title: Urinary 11-dehydro-thromboxane B2 is associated with cardiovascular events and mortality in patients with atrial fibrillation.
abstract: BACKGROUND
  Patients with nonvalvular atrial fibrillation (AF) show high residual cardiovascular (CV) risk despite oral anticoagulants. Urinary 11-dehydro-thromboxane B2 (TxB2) is associated with an increased risk of CV events (CVEs), but its predictive value in patients with anticoagulated AF is unknown.
  
  
  METHODS
  A prospective single-center cohort study, including 837 patients with AF, was conducted. Mean time of follow-up was 30.0 months, yielding 2,062 person-years of observation. Urinary 11-dehydro-TxB2 was measured at baseline. The primary end point was the occurrence of a CVE including fatal/nonfatal myocardial infarction and ischemic stroke, transient ischemic attack, cardiac revascularization, and CV death.
  
  
  RESULTS
  Mean age of patients was 73.1 years, and 43.6% were women. Median 11-dehydro-TxB2 levels were 100 (interquartile range 50-187) ng/mg of urinary creatinine. Overall, the anticoagulation control was adequate (63.9% of mean time in therapeutic range). A CVE occurred in 99 (11.8%) patients, and 55 were CV deaths. At baseline, 11-dehydro-TxB2 levels were higher in patients with a CVE compared with those without (186 [107-400] vs 98 [52-170], P < .001). An increased rate of CVEs (log-rank test, P < .001) and CV deaths (P < .001) was observed across tertiles of 11-dehydro-TxB2. Cardiovascular events were associated with age (hazard ratios [HR] 1.72 per 1 SD, 95% CI 1.33-2.21, P < .001), diabetes mellitus (HR 1.89, 95% CI 1.20-2.96, P = .005), heart failure (HR 1.60, 95% CI 1.01-2.54, P = .044), history of stroke/transient ischemic attack (HR 1.96, 95% CI 1.25-3.06, P = .003), and 11-dehydro-TxB2 (HR 1.64 per 1 SD, 95% CI 1.42-1.89, P < .001).
  
  
  CONCLUSIONS
  Urinary 11-dehydro-TxB2 levels are associated with a residual risk of CVEs and CV mortality in patients with AF despite anticoagulant treatment.
authors.affiliation: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Umberto I Policlinico of Rome, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Pastori
authors.affiliation: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Umberto I Policlinico of Rome, Rome, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pignatelli
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Farcomeni
authors.affiliation: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Umberto I Policlinico of Rome, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cangemi
authors.affiliation: Division of Cardiology and CPC Clinical Research, University of Colorado School of Medicine, Aurora, CO.
authors.forename: William R
authors.initials: WR
authors.lastname: Hiatt
authors.affiliation: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Umberto I Policlinico of Rome, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Bartimoccia
authors.affiliation: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Umberto I Policlinico of Rome, Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Nocella
authors.affiliation: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Umberto I Policlinico of Rome, Rome, Italy.
authors.forename: Tommasa
authors.initials: T
authors.lastname: Vicario
authors.affiliation: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Umberto I Policlinico of Rome, Rome, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Bucci
authors.affiliation: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Umberto I Policlinico of Rome, Rome, Italy; Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Carnevale
authors.affiliation: Centre for Cardiovascular Sciences, University of Birmingham, City Hospital, Birmingham, United Kingdom.
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
authors.affiliation: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Umberto I Policlinico of Rome, Rome, Italy. Electronic address: francesco.violi@uniroma1.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000401:mortality* / Q000652:urine; D015415:Biomarkers / Q000652:urine; D016757:Death, Sudden, Cardiac / Q000453:epidemiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D009203:Myocardial Infarction / Q000453:epidemiology*; D011446:Prospective Studies; D018570:Risk Assessment; D020521:Stroke / Q000453:epidemiology*; D015996:Survival Rate / Q000639:trends; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine; D013997:Time Factors
chemical_list: D015415:Biomarkers; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2