Serum NOX2 and urinary isoprostanes predict vascular events in patients with atrial fibrillation.
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.
Pasquale
P
Pignatelli
Daniele
D
Pastori
Roberto
R
Carnevale
Alessio
A
Farcomeni
Roberto
R
Cangemi
Cristina
C
Nocella
Simona
S
Bartimoccia
Tommasa
T
Vicario
Mirella
M
Saliola
Gregory Y H
GY
Lip
Prof. Francesco Violi, I Clinica Medica, Viale del Policlinico 155, Roma, 00161, Italy, Tel.: +39 064461933, Fax: +39 0649970103, E-mail: francesco.violi@uniroma1.it.
Francesco
F
Violi
D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000201:enzymology / Q000401:mortality / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002545:Brain Ischemia / Q000209:etiology; D002423:Cause of Death; D002561:Cerebrovascular Disorders / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000652:urine; D005260:Female; D006801:Humans; D015994:Incidence; D002546:Ischemic Attack, Transient / Q000209:etiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000097:blood*; D018384:Oxidative Stress; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D012384:Rome / Q000453:epidemiology; D020521:Stroke / Q000209:etiology; D013997:Time Factors
D015415:Biomarkers; D008562:Membrane Glycoproteins; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
Arrhythmia; NOX2; atrial fibrillation; cardiovascular events; urinary isoprostanes