Sex-specific association of time-varying haemoglobin values with mortality in incident dialysis patients.
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.
Sturm
Gisela
G
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schopfstr. 41, Innsbruck, Austria.
Lamina
Claudia
C
Zitt
Emanuel
E
Lhotta
Karl
K
Lins
Friederike
F
Freistätter
Otto
O
Neyer
Ulrich
U
Kronenberg
Florian
F
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
D006454:Hemoglobins