Pulse Wave Research Articles

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.

Parallel improvement of arterial stiffness with weight loss following intensification of antidiabetic treatment

Abstract Background Arterial stiffness is a marker that can 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 in T2DM patients as well as potential associations with their weight status before and after treatment. Patients and Methods We enrolled 118 consecutive patients under stable antidiabetic therapy. According to their physician they start treatment with an additional antidiabetic agent; either dipeptidyl peptidase-4 inhibitor (DPP-4i, n=19), or glucagon like peptide-1 receptor agonist (GLP-1RA, n=50) or sodium/glucose cotransporter-2 inhibitor (SGLT-2i, n=49). Body Mass Index (BMI) along with carotid-femoral pulse wave velocity (PWV) as a biomarker of arterial stiffness were measured at baseline and 3 months after treatment intensification. Results There were no differences between the study groups regarding their sex, age and other traditional risk factors or the values of PWV and BMI at baselined (p=NS for all). All groups achieved better glycemic control in terms of HbA1c values between baseline and follow-up; from 7.4±1.2% to 7.4±1.2% in the DPP4i group (p&amp;lt;0.001 for all), from 8.6±0.7% to 6.7±0.8% in the GLP-1RA group (p=0.07) and from 7.7±1.1% to 6.7±0.7% in the SGLT-2i group (p&amp;lt;0.001). PWV showed a decrease from 10.6±2.7 to 9.0±1.6 m/sec (p=0.001) in the DPP4-i group, 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. Regarding BMI, a reduction in the values between groups from baseline to follow-up was also observed; from 27.4±5.3 to 26.1±5.0 kg/m2 for the DPP-4i group, from 33.6±4.9 to 31.5±4.6 kg/m2 for the GLP-1RA group, from 31.8±5.5 to 30.5±5.6 kg/m2 for the SGLT-2i group (p&amp;lt;0.001 for all). Moreover, in the entire study population there was significant correlation between PWV and BMI improvement following treatment initiation (rho=0.247, p=0.007) (Figure 2). Conclusion Diabetes mellitus treatment intensification with GLP1-RA or SGLT-2i or DPP4i, ameliorated arteriosclerosis, improved PWV and BMI while there is significant association between BMI and PWV improvement.Changes in PWV values among the groupsCorrelation between deltaBMI &amp; deltaPWV

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.

Novel CMR-assessed right ventricular-pulmonary artery coupling index independently associates with exercise capacity and clinical risk in pulmonary arterial hypertension

Abstract Background We defined a novel noninvasive right ventricle (RV)–pulmonary artery (PA) coupling index as the ratio of cardiovascular magnetic resonance (CMR)-assessed RV direct flow (RVDF) and PA pulse wave velocity (PWV), and investigated its associations with exercise capacity and clinical risk in pulmonary arterial hypertension (PAH). Method 43 PAH patients (mean age 46±12 years, M:F 7:36) and 60 healthy volunteers (mean age 46±13 years, M:F 11:48) underwent CMR and cardiopulmonary exercise test (CPET) within one week. From cine CMR, RV ejection fraction (EF) and RV end-diastolic volume (RVEDV) were calculated using volumetric analysis; and tricuspid annular plane systolic excursion (TAPSE), feature tracking. PAPWV was the ratio of early systolic DPA flow and DPA area measured from instantaneous phase and magnitude through plane 2D flow CMR images across the pulmonary trunk, respectively. RVDF was the 4D flow CMR-assessed blood volume entering and exiting the RV in one cardiac cycle, indexed to RVEDV. RV-PA coupling was RVDF/PAPWV. Based on CPET-assessed peak oxygen consumption (PVO2), all 103 participants were stratified into two groups: PVO2&amp;gt;15 ml/kg/min; and PVO2≤15 ml/kg/min. Based on the REVEAL (Registry to Evaluate Early and Long-term PAH Disease Management) 2.0 score, the 43 PAH patients were stratified into low risk (score ≤6) and intermediate to high risk (score &amp;gt;6) groups. Results RVDF/PAPWV was significantly lower in PAH vs. controls (7.9 vs. 20.4 %/(m/s), P&amp;lt;0.001); and in PAH patients with intermediate to high risk vs. low risk (4.6 vs. 9.4 %/(m/s), P=0.001). On multivariable analyses, RVDF/PAPWV was an independent predictor of PVO2≤15 ml/kg/min (=0.302, P=0.001) among all participants, and of REVEAL 2.0 score &amp;gt;6 (=0.621, P=0.009) among PAH patients. Compared to RVEF and TAPSE, RVDF/PAPWV had numerically higher discrimination (p values non-significant based on Delong test) for PVO2≤15 ml/kg/min (AUC=0.914 vs. 0.872, 0.843); and among PAH patients, REVEAL 2.0 score &amp;gt;6 (AUC=0.851 vs. 0.723 and 0.728) (Figure). Conclusion CMR-derived noninvasive RVDF/PAPWV independently associates with exercise capacity and PAH clinical risk, supporting its utility as an imaging marker of disease progression and therapeutic response.

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 &amp;lt; .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 &amp;lt; .05, integrated discrimination improvement, 7.9% [95% CI, 4.9%-11.0%]; p &amp;lt; .05) compared to any individual arterial-related indicator. These findings were confirmed in internal validation sets (p for DeLong tests &amp;gt;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

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.

Comprehensive echocardiographic and biomarker assessment of patients with diabetic ketoacidosis

BackgroundSystemic stress, inflammation, and hydroelectrolytic and acid‒base abnormalities observed during diabetic ketoacidosis (DKA) can cause changes in the heart and even induce cardiovascular damage. We aimed to evaluate the structure and function of the heart during and after a DKA episode via echocardiography and biomarker assessment.MethodsWe performed a transthoracic echocardiogram (TTE) in subjects with an episode of DKA in the first 4–6 h of treatment. We evaluated left ventricular wall thickness, diameters and volumes, as well as systolic and diastolic function using tissue Doppler imaging, pulsed wave Doppler and left ventricular ejection fraction (LVEF). Left ventricular function was also assessed with global longitudinal strain (GLS). We obtained cardiac troponin levels in the first 24 h after admission. A second TTE was performed following the same protocol 6–12 h after the resolution of the DKA episode.ResultsWe included a total of 20 subjects. The mean age was 33 ± 13.6 years; 70% were female, and 70% had type 1 DM. 75% of the patients experienced severe episodes, and the rest experienced moderate episodes. Left ventricular isovolumetric contraction and ejection time were significantly shorter during DKA and prolonged after the resolution of the episodes (47.6 ± 9.9 vs. 62.2 ± 14.1, p = < 0.001) and (218.6 ± 37.9 vs. 265.06 ± 34.7). The isovolumetric relaxation time was also shorter during DKA, (41.72 ± 8.29 vs. 59.32 ± 17.98, p = < 0.001). Volumes and diameters of the left ventricle increased significantly after DKA resolution. We found no difference between LVEF or GLS during and after DKA resolution. 20% of the participants had troponin elevations, half of whom had moderate episodes and half of whom had severe episodes. 35% had LV dysfunction, 28.5% both in GLS and LVEF. 28.5% occurred after DKA resolution, with alterations in GLS.ConclusionsDiabetic ketoacidosis induces changes in the structure and function of the heart, which are mostly transient, reflect the presence of a hyperdynamic state and resolve after the resolution of the episode. Some subjects present with evidence of myocardial injury with elevated cardiac troponin and left ventricular dysfunction.Graphical abstractIcons in the graphical abstract are made by Freepik from www.flaticon.com.

Objective functional improvement and vital prognosis after TAVR in patients with low-gradient aortic stenosis. Development of a predictive score

Abstract Introduction Patients with low-gradient aortic stenosis (mean gradient &amp;lt; 40 mmHg) (LGAS) supose a clinical challenge because in these patients the degree of functional recovery after TAVR could be lower and their prognostic evolution more adverse. This is relevant for the optimal indication of TAVR, especially with the growing number of patients with a borderline indication due to comorbidities or advanced age with certain degree of frailty. Purpose To develop a clinical model to predict the response to TAVR in LGAS patients based in non invasive physiological parameters at baseline. Methods In a cohort of patients undergoing TAVR a prospective evaluation of multiple pathophysiological parameters was performed derived from pre- and post-TAVR assessment with echocardiography, computed tomography, and non-invasive arterial pulse wave analysis with the Sphygmocor XCEL system. Objective functional improvement 6 months after TAVR was assessed by the 6-minute walk test and NT-proBNP levels. Clinical follow-up was performed at 1 year. Results Of the 450 patients included, 310 showed high aortic gradient and 140 (31%) low gradient, with an objective functional improvement in 90% and 64% (p&amp;lt;0.001) respectively, and with 1-year mortality of 4% and 12% (p=0.001). In the LGAS group, 1-year mortality was 20% in the subgroup without functional improvement and 8% (p=0.001) in the subgroup showing functional improvement. In the LGAS group, the pathophysiological parameters predictive of functional improvement were the augmentation index75 ≥ 45% (OR 4, CI 95% 1.9–11.3; p=0.006), posterior wall thickness ≤ 12 mm (OR 3.2, CI 95% 1.4–8; p=0.01) and absence of atrial fibrillation (OR 2.7, CI 95% 1.5–8.4; p=0.01). To generate a simple integer-based point score for each predictive variable, each beta coefficient was divided by the absolute value of the smallest coefficient, multiplied by 5, and rounded to the nearest integer. The values were 7, 6 and 5 respectively. Among the low-gradient population, in 55 patients with 0-6 score points the functional improvement was only 29%, while in the remaining 85 patients with 7-18 score points the functional improvement was 86% (p&amp;lt;0.001). Conclusions LGAS patients account for a relatively high proportion of patients undergoing TAVR. They show less objective functional recovery, which is associated with a significantly higher mortality at follow-up. We have developed a score based on 3 variables (augmentation index75, posterior wall thickness and atrial fibrillation) that can help predict the functional and prognostic response to TAVR in these patients.

Electron-positron pair creation under Gaussian and super-Gaussian pulse trains

The electron-positron pair (EPP) creation under Gaussian and super-Gaussian pulse trains are studied by the computational quantum field theory (CQFT) in the single-photon regime. The details of the EPP creation are studied from the time evolution of the EPP number, energy spectra and spatial distribution of the electrons. The results indicate that the final created EPPs is the non-linear accumulation of the multi-pulses, which depends on the time interval, pulse shape and pulse number. The optimal time interval can be chosen based on the pulse resonance condition, which is derived by the perturbation method. Besides, steeper super-Gaussian pulses and adding more pulses facilitate the EPP creation as well. The results indicate that, under optimal multi-pulse parameters, the number of the EPPs obtained is much larger than the sum of the EPPs created under the same number of single pulses. This finding not only can enhance the EPP creation, but also can improve the multi-pulse utilization and guide future experimental research on the EPP creation.

Integrated Control of Thermal Residual Stress and Mechanical Properties by Adjusting Pulse-Wave Direct Energy Deposition

Directed energy deposition with laser beam (DED-LB) components experience significant residual stress due to rapid heating and cooling cycles. Excessive residual tensile stress can lead to cracking in the deposited sample, resulting in service failure. This study utilized digital image correlation (DIC) and thermal imaging to observe the in situ temporal evolution of strain and temperature gradients across all layers of a deposited 316 L stainless steel thin wall during DED-LB. Both continuous-wave (CW) and pulsed-wave (PW) laser modes were employed. Additionally, the characteristics of thermal cracks and geometric dislocation density were examined. The results reveal that PW mode generates a lower temperature gradient, which in turn reduces thermal strain. In CW mode, the temperature–stress relationship curve of the additive manufacturing sample enters the “brittleness temperature zone”, leading to the formation of numerous hot cracks. In contrast, PW mode samples are almost free of cracks, as the metal avoids crack-sensitive regions during solidification, thereby minimizing hot crack formation. Overall, these factors collectively contribute to reduced residual stress and improved mechanical properties through the adjustment of pulsed-wave laser deposition.

Plasma Lipidomic Profiles Improve upon Traditional Risk Factors for the Prediction of Arterial Stiffness Among Patients with Type 2 Diabetes Mellitum: A Randomized, Placebo-Controlled Trial

Background: Exercise or vitamin D intervention can reduce the risk of arterial stiffness; however, the underlying mechanisms of lipid metabolism remain unexplored. To examine the effects of a 12-week moderate and vigorous exercise program (65–80% maximal heart rate, 60 min/time, 2~3 times/week) with or without vitamin D supplementation (1000 IU/day) on the reduction in arterial stiffness and further explore whether the effects of interventions could be associated with the basal lipidome among patients with Type 2 diabetes mellitum (T2DM). Method: 61 patients with T2DM were randomly assigned to the following groups: control (CON, n = 15), exercise (EX, n = 14), vitamin D (VD, n = 16), and exercise + vitamin D (EX + VD, n = 16). Arterial stiffness risk factors (ankle–brachial index (ABI); brachial–ankle pulse wave velocity (baPWV), systolic blood pressure (SBP), and diastolic blood pressure (DBP)) were evaluated before and after the intervention. The plasma lipidome was determined using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Machine learning was applied to establish prediction models for the responsiveness to arterial stiffness. Result: Vitamin D supplementation could inhibit the decrease in the ankle–brachial index (mean ± SD: EX + VD and VD, −0.001 ± 0.058; EX + CON, −0.047 ± −0.089; p = 0.03). We observed high inter-individual variability in the arterial stiffness risk factors in response to the interventions. We also found that optimally selecting the lipid predictors at baseline, such as SM d44:6, LPE 18:2, and Hex2Cer 29:0, could enhance the predictive power by 100% for arm SBP changes in the exercise group. Basal levels of Cer (33:1) and GM3 (44:4) could enhance the predictive power by 100% for changes in baPWV in the vitamin D group. Conclusions: A 12-week vitamin D supplementation was beneficial in preventing arterial stiffness. Compared with traditional clinical risk factors, specific lipids at baseline could significantly improve the ability to predict intervention-induced changes in the reduction of arterial stiffness.

Vascular Chemerin from PVAT contributes to Norepinephrine and Serotonin-Induced Vasoconstriction and Vascular Stiffness in a Sex-Dependent Manner.

The adipokine chemerin supports normal blood pressure and contributes to adiposity-associated hypertension, evidenced by falls in mean arterial pressure in Dahl SS rats given an antisense oligonucleotide against chemerin. In humans, circulating chemerin is positively associated with hypertension and aortic stiffness. Mechanisms of chemerin's influence on vascular health and disease remain unknown. We identified chemerin production in the vasculature-the blood vessel and its perivascular adipose tissue (PVAT). Here, using RNAScope®, QPCR, isometric contractility, high frequency ultrasound imaging, and western blot in the Dahl SS rat, we test the hypothesis that endogenous chemerin amplifies agonist-induced vasoconstriction through Chemerin1 and that chemerin drives aortic stiffness in the thoracic aorta. CMKLR1 (Chemerin1) expression was higher in the media, and Rarres2 (chemerin) expression was higher in the PVAT. Chemerin1 antagonism via selective inhibitor CCX832 reduced maximal contraction to norepinephrine (NE) and serotonin (5-HT), but not angiotensin II, in isolated thoracic aorta (PVAT intact) from male Dahl SS rat. In females, CCX832 did not alter contraction to NE or 5-HT. Male, but not female, genetic chemerin knockout Dahl SS rats had lower aortic arch pulse wave velocity than wild types, indicating chemerin's role in aortic stiffness. Aortic PVAT from females expressed less chemerin protein than males, suggesting PVAT as the primary source of active chemerin. We show that chemerin made by the PVAT amplifies NE and 5-HT-induced contraction and potentially induces aortic stiffening in a sex-dependent manner, highlighting the potential for chemerin to be a key factor in blood pressure control and aortic stiffening.

Association between pulse wave velocity and cerebral microbleeds: a systematic review and meta-analysis.

Cerebral microbleeds are associated with events that are among the highest mortality and disability events combined worldwide, as well as with hypertensive vasculopathy. The aim of the present study was to investigate the relationship between a marker of hypertensive vasculopathy, arterial stiffness assessed by pulse wave velocity, and cerebral microbleeds. A systematic review and meta-analysis was performed using PubMed, Scopus, and Web of Science, according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Cochrane Collaboration Handbook statements. Data extraction, quality assessment and statistical analyses were performed following pre-established criteria. Twenty-one studies involving 18,436 participants were included. Higher levels of pulse wave velocity were associated with a higher presence of cerebral microbleeds p-OR = 1.26 (95% CI; 1.09-1.45), with considerable heterogeneity; even adjusting for potential confounding variables p-OR = 1.12 (95% CI, 1.05-1.20), with substantial heterogeneity. Only the percentage of women was related to p-OR in the adjusted model. Sensitivity analyses confirmed the robustness of our results. Adjusted models showed publication bias. Higher levels of arterial stiffness are associated with greater presence of cerebral microbleeds. This phenomenon may be caused by damage to the brain under higher blood flow loads, in turn due to age-induced reversal of the stiffness gradient between large and small vessels. As the world's population is undergoing demographic ageing, our results underline the importance of establishing pulse wave velocity as a cardiovascular marker for early screening and delaying the onset of the characteristic signs of both diseases.