Red blood cell distribution width (RDW) is a measure of red blood cell volume variations (anisocytosis) and is reported as part of a standard complete blood count. In recent years, numerous studies have noted the importance of RDW as a predictor of poor clinical outcomes in the settings of various diseases, including coronary artery disease (CAD). In this paper, we discuss the prognostic value of RDW in CAD and describe the pathophysiological connection between RDW and acute coronary syndrome. In our opinion, the negative prognostic effects of elevated RDW levels may be attributed to the adverse effects of independent risk factors such as inflammation, oxidative stress, and vitamin D3 and iron deficiency on bone marrow function (erythropoiesis). Elevated RDW values may reflect the intensity of these phenomena and their unfavorable impacts on bone marrow erythropoiesis. Furthermore, decreased red blood cell deformability among patients with higher RDW values impairs blood flow through the microcirculation, resulting in the diminution of oxygen supply at the tissue level, particularly among patients suffering from myocardial infarction treated with urgent revascularization.
Red blood cell distribution width (RDW) is a parameter routinely measured by most modern hematology analyzers. RDW is defined as the quotient of standard deviation of red blood cell volume and its mean volume and is expressed as a percentage according to the following formula: RDW = (standard deviation of red blood cell volume/mean cell volume) × 100. Higher RDW values reflect greater variations in red blood cell volume [
One of the first studies to assess the role of RDW in cardiovascular disease was published by Felker et al. in 2007. The authors noted the usefulness of RDW as a prognostic marker among patients with heart failure (HF) [
The aim of this review is to describe the prognostic utility of RDW in patients with coronary artery disease (CAD) and to elucidate the mechanism underlying the relationship between elevated RDW values and poor patient prognosis in this particular group of patients.
In recent years, numerous papers have been published regarding the value of RDW in the risk stratification of patients with CAD [
Summary of the most relevant studies investigating prognostic and diagnostic value of RDW in patients with CAD.
Study | Type of study design | Study population | Main findings | References |
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RDW as a predictor of mortality and adverse cardiovascular events in patients with CAD | ||||
Tonelli et al. (2008) | Post hoc analysis of data from a randomized trial | 4,111 patients with CAD but no concomitant HF | RDW is an independent predictor of all-cause death, cardiovascular death, and cardiovascular events in patients with history of MI. | [ |
Poludasu et al. (2009) | Retrospective | 859 patients who underwent PCI | Higher RDW level is an independent risk factor for death in patients undergoing PCI but only without anemia at baseline. | [ |
Nabais et al. (2009) | Retrospective | 1,796 patients with ACS | Higher RDW level is an independent risk factor for 6-month death/MI in patients with ACS. | [ |
Dabbah et al. (2010) | Prospective | 1,709 patients with MI | Baseline RDW and increase in RDW during hospitalization are associated with mortality in patients with MI. | [ |
Cavusoglu et al. (2010) | Prospective, cohort study | 389 unselected, male patients who were referred to coronary angiography | RDW is a predictor of all-cause mortality in unselected patients referred to coronary angiography. | [ |
Wang et al. (2011) | Prospective | 1,654 patients with ACS | RDW is a risk factor for death, heart failure, and recurrent MI in short-term follow-up. | [ |
Azab et al. (2011) | Retrospective | 619 patients with NSTEMI | RDW is a predictor of long-term mortality in patients with NSTEMI. | [ |
Uyarel et al. (2011) | Retrospective | 2,506 STEMI patients treated with primary PCI | RDW is a predictor of in-hospital and long-term cardiovascular mortality in patients with STEMI treated with primary PCI. | [ |
Lappé et al. (2011) | Post hoc analysis of prospective single-center registry | 1,489 patients with angiographically documented CAD and 449 normal patients | RDW is a predictor of long-term all-cause mortality in both CAD and no-CAD patients. | [ |
Vaya et al. (2012) | Prospective | 119 patients with MI | RDW is a predictor of recurrent cardiovascular events in patients with MI. | [ |
Gul et al. (2012) | Prospective | 310 patients with NSTEMI or UA | RDW is independently associated with long-term cardiovascular mortality in NSTEMI/UA patients. | [ |
İlhan et al. (2012) | Retrospective | 763 patients with MI treated with primary PCI | RDW is associated with in-hospital mortality but is not associated with impaired postinterventional TIMI flow. | [ |
Fatemi et al. (2013) | Post hoc analysis of prospective multicenter registry | 1,689 patients who underwent PCI | RDW is an independent predictor of 1-year mortality and improves discriminative risk value in patients undergoing PCI. | [ |
Tsuboi et al. (2013) | Retrospective | 560 diabetic patients with SCAD who underwent elective PCI | Increased RDW is associated with all-cause long-term mortality in diabetic patients undergoing elective PCI. | [ |
Warwick et al. (2013) | Post hoc observational analysis | 8,615 patients who underwent isolated CABG | RDW is significantly associated with in-hospital and long-term mortality in patients undergoing isolated CABG. | [ |
Lee et al. (2013) | Post hoc analysis of prospective multicenter registry | 1,596 patients with MI | Adding RDW to traditional risk factors significantly improves prediction for 12-month MACEs in patients with MI. | [ |
Ren et al. (2013) | Post hoc observational analysis | 1,442 patients with SCAD | RDW is a predictor of 1-year mortality and 1-year ACS in Chinese patients with SCAD. | [ |
Osadnik et al. (2013) | Retrospective | 2,550 patients with SCAD who underwent elective PCI | RDW is associated with comorbidity burdens and with long-term all-cause mortality in patients with SCAD undergoing elective PCI. | [ |
Yao et al. (2014) | Post hoc observational analysis | 2,169 patients with CAD who underwent PCI with DES implantation | Elevated RDW is an independent predictor of mortality and cardiovascular adverse events in patients who underwent PCI with DES implantation. | [ |
Vieira et al. (2014) | Prospective | 682 patients with ACS | RDW among other markers adds prognostic value to the GRACE risk score in patients with ACS and high risk defined by GRACE. | [ |
Sangoi et al. (2014) | Post hoc observational analysis | 109 patients with MI | RDW has additional prognostic value on the GRACE risk score in prediction of in-hospital mortality. | [ |
Sun et al. (2014) | Retrospective | 691 MI patients without HF at baseline | RDW predicts all-cause and cardiovascular mortality in patients with MI who are free of HF. | [ |
Arbel et al. (2014) | Post hoc analysis of prospective single-center registry | 3,222 patients who underwent coronary angiography | RDW is independently associated with 3-year MACEs in consecutive patients referred to coronary angiography. | [ |
Arbel et al. (2014) | Post hoc analysis of prospective single-center registry | 535 patients with STEMI treated with primary PCI | RDW above 14 is an independent predictor of long-term all-cause mortality in patients with STEMI undergoing primary PCI. | [ |
Bekler et al. (2015) | Retrospective | 202 patients with NSTEMI or UA | Increased RDW is independently associated with long-term mortality in patients with non-ST elevation ACS. | [ |
Liu et al. (2015) | Retrospective | 1891 patients ≥65 years old who underwent elective PCI | RDW is a predictor of intermediate-term all-cause mortality in elderly CAD patients treated with elective PCI. | [ |
Timoteo et al. (2015) | Prospective | 787 patients with ACS | Inclusion of RDW in a model with GRACE risk score improves predictive value for all-cause mortality. | [ |
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RDW as a marker of disease severity and clinical manifestation of CAD | ||||
Lippi et al. (2009) | Prospective | 2,304 adult patients who were admitted to the emergency department for chest pain suggestive of ACS | The combined measurement of cardiac troponin T and RDW increases diagnostic sensitivity to 99% in diagnosing ACS (diagnostic sensitivity of cardiac troponin T alone was 94%). | [ |
Ephrem and Kanei (2012) | Retrospective | 503 patients, with UA or NSTEMI | Elevated RDW is independently associated with higher recourse to CABG in patients presenting with UA or NSTEMI. | [ |
Uysal et al. (2012) | Prospective | 370 patients with STEMI versus 156 adults with normal coronary angiography as control groups | High RDW level is associated with STEMI in young patients. There is no difference in the RDW level between groups of elderly patients with STEMI versus patients with normal coronary angiography. | [ |
Isik et al. (2012) | Prospective, cross-sectional | 193 patients who underwent coronary angiography for SCAD | RDW is associated with the presence, severity, and complexity of CAD, as determined using SYNTAX score. | [ |
Ma et al. (2013) | Prospective, cohort study | 677 patients who underwent coronary angiography due to the presence of angina-like chest pain and/or positive treadmill stress test | RDW is associated with the presence and severity of CAD, as determined using Gensini score. | [ |
Ephrem (2013) | Retrospective | 503 patients with UA or NSTEMI | Increased RDW level is independently associated with hospital readmission in patients with UA or NSTEMI. | [ |
Duran et al. (2013) | Prospective, cross-sectional | 226 patients with ACS | Elevated RDW level is associated with the absence of coronary collateral vessel (graded according to the Rentrop scoring system) in patients with ACS. | [ |
Akin et al. (2013) | Prospective | 580 patients with MI | RDW is associated with severity of CAD (assessed by SYNTAX score) in patients with MI. | [ |
Tanboga et al. (2014) | Retrospective | 662 patients with STEMI who underwent primary PCI | RDW level is a predictor of angiographic coronary thrombus burden. | [ |
Akilli et al. (2014) | Prospective | 917 patients who underwent dobutamine stress echocardiography | High RDW level is associated with the positive result of dobutamine stress echocardiography and correlates with the extent of ischemia. Moreover, RDW increases the diagnostic accuracy of dobutamine stress echocardiography. | [ |
Bekler et al. (2014) | Retrospective | 251 patients with NSTEMI or UA | RDW level is associated with the presence of fragmented QRS complexes in patients with NSTEMI or UA. | [ |
Tanboga et al. (2014) | Prospective, cross-sectional | 322 patients with NSTEMI | RDW is a predictor of an impaired coronary collateral circulation (Rentrop grades 0-1) in patients with NSTEMI. | [ |
Acet et al. (2014) | Retrospective | 379 patients with STEMI | RDW is an independent predictor of GRACE risk score in patients presented with STEMI. | [ |
Polat et al. (2014) | Retrospective | 193 patients with NSTEMI or UA | RDW is a predictor of high GRACE score and in-hospital mortality in patients with NSTEMI or UA. | [ |
Wang et al. (2015) | Retrospective | 424 patients with STEMI who underwent primary PCI | High RDW is an independent predictor of the presence of three-branch and left main lesions and thrombotic burden in patients with STEMI. | [ |
Şahin et al. (2015) | Retrospective | 326 patients with SCAD who underwent coronary angiography | RDW is independently associated with poor coronary collateral circulation (Rentrop grades 0-1) in patients with SCAD. | [ |
Baysal et al. (2015) | Retrospective | 102 patients with STEMI who underwent thrombolysis | RDW level at admission is an independent predictor of the thrombolysis failure in patients with STEMI. | [ |
Li et al. (2015) | Retrospective | 203 patients who underwent coronary angiography and dynamic electrocardiography (Holter) | RDW value is independently associated with diurnal corrected QT variation in patients with SCAD. | [ |
Li et al. (2015) | Retrospective | 392 patients with CAD | High RDW is associated with elevated FRS in patients with CAD. | [ |
Sahin et al. (2015) | Prospective, cross-sectional | 335 patients with NSTEMI | RDW is a predictor of high SYNTAX score but is not associated with long-term mortality in patients with NSTEMI. | [ |
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RDW as a predictor of complications and patients outcomes after invasive treatment of CAD | ||||
Karabulut et al. (2012) | Retrospective | 556 patients with STEMI treated with primary coronary intervention | RDW is an independent predictor of abnormal reperfusion (TIMI flow less than 3). | [ |
Isik et al. (2012) | Prospective | 100 patients with STEMI treated with primary coronary intervention | High RDW is associated with the presence of electrocardiographic no-reflow. | [ |
Akyel et al. (2013) | Retrospective | 90 patients with coronary artery grafts who underwent coronary angiography | RDW is a predictor of saphenous vein graft disease. | [ |
Ertaş et al. (2013) | Retrospective | 132 patients without history of AF who underwent nonemergency CABG | Preoperative RDW level is a predictor of new-onset AF after surgery. | [ |
Fatemi et al. (2013) | Retrospective | 6,689 patients who underwent coronary artery stent implantation | RDW is independently associated with postprocedural major bleeding in patients who underwent PCI with stent implantation. | [ |
Yildiz et al. (2014) | Retrospective | 269 patients with SCAD or UA who underwent BMS implantation | Preprocedural RDW is an independent risk factor for ISR in patients who underwent BMS implantation. | [ |
Kurtul et al. (2015) | Prospective | 662 patients with ACS treated with PCI | RDW is an independent risk factor for the development of CI-AKI. | [ |
Kurtul et al. (2015) | Retrospective | 251 patients with history of BMS implantation who underwent control coronary angiography | RDW level before control coronary angiography is a predictor of the presence of ISR. | [ |
Zhao et al. (2015) | Retrospective | 293 patients with SCAD who underwent DES implantation | RDW level at both admission and follow-up is an independent predictor of ISR. | [ |
Akin et al. (2015) | Prospective, cross-sectional | 630 patients with STEMI who underwent primary PCI | Authors confirmed that RDW is an independent risk factor for the development of CI-AKI. | [ |
Mizuno et al. (2015) | Prospective | 102 patients with STEMI who underwent primary PCI | RDW has potential predictive ability, only if used with Mehran risk score, for CI-AKI in patients with STEMI. | [ |
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RDW as a predictor of cardiovascular events in a general population | ||||
Patel et al. (2010) | Meta-analysis | 11,827 older adults | In population of older adults RDW is strongly associated with CVD mortality. | [ |
Veeranna et al. (2013) | Prospective, cross-sectional | 8,513 adults free of CVD | RDW is independently associated with CAD mortality in a cohort with no preexisting CVD. | [ |
Borné et al. (2014) | Prospective, cohort study | 26,820 subjects (aged 45–73) without history of MI or stroke | RDW is associated with increased incidence of fatal ACS, but not with incidence of nonfatal ACS. | [ |
Skjelbakken et al. (2014) | Prospective, cohort study | 25,612 participants recruited from a general population | RDW is associated with first-ever MI in general population independent of traditional cardiovascular risk factors and anemia. | [ |
RDW: red blood cell distribution width; CAD: coronary artery disease; HF: heart failure; MI: myocardial infarction; PCI: percutaneous coronary intervention; ACS: acute coronary syndrome; NSTEMI: non-ST elevation myocardial infarction; STEMI: ST elevation myocardial infarction; UA: unstable angina; TIMI: thrombolysis in myocardial infarction; SCAD: stable coronary artery disease; CABG: coronary artery by-pass graft; MACEs: major adverse cardiac events; DES: drug-eluting stent; GRACE: Global Registry of Acute Coronary Events; AF: atrial fibrillation; BMS: bare-metal stent; ISR: in-stent restenosis; FRS: Framingham Risk Score; CVD: cardiovascular disease; CI-AKI: contrast-induced acute kidney injury.
One of the studies that assessed the prognostic role of RDW was conducted at our center. We demonstrated that RDW was an independent risk factor for long-term mortality in patients undergoing PCI for SCAD [
Tonelli et al. determined that RDW was a risk factor for MI, stroke, and symptomatic HF in patients with CAD [
The results of large, prospective studies with long-term follow-up periods (Tromsø and National Health and Nutrition Examination Survey) show that elevated RDW values increase the risk of MI and mortality due to CAD in the general population, regardless of other known CAD risk factors [
One of the most important limitations affecting the long-term outcomes of CAD invasive treatment is restenosis [
One limitation to the clinical usefulness of RDW in predicting adverse clinical outcomes is its moderate sensitivity and specificity [
The main limitation of the vast majority of cited studies is that they were observational and described only the statistical relationship between elevated RDW value and outcomes of patients with CAD, but not the pathophysiological mechanism explaining that phenomenon. Moreover, only a few published studies included factors influencing the hematopoiesis, that is, levels of folic acid, vitamin B12, markers of inflammation, and iron status as potential confounding factors [
In summary, RDW is a significant predictor of both all-cause mortality and adverse cardiovascular events in patients with CAD. Increased values of this parameter are associated with greater numbers of comorbidities and a higher likelihood of complications among patients with CAD treated via PCI.
In the following sections, the potential mechanisms explaining why elevated RDW levels are a strong, negative predictive factor among patients with CAD will be discussed.
The influence of RDW on prognosis among patients with cardiovascular disease has been extensively studied [
Anemia is a well-documented mortality risk factor among patients with CAD and is prevalent in cases of elevated RDW values [
There are reports indicating that elevated RDW values correlate with unfavorable lipid profiles [
Lipid disorders decrease red cell membrane fluidity, and higher CEM levels result in the deterioration of blood flow through the microcirculation [
Previous studies have noted that statin therapy increases erythrocyte deformability [
Another explanation for the relationship between RDW and prognosis may be chronic inflammation. It is believed that even low-intensity inflammation plays a crucial role in atherogenesis and may be responsible for platelet activation [
Veeranna et al. observed the correlation between
Another factor potentially affecting RDW is vitamin D3 deficiency, a well-established CAD risk factor [
Oxidative stress is responsible for shortening the lifespan of red blood cells, which intensifies both the production and the release of young cellular forms into the circulation, which is reflected by increased RDW levels [
Impaired kidney function increases mortality among patients with CAD [
The above-mentioned data indicate a correlation between RDW and other known atherosclerosis-predictive factors, although it is impossible to clearly identify the mechanism by which high erythrocyte anisocytosis serves as a negative prognostic marker in patients with CAD. In our opinion, the prognostic value of RDW results primarily from the negative impacts of inflammation and oxidative stress, as well as those of iron and vitamin D3 deficiency, on bone marrow erythropoiesis. Additionally, concurrent red blood cell deformability diminution may result in impaired flow through the microcirculation. It is also impossible to unambiguously ascertain which concomitant factors, including lipid, glycemic and iron metabolism disturbances, anemia, vitamin D3 deficiency, oxidative stress, inflammation, and the diminution of erythrocyte membrane deformability, are the primary causes of the poor prognoses observed in patients with CAD. In the authors’ opinion, the predictive utility of RDW results from the summation of each of the above-mentioned factors’ negative impacts on bone marrow erythropoietic function. Therefore, the prognostic value of RDW reflects the intensification of these phenomena.
RDW is an important risk factor for both mortality and cardiovascular events in patients with SCAD or acute coronary syndrome. It has not yet been determined whether anisocytosis is the cause of the poorer prognosis observed among these patients or if it is simply a marker of multiple pathological states connected with said prognosis. In contrast to the markers of inflammation and oxidative stress, which are not routinely analyzed, RDW provides valuable information concerning prognosis in patients with CAD.
The authors declare no conflict of interests regarding the publication of this paper.
This study utilized information and materials gathered during the implementation of the grants entitled “The Causes of Elevated Red Blood Cell Distribution Width Values in Patients with Stable Coronary Artery Disease Undergoing Elective Coronary Angiography,” KNW-1-122/N/4/0, and “The Relationship between Coronary Artery Calcium Score and Coronary Artery Disease Severity Evaluated by MDCT Angiography and Hematological Indices,” KNW-1-179/N/5/0, which were funded by the Medical University of Silesia, Poland. The authors would like to thank American Journal Experts and Michał Krawczyk for their assistance with the editing of this paper. They are grateful to Professor Lech Poloński for reviewing the paper.