Red Cell Distribution Width as a Marker for Predicting In-Stent Rest Enosis after Percutaneous Coronary Intervention

Abstract

Objective: Red Cell Distribution Width (RDW) has recently been considered as a predictor of a variety of cardiovascular diseases. However, no data is currently available with respect to the role of RDW in predicting In-Stent Rest enosis (ISR) after successful coronary stent implantation.

Methods: A cohort of 1733 consecutive patients was retrospectively enrolled who had a received coronary angiography follow-up at mean 7 months after stinting. Of them, 271 lesions were implanted with a Bare-Metal Stent (BMS) while 404 lesions with a Drug-Eluting Stent (DES). The relationship of admission RDW value and angiography-proven ISR at 7 months were evaluated.

Results: There were 106 patients with ISR (106/675, 15.7%; BMS, n=271, ISR=82, 30.3%; DES, n=404, ISR=24, 5.9%) and 569 patients without ISR at 7-month angiographic follow-up. Baseline RDW values were significantly higher in patients with ISR (RDW: 13.9±2.2 versus 12.5±2.0, p<0.001). In addition, the elevated RDW levels were found to be associated with ISR regardless of BMS or DES implantation. Moreover, there was a positive correlation between levels of RDW and CRP in patients with ISR (&ga= 0.661, p=0.000). Finally, in a Receiver Operating Characteristic (ROC) curve analysis, an RDW = 13.4% on admission had 71% sensitivity and 68% specificity in predicting the ISR after successful PCI.

Conclusion: The present study provides the first line of evidence for the use of RDW, an easy, inexpensive, routinely reported marker, as an independent predictor for ISR after successful coronary stent implantation.

Keywords: Red cell distribution width; Coronary artery disease; Stent; Instent rest enosis

Introduction

In-Stent Rest enosis (ISR) and Stent Thrombosis (ST) are major complications after Percutaneous Coronary Intervention (PCI) and coronary stent placement [1-3]. Compared with Bare-Metal Stent (BMS), Drug-Eluting Stent (DES) are associated with a further reduction in ISR and repeat revascularization with similar rates of death, reinfarction, and ST [4]. Nonetheless, repeat revascularization is still performed in ~5-7% of patients treated with primary PCI and DES, and angiographic rest enosis occurs ~15% of lesions, especially in patients with ST-segment elevation myocardial infarction [5]. Besides technical factors, the other status of an individual is strong predictor of the risk of ISR. Therefore, identifying biomarkers and studying their differential diagnostic values are critical for a more efficient personalized intervention, patient management, and adverse effects reduction [6].

Red Blood Cell Distribution Width (RWD) is a measure of the variability in the size of circulating erythrocytes and it has been utilized in the differential diagnosis of anemia [7]. More recently, elevated RDW was reported to be a marker and independent predictor in a variety of cardiovascular diseases including acute and Table Coronary Artery Disease (CAD) [8,9], heart failure [10], peripheral vascular disease [11], stroke [12], slow coronary flow [13], cardiac syndrome X [14], even the thrombosis and bleeding after successfully Percutaneous Coronary Intervention (PCI) [15,16]. However, the study on role of RDW in patients ISR after PCI has currently not been investigated. Additionally, although the higher RDW level has been established by previous studies in several cardiovascular diseases, the underlying mechanism has not clearly been elucidated yet. It has been postulated that RDW may be a marker of underlying inflammation, malnutrition, older age, and underlying renal dysfunction predisposing patients with higher baseline RDW to increased morbidity and mortality [17]. ISR is not rare complication in patients undergoing PCI even in the era of drugeluting stent and patients who ISR tend to be similar characteristics to those with higher RDW values such as inflammation, older age and renal insufficiency [1]. Thus, we hypothesized that baseline RDW values might be a predictor of ISR after successful PCI.

In the present study, therefore, we retrospectively angiographic ally evaluate admission RDW level and its relations to ISR after successful PCI in patients. To exclude the stent types also influence the effects of RDW on predicting the ISR, we specially enrolled the all patients who have received either BMS or DES implantation.

Methods

Study population

The study population consisted of 675 consecutive patients who underwent PCI between April 2004 to December 2005 in our single center. These patients were selected from 5144 patients according to our inclusion and exclusion criteria. The study complied with the Declaration of Helsinki. The study protocol was approved by the Fuwai hospital ethnic's committee review board. Informed written consent was obtained from all patients included in this analysis.

The patients who fulfilled inclusion criteria were enrolled in the study: (1) patients who received no more than one stent implantation regardless of BMS or DES in a pericardial coronary artery including Left Main artery (LM) or Left Anterior Descending (LAD) or Left Cyclotron Branch (LCX) or Right Coronary Artery (RCA) or their major branches; (2) patients who had angiographic follow-up at mean 7 months with a range 6-9 months after the stent implantation due to a variety of indications; (3) patients who had entire demographic, clinical angiographic, and stenting-related data. Primary angioplasty and/or stent implantation more than one arteries and/or lesions were not included. Exclusion criteria were acute myocardial infarction, renal dysfunction, left ventricular ejection fraction <45%. All patients received an optimal secondary prevention treatment after stent implantation according to currently available guidelines.

In addition, all subjects enrolled in this study had normal hepatic function. The hyperlipidemia was defined as low-density lipoprotein cholesterol 160mg/dl and/or Triglyceride (TG) =200 mg/dl. Patients with history or evidence of valvular heart disease, congestive heart failure, echocardiographic ally proven left ventricular hypertrophy, a history of dysphasia, swallowing as well as intestinal motility disorders, untreated thyroid disease, sinus node dysfunction or conduction disturbance, estrogen replacement therapy, carcinoma, poorly controlled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >105 mmHg), recent major operation (<3 months), autoimmune disease were also excluded from the study.

Finally, patients who have had previous history of anemia, have received previous red blood cell transfusion or were on treatment for anemia, such as supplemental iron, foliate or an erythropoiesisstimulating agent were not included in this study. Patients with known hematological disease such as hemolytic anemia, neoplastic metastases to the bone marrow, iron replacement therapy that could increase plasma RDW levels were excluded. Patients who were lost to follow-up were also excluded.

Determination of RDW

Hemoglobin, RDW, and White Blood Cell (WBC) counts were determined by the automated hematology analyzer XE-1200 (Sysmex, Kobe, Japan) before PCI. The normal range of RDW (%) in our laboratory was 10-15% [13,14]. The other biochemical measurements were performed using a molecular analyzer (Roche Diagnostics, Manheim, Germany).

Stent implantation

Coronary stent implantations were performed by ten principle operators affiliated to our center, and indications were according to the operator deemed appropriate at the time. There was no strict protocol on how or which intervention list should perform the procedure, and there was no restriction on the choice or kind or the numbers of stents deployed. Routine use of intravascular ultrasound was deemed unnecessary unless there was a specific indication. Balloon pre-dilatation was performed followed by stent implantation using conventional technique for almost all of our patients. Postdilatation was used only if the primary angiographic result was not satisfactory. Pre-procedural intravenous heparin was given to maintain an activated clotting time =250 seconds, and all patients received aspirin (at least 75 mg) and clopidogrel (300 mg loading dose followed by 75 mg once daily for at least 12 months).

Angiographic analysis and ISR definition

The cineangiography on all eligible patients were reviewed and analyzed by two independent experienced interventional cardiologists. Quantitative Coronary Angiographic (QCA) analysis was performed on all patients in pre-percutaneous transluminal coronary stent and immediate post-stent as well as angiographic follow-up at approximately 7 months.

ISR was defined as >50% diameter steno sis by QCA within a previously stinted vessel segment, and was classified as focal (<10mm long), diffuse (>10mm long), proliferative (>10mm long and extending outside the stent edges), or totally occluded according to previously reported [5]. Two coronary segments (in-stent and in-segment) were subjected to QCA. The in-stent analysis comprised only the segment of the lesion encompassing the stent. The in-segment was defined as the in-stent segment plus segments 5 mm proximal and distal to the edge of the stent. Minimal Luminal Diameter (MLD) and percentage of diameter steno sis were measured for each segment. In-segment and in-stent late Lumen Loss (LL) was calculated as post-procedure MLD minus follow-up MLD. ISR was classified according to a modified Mehran classification [10].

Statistical analysis

Categorical variables were expressed as percent frequencies and continuous variables as mean±SD. χ2 or Fisher test was used to compare categorical variables; Student t test was performed for comparison of continuous variables. The univariate and multivariate analysis was used for baseline clinical characteristics, serum markers, and RDW. Association between RDW and CRP was test using Spearman correlation coefficient. Receiver Operating Characteristic (ROC) curve analysis was performed to define the optimal CADspecific cut-off points. A P value <0.05 was considered statistically significant.

Results

Baseline clinical characteristics

Between the periods of the study, a total of 5144 patients had a successful PCI, while 675 consecutive patients fulfilled our enrolled criteria. There were 106 patients with ISR (106/675, 15.7%) including 82 patients with a BMS implantation from a total of 271 patients (82/271, 30.3%) and 24 with a DES from a total of 404 (24/404, 5.9%) and 569 patients without ISR at 7-month angiographic follow-up.

Baseline clinical characteristics of patients with or without ISR were showed in Table 1. There was a predominance of males (87.0%). The average age was 57.2±10.8 years with a range of 34-82 years. More than half of them had at least one of risk factors for CAD. 514 patients (514/675, 76.1%) of them were diagnosed as sTable angina. Most baseline clinical characteristics were not significantly different, except for the age and rate of prior myocardial infarction, current smoker, and diabetes mellitus. In addition, there were no significantly differences in previous medications except for the lower percentage of calcium channel blocker administration in patients with ISR.