title: Association between baseline vitamin D metabolite levels and long-term cardiovascular events in patients with rheumatoid arthritis from the CIMESTRA trial: protocol for a cohort study with patient-record evaluated outcomes.
abstract: Cardiovascular morbidity and mortality is increased in patients with rheumatoid arthritis (RA), and among these patients, the prevalence of hypovitaminosis D is high. Moreover, low vitamin D levels have been associated with increased cardiovascular risk in healthy subjects.
  
  
  
  To evaluate the long-term risk of cardiovascular events in patients having low total 25-hydroxyvitamin D levels at baseline compared with patients with normal levels, in an efficiently treated, closed cohort of patients with an early diagnosis of RA.
  
  
  
  This study is a prospective, closed, blinded endpoint cohort study, based on secondary analyses from a previous randomised trial (CIMESTRA study; NCT00209859, approved September 1999) including 160 patients with an early diagnosis of RA from Danish University clinics. Primary outcome will be the proportion of patients with any cardiovascular event in the follow-up period, evaluated using systematic journal audits. Logistic regression models will test the hypothesis that there are more cardiovascular events in enrolled patients with a low level of vitamin D (< 50 nmol/L). Secondarily, Cox regression models, based on survival analysis, will determine the extent to which independent variables (including different levels of vitamin D at baseline) predict whether a cardiovascular event will occur, and also when this will be.
  
  
  
  All patients have received verbal and written information before enrolment, and have given written consent at baseline. To disseminate comprehension of factors of prognostic importance to cardiovascular outcome in RA, we will attempt to have a first draft ready no later than 1 year after the adjudication process has finished. If low vitamin D levels can predict cardiovascular events in RA, it is relevant to take into account in a prediction model, to be considered by patients, physicians and other decision-makers.
  
  
  
  The parental controlled trial is registered as NCT00209859.
authors.affiliation: Department of Rheumatology, Odense University Hospital, University of Southern Denmark, Odense, Denmark.|Odense Patient data Explorative Network (OPEN), University of Southern Denmark, Odense, Denmark.
authors.forename: M
authors.identifier: 0000-0002-3100-0850
authors.initials: M
authors.lastname: Herly
authors.affiliation: Department of Rheumatology, Centre of Cancer and Inflammation, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Stengaard-Pedersen
authors.affiliation: King Christian 10th Hospital for Rheumatic Diseases, Southern University of Denmark, Graasten, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Hørslev-Petersen
authors.affiliation: Department of Rheumatology, COPECARE, Copenhagen University Hospital, Glostrup, Denmark.
authors.forename: M L
authors.initials: ML
authors.lastname: Hetland
authors.affiliation: Department of Rheumatology, COPECARE, Copenhagen University Hospital, Glostrup, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Østergaard
authors.affiliation: Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
authors.forename: R
authors.identifier: 0000-0002-6600-0631
authors.initials: R
authors.lastname: Christensen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Denmark.
authors.forename: B B
authors.initials: BB
authors.lastname: Løgstrup
authors.affiliation: Departments of Clinical Medicine and Endocrinology, Aalborg University, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Vestergaard
authors.affiliation: Department of Rheumatology, Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Pødenphant
authors.affiliation: Department of Rheumatology, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Junker
authors.affiliation: Department of Rheumatology, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Ellingsen
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D011446:Prospective Studies; D012307:Risk Factors; D014808:Vitamin D Deficiency / Q000097:blood* / Q000175:diagnosis
chemical_list: D015415:Biomarkers
keywords: Cardiovascular co-morbidity; Rheumatoid Arthritis; Vitamin D metabolites