scholarly journals Vascular Protective Effects of New Oral Anticoagulants in Patients with Atrial Fibrillation

2021 ◽  
Vol 10 (19) ◽  
pp. 4332
Author(s):  
Gyeong-Won Jang ◽  
Jung Myung Lee ◽  
Seung Woo Choi ◽  
Joan Kim ◽  
Young Shin Lee ◽  
...  

This study was designed to determine the efficacy of a new oral anticoagulant (NOAC) therapy for the prevention of endothelial dysfunction and atherosclerosis progression in patients with atrial fibrillation (AF). Sixty-five AF patients with a CHA2DS2-VASc score ≥2 without previous history of cardiovascular disease were registered and randomly assigned to either an NOAC group (dabigatran or rivaroxaban) or the warfarin group. Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements reflecting endothelial function were taken using Endo-PAT2000. Carotid intima–media thickness (IMT) was measured at baseline, 12 months, and 24 months, and several biomarkers were also analyzed. For the primary end point, the reactive hyperemia index (RHI) for the NOAC group was 1.5 ± 0.4 and that for the warfarin group was 1.6 ± 0.5. The left and right carotid IMT was 0.7 mm in the NOAC groups and 0.8 mm in the warfarin group. At 12 months, RHI was 1.6 ± 0.3 for the dabigatran group, 1.6 ± 0.5 for the rivaroxaban group, and 1.6 ± 0.3 for the warfarin group. The three groups did not differ statistically with respect to change in left and right carotid IMT at 12 and 24 months, respectively. The biomarkers for endothelial function and atherosclerosis were not significantly different. There was a trend of reduced P-selectin levels in the NOAC group compared to the warfarin group. In patients with AF, there were no significant differences in the prevention of endothelial dysfunction and atherosclerosis progression between the NOAC and warfarin groups.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Christian Heiss ◽  
Richard E Sievers ◽  
Nicolas Amabile ◽  
Tony Y Momma ◽  
Shobha Natarajan ◽  
...  

In humans, endothelial function serves as a surrogate marker for cardiovascular health and is measured as changes in arterial diameter after temporary ischemia (flow-mediated dilation; FMD). We developed an FMD-related approach to study conduit artery vasodilation in living rats, and demonstrate a reduction in FMD in older versus younger animals consistent with age-related endothelial dysfunction. Diameter and Doppler-flow measurements were obtained from the femoral artery using high-resolution ultrasound (35 MHz). We observed dose-dependent vasodilation using both endothelium-dependent and endothelium-independent pharmacologic vasodilators (acetylcholine and nitroglycerine). Flow-dependent vasodilation was observed in response to flow increase induced both by adenosine and local saline infusion. Transient hindlimb ischemia led to reactive hyperemia with sequential flow velocity increase and femoral artery dilation, the latter of which was completely abolished by NO-synthase (NOS) inhibition with L-NMMA. To demonstrate its applicability in a model of endothelial dysfunction, we show that FMD is significantly reduced in older versus younger animals. While FMD was completely NOS-dependent in younger animals, NOS-dependent mechanisms accounted for only half of the FMD in older animals, with the remainder being blocked by charybdotoxin (CTx) and apamin suggesting contribution of endothelium-derived-hyperpolarizing-factor. Using this new integrative physiologic model to reproducibly study FMD in living rats, we show that age-dependent endothelial dysfunction is accompanied by a shift in mechanisms underlying vasodilatory endothelial function.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Hisanori Kanazawa ◽  
Hiroshige Yamabe ◽  
Seigo Sugiyama ◽  
Satomi Iwashita ◽  
Tadashi Hoshiyama ◽  
...  

Introduction: Endothelial function has been shown to be deteriorated by the presence of atrial fibrillation (AF). Therefore, we hypothesized that serial change in the endothelial function can predict the recurrence of AF after catheter ablation (CA). Objectives: The purpose of this study was to examine the predictive value of endothelial function as a marker for recurrence of AF after CA. Methods: The consecutive 156 AF patients who underwent CA for AF were included in this study. All patients assessed their endothelial function by the reactive hyperemia-peripheral arterial tonometry (RH-PAT) and the RH-PAT index (RHI) was measured before CA, and 3 and 6 months after CA. To investigate the factors correlated with AF recurrence, clinical variables and RHI before CA, 3 and 6 months after CA were examined in patients with and without recurrence of AF. The recurrence of AF was defined as the occurrence of AF at the time of 6 months after CA. Results: AF recurrence was not observed in 125 patients (80%), but was observed in the remaining 31 patients (20%). Disease duration of AF (p=0.028), RHI before CA (p<0.001), RHI 3 month after CA (p=0.037), the difference in RHI before and 3 month after CA (p<0.001) were significantly correlated with AF recurrence. The multivariate Cox hazard analysis revealed that the difference in RHI before and 3 month after CA independently correlated with the recurrence of AF (p<0.001, Hazard ratio: 0.168). Furthermore, the value of RHI 3 month after CA, which decreased 0.015 or more compared with that before CA, was the independent predictor of AF recurrence (sensitivity: 0.613, specificity: 0.880, area under curve 0.722). Kaplan-Meier analysis demonstrated a significantly higher probability of AF recurrence when the RHI value 3 months after CA showed a decrease over 0.015 (log-rank test: p<0.001). Conclusions: The change in the endothelial function following CA sensitively reflects the recurrence of AF. The decrease in the RHI 3 months after CA compared to that before CA, with a cu-off value of 0.015, was an independent significant predictor of AF recurrence. Therefore, no recurrence of AF can be expected by the absence of decrease in RHI. We might be able to stop anti-arrhythmic drugs and anticoagulants according to the RHI improvement 3 month after CA.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Abdul Shokor Parwani ◽  
Daniel Blaschke ◽  
Alexander Wutzler ◽  
Martin Huemer ◽  
Phillip Attanasio ◽  
...  

Introduction: Thromboembolic events are the most feared complication of radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). The traditional periprocedural anticoagulation approach is discontinuation of vitamin K antagonist and bridging with heparin. Newly procedures are done under therapeutic INR 2-3. Recent studies used periprocedural new direct oral anticoagulants (NOACs). Hypothesis: We evaluated the available evidence on the efficacy and safety of NOACs for periprocedural anticoagulation during RFCA of AF. Methods: Pubmed, Embase and Cochrane Central were searched. Retrospective and prospective studies published as peer-reviewed full-size articles were included if they reported embolic events and major and minor bleeding. Results: Fifteen studies were identified (14 observational studies, 1 small randomized trial). A total of 7050 patients were included (NOACs group: 2887 ). A total of 37 thromboembolic complications occurred (0,5%) with 17 events in the NOAC group (0,6%) and 20 in the warfarin group (0,5%) (odds ratio 0.97, 95% confidence interval (CI) 0.48 to 1.99). Major bleeding were numerically higher in the warfarin group compared to the NOACs group. However, the difference did not reach statistical significance (odds ratio 0.69, CI 0.43 to 1.10). Subgroup analysis did not reveal any differences in event rates. Conclusions: Our review suggests that dabigatran etexilate and rivaroxaban are as effective and safe as warfarin for periprocedural anticoagulation in patients undergoing RFCA of AF. However, it has to be acknowledged that the current evidence is mainly based on observational studies.


2020 ◽  
Vol 52 (09) ◽  
pp. 642-646
Author(s):  
Yanjin Hu ◽  
Zhi Yao ◽  
Guang Wang

AbstractEndothelial dysfunction is the important early step in the development of atherosclerosis. Hypothyroidism caused by Hashimoto’s thyroiditis and other thyroid disease is one of the risk factors of endothelial dysfunction. The present study tried to investigate the endothelial function and its associated factors in Hashimoto thyroiditis with euthyroidism. A total of 95 newly diagnosed Hashimoto’s thyroiditis patients with euthyroidism and 45 healthy controls were studied. Hashimoto’s patients were divided into 3 subgroups namely, single thyroglobulin antibody (TGAb) positive subgroup, single thyroid peroxidase antibody (TPOAb) positive subgroup, and both TGAb and TPOAb positive subgroup. Endothelial function was tested by the reactive hyperemia index (RHI). Hashimoto’s thyroiditis patients had lower RHI than healthy controls (1.73±0.42 vs 1.96±0.51, p<0.05). Hashimoto’s thyroiditis with single TGAb positive patients had higher RHI than single TPOAb positive (1.98±0.57 vs. 1.69±0.33, p<0.05) and TGAB + TPOAb positive patients (1.98±0.57 vs. 1.68±0.42, p<0.05). RHI were negatively associated with total cholesterol (TC, r=−0.215, p<0.05), low density lipoprotein cholesterol (LDL-C, r=−0.268, p<0.05), triglyceride (TG, r=−0.192, p<0.05), and TPOAb (r=−0.288, p<0.05). In the regression analysis, LDL-C (β=−0.146, p<0.05), TG (β=−0.034, p<0.05) and TPOAb (β=−0.001, p<0.05) were independently associated with RHI. Hashimoto’s patients had poor endothelial function. TPOAb levels were negatively associated with endothelial function.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
I K Moon ◽  
S R Lee ◽  
E K Choi ◽  
E J Lee ◽  
J H Jung ◽  
...  

Abstract Background Patients with atrial fibrillation (AF) often have concomitant valvular heart disease (VHD), especially in Asia. There are limited data on non-vitamin K antagonist oral anticoagulants (NOAC) impact on outcomes for stroke prevention and bleeding for these patients in real world clinical practice. Purpose To investigate the effectiveness and safety of NOACs compared with warfarin in patients with AF and associated Evaluated Heartvalves, Rheumatic or Artificial (EHRA) type 2 VHD. Methods We identified oral anticoagulants naive patients with AF and EHRA type 2 VHD from the Korean National Health Insurance Service database between 2014 and 2016 (n=2,671 taking warfarin; n=3,058 taking NOAC). Six clinical outcomes including ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding (GI), major bleeding, all-cause death, and their composite outcome and fatal clinical events (any events that led to death within 30-day of its occurrence) were evaluated. Inverse probability of treatment weighting (IPTW) method was used to balance covariates between the two groups. Results After weighted using 5% trimmed IPTW method (n=2371 taking warfarin; n=2792 taking NOAC), the mean age was 71.2 years, male was 57% and CHA2DS2-VASc score was 3.9. During a mean 1.4-year follow-up, weighted incidence rate of ischemic stroke, ICH, GI bleeding, and all-cause death were lower in the NOAC group than in the warfarin group. Compared to warfarin, NOACs were associated with lower risks of ischemic stroke (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.53–0.96), GI bleeding (HR 0.50, 95% CI 0.35–0.72) and major bleeding (HR 0.61, 95% CI 0.45–0.80). Although NOAC and warfarin groups showed similar incidence rate of ICH, NOAC group was associated with a significantly lower risk of fatal ICH compared to warfarin group (HR 0.28, 95% CI 0.07–0.83). Overall, NOACs were associated with a lower risk of the composite outcome (HR 0.68, 95% CI 0.58–0.80). For an exploratory analysis, patients with EHRA type 1 VHD (n=366 taking warfarin; n=345 taking NOAC) was evaluated. In multivariable Cox regression analysis, NOAC group showed a comparable risk of ischemic stroke, ICH, all-cause death and composite outcome. Clinical outcome in AF patients with VHD Conclusion In this nationwide Asian AF population with EHRA type 2 VHD, NOAC use was associated with lower risks of ischemic stroke, major bleeding, all-cause death, and the composite outcome compared to warfarin.


2007 ◽  
Vol 204 (11) ◽  
pp. 2693-2704 ◽  
Author(s):  
Tsin W. Yeo ◽  
Daniel A. Lampah ◽  
Retno Gitawati ◽  
Emiliana Tjitra ◽  
Enny Kenangalem ◽  
...  

Severe falciparum malaria (SM) is associated with tissue ischemia related to cytoadherence of parasitized erythrocytes to microvascular endothelium and reduced levels of NO and its precursor, l-arginine. Endothelial function has not been characterized in SM but can be improved by l-arginine in cardiovascular disease. In an observational study in Indonesia, we measured endothelial function using reactive hyperemia–peripheral arterial tonometry (RH-PAT) in 51 adults with SM, 48 patients with moderately severe falciparum malaria (MSM), and 48 controls. The mean RH-PAT index was lower in SM (1.41; 95% confidence interval [CI] = 1.33–1.47) than in MSM (1.82; 95% CI = 1.7–2.02) and controls (1.93; 95% CI = 1.8–2.06; P &lt; 0.0001). Endothelial dysfunction was associated with elevated blood lactate and measures of hemolysis. Exhaled NO was also lower in SM relative to MSM and controls. In an ascending dose study of intravenous l-arginine in 30 more patients with MSM, l-arginine increased the RH-PAT index by 19% (95% CI = 6–34; P = 0.006) and exhaled NO by 55% (95% CI = 32–73; P &lt; 0.0001) without important side effects. Hypoargininemia and hemolysis likely reduce NO bioavailability. Endothelial dysfunction in malaria is nearly universal in severe disease, is reversible with l-arginine, and likely contributes to its pathogenesis. Clinical trials in SM of adjunctive agents to improve endothelial NO bioavailability, including l-arginine, are warranted.


2021 ◽  
Vol 27 ◽  
pp. 107602962110447
Author(s):  
Hongxia Li ◽  
Lei Zhang ◽  
Ming Xia ◽  
Chi Zhang ◽  
Tingbo Jiang

Background Novel oral anticoagulants and warfarin are widely used for stroke prevention in patients with atrial fibrillation. The anticoagulation status of patients receiving warfarin or rivaroxaban has been studied. In this study, we aimed to evaluate the effect of dabigatran and warfarin on preventing thrombin generation (TG). Methods This retrospective study enrolled 237 nonvalvular atrial fibrillation (NVAF) subjects treated with 110 mg dabigatran etexilate twice daily and 224 NVAF patients received adjusted-dose warfarin (international normalized ratio [INR] of 2 to 3)). Coagulation assays, prothrombin fragment 1  +  2 (F1+2), calibrated automated thrombogram, and thrombin–antithrombin complex (TAT) were detected at the steady state. Results Activated partial thromboplastin time (APTT), antithrombin III activity, fibrinogen, and lag time showed no difference between the two groups. Compared to the dabigatran group, prothrombin time and INR values were higher in the warfarin group (all P < .001). Thrombin time, endogenous thrombin potential, peak TG (Cmax), F1+2, and TAT were lower in the warfarin group. The inhibition of TG was still stronger in the warfarin group when the patients were divided into subgroups. Conclusion Conventional coagulation assays are suboptimal for assessing the coagulation status of dabigatran. TG could be used as supplementary assays to evaluate the anticoagulation effect of oral anticoagulants. Our results suggest that warfarin may inhibit TG more aggressively than dabigatran in patients regardless of age and kidney function.


Author(s):  
Hisanori Kanazawa ◽  
Koichi Kaikita ◽  
Miwa Ito ◽  
Yusei Kawahara ◽  
Tadashi Hoshiyama ◽  
...  

Background The clinical implication of vascular endothelial dysfunction in patients with atrial fibrillation (AF) remains unclear. This study aimed to elucidate the correlation between changes in vascular endothelial function assessed by reactive hyperemia‐peripheral arterial tonometry and the effect of sinus rhythm restoration after catheter ablation (CA) for AF. Methods and Results Consecutive 214 patients who underwent CA for AF were included in this single center, retrospective study. The natural logarithmic transformed reactive hyperemia‐peripheral arterial tonometry index (LnRHI) of all patients was measured before CA as well as 3 and 6 months after CA. LnRHI in sinus rhythm was significantly higher than that in AF before CA. Multivariate logistic regression analysis revealed that the presence of AF was an independent risk factor for lowering of LnRHI (odds ratio, 4.092; P =0.002) before CA. The LnRHI was significantly improved 3 and 6 months after CA in patients without AF recurrence. Multivariate Cox hazard analysis revealed that changes in LnRHI from before to 3 months after CA independently correlated with recurrence of AF (hazard ratio, 0.106; P =0.001). Receiver operating characteristic analysis showed the decrease in LnRHI levels from before to 3 months after CA as a significant marker that suspects AF recurrence (area under the curve, 0.792; log‐rank test, P <0.001). Conclusions The presence of AF was independently correlated with the impaired vascular endothelial function assessed by the reactive hyperemia‐peripheral arterial tonometry. Long‐term sinus rhythm restoration after CA for AF might contribute to the improvement of vascular endothelial function, which may reflect the nonrecurrence of AF.


2020 ◽  
pp. 0271678X2095695
Author(s):  
Wenjin Liu ◽  
Zhensen Chen ◽  
Dakota Ortega ◽  
Xuebing Liu ◽  
Xiaoqin Huang ◽  
...  

Vascular dysfunctions, including arterial stiffness and endothelial dysfunction, are prevalent in hypertensive subjects. We aimed to study their relations to subclinical intracranial vascular health in this study. A total of 200 older hypertensive males without overt cardiovascular or cerebrovascular diseases were recruited. Arterial elasticity was measured as carotid-femoral pulse wave velocity (cfPWV) and endothelial function was measured as digital reactive hyperemia index (RHI). Cerebrovascular health was evaluated using MRI in four aspects: intracranial atherosclerosis, brain perfusion as cerebral blood flow (CBF), vascular rarefaction analyzed as visible arterial branches on angiography using a custom-developed analysis technique and small vessel disease measured as white matter hyperintensity (WMH). There was a significant negative association between cfPWV and CBF, suggesting a link between arterial stiffness and CBF decline. Higher cfPWV was also associated with presence of intracranial stenotic plaque and greater WMH volume. RHI was positively related to CBF, indicating that endothelial dysfunction was associated with reduced CBF. All the associations remained significant after adjustment for confounding variables. Arterial stiffness and endothelial dysfunction are associated with reduced brain perfusion in older hypertensive males. Arterial stiffness is also associated with global cerebral vascular injury, affecting both small and medium-to-large arteries.


Author(s):  
Maryna Stoikevych ◽  
Nataliia Nedzvetska ◽  
Nataliia Fedorova

Abstract. Currently, inflammatory bowel disease (IBD) is the most complex and not fully resolved problem in modern gastroenterology. IBD, with its two main subtypes, Crohn's disease (CD) and ulcerative colitis (UC), is a complex multifactorial pathology caused by external and internal factors, including host genetics, the immune system, environmental factors, and the gut microbiome. The possible involvement of endothelial dysfunction is also discussed. There is evidence that in diseases characterized by chronic systemic inflammation, it affects the properties of the arteries and causes both endothelial dysfunction and changes in arterial stiffness. The aim is to study the functional state of the vascular endothelium in patients with inflammatory bowel diseases. Material and methods. A total of 69 patients with IBD aged 18 to 70 years (44.0 ± 1.4 years) were examined. All patients were divided into 2 groups depending on the nosology. 1st group consisted of 45 patients with UC, among them 23 women (51.1 %) and 22 men (48.9 %), 2nd group – 24 patients with HC, of which 14 women (58.3 %) and 10 men (41.7 %). To assess endothelial function, the method for determining endothelium-dependent vasodilation of the brachial artery (BA) in a test with reactive hyperemia was used to assess the change in BA diameter (dPA), a ATL PHILIPS HDI 5000 SONOS CT ultrasound machine with a 7.5 MHz linear transducer was used. The endothelial function index was calculated as the difference between dPA after decompression and the initial value, expressed as a percentage. The content of a soluble vascular cell adhesion molecule 1 (VCAM-1) was determined in blood serum by an enzyme immunoassay using a test system («Bender MedSystems GmbH», Austria) using an enzyme immunoassay analyzer «Stat Fax 303 Plus» («Awareness Technology Inc.», USA). The number of desquamated endothelial cells in the peripheral blood was determined by the method of J. Hladovec. Results. In the study of endothelium-dependent vasodilation (EDVD) PA in a test with reactive hyperemia, dysfunctions of the vascular endothelium were found in 75.4 % of the examined patients. Changes in vascular endothelial function were found in 82.3 % of patients with UC and 62.5 % with CC, mainly due to endothelial dysfunction (ED). Significant differences were found between the indicators of the average increase in dPA in the test with reactive hyperemia with decreased endothelial function (DEF) and normal endothelial function (NEF), as well as with DEF and ED in patients with severe UC. ED was observed 5.2 times more often than NEF (c2 = 56.8; p < 0.001) and 2.6 times more often than PFE (c2 = 31.5; p < 0.001). With moderate severity of the disease, DEF and ED occurred with the same frequency and 2.2 times higher than the number of patients with NEF (c2 = 11.3; p = 0.0008), changes in endothelium-dependent vasodilation were accompanied by a significant increase in the VCAM-1 level in serum of all IBD patients, but the highest expression of VCAM-1 was observed in UC. At the same time, the concentration of VCAM-1 was inversely correlated with endothelium-dependent vasodilation of BA (r = - 0.54, p < 0.01), which is confirmed by the quantitative characteristics of the level of VCAM-1 in various states of the endothelium. The study of the content of circulating desquamated endothelial cells in the peripheral blood made it possible to establish an increase in their number by 5 times with ED – up to (15.5 ± 4.8) × 104/L (p < 0.05), 2 times with DEF – up to (5.7 ± 0.3) × 104/L (p < 0.001) versus (3.1 ± 0.4) × 104/L in the control group. An inverse correlation was found between the number of desquamated endothelial cells and endothelium-dependent BA vasodilation (r = - 0.59, p < 0.01). Conclusions. The results of a comprehensive study of the functional state of the vascular endothelium indicate that the course of IBD is accompanied by a syndrome of endothelial dysfunction (with a predominance of DE), which is characterized by a decrease in endothelium-dependent vasodilation of BA, an increase in the level of VCAM-1 and the content of circulating desquamated endothelial cells in the blood. Keywords: inflammatory bowel disease, Crohn's disease, ulcerative colitis, endothelial dysfunction.


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