El ancho de distribución eritrocitaria aporta valor pronóstico adicional en pacientes ambulatorios con insuficiencia cardiaca crónica

doi:10.1016/j.recesp.2011.12.006

Revista Española de Cardiología

Volume 65, Issue 7, July 2012, Pages 606-612

https://doi.org/10.1016/j.recesp.2011.12.006 Get rights and content

Resumen

Introducción y objetivos

El ancho de distribución eritrocitaria ha surgido como un marcador biológico con valor pronóstico en enfermedades cardiovasculares. Su valor adicional en la estratificación de riesgo de pacientes con insuficiencia cardiaca crónica no se encuentra establecido.

Métodos

Se estudió consecutivamente a 698 pacientes ambulatorios con insuficiencia cardiaca crónica (edad, 71 años [intervalo intercuartílico, 62-77]; el 63% varones; fracción de eyección del ventrículo izquierdo, 40 ± 14%). A su inclusión, se midió el ancho de distribución eritrocitaria y se registraron variables clínicas, bioquímicas y ecocardiográficas. La mediana de seguimiento fue 2,5 años [1,2-3,7].

Resultados

En total, fallecieron 211 pacientes y 206 precisaron hospitalización por insuficiencia cardiaca descompensada. El análisis de Kaplan-Meier mostró un incremento tanto de la probabilidad de muerte como de ingreso por insuficiencia cardiaca a través de cuartiles de ancho de distribución eritrocitaria (log rank, p < 0,001). El análisis ROC identificó el valor de ancho de distribución eritrocitaria del 15,4% como mejor punto de corte, asociado a un incremento independiente del riesgo tanto de muerte (hazard ratio = 2,63; intervalo de confianza del 95%, 2,01-3,45; p < 0,001) como de ingreso por insuficiencia cardiaca (hazard ratio = 2,37; intervalo de confianza del 95%, 1,80-3,13; p < 0,001). Este valor predictivo se mantuvo con o sin anemia. Además, la adición del ancho de distribución eritrocitaria a la estratificación de riesgo de muerte o ingreso por insuficiencia cardiaca a 1 año se asoció con una mejora tanto del índice relativo de discriminación integrada (33%; p < 0,001) como de la reclasificación neta de eventos (10,3%; p = 0,001).

Conclusiones

El ancho de distribución eritrocitaria es un marcador de riesgo independiente y añade información pronóstica sobre pacientes ambulatorios con insuficiencia cardiaca crónica. Los hallazgos indican su incorporación al manejo de estos pacientes.

Abstract

Introduction and objectives

Red blood cell distribution width has emerged as a new prognostic biomarker in cardiovascular diseases. Its additional value in risk stratification of patients with chronic heart failure has not yet been established.

Methods

A total of 698 consecutive outpatients with chronic heart failure were studied (median age 71 years [interquartile range, 62-77], 63% male, left ventricular ejection fraction 40 [14]%). On inclusion, the red cell distribution width was measured and clinical, biochemical, and echocardiographic variables were recorded. The median follow-up period was 2.5 years [interquartile range 1.2-3.7].

Results

A total of 211 patients died and 206 required hospitalization for decompensated heart failure. Kaplan-Meier analysis showed an increase in the probability of death and hospitalization for heart failure with red cell distribution width quartiles (log rank, P<.001). A ROC analysis identified a red cell distribution width of 15.4% as the optimal cut-off point for a significantly higher risk of death (P<.001; hazard ratio=2.63; 95% confidence interval, 2.01-3.45) and hospitalization for heart failure (P<.001; hazard ratio=2.37; 95% confidence interval, 1.80-3.13). This predictive value was independent of other covariates, and regardless of the presence or not of anaemia. Importantly, the addition of red cell distribution width to the clinical risk model for the prediction of death or hospitalization for heart failure at 1 year had a significant integrated discrimination improvement of 33% (P<.001) and a net reclassification improvement of 10.3% (P=.001).

Conclusions

Red cell distribution width is an independent risk marker and adds prognostic information in outpatients with chronic heart failure. These findings suggest that this biological measurement should be included in the management of these patients.

Full English text available from: www.revespcardiol.org

Section snippets

Introducción

El índice del ancho de distribución eritrocitaria (ADE) describe el grado de heterogeneidad en el tamaño de los hematíes, y tanto la destrucción como el déficit en su producción conllevan un aumento de su valor1, 2. Este parámetro fue introducido como ayuda al diagnóstico diferencial de las anemias hipocromas, pero en los últimos años diversos trabajos han mostrado su asociación con un aumento de mortalidad en pacientes con insuficiencia cardiaca (IC)3, 4, 5, 6, 7, 8, así como en otras

Población

Se estudió a 698 pacientes ambulatorios revisados consecutivamente en una consulta monográfica de IC de enero de 2003 a diciembre de 2005. En dicha visita se recogieron todas las variables demográficas, clínicas y analíticas de cada paciente. Todos los pacientes disponían de una ecocardiografía en los últimos 3 meses (Sonos 5500, Philips, Massachusetts, Estados Unidos), con las medidas y proyecciones recomendadas¹¹. El seguimiento posterior de los pacientes se realizó mediante visitas

Ancho de distribución eritrocitaria y población general

En total se estudió a 698 pacientes (mediana de edad, 71 años [62-77]; el 63% varones; fracción de eyección del ventrículo izquierdo, 40 ± 14%), en los que la mediana del valor del ADE fue del 14,8% [13,8-16]. La tabla 1 describe las características de la población distribuidas por cuartiles de ADE. El valor del ADE se asoció de manera directa con edad, clase funcional de la New York Heart Association, mayor prevalencia de sexo femenino, hipertensión arterial, broncopatía obstructiva crónica,

Discusión

En una amplia población de pacientes ambulatorios con IC crónica, el valor aumentado del ADE mostró una asociación significativa con una peor evolución, tanto con mayor mortalidad como hospitalización por IC descompensada. Además, el ADE se comportó como una variable pronóstica capaz de aportar información adicional a la de las demás variables clínicas de riesgo.

Desde que Felker et al identificaron el ADE como el marcador de laboratorio con mayor poder pronóstico en la población del estudio

Conclusiones

Este estudio muestra que, en pacientes ambulatorios con IC crónica, el valor del ADE es un marcador de riesgo incrementado de que se produzcan tanto muerte como ingreso hospitalario por IC, lo que proporciona una mejora de la discriminación de riesgo, independiente de otras variables y de la presencia o no de anemia, por lo que resulta aconsejable su inclusión tanto en los modelos de riesgo como en la estratificación pronóstica en la práctica clínica habitual; se propone el valor del 15,4% como

Conflicto de intereses

Ninguno.

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Validation and potential mechanisms of red cell distribution width as a prognostic marker in heart failure
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Red blood cell distribution width predicts long-term outcome regardless of anaemia status in acute heart failure patients
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Red cell distribution width has incremental prognostic value to B-type natriuretic peptide in acute heart failure
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Red blood cell distribution width and 1-year mortality in acute heart failure
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Red blood cell distribution width and the risk of death in middle-aged and older adults
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Cited by (34)

Prognostic Value of Blood Panel Parameters in Patients With Dilated Cardiomyopathy and Advanced Heart Failure
2018, Transplantation Proceedings
Citation Excerpt :
Thus, our study, with ambulatory advanced HF patients, offers more information about this specific group. Although other studies identified a linear relation between RDW and mortality in HF, our RDW cut-off point of 15% is similar to that in another Spanish study [2]. To establish a cut-off point is important in our daily clinical practice because it helps us to do a narrower follow-up for patients with RDW>15%.
Patients with dilated cardiomyopathy (DCM) and left ventricular dysfunction have a varied clinical course, not only dependent on left ventricular ejection fraction (LVEF) and symptoms. Finding prognostic markers for stratification in these 2 conditions is a critical area of research. Our aim was determine the prognostic value of blood panel basic parameters.
We analyzed all patients with idiopathic or familial DCM and LVEF <30% coming to our heart failure unit for evaluation for non-urgent heart transplant during the period of 2009 to 2011. With 5 years of follow-up data, we could study the prognostic value of blood panel parameters. Moreover, we determined the combination of platelet count and neutrophil to lymphocyte ratio score from the BIOSTAT-CHF study.
Eighty-seven patients were included in the study. After 5 years follow-up, 49 patients (57%) remain alive (group A) and 38 (43%) either died or needed a heart transplant. There were no differences between groups with regard to age or sex. Patients with good progress showed a lower red cell distribution width (RDW), a higher lymphocyte count, and a lower neutrophil/lymphocyte ratio in the initial blood panel. An RDW ≥15% was associated with long-term mortality or heart transplant.
A basic blood panel could be a useful tool in assessing patients with heart failure. Larger studies are necessary to confirm our findings. A multimarker strategy could also be useful for stratification of patients with advanced heart failure.
A simple score for early risk stratification in acute heart failure
2017, International Journal of Cardiology
Citation Excerpt :
RDW is a measurement of size variability in red blood cells and is a simple parameter of the FBC, widely available, low cost and with acceptable accuracy as a prognostic marker in HF patients [44]. Although it is generally used for the differential diagnosis of anemia and hematological disorders [45], there is growing evidence linking elevated RDW with poor cardiovascular outcome in several discrete populations [46], such as in patients with stable CAD [47], acute coronary syndromes [48], acute MI [49], stroke [50], and acute or chronic HF [19,20,51–57]. This is independent of MCV, Ht or Hb values.
The use of many acute heart failure (AHF) risk scores is cumbersome. We therefore developed a simple AHF risk score (AHFRS) for early risk stratification.
The study consisted of a prospective derivation cohort (PDC; N = 104; age, 77[21] years; LVEF (%), 35[29]) and a retrospective validation cohort (RVC; N = 141; age, 76[15] years; LVEF (%), 35[25]). Clinical, echocardiography and laboratory assessment was performed at admission. The study end-point was death from any cause or HF-rehospitalization at 1 year.
In the PDC 46 (44.2%) patients experienced the end-point. Independent prognostic factors of outcome were hypertension (HTN) history, myocardial infarction (MI) history, and admission red cell distribution width (RDW). Multivariate logistic regression indicated 8-, 4-, and 3-times higher odds ratio for development of study end-point in patients without a HTN history, with MI history, and RDW ≥ 15% (median) respectively. Thus in AHFRS, 2 points were assigned for absence of HTN history, 1 point for presence of MI history, and 1 point for RDW values ≥ 15% (0 best possible, whereas 4 worst possible score). The AHFRS identified patients who developed the end-point in the PDC with an area under the ROC curve (AUC) of 0.80 [95% C.I.: (0.71, 0.87)] denoting a high discriminative ability. These findings were confirmed in the RVC, in which the endpoint occurred in 52 (36.9%) patients and the AUC for the AHFRS was 0.82 [95% C.I.: (0.73, 0.89)].
AHFRS is easily obtained at admission and accurately risk stratifies AHF patients.
Red Cell Distribution Width in Obstructive Sleep Apnea
2017, Archivos de Bronconeumologia
Citation Excerpt :
Its main application at present is for the differential diagnosis of anemia,4 and values are not affected by the patient's nutritional status, sex or age.5 Recent studies show that increased RDW, even with normal reference ranges, is strongly associated with a greater risk of death and cardiovascular disease in middle-aged and elderly individuals.6–15 RDW can act as a biomarker for cardiovascular risk that is sensitive to systemic inflammatory changes and to mobilization of iron deposits during oxidative stress.11
Red cell distribution width (RDW) describes heterogeneity in the size of red blood cells. An increase in RDW has been associated with excess mortality in heart failure and other chronic diseases. Since there is an increased risk of cardiovascular morbidity and mortality in obstructive sleep apnea (OSA), it is possible that these patients have a high RDW.
We recruited subjects aged 18–60 years referred to the sleep-disordered breathing unit for suspected OSA. Subjects with any comorbidity were excluded. Apnea-hypopnea index (AHI) was calculated from the respiratory polygraphy. The RDW was obtained from the complete blood count. Changes in RDW after one year of treatment with continuous positive airway pressure (CPAP) were determined.
We included 34 healthy subjects and 138 with OSA, aged 40.5±9.8 and 45.6±9.2 (P=.004) years, respectively. The RDW was higher in subjects with OSA compared to healthy subjects: 13.40 (12.40–14.40) vs. 13.15 (12.07–14.23) (P=.036). AHI showed a positive independent relationship with RDW in both the whole population (r=0.223; P=.002) and the OSA group (r=0.231; P=.005). No significant changes were found in RDW after one year of CPAP therapy.
RDW increase in patients with OSA is directly associated with severity, although levels are not modified by the effective treatment of OSA with CPAP.
El ancho de distribución eritrocitaria (ADE) describe el grado de heterogeneidad en el tamaño de los hematíes. Un incremento de ADE se ha asociado con exceso de mortalidad en insuficiencia cardiaca y otras enfermedades crónicas. Dado que existe mayor riesgo de morbimortalidad cardiovascular en apnea obstructiva del sueño (AOS), es posible que estos pacientes presenten un ADE elevado.
Se reclutaron sujetos de 18 a 60 años remitidos a la Unidad de Trastornos Respiratorios del Sueño (UTRS) por sospecha de AOS. Se excluyeron sujetos con cualquier comorbilidad. En la poligrafía respiratoria se determinó el índice de apnea-hipopnea (IAH). El ADE se obtuvo a partir del hemograma. Al año de seguimiento se determinaron los cambios de ADE tras tratamiento con presión positiva continua en la vía respiratoria (CPAP).
Se incluyeron 34 sujetos sin AOS y 138 con AOS con una edad de 40,5 ± 9,8 y 45,6 ± 9,2 (p = 0,004) respectivamente. El ADE fue mayor en sujetos con AOS que en sujetos sanos: 13,40 (12,40-14,40) vs 13,15 (12,07-14,23) (p = 0,036). El IAH mostró una relación positiva e independiente con ADE tanto en el conjunto de la población (r = 0,223; p = 0,002) como en el grupo con AOS (r = 0,231; p = 0,005). No se observaron cambios significativos de ADE tras un año de tratamiento con CPAP.
El ADE está aumentado en AOS en relación directa con su gravedad, sin embargo, sus niveles no se ven modificados por el tratamiento efectivo de la AOS con CPAP.
Red Cell Distribution Width and the Risk of Mortality in Patients With Acute Heart Failure With or Without Cardiorenal Anemia Syndrome
2016, American Journal of Cardiology
Citation Excerpt :
Felker et al4 found that a greater RCDW was independently associated with greater morbidity and mortality in patients with CHF participated in the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) program and replicated this finding in the Duke Databank. RCDW not only predicted short-term mortality in patients presenting in the emergency department with AHF6 but also long-term mortality in ambulatory outpatients with CHF.15 RCDW retained its predictive value even after adjusting for other powerful biomarkers, such as NT-proBNP,16 and regardless of anemia status.5,9
Red cell distribution width (RCDW) has not been fully investigated for its prognostic impact in patients with acute heart failure (AHF) with or without the cardiorenal anemia syndrome (CRAS). A total of 978 patients (age 75 ± 14 years, 70% men, 43% with CRAS) hospitalized for AHF were enrolled. During a median follow-up duration of 31 months, 472 subjects (48%) died. The postdischarge mortality was positively associated with the increasing RCDW. After accounting for age, gender, co-morbidities, hemoglobin, renal function, sodium level, and N-terminal probrain natriuretic peptide, RCDW remained an independent predictor of mortality (hazard ratio [HR] and 95% CI for a 1% increase of RCDW: 1.09, 1.00 to 1.17, p = 0.04). In the subgroups of patients with or without CRAS, RCDW was an independent predictor of total mortality for both subgroups (HR 1.05, 95% CI 1.00 to 1.10 and HR 1.11, 95% CI 1.07 to 1.15, respectively). In conclusion, elevated RCDW was independently associated with mortality in patients hospitalized for AHF, with or without CRAS.
Prognostic value of red blood cell distribution width in heart failure patients: A meta-analysis
2015, International Journal of Cardiology
Red cell distribution width and additive risk prediction for major bleeding in non-ST-segment elevation acute coronary syndrome
2014, Revista Espanola de Cardiologia
El ancho de distribución eritrocitaria se ha relacionado con incremento del riesgo hemorrágico intrahospitalario en pacientes con síndrome coronario agudo sin elevación del ST. Sin embargo, se desconoce su utilidad para predecir complicaciones hemorrágicas tras el ingreso hospitalario. El objetivo fue evaluar el papel complementario del ancho de distribución eritrocitaria sobre la escala CRUSADE en la predicción del riesgo a largo plazo de hemorragias en estos pacientes.
Se midió el ancho de distribución eritrocitaria al ingreso en 293 pacientes con síndrome coronario agudo sin elevación del ST; a todos se les dio seguimiento clínico y se registró la aparición de hemorragias mayores, definidas según los criterios del Bleeding Academic Research Consortium.
Durante un seguimiento de 782 [intervalo intercuartílico, 510-1.112] días, 30 pacientes (10,2%) presentaron eventos hemorrágicos. El análisis por cuartiles reveló un incremento abrupto de hemorragias a partir del cuarto cuartil (> 14,9%; p = 0,001). Tras el análisis multivariable, el ancho de distribución eritrocitaria > 14,9% se asoció con mayor riesgo de eventos (hazard ratio = 2,67; intervalo de confianza del 95%, 1,17-6,10; p = 0,02). Los pacientes con valores ≤ 14,9% y CRUSADE ≤ 40 presentaron las menores tasas de hemorragias, mientras que los pacientes con valores > 14,9% y CRUSADE > 40 puntos (alto y muy alto riesgo) presentaron las mayores (log rank test, p < 0,001). Además, la adición del ancho de distribución eritrocitaria a la escala CRUSADE para predecir hemorragias mostró tasas de mejora integrada del 5,2% (p < 0,001) y de reclasificación del 10% (p = 0,001).
Los valores elevados del ancho de distribución eritrocitaria se asocian a mayor riesgo hemorrágico y aportan información adicional a la escala CRUSADE.
Red cell distribution width has been linked to an increased risk for in-hospital bleeding in patients with non–ST-segment elevation acute coronary syndrome. However, its usefulness for predicting bleeding complications beyond the hospitalization period remains unknown. Our aim was to evaluate the complementary value of red cell distribution width and the CRUSADE scale to predict long-term bleeding risk in these patients.
Red cell distribution width was measured at admission in 293 patients with non–ST-segment elevation acute coronary syndrome. All patients were clinically followed up and major bleeding events were recorded (defined according to Bleeding Academic Research Consortium Definition criteria).
During a follow-up of 782 days [interquartile range, 510-1112 days], events occurred in 30 (10.2%) patients. Quartile analyses showed an abrupt increase in major bleedings at the fourth red cell distribution width quartile (> 14.9%; P = .001). After multivariate adjustment, red cell distribution width > 14.9% was associated with higher risk of events (hazard ratio = 2.67; 95% confidence interval, 1.17-6.10; P = .02). Patients with values ≤ 14.9% and a CRUSADE score ≤ 40 had the lowest events rate, while patients with values > 14.9% and a CRUSADE score > 40 points (high and very high risk) had the highest rate of bleeding (log rank test, P < .001). Further, the addition of red cell distribution width to the CRUSADE score for the prediction of major bleeding had a significant integrated discrimination improvement of 5.2% (P < .001) and a net reclassification improvement of 10% (P = .001).
In non–ST-segment elevation acute coronary syndrome patients, elevated red cell distribution width is predictive of increased major bleeding risk and provides additional information to the CRUSADE scale.
Full English text available from: www.revespcardiol.org/en

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Artículo originalEl ancho de distribución eritrocitaria aporta valor pronóstico adicional en pacientes ambulatorios con insuficiencia cardiaca crónicaRed Blood Cell Distribution Width Adds Prognostic Value for Outpatients With Chronic Heart Failure

Resumen

Introducción y objetivos

Métodos

Resultados

Conclusiones

Abstract

Introduction and objectives

Methods

Results

Conclusions

Section snippets

Introducción

Población

Ancho de distribución eritrocitaria y población general

Discusión

Conclusiones

Conflicto de intereses

Índice de distribución de glóbulos rojos (RDW): su aplicación en la caracterización de anemias microcíticas e hipocrómicas

Medicina (B Aires)

The red blood cell distribution width

J Emerg Med

Red cell distribution width as a novel prognostic marker in heart failure: data from the CHARM Program and the Duke Databank

J Am Coll Cardiol

Validation and potential mechanisms of red cell distribution width as a prognostic marker in heart failure

J Card Fail

Red blood cell distribution width predicts long-term outcome regardless of anaemia status in acute heart failure patients

Eur J Heart Fail

Red cell distribution width has incremental prognostic value to B-type natriuretic peptide in acute heart failure

Eur J Heart Fail

Red blood cell distribution width and 1-year mortality in acute heart failure

Eur J Heart Fail

Red cell distribution width and mortality in predominantly African-American population with decompensated heart failure

J Card Fail

Red blood cell distribution width and the risk of death in middle-aged and older adults

Arch Intern Med

Red cell distribution width in heart failure: prediction of clinical events and relationship with markers of ineffective erythropoiesis, inflammation, renal function, and nutritional state

Am Heart J

Recommendations for a standardized report for adult transthoracic echocardiography: a report from the American Society of Echocardiography's Nomenclature and Standards Committee and Task Force for a Standardized Echocardiography Report

J Am Soc Echocardiogr

The strenghthening the reporting of observational studies ini epidemiology (STROBE) statement: guidelines for reporting observational studies

Lancet

A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation

Ann Intern Med

Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond

Stat Med

Artículo original
El ancho de distribución eritrocitaria aporta valor pronóstico adicional en pacientes ambulatorios con insuficiencia cardiaca crónicaRed Blood Cell Distribution Width Adds Prognostic Value for Outpatients With Chronic Heart Failure