Serum NOX2 and urinary isoprostanes predict vascular events in patients with atrial fibrillation.

Abstract

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.

• Authors: Pasquale Pignatelli, Daniele Pastori, Roberto Carnevale, Alessio Farcomeni, Roberto Cangemi, Cristina Nocella, Simona Bartimoccia, Tommasa Vicario, Mirella Saliola, Gregory Y H Lip, Francesco Violi
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 113 Issue 3 Pg. 617-24 (Mar 2015) ISSN: 2567-689X [Electronic] Germany
• PMID: 25392853 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Membrane Glycoproteins
• 8-epi-prostaglandin F2alpha
• Dinoprost
• CYBB protein, human
• NADPH Oxidase 2
• NADPH Oxidases

Topics

• Aged
• Aged, 80 and over
• Area Under Curve
• Atrial Fibrillation (blood, complications, diagnosis, enzymology, mortality, urine)
• Biomarkers (blood, urine)
• Brain Ischemia (etiology)
• Cause of Death
• Cerebrovascular Disorders (diagnosis, etiology, mortality)
• Dinoprost (analogs & derivatives, urine)
• Female
• Humans
• Incidence
• Ischemic Attack, Transient (etiology)
• Kaplan-Meier Estimate
• Male
• Membrane Glycoproteins (blood)
• Middle Aged
• Myocardial Infarction (diagnosis, etiology, mortality)
• NADPH Oxidase 2
• NADPH Oxidases (blood)
• Oxidative Stress
• Predictive Value of Tests
• Proportional Hazards Models
• Prospective Studies
• ROC Curve
• Risk Factors
• Rome (epidemiology)
• Stroke (etiology)
• Time Factors