Abstract
OBJECTIVES:
The red blood cell distribution width has been associated with an increased risk of cardiovascular events. In the present study, we assessed the relationship between red cell distribution width values and cardiac troponin I levels in patients admitted with non-ST-elevation acute coronary syndrome.
METHODS:
We analyzed blood parameters in 251 adult patients who were consecutively admitted to the intensive coronary care unit with non-ST-elevation acute coronary syndrome over a 1-year period. For all patients, a baseline blood sample was collected for routine hematological testing. Cardiac troponin I was measured at baseline and after 6 h. The patients were diagnosed with non-ST-elevation myocardial infarction or unstable angina based on the elevation of cardiac troponin I levels.
RESULTS:
The red cell distribution width was higher in the group with non-ST-elevation myocardial infarction compared with the patient group with unstable angina (14.6±1.0 vs 13.06±1.7, respectively; p = 0.006). Coronary thrombus was detected more frequently in the group of patients with non-ST-elevation myocardial infarction than in the patients with unstable angina (72% vs 51%, respectively; p = 0.007). Using receiver operating characteristic curve analysis for the prediction of non-ST-elevation myocardial infarction based on the red cell distribution width, the area under the curve was 0.649 (95% confidence interval: 0.546-0.753; p = 0.006), suggesting a modest model for the prediction of non-ST-elevation myocardial infarction using the red cell distribution width. At a cut-off value of 14%, the sensitivity and specificity of the red cell distribution width were 73% and 59%, respectively. Additionally, the red cell distribution width was positively correlated with cardiac troponin I (r = 0.19; p = 0.006).
CONCLUSION:
A greater baseline red cell distribution width value was associated with myocardial injury and elevated cardiac troponin I levels in non-ST-elevation acute coronary syndrome. Therefore, the red cell distribution width could be considered for risk stratification of acute coronary syndrome patients admitted to emergency departments.
Atherosclerosis; Red Blood Cell; Myocardial Injury; Acute Coronary Syndrome; Cardiac Biomarker
INTRODUCTION
Cardiac troponin I (cTnI) is the preferred biomarker for predicting not only
short-term (30 days) but also long-term (1 year and beyond) outcomes with respect to
myocardial infarction (MI) and death (11. Hamm CW, Goldmann BU, Heeschen C, Kreymann G, Berger J, Meinertz
T. Emergency room triage of patients with acute chest pain by means of rapid
testing for cardiac troponin T or troponin I. N Engl J Med.
1997;337(23):1648-53,
http://dx.doi.org/10.1056/NEJM199712043372302.
http://dx.doi.org/10.1056/NEJM1997120433...
,22. Antman EM, Tanasijevic MJ, Thompson B, Schactman M, McCabe CH,
Cannon CP, et al. Cardiac-specific troponin I levels to predict the risk of
mortality in patients with acute coronary syndromes.
N Engl J Med. 1996;335(18):1342-9.). Elevated troponin levels are associated
with increased risk and are additive to other risk factors, such as
electrocardiography (ECG) changes and markers of inflammatory activity (33. James SK, Lindahl B, Siegbahn A, Stridsberg M, Venge P, Armstrong
P, et al. N-terminal pro-brain natriuretic peptide and other risk markers for
the separate prediction of mortality and subsequent myocardial infarction in
patients with unstable coronary artery disease: a Global Utilization of
Strategies To Open occluded arteries (GUSTO)-IV substudy. Circulation.
2003;108(3):275-81,
http://dx.doi.org/10.1161/01.CIR.0000079170.10579.DC.
http://dx.doi.org/10.1161/01.CIR.0000079...
). The red cell distribution width (RDW) has
also been proposed as an independent predictor. It has been reported that the
diagnostic accuracy of troponins within 2-4 h of symptom onset is limited due to the
specific kinetics of this protein in the injured myocardium (44. Apple FS, Wu AH. Myocardial infarction redefined: role of cardiac
troponin testing. Clin Chem. 2001;47(3):37.). The identification of patients with elevated troponin
levels is especially useful for selecting the appropriate treatment in patients with
non-ST-elevation acute coronary syndrome (NSTE-ACS).
The RDW is a measure of the heterogeneity of red blood cell size obtained from red
blood cell size distribution curves. This parameter has been shown to be predictive
of morbidity and mortality in various cardiovascular diseases, such as heart
failure, stable coronary artery disease and acute myocardial infarction (AMI) (55. Dabbah S, Hammerman H, Markiewicz W, Aronson D. Relation between
red cell distribution width and clinical outcomes after acute myocardial
infarction. Am J Cardiol. 2010;105(3):312-7,
http://dx.doi.org/10.1016/j.amjcard.2009.09.027.
http://dx.doi.org/10.1016/j.amjcard.2009...
,66. Patel KV, Ferrucci L, Ershler WB, Longo DL, Guralnik JM. Red
blood cell distribution width and the risk of death in middle-aged and older
adults. Arch Intern Med. 2009;169(5):515-23,
http://dx.doi.org/10.1001/archinternmed.2009.11.
http://dx.doi.org/10.1001/archinternmed....
).
The RDW has also been proposed as an independent predictor of mortality in
non-ST-elevation MI (NSTEMI) (77. Azab B, Torbey E, Hatoum H, Singh J, Khoueiry G, Bachir R, et al.
Usefulness of red cell distribution width in predicting all-cause long-term
mortality after non-ST-elevation myocardial infarction. Cardiology.
2011;119(2):72-80, http://dx.doi.org/10.1159/000329920.
http://dx.doi.org/10.1159/000329920...
). In the
present study, our aim was to investigate the relationship between the RDW and cTnI
in patients with NSTE-ACS.
METHODS
A total of 251 consecutive patients were hospitalized in our hospital with a
diagnosis of NSTE-ACS. Acute coronary syndrome (ACS) was defined as presentation
with symptoms of ischemia in association with ECG changes (ST segment deviation,
T-wave inversion and new Q-wave), positive cardiac enzymes, new documentation of
CAD, or a previous diagnosis of CAD, as defined by similar previous studies (88. Tamhane UU, Aneja S, Montgomery D, Rogers EK, Eagle KA, Gurm HS.
Association between admission neutrophil to lymphocyte ratio and outcomes in
patients with acute coronary syndrome. Am J Cardiol. 2008;102(6):653-7,
http://dx.doi.org/10.1016/j.amjcard.2008.05.006.
http://dx.doi.org/10.1016/j.amjcard.2008...
). Symptomatic patients were assessed using a
standard diagnostic flowchart that included clinical and ECG monitoring as well as
biochemical measurements of markers of myocardial necrosis. Patients who were
diagnosed with NSTEMI or unstable angina (UA) according to elevation of cTnI levels
were included in this study. The study protocol was approved by the institutional
review board at our center, and written informed consent was obtained from all
patients. Demographic characteristics; medical histories; laboratory studies,
including white blood cell (WBC) counts peripheral differential counts; and a
variety of hospital outcomes data were collected. Clinical information was obtained
regarding the patients' history of systemic hypertension (HTN); diabetes
mellitus (DM); dyslipidemia; smoking; and previous CAD, including coronary
angioplasty or myocardial revascularization and a family history of premature CAD.
Venous blood was collected for blood parameter assessment after admission to the
intensive care unit. At our hospital, blood samples are collected from the
antecubital vein by an atraumatic puncture and are sent to the laboratory for
analysis within 1 h after collection. Venous blood was collected in a tube
containing K3 EDTA for measurement of hematologic indices and for baseline
determination of cTnI levels in all patients. Hemoglobin (Hb), the RDW and the WBC
count were also measured as part of the automated complete blood count using a
Coulter LH 780 Hematology Analyzer (Beckman Coulter Ireland Inc., Mervue, Galway,
Ireland). The normal reference range for the RDW in our laboratory is 11.5 to 14.0%.
Because of the known association between anemia and adverse cardiovascular events,
we performed additional analyses in the population of patients who were not anemic
on presentation in an attempt to determine whether the predictive power of the RDW
was either related to or affected by baseline Hb levels. Using the WHO definition of
anemia (Hb<13 g/dl), there were a total of 184 patients who were classified as
non-anemic. Patients with a history of trauma, surgery, neoplasm, or infectious
disease in the last 30 days prior to hospitalization, as well as those currently
using immunosuppressants (including corticosteroids) and prior aspirin users were
excluded. cTnI levels were assessed using a chemiluminescent immunoenzymatic assay
(Access AccuTnI, Beckman Coulter, Fullerton, CA, USA). The detection limit of this
assay is 0.01 ng/ml and the 99th percentile in an apparently healthy
reference population is reported to be 0.04 ng/ml. To confirm or rule out the
presence of NSTEMI, cTnI measurement was repeated after 6 h. Additionally,
transthoracic echocardiography was performed on each patient after admission to the
intensive cardiac care unit. All measurements were performed using a commercially
available machine (Vivid 7, GE Healthcare, Horten, Norway) with a 3.5-MHz
transducer. The Simpson method was used in the 2-dimensional echocardiographic
apical 4-chamber view to assess the left ventricular ejection fraction (LVEF).
Coronary angiographies were also performed in our clinic using the standard Judkins
technique 24 h after hospital admission.
Statistical analysis
Continuous variables are expressed as the mean±SD. Categorical variables are expressed as percentages. Student's t-test or analysis of variance was used to compare parametric continuous variables. The Mann-Whitney U-test or the Kruskal-Wallis test was used to compare nonparametric continuous variables. To compare categorical variables, the χ2-test was used. Relationships between variables were examined using Pearson's correlation coefficient. Receiver operating characteristic (ROC) curves for RDW values were plotted to determine the optimal cut-off values for individual parameters in order to predict NSTEMI and to establish the optimal cut-off points for use in clinical decision-making. Multivariate logistic regression analysis was also used to identify the independent predictors of NSTEMI in patients with chest pain. All variables showing significance values of less than 0.1 in the univariate analysis (total cholesterol, LDL-C, cTnI, ischemic ECG changes, aspirin use, LVEF, RDW, coronary thrombus, neutrophil count, multiarterial CAD, neutrophil/lymphocyte ratio and WBC count) were included in the model. Two-tailed p-values of less than 0.05 were considered to indicate statistical significance. All statistical analyses were performed using the SPSS program (version 20.0; SPSS Inc., Chicago, IL, USA).
RESULTS
A total of 184 patients constituted the study population. The baseline clinical, laboratory and angiographic characteristics of the study population, stratified by cTnI values, are shown in Tables 1 and 2. Based on the troponin values, the patients were classified as having NSTEMI if at least one cTnI value was increased above the 99th percentile URL; otherwise, UA was diagnosed. The participants in the group of patients with NSTEMI had significantly higher total cholesterol and LDL-C levels. Additionally, the LVEF was significantly lower in the group with NSTEMI compared with the group with UA. In contrast, the neutrophil count and the NLR were significantly higher in the group of patients with NSTEMI. Moreover, ischemic ECG changes were more prevalent in the group with NSTEMI compared with the group with UA (p = 0.001) and coronary thrombus was reported more frequently in the group with NSTEMI compared with the group with UA (72% vs 51%, respectively; p = 0.007).
Baseline characteristics of the study population, stratified according to the final diagnosis of the study patients.
Blood parameters of the study population, stratified according to cardiac troponin I elevation.
The RDW was higher in the group with NSTEMI compared with the patient group with UA (14.6±1.0% vs 13.06±1.7%, respectively; p<0.001). When we analyzed the patient characteristics according to the classification stratified by the cut-off RDW value (≥14.0% vs <14.0%), we found that patients with higher RDW values were older and had higher LDL-C and cTnI values, a lower LVEF, a greater total number of diseased coronary arteries and lower MCH values than the patients with lower RDW values did (Table 3).
Baseline characteristics of the entire cohort, stratified by the upper tertile of the baseline RDW values (≥14.05% vs <14.05%).
In the correlation analyses, the RDW was positively correlated with LDL-C (r = 0.21; p = 0.012) and cTnI (r = 0.19; p = 0.045) levels (Figure 1). Conversely, the RDW was negatively correlated with the LVEF (r = -0.26; p = 0.0032). Additionally, the RDW was significantly correlated with the WBC count (r = 0.18; p = 0.041) and the total number of diseased coronary arteries (r = 0.25; p = 0.003). In the multivariate analysis, multiarterial coronary disease, the WBC count, the neutrophil/lymphocyte ratio, ischemic ECG changes, the RDW, the neutrophil count and a history of CABG were independently correlated with NSTEMI in the patients admitted to the hospital with chest pain (Table 4). Regarding the diagnostic accuracy of the RDW, we calculated the composite score for sensitivity and specificity (i.e., the area under the curve (AUC)), as determined by the ROC curve analysis for the prediction of NSTEMI by the RDW. Overall, the AUC was 0.649 (95% confidence interval: 0.546-0.753; p<0.01), suggesting a modest model for the prediction of NSTEMI using the RDW. Using a cut-off value of 14.05%, the sensitivity and specificity of the RDW were 73% and 56%, respectively (Figure 2).
Receiver operating characteristic (ROC) curve analysis for prediction of NSTEMI by red blood cell distribution width (RDW). The area under the curve (AUC) is 0.649 (95% confidence interval: 0.546-0.753; p<0.001) for RDW.
DISCUSSION
The principal finding of our study was that the RDW might predict increased myocardial injury in patients with NSTE-ACS. In particular, in the study group, the degree of myocardial dysfunction (based on the LVEF) and the levels of inflammatory mediators in the blood were associated with RDW values. Our study especially demonstrates an important relationship between RDW and increased cTnI levels in patients with NSTE-ACS.
The RDW has been reported to be a predictor of coronary heart disease events in
different cardiovascular conditions and of all-cause mortality (99. Centers for Disease Control and Prevention (CDC), National Center
for Health Statistics. National Health and Nutrition Examination Survey data.
Available at: www.cdc.gov/nchs/nhanes.htm. Accessed on March 15,
2010.
www.cdc.gov/nchs/nhanes.htm...
,1010. Helfand M, Buckley DI, Freeman M, Fu R, Rogers K, Fleming C, et
al. Emerging risk factors for coronary heart disease: a summary of systematic
reviews conducted for the U.S. Preventive Services Task Force. Ann Intern Med.
2009;151(7):496-507,
http://dx.doi.org/10.7326/0003-4819-151-7-200910060-00010.
http://dx.doi.org/10.7326/0003-4819-151-...
).
In a study by Cavusoglu et al., the RDW was also found to be a strong independent
predictor of all-cause mortality in the ACS subset of patients based on a
multivariate analysis (1111. Cavusoglu E, Chopra V, Gupta A, Battala VR, Poludasu S, Eng C,
et al. Relation between red blood cell distribution width (RDW) and all-cause
mortality at two years in an unselected population referred for coronary
angiography. Int J Cardiol. 2010;141(2):141-6.). In a study by
Sandip et al. (1212. Zalawadiya SK, Veeranna V, Niraj A, Pradhan J, Afonso L. Red
cell distribution width and risk of coronary heart disease events. Am J
Cardiol. 2010;106(7):988-93,
http://dx.doi.org/10.1016/j.amjcard.2010.06.006.
http://dx.doi.org/10.1016/j.amjcard.2010...
), a greater CAD risk
category was associated with a linear increase in the RDW value, suggesting that the
RDW is a potent predictor of CAD risk. In another study, Tonelli et al. (1313. Tonelli M, Sacks F, Arnold M, Moye L, Davis B, Pfeffer M.
Relation between red blood cell distribution width and cardiovascular event rate
in people with coronary disease. Circulation. 2008;117(2):163-8,
http://dx.doi.org/10.1161/CIRCULATIONAHA.107.727545.
http://dx.doi.org/10.1161/CIRCULATIONAHA...
) reported that among patients with CAD and
without heart failure, mortality rates were significantly increased in patients with
elevated RDW values compared with patients with RDW values within the normal
range.
Chronic subclinical inflammation appears to be a potential pathophysiologic mechanism
underlying the association between the RDW and CAD and other cardiovascular events
(1414. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis.
Circulation. 2002;105(9):1135-43,
http://dx.doi.org/10.1161/hc0902.104353.
http://dx.doi.org/10.1161/hc0902.104353...
). Inflammation leads to anisocytosis
due to the release of immature red blood cells into the peripheral circulation. The
association between inflammation and an increased RDW is supported by findings of
increased levels of CRP, interleukin-6 and soluble tumor necrosis factor receptors 1
and 2 in patients with elevated RDW values (1515. Lippi G, Targher G, Montagnana M, Salvagno GL, Zoppini G, Guidi
GC. Relation between red blood cell distribution width and inflammatory
biomarkers in a large cohort of unselected outpatients. Arch Pathol Lab Med.
2009;133(4):628-32.,1616. Forhecz Z, Gombos T, Borgulya G, Pozsonyi Z, Prohaszka Z,
Janoskuti L. 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.
2009;158(4):659-66,
http://dx.doi.org/10.1016/j.ahj.2009.07.024.
http://dx.doi.org/10.1016/j.ahj.2009.07....
). In our study, we found
that indicators of inflammation such as the total leukocyte count and the neutrophil
count were significantly correlated with higher RDW values. In addition to these
markers, the neutrophil/lymphocyte ratio and thrombus formation in diseased
coronaries were significantly associated with higher RDW values.
Another mechanism suggested to underlie the association between the RDW and an
increased frequency of CAD events is oxidative stress. High oxidative stress has
been shown to be associated with an increased risk of cardiovascular events (1717. Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL, Edwards
PA, et al. Atherosclerosis: basic mechanisms. Oxidation, inflammation, and
genetics. Circulation. 1995;91(9):2488-96.). Additionally, high oxidative stress
reduces red blood cell survival, causes anisocytosis and promotes the release of
premature red blood cells into the peripheral circulation (1818. Ghaffari S. Oxidative stress in the regulation of normal and
neoplastic hematopoiesis. Antioxid Redox Signal. 2008;10(11):1923-40,
http://dx.doi.org/10.1089/ars.2008.2142.
http://dx.doi.org/10.1089/ars.2008.2142...
).
In a study by Lippi et al. (1919. Lippi G, Filippozzi L, Montagnana M, Salvagno GL, Franchini M, Guidi GC, et al. Clinical usefulness of measuring red blood cell distribution width on admission in patients with acute coronary syndromes. Clin Chem Lab Med. 2009;47(3):353-7.), researchers investigated the role of the RDW in patients with chest pain suggestive of ACS. These researchers reported that the combined measurement of cardiac troponin and the RDW at admission increased the already impressive sensitivity of cardiac troponin from 94% to 99% in diagnosing ACS. In another study, by Cemin et al. (2020. Cemin R, Donazzan L, Lippi G, Clari F, Daves M. Blood cells characteristics as determinants of acute myocardial infarction. Clin Chem Lab Med. 2011;49(7):1231-6. 2.), investigators studied the relationship between red blood cells, platelet morphology and AMI and also assessed whether they could supplement the role of traditional cardiac biomarkers in the early identification of patients with AMI. The researchers found that the RDW predicted AMI with statistical significance only in female patients. In our study, we found that among the clinical variables, ischemic ECG findings, LDL-C levels, coronary thrombus and a history of CABG were significant predictors of cardiac troponin increase in the patients with NSTE-ACS. Among the hematologic parameters, the WBC count and the RDW were significant predictors of increased cardiac troponin levels. The RDW is thus a simple and economical laboratory measurement that has relatively good diagnostic accuracy in predicting NSTEMI in patients with NSTE-ACS. Considering the fact that the specific kinetics of troponin in the injured myocardium limit its usefulness within 2-4 h of symptom onset, baseline RDW measurement seems helpful for predicting myocardial injury at an earlier time point. We suggest that the RDW should be considered along with conventional cardiac markers for the prediction of NSTEMI in patients with NSTE-ACS and should serve as a guide for making appropriate treatment decisions.
Limitations
The main limitations of our study were the small number of study groups, the
single-center design and inclusion limited to patients admitted to the intensive
care unit. Because our study thus represents a very specific population, the
results cannot be generalized. Increased RDW values are noted in clinical
settings such as hemolysis; increased red cell destruction after blood
transfusion; and ineffective red cell production, such as during iron, vitamin
B12, or folate deficiency. The RDW can also be increased in clinical conditions
such as pregnancy, thrombotic thrombocytopenic purpura and inflammatory diseases
(2121. Clarke K, Sagunarthy R, Kansal S. RDW as an additional marker in
inflammatory bowel disease/undifferentiated colitis. Dig Dis Sci. 2008;
53(9):2521-3, http://dx.doi.org/10.1007/s10620-007-0176-8.
http://dx.doi.org/10.1007/s10620-007-017...
22. Shehata HA, Ali MM, Evans-Jones JC, Upton GJ, Manyonda IT. Red
cell distribution width (RDW) changes in pregnancy. Int J Gynaecol
Obstet. 1998;62(1):43-6.-2323. Nagajothi N, Braverman A. Elevated red cell distribution width
in the diagnosis of thrombotic thrombocytopenic purpura in patients presenting
with anemia and thrombocytopenia. South Med J. 2007;100(3):257-9,
http://dx.doi.org/10.1097/01.smj.0000257403.04625.36.
http://dx.doi.org/10.1097/01.smj.0000257...
). Only Hb levels were measured in the present study, whereas
parameters such as iron, vitamin B12 and folate were not assessed. None of our
patients received blood transfusion and no pregnant women or individuals with
inflammatory diseases, thrombotic thrombocytopenic purpura, or malnutrition were
included.
A greater baseline RDW value is associated with myocardial injury; therefore, the RDW could be considered as an additional marker for evaluating patients with NSTE-ACS. RDW is also a widely available marker that, in contrast to other novel markers of cardiovascular risk, can be obtained at no additional cost.
REFERENCES
-
1Hamm CW, Goldmann BU, Heeschen C, Kreymann G, Berger J, Meinertz T. Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I. N Engl J Med. 1997;337(23):1648-53, http://dx.doi.org/10.1056/NEJM199712043372302.
» http://dx.doi.org/10.1056/NEJM199712043372302 -
2Antman EM, Tanasijevic MJ, Thompson B, Schactman M, McCabe CH, Cannon CP, et al. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med. 1996;335(18):1342-9.
-
3James SK, Lindahl B, Siegbahn A, Stridsberg M, Venge P, Armstrong P, et al. N-terminal pro-brain natriuretic peptide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in patients with unstable coronary artery disease: a Global Utilization of Strategies To Open occluded arteries (GUSTO)-IV substudy. Circulation. 2003;108(3):275-81, http://dx.doi.org/10.1161/01.CIR.0000079170.10579.DC.
» http://dx.doi.org/10.1161/01.CIR.0000079170.10579.DC -
4Apple FS, Wu AH. Myocardial infarction redefined: role of cardiac troponin testing. Clin Chem. 2001;47(3):37.
-
5Dabbah S, Hammerman H, Markiewicz W, Aronson D. Relation between red cell distribution width and clinical outcomes after acute myocardial infarction. Am J Cardiol. 2010;105(3):312-7, http://dx.doi.org/10.1016/j.amjcard.2009.09.027.
» http://dx.doi.org/10.1016/j.amjcard.2009.09.027 -
6Patel KV, Ferrucci L, Ershler WB, Longo DL, Guralnik JM. Red blood cell distribution width and the risk of death in middle-aged and older adults. Arch Intern Med. 2009;169(5):515-23, http://dx.doi.org/10.1001/archinternmed.2009.11.
» http://dx.doi.org/10.1001/archinternmed.2009.11 -
7Azab B, Torbey E, Hatoum H, Singh J, Khoueiry G, Bachir R, et al. Usefulness of red cell distribution width in predicting all-cause long-term mortality after non-ST-elevation myocardial infarction. Cardiology. 2011;119(2):72-80, http://dx.doi.org/10.1159/000329920.
» http://dx.doi.org/10.1159/000329920 -
8Tamhane UU, Aneja S, Montgomery D, Rogers EK, Eagle KA, Gurm HS. Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome. Am J Cardiol. 2008;102(6):653-7, http://dx.doi.org/10.1016/j.amjcard.2008.05.006.
» http://dx.doi.org/10.1016/j.amjcard.2008.05.006 -
9Centers for Disease Control and Prevention (CDC), National Center for Health Statistics. National Health and Nutrition Examination Survey data. Available at: www.cdc.gov/nchs/nhanes.htm. Accessed on March 15, 2010.
» www.cdc.gov/nchs/nhanes.htm -
10Helfand M, Buckley DI, Freeman M, Fu R, Rogers K, Fleming C, et al. Emerging risk factors for coronary heart disease: a summary of systematic reviews conducted for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;151(7):496-507, http://dx.doi.org/10.7326/0003-4819-151-7-200910060-00010.
» http://dx.doi.org/10.7326/0003-4819-151-7-200910060-00010 -
11Cavusoglu E, Chopra V, Gupta A, Battala VR, Poludasu S, Eng C, et al. Relation between red blood cell distribution width (RDW) and all-cause mortality at two years in an unselected population referred for coronary angiography. Int J Cardiol. 2010;141(2):141-6.
-
12Zalawadiya SK, Veeranna V, Niraj A, Pradhan J, Afonso L. Red cell distribution width and risk of coronary heart disease events. Am J Cardiol. 2010;106(7):988-93, http://dx.doi.org/10.1016/j.amjcard.2010.06.006.
» http://dx.doi.org/10.1016/j.amjcard.2010.06.006 -
13Tonelli M, Sacks F, Arnold M, Moye L, Davis B, Pfeffer M. Relation between red blood cell distribution width and cardiovascular event rate in people with coronary disease. Circulation. 2008;117(2):163-8, http://dx.doi.org/10.1161/CIRCULATIONAHA.107.727545.
» http://dx.doi.org/10.1161/CIRCULATIONAHA.107.727545 -
14Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105(9):1135-43, http://dx.doi.org/10.1161/hc0902.104353.
» http://dx.doi.org/10.1161/hc0902.104353 -
15Lippi G, Targher G, Montagnana M, Salvagno GL, Zoppini G, Guidi GC. Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients. Arch Pathol Lab Med. 2009;133(4):628-32.
-
16Forhecz Z, Gombos T, Borgulya G, Pozsonyi Z, Prohaszka Z, Janoskuti L. 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. 2009;158(4):659-66, http://dx.doi.org/10.1016/j.ahj.2009.07.024.
» http://dx.doi.org/10.1016/j.ahj.2009.07.024 -
17Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL, Edwards PA, et al. Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation. 1995;91(9):2488-96.
-
18Ghaffari S. Oxidative stress in the regulation of normal and neoplastic hematopoiesis. Antioxid Redox Signal. 2008;10(11):1923-40, http://dx.doi.org/10.1089/ars.2008.2142.
» http://dx.doi.org/10.1089/ars.2008.2142 -
19Lippi G, Filippozzi L, Montagnana M, Salvagno GL, Franchini M, Guidi GC, et al. Clinical usefulness of measuring red blood cell distribution width on admission in patients with acute coronary syndromes. Clin Chem Lab Med. 2009;47(3):353-7.
-
20Cemin R, Donazzan L, Lippi G, Clari F, Daves M. Blood cells characteristics as determinants of acute myocardial infarction. Clin Chem Lab Med. 2011;49(7):1231-6. 2.
-
21Clarke K, Sagunarthy R, Kansal S. RDW as an additional marker in inflammatory bowel disease/undifferentiated colitis. Dig Dis Sci. 2008; 53(9):2521-3, http://dx.doi.org/10.1007/s10620-007-0176-8.
» http://dx.doi.org/10.1007/s10620-007-0176-8 -
22Shehata HA, Ali MM, Evans-Jones JC, Upton GJ, Manyonda IT. Red cell distribution width (RDW) changes in pregnancy. Int J Gynaecol Obstet. 1998;62(1):43-6.
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23Nagajothi N, Braverman A. Elevated red cell distribution width in the diagnosis of thrombotic thrombocytopenic purpura in patients presenting with anemia and thrombocytopenia. South Med J. 2007;100(3):257-9, http://dx.doi.org/10.1097/01.smj.0000257403.04625.36.
» http://dx.doi.org/10.1097/01.smj.0000257403.04625.36
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No potential conflict of interest was reported.
Publication Dates
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Publication in this collection
Jan 2015
History
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Received
4 Aug 2014 -
Reviewed
1 Sept 2014 -
Accepted
7 Nov 2014