title: Vitamin D status and outcomes in heart failure patients.
abstract: OBJECTIVE
  Vitamin D status has been implicated in the pathophysiology of heart failure (HF). The aims of this study were to determine whether a low vitamin D status is associated with prognosis in HF and whether activation of the renin-angiotensin system (RAS) and inflammatory markers could explain this potential association.
  
  
  RESULTS
  We measured 25-hydroxy-vitamin D (25(OH)D), plasma renin activity (PRA), interleukin-6 (IL-6), C-reactive protein (CRP), and the incidence of death or HF rehospitalization in 548 patients with HF. Median age was 74 (64-80) years, left ventricular ejection fraction was 30% (23-42), and mean follow-up was 18 months. Low 25(OH)D levels were associated with female gender (P< 0.001), higher age (P= 0.002), and higher N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (P< 0.001). Multivariable linear regression analysis showed that PRA (P= 0.048), and CRP levels (P= 0.006) were independent predictors of 25(OH)D levels. During follow-up, 155 patients died and 142 patients were rehospitalized. Kaplan-Meier analysis showed that lower 25(OH)D concentration was associated with an increased risk for the combined endpoint (all-cause mortality and HF rehospitalization; log rank test P= 0.045) and increased risk for all-cause mortality (log rank test P= 0.014). After adjustment in a multivariable Cox regression analysis, low 25(OH)D concentration remained independently associated with an increased risk for the combined endpoint [hazard ratio (HR) 1.09 per 10 nmol/L decrease; 95% confidence interval (CI) 1.00-1.16; P= 0.040] and all-cause mortality (HR 1.10 per 10 nmol/L decrease; 95% CI 1.00-1.22; P= 0.049).
  
  
  CONCLUSIONS
  A low 25(OH)D concentration is associated with a poor prognosis in HF patients. Activation of the RAS and inflammation may confer the adverse effects of low vitamin D levels.
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Licette C Y
authors.initials: LC
authors.lastname: Liu
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.forename: Eveline
authors.initials: E
authors.lastname: van der Veer
authors.forename: Anne M
authors.initials: AM
authors.lastname: Belonje
authors.forename: Mariusz K
authors.initials: MK
authors.lastname: Szymanski
authors.forename: Herman H W
authors.initials: HH
authors.lastname: Silljé
authors.forename: Wiek H
authors.initials: WH
authors.lastname: van Gilst
authors.forename: Tiny
authors.initials: T
authors.lastname: Jaarsma
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000401:mortality / Q000503:physiopathology*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology; D012307:Risk Factors; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000401:mortality / Q000503:physiopathology*
chemical_list: D015850:Interleukin-6; D014807:Vitamin D; D002097:C-Reactive Protein; C104450:25-hydroxyvitamin D; D012083:Renin