The temporal trend of vascular function in women with gestational diabetes.

The objective of the study was to assess the temporal changes in vascular function during pregnancy in healthy women and in those with gestational diabetes mellitus (GDM). Assessment of vascular function was done at three time points, 11-13+6 weeks+days, 20-22+6 weeks+days and 30-32+6 weeks+days, by flow-mediated dilatation (FMD), augmentation index (AIx) and carotid-radial pulse wave velocity (crPWV) in women ( n=100) with singleton pregnancies. Out of the 100 women, 20 developed GDM, who were compared with 20 healthy, age-matched pregnant women in a nested case-control design. Women with GDM had lower FMD% in the third compared to the first trimester (6.77 (4.36-9.96) vs 9.76 (6.66-16.61)%; p = 0.026); however, FMD% was similar on inter-group comparison between GDM and healthy pregnancies. AIx was significantly higher in GDM than healthy pregnancies at both first (15.35 ± 10.57 vs 6.45 ± 9.81%; p<0.05) and second trimesters (15.00 ± 8.44 vs 2.50 ± 9.01%; p<0.05). A higher AIx in early pregnancy differentiates women with GDM from those with healthy pregnancies.

Machine learning algorithms for detection of visuomotor neural control differences in individuals with PASC and ME.

The COVID-19 pandemic has affected millions worldwide, giving rise to long-term symptoms known as post-acute sequelae of SARS-CoV-2 (PASC) infection, colloquially referred to as long COVID. With an increasing number of people experiencing these symptoms, early intervention is crucial. In this study, we introduce a novel method to detect the likelihood of PASC or Myalgic Encephalomyelitis (ME) using a wearable four-channel headband that collects Electroencephalogram (EEG) data. The raw EEG signals are processed using Continuous Wavelet Transform (CWT) to form a spectrogram-like matrix, which serves as input for various machine learning and deep learning models. We employ models such as CONVLSTM (Convolutional Long Short-Term Memory), CNN-LSTM, and Bi-LSTM (Bidirectional Long short-term memory). Additionally, we test the dataset on traditional machine learning models for comparative analysis. Our results show that the best-performing model, CNN-LSTM, achieved an accuracy of 83%. In addition to the original spectrogram data, we generated synthetic spectrograms using Wasserstein Generative Adversarial Networks (WGANs) to augment our dataset. These synthetic spectrograms contributed to the training phase, addressing challenges such as limited data volume and patient privacy. Impressively, the model trained on synthetic data achieved an average accuracy of 93%, significantly outperforming the original model. These results demonstrate the feasibility and effectiveness of our proposed method in detecting the effects of PASC and ME, paving the way for early identification and management of the condition. The proposed approach holds significant potential for various practical applications, particularly in the clinical domain. It can be utilized for evaluating the current condition of individuals with PASC or ME, and monitoring the recovery process of those with PASC, or the efficacy of any interventions in the PASC and ME populations. By implementing this technique, healthcare professionals can facilitate more effective management of chronic PASC or ME effects, ensuring timely intervention and improving the quality of life for those experiencing these conditions.

Clinical Validation of Carotid-Femoral Pulse Wave Velocity Measurement Using a Multi-Beam Laser Vibrometer: The CARDIS Study.

BACKGROUND: Carotid-femoral pulse wave velocity (cfPWV) is the gold standard for noninvasive arterial stiffness assessment, an independent predictor of cardiovascular disease, and a potential parameter to guide therapy. However, cfPWV is not routinely measured in clinical practice due to the unavailability of a low-cost, operator-friendly, and independent device. The current study validated a novel laser Doppler vibrometry (LDV)-based measurement of cfPWV against the reference technique. METHODS: In 100 (50 men) hypertensive patients, cfPWV was measured using applanation tonometry (Sphygmocor) and the novel LDV device. This device has 2 handpieces with 6 laser beams each that simultaneously measure vibrations from the skin surface at carotid and femoral sites. Pulse wave velocity is calculated using ECG for the identification of cardiac cycles. An ECG-independent method was also devised. Cardiovascular risk score was calculated for patients between 40 and 75 years old using the WHO risk scoring chart. RESULTS: LDV-based cfPWV correlated significantly with tonometry (r=0.86, P<0.0001 ECG-dependent [cfPWVLDV_ECG] and r=0.80, P<0.001 ECG-independent [cfPWVLDV_w/oECG] methods). Bland-Altman analysis showed nonsignificant bias (0.65 m/s) and acceptable SD (1.27 m/s) between methods. Intraobserver coefficient of variance for LDV was 4.7% (95% CI, 3.0%-5.5%), and interobserver coefficient of variance was 5.87%. CfPWV correlated significantly with CVD risk (r=0.64, P<0.001; r=0.41, P=0.003; and r=0.37, P=0.006 for tonometry, LDV-with, and LDV-without ECG, respectively). CONCLUSIONS: The study demonstrates clinical validity of the LDV device. The LDV provides a simple, noninvasive, operator-independent method to measure cfPWV for assessing arterial stiffness, comparable to the standard existing techniques. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03446430.

Assessment of baroreflex sensitivity during isometric handgrip exercise and oscillatory lower body negative pressure.

Objectives: Baroreflex sensitivity (BRS) is an estimate of autonomic control of cardiovascular system via the baroreflex arc. It has been suggested that exercise pressure reflex and muscle metaboreflex override baroreflex during exercise to decrease baroreflex gain, which facilitates the simultaneous rise in blood pressure (BP) and heart rate during the exercise. This study investigated the effects of isometric handgrip exercise (IHE) on baroreflex gain and frequency dependence of baroreflex sensitivity while fluctuations in arterial BP were generated. Methods: Thirteen healthy men performed IHE at 20% and 30% of their maximum voluntary contraction (MVC), while oscillatory lower body negative pressure (OLBNP) of 40 mmHg was applied in 0.1 and 0.25 Hz frequencies. Results: Compared to the OLBNP at 0.25 Hz frequency alone, the baroreflex gain for diastolic BP (DBP) was significantly reduced with the addition of IHE at 20% and 30% of MVC in the high frequency band. At rest (without IHE and OLBNP) the baroreflex gain was significantly more in the high frequency band for DBP, but the baroreflex gain for DBP was not significantly different when IHE + OLBNP were applied at 20% and 30% of MVC in both frequencies. Conclusions: The significant reduction of DBP baroreflex gain with the addition of graded IHE might indicate that exercise pressure reflex and muscle metaboreflex override baroreflex during exercise to decrease baroreflex gain at a high frequency band (0.25 Hz). The frequency-dependent phenomenon of BRS was altered when IHE and OLBNP were applied, meaning that the frequency dependence of BRS was nullified during IHE.

Differential role of central and peripheral arterial stiffness in determining brachial artery resting retrograde flow in patients with ischemic heart disease vs healthy subjects.

Retrograde flow in endothelial cell cultures has been shown to induce a pro-atherogenic phenotype. Despite its potential role as a pathophysiological link between cardiovascular risk factors and atherosclerotic disease, resting retrograde flows between patients with cardiovascular disease and healthy subjects have not been compared. Further, the vascular characteristics governing retrograde flow in human arteries have not been systematically investigated. Association of central and peripheral vascular characteristics with retrograde flow profile was investigated in 32 healthy subjects and 47 patients with ischemic heart disease. Endothelial dysfunction was assessed by brachial ultrasound-based calculation of flow-mediated dilation (FMD) and sub-clinical atherosclerosis was estimated from carotid-intima media thickness (CIMT). Retrograde blood flow velocity (RBFV) and shear rate were comparable between the two groups (RBFV 1.82(0.97-3.32) vs 1.78(1.24-2.65) cm/s p = 0.79). Augmentation index was a significant determinant of retrograde flow in both patients and healthy subjects. Carotid artery incremental elastic modulus was an independent determinant of retrograde flow patterns in healthy subjects while ejection fraction, cf/cr PWV ratio and forearm vascular conductance emerged as independent determinants in patients. Retrograde flow patterns were also associated with FMD (RBFV r = -0.43, p = 0.004) and CIMT (r = 0.30, p = 0.041) in patients. The results of the study suggest a difference in the determinants of retrograde flow in patients and healthy subjects, with central arterial stiffness being a major contributor in healthy subjects while interaction between central, peripheral, and cardio-arterial factors influence retrograde flow in patients with ischemic heart disease.

Brachial Artery "Low-Flow Mediated Constriction" Is Associated with Myocardial Perfusion Defect Severity and Mediated by an Altered Flow Pattern during Occlusion.

INTRODUCTION: The relationship between low flow-mediated constriction (LFMC), a new proposed measure of endothelial function, with cardiovascular disease severity and its hypothesized stimulus, that is, low flow, has not been comprehensively evaluated. The study evaluated association between change in brachial artery diameter during constriction with severity of myocardial perfusion defect (PD) and alterations in different components of flow profile. METHODS: Brachial artery responses to occlusion were assessed in 91 patients and 30 healthy subjects. Change in anterograde and retrograde blood flow velocities (delta anterograde blood flow velocity and retrograde blood flow velocity), anterograde shear rate and retrograde shear rate (delta ASR and RSR, respectively), and oscillatory shear index (delta) during forearm occlusion at 50 mm Hg above systolic pressure, from baseline was calculated. Myocardial perfusion was evaluated in patients using exercise single positron emission computed tomography and % myocardial PD was calculated from summed stress score. RESULTS: LFMC emerged as independent predictor of defect severity after correcting for age and gender (p = 0.014). Sixty-seven patients (73.6%) and 15 healthy subjects (50%) showed constriction during occlusion. In stepwise backward regression analysis, RSR contributed 35.5% and ASR contributed 20.1% of the total 63.9% variability in artery diameter during occlusion. CONCLUSION: The results suggest that LFMC is independently associated with myocardial perfusion severity and is "mediated" by an altered flow profile during occlusion.

Improvement in Angiotensin 1-7 precedes and correlates with improvement in Arterial stiffness and endothelial function following Renin-Angiotensin system inhibition in type 2 diabetes with newly diagnosed hypertension.

BACKGROUND AND AIM: Studies in cell cultures and animal models have revealed the possible pathophysiological factors associated with vascular endothelial dysfunction. However, the same in human subjects has not been clearly established. The current study uses a novel approach to identify the factors associated with endothelial function and arterial function by altering these vascular parameters using Angiotensin-Converting-Enzyme (ACE) inhibition. METHODS: Diabetic patients with newly diagnosed hypertension (n = 60) were recruited for the study. Flow-mediated-dilation (FMD), carotid-femoral (cf), carotid-radial (cr) Pulse-wave-velocity (PWV), Augmentation-Index, Carotid-Intima-Media-Thickness (CIMT), serum levels of Renin, Angiotensin II (AngII), Angiotensin-Converting-Enzyme2 (ACE2), Angiotensin1-7 (Ang1-7), E-selectin, Vascular-Cell-Adhesion-Molecule-1 (VCAM-1), Highly-sensitive-C-Reactive-Protein (hsCRP) and Interleukin-10 were measured at baseline (V1), after 1 week (V2) and 3 months (V3) of ACE inhibition in patients of diabetes with newly diagnosed hypertension. The amplitude of change after 1 week (V2-V1) and 3 months (V3-V1) for the clinical and various parameters were correlated with the change in endothelial function and arterial stiffness. RESULTS: Carotid radial-PWVV2-V1 (p = 0.001) and Ang1-7V2-V1 (p = 0.01) emerged as independent predictors of FMDV2-V1. ReninV2-V1 and VCAM-1V2-V1 independently predicted E-selectinV2-V1 [(p = 0.01) and (p = 0.001), respectively]. ACE 2V2-V1 was the only independent predictor of cf-PWVV2-V1. The same parameters remained as independent predictors of the respective vascular factors after 3 months of ACE inhibition. CONCLUSION: The study highlights the role of AngII/Ang1-7 balance in alteration of endothelial function and central arterial stiffness in humans in addition to identifying the interrelationship between the renin-angiotensin-aldosterone-system components and clinically ascertainable parameters.

Imbalance between Angiotensin II - Angiotensin (1-7) system is associated with vascular endothelial dysfunction and inflammation in type 2 diabetes with newly diagnosed hypertension.

AIM: Diabetes is associated with Renin-angiotensin-aldosterone-system (RAAS) activation. Protective role of Angiotensin (1-7) has been recently identified. The study aims to identify associations between imbalance in RAAS components with vascular endothelial dysfunction and inflammation in diabetics with newly diagnosed hypertension. METHODS: Brachial Flow-mediated-dilation (FMD), Carotid Intima-media-thickness (CIMT), pulse-wave-velocity (PWV), Serum E-selectin, Vascular-Cell-Adhesion-Molecule-1 (VCAM-1), high-sensitivity C-Reactive Protein (hsCRP), Interleukin-10 (IL-10), Renin, AngiotensinII, Angiotensin-Converting-Enzyme 2 (ACE2) and Angiotensin1-7 were measured in 60 diabetic patients with newly diagnosed hypertension. Patients with AngiotensinII/Angiotensin1-7 ratio <1 were classified as Favourable-Axis (FA) group (n = 22) and those with ratio >1 were classified as Unfavourable-Axis (UA) group (n = 38). RESULTS: hsCRP was higher [9.52 (4.64-16.19) vs 3.62 (1.77-13.09) (mg/l), p = 0.04], IL-10 was lower [2.26 (1.34-12.05) vs 10.98 (4.44-17.78) (pg/ml),p = 0.006], %FMD was lower [(5.51 ±â€¯2.97) vs (7.66 ±â€¯3.38) (%), p = 0.01] and CIMT was higher in UA compared to FA group [0.7 (0.55-0.79) vs 0.51 (0.49-0.65) (mm), p = 0.001]. Renin correlated positively with pressure, PWV, E-selectin and VCAM-1, opposing associations were obtained for Angiotensin1-7 and ACE2. CONCLUSION: Imbalance between AngiotensinII - Angiotensin1-7 is associated with increased inflammation and vascular dysfunction in diabetics and can contribute to development of hypertension in these patients.

Regional arterial stiffness in central and peripheral arteries is differentially related to endothelial dysfunction assessed by brachial flow-mediated dilation in metabolic syndrome.

The interrelationship between endothelial function and arterial stiffness may be different for central and peripheral arteries due to their structural and functional differences. The study aims to assess the interrelationship between central and peripheral vascular function and haemodynamics in metabolic syndrome. Thirty-seven patients [63.0 (57.5-66.0) years, 68.4% males] of metabolic syndrome (National Cholesterol Education Program - Adult Treatment Panel-III criteria) were studied. Carotid-femoral, carotid-radial pulse wave velocity and augmentation index (AIx@75) were assessed using applanation tonometry. Endothelial function was evaluated by brachial flow-mediated dilation using B-mode ultrasonography. Central and peripheral pressures were measured by radial tonometry and sphygmomanometer, respectively. Carotid-radial pulse wave velocity correlated significantly with peripheral diastolic blood pressure ( r = 0.33, p = 0.04) and inversely with flow-mediated dilation ( r = -0.61, p = 0.0001). AIx@75 correlated significantly with carotid-femoral pulse wave velocity ( r = 0.35, p = 0.03) and with aortic pulse pressure ( r = 0.43, p = 0.01). In principal component analysis, an inverse relationship was observed between flow-mediated dilation and carotid-radial pulse wave velocity but not with carotid-femoral pulse wave velocity. Regional arterial stiffness assessed by pulse wave velocity in central-elastic and peripheral-muscular arteries differentially relates to endothelial dysfunction. The central arteries might be predominantly influenced by endothelial dysfunction-induced structural changes, while the peripheral arteries are majorly affected by functional alterations.

Decreased Spontaneous Baroreflex Sensitivity as an Early Marker for Progression of Haemorrhage.

INTRODUCTION: Blood donation provides an ideal setup for assessment of cardiovascular responses to mild hypovolemia for understanding the underlying mechanisms. AIM: To evaluate cardiovascular responses in time and magnitude by estimating the spontaneous baroreflex sensitivity (BRS) during and after donation of 450 ml of blood. METHODS: Continuous beat-to-beat blood pressure and lead II ECG was recorded before, during and after blood donation in 54 healthy volunteers (age 34.7 ± 5.08 years; weight 77.9 ± 8.20 kg), followed by offline analyses of baroreflex sensitivity. RESULTS: The systolic, diastolic or mean blood pressures did not change during or after the blood donation. Decrease in pulse pressure and increase in heart rate was observed post donation. The spontaneous BRS decreased during [8.68 (6.038-12.69) ms/mmHg] and after blood donation [9.401 (6.396-11.59) ms/mmHg] as compared to the baseline [12.83 (6.884-18.18) ms/mmHg] with a significant decrease in α-HF on spectral analysis. CONCLUSION: Mild blood loss (450 ml) results in non-hypotensive haemorrhage with a decrease in spontaneous BRS before the rise of heart rate during blood donation.