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Sex-specific association of time-varying haemoglobin values

with mortality in incident dialysis patients

Gisela Sturm1, Claudia Lamina1, Emanuel Zitt2, Karl Lhotta2,3, Friederike Lins3,Otto

Freisttter3

, Ulrich Neyer2,3,*

and Florian Kronenberg1,*

1 Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology,

Innsbruck Medical University, Schpfstr. 41, 6020 Innsbruck, Austria 2Department of Nephrology and Dialysis,

Academic Teaching Hospital Feldkirch, Carinagasse 47, 6800 Feldkirch, Austria 3 Vorarlberg Institute for Vascular

Investigation and Treatment (VIVIT), Carinagasse 47, 6800 Feldkirch, Austria

Florian Kronenberg; E-mail: Florian.Kronenberg@i-med.ac.at

Abstract

Background. Previous studies in dialysis patients showed anassociation 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 applyinga time-dependent Cox regression analysis using

all the measuredlaboratory values for up to more than 7 years. In total, 12242

haemoglobin measurements with a median of 47 (range 3270)per patient were

available to evaluate the impact of haemoglobinlevels and their variability on all-

cause mortality in a sex-stratifiedanalysis. Non-linear P-splines were used to allow a

flexiblemodelling of the association with mortality.

Results. We observed an inverse relationship between the increasinghaemoglobin

values and the decreasing risk of mortality. Thelinear component of the non-linear

spline was highly significantfor both men (P = 0.00005) and women (P =

0.0000000052). Thenon-linear component was also significant but less

pronounced

than the linear component. The inverse relationship was clear

to seehaemoglobin levels of up to 1213 g/L in women,which reached a plateau for the

higher values of haemoglobin.For men, an inverse trend was observed but clearly

attenuatedwhen compared to women. After adjustment for additional parametersof

inflammation and malnutrition as well as diabetes, the linearcomponent was more

significant in women (P = 0.0018) than inmen (P = 0.023).

mailto:Florian.Kronenberg@i-med.ac.atmailto:Florian.Kronenberg@i-med.ac.at

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Conclusions. This study applied for the first time a time-dependentCox regression

analysis over a long-term observation periodof several years using all available

measurements. Besides themethodological advantages, our data indicate a sex-

specificlinear as well as non-linear effect of haemoglobin levels onall-cause

mortality, which was markedly more pronounced in women.

Keywords: end-stage renal disease; haemoglobin; mortality; prospective

observational study; time-dependent Cox regression