Peripheral Endothelial Dysfunction In Patients Research Articles

63 Peripheral endothelial function in patients affected by pulmonary hypertension. Relationship between endothelial function, haemodynamic parameters, and therapy response

Abstract Aims Pulmonary hypertension (PH) is defined as a mean pulmonary arterial pressure (mPAP) of 25 mmHg or greater at rest, confirmed by right heart catheterization (RHC). The World Health Organization has classified PH into five clinical subgroups. Pulmonary arterial hypertension (PAH) (group 1) is characterized by loss and obstructive remodelling of the pulmonary vascular bed. These patients are characterized haemodynamically by the presence of precapillary PH, defined as an mPAP of 25 mm Hg or greater, pulmonary artery wedge pressure (PAWP) of 15 mm Hg or less, and pulmonary vascular resistance (PVR) of three Wood units (WU) or greater. Pulmonary hypertension due to left-sided heart disease (LHD) (PH-LHD) (group 2) occurs in HF. Patients with PH-LHD usually have isolated postcapillary PH (PAWP >15 mm Hg and PVR <3 WU), although some of them have combined postcapillary and precapillary PH (PAWP >15 mm Hg and PVR ≥3 WU). PH due to chronic lung disease (CLD) (PH-CLD) and/or hypoxia (group 3) can occur in many lung diseases. These patients have precapillary PH. Chronic thromboembolic PH (CTEPH) (group 4) is characterized by obstruction of the pulmonary vasculature by organized thromboembolic material and vascular remodelling, resulting from prior pulmonary embolism. Patients with unclear and/or multifactorial mechanisms are listed as group 5. Specific pulmonary vasodilators are approved only in PAH patients. While research was predominantly focused on pulmonary vasculature, little is known about the peripheral endothelial damage in different vascular beds in PH patients. To evaluate the relationship between the peripheral endothelial function and the haemodynamic parameters, in order to provide a non-invasive method for the indirect evaluation of mean pulmonary pressure and vascular resistance, to predict if the PH is a precapillary or postcapillary, to select more accurately the patients who should undergo RHC. Moreover, we investigate if there is a possible correlation between endothelial dysfunction and response to specific PH therapies. Methods and results Patients with suspected PH, based on symptoms, medical history, and clinics will undergo physical examination, ECG, echocardiography, and RHC. In all patients, endothelial function was assessed by FMD. Medical history, heart rate, systolic blood pressure, body mass index, WHO functional class, and medications were recorded. All patients underwent blood analysis, erythrocyte sedimentation rate (ERS), high sensitivity C-reactive protein (CRP), and NT-proBNP levels were assayed. Increased peripheral endothelial dysfunction in patients with precapillary PH, with a linear correlation between endothelium dysfunction and increased PVR at the right catheterization. To differentiate pre and post capillary PH forms by cut-off values of the FMD. The degree of endothelial dysfunction could be a marker of therapy response. Sequential combination therapy in the pre-capillary PH forms could be the one with a worst endothelial response than up-front combination therapy.

Impact of glycemic variability on coronary and peripheral endothelial dysfunction in patients with coronary artery disease

Background: Previous studies have reported that glucose variability leads to endothelial dysfunction and progression of coronary atherosclerosis. However, few studies have directly evaluated the relation between glucose variability and coronary endothelial function in patients with coronary artery disease (CAD).Methods: A total of 38 patients with chronic CAD and a history of coronary drug-eluting stent implantation were enroled. Coronary endothelial function was evaluated by measuring the coronary vasoreactivity using quantitative coronary angiography in the segment distal to implanted stent in response to intracoronary acetylcholine (ACh) infusion (10−7 mol/l). Peripheral endothelial function was also assessed with reactive hyperemia index (RHI). The mean amplitude of glycemic excursion (MAGE) was calculated as a primary metric of glucose variability using a flash glucose monitoring system.Results: Of 38 patients, 17 (45%) had diabetes mellitus. The mean levels of glycated hemoglobin, MAGE, and RHI were 6.3 ± 0.8%, 71.4 ± 29.8 mg/dl, and 1.85 ± 0.63. In the distal segment to coronary stent, lumen diameter was constricted by 0.6 ± 7.3% in response to intracoronary ACh infusion compared to that at baseline. While peripheral endothelial function assessed with RHI was not significantly associated with MAGE (r = −0.16, p = 0.35), coronary endothelial function was correlated with MAGE (r = −0.38, p = 0.02).Conclusion: Greater glucose variability was significantly associated with coronary rather than peripheral endothelial dysfunction in patients with CAD, suggesting an impact of glucose variability on coronary atherosclerosis.

Peripheral Endothelial Function After Arterial Switch Operation for D-looped Transposition of the Great Arteries.

Coronary artery re-implantation during arterial switch operation in patients with D-looped transposition of thegreat arteries (D-TGA) can alter coronary arterial flow and increase shear stress, leading to local endothelial dysfunction, although prior studies have conflicting results. Endothelial pulse amplitude testing can predict coronary endothelial dysfunction by peripheral arterial testing. This study tested if, compared to healthy controls, patients with D-TGA after arterial switch operation had peripheral endothelial dysfunction. Patient inclusion criteria were (1) D-TGA after neonatal arterial switch operation; (2) age 9-29 years; (3) absence of known cardiovascular risk factors such as hypertension, diabetes, hypercholesterolemia, vascular disease, recurrent vasovagal syncope, and coronary artery disease; and (4) ability to comply with overnight fasting. Exclusion criteria included (1) body mass index ≥85th percentile, (2) use of medications affecting vascular tone, or (3) acute illness. We assessed endothelial function by endothelial pulse amplitude testing and compared the results to our previously published data in healthy controls (n = 57). We tested 20 D-TGA patients (16.4 ± 4.8 years old) who have undergone arterial switch operation at a median age of 5 days (0-61 days). Endothelial pulse amplitude testing indices were similar between patients with D-TGA and controls (1.78 ± 0.61 vs. 1.73 ± 0.54, p = 0.73).In our study population of children and young adults, there was no evidence of peripheral endothelial dysfunction in patients with D-TGA who have undergone arterial switch operation. Our results support the theory that coronary arterial wall thickening and abnormal vasodilation reported in these patients is a localized phenomenon and not reflective of overall atherosclerotic burden.

Effects of bosentan on peripheral endothelial function in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension.

Endothelin receptor antagonists (ERAs) have been shown to improve the prognosis of patients with pulmonary arterial hypertension (PAH). However, the effect of the oral dual ERA bosentan on peripheral endothelial dysfunction (PED), as assessed by flow-mediated vasodilation (FMD), in patients with pulmonary hypertension is not well characterized. We investigated the effect of bosentan on PED in patients with PAH or inoperable chronic thromboembolic pulmonary hypertension (CTEPH). A total of 18 patients with PAH and 8 with CTEPH were treated with bosentan. All patients underwent FMD assessment before and after 3 months of bosentan treatment. Whereas FMD increased from 6.01% ± 2.42% at baseline to 8.07% ± 3.18% after 3 months (P < 0.0001) in patients with PAH, those with CTEPH showed no change in FMD after bosentan therapy. In addition, FMD at baseline showed no correlation with pulmonary vascular resistance (r = 0.09) or plasma brain natriuretic peptide levels (r = -0.23) in patients with PAH. Bosentan treatment ameliorated PED in patients with PAH but not in those with inoperable CTEPH. In addition, FMD did not correlate with PAH severity.

Endothelial dysfunction during acute alcohol withdrawal syndrome

BackgroundEndothelial dysfunction (EF) is a central phenomenon in a variety of conditions associated with increased cardiovascular morbidity. Here, we investigated EF during acute alcohol withdrawal syndrome before and 24h after medication. We aimed to analyze microcirculation, applying the post-occlusive reactive hyperemia (PORH) test and spectral analysis of skin vasomotion as markers of EF. Additionally, we explored whether segmentation of spectral analysis data may disclose more detailed information on dynamic blood flow behavior. MethodsWe investigated 30 unmedicated patients during acute alcohol withdrawal syndrome and matched controls. Patients were reinvestigated after 24h when half of them had been treated with clomethiazole. Capillary blood flow was assessed on the right forearm after compression of the brachial artery. Parameters of PORH such as time to peak (TP), slope and PORH indices were calculated. Spectral analysis was performed in order to study five different frequency bands. Withdrawal symptoms were quantified by means of the alcohol withdrawal scale (AW scale). ResultsWe observed a blunted hyperemic response in patients after occlusion of the brachial artery indicated by significantly increased TP and decreased PORH indices. In contrast, vasomotion as investigated by spectral analysis was not altered. Segmentation analysis revealed some alterations in the cardiac band at rest, and indicated differences between treated and untreated patients after 24h. ConclusionOur results suggest peripheral endothelial dysfunction in patients during acute alcohol withdrawal. No major influence of treatment was observed. Future studies need to address the relation of EF to cardiac morbidity during alcohol withdrawal.

Peripheral endothelial dysfunction in patients suffering from acute schizophrenia: A potential marker for cardiovascular morbidity?

Patients suffering from schizophrenia have an increased standardized ratio for cardiovascular mortality compared to the general population. Endothelial function was identified as a prominent parameter for cardiac risk stratification in patients with heart disease. Here, we aimed to analyze the reactivity of the microcirculation applying the post-occlusive reactive hyperemia (PORH) test and spectral analysis of skin vasomotion as markers of endothelial function. We investigated 21 unmedicated patients suffering from paranoid schizophrenia as well as 21 matched controls. The capillary blood flow was assessed on the right forearm after compression of the brachial artery. Parameters of PORH such as time to peak (TP) or PORH index were calculated. In addition, spectral analysis of skin vasomotion was performed and five frequency bands (endothelial, sympathetic, vascular myogenic, respiratory and heart beat activity) were studied. Psychotic symptoms were quantified using the Positive and Negative Syndrome Scale (PANSS) and correlated to the parameters obtained. We report a blunted hyperemic response in patients after occlusion of the brachial artery indicated by significantly increased TP and decreased PORH indices. In contrast, vasomotion as investigated by spectral analysis of skin flow was rather sparsely altered showing differences at rest for the sympathetic and cardiac components only. Our results are suggestive of peripheral endothelial dysfunction in unmedicated patients suffering from schizophrenia. Future, prospective studies should address the relation of endothelial dysfunction to cardiac morbidity in patients with schizophrenia.

Peripheral endothelial dysfunction in patients with pulmonary arterial hypertension

Pulmonary endothelium plays an important role in the mechanism of pulmonary arterial hypertension (PAH). However, there is only a few data regarding the systemic endothelium in this syndrome. This study focused on the systemic endothelial involvement in PAH. Endothelial function was evaluated in 54 patients with idiopathic (n=28), scleroderma-associated (n=10), chronic thromboembolic (n=7), or Eisenmenger (n=9) PAH and 21 controls (13 healthy; eight scleroderma and normal pulmonary pressure). All underwent clinical evaluation, pulmonary assessment, echocardiography, and pulmonary cardiac stress test. Endothelial function was evaluated by measuring the forearm blood flow dilatation response to brachial arterial occlusion by a non-invasive plethysmograph, yielding a peripheral arterial tone (PAT) ratio. The PAT ratio was significantly lower (p<0.05) than healthy controls in all patients except the Eisenmenger group (control: 2.20+/-0.25; idiopathic 1.84+/-0.51; scleroderma 1.66+/-0.66; thromboembolic 1.89+/-0.32; Eisenmenger 2.17+/-0.62). The impaired hyperemic response significantly correlated with disease severity, as measured by NYHA classification (r=-0.210, p=0.035), pulmonary pressure (r=-0.228, p=0.035), 6 min walking distance (r=0.215, p=0.047), and oxygen desaturation on effort (r=0.207, p=0.038). Mean systolic pulmonary pressure among patients was 54-99 mmHg. A systemic component of endothelial dysfunction might be involved in idiopathic, scleroderma-associated and chronic thromboembolic PAH that is correlated with disease severity.

Acute Effect of Rheopheresis on Peripheral Endothelial Dysfunction in Patients Suffering From Sudden Hearing Loss

Single low density lipoprotein (LDL) fibrinogen apheresis has shown beneficial effects in the treatment of patients with sudden sensorineural hearing loss (SSHL). Pathophysiologically, a microcirculatory disorder of the inner ear, probably caused by disturbed endothelial function, is discussed as a final common pathway of a variety of SSHL etiologies. Thus, we carried out a prospective pilot study on the efficacy of Rheopheresis on vascular function in these patients, embedded into an ongoing randomized controlled multicenter trial investigating the efficacy of Rheopheresis for the treatment of SSHL. Potential modulation of systemic endothelial dysfunction by Rheopheresis was examined by measuring flow-associated vasodilatation of the brachial artery (according to the criteria of the American College of Cardiology) in a small group of patients suffering from SSHL (N=6, 5m/1f, mean age 56+/-11 years) within the last 3 days. At baseline, five of the six patients with acute hearing loss showed endothelial dysfunction as evidenced by diminished flow-mediated vasodilatation (FMD<5%). After a single Rheopheresis treatment, flow-mediated vasodilatation improved significantly (from 3.9+/-3.6% to 7.2+/-2.4%, P=0.05, mean+/-SD, two-sided paired T-test). This was paralleled by a reduction in fibrinogen (364+/-216 mg/dL to 142+/-96 mg/dL, P=0.03), total cholesterol (228+/-23 to 98+/-10, P<0.0001) and LDL cholesterol levels (153+/-8 mg/dL to 83+/-23 mg/dL, P<0.01). Based on this case series we conclude that single Rheopheresis treatment might have an acute beneficial effect on endothelial dysfunction in patients suffering from SSHL.