title: Sex-specific association of time-varying haemoglobin values with mortality in incident dialysis patients.
abstract: BACKGROUND
  Previous studies in dialysis patients showed an association between haemoglobin levels and all-cause mortality, however, without addressing sex differences.
  
  
  METHODS
  We followed up 235 incident dialysis patients of the region of Vorarlberg in a prospective cohort study applying a time-dependent Cox regression analysis using all the measured laboratory values for up to more than 7 years. In total, 12 242 haemoglobin measurements with a median of 47 (range 3-270) per patient were available to evaluate the impact of haemoglobin levels and their variability on all-cause mortality in a sex-stratified analysis. Non-linear P-splines were used to allow a flexible modelling of the association with mortality.
  
  
  RESULTS
  We observed an inverse relationship between the increasing haemoglobin values and the decreasing risk of mortality. The linear component of the non-linear spline was highly significant for both men (P = 0.00005) and women (P = 0.0000000052). The non-linear component was also significant but less pronounced than the linear component. The inverse relationship was clear to see haemoglobin levels of up to 12-13 g/L in women, which reached a plateau for the higher values of haemoglobin. For men, an inverse trend was observed but clearly attenuated when compared to women. After adjustment for additional parameters of inflammation and malnutrition as well as diabetes, the linear component was more significant in women (P = 0.0018) than in men (P = 0.023).
  
  
  CONCLUSIONS
  This study applied for the first time a time-dependent Cox regression analysis over a long-term observation period of several years using all available measurements. Besides the methodological advantages, our data indicate a sex-specific linear as well as non-linear effect of haemoglobin levels on all-cause mortality, which was markedly more pronounced in women.
authors.affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schopfstr. 41, Innsbruck, Austria.
authors.forename: Gisela
authors.initials: G
authors.lastname: Sturm
authors.forename: Claudia
authors.initials: C
authors.lastname: Lamina
authors.forename: Emanuel
authors.initials: E
authors.lastname: Zitt
authors.forename: Karl
authors.initials: K
authors.lastname: Lhotta
authors.forename: Friederike
authors.initials: F
authors.lastname: Lins
authors.forename: Otto
authors.initials: O
authors.lastname: Freistätter
authors.forename: Ulrich
authors.initials: U
authors.lastname: Neyer
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood* / Q000209:etiology; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000401:mortality* / Q000628:therapy*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012044:Regression Analysis; D006435:Renal Dialysis; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012727:Sex Characteristics; D015996:Survival Rate; D013997:Time Factors
chemical_list: D006454:Hemoglobins