin to the traditional treatment and this result has been obtained after 3-month. Significantly improvement in urine Albumin to Creatinine ratio might suggest an amelioration of endothelial function in those patients that could be involved in reducing arterial stiffness.

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) <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<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<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<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.

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<0,001), in UACR (326±61 to 142±47 mg/g vs 345±48 to 306±60 mg/g, p<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<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.

Validation and development of a scoring system for comprehensively evaluating arterial damage in the elderly chinese

Abstract Background and aims Existing assessments on arterial damage focus on specific segments of arterial system (e.g., carotid artery), lacking a comprehensive index to evaluate overall arterial health. We aimed to integrate existing assessments for arterial damage and develop a new score, named Arterial Damage Index (ADI), to comprehensively evaluate arterial health status of the whole-body arterial system. Methods A total of 3075 community-dwelling elderly Chinese (age ≥65 years) from the North Shanghai Study (2014–2022) were included. Assessments on arteries including ankle-brachial index (ABI), pulse wave velocity (PWV), carotid intima-media thickness (CIMT) and plaques, pulse pressure (PP), and inter-arm (IASBPD) and -leg (ILSBPD) systolic blood pressure difference were included for screening. Cox proportional hazards regressions of MACEs (non-fatal myocardial infarction, non-fatal stroke, and all-cause mortality) were conducted to acquire the ADI algorithm. Internal and external validation on ADI were also performed. Results Over a median follow-up period of 6.4 years, 316 individuals (10.3%) experienced an incident of MACE. After screening, PWV, ABI, PP, CIMT, and carotid plaque were included for ADI scoring system. Survival analysis revealed a significant difference in the rates of composite events across different ADI stratifications (p for trend < .05). ADI showed superior discriminative performance (C-index 0.65±0.02) compared to any individual arterial-related indicator. Calibration curve shows the predictive model showed that the predicted and actual probabilities were broadly consistent. Additionally, ADI provided better incremental value when added to the base model (net reclassification improvement, 36.2% [95% CI, 15.3%-52.1%]; p < .05, integrated discrimination improvement, 7.9% [95% CI, 4.9%-11.0%]; p < .05) compared to any individual arterial-related indicator. These findings were confirmed in internal validation sets (p for DeLong tests >0.05), and was externally validated in 2155 participants from a community-based cardiovascular disease cohort among residents in Beijing, China. Conclusion ADI can comprehensively assess arterial damage and provide a valuable tool for further assessment of future cardiovascular risk.central illustration

E-selectin and asymmetric dimethylarginine plasma levels in adult cyanotic congenital heart disease patients: relation to biochemical parameters, vascular function, and clinical status.

Abstract Background and Aim Patients with cyanosis secondary to congenital heart disease (CHD) are characterized by erythrocytosis and increased blood viscosity, which contributes to endothelial dysfunction, increased arterial stiffness, and impaired vascular function, which may affect the final clinical presentation. Asymmetric dimethylarginine (ADMA) and e-selectin (e-sel) are valuable biomarkers for prognosis of endocardial dysfunction and vascular damage. Their concentration levels in blood serum have the potential to be a rapid and easily accessible tool that reflects the severity of the disease. We aimed to assess e-sel and ADMA levels, their relationship with clinical status, as well as endothelial and vascular function. Methods A cross-sectional study including 36 adult CHD cyanotic patients [(17 males)(42.3 +/- 16.3 years)] with arterial blood oxygen saturation less than 92% and 20 healthy controls [(10 males)( 38.2 +/- 8.5 years)] was performed. All patients underwent clinical examination, blood testing, and cardiopulmonary tests. Endothelial function was assessed using intima-media thickness and flow-mediated dilatation (FMD). Vascular function using applanation tonometry methods was completed while considering aortic systolic pressure, aortic pulse pressure (AoPP), augmentation pressure (AP), augmentation index (AI), pulse pressure amplification (PPampl), and pulse wave velocity (PWV). Results Concentrations of e-sel and ADMA were significantly higher in patients with CHD than in controls (56.3 ± 13.6 ng/mL vs. 15.5 +/- 8.6 ng/mL, p<0.001) and (1.48 ± 0.48 ng/mL vs. 0.46 ± 0.1 ng/mL, p<0.001) respectively. E-sel levels correlated with gender, blood oxygen saturation, red blood cell, hemoglobin concentration, hematocrit, augmentation pressure, forced expiratory one second volume, forced vital capacity, and oxygen uptake. ADMA levels were found to correlate with age only. Conclusions E-sel level, unlike ADMA concentration, reflects the degree of severity of erythrocytosis and hypoxia and, thus, the physical status of patients with cyanotic CHD. E-selectin predicts increased augmentation pressure.Figure 1.A) ROC analysis for e-selectin

Patients vaccinated against COVID-19 present better coronary flow, myocardial work and NTproNP levels than non-vaccinated at 4 months post COVID infection

Abstract Introduction COVID-19 affected patients present impaired subclinical markers of cardiovascular and endothelial function post resolution of infection. Whether vaccination impedes impairment of myocardial and vascular function has not been clarified. Purpose We investigated the effect of COVID-19 infection on markers of endothelial, vascular and myocardial function in vaccinated and non-vaccinated subjects at four months after the infection. Methods We recruited 60 vaccinated and 60 non-vaccinated patients with similar clinical characteristics, who were examined in a dedicated post-COVID-19 outpatient clinic during a scheduled follow-up visit at four months after a confirmed COVID-19 infection. We measured (i) perfused boundary region (PBR) of the sublingual arterial (increased PBR indicates reduced endothelial glycocalyx thickness), (ii) flow-mediated dilatation (FMD), (iii) coronary flow reserve (CFR) by Doppler echocardiography, (iv) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (v) global left and right ventricular longitudinal strain (GLS), (vi) myocardial global work index (GWI) global constructive work (GCW), global wasted work (GWW) and the myocardial global work efficiency (GWE) and v) NTproBNP blood levels. Results Among vaccinated patients 54,2% had mild disease, 33,3% had moderate disease and 12,5% had severe disease, while among non-vaccinated 29,1% had mild disease, 32,9% had moderate disease and 38% had severe disease(p<0.05). At four months, vaccinated patients presented with higher LVGLS, GCW values and CFR compared to non-vaccinated (p>0.05 table), while GWI, GWW and GWE were similar between the two groups(p>0.5). Moreover, in vaccinated patients RVGLS and RV FWLS were significantly higher than in non-vaccinated patients (p>0.05). Also, NTproBNP leves were significantly lower in vaccinated than in non-vaccinated patients (p<0.05). At four months, in vaccinated patients , we observed a marginally lower brachial and central systolic blood pressure compared with non-vaccinated (p=0.045, p=0.048 respectively.) Vaccinated patients displayed similar FMD and PWV values compared to non-vaccinated (p>0.05 for all the comparisons). Conclusion Patients vaccinated against COVID-19 suffered from milder disease resulting to better cardiac function and lower NTproNP levels than non-vaccinated 4 months post COVID infection.

Differences in left atrial stain, endothelial glycocalyx, arterial elasticity and myocardial efficiency between ESUS, lacunar, cardioembolic and atherosclerotic type of stroke

Abstract Background Patients with stroke are at greater risk of developing cardiovascular complications. Purpose We addressed endothelial glycocalyx, arterial stiffness, left atrial and ventricular function in patients with lacunar, atherosclerotic, cardioembolic and stroke of undetermined source (ESUS). Methods We recruited 194 patients (aged 58.8± 10.8 years old) with acute cerebral stroke (47 lacunar, 50 atherosclerotic,48 ESUS and 49 cardioembolic) and 50 controls with similar risk factors and 40 controls with similar profile regarding common risk factors (diabetes, hypertension, hyperlipidemia, coronary artery disease, smoking; p>0.05 for all comparisons). We measured: (1) perfused boundary region (PBR) of the sublingual microvessels (diameter range 5–25 μm), a marker inversely related with glycocalyx thickness, (2) pulse wave velocity carotid-to-femoral (PWV), central systolic blood pressure (cSBP), and central diastolic blood pressure (cDBP), (3) Left atrial (LA) strain using speckle-tracking imaging, (4) left ventricular global longitudinal strain and (5) left ventricular myocardial work index (GWI), constructive work (GCW), wasted work (GWW) and work efficiency (GWE), (6) ventriculoarterial coupling, expressed by the ratio PWV/GLS. Results Compared with controls, patients with stroke had higher PWV (11.98±3.21 vs 9.61±1.28 m/sec, p=0.001), PBR (2.20±0.31 vs 1.94±0.20, p=0.019) and central SBP (137.41±24.83 vs 121.15±17.46 mmHg, p=0.018), while LV ventricular (-16.44±4.70 vs -20.89±2.45%, p=0.001) and atrial deformation (26.81±9.32 vs 37.05±5.08%, p<0.001) were more impaired in patients with stroke (p < 0.05). Patients with ESUS had more impaired LA reservoir strain and contraction strain compared to the other 2 stroke types (ESUS 22.9±8.72%, -13.90±4.96%, Lacunar 29.71±10.52%, -16.11±6.10%, atherosclerotic 26.78±10.14%, -13.74±5.65%, p<0.05). Also, patients with ESUS demonstrated better PBR compared to the lacunar and atherosclerotic types (ESUS 2.10±0.27 μm, Lacunar 2.26±0.29 μm, atherosclerotic 2.19±0.29μm, p<0.05). Patients with atherosclerotic stroke had higher PWV compared with other stroke types (Atherosclerotic: 13.59±3.87 m/sec, Lacunar: 11.41±2.35 m/sec, Cardioembolic: 10.66±3.28 m/sec, ESUS: 11.72±2.67 m/sec). Also, patients with atherosclerotic stroke demonstrated the worst PWV/GLS ratio (Atherosclerotic: -0.97±0.35, Lacunar: -0.69±0.25, Cardioembolic: -0.76±0.21, ESUS: -0.70±0.28). Patients with cardioembolic stroke showed similar trend with ESUS, as far LA strain is considered. Conclusion Patients with stroke have impaired atrial strain, endothelial glycocalyx and arterial stiffness, compared with controls. Arterial stiffness and ventriculoarterial coupling are more affected in atherosclerotic strokes. LA strain is more impaired in the ESUS and cardioembolic stroke albeit that endocalyx, though abnormal,is less impaired in these stroke types.

A direct comparison of non-invasive blood markers of liver fibrosis as associates of cardiovascular risk. The Athens cardiometabolic registry

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease (CVD). This risk increases further with advanced liver fibrosis. To date, non-invasive tests (NIT) for liver fibrosis risk have not been established as diagnostic or prognostic biomarkers of CVD. Purpose The purpose of the study was to compare NIT of liver fibrosis with respect to their associations with vascular injury and cardiovascular (CV) events. Methods Individuals without clinically overt CVD and patients with CVD (total n=1,692), consecutively recruited in the Athens Cardiometabolic Registry, were analysed in this study. We retrospectively evaluated the association of NIT (i.e. Fibrosis-4 index (FIB-4), NAFLD Fibrosis score (NFS), BARD score) with indices of subclinical arterial injury (i.e. carotid wall thickness and atherosclerotic plaque for subclinical atherosclerosis, pulse wave velocity (PWV), for arterial stiffness) and the incidence of CV events. Patients were followed-up for CV events for a median time of 39 months. Results Elevated FIB-4 (>2.67) was associated with vascular damage [adjusted odds ratio (aOR)=2.97, 95% confidence intervals (CI)= 1.71-5.78 for maximal wall thickness (maxWT) and aOR=4.58, 95% CI=2.44-8.60 for PWV] across the entire study population, including those with or without clinically overt CVD. NFS> 0.675 showed similar associations but lacked significant correlation with arterial stiffness in coronary artery disease patients. FIB-4> 2.67 and BARD> 2 were associated with increased risk of the composite endpoint of CV death, acute myocardial infarction, or coronary revascularization [adjusted hazard ratio, (aHR)=2.00, 95% CI= 1.12-3.55 and aHR=3.36, 95% CI=1.03-11.0 for FIB-4 (n=842) and BARD (n=887) respectively]. FIB-4 and BARD as continuous variables confered incremental prognostic value compared to European Systematic Coronary Risk Evaluation 2 (SCORE2). Conclusion In a population with a wide range of cardiometabolic risk, FIB-4 was associated with both markers of atherosclerotic disease and arterial stiffness as well as with adverse CV events. These data support further investigation of FIB-4 as a biomarker of CV risk.

Lower modified rodnan skin score values and complement 4 levels are associated with arterial endothelial dysfunction in patients with systemic sclerosis

Abstract Background Systemic sclerosis (SSc) is a multisystem autoimmune disease affecting skin and multiple organs. Although immunopathological evidence supports direct arterial involvement leading to tissue ischemia in SSc, factors associated with arterial involvement are not precisely determined due to the rarity of SSc. In this study, we aimed to investigate aortic stiffness and endothelial functions in patients with SSc. Methods Patients under treatment of our Rheumatology department and healthy controls have been included in our study. Aortic stiffness was examined by pulse wave velocity (PWV) exam and endothelial functions were assessed by flow mediated dilation (FMD). Individuals with known atherosclerotic risk factors were excluded from our study. A thorough biochemical examination of all individuals and immunologic markers of patients with SSc was completed. All of the organ involvements in patients with SSc were noted and modified Rodnan skin score (MRSS) was calculated. Results A total of 61 patients and 75 healthy controls were included in our study. Brachial-ankle PWV values were significantly higher (6.89±0.93 vs 6.49±0.22 m/sec; p:0.001) and brachial FMD values were significantly lower (16.7±6.7 % vs 18.7±3.8 %; p: 0.03) in patients with SSc. We have also grouped individuals according to severe FMD impairment (FMD < 10%). None of the healthy controls had severe impairment whereas 15 patients with SSc had FMD values lower than 10%. Higher anti-smooth muscle (Sm) antibody positiveness (40 % vs 15.4 %), lower complement 4 levels (23.6±16.7 vs 31.1±11.1 mg/dL), higher plasma iron values (70.3±43.6 vs 31.4±45.2 mcg/dL) and lower MRSS values (11.4±4.8 vs 20.7±10.9) were observed in SSc patients with severe FMD impairment. When we have put these variables in multivariate logistic regression analysis (backward elimination model), we have found an independent association of complement 4 levels (OR: 0.03, [95 % CI: 0.01-0.491], p:0.04) and MRSS values (OR: 0.853, [95 % CI: 0.761-0.955], p:0.006) with significant FMD impairment in patients with SSc. Conclusion Arterial stiffness is significantly increased and endothelial functions, as assessed by FMD is significantly decreased in patients with SSc, when compared to healthy controls. Lower complement 4 levels and lower modified Rodnan skin scores seem to be independently associated with significant severe FMD impairment. Although our study included a remarkable amount of patients with SSc, an infrequent autoimmune disease, number of patients included in our study is not adequate to make more precise comments. Further prospective studies with higher amount of patients are required for certain results.

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.

Optimal blood pressure values to reduce arterial stiffness, an analysis from UK Biobank

Abstract Introduction Increased arterial stiffness is a powerful independent risk factor for adverse cardiovascular events. While pulse wave velocity has been used extensively as a biomarker of vascular health reflecting functional and structural arterial changes, its use in clinical practice was limited. The Arterial Stiffness Index (ASI) simplifies the assessment of arterial stiffness using a pulse waveform obtained at the finger with an infrared sensor with BP measured using an automated device. Age and raised blood pressure (BP) are major contributors to increased arterial stiffness, but time trajectories of ASI in the general population and optimal BP values to reduce arterial stiffening are scarcely known. Purpose To establish temporal changes of ASI and identify BP values associated with longer-term improvement of arterial stiffness. Methods The study analysed data from UK Biobank (baseline n=154,684, median age 54, interquartile range (IQR) [40-72] years; 52% female; 91% white, 28% hypertension). ASI was measured using PulseTrace PCA2 device (CareFusion, USA) at baseline with measurements repeated in 4617 individuals after a median follow up of 3.0, IQR [2.8-3.3] years. BP was measured during the same time points. Multivariable (adjusted for age, sex, diabetes, and use of BP-lowering drugs) linear regression was used to determine the association of BP with baseline and the association of BP and ASI changes during follow up. ROC analysis was used to determine BP values associated with improvement (reduction) of ASI during follow up. Continuous data are presented as median [IQR] and compared using Wilcoxon test. R software packages were used for analyses. Results At baseline, ASI (m/sec) was higher in those with systolic BP (SBP) &amp;gt;140 mmHg (9.60 [7.15-11.85] vs. 8.67 [6.77-10.70] for SBP ≤140 mmHg, p&amp;lt;0.001) and in those with diastolic BP (DBP) &amp;gt;90 mmHg (9.90 [7.48-12.16] vs 8.81 [6.78-10.90] for DBP ≤90 mmHg, p&amp;lt;0.001). Both SBP and DBP were independently associated with ASI at baseline (B±SE 0.08±0.02 and 0.79±0,29m, respectively; p&amp;lt;0.001 for both). During follow up, the population level SBP remained unchanged (change 0 [-8 - 8] mmHg), with some reduction in DBP (-1.0 [-6.0 - 3.5]) mmHg. SBP reduced in 2234 (48%) and DBP in 2517 (55%). ASI increased by 0.56 [-1.46 - 2.78] m/s, with ASI reduction observed in 1935 (42%). An increase in DBP but not in SBP was independently associated with an increase in ASI (B±SE DBP 0.04±0.01, p&amp;lt;0.001; SBP 0.007±0.006, p=0.22; DBP 0.04±0.007, p&amp;lt;0.001). The baseline BP was predictive of the magnitude of changes in ASI: SBP 132 mmHg (AUC 0.53, p=0.001) and DBP 83 mmHg (AUC 0.54, p&amp;lt;0.001). Conclusions Increased arterial stiffness is associated with higher BP, particularly with higher DBP. Raised ASI is reversible, providing BP is adequately controlled with optimal BP being &amp;lt;132/83 mmHg.

Arterial-myocardial coupling in primary AL amyloidosis. A validation study of vascular involvement

Abstract Background Primary AL amyloidosis is a rare yet lethal systemic disorder. Previously published own and others’ work indicated that vascular involvement in AL cardiac amyloidosis defined as low blood pressure or paradoxical vasodilation may independently affect survival. Mechanistic data will pave the way to validate the clinical role of vascular involvement in these patients. Purpose We sought to explore the presence of arterial-myocardial coupling in AL amyloidosis by investigating associations between markers of vascular and cardiac involvement. Methods We consecutively recruited n=152 newly diagnosed patients with AL amyloidosis that underwent thorough vascular examination including reactive vasodilation (flow mediated vasodilation, FMD and vasodilation in response to cold-pressor test) using high resolution ultrasonography. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (PWV) and aortic pressures and markers of arterial wave reflections were estimated using radial artery tonometry. In a subgroup of patients, transthoracic echocardiography (n=152) and cardiac magnetic resonance (CMR) (n=59) were performed. Results Vascular reactivity correlated with global longitudinal strain (GLS), left ventricle ejection fraction (LVEF)/GLS ratio and worse LV volumes. Vasodilation post-cold pressure test was correlated with LV mass. cSBP exhibited a negative correlation with markers of heart involvement, wall thickness markers, GLS, and CMR tissue characterization markers. A positive correlation between cSBP and LVEF, rotation and twist strain, myocardial work and contractility markers and late gadolinium enhancement (LGE). cDBP was associated with systolic function and contractility markers, with myocardial work indices and LGE. A negative relationship with GLS, LA strain, RV GLS and LA diameter and E/e’ was noted. In addition, T2 was negatively correlated with cDBP. SBP was correlated positively with LVEF, contractility markers, and LGE myocardium and negatively correlated with biomarkers of heart involvement, GLS, CMR structure and tissue characterization. DBP was positively correlated with LGE and myocardial work. A negative relation with NTproBNP, E/e’, RVSP, LA diameter and T2 mapping was noted. Time of wave reflections (Tr) was negatively correlated with rotation strain and positively correlated with circumferential strain, LA strain and LV structure. Ai@75 was positively correlated with myocardial work and contractility markers, and LGE. Ai@75 was negatively correlated with markers of heart involvement, LV structure, E/e’, worse GLS and adverse CMR tissue characterization. Conclusion Markers of peripheral vascular dysfunction were associated with cardiac structure and function acquired both with echocardiography and CMR in AL amyloidosis. This arterial-myocardial coupling supports the clinical role of peripheral vascular involvement in this disease and warrants further investigation.

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.

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