Decrease In Endothelial Function Research Articles

Impact of psychoemotional stress and physical activity on endothelial function in hypertensive patients with obesity

Objective . To study the effect of chronic emotional stress and physical activity on endothelial function in patients with arterial hypertension (HTN) and obesity. Design and methods. We enrolled 76 male patients with HTN stage I and II. Group 1 consisted of 36 patients with HTN and obesity, group 2–40 hypertensive patients without obesity. Ultrasound of the brachial artery was performed to assess endothelial function after reactive hyperemia (flow-mediated dilation) and nitrate administration (nitrate-mediated dilation). Serum cortisol level was determined by enzyme-linked immunosorbent assay. PSM‑25 scale was used to access psycho-emotional stress. The level of reactive and personal anxiety was measured by the Spielberger and Khanin’s questionnaire. Brief international physical activity questionnaire was used (IPAQ) for physical activity evaluation. Results. In patients with HTN and obesity a more significant deterioration of the flow-mediated and nitrate-mediated dilation (FMD and NMD) was found compared to hypertensive patients without obesity, and to healthy individuals. In both groups physically inactive patients showed a significant decrease in endothelial function compared to physically active patients. In group 1, an inverse correlation between FMD with the level of reactive anxiety and trait anxiety (r = –0,54; r = –0,46, respectively; p < 0,05) and a direct correlation with the level of physical activity (r = 0,42; p = 0,01) was found. In group 2, FMD and NMD inversely correlated with psycho-emotional stress (r = –0,42; r = –0,33, respectively; p < 0,05) and directly correlated with the level of physical activity (r = 0,46; r = 0,33, respectively; p < 0,05). In both groups, there were direct correlations between cortisol levels with personal and reactive anxiety scores. Furthermore, there was an inverse association between FMD and cortisol levels in group 1 (r = –0,36; p = 0,05) and group 2 (r = –0,41; p = 0,02). Conclusions. Our findings suggest a strong connection between chronic emotional stress and physical inactivity with endothelial dysfunction in hypertensive patients.

Abstract 19288: Acute and Chronic Affects of Indoor Air Pollution on Endothelial Function

Objective: Pollution exposure has been linked to accelerated atherosclerosis. Endothelial dysfunction is a reversible indicator for early atherosclerosis, but it is unknown if indoor air pollution from biomass fuel cookstoves is associated with acute and chronic endothelial dysfunction. Methods: We enrolled 76 adults in Puno, Peru (3825 m above sea level); 56 from a rural community that almost exclusively use biomass fuels for cooking (biomass fuel users) and 20 from urban communities that use clean fuels for cooking (clean fuel users). We measured flow-mediated dilatation (FMD) of the brachial artery before and after cooking. We compared baseline FMD in biomass vs. clean fuel users and evaluated for acute effects of cooking by looking and changes in FMD before and after cooking with biomass vs. clean fuels Results: Mean age was 53 ± 9.1 years with 54% male. Biomass fuel users had similar age, blood pressure, and BMI but had lower LDL-cholesterol compared to clean fuel users (p&lt;0.05). Mean baseline FMD was 5.2 ± 2.3% vs. 6.3 ± 3.2% in clean vs. biomass fuel users respectively (p=0.22). Adjusting for age, sex, blood pressure, BMI, and LDL-cholesterol demonstrated no difference in baseline FMD between biomass and clean fuel users (p=0.92). Among biomass fuel users, mean FMD dropped to 3.8 ± 3.0% after one hour of biomass fuel smoke exposure from cooking (p&lt;0.001). This did not occur when FMD was repeated in clean fuel users one hour after baseline exam (FMD: 4.9 ± 2.9%, p=0.29). Conclusion: Biomass fuel smoke exposure causes acute decrease in endothelial function in this population with already abnormal function. However, we found no differences in baseline endothelial function in these two heterogeneous populations. Larger studies are needed to determine if biomass fuel exposure is associated with chronic endothelial dysfunction and if interventions aimed to decrease biomass fuel smoke exposure can improve endothelial function and thus cardiovascular mortality.

Impact of shear rate pattern on upper and lower limb conduit artery endothelial function in both spinal cord-injured and able-bodied men.

What is the central question of this study? This study addresses the following two central questions. (i) What is the impact of vascular deconditioning after spinal cord injury (SCI) on shear rate patterns and endothelial function? (ii) What is the impact of acutely altered shear rate on endothelial function in both SCI and able-bodied control subjects? What is the main finding and its importance? Two main findings in the present study were as follows: (i) reduced superficial femoral artery endothelial function in the SCI group; and (ii) acutely altered shear rate decreased endothelial function in both SCI and able-bodied control subjects. These findings may shed some light on future interventions taking into account these regulatory mechanisms. Spinal cord injury (SCI) induces vascular deconditioning below the level of the lesion and disrupts sympathetic innervation of blood vessels. It is unclear how these changes affect shear rate (SR) profiles and endothelial function when compared with able-bodied (AB) persons. Recent evidence suggests that periods of increased retrograde SR are associated with acute decreases in endothelial function, but is unknown how modified SR patterns influence sublesional vasculature in SCI. The present study examined the acute and chronic effects of altered SR patterns and oscillatory shear index on endothelial function via relative flow-mediated dilatation (FMD%) in both the brachial and superficial femoral arteries (BA and SFA, respectively) of eight individuals with SCI and eight matched AB control subjects. Baseline BA SR patterns and FMD% were similar between groups, while SFA anterograde SR was higher (P < 0.01) and FMD% lower (P = 0.04) in SCI versus AB subjects. Shear rate patterns were then acutely altered through the BA and SFA using a subsystolic cuff-inflation model. Bilateral FMD assessments were conducted before and after 30 min of unilateral inflation of a forearm or thigh blood pressure cuff to 75 mmHg. Cuff inflation resulted in concomitant increases in both anterograde (P < 0.05) and retrograde SR (P < 0.05), as well as acute decreases in FMD% (P < 0.05) in the BA and SFA in both groups. These results highlight that brief manipulation of SR patterns can acutely impair FMD% in conditions of both normal and altered sympathetic innervation and arterial remodelling. This information is crucial when designing strategies to combat impaired vascular function in both healthy and clinical populations.

Alterations in endothelial function and fractional O2 extraction in long‐term cancer survivors treated with chemotherapy and radiation

Chemotherapy and radiation cancer therapeutics increase arterial stiffness and decrease aerobic exercise capacity. During exercise, the profile of microvascular fractional O2 extraction measured via near‐infrared spectroscopy (NIRS) derived muscle deoxygenation (Δdeoxy‐[Hb+Mb]) provides information on the dynamic matching of O2 delivery‐to‐O2 utilization. We tested the hypothesis that cancer survivors would have an altered profile of Δdeoxy‐[Hb+Mb] during exercise that would be related to decreases in endothelial function. To date, 2 cancer survivors (CS) and 1 healthy control (HC) completed a brachial artery flow‐mediated dilation test (FMD) and ramp exercise test on a cycle ergometer. During exercise Δdeoxy‐[Hb+Mb] of the vastus lateralis and rectus femoris was measured, normalized from baseline (0%) to the gas exchange threshold (GET) (100%). The power output at GET (POGET) was lower in CS compared to HC. CS had a smaller shear rate normalized FMD compared to HC (1.07 × 10‐5 vs. 3.54 × 10‐5 %Δ/s‐1 s, respectively). Both groups displayed a linear increase in %Δdeoxy‐[Hb+Mb]. The %Δdeoxy‐[Hb+Mb] slope of the vastus lateralis was greater in CS compared to HC when plotted as a function of POGET (2.04 vs. 0.80 % W‐1, respectively) and %POGET (1.84 vs. 1.17 % %W‐1, respectively). A greater %Δdeoxy‐[Hb+Mb] slope of the rectus femoris was also observed in CS compared to HC (1.29 vs. 0.74 % W‐1 and 1.17 vs. 1.09 % %W‐1, respectively). In conclusion, the greater reliance on fractional O2 extraction in CS during exercise suggests an impaired matching of O2 delivery‐to‐O2 utilization relationship during exercise compared to HC, which may be the result of decreased endothelial function.

Elevation in blood flow and shear rate prevents hyperglycemia-induced endothelial dysfunction in healthy subjects and those with type 2 diabetes

Hyperglycemia, commonly present after a meal, causes transient impairment in endothelial function. We examined whether increases in blood flow (BF) protect against the hyperglycemia-mediated decrease in endothelial function in healthy subjects and patients with type 2 diabetes mellitus (T2DM). Ten healthy subjects and 10 age- and sex-matched patients with T2DM underwent simultaneous bilateral assessment of brachial artery endothelial function by means of flow-mediated dilation (FMD) using high-resolution echo-Doppler. FMD was examined before and 60, 120, and 150 min after a 75-g oral glucose challenge. We unilaterally manipulated BF by heating one arm between minute 30 and minute 60. Oral glucose administration caused a statistically significant, transient increase in blood glucose in both groups (P < 0.001). Forearm skin temperature, brachial artery BF, and shear rate significantly increased in the heated arm (P < 0.001), and to a greater extent compared with the nonheated arm in both groups (interaction effect P < 0.001). The glucose load caused a transient decrease in FMD% (P < 0.05), whereas heating significantly prevented the decline (interaction effect P < 0.01). Also, when correcting for changes in diameter and shear rate, we found that the hyperglycemia-induced decrease in FMD can be prevented by local heating (P < 0.05). These effects on FMD were observed in both groups. Our data indicate that nonmetabolically driven elevation in BF and shear rate can similarly prevent the hyperglycemia-induced decline in conduit artery endothelial function in healthy volunteers and in patients with type 2 diabetes. Additional research is warranted to confirm that other interventions that increase BF and shear rate equally protect the endothelium when challenged by hyperglycemia.

Remote ischemic preconditioning prevents reduction in brachial artery flow-mediated dilation after strenuous exercise

Strenuous exercise is associated with an immediate decrease in endothelial function. Repeated bouts of ischemia followed by reperfusion, known as remote ischemic preconditioning (RIPC), is able to protect the endothelium against ischemia-induced injury beyond the ischemic area. We examined the hypothesis that RIPC prevents the decrease in endothelial function observed after strenuous exercise in healthy men. In a randomized, crossover study, 13 healthy men performed running exercise preceded by RIPC of the lower limbs (4 × 5-min 220-mmHg bilateral occlusion) or a sham intervention (sham; 4 × 5-min 20-mmHg bilateral occlusion). Participants performed a graded maximal treadmill running test, followed by a 5-km time trial (TT). Brachial artery endothelial function was examined before and after RIPC or sham, as well as after the 5-km TT. We measured flow-mediated dilation (FMD), an index of endothelium-dependent function, using high-resolution echo-Doppler. We also calculated the shear rate area-under-the-curve (from cuff deflation to peak dilatation; SR(AUC)). Data are described as mean and 95% confidence intervals. FMD changed by <0.6% immediately after both ischemic preconditioning (IPC) and sham interventions (P > 0.30). In the sham trial, FMD changed from 5.1 (4.4-5.9) to 3.7% (2.6-4.8) following the 5-km TT (P = 0.02). In the RIPC trial, FMD changed negligibly from 5.4 (4.4-6.4) post-IPC and 5.7% (4.6-6.8) post 5-km TT (P = 0.60). Baseline diameter, SR(AUC), and time-to-peak diameter were all increased following the 5-km TT (P < 0.05), but these changes did not influence the IPC-mediated maintenance of FMD. In conclusion, these data indicate that strenuous lower-limb exercise results in an acute decrease in brachial artery FMD of ~1.4% in healthy men. However, we have shown for the first time that prior RIPC of the lower limbs maintains postexercise brachial artery endothelium-dependent function at preexercise levels.

The Exposure-Dependent Effects of Aged Secondhand Smoke on Endothelial Function

The aim of this study was to investigate whether exposure to a range of relatively low concentrations of aged secondhand smoke (SHS), similar to those encountered commonly in the community, would impair endothelial function in a concentration-dependent manner. Exposure to SHS impairs endothelial function in humans. The concentration-dependent relationship for aged SHS effects on endothelial function after an exposure of short duration is unknown. Thirty-three healthy nonsmokers were exposed to 1 of 2 low levels of aged SHS or to conditioned filtered air for 30 min. The primary end point was change in maximal percent brachial artery flow-mediated dilation after exposure. In a linear regression model for each increase in SHS exposure by 100 μg/m(3) respirable suspended particles, the absolute maximal percent brachial artery flow-mediated dilation was reduced by 0.67%. We did not find evidence of a threshold for the effect of SHS on flow-mediated dilation. Short-term exposure to real-world levels of aged SHS for 30 min resulted in a concentration-dependent decrease in endothelial function as measured by flow-mediated dilation.

Postprandial impairment of flow-mediated dilation and elevated methylglyoxal after simple but not complex carbohydrate consumption in dogs

Hyperglycemia produces oxidative stress, which may impair endothelial function. Methylglyoxal, a reactive intermediate metabolite of glucose, is known to cause oxidative stress and is produced when excess carbohydrate is consumed in diabetic patients, but postprandial responses in healthy patients are unknown. We hypothesize that methylglyoxal levels will cause impaired endothelial function via increased oxidative stress after consuming a high glycemic index meal in healthy animals. Normal-weight laboratory beagles (n = 6) were used in a crossover study that tested postprandial responses of 4 complex carbohydrate sources (barley, corn, peas, rice) vs a simple carbohydrate (glucose). Blood samples were taken prefeeding and at timed intervals after feeding to measure serum glucose, insulin, nitrotyrosine, and methylglyoxal. Flow-mediated dilation (FMD), cardiac function (echocardiography), and blood pressure measurements were determined before and 60 minutes after feeding. The mean (±SEM) glycemic indices of the complex carbohydrate sources were 29 ± 5 for peas, 47 ± 10 for corn, 51 ± 7 for barley, and 55 ± 6 for rice. Postprandial FMD was lowest in the glucose group and significantly different from both the corn group and the FMD value for all complex carbohydrates combined. Methylglyoxal was significantly elevated at 60 minutes postprandial after glucose compared with the other carbohydrate sources. No significant effects of carbohydrate source were observed for blood pressure, nitrotyrosine, or echocardiographic variables. The novel finding of this study was that methylglyoxal levels increased after a single feeding of simple carbohydrate and may be linked to the observed postprandial decrease in endothelial function. Thus, consuming low-glycemic-index foods may protect the cardiovascular system by reducing oxidative stress.

Sympathetic regulation of vascular function in health and disease

The sympathetic nervous system (SNS) is known to play a pivotal role in short- and long-term regulation of different functions of the cardiovascular system. In the past decades increasing evidence demonstrated that sympathetic neural control is involved not only in the vasomotor control of small resistance arteries but also in modulation of large artery function. Sympathetic activity and vascular function, both of which are key factors in the development and prognosis of cardiovascular events and disease, are linked at several levels. Evidence from experimental studies indicates that the SNS is critically influenced, at the central and also at the peripheral level, by the most relevant factors regulating vascular function, such as nitric oxide (NO), reactive oxygen species (ROS), endothelin (ET), the renin-angiotensin system. Additionally, there is indirect evidence of a reciprocal relationship between endothelial function and activity of the SNS. A number of cardiovascular risk factors and diseases are characterized both by increased sympathetic outflow and decreased endothelial function. In healthy subjects, muscle sympathetic nerve activity (MSNA) appears to be related to surrogate markers of endothelial function, and an acute increase in sympathetic activity has been associated with a decrease in endothelial function in healthy subjects. However, direct evidence of a cause-effect relationship from human studies is scanty. In humans large artery stiffness has been associated with increased sympathetic discharge, both in healthy subjects and in renal transplant recipients. Peripheral sympathetic discharge is also able to modulate wave reflection. On the other hand, large artery stiffness can interfere with autonomic regulation by impairing carotid baroreflex sensitivity.

Nocturnal release of leukocyte-derived microparticles in males with obstructive sleep apnoea

To the Editors: Multiple pathophysiological mechanisms have been proposed to contribute to the increased cardiovascular morbidity in obstructive sleep apnoea (OSA), including autonomic dysfunction, inflammation, oxidative stress and endothelial dysfunction 1. Microparticles (MPs) are small membrane vesicles that are shed from circulating cells or from the components of the vessel wall in response to activation and apoptosis. There is growing evidence in support of a potential role of MPs in the field of cardiovascular diseases. Increased levels of MPs derived from various cell types are found in patients at risk of cardiovascular diseases 2. By modulating inflammation, coagulation, vasomotor reactivity and angiogenesis, MPs might directly contribute to cardiovascular diseases 2. Recent case–control studies suggest a potential involvement of MPs in OSA-associated cardiovascular morbidity 3–6. An increase in morning levels of MPs derived from activated leukocytes has been demonstrated in otherwise healthy male OSA patients with marked nocturnal desaturations 5. In vitro , nitric oxide (NO) production by endothelial cells incubated with MPs from OSA patients correlates negatively with circulating levels of activated leukocyte-derived MPs 5. Ex vivo , mice previously injected with MPs from OSA patients display endothelial dysfunction, reduced endothelial NO release and increased adhesion molecule expression 5. A decrease in endothelial function from evening to morning has previously been demonstrated in patients with OSA and found to correlate with the severity of sleep-disordered breathing 7. Since recent data suggest a potential role MPs in endothelial dysfunction 5, we aimed to study evening-to-morning change in activated leukocyte-derived MPs levels in otherwise healthy patients with OSA. …

Reduced brachial flow-mediated vasodilation in young adult ex extremely low birth weight preterm: a condition predictive of increased cardiovascular risk?

Background. Sporadic data present in literature report how preterm birth and low birth weight constitute the risk factors for the development of cardiovascular diseases in later life.Aim. To assess the presence of potential alterations to endothelial function in young adults born preterm at extremely low birth weight (<1000 g; ex ELBW).Method. Thirty-two ex-ELBW subjects (10 males [M] and 22 females [F], aged 17–28 years, mean [±DS] 20.1 ± 2.5 years) were compared with 32 healthy, age-matched subjects born at term (C, 9 M and 23 F). Exclusion criteria: 1) pathological conditions known to affect endothelial function; 2) administration of drugs known to affect endothelial function. Endothelial function was assessed by non-invasive finger plethysmography, previously validated by the US Food and Drug Administration (Endopath; Itamar Medical Ltd., Cesarea, Israel).Results. Endothelial function was significantly reduced in ex-ELBW subjects compared to C (1.94 ± 0.37 vs 2.68 ± 0.41, p < 0.0001). Moreover, this function correlated significantly with gestational age (r = 0.56, p < 0.0009) and birth weight (r = 0.63, p < 0.0001).Conclusions. The results obtained reveal a significant decrease in endothelial function of ex-ELBW subjects compared to controls, underlining a probable correlation with preterm birth and low birth weight. Taken together, these results suggest that an ELBW may underlie the onset of early circulatory dysfunction predictive of increased cardiovascular risk.

Adverse Impact of Mood on Flow-Mediated Dilation

To examine the impact of mood states on endothelial function, as measured noninvasively by brachial artery flow-mediated dilation (FMD). Substantial literature indicates that negative mood is linked to cardiovascular disease (CVD). However, the mechanisms underlying this relationship are not well defined. CVD is often preceded by dysfunction of the endothelium. Healthy adults (n = 70; mean age, 36 years) completed the Profile of Mood States (POMS), which contains six subscales (depression/dejection; tension/anxiety; anger/hostility; confusion/bewilderment; fatigue/inertia; vigor/activity) that are used to compute a total mood disturbance score for overall psychological distress. FMD was calculated (maximum percentage change in brachial artery diameter) from ultrasound assessment of arterial diameter at baseline and for 10 minutes after occlusion. Regressions showed that increases in POMS total mood disturbance scores were associated with decreases in endothelial function. Mood disturbance explained 10% of the variance in FMD (p < .01), after controlling for age, sex, mean arterial pressure, body mass index, and socially desirable response bias. An exploratory set of separate regressions conducted to decompose the link between FMD and total mood disturbance revealed that the following POMS subscales were inversely correlated with FMD: depression/dejection, tension/anxiety, anger/hostility, fatigue/inertia (p's < .05), and confusion/bewilderment (p < .01). Mood disturbance could contribute to CVD via impaired vasodilation. These preliminary results show that even mild levels of adverse psychological states, particularly depressed, anxious, angry, confused, and fatigued states, might be linked to increased cardiovascular risk.

Including rapeseed protein in a high‐fat meal prevents postprandial vascular endothelial dysfunction in rats

High saturated fat/ high sucrose meals induce oxidative stress associated with vascular endothelial dysfunction, an early hallmark in atherogenesis, but the impact of meal protein on vascular homeostasis remains misunderstood. Here, we investigated the potential of rapeseed protein, an emergent cysteine‐rich protein, to modulate the adverse effects of a high‐fat meal (HFM).In a cross‐over design, 12 healthy rats received 3 isoenergetic HFM (saturated fat: 60%; sucrose: 20%; proteins: 20% of total energy) with the protein source being either total milk protein (C), rapeseed protein (R), or milk protein supplemented with cysteine and arginine up to the same level as in R (AA). Endothelium‐related vascular reactivity, measured as acetylcholine‐induced transient fall in blood pressure, and plasma triglycerides, hydroperoxides and cGMP were measured before and 2, 4 and 6 h after meal.While plasma triglycerides rose similarly in all meals, the decrease in endothelial function after C was attenuated after AA and steadily blunted after R. The postmeal decrease in plasma cGMP was lessened 2h after R, as compared to after meal C. Plasma hydroperoxydes increased after the 3 meals, but were lower 6h after meals AA and R than after C.These results show that rapeseed protein specifically suppresses the acute deleterious effects of HFM on endothelial function, and this may be mediated in part by cysteine and arginine.

The clinical significance of abnormal diurnal blood pressure variation in healthy late middle‐aged and older adults

Objective. A fall in nocturnal blood pressure (BP) is generally observed in normotensive subjects as well as in those with mild to moderate essential hypertension, regardless of the level of daytime BP. Among elderly hypertensive subjects, extreme‐dippers with a marked nocturnal fall in BP as well as non‐dippers with nocturnal fall absence are at increased risk for cardiovascular and cerebrovascular complications. However, the relationship between these abnormal diurnal BP variation patterns in normotensive elderly subjects has not been investigated. Methods. We classified 45 healthy late middle‐aged and older adults into three groups according to the nocturnal systolic BP fall pattern examined by 24‐h ambulatory BP monitoring (dipper, non‐dipper and extreme‐dipper), and compared the parameters of initial atherosclerosis, endothelial function and autonomic function. As a parameter of atherosclerotic factors, the intima‐media thickness (IMT) of the carotid artery was examined, and as a parameter of endothelial function, brachial artery endothelium‐dependent flow‐mediated dilation (FMD) was ultrasonographyically measured. Autonomic function was assessed by power spectral analysis of heart rate variability (HRV). Results. No difference was observed in the severity of IMT between the three groups. The percent change of FMD in subjects in the extreme‐dipper group was significantly lower than that of subjects in the dipper group, indicating that extreme‐dippers in healthy elderly subjects may be associated with endothelial dysfunction. Also, HRV due to sympathetic modulation of subjects in the extreme‐dipper group was significantly higher than that of subjects in the dipper and non‐dipper groups, suggesting the activation of sympathetic tone. Conclusion. In healthy elderly subjects, the extreme‐dipper type may reflect a decrease in endothelial function, i.e. initial stage atherosclerosis, rather than the dipper type.

Prolonged deterioration of endothelial dysfunction in response to postprandial lipaemia is attenuated by vitamin C in Type 2 diabetes

Endothelial dysfunction (ED) has been described in Type 2 diabetes (T2DM). We have described previously a diminution of flow-mediated arterial dilatation and, by implication, further ED in T2DM in response to postprandial lipaemia (PPL) at 4 h. This is possibly mediated by oxidative stress/alteration of the nitric oxide (NO) pathway. T2DM subjects tend to exhibit both exaggerated and prolonged PPL. We therefore studied the relationship of PPL to the duration of ED in T2DM subjects and oxidative stress with or without the antioxidant, vitamin C. Twenty subjects with T2DM with moderate glycaemic control (mean HbA1c 8.4%) were studied. After an overnight fast, all subjects consumed a standard fat meal. Endothelial function (EF), lipid profiles, and venous free radicals were measured in the fasting, peak lipaemic phase (4 h) and postprandially to 8 h. The study was repeated in a double-blinded manner with placebo, vitamin C (1 g) therapy for 2 days prior to re-testing and with the fat meal. Oxidative stress was assessed by lipid-derived free radicals in plasma, ex vivo by electron paramagnetic resonance spectroscopy (EPR) and by markers of lipid peroxidation (TBARS). Endothelial function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery. There was a significant decrease in endothelial function in response to PPL from baseline (B) 1.3 +/- 1.3% to 4 h 0.22 +/- 1.1% (P < 0.05) and 8 h 0.7 +/- 0.9% (P < 0.05) (mean +/- sem). The endothelial dysfunction seen was attenuated at each time point with vitamin C. Baseline EF with vitamin C changed from (fasting) 3.8 +/- 0.9-2.8 +/- 0.8 (at 4 h) and 2.9 +/- 1.3 (at 8 h) in response to PPL. Vitamin C attenuated postprandial (PP) oxidative stress significantly only at the 4-h time point [301.1 +/- 118 (B) to 224.7 +/- 72 P < 0.05] and not at 8 h 301.1 +/- 118 (B) to 260 +/- 183 (P = NS). There were no changes with placebo treatment in any variable. PPL was associated with a PP rise in TG levels (in mmol/l) from (B) 1.8 +/- 1 to 2.7 +/- 1 at 4 h and 1.95 +/- 1.2 at 8 h (P = 0.0002 and 0.33, respectively). PPL is associated with prolonged endothelial dysfunction for at least 8 h after a fatty meal. Vitamin C treatment improves endothelial dysfunction at all time points and attenuates PPL-induced oxidative stress. This highlights the importance of low-fat meals in T2DM and suggests a role for vitamin C therapy to improve endothelial function during meal ingestion.

White coat phenomenon, anxiety and endothelial function in healthy normotensive elderly subjects

Objective. The white coat phenomenon (WCP) is a blood pressure (BP) elevation specifically observed in the clinical setting. Though WCP has been suggested to associate with emotional responses such as anxiety or with cardiovascular complications, its pathogenesis and clinical significance are unclear. We studied the possible association between WCP and anxiety or vascular function in normotensive elderly subjects without major cardiovascular risk factors. Methods. As a parameter of anxiety, the State and Trait Anxiety Inventory (STAI) was used. WCP was evaluated by calculating the difference between the clinic BP and mean daytime ambulatory BP. As parameters of vascular function, brachial artery endothelium‐dependent flow‐mediated dilation (FMD) and the endothelium‐independent dilation response to sublingual glyceryl trinitrate (GTN) were measured using high‐resolution ultrasound. Results. Using confounding factors as covariates, no association was observed between WCP and the STAI‐trait or STAI‐state score. There was a significant negative association between WCP and the percent change of FMD but no association between WCP and the percent change of GTN. Conclusion. WCP in the healthy normotensive elderly subjects may reflect a decrease in endothelial function, i.e. initial stage atherosclerosis, rather than anxiety.

Effect of Atorvastatin and Irbesartan, Alone and in Combination, on Postprandial Endothelial Dysfunction, Oxidative Stress, and Inflammation in Type 2 Diabetic Patients

Postprandial hypertriglyceridemia and hyperglycemia are considered risk factors for cardiovascular disease. Evidence suggests that postprandial hypertriglyceridemia and hyperglycemia induce endothelial dysfunction and inflammation through oxidative stress. Statins and angiotensin type 1 receptor blockers have been shown to reduce oxidative stress and inflammation, improving endothelial function. Twenty type 2 diabetic patients ate 3 different test meals: a high-fat meal, 75 g glucose alone, and a high-fat meal plus glucose. Glycemia, triglyceridemia, endothelial function, nitrotyrosine, C-reactive protein, intercellular adhesion molecule-1, and interleukin-6 were assayed during the tests. Subsequently, diabetics took atorvastatin 40 mg/d, irbesartan 300 mg/d, both, or placebo for 1 week. The 3 tests were performed again between 5 and 7 days after the start of each treatment. High-fat load and glucose alone produced a decrease in endothelial function and increases in nitrotyrosine, C-reactive protein, intercellular adhesion molecule-1, and interleukin-6. These effects were more pronounced when high-fat load and glucose were combined. Short-term atorvastatin and irbesartan treatments significantly counterbalanced these phenomena, and their combination was more effective than either therapy alone. This study confirms an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial function and inflammation, suggesting oxidative stress as a common mediator of such an effect. Short-term treatment with atorvastatin and irbesartan may counterbalance this phenomenon; the combination of the 2 compounds is most effective.

Different effect of hormone replacement therapy, DHEAS and tibolone on endothelial function in postmenopausal women with increased cardiovascular risk

Menopause is associated with an increased cardiovascular risk and with a decrease in endothelial function. Hormone replacement therapy (HRT) improves endothelial function in post-menopausal women (PMW) without established atherosclerosis. New alternative treatments, among which tibolone (T) and DHEAS have been suggested to reduce postmenopausal cardiovascular risk. Although, in vitro animal studies have suggested that T and DHEAS improve endothelial function, their effect in humans has never been tested. The aim of the present study was to compare the effects of HRT (continuous combined 0.625 mg conjugated equine estrogen plus 2.5 mg/d medoxyprogesterone) DHEAS and T on endothelium-dependent flow-mediated vasodilatation (FMD), plasma nitrite, nitrate and endothelin-1 levels in 16 PMW with increased cardiovascular risk in a double-blinded, double-crossover study. Women were randomized and treated for 4 weeks with HRT, T or DHEAS. Brachial artery diameter, FMD, endothelin-1 and plasma nitrite and nitrate levels were measured at baseline and after each treatment phase. Brachial artery diameters remained unchanged after each treatment phase. HRT significantly improved FMD compared to both baseline and to T and DHEAS therapies while no effect of T or DHEAS on FMD was noted. In conclusion, HRT, but neither T nor DHEAS, improves endothelial function and reduces plasma levels of endothelin-1 in PMW at risk of CAD.

Lipoprotein remnants and endothelial dysfunction in the postprandial phase.

The objective of this work was to study whether changes in remnant lipoprotein (RLP) plasma levels during the postprandial phase relate to alterations of the endothelial function. Fasted patients (15 moderately dyslipidemic men) were given an oral fat load (OFL), and blood samples were collected before the OFL ingestion (T0) and 2, 4, 6, and 8 h (T2, T4, T6, T8) thereafter. Endothelial function, determined as flow-mediated dilatation (FMD) of the brachial artery, was assessed at the same time points. Triglyceridemia peaked between T4 (5.48 +/- 0.64 mmol/liter) and T6 (5.34 +/- 0.89 mmol/liter) and decreased at 8 h (4.36 +/- 0.87 mmol/liter) after the OFL. FMD decreased significantly 6 h after the OFL consumption (from 16.03 +/- 1.32% to 11.53 +/- 1.42%, P < 0.01). Cholesterol in RLPs increased steadily up to 6 h and decreased at 8 h (T0 0.53 +/- 0.10, T6 0.81 +/- 0.11, T8 0.73 +/- 0.13 mmol/liter). Fasting levels of triglycerides and cholesterol-RLPs (C-RLPs) correlated significantly with FMD at baseline. The decrease in endothelial function at 6 h also significantly correlated with the area under the curve of triglycerides (R = 0.53, P = 0.04). Postprandial C-RLPs (area under the curve), however, showed the best correlation with the decrease of FMD (R = 0.63, P = 0.012). The correlation persisted in a multivariate analysis. We concluded that C-RLPs contribute significantly to the endothelial dysfunction occurring during the postprandial lipemia.

Changes in coronary endothelial function predict progression of allograft vasculopathy after heart transplantation

Objective Coronary endothelial dysfunction may be an early marker for cardiac allograft vasculopathy (CAV) in orthotopic heart transplant recipients. We used serial studies to evaluate changes in coronary endothelial function in patients with and without clinically evident CAV. Background In serial studies with intravascular ultrasound (IVUS) and Doppler flow wire measurements, we previously demonstrated that annual decrements in coronary endothelial function are associated with progressive intimal thickening. Methods We studied 45 patients annually, beginning at transplantation until pre-specified end-points (angiographic CAV or cardiac death) were reached. At each study, we measured coronary endothelial function using intracoronary infusions of adenosine, acetylcholine, and nitroglycerin. We simultaneously recorded IVUS images and Doppler velocities. Results Of the 45 patients studied, 9 reached end-points during the study (6 had CAV and 3 died). The mean annual change in area response to acetylcholine was −4.5% ± 3.0% in patients who reached end-points and −0.9% ± 1.5% in those who did not ( p = 0.04). The mean annual decrement in flow response to acetylcholine was greater in patients who reached end-points (−31% ± 11% vs −5% ± 5%, p = 0.08). Responses to adenosine and nitroglycerin did not differ. Conclusions When serial responses were evaluated, patients with end-points had more rapid decreases in endothelial function. The rate of disease progression may be more important than the absolute degree of intimal thickening in early CAV. These data implicate endothelial dysfunction in the development of clinically significant vasculopathy and suggest that serial studies of endothelial function may provide important prognostic information about the development of CAV after heart transplantation.