Flow-mediated Dilation Values Research Articles

Abstract 9482: Coronary Spasm in a Patient With Argininosuccinic Aciduria

Case presentation: A 39-year-old male patient was referred for the treatment of hypertension. The patient had been treated for argininosuccinic aciduria (ASA) since eight months of age. Therapeutic drugs including, L-arginine, sodium phenylbutyrate and antiepileptic drugs had been administered. A detailed medical history taking revealed that the patient sometimes complained of chest discomfort under psychological stress. A 12-lead electrocardiogram showed abnormal q waves in lead III and aVF. Transthoracic echocardiography showed hypokinesis of left ventricular posterior wall. Endothelial function was quantified with brachial artery flow-mediated dilatation (FMD). The patient’s FMD value was 2.4% (normal cut off value 7.0%). Coronary computed tomography angiography showed no significant coronary stenosis. Cardiac magnetic resonance revealed transmural late gadolinium enhancement in the mid-ventricular level of the left ventricular posterior wall. The patient was suspected to have prior myocardial infarction. The patient was started on amlodipine and irbesartan, however, he continued to complain of chest discomfort at rest. Cardiac catheterization was performed to make a definitive diagnosis. The acetylcholine spasm provocation test revealed diffuse left and right coronary vasospasm. Transient ST-segment elevation with chest discomfort was observed. The patient was diagnosed as having coronary spastic angina. Chest discomfort was disappeared after additional administration of isosorbide mononitrate. Discussion: ASA is a genetic disorder of the urea cycle, caused by deficiency of argininosuccinate lyase (ASL). Specific laboratory findings are hyperammonemia, argininosuccinic acidemia and low plasma arginine levels. ASL is required to utilize extracellular arginine for NOS-dependent NO synthesis in endothelial cell. Reduction of ASL enzymatic activity leads to decline in NO production even if arginine is supplemented. Efficacy of NO supplementation for treatment of long-term complications in ASA patients has been reported. The precise mechanisms of coronary spasm remain to be elucidated. Our case report might support the significance of endothelial function in the pathogenesis of coronary spasm.

The prognostic role of galectin-3 and endothelial function in patients with heart failure according to left ventricular ejection fraction classification HF group

Abstract Background Heart failure (HF) is nowadays classified in HF with reduced ejection fraction (HFrEF), HF with mildly-reduced EF (HFmrEF) and HF with preserved EF (HFpEF). Endothelial dysfunction, increased arterial stiffness and galectin-3, a biomarker of myocardial fibrosis, have been linked to major adverse cardiovascular events (MACE) in patients with ischemic HF. Purpose The purpose of this prospective, follow-up study was to investigate in patients with stable ischemic HF the prognostic role of circulating galectin-3 levels, endothelial function and arterial stiffness according to left ventricular ejection fraction classification. Methods In this study we prospectively enrolled 340 patients with stable ischemic HF. Patients were categorized in HFrEF (when EF below or equal to 40%), HFmrEF (when EF is more than 40%<ef≤49%)> and below/equal to 49%) and HFpEF (when EF is more/equal to 50% along with the presence of structural or functional dysfunction and/or elevated natriuretic peptides) according to recent guidelines upon 2D echocardiographic assessment. We evaluated flow-mediated dilatation (FMD) of brachial artery as a marker of endothelial function, carotid-femoral pulse-wave velocity (PWV) as a marker of arterial stiffness and galectin-3 levels as a biomarker of fibrosis. Patients were followed-up for MACE and the primary endpoint was defined as cardiovascular death, myocardial infarction, coronary revascularization, stroke, and hospitalization due to HF. <ef≤49%)> Results Interestingly, FMD values exhibited a stepwise improvement according to LVEF (HFrEF: 4.74±2.35% vs. HFmrEF: 4.97±2.81% vs. HFpEF: 5.94±3.46%, p=0.01) which remained statistically significant after the evaluation of possible confounders including age, sex, cardiovascular risk factors and number of significantly stenosed epicardial coronary arteries (b coefficient: 0.990, 95% CI: 0.166–1.814, p=0.019). Multivessel coronary artery disease (CAD) was more frequent in the group of HFrEF (HFrEF: 56% vs. HFmrEF: 64% vs. HFpEF: 73%, p=0.049). Nevertheless, PWV did not display any association with LVEF. Patients who presented MACE exhibited worse FMD values (4.51±2.35% vs. 5.32±2.67%, p=0.02) and the highest tertile of galectin-3 was linked to more MACEs (36% vs. 5.9%, p=0.01). Conclusions FMD values have a linear improvement according to LVEF increase in patients with ischemic HF and worse values are linked to more MACEs. Higher levels of galectin-3 might be used for risk stratification of patients with ischemic HF. Funding Acknowledgement Type of funding sources: None.

Impaired endothelial glycocalyx, vascular dysfunction and myocardial deformation four months after COVID-19 infection are partially improved at twelve months

Abstract Introduction COVID-19 patients present impaired subclinical markers of cardiovascular and endothelial function. Subclinical myocardial and vascular dysfunction during COVID-19 disease have been associated with worse outcomes and higher mortality risk. Purpose We investigated the effect of COVID-19 infection on markers of endothelial, vascular and myocardial function at four and twelve months after the infection Methods We recruited 70 patients who were examined in a dedicated post-COVID-19 outpatient clinic during a scheduled follow-up visit at four and twelve months after a confirmed COVID-19 infection and 70 healthy individuals with similar clinical characteristics. At four and twelve months we measured (i) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness), (ii) flow-mediated dilatation (FMD), (iii) coronary flow reserve (CFR) by Doppler echocardiography, (iv) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (v) global left and right ventricular longitudinal strain (GLS), (vi) myocardial global work index (GWI) global constructive work (GCW), global wasted work (GWW) and the myocardial global work efficiency (GWE) and v) malondialdehyde (MDA), an oxidative stress marker. Results At four months, COVID-19 patients displayed higher values of PBR5–25 compared to control group (p<0.001) which increased at twelve months (p<0.001). FMD, PWV and cSBP values were similar between 4 and 12 months (p>0.05 for all the comparisons) and higher than those in controls (p<0.001, p=0.057, p=0.003 respectively). At four months, COVID-19 patients presented impaired CFR and LVGLS values which were improved at twelve months (p=0.002, p=0.069 respectively), though remained impaired compared to controls (p=0.003 for all the comparisons). At four months, COVID-19 patients had impaired RVGLS values which were significantly improved at twelve months (p=0.001,) and showed no statistically significant difference compared to controls (p>0.05). COVID-19 patients at four months display higher myocardial wasted work and decreased myocardial efficiency compared to controls (p=0.01, p=0.006 respectively). There was a modest improvement in GWW and GWE at twelve months,(p=0.043, p=0.001, respectively); however, these markers remained impaired compared to controls (p>0.05). At four months, MDA was higher in COVID-19 patients compared to control group and significantly decreased at twelve months (p<0.001); however, these values remain higher than in controls (p=0.002) (Table 1). Conclusions SARS-CoV-2 causes endothelial and cardiovascular dysfunction which are partially restored at twelve months after the infection. Funding Acknowledgement Type of funding sources: None.

Acute effects of COVID-19 vaccination on inflammatory, macrovasular and microvascular biomarkers

Abstract Purpose To fight the COVID-19 pandemic, messenger RNA (mRNA) vaccines were the first to be adopted by vaccination programs worldwide. We sought to investigate the short-term effect of mRNA vaccine administration on endothelial function and arterial stiffness. Methods Thirty-two participants (mean age 37±8 years, 20 men) that received the BNT162b2 mRNA COVID-19 vaccine were studied in 3 sessions in a sequence-randomized, sham-controlled, assessor-blinded, cross-over design. Primary outcome was endothelial function assessed by brachial artery flow-mediated dilatation (FMD), and secondary outcomes were aortic stiffness, evaluated with carotid-femoral pulse wave velocity (PWV), microvascular function that was estimated with hyperemic mean blood flow velocity (HMBFV) of the brachial artery, and inflammation measured by high-sensitivity C-reactive protein (hsCRP) and interleukins (hsIL-6 and hsIL-1b) in blood samples. The outcomes were assessed prior to, and at 8h, 24h post the 1st dose of vaccination, and 8h, 24h and 48h post the 2nd. Results There was an increase in hsCRP that was apparent at 24h after both the 1st dose (−0.60 [95% Confidence intervals [CI]: −1.60 to −0.20], p=0.013) and the 2nd dose (max median difference at 48h −6.60 [95% CI: −9.80 to −3.40], p<0.001) compared to sham. Similarly, interleukins also increased. The vaccine did not change PWV. FMD remained unchanged during the 1st dose but decreased significantly by 1.5% (95% CI: 0.1% to 2.9%, p=0.037) at 24h post the 2nd dose (Figure). FMD values returned towards baseline at 48h. HMBFV remained unchanged during the 1st dose but at 48h post the 2nd dose was numerically lower than the sham procedure but the difference between the 2 sessions was not statistically significant (max mean difference at 48h 8.6 [95% CI: −0.6 to 17.8], p=0.067). Conclusions Our study shows that the mRNA vaccine causes a prominent increase in inflammatory markers, especially after the 2nd dose and a transient deterioration of endothelial function at 24h that returns towards baseline at 48h. These results confirm the short-term cardiovascular safety of the vaccine. Funding Acknowledgement Type of funding sources: None.

Endothelial dysfunction in psoriatic arthritis patients: correlations between insulin resistance and disease activity.

Cardiovascular atherosclerotic comorbidities represent an important cause of morbidity and mortality in patients diagnosed with psoriatic arthritis. In both atherosclerosis and Psoriatic arthritis, inflammation plays a pivotal role. Psoriatic arthritis is considered as an independent risk factor for the development of atherosclerosis with accelerated evolution. Development of atherosclerosis is initiated by the endothelial cell dysfunction along with inflammation and insulin resistance. The main aim of the study was to evaluate the endothelial function in Psoriatic arthritis patients, and to identify if it is related to the insulin resistance and Psoriatic arthritis disease activity. In this case-control study, a group of 32 age and gender matched healthy controls was formed and compared to the group of 32 Psoriatic arthritis patients. We assessed the following parameters: Disease Activity in Psoriatic Arthritis Score, Homeostatic Model Assessment for Insulin Resistance, serum levels of the tumor necrosis factor alpha (TNFα), and the endothelial dysfunction by means of the flow-mediated dilation at brachial artery. The Student's t-test, the Pearson correlation and the ANOVA test were used to perform the statistical analysis of the data obtained; p-value <0.05 was considered as statistically significant. Compared to the patients in the control group, TNFα and Homeostatic Model Assessment for Insulin Resistance were increased (p-value <0.001), and flow-mediated dilation at brachial artery was decreased (p-value <0.001) in the disease group. In Psoriatic arthritis patients, significant correlations were found between Disease Activity in Psoriatic Arthritis Score and Homeostatic Model Assessment for Insulin Resistance (r=0.8143, p-value <0.001), and between Disease Activity in Psoriatic Arthritis Score and flow-mediated dilation at brachial artery % (r= -0.8376, p-value <0.001). Psoriatic arthritis patients treated with Methotrexate exhibited reduced values of Disease Activity in Psoriatic Arthritis Score and Homeostatic Model Assessment for Insulin Resistance and increased values of flow-mediated dilation at brachial artery, when compared with the untreated patients. Endothelial dysfunction is present in Psoriatic arthritis patients and has a significant correlation with both, the course of the disease and the insulin resistance.

Influence of endothelial function and arterial stiffness on the behavior of cervicocephalic arterial dissections: An observational study.

BackgroundThe mechanical and physiological properties of the arterial wall might affect the behavior of spontaneous cervicocephalic arterial dissections (CCAD). We aimed to determine the effects of endothelial function and arterial stiffness on the clinical characteristics and outcomes of CCAD using brachial flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (PWV).MethodsFrom a single-center database, we identified patients admitted from April 2011 to December 2021 with a diagnosis of CCAD who underwent both FMD and PWV. FMD was classified as normal and decreased according to institutional thresholds. PWV was categorized into tertiles. Comparative and multivariable analyses were performed to determine the effects of FMD and PWV values on major clinical outcomes.ResultsA total of 146 patients (age: 47 ± 11 years; men: 77.4%) were included. The main presentation was ischemic stroke in 76.7% of the patients, while 23.3% presented with headache or other symptoms. Healing of the dissection was observed in 55.8%. In multivariable analysis, Normal FMD levels (vs. decreased; adjusted OR: 4.52, 95% CI [1.95 −10.52]) were associated with spontaneous healing of the dissection. Highest PWV tertile (vs. lowest; adjusted OR: 17.05, 95% CI [3.07–94.82]) was associated with ischemic presentation. There was a higher ischemic stroke recurrence in the 3rd PWV tertile, and more frequent aneurysmal enlargement in the lowest PWV tertile, but their frequency was low, precluding multivariable analysis.ConclusionIn spontaneous CCAD, preserved endothelial function was associated with spontaneous arterial healing. Arterial stiffness is associated with ischemic presentation.

Lower brachial artery flow-mediated dilation is associated with a worse prognosis and more lung parenchymal involvement in Covid-19: Prospective observational study.

Severe acute respiratory syndrome coronavirus-2 is a highly infectious pathogenic coronavirus, which has appeared toward the end of 2019. The virus seen all over the world caused a pandemic of an acute respiratory disease named coronavirus disease 2019 (Covid-19). It has been shown that the virus that uses angiotensin-converting enzyme 2 receptors is causing endothelial dysfunction resulting in vascular inflammation and coagulopathy. It is possible to assess endothelial dysfunction by the flow-mediated dilatation (FMD) technique. Our study aimed to demonstrate the effect of endothelial dysfunction assessed using the FMD on prognosis and mortality in the patients hospitalized with the diagnosis of Covid-19.In this prospective observational study, endothelial functions of 94 patients hospitalized due to the Covid-19 in the ward or intensive care unit (ICU) were evaluated by FMD. The relationship among endothelial dysfunction and prognosis of disease, biochemical parameters, lung involvement, and mortality was investigated.We found that the FMD% values of the Covid-19 ICU patients compared to those followed up in the ward (2.66 ± 0.62 vs. 5.23 ± 1.46/P < .001) and those who died due to Covid-19 compared to those who were discharged alive (2.57 ± 0.22 vs. 4.66 ± 1.7/P < .001) were significantly lower. There were moderate negative correlation between FMD% and peak values of D-dimer (r = −0.52, P < .001), troponin (r = −0.45, P < .001), ferritin (r = −0.47, P < .001), lactate dehydrogenase (r = −0.49, P < .001), and white blood cells count (r = −0.23, P = .024). Lower FMD% was associated with higher lung parenchymal involvement (P < .001). The optimum cutoff point of FMD in predicting mortality was found to be 3.135% (sensitivity: 1, selectivity: 0.70).According to our results, lower FMD% was associated with higher lung parenchyma involvement, ICU admission, and mortality rate in Covid-19 patients. The best cutoff point for predicting mortality of FMD was 3.135%. Nevertheless, largescale, multicenter studies are needed to evaluate lower FMD values as a risk factor for mortality in Covid-19.

Effect of heat-moisture treated brown rice crackers on postprandial flow-mediated dilation in adults with mild endothelial dysfunction

BackgroundEndothelial dysfunction is an early pathophysiological feature and independent predictor of a poor prognosis in most forms of cardiovascular disease. We evaluated the effect of brown rice crackers (BR-C) on endothelial function. MethodsEffect of heat-moisture treated (HMT) -BR-C on postprandial flow-mediated dilation (FMD) in adults with mild endothelial dysfunction was compared with that of BR-C and white rice crackers (WR-C) in 12 adults with mild endothelial dysfunction (less than 7.0% of FMD) by a randomized, single-blind, three-treatment three-period crossover trial (UMIN 000034898). Since we considered that the FMD increase was associated with the treatment of HMT-BR-C, we examined the effect of three possible factors: postprandial glucose levels, polyphenol content, and polyphenol release from the food matrix. ResultsMean pre-intake baseline FMD values of HMT-BR-C, BR-C, and WR-C were 4.9%, 5.1%, and 4.9%, respectively, and those values 1 h post-intake were 6.3%, 5.1%, and 4.8%, respectively. There was no difference in intergroup comparisons of FMD using Dunnett's multiple comparison test. There was a significant increase in FMD only in HMT-BR-C in intragroup comparisons (P = 0.042 by paired-t test). In comparison with BR-C, no significant difference was noted in the postprandial glucose level nor in the content of total polyphenols and ferulic acid derivatives in HMT-BR-C. However, the 70% ethanol extracted from HMT-BR-C contained a significantly larger amount of free and bound ferulic acids than from BR-C. ConclusionHMT-BR-C intake increased the postprandial FMD response.

The Relationships Between Chocolate Consumption and Endothelial Dysfunction in Patients with Heart Failure

Dietary recommendations, in addition to medications, have recently become important in the treatment of heart failure. Our study aimed to show the positive effects of both milk chocolate and dark chocolate on heart failure through endothelial functions. Twenty patients with heart failure and reduced ejection fraction were included in the study. In this randomized, crossover study, some of the patients consumed milk chocolate and some consumed dark chocolate. We recorded the patients' 6-minute walking tests, flow- mediated dilatation values, plasma catechin, epicatechin, and N-terminal pro-brain natri- uretic peptide values before and after chocolate consumption. After 2 weeks, their chocolate consumption was changed. The same parameters were measured again. A significant decrease was observed in N-terminal pro-brain natriuretic peptide values after consumption of both milk chocolate (356 ± 54.2 and 310 ± 72.1 pg/mL; P = .007) and dark chocolate (341 ± 57 and 301 ± 60.1 pg/mL;P=.028). Flow-mediated dilation values increased after dark chocolate consumption (8.9 ± 3% and 14 ± 4.5%; P = .019). Chocolate consumption acutely decreases N-terminal pro-brain natriuretic pep- tide values in heart failure. Dark chocolate consumption also seems to improve endothelial functions by increasing flow-mediated dilation values.

Endothelial Function in Postmenopausal Women: The Possible Role of Heat Shock Protein 60 and Serum Androgens.

Background: Heat shock protein 60 (HSP60), a potentially homeostatic antigen, is involved in physiological and non-physiological conditions. Experimental data support the role of HSP60 in placental and mitochondrial steroidogenesis. Furthermore, HSP60 is translocated into the endothelial-cell plasma membrane and the extracellular space under stress conditions, promoting the atherosclerotic process. Therefore, we investigated the association between HSP60 and endothelial function in postmenopausal women, considering the possible atherogenic effect of androgenic hormones. Methods: This study included 123 healthy postmenopausal women. Exclusion criteria were treated hypertension or dyslipidaemia, menopause hormone therapy during the last 6months, and previously diagnosed peripheral vascular disease or cardiovascular disease. Fasting venous blood samples were obtained for biochemical and hormonal assessment and evaluation of HSP60. Sonographic assessment of flow-mediated dilation (FMD) occurred immediately after that in one session. Results: Univariate analysis showed that women with FMD values below median 5.12% had lower logHSP60 values (low vs. high FMD, HSP60 values: 2.01 ± 1.16ng/ml vs. 3.22 ± 1.17ng/ml, p-value = 0.031). Multivariable analysis showed that logHSP60 was associated with FMD (b-coefficient = 0.171, p-value = 0.046), adjusting for traditional cardiovascular risk factors (TRFs) and insulin levels. Further adjustment for testosterone and DHEAS rendered the result non-significant. In the multivariable analysis, FMD was associated with insulin (b-coefficient = -0.166, p-value = 0.034), testosterone (b-coefficient = -0.165, p-value = 0.034), DHEAS (b-coefficient = -0.187, p-value = 0.017), adjusting for TRFs. Discussion: The results of this study indicate that the association between androgens and endothelial function is possibly mediated by HSP60 molecules, in women with low insulin resistance and androgenicity. Further prospective studies are needed to explore the significance of our findings.

Increased epicardial adipose tissue thickness correlates with endothelial dysfunction in spondyloarthritis.

We aimed to investigate the relationship between epicardial adipose tissue (EAT) thickness, flow-mediated dilation (FMD), and carotid intima-media thickness (cIMT) in spondyloarthritis (SpA) patients compared to healthy controls. We performed a cross-sectional study including SpA patients aged ≤ 50years without traditional cardiovascular risk factors and healthy controls matched for age and gender. Baseline characteristics, laboratory data, and SpA-related parameters were recorded. All participants underwent ultrasound examination with measurement of EAT thickness, FMD, and cIMT by both an experienced cardiologist and radiologist blinded to clinical data. The relationships between the ultrasound measurements were analyzed using Spearman's correlation coefficient and Person correlation. The study included 94 subjects (47 SpA and 47 healthy controls). The sex-ratio was 2.35; the median age of patients was 36years (IQR: 28-46), and the median disease duration was 11years (IQR: 5-16). Compared to the control group, SpA patients had significantly higher values of EAT thickness (p = 0.001) and cIMT (p < 0.0001). FMD values were significantly lower in SpA patients compared to controls (p = 0.008). The univariate analysis detected a significant negative association between EAT thickness and FMD (p = 0.026; r = - 0.325), and between left cIMT and FMD (p = 0.027; r = - 0.322). No association was found between EAT thickness and cIMT. EAT thickness, FMD, and cIMT were significantly impaired in SpA patients compared with healthy controls supporting evidence of accelerated atherosclerosis in SpA. EAT thickness was correlated to endothelial dysfunction suggesting the role of EAT in predicting the early reversible stages of atherosclerosis. Key Points • Spondyloarthritis is associated with impaired subclinical atherosclerosis markers accurately increased epicardial fat and carotid intima-media thickness and endothelial dysfunction. • Increased epicardial fat thickness is correlated with impaired endothelial function in spondyloarthritis patients.

Brachial flow—mediated dilation and carotid intima—media thickness in glaucoma patients

BackgroundThe purpose of the study was to assess the ultrasound measurements of the brachial artery flow-mediated dilation (FMD) and carotid artery intima-media thickness (IMT) and their relationship in glaucoma patients.MethodsThirty-seven patients with glaucoma and thirty-one healthy controls were included in the study. All glaucoma patients and controls underwent ultrasound measurement of FMD of the brachial artery and ultrasound measurement of IMT of the carotid artery.ResultsThe mean values of brachial FMD were significantly lower among the glaucoma compared with controls (16.4 ± 10.6% vs 20.3 ± 8.5%, p = 0.034). No significant difference was found in carotid IMT (1.2 ± 0.4 vs. 1.1 ± 0.4, p = 0.3), and brachial artery diameter at rest (4.7 ± 0.6 vs. 4.9 ± 0.3, p = 0.2) between the glaucoma patients and controls. The significant difference in brachial artery diameter in hyperemia between the glaucoma patients and controls (5.5 ± 0.6 vs. 5.9 ± 0.4 p = 0.002) was found. A negative correlation among brachial FMD and carotid IMT as well as among brachial FMD and brachial artery diameter at rest was found.ConclusionsImpaired brachial FMD indicates presence of systemic vascular endothelial dysfunction in glaucoma; glaucoma patients with lower values of the brachial FMD are at increased risk of having thickened carotid IMT.

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

BackgroundCoronary 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.MethodsThis 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.ResultsIt 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.ConclusionThe 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.

Flow-mediated dilation reference values for evaluation of endothelial function and cardiovascular health.

Endothelial function is essential for cardiovascular health, and flow-mediated dilation (FMD) is an established technique to measure it. This paper aims to assess FMD values in apparently healthy individuals and provides reference values to facilitate wider clinical use. In 1,579 apparently healthy individuals (aged 18-76), fasted FMD values (data from 44 studies, 6 institutions, 22 operators) were normally distributed and inversely univariately correlated with age, body mass index, glucose, cholesterol, blood pressure, and brachial artery (BA) diameter. Significant multivariate predictors of FMD were age (-0.4%/decade), BMI (0.04%/kg/m2), smoking (-0.7%), and BA diameter (-0.44%/mm) that together explained 19% of the variability independent of operator, institution or ultrasound machine. Individuals in the high FMD tertile (>6.8%) were younger, had smaller BA diameter, lower blood pressure and cholesterol. In individuals with low- and intermediate fatal cardiovascular risk (SCORE), 26% and 53% of individuals, respectively, had FMD values in the low tertile (<5.4%). After adding data from 385 patients with stable coronary artery disease (CAD), ROC analysis (c = 0.841, P < 0.001) showed that FMD of >6.5% excluded CAD (95% sensitivity; 60% specificity) and FMD <3.1% excluded 95% healthy individuals (95% specificity, 31% sensitivity). A meta-analysis and meta-regression of 82 clinical trials (11 countries, n = 3,509) using similar FMD methodology showed that despite considerable heterogeneity (I2 = 0.97) FMD in healthy individuals was on average 6.4% (95%CI: 6.2%, 6.7%) with no significant differences between countries but a significant age-dependent decline (-0.3%/decade, R2 = 0.13). We provide an age-adapted frame of FMD reference intervals in apparently healthy individuals for use as a biomarker of cardiovascular health. As the degree of vascular endothelial function integrates environmental and genetic factors with classical CV risk factors, FMD may more comprehensively classify individuals with and without standard modifiable cardiovascular risk factors and serve as a target for cardiovascular prevention.

THE EFFECT OF COVID-19 VACCINE ON ARTERIAL FUNCTION

Objective: To fight the COVID-19 pandemic, messenger RNA (mRNA) vaccines were the first to be adopted by vaccination programs worldwide. We sought to investigate the short-term effect of mRNA vaccine administration on endothelial function and arterial stiffness. Design and method: Thirty-two participants (mean age 37 ± 8 years, 20 men) that received the BNT162b2 mRNA COVID-19 vaccine were studied in 3 sessions in a sequence-randomized, sham-controlled, assessor-blinded, cross-over design. The primary outcome was endothelial function assessed by brachial artery flow-mediated dilatation (FMD), and secondary outcomes were aortic stiffness, evaluated with carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx@75), and inflammation measured by high-sensitivity C-reactive protein (hsCRP) in blood samples. The outcomes were assessed prior to, and at 8 h, 24 h post the 1st dose of vaccination, and 8 h, 24 h, and 48 h post the 2nd. Results: There was an increase in hsCRP that was apparent at 24 h after both the 1st dose (-0.60 [95% Confidence intervals [CI]: -1.60 to -0.20], p = 0.013) and the 2nd dose (max median difference at 48 h -6.60 [95% CI: -9.80 to -3.40], p &lt; 0.001) compared to sham. The vaccine did not change PWV or AIx@75. FMD remained unchanged during the 1st dose but decreased significantly by 1.5% (95% CI: 0.1% to 2.9%, p = 0.037) at 24 h post the 2nd dose. FMD values returned towards baseline at 48 h. Conclusions: Our study shows that the mRNA vaccine causes a prominent increase in inflammatory markers, especially after the 2nd dose, and a transient deterioration of endothelial function at 24 h that returns towards baseline at 48 h. These results confirm the short-term cardiovascular safety of the vaccine.

Radial Peripapillary Capillary Plexus Perfusion and Endothelial Dysfunction in Early Post-SARS-CoV-2 Infection.

Background: Endothelial cells damage and thromboinflammation are considered key elements in the generation of organ impairment in patients with COVID-19 disease. The endothelial function is evaluated by measuring flow-mediated dilation (FMD). We aimed to analyze the association between FMD impairment and retinal vascular parameters in early post-COVID-19 patients. 00118-00199Tomography (OCT), OCT Angiography (OCTA) and slit lamp examination were performed. FMD ≤ 7% was considered as pathological. Our primary outcome was to assess potential differences in the radial peripapillary capillary plexus flow index (RPCP-FI) and RPCP density (RPCP-D) values between post-COVID-19 patients with and without FMD impairment. The associations of other retinal vascular parameters with FMD impairment were assessed as secondary endpoints. Results: FMD impairment was detected in 31 patients (37.8%). RPCP-FI (p = 0.047), age (p = 0.048) and prevalence of diabetes (p = 0.046) significantly differed in patients with FMD ≤ 7% in regression analysis. RPCP-FI was linearly correlated with FMD values (R = 0.244, p =0.027). SCT was found to be lower in patients with impaired FMD (p = 0.004), although this difference was only a trend in binary logistic regression output (p = 0.07). Conclusions: Early post-COVID-19 patients showed a higher prevalence of FMD impairment compared to the general population. Age, diabetes and RPCP-FI were independently correlated with the presence of endothelial impairment in the early post-infective period.

Flow mediated dilatation: searching high and low for a technique

Abstract Funding Acknowledgements Type of funding sources: None. Background Endothelial dysfunction has a central role in atherosclerosis physiology. Flow mediated dilatation (FMD) is a non-invasive method for determining endothelial function. Cuff occlusion of forearm for 5 minutes followed by sudden release cause hyperaemia response with increased flow rate and shear stress in brachial artery. FMD measures the ratio of arterial diameter change mediated by nitric oxide (NO) in response to this increase in shear stress. FMD was first defined in 1992 but has not gained wide clinical utility due to contradictory study results. The main reason for inconsistencies is the lack of standardized definition of FMD technique. We need more studies on different steps of FMD procedure. Purpose The optimal cuff position for FMD measurements is not precisely defined. When brachial arterial flow is disturbed by occlusion, different mediators play role in hyperaemia induced dilatation. Occlusion distal to brachial artery causes mainly NO and endothelium mediated dilatation upstream. Therefore, a forearm occlusion cuff position is proposed. Currently, there is no precise definition of the cuff position in forearm. We compared proximal and distal forearm cuff occlusion positions for FMD measurements. Methods We analysed FMD in fifty healthy volunteers (mean age 31,9 ± 9,5 years; 54 % female). The subjects underwent measurements with two different occlusion positions on the same day. The sequence of occlusion cuff position was determined with randomization. We have waited for an appropriate interval between measurements. We made sure that brachial artery has returned to its basal diameter and flow conditions before second measurement. Flow and diameter measurements were made with strict adherence to predefined timelines after cuff release. Same operator performed and recorded all FMD measurements. Results Measurements of basal diameter (p=0,97) and basal flow (p=0,53) were not different. We used random intercept mixed effects model for comparison of proximal and distal occlusion positions. This enabled interpretation of FMD results with refinement of sequence and basal diameter’s possible effects. The FMD values of proximal forearm occlusion cuff position were 2,2 % higher compared to distal position. (p=0,027) The sequence of occlusion cuff position did not have significant effect on consecutive FMD measurements. (p=0,405). Conclusions We have shown that the forearm occlusion cuff position affects FMD measurements. This effect can be responsible for inter-study differences of FMD. Further research is required for interpretation of this difference in terms of molecular mechanisms and its applicability in clinical practice.

Abstract 136: Vascular Impairment From Acute Exposure To E-cigarette Aerosol Is Rescued By Inhibition Of The Receptor For Advanced Glycation End Products (RAGE)

Introduction: E-cigarette use is known to induce vascular impairment by altering vasomotor and cellular functions of the vascular wall, but the molecular mechanism of e-cigarette-induced vascular impairment is largely unexplored. We investigated whether inhibition of RAGE prevents impairment of vasomotor function from acute e-cigarette exposure Hypothesis: Impairment of endothelial vasodilatory function requires the activation of RAGE. Methods: Anesthetized rats (n=8/group) were exposed to aerosols from flavorless tank style e-cigarettes with and without freebase nicotine (12 mg/ml) or air in a single session of 10 cycles of pulsatile 5s exposure over 5 minutes. For each exposure condition, groups received either 1 mg/kg of RAGE inhibitor FPS-ZM1 or vehicle i.p. 1 hour before exposure (i.e., total of 6 groups). Femoral artery flow-mediated dilation (FMD) was measured using micro-ultrasound before and after exposure. Results: Exposure to e-cigarette aerosol with and without nicotine impaired FMD in vehicle groups (8.3±2.7% pre-exposure vs 4.7±2.4% post-exposure, p=0.01; 9.3±4.6% pre- vs 4.8±2.7% post-, p=0.03, respectively), with no change in air control (9.7±3.2% pre- vs 9.3±3.5% post-, p=0.81). Post-exposure FMD in both aerosol groups with vehicle was lower than that in the air group with vehicle (p=0.01 for each aerosol vs air). However, FPS-ZM1 prevented the FMD impairment by aerosol exposure (with nicotine 9.1±3.5% pre- vs 8.9±2.1% post-, p=0.90; without nicotine 9.5±4.3% pre- vs 7.1±2.0% post-, p=0.17), with no change in air control (7.6±2.7% pre- vs 7.4±3.1% post-, p=0.86). Post-exposure FMD values in both aerosol groups receiving FPS-ZM1 were comparable to the air control (p=0.4 and 0.8, respectively). There were no significant difference in post-exposure FMD in the air groups receiving FPS-ZM1 or vehicle (p&gt;0.99). Conclusions: RAGE mediates e-cigarette-induced acute impairment of endothelial vasodilatory function.

Assessment of Surrogate Markers for Cardiovascular Disease in Familial Mediterranean Fever-Related Amyloidosis Patients Homozygous for M694V Mutation in MEFV Gene.

Cardiovascular disease (CVD) remains underestimated in familial Mediterranean fever-associated AA amyloidosis (FMF-AA). We aimed to compare early markers of endothelial dysfunction and atherosclerosis in FMF-AA with a homozygous M694V mutation (Group 1 = 76 patients) in the Mediterranean fever (MEFV) gene and in patients with other genotypes (Group 2 = 93 patients). Measures of increased risk for future CVD events and endothelial dysfunction, including flow-mediated dilatation (FMD), pentraxin-3 (PTX3), and carotid intima-media thickness (cIMT), and fibroblast growth factor 23 (FGF23) as a marker of atherosclerotic vascular disease were compared between groups. The frequency of clinical FMF manifestations did not differ between the two groups apart from arthritis (76.3% in Group 1 and 59.1% in Group 2, p < 0.05). FMD was significantly lower in Group 1 when compared with Group 2 (MD [95% CI]: −0.6 [(−0.89)–(−0.31)]). cIMT, FGF23, and PTX3 levels were higher in Group 1 (cIMT MD [95% CI]: 0.12 [0.08–0.16]; FGF23 MD [95% CI]: 12.8 [5.9–19.6]; PTX3 MD [95% CI]: 13.3 [8.9–17.5]). In patients with FMF-AA, M694V homozygosity is associated with lower FMD values and higher cIMT, FGF23, and PTX3 levels, suggesting increased CVD risk profiles. These data suggest that a genotype–phenotype association exists in terms of endothelial dysfunction and atherosclerosis in patients with FMF-AA.

Post-Bariatric Hypoglycemia Is Associated with Endothelial Dysfunction and Increased Oxidative Stress.

Post-bariatric hypoglycemia (PBH) is a potentially serious complication that may occur after bariatric surgery. Recurrent hypoglycemia may exert detrimental effects on vascular function. The aim of the present study was to evaluate endothelial function and oxygen reactive compounds in patients who experience PBH compared with controls. We performed a cross-sectional study on subjects with PBH (HYPO) and those without (NO-HYPO), detected by seven-day continuous glucose monitoring (CGM) performed at least twelve months after bariatric surgery. We enrolled 28 post-bariatric subjects (17.9% males, mean age 40.6 ± 10.7 years), with 18 in the HYPO group and 10 in the NO-HYPO group. In the two groups, we measured brachial artery flow-mediated dilation (FMD), oxidized low-density lipoproteins (oxLDL) and reactive oxygen metabolites (D-ROMs). The HYPO group had significantly lower FMD values than the NO-HYPO group (3.8% ± 3.0 vs. 10.5% ± 2.0, p < 0.001). A significant correlation was found between FMD and the time spent in hypoglycemia (rho = −0.648, p < 0.001), the number of hypoglycemic events (rho = −0.664, p < 0.001) and the mean glucose nadir (rho = 0.532, p = 0.004). The HYPO group showed significantly higher levels of D-ROMs (416.2 ± 88.7 UCARR vs. 305.5 ± 56.3 UCARR, p < 0.001) and oxLDLs (770.5 ± 49.7 µEq/L vs. 725.1 ± 51.6 µEq/L, p = 0.035) compared to the NO-HYPO group. In the multiple linear regression analysis, hypoglycemia independently predicted FMD values (β = −0.781, p < 0.001), D-ROMs (β = 0.548, p = 0.023) and oxLDL levels (β = 0.409, p = 0.031). PBH is associated with impaired endothelial function accompanied by increased oxidative stress.