title: Cosinor modelling of seasonal variation in 25-hydroxyvitamin D concentrations in cardiovascular patients in Norway.
abstract: OBJECTIVE
  Seasonal variation may reduce the validity of 25-hydroxyvitamin D (25OHD) as a biomarker of vitamin D status. Here we aimed to identify potential determinants of seasonal variation in 25OHD concentrations and to evaluate cosinor modelling as a method to adjust single 25OHD measurements for seasonal variation.
  
  
  METHODS
  In Caucasian cardiovascular patients (1999-2004), we measured 25OHD by liquid chromatography tandem mass spectrometry in 4116 baseline and 528 follow-up samples. To baseline values, we fitted a cosinor model for monthly concentrations of 25OHD. Using the model, we estimated each patient's adjusted annual 25OHD value. Further, we studied how covariates affected the annual mean 25OHD concentration and seasonal variation of the study cohort. To evaluate the model, we predicted follow-up measurements with and without covariates and compared accuracy with carrying forward baseline values and linear regression adjusting for season, common approaches in research and clinical practice, respectively.
  
  
  RESULTS
  The annual mean (59.6 nmol/l) was associated with participants' age, gender, smoking status, body mass, physical activity level, diabetes diagnosis, vitamin D supplement use and study site (adjusted models, P<0.05). Seasonal 25OHD variation was 15.8 nmol/l, and older age (>62 years) was associated with less variation (adjusted model, P=0.025). Prediction of follow-up measurements was more accurate with the cosinor model compared with the other approaches (P<0.05). Adding covariates to cosinor models did not improve prediction (P>0.05).
  
  
  CONCLUSIONS
  We find cosinor models suitable and flexible for analysing and adjusting for seasonal variation in 25OHD concentrations, which is influenced by age.
authors.affiliation: Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Degerud
authors.affiliation: The Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: R
authors.initials: R
authors.lastname: Hoff
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
authors.forename: O
authors.initials: O
authors.lastname: Nygård
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Strand
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Cardiology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: D W
authors.initials: DW
authors.lastname: Nilsen
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
authors.forename: J E
authors.initials: JE
authors.lastname: Nordrehaug
authors.affiliation: Bevital AS, Bergen, Norway.
authors.forename: Ø
authors.initials: Ø
authors.lastname: Midttun
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.|Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
authors.forename: P M
authors.initials: PM
authors.lastname: Ueland
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
authors.forename: S
authors.initials: S
authors.lastname: de Vogel
authors.affiliation: Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: J
authors.initials: J
authors.lastname: Dierkes
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood*; D015331:Cohort Studies; D019587:Dietary Supplements; D015444:Exercise; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009664:Norway; D016032:Randomized Controlled Trials as Topic; D012621:Seasons; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D044465:White People
chemical_list: D015415:Biomarkers; D014807:Vitamin D; D002097:C-Reactive Protein; C104450:25-hydroxyvitamin D