Boris Schnorbus

Effect of nighttime aircraft noise exposure on endothelial function and stress hormone release in healthy adults

Aims Aircraft noise disturbs sleep, and long-term exposure has been shown to be associated with increases in the prevalence of hypertension and an overall increased risk for myocardial infarction. The exact mechanisms responsible for these cardiovascular effects remain unclear. Methods and results We performed a blinded field study in 75 healthy volunteers (mean age 26 years), who were exposed at home, in random order, to one control pattern (no noise) and two different noise scenarios [30 or 60 aircraft noise events per night with an average maximum sound pressure level (SPL) of 60 dB(A)] for one night each. We performed polygraphy during each study night. Noise caused a worsening in sleep quality (P < 0.0001). Noise60, corresponding to equivalent continuous SPLs of 46.3 dB (Leq) and representing environmental noise levels associated with increased cardiovascular events, caused a blunting in FMD (P = 0.016). As well, although a direct comparison among the FMD values in the noise groups (control: 10.4 ± 3.8%; Noise30: 9.7 ± 4.1%; Noise60: 9.5 ± 4.3%, P = 0.052) did not reach significance, a monotone dose-dependent effect of noise level on FMD was shown (P = 0.020). Finally, there was a priming effect of noise, i.e. the blunting in FMD was particularly evident when subjects were exposed first to 30 and then to 60 noise events (P = 0.006). Noise-induced endothelial dysfunction (ED) was reversed by the administration of Vitamin C (P = 0.0171). Morning adrenaline concentration increased from 28.3 ± 10.9 to 33.2 ± 16.6 and 34.1 ± 19.3 ng/L (P = 0.0099). Pulse transit time, reflecting arterial stiffness, was also shorter after exposure to noise (P = 0.003). Conclusion In healthy adults, acute nighttime aircraft noise exposure dose-dependently impairs endothelial function and stimulates adrenaline release. Noise-induced ED may be in part due to increased production in reactive oxygen species and may thus be one mechanism contributing to the observed association of chronic noise exposure with cardiovascular disease.

Effects of clopidogrel, prasugrel and ticagrelor on endothelial function, inflammatory and oxidative stress parameters and platelet function in patients undergoing coronary artery stenting for an acute coronary syndrome. A randomised, prospective, controlled study

Introduction Particularly in the setting of acute coronary syndromes, the interplay between vascular and platelet function has been postulated to have direct clinical implications. The present trial is designed to test the effect of clopidogrel, prasugrel and ticagrelor on multiple parameters of vascular function, platelet aggregation, oxidative and inflammatory stress before and up to 4 weeks after coronary artery stenting. Methods and analysis The study is designed as a three-arm, parallel design, randomised, investigator-blinded study. Patients with unstable angina or non-ST elevation myocardial infarction undergoing coronary intervention with a drug-eluting stent will be randomised to receive 600 mg clopidogrel, 60 mg prasugrel or 180 mg ticagrelor followed by oral therapy with the same drug. The primary endpoint of the trial is the impact of antiplatelet treatments on endothelial function as assessed by flow-mediated dilation at 1 day, 1 week and 1 month in patients who have undergone stenting. Secondary endpoints include the impact of study medications on parameters of macrovascular and microvascular function, platelet reactivity, oxidative and inflammatory stress. The study recruitment is currently ongoing and, after an interim analysis which was performed at 50% of the initially planned population, it is planned to continue until July 2015. Ethics and dissemination The protocol was approved by the local ethics committee. The trial will provide important pathophysiological insight on the relationship between platelet aggregation and endothelial function, two parameters that have been shown to influence patients’ prognosis. Trial registration number ClinicalTrials.gov Identifier: NCT01700322; EudraCT-Nr.: 2011-005305-73. Current V.1.3, from 24 February 2014.

Supervised exercise training in peripheral arterial disease increases vascular shear stress and profunda femoral artery diameter

Background Arteriogenesis is promoted by flow- and pressure-related forces such as tangential wall stress and laminar shear stress. Exercise training (ET) is known to promote arteriogenesis in peripheral arterial disease (PAD) patients. It remains unclear whether supervised ET (SET) promotes arteriogenesis more efficiently than non-SET (nSET). Methods and results Forty PAD patients participated in a SET or nSET training programme (n = 20 each) and were compared to 20 healthy individuals without any history of cardiovascular events. Femoral artery diameter, flow and velocity were measured by ultrasound. Tangential wall stress and laminar shear stress were calculated for femoral arteries. Follow-up was performed after a mean of 7.65 ± 1.62 months. At follow-up, only the SET group showed a significant increase in lumen diameter of the profunda femoral artery (p = 0.03), accompanied by an increase of tangential wall stress (p = 0.002). Laminar shear stress decreased, but remained higher for the SET group compared to controls (p < 0.01). Individual changes in walking distance were higher for SET patients (p = 0.01) than nSET patients (p = 0.07). Profunda femoral lumen diameter and tangential wall stress correlated directly with walking distance (r = 0.446; p < 0.001), as well as with each other (r = 0.743; p < 0.0001). Conclusions Our results indicate that SET promotes arteriogenesis more efficiently than nSET. Femoral lumen diameter and flow might help with the monitoring of ET efficiency and potential arteriogenesis.

Both flow-mediated dilation and constriction are associated with changes in blood flow and shear stress: Two complementary perspectives on endothelial function

INTRODUCTION Flow-mediated dilation (FMD) quantifies endothelium-dependent vasomotor responses to short-term increases in blood flow. Low-flow mediated vasoconstriction (L-FMC) has been more recently introduced as additional measure of endothelial function, and its relationship with changes in blood flow, cardiovascular risk factors and FMD ha∧s been less well characterized. MATERIALS AND METHODS We evaluated radial artery FMD and L-FMC along with the changes in blood flow and shear rate/stress in 584 patients with known or suspected coronary artery disease (72.9% men, mean age 67+/-11 years). Baseline blood flow and shear rate showed a modest association with radial artery FMD and L-FMC (R2 = 0.04 and R2 = 0.02, P < 0.0001). Resting diameter showed a stronger association with FMD but not with L-FMC (R2 = 0.11, P < 0.0001 and R2 = 0.005, P = 0.09). Analysis with generalized additive models showed that age, sex and presence and extent of coronary artery disease were strongly related to both endothelial function measures (P < 0.001 for both), but they explained only 12.4% and 10.1% of the variance in L-FMC and FMD. When the corresponding changes in blood flow were added to these statistical models, the % of variance explained raised to 20.4% and 17.7% for L-FMC and FMD. L-FMC was a strong predictor of FMD even after correction for the changes in blood flow. DISCUSSION Changes in blood flow are the most important determinants of both L-FMC and FMD. These observations support the concept that both FMD and L-FMC measure endothelium-dependent, shear-induced, vasomotion.

Predictive value of brachial reactive hyperemia and flow-mediated dilation in stable coronary artery disease.

BACKGROUND The purpose of this study was to determine the predictive value of a single measurement of reactive hyperemia (RH) and brachial flow-mediated dilation (FMD) in patients with established stable coronary artery disease (CAD). METHODS RH and brachial artery FMD were ultrasonographically measured in 325 patients with stable CAD. Patients were followed for cerebro-cardiovascular events. The median follow-up was 3.7 years (range 0.01-5.7 years). RESULTS Sixty-seven patients (20.6%) had an cerebro-cardiovascular event. Patients with subsequent events had lower FMD (4.9 ± 3.3% versus 6.3 ± 3.5%, p = 0.003), higher brachial artery resting diameter (5.1 ± 0.7 mm versus 4.8 ± 0.7 mm, p = 0.002) and lower NMD (11.2 ± 5.1% versus 12.8 ± 5.4%, p = 0.02), while the mean hyperemic flow velocity and shear stress did not differ from patients without cerebro-cardiovascular events. Cox proportional hazard model adjusted for sex, age, BMI, and traditional cardiovascular risk factors revealed a hazard ratio of 0.84 for lower FMD (p = 0.01). CONCLUSIONS We conclude that single spot measurements of peak RH do not provide long-term prognostic information, but evaluation of conduit artery FMD predicts long-term cerebro-cardiovascular events in patients with stable CAD. The prognostic value of FMD is incremental to traditional cardiovascular risk factors and may therefore be of clinical importance.

Twelve-month outcomes after bioresorbable vascular scaffold implantation in patients with acute coronary syndromes. Data from the European Multicenter GHOST-EU Extended Registry

AIMS The aim of this study was to report on the midterm outcomes of patients undergoing percutaneous coronary intervention with bioresorbable vascular scaffolds (BVS) for the treatment of acute coronary syndromes (ACS) and compare with those of patients with stable coronary artery disease (sCAD). METHODS AND RESULTS One thousand four hundred and seventy-seven (1,477) patients underwent implantation of one or more BVS (Absorb BVS; Abbott Vascular, Santa Clara, CA, USA) at 11 European centres and were included in the GHOST-EU registry. Admissions comprised 47.1% of the patients (951 BVS) with ACS, and 52.8% (1,274 BVS) with sCAD. During a median follow-up of 384 (359-460) days, patient-oriented endpoints (PoCE), including all-cause death, any infarction, any revascularisation, were recorded in 271 patients (12-month incidence in ACS patients: 18.5% vs. 11.6% in the sCAD group, p<0.001). Device-oriented composite endpoints (DoCE), cardiac death, target vessel infarction and target lesion revascularisation, were observed in 98 patients (12-month incidence of 4.2% in the sCAD group, 6.4% in the ACS group; p=0.052). The 12-month incidence of definite scaffold thrombosis was 2.6% in ACS patients and 0.8% in XIENCE patients (p=0.006). In multivariate analysis, ACS was a predictor of DoCE (HR: 2.26 [1.34-3.81], p=0.002), PoCE (HR: 1.71 [1.13-2.58], p=0.011), and stent thrombosis (HR: 2.51 [1.13-5.60], p=0.025). In contrast, the incidence of target lesion revascularisation was not different between groups. There was no difference in the incidence of any of these endpoints among the different clinical presentations (unstable angina, non-ST-elevation infarction and ST-elevation infarction). CONCLUSIONS PoCE, DoCE and scaffold thromboses were more frequent in ACS patients, without any difference among different forms of ACS.

Interferon- and ribavirin-free therapy with new direct acting antivirals (DAA) for chronic hepatitis C improves vascular endothelial function

INTRODUCTION Chronic Hepatitis C virus infection (HCV) is associated with extrahepatic manifestations and an increased prevalence in cardiovascular disease. New direct acting antivirals (DAA) have revolutionized HCV treatment with high rates of sustained virological response (SVR). Recently it was demonstrated, that SVR reduces morbidity and overall mortality more than can be solely explained by hepatic effects, suggesting that treatment with DAA also affects cardiovascular disease. The aim of this pilot study was to identify possible underlying mechanisms behind the HCV-associated cardiovascular mortality reported by others. METHODS AND RESULTS 20 HCV patients (10 genotype GT1, 10 GT3) were treated with interferon (IFN)- and ribavirin (RBV)-free DAA regimens for 12 weeks (SVR12). Primary endpoint was an improvement in endothelial function (flow-mediated dilation, FMD) at SVR12 compared to baseline. Patient demographics, FMD, markers for endothelial function and inflammation, coagulation and oxidative stress were measured at baseline, end of treatment and SVR12. All patients achieved SVR12. There was a significant increase in FMD from 9.4 ± 5.2% at baseline to 11.9 ± 4.5% at SVR12 (p = 0.04). Concomitantly, there were significant reductions in levels of endothelium-derived adhesion molecules E-selectin, VCAM-1 and ICAM-1. While APRI values were also significantly lower, liver stiffness did not change significantly. There were no relevant changes in systemic inflammation, oxidative stress, insulin resistance or coagulation pathways. CONCLUSIONS Successful DAA therapy was associated with improvements in endothelial function and a reduction of soluble adhesion molecules. Our findings indicate that HCV infection affects the endothelium and that DAA-treatment reverses these effects and enhances endothelial function.

A False-Positive FFR: Drift and Failure to Equalize may cause Troubles!

The results of FFR measurements determine further therapies. Therefore it is important that all steps necessary to obtain correct data are respected. We show the effect of an incorrect equalization.