Atrial Fibrillation and Early Vascular Aging: Clinical Implications, Methodology Issues and Open Questions-A Review from the VascAgeNet COST Action.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with adverse CV outcomes. Vascular aging (VA), which is defined as the progressive deterioration of arterial function and structure over a lifetime, is an independent predictor of both AF development and CV events. A timing identification and treatment of early VA has therefore the potential to reduce the risk of AF incidence and related CV events. A network of scientists and clinicians from the COST Action VascAgeNet identified five clinically and methodologically relevant questions regarding the relationship between AF and VA and conducted a narrative review of the literature to find potential answers. These are: (1) Are VA biomarkers associated with AF? (2) Does early VA predict AF occurrence better than chronological aging? (3) Is early VA a risk enhancer for the occurrence of CV events in AF patients? (4) Are devices measuring VA suitable to perform subclinical AF detection? (5) Does atrial-fibrillation-related rhythm irregularity have a negative impact on the measurement of vascular age? Results showed that VA is a powerful and independent predictor of AF incidence, however, its role as risk modifier for the occurrence of CV events in patients with AF is debatable. Limited and inconclusive data exist regarding the reliability of VA measurement in the presence of rhythm irregularities associated with AF. To date, no device is equipped with tools capable of detecting AF during VA measurements. This represents a missed opportunity to effectively perform CV prevention in people at high risk. Further advances are needed to fill knowledge gaps in this field.

Assessment of Arterial Stiffness and Biochemical Markers in Systemic Lupus Erythematosus in the Diagnosis of Subclinical Atherosclerosis.

Patients with systemic lupus erythematosus (SLE) are 2-10 times more likely to develop cardiovascular disease (CVD) than the general population. The assessment of the risk of developing CVD is an important direction for further clinical management. The study was conducted retrospectively and included patients with SLE. The aim of the study was to assess the measurements of pulse wave velocity (PWV), carotid intima-media thickness (CIMT), ankle-brachial index (ABI) and biochemical parameters. Subclinical atherosclerosis was also assessed. The study included 98 patients with SLE with an age- and sex-matched control group of 68 healthy adults. Statistical significance was found in the SLE group and the controls for N-terminal fragment of pro-B-type natriuretic peptide (NT proBNP) (144.87 vs. 36.41 pg/mL, p = 0.0018), high-sensitivity cardiac troponin (hs-cTn) (25.43 vs. 6.38 ng/L, p = 0.0303) and D-Dimer levels (0.73 vs. 0.36 µg/mL, p = 0.0088), left CIMT (1.03 vs. 0.62 mm, p < 0.0001), right CIMT (0.93 vs. 0.63 mm, p < 0.0001) and PWV CF (9.74 vs. 7.98 m/s, p = 0.0294). A positive correlation was found between NT proBNP and PWV CF (r = 0.6880, p = 0.0498) and hs-cTn and PVW carotid-femoral (CF) (r = 0.8862, p = 0.0499) in SLE. A positive correlation was reported between PWV CF and systolic blood pressure (r = 0.5025, p = 0.0487). The measurement of carotid-femoral PWV is a simple, non-invasive, and reproducible method and may independently predict future CVD events and their cause. Further studies are warranted to establish the prognostic value of PWV in patients with SLE, as it may be superior to CIMT measurements in the early stages of vascular disorders.

Ultrasonographic assessment of brachial artery reactivity as a predictor of adverse outcome in patients undergoing emergency laparotomy for perforated peritonitis - Prospective observational study.

Background and Aims: This study aimed to assess if pre- and postoperative parameters of brachial artery reactivity (BAR), like flow-mediated dilation (FMD) and hyperaemic velocity (HV), could predict in-hospital mortality in perforation peritonitis patients undergoing emergency laparotomy. Methods: In this prospective observational study, adult patients with perforation peritonitis undergoing emergency laparotomy were recruited. FMD and HV were measured preoperatively, postoperatively and at 24 and 48 h post-surgery. Adult patients undergoing elective laparotomy served as the control group. The primary outcome was in-hospital mortality. Baseline and BAR parameters were compared between survivors and non-survivors. Risk factors for mortality were identified by univariate analysis. Prognostic performances of BAR parameters were assessed by different models using logistic regression. All statistical analyses were performed on STATA version 13 for Mac OS. Results: Seventy-six emergency laparotomy patients were recruited, and 26 died during the hospital stay. FMD and HV were comparable at all time points between survivors and non-survivors, except that HV was higher in survivors at 48 h post-surgery (median [interquartile range] 1.28 [1.16-1.49] vs. 1.16 [0.86-1.35], P = 0.010]. HV at 48 h predicted mortality (adjusted odds ratio [OR] [95% confidence interval] 21.05 [1.04-422.43], P = 0.046), and a model consisting of age, Acute Physiology and Chronic Health Evaluation (APACHE) score and HV at 48 h was the best predictor of mortality (area under the receiver operating characteristic (AUROC) curve 0.82). Conclusion: HV, as measured by ultrasonography of the brachial artery at 48 h postoperatively, is a good predictor of mortality in patients undergoing emergency laparotomy for perforation peritonitis.

Derivation, validation, and transcriptomic assessment of pediatric septic shock phenotypes identified through latent profile analyses: Results from a prospective multi-center observational cohort.

Background: Sepsis poses a grave threat, especially among children, but treatments are limited due to clinical and biological heterogeneity among patients. Thus, there is an urgent need for precise subclassification of patients to guide therapeutic interventions. Methods: We used clinical, laboratory, and biomarker data from a prospective multi-center pediatric septic shock cohort to derive phenotypes using latent profile analyses. Thereafter, we trained a support vector machine model to assign phenotypes in a hold-out validation set. We tested interactions between phenotypes and common sepsis therapies on clinical outcomes and conducted transcriptomic analyses to better understand the phenotype-specific biology. Finally, we compared whether newly identified phenotypes overlapped with established gene-expression endotypes and tested the utility of an integrated subclassification scheme. Findings: Among 1,071 patients included, we identified two phenotypes which we named 'inflamed' (19.5%) and an 'uninflamed' phenotype (80.5%). The 'inflamed' phenotype had an over 4-fold risk of 28-day mortality relative to those 'uninflamed'. Transcriptomic analysis revealed overexpression of genes implicated in the innate immune response and suggested an overabundance of developing neutrophils, pro-T/NK cells, and NK cells among those 'inflamed'. There was no significant overlap between endotypes and phenotypes. However, an integrated subclassification scheme demonstrated varying survival probabilities when comparing endophenotypes. Interpretation: Our research underscores the reproducibility of latent profile analyses to identify clinical and biologically informative pediatric septic shock phenotypes with high prognostic relevance. Pending validation, an integrated subclassification scheme, reflective of the different facets of the host response, holds promise to inform targeted intervention among those critically ill.

Dynamic Assessment of Plasma von Willebrand Factor and ADAMTS13 Predicts Mortality in Hospitalized Patients with SARS-CoV-2 Infection.

BACKGROUND: Plasma levels of von Willebrand factor (VWF) are significantly elevated in patients with coronavirus disease 2019 (COVID-19). However, dynamic changes and prognostic value of this biomarker in hospitalized patients with COVID-19 have not been determined. METHODS: A total of 124 patients infected with SARS-CoV-2 were prospectively recruited for the study. Serial blood samples were obtained at the time of admission (D1), 3-4 days following standard-care treatments (D2), and 1-2 days prior to discharge or any time collected prior to death (D3). Plasma VWF antigen, ADAMTS13 antigen, and ADAMTS13 proteolytic activity, as well as the ratio of VWF/ADAMTS13 were determined, followed by various statistical analyses. RESULTS: On admission, plasma levels of VWF in COVID-19 patients were significantly elevated compared with those in the healthy controls, but no statistical significance was detected among patients with different disease severity. Plasma ADAMTS13 activity but not its antigen levels were significantly lower in patients with severe or critical COVID-19 compared with that in other patient groups. Interestingly, the ratios of plasma VWF antigen to ADAMTS13 antigen were significantly higher in patients with severe or critical COVID-19 than in those with mild to moderate disease. More importantly, plasma levels of VWF and the ratios of VWF/ADAMTS13 were persistently elevated in patients with COVID-19 throughout hospitalization. Kaplan-Meier and Cox proportional hazard regression analyses demonstrated that an increased plasma level of VWF or ratio of VWF/ADAMTS13 at D2 and D3 was associated with an increased mortality rate. CONCLUSIONS: Persistent endotheliopathy, marked by the elevated levels of plasma VWF or VWF/ADAMTS13 ratio, is present in all hospitalized patients following SARS-CoV-2 infection, which is strongly associated with mortality.

Endothelial function assessment by flow-mediated dilation of the brachial artery in acute kidney injury and chronic kidney disease.

Background: Endothelial dysfunction has a significant role in the pathogenesis of cardiovascular events in patients with kidney dysfunction. The present study aimed to compare the level of endothelial dysfunction in patients with chronic kidney disease (CKD) and acute kidney injury (AKI) by brachial artery flow-mediated dilation (FMD) technique. Also, we sought to find whether this non-invasive technique may assist in accurately distinguishing the acute or chronic nature of kidney failure in patients presenting with uremia for the first time. Methods: Demographic and medical characteristics, and laboratory and renal ultrasonography data of the patients with AKI and CKD were collected and compared with a control group. Brachial artery FMD was measured using a Toshiba aplio 300 device with a 7.5 MHz linear probe. Results: In a total of 175 patients with a mean (SD) age of 55.96(15.54) years, FMD% was significantly lower in the CKD and AKI patients compared to the control group (Mean±SD: 16.28%±10.52%), 16.28 %±4.35%, and 24.24±5.71, respectively, p<0.001). Among the different causes of AKI, contrast-induced nephropathy (10.78%±1.75%), volume depletion (14.87%±1.22%), and post-renal AKI (15.96%±1.54%) had the lowest levels of FMD. Also, a significant correlation between FMD and eGFR (r=0.26, P<0.001), serum Hb (r=0.18, P=0.013), Na (r=0.19, P=0.011), BUN (r=-0.21, P=0.005) and Cr (r=- 0.13, P=0.084) was reported. Conclusion: Compared to the control group, CKD and AKI patients showed greater levels of endothelial dysfunction as evidenced by lower brachial artery FMD. However, the FMD technique did not appear to be a practical method in differentiating CKD and AKI in patients presenting with uremia for the first time.

External validation and biomarker assessment of a high-risk, data-driven pediatric sepsis phenotype characterized by persistent hypoxemia, encephalopathy, and shock.

Objective: Identification of children with sepsis-associated multiple organ dysfunction syndrome (MODS) at risk for poor outcomes remains a challenge. Data-driven phenotyping approaches that leverage electronic health record (EHR) data hold promise given the widespread availability of EHRs. We sought to externally validate the data-driven 'persistent hypoxemia, encephalopathy, and shock' (PHES) phenotype and determine its association with inflammatory and endothelial biomarkers, as well as biomarker-based pediatric risk-strata. Design: We trained and validated a random forest classifier using organ dysfunction subscores in the EHR dataset used to derive the PHES phenotype. We used the classifier to assign phenotype membership in a test set consisting of prospectively enrolled pediatric septic shock patients. We compared biomarker profiles of those with and without the PHES phenotype and determined the association with established biomarker-based mortality and MODS risk-strata. Setting: 25 pediatric intensive care units (PICU) across the U.S. Patients: EHR data from 15,246 critically ill patients sepsis-associated MODS and 1,270 pediatric septic shock patients in the test cohort of whom 615 had biomarker data. Interventions: None. Measurements and Main Results: The area under the receiver operator characteristic curve (AUROC) of the new classifier to predict PHES phenotype membership was 0.91(95%CI, 0.90-0.92) in the EHR validation set. In the test set, patients with the PHES phenotype were independently associated with both increased odds of complicated course (adjusted odds ratio [aOR] of 4.1, 95%CI: 3.2-5.4) and 28-day mortality (aOR of 4.8, 95%CI: 3.11-7.25) after controlling for age, severity of illness, and immuno-compromised status. Patients belonging to the PHES phenotype were characterized by greater degree of systemic inflammation and endothelial activation, and overlapped with high risk-strata based on PERSEVERE biomarkers predictive of death and persistent MODS. Conclusions: The PHES trajectory-based phenotype is reproducible, independently associated with poor clinical outcomes, and overlap with higher risk-strata based on validated biomarker approaches.

Atherosclerosis, Diabetes Mellitus, and Cancer: Common Epidemiology, Shared Mechanisms, and Future Management.

The involvement of cardiovascular disease in cancer onset and development represents a contemporary interest in basic science. It has been recognized, from the most recent research, that metabolic syndrome-related conditions, ranging from atherosclerosis to diabetes, elicit many pathways regulating lipid metabolism and lipid signaling that are also linked to the same framework of multiple potential mechanisms for inducing cancer. Otherwise, dyslipidemia and endothelial cell dysfunction in atherosclerosis may present common or even interdependent changes, similar to oncogenic molecules elevated in many forms of cancer. However, whether endothelial cell dysfunction in atherosclerotic disease provides signals that promote the pre-clinical onset and proliferation of malignant cells is an issue that requires further understanding, even though more questions are presented with every answer. Here, we highlight the molecular mechanisms that point to a causal link between lipid metabolism and glucose homeostasis in metabolic syndrome-related atherosclerotic disease with the development of cancer. The knowledge of these breakthrough mechanisms may pave the way for the application of new therapeutic targets and for implementing interventions in clinical practice.

Assessment of early vascular changes in adult females with polycystic ovary syndrome: correlation with insulin resistance.

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in females in the reproductive period with estimated prevalence of 5% to 18% [1]. It contributes to the mortality and morbidity in patients with PCOS due to the increased risk of different metabolic and cardiovascular (CV) complications [2]. Despite the presence of obesity in 40-60% of cases [3], the disease may occur in non-obese women. The occurrence of metabolic disorders in non-obese PCOS patients, suggests that the syndrome itself may play a role in the development of metabolic and CV co-morbidities [4]. The identification of early stages of atherosclerosis in patients with PCOS might be useful in the development of new strategies to control modifiable CV risk factors [5]. Assessment of vascular endothelial function (ED) as an initial reversible step in atherosclerosis development, may serve as an integral index for CV risk factor burden [6]. In addition, carotid intima media thickness (CIMT) is a helpful marker for atherosclerosis and for the identification of increased risk of CV disease [7]. Our study assessed the early vascular changes in Egyptian women with PCOS both physically and functionally by looking at the CIMT using high resolution Doppler ultrasound and by measuring ED using brachial artery flow-mediated vasodilatation (FMD). Our results indicate that patients with PCOS have significant ED and premature atherosclerosis which is, to a great extent, independent of obesity and IR. This suggests that PCOS patients are at increased risk for premature CVD and may benefit from early detection and management.

Longitudinal Assessment of Plasma Syndecan-1 Predicts 60-Day Mortality in Patients with COVID-19.

Background: Endotheliopathy is a common pathologic finding in patients with acute and long COVID-19. It may be associated with disease severity and predispose patients to long-term complications. Plasma levels of a proteoglycan, syndecan-1, are found to be significantly elevated in patients with COVID-19, but its roles in assessing disease severity and predicting long-term outcome are not fully understood. Methods: A total of 124 consecutive hospitalized patients with SARS-CoV-2 infection were prospectively enrolled and blood samples were collected on admission (T1), 3−4 days following treatment (T2), and 1−2 days prior to discharge or death (T3). Plasma levels of syndecan-1 were determined using an immunosorbent assay; various statistical analyses were performed to determine the association between plasma syndecan-1 levels and disease severity or the 60-day mortality rate. Results: Compared with those in the healthy controls, plasma levels of syndecan-1 in patients with critical COVID-19 were significantly higher (p < 0.0001). However, there was no statistically significant difference among patients with different disease severity (p > 0.05), resulting from large individual variability. Longitudinal analysis demonstrated that while the levels fluctuated during hospitalization in all patients, plasma syndecan-1 levels were persistently elevated from baseline in critical COVID-19 patients. Cox proportional hazard regression analyses revealed that elevated plasma levels of syndecan-1 (>260 ng/mL at T1, >1018 ng/mL at T2, and >461 ng/mL at T3) were significantly associated with the 60-day mortality rate. Conclusions: Endotheliopathy, marked by glycocalyx degradation and elevated plasma syndecan-1, occurs in nearly all hospitalized patients with SARS-CoV-2 infection; elevated plasma syndecan-1 is associated with increased mortality in COVID-19 patients.

Long-term assessment of systemic microcirculatory function and plasma cytokines after coronavirus disease 2019 (COVID-19).

Systemic microvascular dysfunction has been shown to be present in COVID-19, and serum cytokines are known to be involved in the regulation of vascular function. We sought to evaluate systemic microvascular endothelial function, with laser doppler perfusion monitoring (LDPM), and plasma levels of cytokines after acute COVID-19. Individuals admitted to a Cardiology hospital with acute COVID-19 and followed for 12-15 months after recovery underwent noninvasive evaluation of systemic endothelium-dependent microvascular reactivity by cutaneous LDPM with local thermal hyperemia (LTH). A multiplex biometric immunoassay panel was used to assess 48 serum cytokines and chemokines. Twenty patients and 14 control volunteers were enrolled. The areas under the curves of vasodilation induced by LTH were significantly increased after recovery (P=0.009) and were not different from values obtained in healthy volunteers (P = 0.85). The peak microvascular flow during LTH did also significantly increase (P = 0.02), and was not different form values obtained in healthy volunteers (P = 0.55). Several cytokines displayed significantly reduced serum concentrations after recovery from COVID-19. In conclusion, endothelium-dependent systemic microvascular reactivity improved after recovery from COVID-19 in patients with cardiovascular diseases, in parallel with a reduction in the levels of several serum cytokines and chemokines involved in the regulation of vascular function and inflammation.

Long-term assessment of systemic microcirculatory function and plasma cytokines after coronavirus disease 2019 (COVID-19)

Abstract Systemic microvascular dysfunction has been shown to be present in COVID-19, and serum cytokines are known to be involved in the regulation of vascular function. We sought to evaluate systemic microvascular endothelial function, with laser doppler perfusion monitoring (LDPM), and plasma levels of cytokines after acute COVID-19. Individuals admitted to a Cardiology hospital with acute COVID-19 and followed for 12-15 months after recovery underwent noninvasive evaluation of systemic endothelium-dependent microvascular reactivity by cutaneous LDPM with local thermal hyperemia (LTH). A multiplex biometric immunoassay panel was used to assess 48 serum cytokines and chemokines. Twenty patients and 14 control volunteers were enrolled. The areas under the curves of vasodilation induced by LTH were significantly increased after recovery (P=0.009) and were not different from values obtained in healthy volunteers (P= 0.85). The peak microvascular flow during LTH did also significantly increase (P= 0.02), and was not different form values obtained in healthy volunteers (P= 0.55). Several cytokines displayed significantly reduced serum concentrations after recovery from COVID-19. In conclusion, endothelium-dependent systemic microvascular reactivity improved after recovery from COVID-19 in patients with cardiovascular diseases, in parallel with a reduction in the levels of several serum cytokines and chemokines involved in the regulation of vascular function and inflammation.

Biological Assessment of the NO-Dependent Endothelial Function.

Nitric oxide (NO) is implicated in numerous physiological processes, including vascular homeostasis. Reduced NO bioavailability is a hallmark of endothelial dysfunction, a prequel to many cardiovascular diseases. Biomarkers of an early NO-dependent endothelial dysfunction obtained from routine venous blood sampling would be of great interest but are currently lacking. The direct measurement of circulating NO remains a challenge due by its high reactivity and short half-life. The current techniques measure stable products from the NO signaling pathway or metabolic end products of NO that do not accurately represent its bioavailability and, therefore, endothelial function per se. In this review, we will concentrate on an original technique of low temperature electron paramagnetic resonance spectroscopy capable to directly measure the 5-α-coordinated heme nitrosyl-hemoglobin in the T (tense) state (5-α-nitrosyl-hemoglobin or HbNO) obtained from fresh venous human erythrocytes. In humans, HbNO reflects the bioavailability of NO formed in the vasculature from vascular endothelial NOS or exogenous NO donors with minor contribution from erythrocyte NOS. The HbNO signal is directly correlated with the vascular endothelial function and inversely correlated with vascular oxidative stress. Pilot studies support the validity of HbNO measurements both for the detection of endothelial dysfunction in asymptomatic subjects and for the monitoring of such dysfunction in patients with known cardiovascular disease. The impact of therapies or the severity of diseases such as COVID-19 infection involving the endothelium could also be monitored and their incumbent risk of complications better predicted through serial measurements of HbNO.

Clinical assessment of endothelial function in convalescent COVID-19 patients: a meta-analysis with meta-regressions.

BACKGROUND: Endothelial dysfunction has been proposed to play a key role in the pathogenesis of coronavirus disease 2019 (COVID-19) and its post-acute sequelae. Flow-mediated dilation (FMD) is recognized as an accurate clinical method to assess endothelial function. Thus, we performed a meta-analysis of the studies evaluating FMD in convalescent COVID-19 patients and controls with no history of COVID-19. METHODS: A systematic literature search was conducted in the main scientific databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using the random effects method, differences between cases and controls were expressed as mean difference (MD) with 95% confidence intervals (95% CI). The protocol was registered on PROSPERO with reference number CRD42021289684. RESULTS: Twelve studies were included in the final analysis. A total of 644 convalescent COVID-19 patients showed significantly lower FMD values as compared to 662 controls (MD: -2.31%; 95% CI: -3.19, -1.44; p < 0.0001). Similar results were obtained in the sensitivity analysis of the studies that involved participants in either group with no cardiovascular risk factors or history of coronary artery disease (MD: -1.73%; 95% CI: -3.04, -0.41; p = 0.010). Interestingly, when considering studies separately based on enrolment within or after 3 months of symptom onset, results were further confirmed in both short- (MD: -2.20%; 95% CI: -3.35, -1.05; p < 0.0001) and long-term follow-up (MD: -2.53%; 95% CI: -4.19, -0.86; p = 0.003). Meta-regression models showed that an increasing prevalence of post-acute sequelae of COVID-19 was linked to a higher difference in FMD between cases and controls (Z-score: -2.09; p = 0.037). CONCLUSIONS: Impaired endothelial function can be documented in convalescent COVID-19 patients, especially when residual clinical manifestations persist. Targeting endothelial dysfunction through pharmacological and rehabilitation strategies may represent an attractive therapeutic option.Key messagesThe mechanisms underlying the post-acute sequelae of coronavirus disease 2019 (COVID-19) have not been fully elucidated.Impaired endothelial function can be documented in convalescent COVID-19 patients for up to 1 year after infection, especially when residual clinical manifestations persist.Targeting endothelial dysfunction may represent an attractive therapeutic option in the post-acute phase of COVID-19.

Endothelial Function Assessment by Flow-Mediated Dilation Method: A Valuable Tool in the Evaluation of the Cardiovascular System.

Cardiovascular diseases (CVDs) in the course of atherosclerosis are one of the most critical public health problems in the world. Endothelial cells synthesize numerous biologically active substances involved in regulating the functions of the cardiovascular system. Endothelial dysfunction is an essential element in the pathogenesis of atherosclerosis. Thus, the assessment of endothelial function in people without overt CVD allows for a more accurate estimate of the risk of developing CVD and cardiovascular events. The assessment of endothelial function is primarily used in scientific research, and to a lesser extent in clinical practice. Among the tools for assessing endothelial function, we can distinguish biochemical and physical methods, while physical methods can be divided into invasive and non-invasive methods. Flow-mediated dilation (FMD) is based on the ultrasound assessment of changes in the diameter of the brachial artery as a result of increased blood flow. FMD is a non-invasive, safe, and repeatable test, but it must be performed by qualified and experienced medical staff. The purpose of this paper is to present the literature review results on the assessment of endothelial function using the FMD method, including its methodology, applications in clinical practice and research, limitations, and future perspectives.

Preoperative Vascular Function Assessment and Perioperative Vascular Events in Patients Posted for Elective Non-cardiac Surgeries.

Background Coronary atherosclerosis is usually asymptomatic until a major cardiac event occurs. Surgery is one of the major stress factors that play a role in hastening vascular deterioration in susceptible patients. Non-invasive tests to detect atherosclerosis and endothelial dysfunction have started gaining popularity nowadays, and of the several options, carotid artery intima-media thickness (IMT) and radial artery flow-mediated dilation (FMD) are two promising tests for detecting cardiovascular impairment. Methods This was a pilot study that was undertaken on 100 patients in a tertiary care medical center (Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry) between June 2015 and August 2016 with the aim of studying the prevalence of endothelial dysfunction and early atherosclerosis in the given population, and to find out the predictive power of preoperative vascular functional assessment in the prediction of perioperative cardiovascular events in the same population. We had selected patients who had at least two risk factors for endothelial dysfunction and were posted for elective non-cardiac surgical procedures via convenience sampling. Flow-mediated vasodilatation of the radial artery (FMD) and carotid intima-media thickness (CIMT) were measured on the previous day of surgery, while a fasting lipid profile was collected from the patients on the morning of the surgery. Endothelial dysfunction was defined as FMD<4.5%, while atherosclerosis was defined as CIMT>0.07 cm. Demographic details and baseline hemodynamic parameters of the patients were also noted preoperatively as well as intra-operatively, and patients were followed up for any major clinical adverse cardiovascular event post-operatively till they were discharged from the hospital. Results It was found that the prevalence of endothelial dysfunction was 23%, while the prevalence of early atherosclerosis was 33% in our study population. However, it was found that FMD and CIMT did not correlate with each other significantly, nor did they correlate significantly with perioperative cardiovascular events. The risk factors of the patients also did not correlate with the FMD and CIMT values of the patients in which they were impaired. Moreover, they did not have any significant correlation with the perioperative events that occurred. Conclusion The prevalence of endothelial dysfunction in our tertiary center was found to be 23%, and the prevalence of atherosclerosis was 33% in patients posted for elective non-cardiac surgery who had multiple risk factors. It was also found that non-invasive preoperative vascular assessment was not quite effective as hypothesized in predicting perioperative cardiovascular events.

Assessment of Endothelial Dysfunction by Brachial Artery Flow-Mediated Dilatation in Postmenopausal Women at Low Risk for Cardiovascular Disease.

OBJECTIVE: The objective is to compare endothelial dysfunction measured by brachial artery flow-mediated dilation (BAFMD) in nonobese, nondiabetic post-menopausal women with their age-matched menstruating controls and to identify the correlation of BAFMD with Framingham risk score (FRS) and with the individual parameters of FRS in low-risk women. METHODS: This study was done in the department of Obstetrics and Gynaecology, Chandigarh, India, for 1 year. Fifty postmenopausal and 50 menstruating females aged 45-55 years who were nondiabetic and nonobese and were low risk according to FRS were selected as cases and controls, respectively. All cases and controls were age-matched. The diameter of the brachial artery and the blood flow in it was measured at rest. Ischemia was produced and released after 5 min. The maximum blood flow velocity diameter of the brachial artery was measured. After 10 min of reactive hyperemia, 400 µg of sublingual nitrate was given, and vasodilatation mediated by nitroglycerine was subsequently measured. RESULTS: Menopause did not have any significant effect on the endothelial dysfunction as measured by the brachial artery flow-mediated dilatation (P = 0.74) but did influence vascular smooth muscle as measured by nitroglycerine-mediated dilatation (P = 0.028). A significant correlation was found between flow-mediated dilatation with FRS helps us conclude that flow-mediated dilation is a reliable tool to estimate the cardiovascular risk (P < 0.001). A strong correlation was found between nitroglycerine-mediated dilatation and flow-mediated dilatation, demonstrating that both endothelial dysfunction and vascular smooth muscle are interrelated (P < 0.001). CONCLUSION: Menopause did not affect endothelial function, but it has a significant effect on vascular smooth muscle function. To know the effect of longer duration of menopause on vascular function in elderly women further studies with large number of postmenopausal women of different duration of menopause, may be needed.

ASSESSMENT OF ENDOTHELIAL DYSFUNCTION IN PREGNANT WOMEN WITH OBESITY AND PREECLAMPSIA.

OBJECTIVE: The aim: To assess the values of endothelial vascular growth factor (VEGF) in blood serum and circulating endothelial microparticles CD32+CD40+ in the peripheral blood of pregnant women depending on the severity of obesity and presence of preeclampsia. PATIENTS AND METHODS: Materials and methods: the study included 122 pregnant women divided into groups in accordance with their height and weight parameters and presence of preeclampsia. We studied the serum VEGF concentration by enzyme-linked immunosorbent assay, carried out the count of CD32+CD40+ circulating endothelial microparticles in the peripheral blood by using flow cytometry. RESULTS: Results: It has been found out the serum VEGF concentration in pregnant women with obesity decreases with rising level of obesity and the preeclampsia manifestation. In contrast to the decrease in this marker, there is an increase in the number of circulating endothelial microparticles CD32+CD40+ in the peripheral blood of pregnant women with obesity and preeclampsia. This pattern of these indicators points out the presence of endothelial dysfunction, which may contribute to occurrence of preeclampsia in pregnant women with concomitant obesity. CONCLUSION: Conclusions: The indicators of VEGF concentration and the count of circulating endothelial microparticles CD32+CD40+ in the blood serum can serve as reliable markers for evaluating the severity of endothelial dysfunction in pregnant women with concomitant obesity and preeclampsia.

Non-Invasive Assessment of Endothelial Dysfunction in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is characterised by an increased pressure in the pulmonary arterial circulation, resulting in the elevation of pulmonary vascular resistance. Pulmonary endothelial dysfunction and inflammation, triggered by shear stress and hypoxia, constitute the hallmarks of pulmonary vasculopathy by promoting endothelial and smooth muscle cells proliferation, vasoconstriction, and thrombosis. While research was predominantly focused on pulmonary vasculature, the investigation of peripheral endothelial damage in different vascular beds has attracted the interest over the last years. As a result, effective non-invasive methods that can assess the endothelial function and the architectural integrity have been utilized for the evaluation of pulmonary and peripheral vasculature. Non-invasive plethysmography, pulmonary flow reserve, nailfold videocapillaroscopy, near-infrared spectroscopy, and imaging techniques such as magnetic resonance angiography and perfusion imaging coupled by a number of biomarkers can be used for the assessment of peripheral vascular function in PAH individuals. In this review, we summarise and critically approach the current evidence of more systemic derangement of vascular function in PAH defined by novel, non-invasive methods employed for functional and morphological assessment of endothelium and microcirculation.

Assessment of the impact of HIV infection and anti-retroviral treatment on the cardiometabolic health of pregnant mothers and their offspring (ARTMOMSBABES).

BACKGROUND: The risk of cardiovascular diseases (CVDs) is becoming more prevalent in pregnant women though not much data is available for pregnant women with human immunodeficiency virus (HIV). Foetoplacental vascular endothelial dysfunction is thought to be at the origin of chronic diseases such as diabetes and obesity later on in life. Because HIV and anti-retroviral treatment (ARTs) are associated with endothelial dysfunction, children exposed in utero to these conditions may be at greater risk of developing CVDs. Despite the high prevalence of HIV in pregnant South African women, little is known about the effects of ART on the cardiovascular health of the mother and offspring. Hence, the proposed study intends to investigate how HIV/ARTs may affect the cardiovascular health of the mother and offspring at different time points during the pregnancy and up to 2 years after birth. METHODS: A longitudinal case-control study in HIV positive pregnant women on ART and HIV negative pregnant women will be conducted. All pregnant women will be assessed for cardio-metabolic risk factors and markers (lipids, anthropometric and glycaemic indies, oxidative stress), hemodynamic status (blood pressure parameters) and vascular function (arterial compliance, retinal microvasculature, uterine artery mean pulsatility index). Child health will be monitored in utero and postnatally via routine foetal health screening, placental integrity, anthropometry, blood pressure parameters, markers of oxidative stress and endothelial function in cord blood and cardiovascular epigenetic markers in urine. DISCUSSION: There is a paucity of studies in South Africa and sub-Sahara Africa as a whole that utilised a longitudinal study model to assess the effects of ARTs on vascular endothelial changes in pregnant women living with HIV and the cardiometabolic health of their offspring. This study will therefore help to monitor changes in cardiometabolic risk during pregnancy and in children exposed in utero to HIV-infection and ART use. Findings from this study will provide useful information for developing guidelines on the use of ARTs in pregnancy and management of cardiometabolic health of the offspring of HIV positive mothers.