scholarly journals Rivaroxaban compared with low-dose aspirin in individuals with type 2 diabetes and high cardiovascular risk: a randomised trial to assess effects on endothelial function, platelet activation and vascular biomarkers

Diabetologia ◽  
2021 ◽  
Author(s):  
Frank Pistrosch ◽  
Jan B. Matschke ◽  
Dorothea Schipp ◽  
Bernhard Schipp ◽  
Elena Henkel ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Flow ◽  
Arterial Stiffness ◽  
Endothelial Function ◽  
Factor Xa ◽  
Factor Xa Inhibitor ◽  
Subclinical Inflammation ◽  
Direct Factor

Abstract Aims/hypothesis Individuals with type 2 diabetes mellitus and subclinical inflammation have stimulated coagulation, activated platelets and endothelial dysfunction. Recent studies with the direct factor Xa inhibitor rivaroxaban in combination with low-dose aspirin demonstrated a significant reduction of major cardiovascular events, especially in individuals with type 2 diabetes and proven cardiovascular disease. Therefore, we asked the question of whether treatment with rivaroxaban could influence endothelial function, arterial stiffness and platelet activation. Methods We conducted a multi-centre, prospective, randomised, open-label trial in 179 participants with type 2 diabetes (duration 2–20 years), subclinical inflammation (high-sensitivity C-reactive protein 2–10 mg/l) and at least two traits of the metabolic syndrome to compare the effects of the direct factor Xa inhibitor rivaroxaban (5 mg twice daily) vs aspirin (100 mg every day) on endothelial function (assessed by forearm occlusion plethysmography), skin blood flow (assessed by laser-Doppler fluxmetry), arterial stiffness (assessed by pulse wave velocity) and serum biomarkers of endothelial function and inflammation. Furthermore, we investigated phosphorylation of vasodilator-stimulated phosphoprotein (VASP) in platelets, the concentration of platelet-derived microparticles (PMPs) and the effects of isolated PMPs on HUVEC proliferation in vitro. Results Rivaroxaban treatment for 20 weeks (n = 89) resulted in a significant improvement of post-ischaemic forearm blood flow (3.6 ± 4.7 vs 1.0 ± 5.2 ml/100 ml, p = 0.004), a numerically increased skin blood flow and reduced soluble P-Selectin plasma level vs aspirin. We did not find significant differences of arterial stiffness or further biomarkers. Neither rivaroxaban nor aspirin influenced VASP phosphorylation of platelets. The number of PMPs increased significantly with both rivaroxaban (365.2 ± 372.1 vs 237.4 ± 157.1 μl−1, p = 0.005) and aspirin (266.0 ± 212.7 vs 201.7 ± 162.7 μl−1, p = 0.021). PMPs of rivaroxaban-treated participants stimulated HUVEC proliferation in vitro compared with aspirin. Rivaroxaban was associated with a higher number of bleeding events. Conclusions/interpretation Our findings indicate that the direct factor Xa inhibitor rivaroxaban improved endothelial function in participants with type 2 diabetes and subclinical inflammation but also increased the risk of bleeding. Trial registration: ClinicalTrials.gov NCT02164578. Funding The study was supported by a research grant from Bayer Vital AG, Germany. Graphical abstract

scholarly journals In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939-an oral, direct Factor Xa inhibitor

2005 ◽  
Vol 3 (3) ◽  
pp. 514-521 ◽  
Author(s):  
E. PERZBORN ◽  
J. STRASSBURGER ◽  
A. WILMEN ◽  
J. POHLMANN ◽  
S. ROEHRIG ◽  
...  
Keyword(s):  
Factor Xa ◽  
In Vivo Studies ◽  
Factor Xa Inhibitor ◽  
The Novel ◽  
Direct Factor ◽  
Antithrombotic Agent

[34] ENDOTHELIAL FUNCTION IS ASSOCIATED WITH ARTERIAL STIFFNESS IN SUBJECTS WITH TYPE 2 DIABETES

2009 ◽  
Vol 19 ◽  
pp. S9
Author(s):  
G. Daniele ◽  
L. Ghiadoni ◽  
R. Bruno ◽  
C. Bianchi ◽  
L. Pucci ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Arterial Stiffness ◽  
Endothelial Function

Effect of vildagliptin versus glibenclamide on endothelial function and arterial stiffness in patients with type 2 diabetes and hypertension: a randomized controlled trial

2018 ◽  
Vol 55 (12) ◽  
pp. 1237-1245 ◽  
Author(s):  
Luciana Neves Cosenso-Martin ◽  
Luiz Tadeu Giollo-Júnior ◽  
Letícia Aparecida Barufi Fernandes ◽  
Cláudia Bernardi Cesarino ◽  
Marcelo Arruda Nakazone ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Randomized Controlled Trial ◽  
Arterial Stiffness ◽  
Endothelial Function ◽  
Controlled Trial ◽  
Randomized Controlled

Vascular dysfunction and insulin stimulated blood flow : impact of physical inactivity and type 2 diabetes

2014 ◽  
Author(s):  
◽  
Leryn J. Boyle
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Blood Flow ◽  
Insulin Sensitivity ◽  
Endothelial Function ◽  
Physical Inactivity ◽  
Vascular Dysfunction ◽  
Insulin Stimulation

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Individuals with type 2 diabetes (T2D) have blunted femoral artery insulin mediated blood flow which is critical for the delivery and uptake of glucose into skeletal muscle. However, it is unclear in humans the precise mechanisms by which insulin resistance impairs insulin stimulated blood flow. Further, chronic physical inactivity is a powerful stimulus for reduced insulin sensitivity and vascular dysfunction; however, the effects of short term, modest reductions in physical activity are limited. Thus, we examined 1) if inactivity for 5 days would impair endothelial function in healthy individuals (study one) 2) if reducing whole body insulin sensitivity, via 5 days of inactivity, would impair the blood flow response to insulin stimulation in parallel with glycemic control (study two) and 3) phosphorylation of endothelial nitric oxide (eNOS) and endothelin-1 (ET-1) production to insulin stimulation would be decreased and increased, respectively, in insulin resistant individuals (study three). We demonstrated significant reductions in endothelial function with only 5 days of reduced daily steps while blood flow to glucose ingestion was unaltered. Further, in obese humans with type 2 diabetes it does not appear that that the reduction in blood flow to 1 hr of insulin stimulation is due to altered peNOS or ET-1. Collectively, these data suggest that reduced daily physical activity and chronic insulin resistance mediate negative impacts on vascular function and insulin stimulated blood flow and signaling.

scholarly journals Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS?

2019 ◽  
Vol 20 (15) ◽  
pp. 3775 ◽  
Author(s):  
Cesar A. Meza ◽  
Justin D. La Favor ◽  
Do-Houn Kim ◽  
Robert C. Hickner
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Dysfunction ◽  
Vascular Complications ◽  
Enzymatic Production

NADPH oxidases (NOX) are enzyme complexes that have received much attention as key molecules in the development of vascular dysfunction. NOX have the primary function of generating reactive oxygen species (ROS), and are considered the main source of ROS production in endothelial cells. The endothelium is a thin monolayer that lines the inner surface of blood vessels, acting as a secretory organ to maintain homeostasis of blood flow. The enzymatic production of nitric oxide (NO) by endothelial NO synthase (eNOS) is critical in mediating endothelial function, and oxidative stress can cause dysregulation of eNOS and endothelial dysfunction. Insulin is a stimulus for increases in blood flow and endothelium-dependent vasodilation. However, cardiovascular disease and type 2 diabetes are characterized by poor control of the endothelial cell redox environment, with a shift toward overproduction of ROS by NOX. Studies in models of type 2 diabetes demonstrate that aberrant NOX activation contributes to uncoupling of eNOS and endothelial dysfunction. It is well-established that endothelial dysfunction precedes the onset of cardiovascular disease, therefore NOX are important molecular links between type 2 diabetes and vascular complications. The aim of the current review is to describe the normal, healthy physiological mechanisms involved in endothelial function, and highlight the central role of NOX in mediating endothelial dysfunction when glucose homeostasis is impaired.

Hyperglycemia and hyperlipidemia are associated with endothelial dysfunction during the development of type 2 diabetes

2007 ◽  
Vol 85 (5) ◽  
pp. 562-567 ◽  
Author(s):  
Elena B. Okon ◽  
Ada W.Y. Chung ◽  
Hongbin Zhang ◽  
Ismail Laher ◽  
Cornelis van Breemen
Keyword(s):  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Plasma Levels ◽  
Early Stage ◽  
Cardiovascular Complications ◽  
Older Age ◽  
Metabolic Markers

Diabetes mellitus impairs endothelial function, which can be considered as the hallmark in the development of cardiovascular diseases. Hyperglycemia, hyperinsulinemia, and hyperlipidemia are believed to contribute to endothelial dysfunction. In the present study, we investigated the possible links among these plasma metabolic markers and endothelial function in a mouse model during the development of type 2 diabetes. C57BL/6J-Lepob/ob mice at 8, 12, and 16 weeks were used to study endothelial function during the establishment of type 2 diabetes. Endothelial function was accessed in vitro in the thoracic aorta by measuring acetylcholine (ACh)-stimulated vasodilatation. Blood plasma was obtained for the measurements of glucose, insulin, triglycerides, and cholesterol levels. Correlation and multiple regression analysis revealed strong negative associations between the ACh responsiveness and the plasma levels of glucose, insulin, and lipid profiles at the age of 8 weeks. Associations were observed at neither older age nor in C57BL/6J mice. In conclusion, the increase in plasma levels of glucose, insulin, and lipids is associated with the impairment of the endothelial function during the early stage of the development of type 2 diabetes. The loss of correlation at an older age suggests multifactorial regulation of endothelial function and cardiovascular complications at later stages of the disease.

ARTERIAL STIFFNESS AND ENDOTHELIAL FUNCTION FOR THE RISK ASSESSMENT OF NEW DIABETIC RETINOPATHY DEVELOPMENT IN TYPE 2 DIABETES

2018 ◽  
Vol 71 (11) ◽  
pp. A2085
Author(s):  
Evangelos Oikonomou ◽  
Alexios Antonopoulos ◽  
Nikolaos Gouliopoulos ◽  
Gerasimos Siasos ◽  
Marilita Moschos ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Assessment ◽  
Diabetic Retinopathy ◽  
Arterial Stiffness ◽  
Endothelial Function

Relative Effects of Telmisartan, Candesartan and Losartan on Alleviating Arterial Stiffness in Patients with Hypertension Complicated by Diabetes Mellitus: An Evaluation Using the Cardio-Ankle Vascular Index (CAVI)

2008 ◽  
Vol 36 (5) ◽  
pp. 1094-1102 ◽  
Author(s):  
G Uehara ◽  
H Takeda
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Arterial Stiffness ◽  
Binding Capacity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ

Using the cardio-ankle vascular index (CAVI) as an indicator, we assessed improvement of arterial stiffness in 95 outpatients with hypertension complicated by type 2 diabetes mellitus who were treated orally for ≤ 12 months with telmisartan 40 mg/day, losartan 50 mg/day or candesartan 8 mg/day. At 1 year, in the telmisartan and losartan groups CAVI did not change whereas in the candesartan group CAVI showed a statistically significant decrease of 2.70%. Although telmisartan is believed to enhance the activity of peroxisome proliferator-activated receptor (PPAR-γ) in vitro, it did not ameliorate arterial stiffness in our patients. Candesartan, however, improved arterial stiffness independently of blood pressure lowering and without PPAR-γ agonist action, possibly by direct action resulting from its potent affinity and binding capacity for the angiotensin II type 1 receptor. We conclude that candesartan is a potentially useful therapy against arterial stiffness in hypertensive patients with type 2 diabetes mellitus.

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