Impaired Flow-mediated Dilation Research Articles

Premature atherosclerosis in systemic sclerosis patients: Its relation to disease parameters and to traditional risk factors.

To detect premature atherosclerosis in systemic sclerosis (SSc) patients and its relation to disease parameters and traditional risk factors. This study included 40 SSc patients and 40 healthy age and sex matched controls. All patients were subjected to full history taking, clinical examination, relevant laboratory and radiological investigations. Doppler ultrasonography (US) of the common carotid was performed to measure intima-media thickness (ccIMT) and Doppler US of the brachial artery was performed to measure flow mediated dilatation (FMD). The mean value of ccIMT was 0.59 ± 0.2 mm in SSc patients and 0.51 ± 0.09 mm in controls and the difference was significant (P = 0.03). A statistically significant difference was found in mean brachial artery diameter before and after hyperemia, in flow change and in FMD between SSc patients and controls. ccIMT showed significant positive correlation with age, C-reactive protein (CRP), cholesterol, triglycerides and low density lipoprotein (P < 0.05). FMD showed significant positive correlation with daily dose of steroids (P = 0.04). Brachial artery diameter after hyperemia showed significant negative correlation with erythrocyte sedimentation rate (ESR). Peak systolic velocity before ischemia showed significant positive correlation with body mass index (BMI) and significant negative correlation with insulin level. Our findings confirm the presence of premature atherosclerosis in SSc patients assessed by significant impairment of FMD, flow change and ccIMT, and it is associated with traditional cardiovascular risk factors such as age, dyslipidemia and obesity (BMI) as well as with the use of steroids and markers of inflammation such as CRP and ESR.

Black Tea Increases Circulating Endothelial Progenitor Cells and Improves Flow Mediated Dilatation Counteracting Deleterious Effects from a Fat Load in Hypertensive Patients: A Randomized Controlled Study.

(1) Background: Endothelial dysfunction predicts cardiovascular events. Circulating angiogenic cells (CACs) maintain and repair the endothelium regulating its function. Tea flavonoids reduce cardiovascular risk. We investigated the effects of black tea on the number of CACs and on flow-mediated dilation (FMD) before and after an oral fat in hypertensives; (2) Methods: In a randomized, double-blind, controlled, cross-over study, 19 patients were assigned to black tea (150 mg polyphenols) or a placebo twice a day for eight days. Measurements were obtained in a fasted state and after consuming whipping cream, and FMD was measured at baseline and after consumption of the products; (3) Results: Compared with the placebo, black tea ingestion increased functionally active CACs (36 ± 22 vs. 56 ± 21 cells per high-power field; p = 0.006) and FMD (5.0% ± 0.3% vs. 6.6% ± 0.3%, p < 0.0001). Tea further increased FMD 1, 2, 3, and 4 h after consumption, with maximal response 2 h after intake (p < 0.0001). Fat challenge decreased FMD, while tea consumption counteracted FMD impairment (p < 0.0001); (4) Conclusions: We demonstrated the vascular protective properties of black tea by increasing the number of CACs and preventing endothelial dysfunction induced by acute oral fat load in hypertensive patients. Considering that tea is the most consumed beverage after water, our findings are of clinical relevance and interest.

Arterial stiffness and arterial function in adult cyanotic patients with congenital heart disease

BackgroundMortality in cyanotic patients with congenital heart diseases (CHD) is high, mainly due to cardiovascular complications. It is known that endothelial dysfunction, increased arterial stiffness, and impaired vascular function have negative influence on cardiovascular prognosis. The aim of the study was to assess parameters of arterial stiffness and vascular dysfunction in cyanotic patients with CHD as well as their potential relation to impaired blood oxygen saturation and polycythemia parameters typical for cyanosis. MethodsA total of 36 CHD cyanotic patients (17 males) (42.3±16.3 years) and 35 healthy individuals (16 males) (39.6±10.4 years) were enrolled. Assessed parameters were intima media thickness and flow-mediated dilatation (FMD). Assessed parameters using applanation tonometry methods were aortic systolic pressure, aortic pulse pressure (AoPP), augmentation pressure (AP), augmentation index (AI), pulse pressure amplification (PPampl), and pulse wave velocity (PWV). ResultsAoPP (37.3±11.1mmHg vs. 29±6.5mmHg; p=0.002), AP (10.1±7.3mmHg vs. 1.1±3.9mmHg; p=0.00001), AI (24.7±13.5% vs. 3.0±13.6%; p=0.00001), and PWV (7.4±2.1m/s vs. 6.3±0.7m/s; p=0.003) were higher, and PPampl was lower (135.3±16.1% vs. 160.4±12.8%; p=0.00001) in the studied group compared to controls and proved the presence of the increased stiffness of arteries. Impairment of FMD was observed (9.0±5.6 vs. 10.9±4.7; p=0.04). No significant correlations were found between analyzed arterial parameters and biochemical ones characterizing cyanotic patients depicting rheological properties of blood. ConclusionsCyanotic patients with CHD are characterized by increased arterial stiffness estimated with pulse wave analysis parameters and by deteriorated arterial function expressed with worse vasodilatative response in comparison with healthy population. It may confirm relevance of those mechanisms in development of increased rate of cardiovascular events in this population. Association between oxygen saturation or polycythemia and arterial stiffening or vascular dysfunction was not found in these patients.

Impaired flow-mediated dilation in hospitalized patients with community-acquired pneumonia

BackgroundCommunity-acquired pneumonia (CAP) is complicated by cardiovascular events as myocardial infarction and stroke but the underlying mechanism is still unclear. We hypothesized that endothelial dysfunction may be implicated and that endotoxemia may have a role. MethodsFifty patients with CAP and 50 controls were enrolled. At admission and at discharge, flow-mediated dilation (FMD), serum levels of endotoxins and oxidative stress, as assessed by serum levels of nitrite/nitrate (NOx) and isoprostanes, were studied. ResultsAt admission, a significant difference between patients with CAP and controls was observed for FMD (2.1±0.3 vs 4.0±0.3%, p<0.001), serum endotoxins (157.8±7.6 vs 33.1±4.8pg/ml), serum isoprostanes (341±14 vs 286±10 pM, p=0.009) and NOx (24.3±1.1 vs 29.7±2.2μM). Simple linear correlation analysis showed that serum endotoxins significantly correlated with Pneumonia Severity Index score (Rs=0.386, p=0.006). Compared to baseline, at discharge CAP patients showed a significant increase of FMD and NOx (from 2.1±0.3 to 4.6±0.4%, p<0.001 and from 24.3±1.1 to 31.1±1.5μM, p<0.001, respectively) and a significant decrease of serum endotoxins and isoprostanes (from 157.8±7.6 to 55.5±2.3pg/ml, p<0.001, and from 341±14 to 312±14 pM, p<0.001, respectively). Conversely, no changes for FMD, NOx, serum endotoxins and isoprostanes were observed in controls between baseline and discharge. Changes of FMD significantly correlated with changes of serum endotoxins (Rs=−0.315; p=0.001). ConclusionsThe study provides the first evidence that CAP is characterized by impaired FMD with a mechanism potentially involving endotoxin production and oxidative stress.

Pilot Investigation of PTSD, Autonomic Reactivity, and Cardiovascular Health in Physically Healthy Combat Veterans.

Posttraumatic stress disorder (PTSD), and combat-related PTSD in particular, has been associated with increased rates of cardiovascular disease, and cardiovascular-related death. However, less research has examined possible factors that may link PTSD to poorer cardiovascular health in combat veteran populations. The current pilot study investigated whether psychological symptomology and autonomic reactivity to emotional scripts would relate to poorer cardiovascular health in combat veterans without a current diagnosis of cardiovascular disease. Male veterans (N = 24), who served in combat since Operation Iraqi Freedom, completed a semi-structured interview and self-report measures to assess psychological symptomology. Autonomic reactivity, measured using heart rate variability (HRV; low to high frequency ratio), was obtained during script-driven imagery of emotional memories. Cardiovascular health was assessed using flow-mediated dilation (FMD) of the brachial artery. Correlational analyses and discriminant analysis were used to assess the relationship between psychological symptoms (PTSD, depression, anger, as measured via self-report), autonomic reactivity to emotional scripts (HRV), and FMD. Overall, veterans in the current study showed poor cardiovascular health despite their relatively young age and lack of behavioral risk factors, with 15/24 exhibiting impaired FMD (FMD < 5%). Psychological symptomology was not associated with FMD; whereas autonomic reactivity to emotional (compared to neutral) scripts was found to relate to FMD. Autonomic reactivity to negative scripts correctly classified 76.5% of veterans as having impaired versus normative FMD. Results from this pilot study highlight the importance of cardiovascular screening with combat veterans despite psychological diagnosis. Results also support the need for longitudinal research assessing the use of autonomic reactivity to emotionally valenced stimuli as a potential risk factor for poorer cardiovascular health.

One Minute of Marijuana Secondhand Smoke Exposure Substantially Impairs Vascular Endothelial Function.

BackgroundDespite public awareness that tobacco secondhand smoke (SHS) is harmful, many people still assume that marijuana SHS is benign. Debates about whether smoke‐free laws should include marijuana are becoming increasingly widespread as marijuana is legalized and the cannabis industry grows. Lack of evidence for marijuana SHS causing acute cardiovascular harm is frequently mistaken for evidence that it is harmless, despite chemical and physical similarity between marijuana and tobacco smoke. We investigated whether brief exposure to marijuana SHS causes acute vascular endothelial dysfunction.Methods and ResultsWe measured endothelial function as femoral artery flow‐mediated dilation (FMD) in rats before and after exposure to marijuana SHS at levels similar to real‐world tobacco SHS conditions. One minute of exposure to marijuana SHS impaired FMD to a comparable extent as impairment from equal concentrations of tobacco SHS, but recovery was considerably slower for marijuana. Exposure to marijuana SHS directly caused cannabinoid‐independent vasodilation that subsided within 25 minutes, whereas FMD remained impaired for at least 90 minutes. Impairment occurred even when marijuana lacked cannabinoids and rolling paper was omitted. Endothelium‐independent vasodilation by nitroglycerin administration was not impaired. FMD was not impaired by exposure to chamber air.ConclusionsOne minute of exposure to marijuana SHS substantially impairs endothelial function in rats for at least 90 minutes, considerably longer than comparable impairment by tobacco SHS. Impairment of FMD does not require cannabinoids, nicotine, or rolling paper smoke. Our findings in rats suggest that SHS can exert similar adverse cardiovascular effects regardless of whether it is from tobacco or marijuana.

Flavanol-rich chocolate acutely improves arterial function and working memory performance counteracting the effects of sleep deprivation in healthy individuals.

Sleep deprivation is a risk factor for cardiovascular disease. Cocoa flavonoids exert cardiovascular benefits and neuroprotection. Whether chocolate consumption may mitigate detrimental effects of sleep loss on cognitive performance and cardiovascular parameters has never been studied. We investigated the effects of flavanol-rich chocolate consumption on cognitive skills and cardiovascular parameters after sleep deprivation. Thirty-two healthy participants underwent two baseline sessions after one night of undisturbed sleep and two experimental sessions after one night of total sleep deprivation. Two hours before each testing session, participants were randomly assigned to consume high or poor flavanol chocolate bars. During the tests were evaluated, the Psychomotor Vigilance Task and a working memory task, office SBP and DBP, flow-mediated dilation and pulse-wave velocity. Sleep deprivation increased SBP/DBP. SBP/DBP and pulse pressure were lower after flavanol-rich treatment respect to flavanol-poor treatment (SBP: 116.9 ± 1.6 vs. 120.8 ± 1.9 mmHg, respectively, P = 0.00005; DBP: 70.5 ± 1.2 vs. 72.3 ± 1.2 mmHg, respectively, P = 0.01; pulse pressure: 46.4 ± 1.3 vs. 48.4 ± 1.5 mmHg, P = 0.004). Sleep deprivation impaired flow-mediated dilation (5.5 ± 0.5 vs. 6.5 ± 0.6%, P = 0.02), flavanol-rich, but not flavanol-poor chocolate counteracted this alteration (flavanol-rich/flavanol-poor chocolate: 7.0 ± 0.6 vs. 5.0 ± 0.4%, P = 0.000001). Flavanol-rich chocolate mitigated the pulse-wave velocity increase (P = 0.001). Flavanol-rich chocolate preserved working memory accuracy in women after sleep deprivation. Flow-mediated dilation correlated with working memory performance accuracy in the sleep condition (P = 0.04). Flavanol-rich chocolate counteracted vascular impairment after sleep deprivation and restored working memory performance. Improvement in cognitive performance could be because of the effects of cocoa flavonoids on blood pressure and peripheral and central blood flow.

Association Between Psoriasis and Subclinical Atherosclerosis: A Meta-Analysis.

The association between psoriasis and carotid intima-media thickness (CIMT) or impaired flow-mediated dilation (FMD) remains controversial. We aimed to evaluate the extent of subclinical atherosclerosis as measured by CIMT and FMD in patients with psoriasis by conducting a meta-analysis.A systematic literature search was performed using PubMed, Embase, Cochrane databases, China National Knowledge Infrastructure, and VIP databases up to February 2015. Observational studies investigating CIMT or FMD in patients with psoriasis and controls were eligible. Psoriatic patients and controls were at least age- and sex-matched. Random-effects analysis was used to estimate the weighted mean difference (WMD) and 95% confidence interval (CI) between psoriatic patients and controls.A total of 20 studies were identified and analyzed. Meta-analysis showed that psoriatic patients had a significantly thicker CIMT (WMD 0.11 mm; 95% CI 0.08–0.15) and lower FMD (WMD −2.79%; −4.14% to −1.43%) than those in controls. Subgroup analysis indicated that psoriatic arthritis appeared to have less impaired FMD (WMD −2.45%) and thinner CIMT (WMD 0.10 mm). Psoriatic patients with mean age >45 years had much thicker CIMT (WMD 0.13 mm). The impaired FMD (WMD −3.99%) seemed more pronounced in psoriatic patients with mean age <45 years.This meta-analysis suggests that patients with psoriasis are associated with excessive risk of subclinical atherosclerosis. Screening and monitoring CIMT and brachial artery FMD may be recommended to identify a subgroup of psoriatic patients at higher risk for cardiovascular events.

Oxygen dependence of endothelium-dependent vasodilation: importance in chronic obstructive pulmonary disease.

IntroductionEpidemiological studies have shown increased morbidity and mortality in patients with coronary artery disease (CAD) and chronic obstructive pulmonary disease (COPD). We aimed to characterize the oxygen dependence of endothelial function in patients with CAD and coexisting COPD.Material and methodsIn CAD patients with and without COPD (n = 33), we non-invasively measured flow-mediated dilation (FMD) and intima-media thickness (IMT) of the brachial artery (BA), forearm blood flow (FBF), and perfusion of the cutaneous microcirculation with laser Doppler perfusion imaging (LDPI). In an experimental setup, vascular function was assessed in healthy volunteers (n = 5) breathing 12% oxygen or 100% oxygen in comparison to room air.ResultsCOPD was associated with impaired FMD (3.4 ±0.5 vs. 4.2 ±0.6%; p < 0.001) and increased IMT (0.49 ±0.04 vs. 0.44 ±0.04 mm; p <0.01), indicating functional and structural alterations of the BA in COPD. Forearm blood flow and LDPI were comparable between the groups. Flow-mediated dilation correlated with capillary oxygen pressure (pO2, r = 0.608). Subgroup analysis in COPD patients with pO2 > 65 mm Hg and pO2 ≤ 65 mm Hg revealed even lower FMD in patients with lower pO2 (3.0 ±0.5 vs. 3.7 ±0.4%; p < 0.01). Multivariate analysis showed that pO2 was a predictor of FMD independent of the forced expiratory volume and pack years. Exposure to hypoxic air led to an acute decrease in FMD, whereby exposure to 100% oxygen did not change vascular function.ConclusionsOur data suggest that in CAD patients with COPD, decreased systemic oxygen levels lead to endothelial dysfunction, underlining the relevance of cardiopulmonary interaction and the potential importance of pulmonary treatment in secondary prevention of vascular disease.

Impaired Flow-Mediated Dilation Before, During, and After Preeclampsia: A Systematic Review and Meta-Analysis.

Endothelial dysfunction is believed to play a critical role in preeclampsia; however, it is unclear whether this dysfunction precedes the pregnancy or is caused by pathophysiological events in early pregnancy. It is also unclear for how long vascular dysfunction may persist postpartum and whether it represents a mechanism linking preeclampsia with future cardiovascular disease. Our objective was to determine whether women with preeclampsia had worse vascular function compared with women who did not have preeclampsia by performing a systematic review and meta-analysis of studies that examined endothelial dysfunction using flow-mediated dilation. We included studies published before May 29, 2015, that examined flow-mediated dilation before, during, or after preeclampsia. Differences in flow-mediated dilation between study groups were evaluated by standardized mean differences. Out of 610 abstracts identified through PubMED, EMBASE, and Web of Science, 37 studies were eligible for the meta-analysis. When compared with women who did not have preeclampsia, women who had preeclampsia had lower flow-mediated dilation before the development of preeclampsia (≈20-29 weeks gestation), at the time of preeclampsia, and for 3 years postpartum, with the estimated magnitude of the effect ranging between 0.5 and 3 standard deviations. Similar effects were observed when the analysis was limited to studies that excluded women with chronic hypertension, smokers, or both. Vascular dysfunction predates preeclampsia and may contribute to its pathogenesis. Future studies should address whether vascular changes that persist after preeclamptic pregnancies may represent a mechanistic link with increased risk for future cardiovascular disease.

Flow-Mediated Dilation and Neurocognition: Systematic Review and Future Directions.

Previous literature indicates that flow-mediated dilation (FMD) is associated with impaired cognition among patients with stroke. The relationship between FMD and cognition in individuals without cerebrovascular disease has yet to be systematically reviewed. The literature was searched using MEDLINE. Exclusion criteria were as follows: focus on neurological disease (e.g., stroke), animal studies, no quantitative measure of endothelial function or cognition, newborn studies, articles with no original data, and articles that are irrelevant to the topic of interest. Neurocognitive tests were categorized in the following domains: executive function, memory (general, working, episodic/semantic, verbal, visual), global cognitive function, information processing speed, language, psychomotor speed, and visual-spatial ability. The search yielded 700 articles, of which 10 articles, consisting of 2791 participants, met the criteria for inclusion. Most studies conclude that impaired FMD is associated with poorer neuropsychological functioning, particularly in executive functioning (effect sizes: r = 0.07-0.58) and working memory tasks (effect sizes: r = 0.19-0.39). No association was found between other subdomains of memory and FMD. Visual spatial tasks, information processing speed, language tasks, and global cognition were not associated with FMD overall; however fewer studies examined these domains. Even in the absence of cerebrovascular disease, there are links between cognition, particularly executive tasks, and vascular function. Public health implications include the potential value of examining FMD as a predictor of cognitive decline, as well as the potential value of improving cognition through pharmacological and behavioral interventions that improve vascular function. Future studies incorporating neuroimaging measures of cerebral blood flow are warranted.

Serial assessment of arterial structure and function in patients with coarctation of the aorta undergoing stenting

Stenting for CoA has become an acceptable treatment modality in the last 20years. However little is known about arterial changes after this procedure. To assess arterial structure and function including peripheral reactivity and stiffness and intima-media thickness (IMT) pre and post stenting for coarctation of the aorta (CoA). Twenty-one patients [median age: 15years (8-39)] were studied at baseline, 1day, 6months and 1year after stenting. Twenty-one healthy subjects (1:1 matched) were used as controls. Left ventricular (LV) mass, ejection fraction, flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of left brachial artery, common carotid (CC) and right subclavian artery (RSCA) IMT and pulse wave velocity (PWV) were assessed by echocardiography and vascular ultrasound. CoA patients had higher LV indexed mass (p<0.0001), impaired FMD (p<0.0001) and NMD (p<0.0001), increased PWV (p<0.0001), carotid and RSCA IMT (both p<0.0001). All procedures were successful and resulted in significant gradient reduction (p<0.001). One year after stenting there was improvement in LV function (p=0.034) and although there was significant reduction of LV mass (103.29±24.77 vs. 74.39±22.07g/m(2), p<0.0001) values did not normalize. There was no significant change in FMD, NMD, PWV and CC or RSCA IMT. In patients with CoA, arterial reactivity is impaired and LV mass, arterial stiffness and thickness are increased. Although stenting is successful to relieve the obstruction resulting in better LV function and mass reduction, arterial structure and function remains abnormal after 1year of follow-up.

Impairment of Endothelial Function by Little Cigar Secondhand Smoke.

Little cigars and cigarillos are gaining in popularity as cigarette use wanes, mainly due to relaxed regulatory standards that make them cheaper, easier to buy individually, and available in a variety of flavors not allowed in cigarettes. To address whether they should be regulated as strictly as cigarettes, we investigated whether little cigar secondhand smoke (SHS) decreases vascular endothelial function like that of cigarettes. We exposed rats to SHS from little cigars, cigarettes, or chamber air, for 10 minutes and measured the resulting acute impairment of arterial flow-mediated dilation (FMD). SHS from both little cigars and cigarettes impaired FMD. Impairment was greater after exposure to little cigar SHS than by cigarette SHS relative to pre-exposure values, although the post-exposure FMD values were not significantly different from each other. Exposure to little cigar SHS leads to impairment of FMD that is at least equal to that resulting from similar levels of cigarette SHS. Our findings support the need to prevent even brief exposure to little cigar SHS, and support tobacco control policies that regulate little cigars as strictly as cigarettes.

Vasculoprotective Effects of Dietary Cocoa Flavanols in Patients on Hemodialysis: A Double-Blind, Randomized, Placebo-Controlled Trial.

Hemodialysis (HD) per se entails vascular dysfunction in patients with ESRD. Endothelial dysfunction is a key step in atherosclerosis and is characterized by impaired flow-mediated dilation (FMD). Interventional studies have shown that cocoa flavanol (CF)-rich supplements improve vascular function. Aim of this study was to investigate the effect of flavanol-rich bioactive food ingredients on acute and chronic HD-induced vascular dysfunction in ESRD. We conducted a randomized, double-blind, placebo-controlled trial from 2012 to 2013. Fifty-seven participants were enrolled, ingested CF-rich beverages (900 mg CF per study day), and were compared with those ingesting CF-free placebo. This included (1) a baseline cross-over acute study to determine safety and efficacy of CF and (2) a subsequent chronic parallel group study with a 30-day follow-up period to study effects of CF on HD-mediated vascular dysfunction entailing (3) an acute substudy during HD in flavanol-naive patients and (4) an acute on chronic study during HD. Primary and secondary outcome measures included changes in FMD and hemodynamics. CF ingestion was well tolerated. Acute ingestion improved FMD by 53% (3.2±0.6% to 4.8±0.9% versus placebo, 3.2±0.7% to 3.3±0.8%; P<0.001), with no effects on BP or heart rate. A 30-day ingestion of CF led to an increase in baseline FMD by 18% (3.4±0.9% to 3.9±0.8% versus placebo, 3.5±0.7% to 3.5±0.7%; P<0.001), with reduced diastolic BP (73±12 to 69±11 mmHg versus placebo, 70±11 to 73±13 mmHg; P=0.03) and increased heart rate (70±12 to 74±13 bpm versus placebo, 75±15 to 74±13 bpm; P=0.01). No effects were observed for placebo. Acute ingestion of CF during HD alleviated HD-induced vascular dysfunction (3.4±0.9% to 2.7±0.6% versus placebo, 3.5±0.7% to 2.0±0.6%; P<0.001). This effect was sustained throughout the study (acute on chronic, 3.9±0.9% to 3.0±0.7% versus placebo, 3.5±0.7% to 2.2±0.6; P=0.01). Dietary CF ingestion mitigates acute HD-induced and chronic endothelial dysfunction in patients with ESRD and thus, improves vascular function in this high-risk population. Larger clinical trials are warranted to test whether this translates into an improved cardiovascular prognosis in patients with ESRD.

Does Lichen Planus Cause Increased Carotid Intima-Media Thickness and Impaired Endothelial Function?

BackgroundLichen planus (LP) has been associated with cardiovascular disease (CVD) risk factors, but there are no studies on the association between LP and subclinical atherosclerosis. We investigated the presence of subclinical atherosclerosis in patients with LP not known to have CVD using carotid intima-media thickness (CIMT) and flow-mediated dilatation (FMD). MethodsThe study included 30 patients with LP and 30 controls. High-resolution ultrasonography was used to assess CIMT and FMD. Participants' biochemical parameters, body mass index (BMI), and waist circumference were recorded in both groups. ResultsFMD was significantly lower (7.45% ± 3.63% vs 11.01% ± 5.34%; P = 0.004) and CIMT was higher (0.8 mm [range, 0.7-0.9 mm] vs 0.6 mm [0.4-0.6 mm]; P < 0.001) in the LP group compared with the control group. After adjustment for age, sex, BMI, high-density lipoprotein cholesterol levels, and C-reactive protein levels, the presence of LP was associated with impairment of FMD (β = −0.441; 95% CI, −9.336 to −0.321; P = 0.037) and an increase in CIMT (β = 0.459; 95% CI, 0.057 to −0.351; P = 0.008). ConclusionsReduced FMD and increased CIMT levels are sensitive indicators of target-organ damage and display increased risk for cardiovascular morbidity and mortality. Our study found that patients with LP showed a tendency toward impaired levels of FMD and increased CIMT. LP may be a novel predictor of early vascular dysfunction and structural changes.

Abstract 12770: The Significant Role of Endothelium and Arterial Wall Properties in Patients With Pseudoexfoliative Glaucoma

Introduction: Primary open-angle glaucoma (POAG) is one of the most prevalent causes of irreversible blindness and is associated with endothelial dysfunction and arterial stiffness. Pseudoexfoliative glaucoma (PEG) is another type of glaucoma observed in pseudoexfoliation syndrome. It is characterized by the deposition of pseudoexfoliative material not only to the anterior segment of the eye, but also to the vessels, heart and other organs. Hypothesis: Endothelial function and arterial stiffness are impaired in patients with POAG and PEG supporting the significant role of vascular function impairment in the progression of the disease. Methods: Forty four POAG patients, 22 PEG and 38 healthy subjects (Cl) were included in this study. All subjects were free of cardiovascular or inflammatory diseases. Endothelial function was evaluated by flow-mediated dilatation (FMD). Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as a measure of arterial wave reflections Results: Between the three study groups CL, POAG, PEG there was no difference in age (67±10years vs. 70±9years vs. 66±12yeras, p=0.12) or prevalence of male sex (70% vs. 57% vs. 50%, p=0.21). Importantly, there was a linear impairment of FMD (7.35±2.77% vs. 6.58±3.18% vs. 4.88±3.29%, p=0.006), PWV (7.98±1.56m/sec vs. 9.20±1.84m/sec vs. 9.22±2.16m/sec, p=0.004) and AIx (21.29±8.77% vs. 25.14±5.71% vs. 28.20±8.75%, p=0.002) from CL to POAG and PEG. Interestingly post hoc test after Scheffe correction revealed also that PEG subjects had not only significantly impaired FMD, compared to control subjects, but also compared to POAG subjects (4.88±3.29% vs. 6.58±3.18%, p=0.02). Conclusions: Endothelial function and arterial stiffness are significantly impaired in patients with pseudoexfoliative glaucoma. These findings shed some light in the pathophysiology of pseudoexfoliative glaucoma and support the theory that pseudoexfoliative fibrils may also accumulate and damage the arterial wall.

Serum amyloid P (SAP) is associated with impaired brachial artery flow-mediated dilation in chronically HIV-1 infected adults on stable antiretroviral therapy

Objective:This study aimed to evaluate the relationship between inflammatory biomarkers and endothelial dysfunction (ED), as measured by brachial artery flow-mediated dilation (FMD).Methods:We conducted a cross-sectional analysis utilizing baseline data of 135 participants with HIV infection on stable antiretroviral therapy (ART) in the Hawaii Aging with HIV-Cardiovascular (HAHC-CVD) study who had available baseline inflammatory biomarkers and brachial artery FMD measurements.Results:We observed significant associations between brachial artery FMD and baseline brachial artery diameter, age, male gender, traditional cardiovascular disease (CVD) risk factors such as BMI, waist to hip ratio, hypertension, systolic blood pressure (BP), diastolic BP, and LDL cholesterol, and 10-year coronary heart disease (CHD) risk estimated by Framingham risk score (FRS). Of all biomarkers tested, higher level of C-reactive protein (CRP) (beta = − 0.695, P = 0.030) and serum amyloid P (SAP) (beta = − 1.318, P = 0.021) were significantly associated with lower brachial artery FMD in univariable regression analysis. After adjusting for baseline brachial artery diameter, age, and selected traditional CVD risk factors in multivariable model, SAP remained significantly associated with brachial artery FMD (beta = − 1.094, P = 0.030), while CRP was not (beta = − 0.391, P = 0.181).Discussion:Serum amyloid P was independently associated with impaired brachial artery FMD and may potentially relate to ED and increased CVD risk in HIV-infected patients on stable ART.

Effect of cholecalciferol on local arterial stiffness and endothelial dysfunction in children with chronic kidney disease.

As cardiovascular factors are the leading cause of mortality in chronic kidney disease (CKD) and as vitamin D deficiency is prevalent in this population, we aimed to examine the effect of oral cholecalciferol on cardiac parameters and biomarkers for endothelial cell activation in children with CKD. Forty-one children with CKD and 24 healthy subjects free of any underlying cardiac or renal disease with low 25-hydroxyvitamin D3 (25OHD) levels were evaluated using echocardiography basally and following Stoss vitamin D supplementation. The local vascular stiffness and endothelial dysfunction markers were compared among the groups. Initial flow-mediated dilatation (FMD) measurements were lower and local arterial stiffness was significantly higher in patients. After vitamin D supplementation, these improved significantly in patients, while no significant change was observed for the healthy group. Homocysteine showed inverse correlation with baseline vitamin D level in CKD children and von Willebrand factor emerged as an independent risk factor for FMD impairment. Our interventional study revealed the favorable effects of high-dose cholecalciferol on cardiovascular and endothelial parameters, implying the importance of vitamin D supplementation in children with CKD.

Aldosterone Impairs Vascular Smooth Muscle Function: From Clinical to Bench Research.

The effect of aldosterone on vascular smooth muscle cell function is still unclear. One method to measure vascular smooth muscle cell function is endothelial-independent vascular dilation, for which the key factor is sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA). Our objective was to investigate the effect of aldosterone on vascular smooth muscle cell function and SERCA regulation. We prospectively analyzed 35 patients with primary aldosteronism (PA; 32 patients with aldosterone-producing adenoma and three patients with idiopathic hyperaldosteronism) and 30 patients with essential hypertension (EH) who were enrolled as the control group. Flow and nitrate-mediated dilation were performed in both groups and 1 year after adrenalectomy in the patients with aldosterone-producing adenoma. In addition, we investigated the effect of aldosterone on SERCA regulation in human aortic smooth muscle cells. This study took place in an academic clinical research center. Participants included 35 patients with PA and 30 patients with EH. Adrenalectomy was undertaken in patients with aldosterone-producing adenoma. The PA patients had significantly lower flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) values than the patients with EH (FMD: 13 ± 6 vs 16 ± 4; NMD: 16 ± 6 vs 19 ± 5; both P < .05). FMD/NMD were significantly correlated with log 24 hour-urine aldosterone (FMD: r = -0.287, P = .048; NMD: r = -0.402, P = .005) but not blood pressure. The impaired FMD and NMD values were significantly restored 1 year after adrenalectomy (FMD: 11 ± 4 to 19 ± 7; NMD: 15 ± 6 to 21 ± 6; both P < .01). Under confocal microscopy, aldosterone was shown to suppress the expression of SERCA2a of human aortic smooth muscle cells. Aldosterone significantly suppressed the expression of SERCA2a from 10(-8) M in mRNA and protein levels. This suppression was through down-regulation of mineralocorticoid receptor dependent mitochondrial transcription factors A and B2. Aldosterone impairs vascular smooth muscle cell function and suppresses SERCA 2a expression.

Prognostic significance of endothelial dysfunction in patients undergoing percutaneous coronary intervention in the era of drug-eluting stents.

BackgroundEndothelial function is a prognostic predictor in patients undergoing percutaneous coronary intervention (PCI). However, in an era with widespread use of drug-eluting stents, the clinical relevance of endothelial dysfunction on restenosis in patients undergoing PCI has not been fully evaluated.MethodsThis study included 80 patients with stable angina pectoris. Flow-mediated dilation (FMD) of the brachial artery was examined 1 week after PCI. Patients were retrospectively followed-up for an average of 21 months after PCI. The primary endpoints included cardiac death, nonfatal myocardial infarction, stroke, coronary revascularization, and critical limb ischemia.ResultsA drug-eluting stent was used in 58 patients and a cardiovascular event was recorded in 34 patients during follow-up. The incidence of all cardiovascular diseases was significantly greater in the low FMD (median FMD <4.2 %) than the high FMD (median FMD ≥4.2 %) group (60 % vs. 25 %, p <0.01). Furthermore, the incidence of coronary revascularization was significantly higher in the low than the high FMD group (p = 0.02), while the incidence of in-stent restenosis did not differ between the two groups. Cox regression analysis showed that low FMD was an independent predictor of cardiovascular events (hazard ratio: 2.77, 95 % confidence interval: 1.23 to 6.19, p = 0.01).ConclusionsImpaired brachial artery FMD independently predicts long-term cardiovascular events after PCI in the era of drug-eluting stents.