dinoprost and Atrial-Fibrillation

Enhanced oxidative stress occurs in atrial fibrillation (AF), however its impact on the efficacy and safety of anticoagulation is unknown. We sought to evaluate whether 8-isoprostaglandin F2 (8-isoprostane) levels are associated with clinical outcomes in anticoagulated AF patients.. In a study involving 243 AF patients (median age 69 years), we measured serum 8-isoprostane, along with prothrombotic markers, including plasma fibrin clot permeability, clot lysis time (CLT), endogenous thrombin potential (ETP), von Willebrand factor (VWF), and fibrinolytic proteins. Ischemic cerebrovascular events, major bleeding, and death were recorded during a median follow-up of 53 months while on anticoagulation, largely on non-vitamin K antagonist oral anticoagulants (NOACs).. Increased 8-isoprostane levels partly through altered fibrin clot structure are associated with thromboembolic events despite anticoagulant therapy in AF patients.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dinoprost; Female; Fibrin; Hemorrhage; Humans; Risk Factors; Stroke; Thromboembolism; Thrombosis; von Willebrand Factor

There are limited prospective data evaluating the role of urinary F2-IsoP and NOX2 as predictive markers in atrial fibrillation (AF). The aim of this study was to analyse the role of urinary prostaglandin PGF2alpha (8-iso-PGF2α) and NOX2, markers of systemic oxidative stress, in predicting cardiovascular (CV) events and mortality in anticoagulated non-valvular AF patients. This was a prospective study including 1,002 anticoagulated AF patients, followed for a median time of 25.7 months (interquartile range: 14.8-50.9). All major CV events, CV deaths and all-cause deaths were considered as primary outcomes of the study. CV events included fatal/nonfatal ischaemic stroke, fatal/nonfatal myocardial infarction (MI), cardiac revascularisation and transient ischaemic attack (TIA). Oxidative stress biomarkers, such as urinary 8-iso-PGF2α and serum sNOX2-dp, a marker of NOX2 activation, were measured. A CV event occurred in 125 patients (12.5 %); 78 CV deaths and 31 non-CV deaths were registered. 8-iso-PGF2α and sNOX2-dp were correlated (Rs=0.765 p< 0.001). A significant increased cumulative incidence of CV events and CV deaths was observed across tertiles for 8-iso-PGF2α and sNOX2-dp. An increased rate of all-cause death was observed across tertiles of urinary 8-iso-PGF2α. In Cox or Fine and Gray models, 8-iso-PGF2α predicted CV events and CV and non-CV deaths. The addition of tertiles of 8-iso-PGF2α to CHA2DS2-VASc score improved ROC curves for each outcome and NRI for CV events (0.24 [0.06-0.53] p=0.0067). The study shows that in AF patients 8-iso-PGF2α and NOX2 levels are predictive of CV events and total mortality. F2-IsoP may complement conventional risk factors in prediction of CV events.

Topics: Aged; Aged, 80 and over; Area Under Curve; Atrial Fibrillation; Biomarkers; Brain Ischemia; Cause of Death; Cerebrovascular Disorders; Dinoprost; Female; Humans; Incidence; Ischemic Attack, Transient; Kaplan-Meier Estimate; Male; Membrane Glycoproteins; Middle Aged; Myocardial Infarction; NADPH Oxidase 2; NADPH Oxidases; Oxidative Stress; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk Factors; ROC Curve; Rome; Stroke; Time Factors

Oxidative stress is suggested to play a role in favoring the occurrence of atrial fibrillation (AF). We analyzed whether vitamin E, a known antioxidant, or markers of oxidative stress are associated with AF recurrence in patients undergoing electric cardioversion.. A total of 144 patients (83 men; mean age, 71.1±5.4 years) underwent successful biphasic electric cardioversion of nonvalvular persistent AF. At baseline, urinary 8-isoprostaglandin F2α and serum soluble NOX2-derived peptide (sNOX2-dp), high-sensitivity C-reactive protein (hs-CRP), and vitamin E levels were measured in each patient. All patients underwent 3 months of clinical follow-up, including an office visit with ECG every week or in cases of symptom recurrence. During the follow-up, 94 patients maintained sinus rhythm, whereas 50 experienced AF recurrence. In unadjusted analysis, left atrial diameter and levels of urinary isoprostanes and serum sNOX2-dp and hs-CRP were significantly higher and serum vitamin E lower in patients with AF recurrence. In multivariable Cox analysis, serum vitamin E (hazard ratio, 0.734; 95% CI, 0.605-0.891; P<0.001) and, to a lesser extent, hs-CRP (P=0.047) remained significantly associated with AF recurrence. Urinary isoprostanes and serum sNOX2-dp levels were inversely correlated with serum vitamin E level (r=-0.626, P<0.001, and r=-0.460, P<0.001, respectively).. The study shows that low serum vitamin E levels are associated with AF recurrence in patients who underwent cardioversion. Because vitamin E inversely correlated with oxidative stress, the findings reinforce the hypothesis of an interplay between oxidative stress and AF.

Topics: Aged; Atrial Fibrillation; Biomarkers; C-Reactive Protein; Dinoprost; Electric Countershock; Female; Follow-Up Studies; Humans; Male; Membrane Glycoproteins; NADPH Oxidase 2; NADPH Oxidases; Oxidative Stress; Recurrence; Retrospective Studies; Vitamin E

Both platelet activation and lipid peroxidation are potential sources of vasoactive eicosanoids that can be produced via the cyclooxygenase pathway, ie, thromboxane (TX) A2, or by free radical-catalyzed peroxidation of arachidonic acid, ie, isoprostanes. We investigated the biosynthesis of TXA2 and F2-isoprostanes, as reflected by the urinary excretion of 11-dehydro-TXB2 and 8-epi-prostaglandin (PG) F2 alpha respectively, in 62 consecutive patients (30 men, 32 women; mean age, 67 +/- 14 years) with acute ischemic stroke.. At least two consecutive 6-hour urine samples were obtained during the first 72 hours after onset of symptoms. Urinary eicosanoids were measured by previously described radioimmunoassays.. Repeated periods of enhanced thromboxane biosynthesis were found in 52% of patients. Urinary 11-dehydro-TXB2 averaged 221 +/- 207 (mean +/- SD; n = 197; range, 13 to 967) pmol/mmol creatinine in 30 patients treated with cyclooxygenase inhibitors (mostly aspirin) at the time of study versus 392 +/- 392 (n = 186; range, 26 to 2533) in 32 untreated patients (P < .001). The corresponding values for 8-epi-PGF2 alpha excretion were 74 +/- 42 (range, 14 to 206) and 83 +/- 65 (range, 24 to 570) pmol/mmol creatinine (P > .05). The correlation between the two metabolites was moderate in both untreated patients (r = .41, P < .001) and patients with cyclooxygenase inhibitors (r = .31, P < .001). In a multiple regression analysis, increased thromboxane production was independently associated with severity of stroke on admission, atrial fibrillation, and treatment with cyclooxygenase-inhibiting drugs.. We conclude that during the first few days after an acute ischemic stroke (1) platelet activation occurs repeatedly in a cyclooxygenase-dependent fashion; (2) platelet activation is not associated with concurrent changes in isoprostane biosynthesis; (3) platelet activation is independently associated with stroke severity and atrial fibrillation; and (4) isoprostane biosynthesis is largely independent of platelet cyclooxygenase activity.

Topics: Acute Disease; Aged; Atrial Fibrillation; Brain Ischemia; Cerebrovascular Disorders; Cyclooxygenase Inhibitors; Dinoprost; Female; Humans; Lipid Peroxides; Male; Middle Aged; Platelet Activation; Reference Values; Thromboxane B2

The variations in the content of endogenic prostanoids and cyclic nucleotides in the blood plasma of the coronary sinus and ascending aorta were studied in patients with the idiopathic stable form of atrial fibrillation before and after sinus rhythm recovery effected by electroimpulse therapy. Changes in the levels and ratios of these compounds in the coronary venous and arterial blood were found to be opposite in their trends. A significant elevation in TxB2 levels and the TxB2/6-keto-PGF1 ratio as well as increased cGMP concentrations in the plasma of the coronary venous blood appear to be suggestive of an unfavourable prognosis because patients with such changes developed atrial fibrillation recurrences soon after electroimpulse therapy.

Topics: Adult; Aorta, Thoracic; Atrial Fibrillation; Coronary Vessels; Cyclic AMP; Cyclic GMP; Dinoprost; Epoprostenol; Female; Humans; Male; Middle Aged; Prostaglandins; Prostaglandins E; Prostaglandins F; Thromboxane A2; Thromboxanes