J Nutr Health Aging

THE JOURNAL OF NUTRITION, HEALTH & AGING©

CHANGE IN RED BLOOD CELL DISTRIBUTION WIDTH DURING THE LAST YEARS OF LIFE IN GERIATRIC PATIENTS N. MARTÍNEZ-VELILLA1,2,5, K. CAMBRA-CONTIN2,3, A. GARCÍA-BAZTÁN1, J. ALONSO-RENEDO1,5, P.A. HERCE4,5, B. IBÁÑEZ-BEROIZ2,3 1. Department of Geriatrics. Complejo Hospitalario de Navarra. Pamplona. Spain; 2. Navarrabiomed-Fundación Miguel Servet.; 3. Red de Investigación en Servicios Sanitarios en Enfermedades Crónicas (REDISSEC).Pamplona. Spain; 4. Centro de Salud San Juan. Pamplona. Spain; 5. Grupo de Investigación en Geriatría. Navarrabiomed. Corresponding author: Nicolás Martínez-Velilla, Servicio de Geriatría del Complejo Hospitalario de Navarra, Irunlarrea 4, 31008 Pamplona, Spain, E-mail: [email protected], Telephone: 00 34 848422222, Fax: 00 34 848428830

Abstract: Objectives: Most of the studies that evaluate the association between red blood cell distribution width (RDW) and mortality assess it on a single occasion instead of doing so through serial measurements. Very few studies have investigated repeated measurements of RDW and its prognostic value, and most of them are focused on patients with cardiovascular diseases. RDW is a dynamic value so we aimed at determining the prognostic value of sequential RDW assessment in the last years of life in patients enrolled in a Department of Geriatrics. Design: This work is part of a prospective study derived from a cohort of 122 patients over 75 years hospitalized in 2005 for the purpose of assessing the prognostic significance of several comorbidity and prognostic indices. Setting: Patients were consecutively recruited for the study at admission in a tertiary hospital and then followed up for at least 5 years. Participants: A total of 55 patients with repeated RDW assessments during all the five years before their death were selected from the total cohort of 122 patients. Results: We found a strong correlation between progressive rise in RDW and mortality risk, especially during the last year of life. There was a gradual significant increase in the RDW values along the last five years of life, with means growing up from 14,8 (95% CI: 13,98-15.62) to 16,37 (15,80-16,94). Conclusion: In our cohort of geriatric patients, RDW is a dynamic variable that is modified during the last five years of life, irrespective of their age, and especially during the last year. Key words: Aging, red cell distribution width, mortality, prognosis.

Introduction Red blood cell distribution width (RDW) is a measure of variability in the size of circulating erythrocytes with higher values reflecting greater heterogeneity in cell sizes (anisocytosis) and is part of a complete blood count (1). It is an inexpensive, easy, routinely reported parameter as a part of the complete blood count test used. Recent studies have suggested that RDW has further clinical significance apart from its possible use in the evaluation of anemia. RDW has proven to be a marker and independent predictor in a variety of cardiovascular and non-cardiovascular diseases (2-7). RDW has likewise been studied as a surrogate marker in many pathological conditions such as rheumatoid arthritis (8), pneumonia (9), inflammatory bowel disease (10), colon cancer (11), systemic lupus erytematosus (12), celiac disease (13) and even dementia (14, 15). It has also been reported that RDW is a consistent predictor of mortality across different study populations (16, 17) and that RDW predicts/ coronary heart disease mortality events more efficiently than high-sensitivity C-reactive protein (18), while RDW combined with standard biological markers improves mortality prediction in some circumstances, like pneumonia (9). Similarly to other haematological variables with prognostic properties (19, 20) these studies have been limited to a single time-point assessment instead of serial measurements but RDW is a dynamic variable, with rapid changes in acute Received September 1, 2014 Accepted for publication October 23, 2014

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disease states (5), so previous studies were unable to determine the influence of changes in RDW over time on long-term outcomes. We have previously reported that RDW stands as a good predictor of mortality in hospitalized older adults, and it could serve as an integrative measure of multiple clinical and subclinical processes taking place simultaneously in complex patients (21). Searching retrospective data directly derived from electronic health records, our objective was to assess the evolution of RDW in the last five years of life in our cohort. The identification of a long-term RDW evolution before death can help to provide hints about the links between RDW variability and disease progression. Methods Study population This is an observational backward study that is part of a prospective study derived from a cohort of 122 patients over 75 years hospitalized in 2005 for the purpose of assessing the prognostic significance of several comorbidity and prognostic indices (22). Patients were consecutively recruited for the study at admission time and then followed up for at least 5 years. Baseline clinical information and a comprehensive geriatric assessment were obtained through structured patient or proxy interviews, bedside assessments, and structured medical reviews. Written informed consent was obtained from all subjects by the same researcher. Details of the previous work

J Nutr Health Aging

CHANGE IN RED BLOOD CELL DISTRIBUTION WIDTH DURING THE LAST YEARS OF LIFE IN GERIATRIC PATIENTS have been published (21). All 122 patients were successfully followed up by means of visits, phone interviews, and the hospital´s medical registry (which is computerized). From this cohort, we selected the patients who had died during the follow-up period and whose RDW values had been assessed in the five years previous to their death (at least five analyses) (n=55). Afterwards, another investigator blinded to all other clinical outcome data, obtained data at the laboratory analyses (including RDW) performed during the established five-year period. All data were obtained from the electronic clinical history. Laboratory methods The laboratory tests were analyzed in one of the four devices available during that period, and the RDW was reported as the coefficient of variation (percentage) of red blood cell volume measured with an automated Beckman Coulter Counter (two LH-750, and three GEN-S). The normal range for RDW in our hospital laboratory is 11.5% to 14.5%. Anemia was defined as haemoglobin levels lower to 13 g/dL in men and 12 g/dL in women, in accordance with the World Health Organization criteria. When several analyses were performed during the same year, we selected the first value in each year. Statistical analysis The primary end point was the RDW evolution during the last 5 years previous to death. The patients’ characteristics were summarized using descriptive statistics such as means with standard deviations, medians with inter-quartile range (IQR), or frequencies and percentages, depending on the nature of the variables. Mean RDW values, together with 95% confidence intervals, were estimated for each year of follow-up, and represented using an error-bar plot. The trend in RDW values along the last five years before death was assessed using a Linear Mixed Model with the RDW as the response variable, ‘years before death’ as a categorical covariate ‘, and ‘the individual’ as a random effect, to account for the intra-individual correlation. The same methodology was used to supplement the information using years before death as a continuous variable. The possible effect of the age of the patients, and its possible relation with years before death, were also assessed by including age in the model. Statistical analyses were performed in IBM SPSS Statistics 20 and in R 2.13.1.

We can see the graphic RDW evolution in the last five years of life in figure 1 and table 2. There is a marked increase in RDW, particularly during the last year of life. This trend is corroborated (table 2) using the linear mixed model that includes time before death as a categorical covariate, which proved to be significant (p

Change in Red Blood Cell Distribution width During the Last Years of Life in Geriatric Patients.

Most of the studies that evaluate the association between red blood cell distribution width (RDW) and mortality assess it on a single occasion instead...
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