Predictor Of Flow-mediated Dilation Research Articles

High-density lipoprotein cholesterol subfraction HDL2 is associated with improved endothelial function in systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) have increased risk of premature atherosclerosis but the exact mechanisms remains unclear. Flow-mediated dilatation (FMD) is an established non-invasive assessment of vascular endothelial function. Lipoprotein subfractions may be better predictors of FMD than conventional cholesterol measurements. We tested the hypothesis that lipoprotein subfractions are independently associated with FMD. Forty-one consecutive adult patients with SLE without known cardiovascular risk factors or disease were recruited in this cross-sectional study. Endothelial function and early atherosclerosis were assessed by brachial FMD and common carotid artery (CCA) intima-media thickness (IMT). High-density lipoprotein (HDL)/low-density lipoprotein (LDL) subfractions were measured. Machine learning models were also constructed to predict FMD and CCA IMT. Median FMD was 4.48% (IQR 5.00%) while median IMT was 0.54 mm (IQR 0.12 mm). Univariate analysis showed lower LDL1 (r=-0.313, p<0.05) and higher HDL2 subfractions (r=0.313, p<0.05) were significantly associated with higher log-transformed FMD. In a multiple linear regression model, HDL2 (β=0.024, SE=0.012, p<0.05) remained an independent predictor of higher FMD after adjusting for age, body mass index, LDL1 and systolic blood pressure. The machine learning model included parameters such as HDL2 (positive association), prednisolone dose, LDL cholesterol and LDL1 for prediction of FMD (r=0.433, p<0.01). Age, LDL cholesterol and systolic blood pressure were independently associated with higher CCA IMT after adjusting for body mass index and HDL2. HDL 2, a large HDL particle, was independently associated with greater FMD and may be a biomarker of vascular health in SLE.

Endothelial dysfunction, oxidative stress and low-grade endotoxemia in COVID-19 patients hospitalised in medical wards.

Endothelial dysfunction, assessed by flow-mediated dilation (FMD), is related to poor prognosis in patients with COVID-19 pneumonia (CP). In this study, we explored the interplay among FMD, NADPH oxidase type 2 (NOX-2) and lipopolysaccharides (LPS) in hospitalised patients with CP, community acquired pneumonia (CAP) and controls (CT). We enrolled 20 consecutive patients with CP, 20 hospitalised patients with CAP and 20 CT matched for sex, age, and main cardiovascular risk factors. In all subjects we performed FMD and collected blood samples to analyse markers of oxidative stress (soluble Nox2-derived peptide (sNOX2-dp), hydrogen peroxide breakdown activity (HBA), nitric oxide (NO), hydrogen peroxide (H2O2)), inflammation (TNF-α and IL-6), LPS and zonulin levels. Compared with controls, CP had significant higher values of LPS, sNOX-2-dp, H2O2,TNF-α, IL-6 and zonulin; conversely FMD, HBA and NO bioavailability were significantly lower in CP. Compared to CAP patients, CP had significantly higher levels of sNOX2-dp, H2O2, TNF-α, IL-6, LPS, zonulin and lower HBA. Simple linear regression analysis showed that FMD inversely correlated with sNOX2-dp, H2O2, TNF-α, IL-6, LPS and zonulin; conversely FMD was directly correlated with NO bioavailability and HBA. Multiple linear regression analysis highlighted LPS as the only predictor of FMD. This study shows that patients with COVID-19 have low-grade endotoxemia that could activate NOX-2, generating increased oxidative stress and endothelial dysfunction.

Aerobic Fitness as a Predictor of Conduit, Resistance and, Microvascular Arterial Function

IntroductionVascular dysfunction increases cardiovascular disease (CVD) risk, whereas aerobic fitness (VO2peak) improves arterial function and decreases CVD risk. However, it is unclear if VO2peak has the same degree of importance across each segment of the arterial tree (e.g., conduit, resistance, and microvasculature). This is relevant given that research has not assessed these three segments in the same cohort.PurposeTo examine the relationship of VO2peak and conduit, resistance, and microvasculature arterial function.MethodsGraded exercise testing assessed VO2peak in 33 males (41±19 years, 25.6±2.6 kg/m‐2, 41.1±13.6 ml/kg‐1/min‐1) and 28 females (30±12 years, 23.3±4.3 kg/m‐2, 33.6±8.5 ml/kg‐1/min‐1). Concurrent brachial artery flow‐mediated dilation (FMD) and forearm near‐infrared spectroscopy (NIRS) examined conduit, resistance, and microvascular arterial function. FMD measured with ultrasonography to continuously record arterial diameters and Doppler velocities for 1 min baseline, 5 min forearm occlusion (250 mmHg), and 3 min recovery. The maximum percent change in diameter compared with baseline defined FMD (%) and was used to evaluate conduit arterial function. Reactive hyperemia (RH) of forearm resistance arteries was calculated as peak brachial blood flow following cuff release. Forearm tissue saturation index using NIRS during FMD was used to evaluate microvasculature function (reperfusion slope and reperfusion magnitude). Multivariate regression analysis was performed using VO2peak, age, sex, and BMI as independent variables.ResultsAge was the only predictor of FMD (β ‐0.48 [‐0.02, ‐0.01], p=0.001), sex was the only predictor of RH, females exhibited lower RH, (β ‐0.66 [‐0.30, ‐0.15], p&lt;0.001), and VO2peak only predicted reperfusion slope (β 0.56 [1.46, 4.52], p&lt; 0.001) and reperfusion magnitude (β 0.36 [3.15, 41.66], p=0.02).ConclusionIn our cohort, aerobic fitness was associated with microvascular function when age, BMI, and sex were included in the model. Only age was associated with conduit artery function, and only sex was associated with resistance arterial function. Each segment of the arterial tree was affected differently by VO2peak, age, and sex. These data show the importance of including several potentially important variables when investigating the association between VO2peak and arterial function.

Association between atrial high rate episode burden and autonomic and vascular function in patients with implanted cardiac device

Abstract Background Patients who experience frequent atrial high rate episodes (AHREs), recorded on implantable cardiac devices, are at an increased risk of stroke and systemic embolism. Increased duration of AHRE is related to higher risk of thromboembolic event. The underlying pathophysiology is unclear; however, autonomic and/or endothelial dysfunction may contribute. Purpose We tested the hypothesis that patients with high AHRE burden have worse autonomic and vascular function compared to patients with low AHRE burden. Design We studied 44 patients split in two groups: high AHRE burden (longest AHRE ≥24 hours; n=22) and low AHRE burden (longest AHRE &amp;lt;24 hours; n=22). Resting time- and frequency-domain measures of HRV were determined to index cardiac autonomic function. High-resolution ultrasound was used to measure brachial artery diameter at rest and during reactive hyperaemia (endothelium-dependent flow mediated dilation (FMD)). Results FMD was higher in the low AHRE burden group compared to high AHRE group (5.5% [95% confidence interval (CI):3.4–7.6] vs 3.1% [95% CI: 1.9–6.2]; p=0.04) (table 1). Mean heart rate (p&amp;lt;0.001) and AHRE burden (p=0.02) were independent predictors of FMD on multivariate analysis. Time-domain, frequency-domain and non-linear indices of HRV were not significantly different between the groups. A slower heart rate (Spearman's rho 0.369; p=0.01) and high AHRE burden (Spearman's rho −0.315; p=0.04) were independently associated with changes seen on FMD following adjustment for multiple variables (p=0.001 and p=0.03 respectively). Conclusion Endothelium-dependent FMD is impaired in patients with high AHRE burden, while HRV derived indices of autonomic function were not affected by AHRE burden. Endothelial dysfunction may play an important role in the adverse outcomes seen in patients who experience frequent AHRE. Funding Acknowledgement Type of funding sources: None.

Idiopathic deep venous thrombosis and arterial endothelial dysfunction in the elderly

Arterial and venous thrombosis have always been regarded as different pathologies and epidemiological studies have examined the association between venous thrombosis and indicators of atherosclerosis and/or arterial thromboembolic events. We measured the flow-mediated dilation (FMD), a well-known marker of arterial endothelial dysfunction, in young-middle-aged and old-aged patients with and without unprovoked deep venous thrombosis (DVT). The aim of this study was to investigate whether DVT was a significant predictor for impaired FMD, considering all the patients and young-middle-aged (age < 65 years) and old-aged (age ≥ 65 years) patients separately. FMD was measured in the brachial artery on a population of 120 subjects with the same atherosclerosis risk factors, 68 male and 52 female, 70 young-middle-aged subjects (mean age ± SD 49.5 ± 10.5 years) and 50 old-aged subjects (76.2 ± 7.7 years). Patients with DVT showed a significant decrease of FMD compared to patients without DVT (6.8 ± 5.5% vs. 10.9 ± 3.5%, p < 0.001). Moreover, old-aged patients showed a significant decrease of FMD compared to the young-middle-aged subjects (7.4 ± 4.1% vs. 9.8 ± 5.3%, p = 0.005). In the whole study population, DVT was strongly associated with FMD (risk factors adjusted β = -4.14, p < 0.001). A significant interaction between age and the presence of DVT on predicting FMD was found (p = 0.003) suggesting a differential behavior of DVT as predictor of FMD. In young-middle-aged group, multivariate model confirmed that DVT was the most significant predictor of continuous FMD (β = -6.06, p < 0.001). On the contrary, DVT was no more a predictor of FMD in the old age group (β = -0.73, p = 0.556). Furthermore, old-aged patients without DVT showed a statistically significant decrease of FMD compared to the young-middle-aged subjects without DVT (8.2 ± 2.1% vs. 12.6 ± 2.7%, p<0.001) and old-aged patients with DVT showed a not statistically significant decrease of the FMD compared to the young-middle-aged patients with DVT (6.7 ± 5.3% vs. 6.8 ± 5.7%, p = 0.932). In conclusion, young-middle-aged patients with spontaneous DVT show an impaired FMD, whereas this impairment in old-aged subjects is evident independently from the presence or absence of DVT. Aging per se may be associated with physiologic abnormalities in the systemic arteries and with endothelial dysfunction.

Subclinical atherosclerosis and endothelial dysfunction in young South-Asian patients with systemic lupus erythematosus

Patients with systemic lupus erythematosus (SLE), especially Asian Indians, are at increased risk of developing premature atherosclerosis. To find out the prevalence and predictors of carotid intima-medial thickness (IMT) and brachial artery flow-mediated dilatation (FMD). Endothelial dysfunction was assessed by FMD in brachial artery and IMT was measured in common carotid artery in SLE patients and healthy controls. Sixty SLE patients (mean age 31 +/- 9 years) and 38 healthy controls (mean age 34 +/- 6 years) were included. The IMT was higher in SLE patients as compared to controls (0.49 +/- 0.08 mm vs. 0.39 +/- 0.05 mm, p < 0.0001). SLE and damage were independent predictors of abnormal IMT. FMD was impaired in SLE patients compared to controls (9.97% vs. 18.97%, p < 0.00001). None of the classical cardiovascular risk factors were predictors of FMD or abnormal IMT. Indian patients with SLE have higher prevalence of subclinical atherosclerosis and endothelial dysfunction. Presence of damage was associated with abnormal IMT in SLE patients.

Abstract: P1197 METABOLIC CONTROL AND ARTERIAL VASOREACTIVITY IN CHILDREN WITH TYPE I DIABETES USING INSULIN PUMP

P1197 Citation: Atherosclerosis Supplement 2009, Vol. 10, Issue 2 METABOLIC CONTROL AND ARTERIAL VASOREACTIVITY IN CHILDREN WITH TYPE I DIABETES USING INSULIN PUMP M Sebestjen, N Battelino, T Battelino, I Keber Department of Angiology, University Clinical Centre Ljubljana, Ljubljana; University Children's Hospital, University Clinical Centre Ljubljana, Ljubljana Children with type I diabetes mellitus have impaired endothelial function which is the first change in atheroslcerotic process. The aim of our study was to find out whether arterial vasoreactivity in children with type I diabetes mellitus using insulin pump is depending on the intensitivity of metabolic control. We studied 97 children with type I diabetes, aged between 7 and 18 years. The children were classified into two groups according to HbA1c below (Group 1) or more than (Group 2) 8,0%. In all participants physical examination, measurements of serum lipids, glucose, HbA1c and ultrasonographic studies of brachial artery vasoreactivity were performed. Children in group 1 were significantly younger than those in group 2 (10,3 ±1,9 and 15,6 ± 1,9 years; respectively (p<0,0001)). The mean values of blood glucose were 8,1 ± 3,2 mmol/l and 9,3 ± 4,0 mmol/l (p=ns), while mean values of HbA1c were 7,4 ± 0,4% and 9,3 ± 1,7%; respetivly (p<0,0001). Total (4,0 ± 0,6 mmol/l and 4,5 ± 0,7 mmol/l (p= 0,007)) and LDL cholesterol (2,0 ± 0,5 mmol/l and 2,4 ± 0,7 mmol/l (p= 0,04)) were lower in group 1 than in group 2. No difference were found in HDL cholesterol, and systolic and diastolic blood pressure. The flow mediated dilatation (FMD) was 6,7 ± 4,5% and 3,2 ± 5,4% (p= 0,02) in group 1 and group 2; respectively. Only HbA1c emerged as independed predictor of FMD. The value of HbA1c is the most important predictor of FMD in children with type I diabetes mellitus using insulin pump. Lifestyle modifications and strickt control of HbA1c early in childhood are important to prevent early atherosclerostic changes in these population.

The Association Between Glycemia and Endothelial Function in Nondiabetic Individuals: The Importance of Body Weight

The aim of this study was to examine the association between glycemia and markers of early atherosclerosis in healthy nondiabetic individuals. In 309 individuals without diabetes or symptomatic cardiovascular disease, we assessed long-term glycemia by glycosylated hemoglobin (HbA1c) and endothelial function by flow-mediated dilatation (FMD) in the brachial artery. HbA1c was negatively associated with FMD (r = -0.162, P = 0.004). Multivariate linear regression analysis after adjusting for common risk factors of cardiovascular disease showed that BMI was an effect modifier of the association between HbA1c and FMD (P = 0.034 for the HbA1c x BMI interaction). We stratified the FMD outcome data into two groups separated by the median BMI (group 1: BMI < or = 26.1 kg/m(2) and group 2: BMI > 26.1 kg/m(2)). In the lower BMI group, HbA1c was an independent predictor of FMD even when adjusted for confounding factors associated with impaired glucose metabolism (r = -0.215, P = 0.009), but in the higher BMI group HbA1c was not associated with FMD (r = -0.051, P = 0.5). In a nondiabetic population, long-term glycemia was associated with endothelial dysfunction only in lean individuals. In the overweight individuals, this association was not apparent, possibly because some of the mechanisms that mediate the effect of glycemia on vascular function are shared by obesity.

Endothelial nitric oxide synthase gene polymorphism, homocysteine, cholesterol and vascular endothelial function

Nitric oxide-dependent vasodilation is impaired early in the pathogenesis of vascular disease. Both the 4ab polymorphism of endothelial nitric oxide synthase (eNOS) and elevated plasma homocysteine are putatively associated with coronary artery disease (CAD). Few studies have investigated the influence of either on endothelial function in normal subjects. We aimed to examine any effect of three eNOS gene polymorphisms and plasma levels of homocysteine, folate and lipids on vascular endothelial function in normal healthy subjects. Community subjects ( n=60) were selected for their eNOS genotype. Largely NO -dependent, flow-mediated dilation (FMD) of the brachial artery and the response to glyceryl trinitrate (GTN) were measured. Neither FMD nor response to GTN in 4a allele carriers was significantly different from that of 4b homozygotes, (7.1±0.5 S.E.M. vs. 7.1±0.6%) and (18.9±1.2 vs. 18.9±0.9%), respectively. Responses were also independent of the other polymorphisms. FMD was significantly correlated with HDL-cholesterol ( P=0.02). After accounting for serum folate, there was a significant inverse correlation between FMD and plasma homocysteine ( P=0.03). In these normal community subjects, plasma homocysteine and HDL-cholesterol were predictors of FMD despite subjects being recruited without regard to these variables and despite normal plasma levels.