Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schopfstr. 41, Innsbruck, Austria.
Nephrol Dial Transplant. 2010 Aug;25(8):2715-22. doi: 10.1093/ndt/gfq101. Epub 2010 Feb 26.
Previous studies in dialysis patients showed an association between haemoglobin levels and all-cause mortality, however, without addressing sex differences.
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.
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).
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.
之前的透析患者研究表明血红蛋白水平与全因死亡率之间存在关联，但未解决性别差异。
我们对沃拉尔贝格地区的 235 例新发生的透析患者进行了前瞻性队列研究，采用时间依赖性 Cox 回归分析，使用所有可测量的实验室值进行分析，最长时间超过 7 年。总共对每个患者的 12242 次血红蛋白测量值进行了评估，中位数为 47（范围 3-270），以在性别分层分析中评估血红蛋白水平及其变异性对全因死亡率的影响。使用非线性格斯模型来允许对死亡率的关联进行灵活建模。
我们观察到血红蛋白值的增加与死亡率的降低呈反比关系。非线性格斯模型的线性部分对于男性（P = 0.00005）和女性（P = 0.0000000052）都具有高度显著性。非线性部分虽然也具有显著性，但不如线性部分显著。在女性中，血红蛋白水平高达 12-13g/L 时，可以看到这种反比关系，而对于更高的血红蛋白值则达到了一个平台期。对于男性，观察到了相反的趋势，但与女性相比明显减弱。在调整炎症和营养不良以及糖尿病等其他参数后，女性的线性部分更为显著（P = 0.0018），而男性则不显著（P = 0.023）。
本研究首次应用时间依赖性 Cox 回归分析，在多年的长期观察期内使用所有可用的测量值进行分析。除了方法学上的优势，我们的数据还表明血红蛋白水平对全因死亡率存在性别特异性的线性和非线性影响，女性的影响更为显著。
