BLOOD DONORS AND BLOOD COLLECTION No association between iron status and self-reported health-related quality of life in 16,375 Danish blood donors: results from the Danish Blood Donor Study Andreas S. Rigas,1 Ole B. Pedersen,2 Cecilie J. Sørensen,3 Erik Sørensen,1 Sebastian R. Kotze ,3 Mikkel S. Petersen,3 Lise W. Thørner,1 Henrik Hjalgrim,4 Christian Erikstrup,3 and Henrik Ullum1
BACKGROUND: Health-related quality of life (HRQL) represents people’s subjective assessment of their mental and physical well-being. HRQL is highly predictive of future health. The effect of iron deficiency without anemia induced by blood donation on HRQL is presently unknown. The aim was to explore the relationship between iron status and self-reported mental component score (MCS; SF-12) and physical component score (PCS; SF-12) in Danish blood donors. STUDY DESIGN AND METHODS: Complete relevant data, including the 12-item short-form health survey (SF12), plasma ferritin levels, age, body mass index, smoking status, C-reactive protein levels, number of donations in the previous 3 years, and PCS and MCS, were available for 8692 men and 7683 women enrolled from March 1, 2010, to December 31, 2010. Multivariable linear and logistic (cutoff at the 10th percentile) regression analyses were used to assess the relationship between iron deficiency (ferritin < 15 ng/mL) and MCS and PCS, respectively. Analyses were performed separately for men and women. RESULTS: There was no significant relationship between iron deficiency and self-reported mental or physical health. CONCLUSION: This study found no association between iron stores and self-reported HRQL among Danish blood donors.
ach year, approximately 237,000 individuals voluntarily donate blood in Denmark alone.1 To optimize the general health of the donor population, a better understanding of the health implications of blood donation is needed. Blood donors are at increased risk of iron deficiency, and the number of blood donations appears to be the strongest predictor hereof.2,3 A link between anemia and a reduced quality of life is well established.4 However, the current knowledge on healthrelated consequences or manifestations of iron deficiency without anemia is limited. Iron is needed for several physiologic processes such as cellular respiration, electron transport, and gene regulation.5
ABBREVIATIONS: BMI 5 body mass index; CRP 5 Creactive protein; HRQL 5 health-related quality of life; MCS 5 mental component summary score; PCS 5 physical component summary score; SF-12 5 12-item short form; SF-36 5 Short Form 36. From the 1Department of Clinical Immunology, Copenhagen University Hospital, Copenhagen, Denmark; the 2Department of Clinical Immunology, Næstved Hospital, Næstved, Denmark; the 3Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark; and the 4Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. Address reprint requests to: Henrik Ullum, Department of Clinical Immunology 2034, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark; e-mail: Henrik. [email protected]
The Danish Blood Donor Study has been supported by The Danish Council for Independent Research (09-069412) and by Danish Regions (02/2611). Received for publication May 15, 2014; revision received November 12, 2014; and accepted December 10, 2014. doi:10.1111/trf.13085 C 2015 AABB V
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IRON STORES AND SELF-REPORTED HRQL
Self-reported health is generally considered a valid and direct measure of health status and well-being and has been shown to predict disease and survival in the general population.6 A widely used scale for self-reported health-related quality of life (HRQL) is the Short Form 36 (SF-36), which has been abridged into a 12-item short form (SF-12) for epidemiologic surveys. The SF-12 is a 12-item questionnaire measuring a physical component summary score (PCS) comprising four scales (physical functioning, role-physical, bodily pain, general health) and a mental component summary score (MCS) comprising four scales (vitality, social functioning, role-emotional, mental health). It has been shown that the correlations between SF-12 and SF-36 in Denmark on PCS and MCS are 0.95 and 0.96, respectively.7 Given the number of individuals at risk of iron deficiency either because of blood donation or inadequate dietary iron intake, more light needs to be shed upon the implications of iron deficiency. It was hypothesized that an impact of iron deficiency without anemia on blood donor health would manifest as a reduced SF-12 MCS and/or PCS score.
MATERIALS AND METHODS The Danish Blood Donor Study3,8 is an ongoing, epidemiologic cohort study, currently comprising around 90,000 healthy blood donors aged 18 to 67 years, representing 95% of all invited donors.8 At inclusion into the Danish Blood Donor Study, blood donors complete a four-page questionnaire, including questions on anthropometric measurements and the SF-12.9 For the purpose of this investigation, plasma ferritin levels were determined in participants enrolled from March 1, 2010, to December 31, 2010. The SF-12 was scored giving weights to the individual items (ranging from 216.15395 to 14.61446) and adding the sum to a constant (57.65693 and 60.58847) in PCS and MCS, respectively.10 Body mass index (BMI, weight per height squared), smoking status, age, number of donations in the previous 3 years, and C-reactive protein (CRP) levels were considered as possible covariates of the association between iron status and self-reported HRQL. The plasma ferritin level was used as a marker of iron stores11 and iron deficiency was defined as a ferritin level below 15 ng/mL.12
Statistical analysis Statistical analysis was performed using computer software (Stata/IC 11.2 for Mac, StataCorp, College Station, TX). The study population was described with percentages for dichotomous data and with mean and standard deviation (SD) for normally distributed data. Median and relevant percentiles were calculated for nonnormally distributed data. Differences between sexes were investi-
gated by t test for normally distributed data, by MannWhitney U test for nonnormally distributed data, and by chi-square test for dichotomous data. The relationships between ferritin levels and MCS and PCS were assessed in age-adjusted and adjusted (BMI, smoking, age, number of donations in the previous 3 years, and CRP) linear regression analyses with MCS and PCS as the outcome variables. CRP levels were entered as a continuous variable. Ferritin levels were entered either as a continuous variable or as a dichotomized variable using a cutoff of 15 ng/mL. MCS and PCS were dichotomized, using the 10th percentile as cutoff to define participants with particularly low self-rated health. The relationship between iron status and dichotomized MCS and PCS was assessed by logistic regression analysis. All analyses were performed separately for men and women, and p values less than 0.05 were considered significant. As has been reported in previous studies using the Danish version of SF-12, the distributions of MCS and PCS were negatively skewed.10 A power transformation of five could approximate a normal distribution for both scores, yielding higher R2 values and a better fit of the residuals compared to the untransformed model. However, because the power five transformed model was only marginally better and because calculations with such a transformation are more difficult to interpret, we chose to perform and present all calculations on the original linear scale. The obtained correlations were checked by running the analyses again on the power five transformed scale.
RESULTS Plasma ferritin levels were measured in 18,070 participants. Among these, 939 participants were missing at least one value in the SF-12 questionnaire (469 men and 470 women) and an additional 623 participants were missing information on either smoking status, weight, height, and/or age. There were no missing values regarding the variable number of donations in the previous 3 years. Finally, 73 men and 60 women had no corresponding CRP value, respectively. Therefore, complete data were available for 8692 men and 7683 women. Basic characteristics are shown in Table 1. Male donors had higher ferritin levels and higher BMI and were older than female donors. In contrast, more female than male donors were smokers. PCS did not differ significantly between men and women whereas MCS was marginally higher among men (Table 1). Low iron stores (ferritin level < 15 ng/mL) were seen in 3.3 and 22.6% of male and female donors, respectively (Table 1). Age-adjusted and adjusted p values and regression coefficients for the association between iron stores and MCS and PCS, respectively, are presented in Table 2. Ageadjusted and adjusted odds ratios (ORs) and p values for Volume 55, July 2015 TRANSFUSION 1753
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TABLE 1. Characteristics of the study population Men
p value, men vs. women
n 5 8692 41 (612) 50.0 (21.6, 32.1, 77.5) 3.3 6.36 (62.85) 54.8 (46.0, 51.2, 56.8) 56.1 (50.4, 53.8, 57.3) 15.9 25.7 (63.7)
n 5 7683 38 (612) 24.5 (10.7, 15.8, 37.3) 22.6 5.48 (62.69) 54.2 (43.5, 50.0, 56.7) 56.1 (50.3, 53.8, 57.4) 17.4 24.5 (64.1)