title: Red cell distribution width is associated with physical inactivity and heart failure, independent of established risk factors, inflammation or iron metabolism; the EPIC-Norfolk study.
abstract: OBJECTIVE
  Red cell distribution width (RDW) is associated with increased risk of heart failure (HF). We examined in a healthy population (1) whether this association is independent of cardiovascular risk factors and iron metabolism and (2) whether RDW associates with physical activity.
  
  
  RESULTS
  Hazard ratios (HRs, highest quartile versus lowest quartile of RDW) for the risk of HF were calculated in 17,533 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort. During a follow-up of 11.2±2.2 years 640 participants developed a HF event. The HR for HF events was 1.44 (95%CI 1.15-1.80, p<0.001). There was a non-linear increase in HF risk across RDW quartiles. Adjustment for established risk factors (sex, age, diabetes, smoking, systolic blood pressure, total and high-density lipoprotein cholesterol) attenuated the HR for HF to 1.40 (95%CI 1.11-1.77, p=0.001). Adjustment for CRP, iron and ferritin levels did not affect the HR for HF. RDW levels are inversely associated with physical activity (per category β=-0.37, 95%CI -0.053 to -0.021, p<0.0001), independent of iron metabolism. However, the association between HF and RDW levels was not changed by physical activity.
  
  
  CONCLUSIONS
  This study confirms that RDW is associated with HF events in an apparently healthy middle-aged population. More importantly, we show that the underlying pathophysiology linking HF with anisocytosis is not reflected by conventional risk factors, nor it is explained by iron metabolism or inflammation. Furthermore, RDW levels were associated with physical inactivity, but this did not influence the RDW-associated-risk of heart failure.
authors.affiliation: Department of Cardiology, University Medical Centre, Utrecht, The Netherlands. Electronic address: mireille_emans@hotmail.com.
authors.forename: Mireille E
authors.initials: ME
authors.lastname: Emans
authors.forename: Carlo A J M
authors.initials: CA
authors.lastname: Gaillard
authors.forename: Roman
authors.initials: R
authors.lastname: Pfister
authors.forename: Michael W
authors.initials: MW
authors.lastname: Tanck
authors.forename: S Matthijs
authors.initials: SM
authors.lastname: Boekholdt
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004909:Erythrocyte Indices; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006306:Health Surveys / Q000379:methods; D006333:Heart Failure / Q000097:blood* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000503:physiopathology; D007501:Iron / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology*; D011446:Prospective Studies; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D007501:Iron
keywords: Anisocytosis; Heart failure; Inflammation; Iron metabolism; Physical activity