Flow-mediated Dilation Research Articles

Limb-Specific Comparison of Flow-Mediated Dilation in Abdominal Obese Pre-menopausal Women

Abstract Purpose Normal aging can lead to arterial wall stiffening and development of atherosclerosis; however, the effects of overweight conditions can expedite the dysfunction of arterial health. In an earlier study, we identified in a group of abdominal obese pre-menopausal woman that during menses, these women had decreased vascular conductance of the brachial artery during dynamic hand-grip exercise. Endothelial function in abdominal obese (AO) premenopausal women could be associated with being highly sedentary which attenuates dilatory responses to FMD of both upper and lower limb vascular function. We hypothesized that the AO women would exhibit limb-specific differences in artery dilation with reduced dilation in the popliteal artery as compared to the brachial artery. Methods Artery dilatory responses in the brachial and popliteal arteries were assessed using flow-mediated dilation (FMD) in age-matched sedentary controls and AO groups during menses. Results Significant differences were found between groups including % BF, BMI, weight, waist to hip ratio, fasting blood glucose, and oxLDL. A between-group comparison revealed significantly lower percent dilation of the popliteal artery in AO participants compared to controls (p < 0.05) not present in the brachial arteries. Our results also indicate a difference in the time-to-peak (TP) of dilation between the control (33.38 ± 3.232) and AO (62.104 ± 5.813) groups (p < 0.01). Following FMD correction with shear rate as the covariate, significant differences in FMD between the brachial and popliteal artery were abolished. Conclusion We conclude that young, AO women show a limb-specific difference in dilation of the upper and lower extremities when compared to controls. Thus, reductions in FMD of the popliteal artery could be due to impaired dilation of the downstream resistance vasculature preventing increases in shear within the leg conduit arteries not as significantly in the arms.

Impact of nonsurgical periodontal treatment on arterial stiffness outcomes related to endothelial dysfunction: A systematic review and meta-analysis.

To assess the available evidence on whether nonsurgical periodontal treatment (NSPT) improves arterial stiffness outcomes in patients with periodontitis (PD). Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and population, intervention, comparison, outcomes, and study design (PICOS) question, electronic databases were screened for clinical interventional studies addressing the impact of NSPT on pulse wave velocity (PWV), carotid intima-media thickness (CIMT), and flow-mediated dilatation (FMD) outcomes in PD patients. Furthermore, the research strategy was implemented using a hand search. Studies were selected, and data were extracted by two independent reviewers. Random effects models were applied to perform a meta-analysis, and methodological index for nonrandomized studies (MINORS) and Cochrane Rob2 tools were used to assess the risk of bias. Fifteen articles were finally included for qualitative synthesis. Among them, eight single-arm cohort studies met the final inclusion criteria for meta-analysis. The Rob2 analysis evidenced that one randomized clinical trial (RCT) had a low risk, three RCTs raised some concerns, and three RCTs had a high risk of bias, while the MINORS scores ranged from 9 to 14. The meta-analysis showed that NSPT significantly impacted FMD (p<0.001) and CIMT (p=0.004), while changes in PWV were not statistically significant. However, there was high heterogeneity among studies (I2=78% for FMD and I2=62% for CIMT). Despite some beneficial effects on FMD and CIMT, due to study limitations, high heterogeneity, and risk of bias, it cannot be concluded that NSPT is effective in improving arterial stiffness. Therefore, further studies are necessary to achieve high-quality evidence on the effect of NSPT on arterial stiffness outcomes in PD patients. PROSPERO ID CRD42024501399. Periodontitis (PD) has been associated with alterations in arterial stiffness outcomes related to early endothelial dysfunction. Based on noninterventional studies, this meta-analysis indicates that nonsurgical periodontal treatment (NSPT) may reduce cardiovascular disease risk in patients with PD. The moderate evidence derived from the studies that were finally included showed that NSPT had beneficial effects on flow-mediated dilatation and carotid intima-media thickness, while this trend was not observed for pulse wave velocity. Moreover, the findings of the present meta-analysis were characterized by high heterogeneity and risk of bias and were derived from uncontrolled clinical trials or randomized clinical trials with limitations. Therefore, more studies with standardized protocols and homogeneous arterial stiffness outcomes are needed to elevate the quality of the present evidence.

The Hidden Dangers: E-Cigarettes, Heated Tobacco, and Their Impact on Oxidative Stress and Atherosclerosis—A Systematic Review and Narrative Synthesis of the Evidence

Electronic cigarettes and heated tobacco products have seen significant growth in sales and usage in recent years. Initially promoted as potentially less harmful alternatives to traditional tobacco, recent scientific evidence has raised serious concerns about the risks they pose, particularly in relation to atherosclerosis. While atherosclerosis has long been associated with conventional tobacco smoking, emerging research suggests that electronic cigarettes and heated tobacco may also contribute to the development of this condition and related cardiovascular complications. In a narrative review, we examined the potential effects of heated tobacco products and electronic cigarettes on oxidative stress and atherosclerosis. Several studies have shown that e-cigarettes and heated tobacco increase oxidative stress through the activation of enzymes such as NADPH oxidase. One of the primary effects of these products is their pro-thrombotic and pro-atherosclerotic impact on endothelial cells and platelets, which promotes inflammatory processes within the arteries. Furthermore, the chemicals found in electronic cigarette liquids may exacerbate inflammation and cause endothelial dysfunction. Furthermore, through a systematic review, we analyzed the effects of chronic exposure to electronic and heated tobacco cigarettes on endothelial function, as assessed by brachial flow-mediated dilation (FMD). Although electronic cigarettes and heated tobacco cigarettes are often perceived as safer alternatives to traditional smoking, they could still present risks to cardiovascular health. It is essential to raise public awareness about the potential dangers associated with these products and implement protective measures, particularly for young people.

Effects of Mediterranean Diet on Endothelial Reactivity in Individuals with High Cardiometabolic Risk: A Randomized Controlled Parallel-Group Preliminary Trial

Background: Endothelial dysfunction is recognized as an early modification involved in the pathogenesis of vascular diseases. Evidence suggests that the Mediterranean Diet (MD) is associated with endothelial function improvement and, in turn, plays an important role in atherosclerosis development and progression. Objectives: To evaluate both acute and sustained effects of the MD on endothelial function in patients with high cardiometabolic risk. Methods: A total of 25 subjects were randomly assigned to either the MD group or the Control Diet (CD) group according to a single-blind, parallel-group study design. Endothelial function was evaluated through non-invasive flow-mediated dilation (FMD) measurements at baseline (T0) and after 8 weeks (Tw8) of the MD or CD intervention, under both 12 h fast condition (fasting) and 2 h post-meal resembling the assigned diet (2 h). Assessments were conducted by a blinded sonographer. Results: FMD at T0-fasting was similar between MD and CD groups (6.11% ± 0.67 vs. 7.90% ± 1.65; p = 0.266). A significant difference in FMD between MD and CD groups was observed at T0-2h (12.14% ± 1.93 vs. 4.01% ± 1.03; p = 0.004), T8w-fasting (9.76% ± 1.18 vs. 5.03% ± 0.89; p = 0.008), and T8w-2h (8.99% ± 1.22 vs. 3.86% ± 0.52; p = 0.003). Oral glucose insulin sensitivity (OGIS) at T0 correlated with FMD percent changes from T0-fasting to T0-2h (r = 0.414, p = 0.044). After adjusting for age, gender, and OGIS, MD was an independent predictor of percent changes in FMD from T0-fasting to T0-2h (β: −0.582, p = 0.003), from T0-fasting to T8w-fasting (β: −0.498, p = 0.013), and from T0-fasting to T8w-2h (β: −0.479, p = 0.018). Conclusions: Adherence to the MD may improve endothelial function in both the short- and medium-term among patients at high cardiometabolic risk.

Abstract 4136796: The effect of replacing typical snacks with pecans on vascular health and diet quality: a randomized controlled trial

Background: Poor diet quality accounts for approximately half of all deaths from cardiometabolic diseases. Food pattern modelling using nationally representative U.S. data suggests that replacing typical snacks consumed with tree nuts will improve diet quality. However, few clinical trials have assessed the potential for tree nuts to improve diet quality. Pecans are rich in polyphenols, which may improve endothelial and vascular function. This study aimed to examine how substitution of usual snack foods with 2 oz/day of pecans affects flow mediated dilation (FMD), carotid-femoral pulse wave velocity (cf-PWV), blood pressure and diet quality after 12 weeks in individuals at increased risk for cardiometabolic disease. Hypothesis: Intake of 2 oz/day of pecans in place of habitually consumed snacks will improve vascular health and diet quality compared to habitual intake. Methods: In this single-blind RCT, adults (46 ± 13 years, 29.8 ± 3.7 kg/m 2 ) with ≥1 criterion for metabolic syndrome who were free from cardiovascular disease, type 2 diabetes and other chronic diseases were included. The experimental group was provided with 2 oz/day of pre-portioned raw, unsalted pecans (~392 kcal) and instructed to replace the snacks they currently consume with the provided pecans. The control group was instructed to continue their usual diet. FMD (primary outcome), cf-PWV, brachial and central blood pressure were measured at baseline and following the intervention period (~12 weeks). At three timepoints (baseline, week 6, and week 12) during the study, participants completed three 24-hour recalls (total 9 recalls). The Healthy Eating Index-2020 (HEI-2020) was calculated to assess diet quality. Results: A total of 138 (69 per group) participants were randomized. No between-group difference in FMD, cf-PWV, or blood pressure was observed. The HEI-2020 was 11.1 points higher (95% CI 5.1, 17.2) in the pecan group compared to the usual diet group at week 12. The following HEI-2020 components were improved in the pecan group vs. the usual diet group: total protein foods (0.5 points [95% CI 0.1, 1.0]), seafood and plant proteins (2.5 points [95% CI 1.6, 3.4]), fatty acids (4.1 points [ 95% CI 2.6, 5.5]), and sodium (1.8 points [95% CI 0.3, 3.2]). Conclusion: Replacement of usual snacks with 2 oz of pecans improved adherence to the Dietary Guidelines for Americans but did not improve endothelial function, blood pressure, or arterial stiffening.

Abstract 4134277: Impairment of Vascular Endothelial Function by Inhalation of Smoke or Aerosol from Tobacco and Marijuana Products is Dependent on Vagus Nerve Input from the Airway

Background: Smoke or vaporizer aerosol from different tobacco or marijuana products can cause vascular endothelial dysfunction in humans and rodents. Mechanisms of acute smoke-induced endothelial dysfunction are complex and remain ambiguous. We reported that endothelial functional impairment by tobacco smoke is dependent on intact vagus nerves, leading us to hypothesize that endothelial function impaired by smoke/aerosol from tobacco or marijuana relies on vagal input from the airway. Methods: We used Sprague-Dawley rats at 10-12 weeks of age (n=8/group; 4M+4F). Rats were anesthetized by ketamine/xylazine and exposed to one session of exposure to smoke/aerosol of tobacco (Marlboro Red) or marijuana (~10% THC) cigarettes, e-cigarettes (JUUL), or IQOS (American HeatSticks). Exposure was pulsatile (10 cycles of 5s 2x/min for 5 min via nosecone). Endothelial function was assessed as flow-mediated dilation (FMD) in the femoral artery pre- (baseline) and post-exposure. Surgical bilateral cervical vagotomy was performed in the anesthetized rats post-baseline FMD (before exposure). Sham surgical procedures were carried out without severing vagus nerves. We used paired Student t tests to compare FMD values in each group pre- and post-exposure. Significance was P &lt;.05. Results: FMD was decreased from pre- to post-exposure in all exposed sham groups as expected, whereas the impairment of FMD by smoke/aerosol exposure was completely abrogated in all vagotomized groups (Figure), with no apparent effect of sex. The pre- vs. post-exposure FMD values (mean±SD) in exposed sham groups were 16.0±3.0% vs. 6.7±3.1% for tobacco cigarettes, 13.1±2.3% vs. 5.0±2.3% for JUUL, 14.3±3.0% vs. 6.0±2.2% for IQOS, and 16.2±4.9% vs. 7.1±3.6% for marijuana. For exposed vagotomized groups, pre- vs. post-exposure FMD values were 13.3±3.7% vs. 12.6±3.7% for tobacco cigarettes, 12.8±2.6% vs. 13.0±3.2% for JUUL, 13.9±2.2% vs. 13.3±2.7% for IQOS, and 14.4±4.2% vs. 15.1±5.0% for marijuana. Heart rate was increased and respiratory rate was decreased in vagotomized groups as expected. Conclusions: Inhaling smoke or aerosol causes vascular endothelial impairment via a common mechanism involving vagal stimulation from the airway.

Abstract 4137933: High ABSI is associated with elevated risk of cardiovascular events

Background: A Body Shape Index (ABSI) has been reported to have associations with cardiovascular risk factors. However, there is no information on the association between ABSI and incidence of cardiovascular events. Methods: We investigated the associations between ABSI and first major cardiovascular events (death from cardiovascular disease, nonfatal acute coronary syndrome, and nonfatal stroke) in 1857 subjects from the database of Flow-Mediated Dilation Japan registry and from Hiroshima University Vascular Function registry. Results: The areas under the curves of ABSI to predict the first major cardiovascular events were 0.672 (95% confidence interval [CI], 0.568-0.761) in men and 0.749 (95% CI, 0.624-0.842) in women. The subjects were divided into two groups based on the cutoff value of ABSI for predicting first major cardiovascular events: a low ABSI group (&lt;0.0822 in men and &lt;0.0814 in women) and a high ABSI group (≥0.0822 in men and ≥0.0814 in women). During a median follow-up period of 41.6 months, 56 subjects died (23 from cardiovascular causes), 16 had nonfatal acute coronary syndrome, and 14 had nonfatal stroke. The Kaplan-Meier curves for first major cardiovascular events were significantly different between the two groups (men, P&lt;0.001; women, P&lt;0.001). Multivariate analysis revealed that high ABSI remained an independent predictor of first major cardiovascular events (men: hazard ratio, 2.33; 95% CI, 1.07 to 5.06; P=0.033; women: hazard ratio, 8.33; 95% CI, 1.06 to 65.49; P=0.044). Conclusions: High ABSI is independently associated with incidence of cardiovascular events. ABSI calculation should be performed for evaluation of risk of cardiovascular events.

A Comprehensive Review of Clinical Studies Applying Flow-Mediated Dilation

Flow-mediated dilation (FMD) is a noninvasive method to evaluate vascular endothelial function, which manifests the vascular inflammatory response, cell proliferation, and autoregulation. Since FMD is noninvasive and assesses commonly in the brachial artery by ultrasound, compared to other invasive methods such as optical coherence tomography (OCT) and intravascular ultrasound (IVUS), it is widely used to evaluate endothelial function and allows serial assessment. In this review, we present the currently accepted mechanisms and methods of FMD measurement with the studies applied in the current clinical practice using FMD. After all, the association with cardiovascular diseases is of substance, and so we introduce clinical studies of FMD related to cardiovascular disease such as diabetes, hyperlipidemia, chronic kidney disease, coronary artery disease, and peripheral vascular disease. In addition, studies related to pregnancy and COVID-19 were also inspected. Yet, endothelial examination is not endorsed as a cardiovascular prevention measure, for the lack of a clear standardized value methodology. Still, many studies recommend practicable FMD and would be a better prognostic value in the cardiovascular prognosis in future clinical research.

Hemoglobin is associated with hypertension-mediated cardiovascular damages in hypertensive patients with high-altitude polycythemia.

High-altitude polycythemia (HAPC) is a pathological state resulting from maladaptation to prolonged high-altitude exposure, posing significant risks to the cardiovascular health of highlanders. However, its influence on hypertension-mediated organ damages (HMODs) in hypertensive individuals remains unclear. We recruited hypertensive patients residing at altitudes above 2500m for over 3years. A case-control matching was conducted in a 1:1 ratio between hypertensive patients with and without HAPC, based on gender and age. Echocardiography, carotid artery ultrasound, and brachial flow-mediated dilation (FMD) were measured as HMODs. A total of 88 hypertensive patients were included in the analysis, with 44 with HAPC and 44 without HAPC. Patients with HAPC showed significantly higher hemoglobin (HGB) levels (217.82 ± 17.34 vs. 160.16 ± 13.25, P<0.001), a larger left atrium (LA) diameter (35.36 ± 4.25 vs. 33.09 ± 3.55, P = 0.008), and a higher proportion of impaired FMD (95.45% vs. 79.55%, P = 0.049) compared to those without HAPC. No significant differences were found between the two groups in diastolic function parameters, left ventricular mass index (LVMI), relative wall thickness (RWT), or intima-media thickness (IMT). After adjusting for age, gender, and other confounding factors, HGB remained significantly associated with LA diameter (β = 0.034, P = 0.023) and impaired FMD (OR = 1.034, 95% CI 1.001-1.069). After matching for age and gender, hypertensive patients with HAPC exhibited a significantly larger LA diameter and a higher prevalence of impaired FMD compared to those without HAPC. Additionally, HGB was identified as an independent risk factor for both increased LA diameter and impaired FMD in hypertensive patients with HAPC.

Endothelial dysfunction in prediabetes and diabetes mellitus in patients with normal coronary arteries

BackgroundDiabetes mellitus (DM) is a global health issue associated with increased cardiovascular disease risk. Endothelial dysfunction is a known precursor to atherosclerosis and cardiovascular disease, and its role in the pathogenesis of DM complications is well-documented. There is limited information in the evaluation of endothelial function in prediabetic patients using flow-mediated dilation (FMD), and studies have not excluded patients with known atherosclerosis or coronary artery disease. Thus, in this study, we aimed to evaluate the endothelial functions using FMD from the brachial artery of DM and prediabetes patients who had normal coronary arteries.MethodsThis study included 73 participants: 25 with DM, 25 with prediabetes, and 23 normoglycemic controls, all with normal coronary arteries on angiography. FMD measurements were conducted following established protocols, and statistical analysis was performed using standard methods to compare FMD levels among groups.ResultsThe groups were comparable in clinical and demographic characteristics, except for fasting plasma glucose levels. Significant differences in FMD levels were observed: 10.1% in the DM group, 16.5% in the prediabetes group, and 14.8% in the control group (P = 0.004). Diabetic patients had significantly lower FMD levels than both prediabetic and normoglycemic individuals. No significant difference in FMD was found between prediabetic and control groups.ConclusionsDiabetic patients exhibited significant endothelial dysfunction compared to normoglycemic individuals, while prediabetic patients did not show similar dysfunction. These findings suggest a window of opportunity in the prediabetic stage for early intervention to prevent advanced endothelial dysfunction.Trial registration numberISRCTN Registry ISRCTN15351014. Registry date: 23/09/2024. Retrospectively registered.

Exercise in Pediatric COVID-19: A Randomized Controlled Trial.

Purpose: This study assessed the impact of a 12-week, home-based exercise training (HBET) program on health-related quality of life (HRQOL, primary outcome), cardiovascular and metabolic parameters in pediatric COVID-19 patients.Methods: In this single-center, randomized controlled trial conducted in Sao Paulo (Brazil) from October 2020 to January 2022, 32 patients (mean age 12 ± 3.3 years; median 4 months [range: 0.7-6.6] between COVID-19 diagnosis [n = 25 mild, n = 4 moderate, n = 3 severe illness] and study entry) from a tertiary hospital were randomly assigned to either HBET or standard of care (CONTROL) in a 2:1 ratio. The HBET group underwent supervised and unsupervised sessions 3 times/week for 12 weeks emphasizing aerobic and bodyweight exercises and the CONTROL group received standard care which included general advice for a healthy lifestyle with no prescribed exercise intervention. HRQOL (Pediatric Quality of Life Inventory [PedsQL], cardiopulmonary exercise test (CPET), brachial flow-mediated dilation (b-FMD) and echocardiography assessments were conducted in both groups. Statistical analysis was performed using an intention-to-treat approach (ITT) for the primary analysis and complete-case (per-protocol) as sensitivity analysis and significance was set at P ≤ 0.05 (P ≤ 0.10 were considered as trend).Results: There was no difference in HRQOL between groups. Intention-to-treat analysis showed a trend toward increased VO2 at anaerobic threshold at post-intervention for the HBET group. Additionally, a sensitivity analysis showed significant changes in peak HR, HRR1min, RER and chronotropic response and tendency towards significance in VE/MVV and chronotropic response for the HBET group. No other between-group differences were detected for CPET, b-FMD and echocardiography variables (all p > 0.05).Conclusions: In this RCT, a 12-week HBET intervention did not impact HRQOL in pediatric COVID-19 patients. However, HBET led to greater improvements in VO2 VAT, heart rate peak and one-minute recovery and in chronotropic response with no changes in other cardiovascular parameters. Further studies are needed to explore the effects of exercise on the recovery of pediatric COVID-19 patients with persistent COVID-19 symptoms.

Comparison of high-intensity interval training and moderate-intensity continuous training on cardiopulmonary function, cardiac autonomic function and vascular function in adolescent boys with obesity: A randomized controlled trial.

Adolescent obesity can impair cardiopulmonary function, vascular elasticity, endothelial function, and vago-sympathetic balance. While moderate-intensity continuous training (MICT) benefits cardiovascular health in obese adolescents, the effects of high-intensity interval training (HIIT) are less understood. We hypothesize that HIIT may be more effective than MICT in improving VO2peak, vascular elasticity, endothelial function, and vago-sympathetic balance in obese adolescent boys. Forty four participants were randomly assigned to the HIIT (10×1-min at 85%-95% peak HR, intersperse with 2-min active recovery at 60%-70% peak HR) or MICT (35min at 65%-75% peak HR) for an 8-week program. The primary outcome measured was the change in VO2peak with secondary outcomes including brachial-ankle pulse wave velocity (baPWV), flow-mediated dilation (FMD), and heart rate variability (HRV). Forty four adolescent boys with obesity (age, 14±1years old, body mass index, 31.6±1.3kg/m2) were enrolled and 43 (97.73%) completed the 8-week exercise. No significant difference of VO2peak was found between the HIIT and MICT group (p=0.243). There was no significant difference of baPWV between the groups (p=0.789). Change in FMD% was significantly higher in the HIIT group compared to the MICT group (p<0.001). The Change in HRV-high frequency (HRV-HF; p=0.009) and HRV-low frequency/high frequency (HRV-LF/HF; p=0.035) was significantly higher in the HIIT group compared to the MICT group. Among adolescent boys with obesity, 8-week HIIT and MICT had similar effects on improving VO2peak. HIIT may be superior to MICT to improve endothelial function and vago-sympathetic balance.

Characterizing vascular and hormonal changes in women across the life span: a cross-sectional analysis.

Vascular dysfunction, marked by lower endothelial function and increased aortic stiffness, is a nontraditional risk factor that precedes the development of cardiovascular disease (CVD). However, the age at which these changes in vascular function occur in women and the degree to which reproductive hormones mediate these changes has not been characterized. Women free from major disease were enrolled across the adult life span (aged 18-70 yr, n = 140). Endothelial function was assessed as flow-mediated dilation (FMD) of the brachial artery during reactive hyperemia using duplex ultrasound and expressed as percent dilation. Aortic stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). Blood samples were obtained to quantify reproductive hormone concentration. Regression models determined age-related breakpoints and mediating factors between age and vascular outcomes. FMD declined with age with a breakpoint and steeper decline occurring at 47 yr of age. Thereafter, age was independently associated with lower FMD (B = -0.13, P < 0.001). cfPWV was relatively stable until a breakpoint at age 48, and age was independently associated with higher cfPWV thereafter (B = 0.10, P < 0.001). Path analysis revealed that the association between age and FMD was partially mediated by follicle-stimulating hormone (abind = 0.051, P = 0.01) and progesterone (abind = 0.513, P < 0.001) but not estradiol (abind = -0.004, P = 0.08). No mediation was present for cfPWV. Age was associated with endothelial dysfunction and aortic stiffness in women beginning at 47 and 48 yr old, respectively, 3 to 4 yr before the average age of menopause. The association between age and endothelial dysfunction was explained in part by elevations in follicle-stimulating hormone and progesterone, but not declining estradiol.NEW & NOTEWORTHY We demonstrate that the age at which endothelial function declines and aortic stiffness increases in healthy women is 47 and 48, respectively. The inflection point in flow-mediated dilation (FMD) is 6 yr earlier than previously reported, and the association between age and FMD was mediated by follicle-stimulating hormone (FSH) and progesterone (P4) but not estradiol (E2).

Reduced microvascular flow-mediated dilation in Syrian hamsters lacking d-sarcoglycan is caused by increased oxidative stress.

d-sarcoglycan mutation reduces mechanotransduction and induces dilated cardiomyopathy with aging. We hypothesized that in young hamsters with d-sarcoglycan mutation, which do not show cardiomyopathy, flow mechanotransduction might be affected in resistance arteries as the control of local blood flow. Flow-mediated-dilation (FMD) was measured in isolated mesenteric resistance arteries, using 3-months old hamsters carrying a mutation in the d-sarcoglycan gene (CH-147) and their control littermates. The FMD was significantly reduced in the CHF-147 group. Nevertheless, passive arterial diameter, vascular structure and endothelium-independent dilation to sodium nitroprusside were not modified. Contraction induced by KCl was not modified, whereas contraction due to phenylephrine was increased. The basal NO production and total eNOS expression levels were not altered. Nevertheless, eNOS phosphorylation, FAKs and RhoA expression were reduced in CH-147. In contrast, p47phox, COX2, iNOS and reactive oxygen species levels were higher in the endothelium of CHF-147 hamsters. Reducing ROS levels using the superoxide dismutase analog Tempol significantly restored the flow-mediated dilation (FMD) levels in CHF-147 hamsters. However, treatment with the COX-2 inhibitor NS-398 showed a non-significant improvement in FMD.

Improved vascular health linked to increased physical activity levels and reduced sedentary behavior in rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by deteriorated vascular health and increased cardiovascular risk. Physical activity (PA) is recommended for cardiovascular management in RA, but evidence on the associations between objectively-measured PA and vascular health markers in RA is limited. In this cross-sectional study, eighty-two post-menopausal women with RA (62±7 years) undertook ultrasound assessments of vascular function and structure, including brachial and superficial femoral artery (BA and SFA) flow-mediated dilation; baseline and post-hyperemia peak diameters; and carotid intima-media thickness. Participants also performed a 7-day accelerometer-based assessment of PA and sedentary behavior (SB). Fitted regression models controlled for age, body mass index and disease activity were conducted to examine associations between vascular and PA outcomes. Regression analyses revealed that prolonged SB (bouts>60min) and total sedentary time were inversely associated with both baseline and peak BA diameters, with each additional hour of SB resulting in decreases of 0.08-0.1mm in these diameters (p≤0.01). Total sedentary time also showed similar negative associations with peak SFA diameters (β=-0.14[-0.24-0.05], p<0.01). Conversely, light-intensity PA and stepping time were positively associated with both baseline and peak BA diameters, with each additional hour increasing these diameters by 0.10-0.24mm (p≤0.02). Finally, standing time was positively associated with SFA peak diameter (β=0.11[0.01-0.20], p=0.02). No associations were found between moderate-to-vigorous PA and vascular outcomes. In conclusion, in patients with RA, SB was negatively, while light PA was positively, associated with BA and SFA diameters. These findings suggest that reducing SB and increasing PA, even at light intensities, may improve vascular health in RA.

Ultrasound assessment of endothelial dysfunction in Egyptian migraine patients

BackgroundIt becomes clearer that migraine is associated with vascular risks; however, preclinical vascular involvement is not sufficiently addressed. Evidences point that migraine attacks affect vascular endothelium. The aim of this study was to investigate endothelial dysfunction in migraineurs through assessment of carotid intima-media thickness (CIMT) and flow-mediated dilatation (FMD) of the brachial artery and their correlation with clinical characteristics of migraine, headache severity, and brain magnetic resonance imaging (MRI) findings.ResultsA statistically significant difference was found between migraineurs and controls where carotid IMT was significantly higher and FMD of the brachial artery was significantly lower in migraineurs compared to controls. Carotid IMT was significantly higher and FMD was significantly lower in chronic migraine compared to episodic migraine patients. Mean IMT values were significantly higher in patients receiving ergots and in patients with subcortical white matter lesions in brain MRI. Mean FMD values were significantly lower in patients receiving ergots. There was a significant negative correlation between FMD and carotid IMT, age of the patients, disease duration, duration of headache attacks, headache frequency, and migraine disability assessment questionnaire (MIDAS) score. There were significant positive correlations between carotid IMT and age of patients, disease duration, headache frequency, MIDAS score, and number of MRI white matter lesions. For diagnosing endothelial dysfunction in migraineurs, the sensitivity and specificity of IMT were 72.5 and 70%, respectively, with a cut-off value of 0.575 mm and that of FMD were 82.5 and 90%, respectively, with a cut-off value of 20.55%.ConclusionMigraine coincides with endothelial dysfunction which promotes atherogenesis and increased risk of cerebral ischemia. FMD could be used as a potential biomarker for endothelial dysfunction in migraine. The affection of IMT and FMD is more in patients receiving ergots which may influence the selection of treatment in migraineurs in the future.

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

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

Age and sex differences in the effects of short- and long-term exposure to air pollution on endothelial dysfunction

Abstract Background Endothelial dysfunction is an integrated index of risk factor burden and a marker of atherosclerotic cardiovascular disease. Air pollution is widely acknowledged as a significant non-traditional risk factor for cardiovascular disease. However, the impact of air pollutants at varying concentrations and exposure durations on endothelial function in different populations remains unclear. Purpose We aimed to use brachial artery flow-mediated dilatation (FMD) to identify demographic differences in the effects of short- and long-term exposure to air pollution on endothelial dysfunction. Methods We measured FMD in 850 participants from October 2016 to January 2020. Location-specific concentrations of fine particulate matter &amp;lt;2.5 μm aerodynamic diameter (PM2.5), inhalable particulate matter &amp;lt;10 μm aerodynamic diameter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) measured by fixed ambient air monitoring stations were collected for short- and long-term exposure assessment. We used the moving average 7- and 14-day exposures before the date of FMD measurements to estimate the short-term exposure effects and the moving average 12-month exposures before the date of FMD measurements to estimate the long-term exposure effects. Multiple linear regression models and restricted cubic splines were used to assess the associations before and after stratified by age and sex. Results This study eventually included 828 participants [551 (66.5%) younger than 65 years and 553 (66.8%) men]. Each 10 μg/m³ increase in 12-month exposure to PM10 and NO2 was significantly and linearly associated with -0.20% (95% CI: -0.37 to -0.03) and -0.58% (95% CI: -0.99 to -0.18) changes in FMD in all participants. 12-month exposure to gaseous pollutants was also significantly but nonlinearly associated with lower FMD. 7-day exposure to Quartile 4 of SO2 was significantly associated with a 0.70% decrease in FMD compared to Quartile 1 (β = -0.70, 95% CI: -1.40 to -0.008). No relationships were observed between 7- and 14-day exposure to PM2.5, PM10, NO2, CO, and endothelial dysfunction. Although interaction effects were limited to SO2 and sex, significant associations with different air pollutants were only found in men and those younger than 65 years after stratified. Conclusions Long-term exposure to air pollution is strongly associated with decreased endothelial function, and susceptibility to air pollution varies significantly with age and sex. Further identification of different susceptible populations and proactive measures to mitigate air pollution may be beneficial in reducing the burden of cardiovascular disease.

The effect of 6-month treatment with coenzyme Q10 on endothelial, vascular and myocardial function in patients with nonalcoholic fatty liver disease

Abstract Background Patients with Non-alcoholic fatty liver disease (NAFLD) hold an increased cardiovascular risk and present impaired markers of vascular, endothelial and myocardial function. Coenzyme Q10 (CQ10) is a powerful antioxidant that enhances mitochondrial function. Patients/methods: 52 patients (52±10 years old) with NAFLD were randomized to 240 mg CQ10 (n=25) or placebo (n=27). We measured at baseline and at six months post-treatment: i) Perfused boundary Region (PBR) of the sublingual arterial microvessels (Microscan, Glycocheck), ii) Carotid femoral pulse wave velocity - PWV (Complior ALAM), iii) Flow-mediated dilation (FMD) of the brachial artery, iv) Global left ventricular longitudinal strain (GLS) by speckle tracking imaging, v) Controlled attenuation parameter (CAP) measurement (FibroScan, Echosens). Results Six months post treatment with cQ10, values of PBR (2.12±0.19 vs. 2.28±0.23 μm), PWV (9.5±2.3 vs. 10.5±2.4m/s), CAP score (278.1±50, 2 vs. 305.3±44.5dB/m), FMD (6.61±4 vs. 5.02±2.6 %) and GLS (-19.3±1.9 vs -18.2±2 %) were improved (p&amp;lt;0.05 for all comparisons). On the contrary, the patients who were treated with placebo did not show statistically significant differences in PBR, PWV, CAP score, FMD and GLS after from 6 months (p&amp;gt;0.05). In the patients who received cQ10, the percentage reduction of CAP score at 6 months was directly proportional to the percent reduction in PWV (r=0.31, p=0.045) and inversely proportional to the percentage increase in FMD (r=-0.58, p=0.014). Conclusion Six-month treatment with CoQ10 reduces liver steatosis in patients with NAFLD. CoQ10 is associated with improved endothelial, vascular and LV myocardial function in patients with NAFLD.

Regular supervised exercise training improves endothelial function, early atherosclerosis, arterial stiffness and endothelial progenitor cells in PCI patients

Abstract Backgrounds A disrupted balance between endothelial injury and repair induces endothelial dysfunction and endothelial progenitor cells (EPC) augment vascular repair. So, exercise improves endothelial function through increased numbers of EPC. We investigated the effect of training on vascular health by measuring the number of circulating EPC, and assessing flow-mediated dilation (FMD), brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (IMT) in patients with percutaneous coronary intervention (PCI). Methods Fifty-nine patients who were done PCI recently were randomized to full medical treatments or additional 3 months regular supervised exercise program (4 times a week, 1 hr a day). FMD, baPWV, carotid IMT, HOMA, hs-CRP and lipid profiles were measured and circulating CD34/KDR, CD34/CD117 and CD34/CD133 EPC were quantified by flow cytometry at baselines and after 3 months. Results Finally 23 patients joined exercise program(control, N=28). There was no significant difference of baseline characteristics and medication between 2 groups. After 3 months, FMD improved significantly in exercise group (6.62% to 11.48%) compared with control group (7.61% to 8.45%) (P&amp;lt;0.001) (fig 1). Carotid IMT reduced significantly in exercise group (0.759mm to 0.707mm) compared with control group (P=0.015) (fig 2). ba-PWV reduced significantly in exercise group (1529cmm/s to 1455 cmm/s) compared with control group (P=0.016) (fig 3). Numbers of CD34/KDR, CD34/CD117 and CD34/CD133 EPCs increased significantly after exercise compared with control group (P= 0.041, 0.011, 0.022, respectively) (fig 4). We also could see to reduce waist to hip ratio in exercise group compared with control group (P&amp;lt;0.001). Conclusions Three months regular supervised exercise improved FMD, ba-PWV, carotid IMT and waist to hip ratio in PCI patients. and it augmented numbers of circulating EPCs. Our results showed that exercise contributes to additional improvement of vascular health in PCI patients with optimal medical treatments.