Independent Predictor Of Flow-mediated Dilation Research Articles

IMPACT OF HEAT–NOT–BURN CIGARETTE PASSIVE SMOKING ON CHILDREN‘S OXIDATIVE STRESS, ENDOTHELIAL AND PLATELET FUNCTION

IMPACT OF HEAT–NOT–BURN CIGARETTE PASSIVE SMOKING ON CHILDREN‘S OXIDATIVE STRESS, ENDOTHELIAL AND PLATELET FUNCTION

Impact of heat-not-burn cigarette passive smoking on children's oxidative stress, endothelial and platelet function

Growing global use of heat-not-burn cigarettes (HNBC) prompts investigation. Prior studies assessed HNBC's effects on cardiovascular health, revealing heightened oxidative stress, platelet activation, and endothelial dysfunction. However, limited understanding exists regarding passive smoking's impact on children exposed to HNBC.This study aims to assess levels of oxidative stress, endothelial and platelet function among children exposed to passive smoke from HNBC, traditional tobacco (TT) cigarettes and unexposed subjects.Seventy-eight children (2–18 years) were divided into three groups: HNBC passive smokers (n = 26), TT cigarette exposed (n = 26), and control (CNT) group (n = 26, unexposed).Oxidative stress was evaluated by serum NADPH oxidase-2 (NOX2) activity, assessed by soluble Nox2-derived peptide (sNOX2-dp), isoprostanes, hydrogen peroxide (H2O2) production, hydrogen break-down activity (HBA) and NO bioavailability. Endothelial function was assessed by brachial flow-mediated dilation (FMD). Platelet function was evaluated by soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin) and thrombus formation by T-TAS analysis.Passive smoking-exposed children (both HNBC and TT) exhibited significantly increased serum sNOX2-dp, isoprostanes, H2O2, sCD40L sP-selectin and thrombus formation versus controls. Conversely, exposed children displayed reduced brachial FMD and serum NO bioavailability. No significant differences were found between children exposed to passive smoking of HNBC vs TT.Multivariable regression linked sNOX2 (standardized coefficient β: 0.284; SE: 0.040; p = 0.01) and H2O2 (standardized coefficient β: 0.243; SE: 0.0; p = 0.02) as independent predictors of FMD, and isoprostanes (standardized coefficient β:0.388; SE: 0.022; p < 0.001) and serum cotinine (standardized coefficient β:0.270; SE: 0.048; p = 0.01) with sNOX2-dp levels.Exposure to HNBC smoke heightened oxidative stress, endothelial dysfunction, platelet activation, and thrombus formation in children. Findings suggest avenues for interventions to curb childhood passive smoking exposure.

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.

A larger low-flow-mediated constrictor response is associated with augmented flow-mediated dilation in the popliteal artery.

In the brachial artery, conflicting evidence exists regarding the relationship between the low-flow-mediated constriction (L-FMC) and subsequent flow-mediated dilation (FMD) responses, which may confound interpretation of the latter. The popliteal artery is a common site for atherosclerotic development, which is preceded by endothelial dysfunction. We aimed to determine whether the magnitude of popliteal L-FMC impacted FMD responses, which is currently unknown. L-FMC and FMD were assessed in the popliteal artery via high-resolution duplex ultrasonography and quantified as the percent change in diameter (from baseline) during ischaemia and in response to hyperaemia, respectively. Using partial correlations and multiple regression analyses, we evaluated the association between popliteal L-FMC on FMD in 110healthy participants (60 females; 42±22 [19-77] years). All variables univariately associated (p<0.05) with popliteal relative FMD (relative L-FMC, log-SRAUC , age, systolic blood pressure, diastolic blood pressure, resting shear rate) were inputted into a model that explained 35% of the variance. The reactive hyperaemia stimulus (log-SRAUC : β=1.10) and relative L-FMC (β=-0.39) were the only independent predictors of FMD (both, p<0.01). Relative L-FMC was negatively correlated to relative FMD, after controlling for the significant univariate predictor variables listed above (R=-0.30; p=0.002). An augmented (ie healthier) L-FMC response was linked with a larger FMD response as determined by the independent inverse association observed between these shear-stress-mediated measures of vasoreactivity.

IN NEWLY DIAGNOSED PATIENTS WITH TYPE 2 DIABETES MELLITUS FLOW-MEDIATED DILATATION IS IMPAIRED AND ASSOCIATED INDEPENDENTLY WITH THE DIAGNOSIS OF DIABETES

Objective: Type 2 diabetes mellitus (T2DM) is associated with endothelial dysfunction that mediates long-term complications. However, it is still unclear whether endothelial dysfunction is evident from the early stages of the disease. We aimed to investigate endothelial dysfunction in newly diagnosed and untreated patients with T2DM. Design and method: We enrolled consecutive patients diagnosed with T2DM no longer than 6 months ago, as well as age and gender matched controls. We recorded a detailed medical history, laboratory exams, office and 24-hour blood pressure (BP) levels and ASCVD (Atherosclerotic Cardiovascular Disease) risk. Endothelial dysfunction was estimated with the gold standard non-invasive method, flow mediated dilatation (FMD). Results: We studied 70 individuals aged 56 ± 10 years (29 T2DM and 41 controls). Only 11 T2DM patients were on treatment with metformin and was administered for less than 3 months. T2DM patients had increased office BP (p &lt; 0001) and systolic BP at night (p = 0.037) compared to controls. FMD was also impaired in T2DM (5.3 ± 2.5% versus 7.7 ± 4.5%, p = 0.014). FMD showed a negative association only with T2DM (p = 0.021), day systolic BP (p = 0.031), and positively with HDL (p = 0.038). In the multivariate analysis, T2DM diagnosis was the only independent predictor of FMD. Conclusions: Our results suggest that endothelial dysfunction is evident in newly diagnosed T2DM patients and independently associated with diabetes diagnosis. BP and cholesterol levels were also associated with FMD highlighting the need for early intervention in factors associated with endothelial dysfunction from the early stages of the disease.

Associations of coenzyme Q10 with endothelial function in hemodialysis patients.

Endothelial dysfunction is common in patients undergoing hemodialysis (HD). However, little is known about the relationship between endothelial dysfunction and coenzyme Q10 (CoQ10) levels in HD patients. Eligible HD patients were enrolled in this study according to prespecified inclusion and exclusion criteria. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Plasma CoQ10, serum malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. The potential confounders identified by univariate analyses (P < 0.15) were selected in a stepwise multiple regression model. In total, 111 HD patients were enrolled in this study. The mean CoQ10 level was 633.53 ± 168.66 ng/mL, and endothelial dysfunction was prevalent (91.0%) using a cut-off value of 10% FMD. A significant correlation was observed between FMD and plasma CoQ10 level (r = 0.727, P < 0.001). After adjusting for potential parameters, a stepwise multivariate linear regression analysis revealed that CoQ10 level was an independent predictor of FMD (β = 0.018, P < 0.001). When CoQ10 was dichotomized using the median value (639.74 ng/mL), the conclusion remained unchanged (β = 0.584, P < 0.001). Pearson's correlation analyses revealed that plasma CoQ10 level was negatively correlated with MDA (r = -0.48, P < 0.001) and 8-OHdG (r = -0.43, P < 0.001) levels. Our data demonstrate that impaired brachial artery FMD was common in HD patients. CoQ10 level was independently associated with FMD, and oxidative stress may constitute a link between CoQ10 level and endothelial dysfunction in these patients.

Asymmetric dimethylarginine and angiopoietin-like protein-2 are independent predictors of cardiovascular risk in pre-dialysis non-diabetic chronic kidney disease patients.

Chronic kidney disease (CKD) is associated with increased cardiovascular (CVD) morbidity and mortality. Hence, this study was carried out to assess the biomarkers of endothelial dysfunction and inflammation as predictors of CVD risk in Indian patients with CKD. In this case control study, we recruited 43 patients with CKD and 43 healthy control volunteers. Circulating levels of endothelial dysfunction markers [asymmetric dimethylarginine (ADMA), angiopoietin-like protein-2 (ANGPTL2), matrix metallopeptidase 9 (MMP-9)] and systemic inflammation [high-sensitivity C-reactive protein (hs-CRP)] were assessed in the study population. All study participants underwent brachial artery flow mediated dilation (FMD) to estimate endothelial dysfunction. Disease severity (e-GFR) was assessed by a nephrologist. CKD patients showed markedly elevated levels of ADMA, ANGPTL2, MMP-9, and hs-CRP. FMD and eGFR were significantly decreased in cases, as compared to the controls. ADMA, ANGPTL2, MMP-9 and hs-CRP showed significant positive correlation with one another and significant negative correlation with FMD and disease severity. We also observed a significant negative correlation of FMD with disease severity and duration of CKD. In the multiple linear regression model, ADMA and ANGPTL2 were found to be independent predictors of FMD. In CKD patients, there is significantly increased endothelial dysfunction and systemic inflammation, which showed a positive correlation with disease severity. Thus, the markers of endothelial dysfunction such as ADMA and ANGPTL2 can be used as predictors of CVD risk in CKD.

Serum heparanase levels are associated with endothelial dysfunction in patients with obstructive sleep apnea.

Obstructive sleep apnea syndrome (OSAS) is well-known to be associated with high risk for cardiovascular (CV) diseases. Heparanase has been recently shown to be related to increased inflammation and vulnerability of the atherosclerotic plaques. Herein we aimed to investigate the relationships between OSAS, heparanase and endothelial dysfunction. A total of 120 patients with varying severity of OSAS and 31 controls without OSAS were enrolled. Flow-mediated dilatation (FMD) was measured as an indicator of endothelial dysfunction. Serum heparanase levels were measured with ELISA. Serum heparanase levels increased in a stepwise fashion from controls to patients with more severe OSAS. When FMD was compared with controls and various degrees of severity of OSAS, a stepwise decrease in FMD was observed. Serum heparanase levels were found to be significantly associated with apnea hypopnea index (AHI) (r = .57, P < .001) and FMD (r= -.37, P < .001) in patients with OSAS. Serum heparanase levels were significantly associated with hemoglobin-A1c and body mass index in patients with OSAS. Serum heparanase and uric acid levels were independent predictors of FMD in linear regression analysis (R2 = .506, P < .001; P < .001 and P = .001 respectively). Serum heparanase levels were significantly increased in patients with OSAS and associated with the severity of OSAS (AHI) and endothelial dysfunction (FMD). Increased heparanase activity in OSAS may be related to increased cardiovascular risk in patients with OSAS.

Endothelial Dysfunction in Renal Transplant Recipients: Role of Vitamin D and Fibroblast Growth Factor-23

BackgroundEndothelial dysfunction can be detected at early stages of chronic kidney disease. Although endothelial functions improve after successful renal transplantation, renal transplant recipients have still worse endothelial functions compared to healthy subjects. Vitamin D deficiency and high fibroblast growth factor−23 (FGF-23) levels may have a role on endothelial dysfunction in chronic kidney disease patients. The aim of this study is to investigate the association between endothelial functions, vitamin D, and FGF-23 levels in renal transplant recipients. MethodsOne hundred nine renal transplant recipients (71 male, 38 female) underwent brachial flow-mediated dilatation (FMD), serum 25-OH vitamin D, and FGF-23 level measurements. Vitamin D and FGF-23 levels were compared between patients with normal and abnormal endothelial functions. Correlations between FMD, vitamin D, and FGF-23 were also investigated. ResultsEndothelial functions were abnormal in 72.5% of the patients. Prevalence of vitamin D deficiency was 80.7%. Vitamin D levels were significantly lower in patients with endothelial dysfunction compared to patients with normal endothelial functions (12.6 ± 6.6 μg/L vs 17.3 ± 10.0 μg/L respectively, P = .02). FGF-23 levels were not different between the two groups. 25-OH vitamin D levels had a significant positive correlation with amount of FMD (r = 0.218 and P = .02) and were an independent predictor of FMD after adjusting for potential confounding factors including age, transplantation duration, body mass index, mean blood pressure, glomerular filtration rate, proteinuria, hemoglobin, and FGF-23 in multivariate regression analysis (beta = 0.194, P = .04). FGF-23 levels were not predictive of FMD in this model (beta: −0.125, P = .197) ConclusionVitamin D deficiency is associated with endothelial dysfunction in renal transplant recipients. Further clinical and experimental studies are necessary to define a causal relationship between the parameters, discover the potential mechanisms, and observe the effect of vitamin D replacement on endothelial functions in renal transplant recipients.

El ácido úrico y la actividad de gammaglutamil transferasa se asocian a los índices de remodelado ventricular izquierdo en pacientes con insuficiencia cardiaca crónica

Introduction and objectivesUric acid and gamma-glutamyl transferase are prognostic indicators in chronic heart failure. Nevertheless, the mechanism underlying the association between uric acid, gamma-glutamyl transferase, and chronic heart failure progression and prognosis remains largely unknown. MethodsThe association of uric acid and gamma-glutamyl transferase with flow-mediated dilation and echocardiographic indices of cardiac remodeling was addressed in 120 patients with chronic ischemic heart failure. To determine the independent contribution of uric acid and gamma-glutamyl transferase to the flow-mediated dilation and echocardiographic indices of remodeling, a series of multiple linear regression models, based on traditional and nontraditional risk factors impacting upon these parameters, were constructed. ResultsUric acid, but not gamma-glutamyl transferase, was an independent predictor of flow-mediated dilation. Uric acid was associated with all the echocardiographic indices of left ventricular dysfunction tested in 3 multiple-regression models. Uric acid correlated with left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left ventricular end-systolic volume, and left ventricular end-diastolic volume (r = 0.337; r = 0.340; r = 0.321; r = 0.294; P = .001, respectively). Gamma-glutamyl transferase was an independent predictor of left ventricular end-systolic volume and left ventricular end-diastolic volume, after adjustment for all variables. Gamma-glutamyl transferase correlated with left ventricular end-diastolic diameter, left ventricular end-diastolic diameter, left ventricular end-systolic volume, and left ventricular end-diastolic volume (r = 0.238, P = .009; r = 0.219, P = .016; r = 0.359, P < .001; r = 0.369, P = .001, respectively). ConclusionsSerum uric acid and gamma-glutamyl transferase levels are associated with left ventricular remodeling in patients with chronic ischemic heart failure.Full English text available from:www.revespcardiol.org/en

Uric Acid and Gamma-glutamyl Transferase Activity Are Associated With Left Ventricular Remodeling Indices in Patients With Chronic Heart Failure

Introduction and objectivesUric acid and gamma-glutamyl transferase are prognostic indicators in chronic heart failure. Nevertheless, the mechanism underlying the association between uric acid, gamma-glutamyl transferase, and chronic heart failure progression and prognosis remains largely unknown. MethodsThe association of uric acid and gamma-glutamyl transferase with flow-mediated dilation and echocardiographic indices of cardiac remodeling was addressed in 120 patients with chronic ischemic heart failure. To determine the independent contribution of uric acid and gamma-glutamyl transferase to the flow-mediated dilation and echocardiographic indices of remodeling, a series of multiple linear regression models, based on traditional and nontraditional risk factors impacting upon these parameters, were constructed. ResultsUric acid, but not gamma-glutamyl transferase, was an independent predictor of flow-mediated dilation. Uric acid was associated with all the echocardiographic indices of left ventricular dysfunction tested in 3 multiple-regression models. Uric acid correlated with left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left ventricular end-systolic volume, and left ventricular end-diastolic volume (r = 0.337; r = 0.340; r = 0.321; r = 0.294; P = .001, respectively). Gamma-glutamyl transferase was an independent predictor of left ventricular end-systolic volume and left ventricular end-diastolic volume, after adjustment for all variables. Gamma-glutamyl transferase correlated with left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left ventricular end-systolic volume, and left ventricular end-diastolic volume (r = 0.238, P = .009; r = 0.219, P = .016; r = 0.359, P < .001; r = 0.369, P = .001, respectively). ConclusionsSerum uric acid and gamma-glutamyl transferase levels are associated with left ventricular remodeling in patients with chronic ischemic heart failure.

Vascular endothelial function and oxidative stress are related to dietary niacin intake among healthy middle-aged and older adults

We tested the hypothesis that vascular endothelial function and oxidative stress are related to dietary niacin intake among healthy middle-aged and older adults. In 127 men and women aged 48-77 yr, brachial artery flow-mediated dilation (FMD) was positively related to dietary niacin intake [%change (Δ): r = 0.20, P < 0.05; mmΔ: r = 0.25, P < 0.01]. In subjects with above-average dietary niacin intake (≥ 22 mg/day, NHANES III), FMD was 25% greater than in subjects with below-average intake (P < 0.05). Stepwise linear regression revealed that dietary niacin intake (above vs. below average) was an independent predictor of FMD (%Δ: β = 1.8; mmΔ: β = 0.05, both P < 0.05). Plasma oxidized low-density lipoprotein, a marker of systemic oxidative stress, was inversely related to niacin intake (r = -0.23, P < 0.05) and was lower in subjects with above- vs. below-average niacin intake (48 ± 2 vs. 57 ± 2 mg/dl, P < 0.01). Intravenous infusion of the antioxidant vitamin C improved brachial FMD in subjects with below-average niacin intake (P < 0.001, n = 33), but not above-average (P > 0.05, n = 20). In endothelial cells sampled from the brachial artery of a subgroup, dietary niacin intake was inversely related to nitrotyrosine, a marker of peroxynitrite-mediated oxidative damage (r = -0.30, P < 0.05, n = 55), and expression of the prooxidant enzyme, NADPH oxidase (r = -0.44, P < 0.01, n = 37), and these markers were lower in subjects with above- vs. below-average niacin intake [nitrotyrosine: 0.39 ± 0.05 vs. 0.56 ± 0.07; NADPH oxidase: 0.38 ± 0.05 vs. 0.53 ± 0.05 (ratio to human umbilical vein endothelial cell control), both P < 0.05]. Our findings support the hypothesis that higher dietary niacin intake is associated with greater vascular endothelial function related to lower systemic and vascular oxidative stress among healthy middle-aged and older adults.

Mean corpuscular volume is associated with endothelial dysfunction and predicts composite cardiovascular events in patients with chronic kidney disease

Mean corpuscular volume (MCV) is a measure of size of red blood cells. Recently a few studies showed an association of macrocytosis with all-cause mortality. We aimed to assess the relationship of MCV with cardiovascular (CV) morbidity and mortality in patients with chronic kidney disease (CKD), and the effect of MCV on endothelial function. This is an observational cohort study with a prospectively maintained cohort of patients with stage 1-5 CKD. Estimated glomerular filtration rate (eGFR), flow mediated dilatation (FMD) and laboratory values were measured at baseline. Multivariate linear and Cox regression analyses were used to predict independent associations of FMD and composite CV events, respectively. A total of 309 patients were included in the study. In contrast to anaemia MCV did not show a significant change among CKD groups. MCV was an independent predictor of FMD in addition to serum haemoglobin, CRP, diabetes, systolic blood pressure (SBP) and eGFR. Median MCV value was 85 fl. Kaplan-Meier analysis showed that at 38 months the survival rate was 97.6% in the group with MCV < 85 compared to 81.6% in the arm with MCV ≥ 85 (P < 0.001, log-rank test). Cox regression analysis showed MCV as a predictor of composite CV events independent of major confounding factors. This is the first study in the literature showing an independent association of MCV and FMD. Our results also determined MCV as an independent predictor of composite CV events independent of anaemia, inflammation, diabetes and eGFR in patients with CKD.

Annexin A5 as Independent Predictive Biomarker for Subclinical Atherosclerosis and Endothelial Dysfunction in Systemic Lupus Erythematosus Patients

Increased atherosclerosis prevalence in patients with systemic lupus erythematosus (SLE) is an epidemiological certainty. SLE patients are linked to endothelial immune conflict, chronic inflammation antiphospholipid antibodies, and high serum annexin A5 levels. Many of these factors belong to the inflammatory cascade which is common to both SLE and ATS. Therefore, there is an overlap between traditional and nontraditional atherosclerosis risk factors in SLE patients. The purpose of the study was to determine the association of conventional cardiovascular risk factors and atherosclerosis characteristics with biomarkers that are known to be implied in atherogenesis in SLE patients. In this study subclinical atheroscler is was evaluated by'carotid intima-medial thickness (IMT) and endothelial dysfunction by flow mediated dilation (FMD) in both SLE patients and controls. 132 SLE patients were recruited: 32 patients were assigned to the atherosclerosis group (ASLE, mean age +/- standard deviation 42.16 +/-9.18 years) and 100 were assigned to non-atherosclerosis group (nASLE, mean age 41.54 +/- 11.79 years). 50 healthy controls were enrolled (control group, mean age 41.4 +/- 11 years). Annexin A5 levels, anti phosphatidyl serine, and anti oxidized LDL antibodies were measured by enzyme-linked immunosorbent assay in both patients and healthy controls. Mean IMT in all SLE patients (0.83 - 0.11 mm) was significantly higher when compared to controls (0.66 +/- 0.04 mm, p < 0.05); mean FMD was significantly smaller in SLE patients (2.98 +/- 1.58%) when compared to controls (10.83 +/- 2.02%, p < 0.05). When all SLE patients and controls were considered together, SLIC presence, body mass index, serum annexin A5 levels, history of hypertension, and age were found to be independent predictors for abnormal IMT. In the SLE group only age and serum annexin A5 levels were found to be independent predictors for IMT. When all SLE patients were considered together, serum annexin A5 and age were found as independent predictors of FMD. In both ASLE and nASLE groups, age and serum annexin A5 levels were found to be independent predictive variables for endothelial dysfunction. This study confirms the presence of both endothelial dysfunction and subclinical atherosclerosis in SLE patients and suggests serum annexin A5 as predictive biomarker for subclinical atherosclerosis in SLE patients.

Relationship between Microbial Translocation and Endothelial Function in HIV Infected Patients

BackgroundCirculating levels of microbial products are increased in HIV infection, and provoke endothelial dysfunction in other disease settings.Methodology/Principal FindingsWe examined data from a cross-sectional single site study at Indiana University (Indiana, N = 85) and a 24- week multicenter prospective study of antiretroviral therapy (ART) initiation (ACTG 5152s, N = 75). Brachial artery flow-mediated dilation (FMD) was measured by ultrasound. Plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14) levels were measured from stored specimens and correlated with FMD values using Pearson correlations. The Indiana subjects were 63% male with a mean age of 39 years and a median CD4 count of 406 cells/mm3 (388 not on ART, 464 on ART). The 5152s subjects were 92% were male with a mean age of 35 years and a median CD4 count of 251 cells/mm3 at entry which increased to 396 cells/mm3 on ART. When analyzing the two cohorts individually or in combination neither sCD14 nor LPS correlated significantly with FMD. In a pre-specified subgroup analysis of the Indiana subjects receiving ART (N = 46, mean ART duration 40 months) LPS was inversely correlated with FMD (r = −0.33, p = 0.02), but not sCD14 (r = −0.01, p = 0.9). Multivariate analysis confirmed LPS as an independent predictor of FMD in this subgroup (p = 0.02).Conclusions/Significance In HIV- infected individuals on prolonged ART, higher LPS levels are associated with worse endothelial function but not in untreated subjects or at 24 weeks after ART initiation. Persistent microbial translocation may contribute to arterial dysfunction and the increased cardiovascular disease risk observed in individuals on long-term ART.

Hashimoto thyroiditis is an independent cardiovascular risk factor in clinically hypothyroid patients

Hypothyroidism is a common disorder that confers an increased cardiovascular risk. The most common cause is Hashimoto thyroiditis (HT) but it can also be caused by thyroidectomy and radioiodine therapy. The aim of the study is to examine whether there is a relation between the cause of hypothyroidism and cardiovascular risk. Subjects and methodsThe study included 20 patients with Hashimoto thyroiditis and hypothyroidism, 20 patients with post-thyroidectomy hypothyroidism, 20 patients with post-radioiodine hypothyroidism, and 20 age and sex matched controls. In all the studied subjects we determined thyroid function tests; TSH and F.T4, thyroid auto-antibodies; anti-TPO and anti-TG antibodies, carotid intima media thickness (CIMT), flow mediated dilation (FMD) and serum nitric oxide. ResultsCIMT showed a trend to be higher in HT group (0.93±0.08mm) compared to other causes of hypothyroidism (P=0.090). Multivariate analysis showed that HT is an independent predictor of CIMT (P=0.015). FMD was significantly lower in HT group (5.74±1.33%) compared to post-thyroidectomy (7.16±1.05%) (P=0.001), and post-radioiodine therapy (7.34±1.34%) (P=0.000). Multivariate analysis showed that HT is an independent predictor of FMD (P=0.000). NO was significantly higher in hypothyroid patients (125.98±5.03μM/ml) compared to controls (39.44±3.63μM/ml) (P=0.001), both univariate and multivariate analyses showed that NO is an independent predictor of both CIMT and FMD (P=0.000). ConclusionTo our knowledge, this is the first study to show that Hashimoto thyroiditis is an independent cardiovascular risk factor in clinically hypothyroid patients.

Patients With Obstructive Sleep Apnea Exhibit Impaired Endothelial Function After Myocardial Infarction

Impaired brachial flow-mediated dilation (FMD) is associated with risk for subsequent cardiovascular events in patients after myocardial infarction (MI). These patients often have obstructive sleep apnea (OSA). We tested the hypothesis that patients with OSA post MI will exhibit more severe impairment in FMD. We studied 64 patients with MI admitted to our hospital. OSA was determined using polysomnography. FMD was measured using high-resolution ultrasonography, with researchers blind to the OSA diagnosis. The mean age was 60 ± 11 years, and the mean BMI was 29 (26, 32 kg/m(2)), 84% of patients were men, 39% had moderate to severe OSA (apnea-hypopnea index [AHI] > 15), and 31% of the patients had mild OSA (5 ≤ AHI < 15). FMD was severely impaired in patients with moderate to severe OSA (0.8% ± 0.7%) as compared with patients without OSA (4.7% ± 0.8%, P = .001) and with mild OSA (3.9% ± 0.8%, P = .015). Linear regression showed that FMD was associated with log nocturnal nadir oxygen saturation (minSaO(2)) (β = 31.17, P = .0001), age (β = -0.11, P = .006). MinSaO(2) was an independent predictor of FMD after adjustment for possible confounders (β = 26.15, P = .001). FMD is severely impaired in patients with moderate to severe OSA post MI, which may be partially related to nocturnal hypoxemia. Patients with OSA may, therefore, be at higher risk for subsequent cardiovascular events after an MI. Identifying and treating OSA may have important implications in the long-term prognosis of patients post MI. Further studies are necessary to determine if the presence of OSA would affect the long-term occurrence of cardiovascular events after an MI.

In patients with aortic stenosis increased flow-mediated dilation is independently associated with higher peak jet velocity and lower asymmetric dimethylarginine levels

Recently, it has been shown that endothelial dysfunction and aortic stenosis (AS) share several risk factors. Endothelial function represents a crucial factor for the regulation of vascular tonus and its malfunction influences the formation of thrombosis and inflammation. However, the role of endothelial dysfunction in AS remains unclear. Echocardiographic, clinical, and laboratory data of 34 patients (age 74.5 ± 7.9 years, 20 men) with at least moderate AS (peak jet velocity 3.8 ± 0.8 m/s) were collected. In all patients, endothelial function was determined by brachial artery flow-mediated dilation (FMD). Patients with rheumatic or endocarditic valve disease, bicuspid valves, a left ventricular ejection fraction of ≤40%, and coronary artery disease were excluded. Sixteen volunteers (age 69.3 ± 9.4 years, 10 men) without valve disease served as controls. Patients with AS had a trend toward a lower FMD than controls with a comparable risk profile (5.4% ± 3.6% vs 7.4% ± 4.1%, P = .1). Univariate correlates of FMD in patients with AS were peak jet velocity, medication with angiotensin-converting enzyme inhibitor, diabetes, diastolic blood pressure, and asymmetric dimethylarginine. Backward elimination identified peak jet velocity (β = 0.51, P = .001), and asymmetric dimethylarginine (β = -0.45, P = .003) as independent predictors of FMD in multivariate analysis. In patients with AS, we found a strong positive relation between the peak jet velocity and a higher FMD. This effect might be mediated by nitric oxide release due to turbulent poststenotic blood flow or the rising transvalvular gradient, and the increasing pulse pressure may be counteracted by a parallel increase in FMD.

Oral contraceptive use, iron stores and vascular endothelial function in healthy women

Background Increased iron stores are associated with greater cardiovascular risk in postmenopausal women. Oral contraceptive pill (OCP) use decreases the volume of menstrual blood loss and increases iron stores, but the link between OCP use, iron stores and cardiovascular risk in premenopausal women has not been characterized. Study Design We conducted a cross-sectional study of 23 healthy OCP users to determine the association between type and duration of OCP exposure, iron stores, and vascular endothelial function [flow-mediated dilation (FMD) in the brachial artery]. Results Median duration of OCP use was 45 months. FMD in the brachial artery was significantly associated with progestin type used (estranes/gonanes vs. drospirenone) and duration of OCP use (both p<.05) but not iron stores. In multivariate analysis, progestin type was the only independent predictor of FMD. Conclusions Use of OCP containing drospirenone was independently associated with greater FMD in the brachial artery and, thus, a potentially more favorable cardiovascular risk profile, when compared with use of OCP containing estranes/gonanes.

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.