Article, Cardiology

The relation between monocyte to HDL ratio and no-reflow phenomenon in the patients with acute ST-segment elevation myocardial infarction

a b s t r a c t

Background: No-reflow phenomenon is a prognostic value in ST-segment elevation myocardial infarction . Monocyte to high density lipoprotein ratio (MHR) has recently emerged as a marker of inflammation and oxidative stress in the cardiovascular disease.

Purpose: In this study, we aimed to investigate the relation between MHR and no-reflow phenomenon in patients with STEMI undergoing primary percutaneous coronary intervention (pPCI).

Material and methods: A total of 600 patients with STEMI (470 men; mean age, 62 +- 12 years) admitted within 12 hours from symptom onset were included into this study. Patients were classified into 2 groups based on post- intervention Thrombolysis in Myocardial Infarction flow grade: no-reflow–TIMI flow grade 0, 1, or 2 (group 1); angiographic success–TIMI flow grade 3 (group 2).

Results: According to admission whole-blood cell count results, the patients in the no-reflow group had signifi- cantly higher monocyte count and MHR values when compared with those of the reflow patients. After multivar- iate backward logistic regression, MHR remained independent predictors of no reflow after pPCI. Adjusted odds ratios were calculated as 1.09 for MHR (Pb .001; confidence interval [CI], 1.07-1.12). Receiver operating charac- teristic curve analysis suggested that the optimum MHR level cutoff point for patients with no-reflow was 22.5, with a sensitivity and specificity of 70.2% and 73.3%, respectively (area under curve, 0.768; 95% CI, 0.725-0.811). Conclusion: In conclusion, MHR levels are one of the independent predictors of no reflow in patients with STEMI after pPCI.

(C) 2016

Introduction

No-reflow (NR) phenomenon manifests as an acute reduction in coronary blood flow in the absence of major epicardial coronary vessel obstruction or flow limitation and vessel spasm or thrombosis [1]. No-reflow phenomenon is an important complication among patients with acute ST-segment elevation myocardial infarction under- going primary percutaneous coronary intervention (pPCI) [2-4]. The pathophysiological mechanisms of NR are not fully understood, although the multifactorial etiologic factors have been considered over the past decades. Experimental models for NR phenomenon include

* Corresponding author at: Department of Cardiology, Gulhane School of Medicine, TevfikSaglam St., 06018 Etlik, Ankara, Turkey. Tel.: +90 312 3044281; fax: +90 312

3044250.

E-mail addresses: [email protected], [email protected] (S. Balta).

neutrophil accumulation, reactive oxygen species, and the coagulation cascade via endothelial dysfunction and microvascular constriction [5]. Thrombus and soft, friable atheromatous plaque are present in patients with STEMI, and may result in distal embolization and NR during pPCI [6]. NR after pPCI is independently associated with increased in- hospital mortality, arrhythmias, and cardiac failure. Persistent NR may also result in postprocedural myocardial infarction or extension of myo- cardial infarction and is associated with a poor long-term prognosis [7]. Inflammation plays a role in the initiation and progression of the atherosclerotic process [8]. Mononuclear leukocytes like macrophages and monocytes are the most crucial cell types for secretion of proinflam- matory cytokines, which lead to the development and exacerbation of atherosclerosis, a lipid-driven inflammatory disease [9]. Activation of monocytes and differentiation into lipid-laden macrophages are funda- mental events in the generation of atherosclerotic lesions. High-density lipoprotein cholesterol (HDL-C), a particle inversely related to cardio- vascular disease, has a number of anti-inflammatory functions. In

http://dx.doi.org/10.1016/j.ajem.2016.05.031

0735-6757/(C) 2016

addition, HDL-C has been shown to have an effect on the coagulation pathway by inhibiting platelet activation and reducing thrombus forma- tion. In this context, now that inflammation is the main leading factor of short- or long-term mortality in patients with STEMI, and increased monocyte count and decreased HDL-C levels have been shown to be as- sociated to inflammation, we have maintained that monocyte to HDL ratio (MHR) may be related with the postprocedural NR in patients with STEMI. Therefore, MHR, a routinely available, inexpensive, and eas- ily calculated index, may predict inflammation [10]. Monocyte to HDL ratio has recently been investigated as a new predictor for major ad- verse cardiovascular outcomes. There is no data, however, regarding the prognostic value of MHR in the prediction of post-procedural NR and in-hospital major adverse cardiovascular events (MACEs) among patients with STEMI undergoing pPCI. Accordingly, we assessed the re- lation MHR and the NR phenomenon in patients who underwent pPCI for acute STEMI in this study.

Materials and methods

Study patients

We analyzed the data of consecutive 888 patients with STEMI in 2 tertiary referral center from 2014 to 2015. Among them, 288 patients were excluded from the study because of not undergoing pPCI (n = 75), missing data (n = 187), or ineligibility to study (n = 26). A total of 600 patients with STEMI (470 men; mean age, 62 +- 12 years) admit- ted within 12 hours from symptom onset were included in this study (Fig. 1). The diagnosis of acute STEMI was established using The Joint European Society of Cardiology, American College of Cardiology Foun- dation, the American Heart Association, and the World Heart Federation committee definition of STEMI [11,12]. Coronary blood flow was ana- lyzed according to Thrombolysis In Myocardial Infarction flow

grade [13]. Coronary NR was defined as TIMI flow grade less than 3 without clear evidence of dissection, stenosis, or vasospasm [14]. Pa- tients were classified into 2 groups based on postintervention TIMI flow grade [13]. No reflow was defined as TIMI flow grades 0 to 2 [14-16], and reflow was defined as TIMI 3 flow grade.

Patients with culprit lesion in the left main coronary artery; left main stenosis greater than 50%; previous coronary artery bypass surgery; car- diogenic shock; pain to balloon time more than 12 hours; treatment with thrombolytics in the previous 24 hours; active infectious or inflam- matory diseases; presence of any chronic inflammatory-autoimmune disease including rheumatological disorders, hematalogical diseases, end-stage liver, and renal failures; and known malignancy were exclud- ed from this study. Study protocol was approved by our local instituonal ethics committee.

Percutaneous coronary intervention

All study participants underwent coronary angiography performed in multiple orthogonal projections using the Judkins technique. To achieve maximal dilatation, each coronary angiogram was preceded by intracoronary injection of 100 ug of nitroglycerine. All pPCI proce- dures were carried out using the standard femoral route with 6F or 7F guiding catheters. The choice of balloon predilatation, primary stenting, and stent type (bare metal stent and drug-eluting stent) was at the dis- cretion of the operator. Coronary blood flow was analyzed according to TIMI flow grade. TIMI flow grades were analyzed by 2 interventional cardiologists blinded to patient clinical data. Intra- and interobserver variabilities were obtained from a random sample of 100 patients. Intra- and Interobserver variability for TIMI grades was assessed by intraclass Correlation coefficients. Both (intra- and interobserver) intraclass correlation coefficients were higher than 0.70 and statistically significant (Pb .001). Intra- and interobserver variability for TIMI 0 and 1

Fig. 1. The flow charts of the current study.

blood analysis and echocardiography”>flow grades were 3% and 4%, respectively, and 2.0% and 2.4%, respective- ly, for TIMI 2 flow grade; both intra- and interobserver variability for TIMI 3 flow grade were 0%.

Multivessel disease was defined as presence of 1 or more lesions with greater than 50% stenosis in 1 or more major epicardial coronary artery or its major branches remote from the infarct related artery (IRA). To evaluate Clot burden, we used the TIMI thrombus scale [17]: TIMI thrombus grade 0, no cine-angiographic characteristics of throm- bus are present; TIMI thrombus grade 1, possible thrombus is present with such angiographic characteristics as decreased contrast density, haziness, irregular lesion contour, or a smooth convex “meniscus” at the site of total occlusion suggestive but not diagnostic of thrombus; TIMI thrombus grade 2, there is definite thrombus, with the largest di- mensions <= 1/2 the vessel diameter; TIMI thrombus grade 3, there is def- inite thrombus but with the largest linear dimension N 1/2 but b 2 vessel diameters; TIMI thrombus grade 4, there is definite thrombus, with the largest dimension >= 2 vessel diameters; TIMI thrombus grade 5, there is total occlusion. In this study, we further categorized TIMI thrombus score into 2 overall grades: a high thrombus grade (grades 4 and 5) and a low thrombus grade (grades 1-3) [18,19].

Upon admission, all the patients received aspirin 300 mg/d, bolus in- travenous unfractioned heparin 5000 IU (70 U/kg), clopidogrel at a loading dose of 300 mg, and maintenance dose of 75 mg and nitroglyc- erine. Primary stenting was performed whenever possible, although balloon predilatation was used in the remaining cases. The technical as- pects of the procedure, duration, and pressure of inflation were deter- mined by individual operators. pPCI was performed with an average door to first balloon time of 74 +- 16 min. The use of other medications, including intravenous tirofiban (12 hours), was left at the discretion of the attending operator (including bolus tirofiban administration). In pa- tients undergoing tirofiban infusion, this was administered after pPCI in the coronary care unit.

Blood analysis and echocardiography

Venous blood samples were drawn from antecubital veins immedi- ately after obtaining the electrocardiogram. Whole-blood counting pa- rameters were analyzed by a Sysmex K-1000 autoanalyzer within 5 minutes of blood sampling. In all study participants, transthoracic echo- cardiography was performed before pPCI in the coronary care unit. Esti- mated glomerular filtratiton rate (eGFR) was calculated using with the Chronic Kidney Disease Epidemiology Collaboration equation [20]. All echocardiographic measurements were done using commercially avail- able machines (Vivid 3 and Vivid 7, GE Medical System, Horten, Norway) with a 3.5-MHz transducer. The Simpson’s method was used to evaluate left ventricular ejection fraction (LVEF) [21].

Statistical analysis

Continous variables were tested for normal distribution by the Kolmogorov-Smirnov test. Continous data were expressed as mean +- SD or median (interquartile range) if not normally distributed and com- pared using independent samples t test or Mann-Whitney U tests. Cate- gorical variables were expressed as percentages and analyzed with the ?2 test. Differences between groups were considered significant at Pb

.05, 2-sided. We investigated the effects of different variables on NR

by calculating odds ratios in univariate analysis for all the variables. Var- iables with an unadjusted Pb .10 in logistic regression analysis for clini- cally important variables were identified as potential risk markers and included in the full model. We reduced the model by using forward elimination, and we eliminated potential risk markers by using likeli- hood ratio tests. A 2-sided Pb .05 was considered significant. Logit model for NR was obtained by applying multivariate logistic regression analysis. A receiver operating characteristic (ROC) curve demonstrates the characteristics of a diagnostic method by plotting the false- positive rate (1-specificity) on the horizontal axis and the true-

positive rate (sensitivity) on the vertical axis for various cutoff values. The ROC area under the curve (AUC) is a popular measure for the accu- racy of a diagnostic test. A diagnostic test that has a greater AUC is a bet- ter predictor of the presence of a disease. To determine the accuracy and respective best cutoff values of MHR and mean platelet volume (MPV) for predicting of NR and in-hospital MACEs among patients with STEMI undergoing pPCI, ROC curves and their corresponding AUC were used. Statistical analyses were performed by using SPSS 15.0 Sta- tistical Package Program for Windows (SPSS Inc., Chicago, Illinois).

Results

We analyzed 600 patients with STEMI eligible for this study (470 men; mean age, 62 +- 12 years) who underwent pPCI. Study partici- pants were divided into 2 groups according to TIMI flow grades after pPCI. The patients with TIMI flow grades 0 to 2 formed the NR group (n = 199; 145 men; mean age, 62 +- 12 years), and patients with TIMI 3 flow grade formed the reflow group (n = 401; 325 men; mean age, 58 +- 12 years), respectively. Baseline clinical and demographical parameters are presented in Table 1. Regarding demographical param- eters, patients with NR were older than patients with reflow (62 +- 12 vs 58 +- 12 years, P= .001). In addition, more men were in the reflow group (81.0% vs72.9%, P= .022). With respect to coronary risk factors, there were statistically significant differences between 2 groups in the presence of diabetes mellitus (b.001) and previous coronary artery dis- ease (CAD) (b.001) as shown in Table 1. On the other hand, median pain to balloon time was longer in patients with NR compared with patients with reflow (6.0 vs 5.5 hours, Pb .001). Moreover, frequency of tirofiban use was higher in patients with NR compared with patients with reflow (33.8% vs 21.2%, P= .001).

The comparison of angiographic and echocardiographic characteris- tics of the 2 groups showed no statistically significant difference apart from admission LVEF, TIMI thrombus grade (high Thrombus burden), and presence of multivessel disease (Table 1). Admission LVEF was lower in the NR group compared with the reflow group as shown in Table 1 (46.0 +- 9.5% vs 48.5 +- 8.4%, P= .002). In addition, the NR group had higher thrombus burden when compared with the reflow group as shown in Table 1 (70.2% vs 44.6%, Pb .001). More patients had multivessel disease in the NR group compared with the reflow group (Table 1; 70.4% vs 44.6%, Pb .001). The most common infarct- related artery was left anterior descending coronary artery in both groups. Percutaneous coronary intervention procedure was similar among groups. The comparison of admission laboratory charecteristics of the study patients including hematological parameters are presented in Table 1. According to admission whole-blood cell count results, the patients in the NR group had significantly higher monocyte count, MPV, MHR, neutrophyl-lympocite ratio (NLR), and lower eGFR values when compared with the reflow patients (Table 1).

Effects of the variables with an unadjusted Pb .10 in logistic regres- sion analysis and clinically important variables on the NR were analyzed by using univariate and multivariate logistic regression analyses. Data for 2 groups were combined, and all the variables were analyzed in uni- variate analysis as the predictor of NR as shown in Table 2. Some vari- ables associated with impairED flow after Primary PCI were significantly different between the 2 study groups. Independent contri- butions of age, sex, hypertension, diabetes, LVEF on admission, eGFR, pain to balloon time, multivessel disease, high TIMI thrombus grade, glycoprotein (Gp) IIb/IIIa inhibitor, previous CAD, NLR, MHR, and MPV were analyzed in multivariate backward logistic regression (Table 2). Age, pain to balloon time, multivessel disease, high TIMI thrombus grade, GpIIb/IIIa inhibitor usage, MHR, and MPV remained independent predictors of NR after primary PCI on multivariate analysis. Adjusted odds ratios were calculated as 1.04 for age (P= .02; confidence interval [CI], 1.02-1.07), 1.49 for pain to balloon time (Pb .001; CI, .22-1.83),

2.10 for multivessel disease (P= .006; CI, 1.23-3.56), 2.88 for high

TIMI thrombus grade (P= .001; CI, 1.51-5.51), 0.31for GpIIb/IIIa

Table 1

Baseline demographical, clinical, angiographical, echocardiographical, and laboratory charecteristics of the study patients

NR (n = 199)

Reflow (n = 401)

P

Age (y)

62 +- 12

58 +- 12

b.001

Sex (male), no. (%)

145 (72.9)

325 (81.0)

.022

BMI (kg/m2)

26.55 +- 2.15

26.35 +- 2.25

.321

Previous CAD, no. (%)

65 (32.7)

72 (18.0)

b.001

Diabetes, no. (%)

73 (36.7)

92 (22.9)

b.001

Hypertension, no. (%)

92 (46.2)

158 (39.4)

.110

Smoking, no. (%)

108 (54.3)

226 (56.4)

.628

Family history, no. (%)

37 (18.6)

87 (21.7)

.377

Pain to balloon time (h)

6 (5.0-6.5)

5.5 (4.0-6.0)

b.001

GpIIb/IIIa inhibitor, no. (%)

67 (33.8)

85 (21.2)

.001

Preprocedural medications

Aspirin, no. (%)

123 (61.8)

267 (66.6)

.248

Diuretic, no. (%)

25 (12.6)

42 (10.5)

.444

BAB, no. (%)

121 (60.8)

268 (66.8)

.145

ACE-I, no. (%)

134 (67.3)

295 (73.6)

.112

Statin, no. (%)

128 (64.3)

276 (68.8)

.268

Admission LVEF (%)

46.0 +- 9.5

48.5 +- 8.4

.002

TIMI thrombus grade

High thrombus burden

139 (70.2)

179 (44.6)

b.001

Low trombus burden

59 (29.8)

222 (55.4)

No. of narrowed vessel, no. (%)

Single vessel, no. (%)

59 (29.8)

222 (55.4)

b.001

Multivessel, no. (%)

140 (70.4)

182 (44.6)

IRA, no. (%)

LAD, no. (%)

91 (45.7)

190 (47.4)

.828

CFX, no. (%)

39 (19.6)

82 (20.4)

RCA, no. (%)

69 (34.7)

129 (32.2)

PCI procedure, no. (%)

Balloon + stenting, no. (%)

163 (81.9)

306 (76.4)

.141

Primary stenting, no. (%)

36 (18.1)

95 (23.6)

Stent type, no. (%)

BMS, no. (%)

163 (81.9)

328 (81.8)

.972

DES, no. (%)

36 (18.1)

73 (18.2)

Final balloon pressure (atm)

16.1 +- 2.4

16.3 +- 2.7

.224

Stent length (mm)

18.0 +- 4.6

17.8 +- 5.1

.575

Stent diameter (mm)

3.2 +- 0.4

3.1 +- 0.4

.109

White blood cell (x109/L)

11.6 (9-15)

11.0 (9-13)

.144

Monocyte count (x109/L)

1.1 (0.8-1.4)

0.7 (0.5-0.9)

b.001

MHR ratio

30.6 (20.2-37.5)

18.3 (12.5-23.0)

b.001

neutrophil-lymphocyte ratio

4.1 (3.0-5.3)

2.8 (2.0-4.3)

b.001

Hemoglobin (g/dL)

14.08 +- 1.78

14.26 +- 1.92

.275

Platelet count (x109/L)

238 (190-289)

247 (202-289)

.205

MPV (fl)

10.05 +- 1.50

9.07 +- 1.22

b.001

Peak CKMB (U/l)

102 (31-146)

89 (24-148)

.305

Total cholesterol (mg/dL)

176 (145-210)

183 (157-216)

.074

Triglyceride (mg/dL)

117 (81-158)

121 (79-172)

.615

Low-density lipoprotein (mg/dL)

115 (90-140)

116 (92-141)

.642

HDL (mg/dL)

38 (31-44)

39 (34-45)

.133

TC/HDL ratio

4.6 (3.9-5.6)

4.8 (4.0-5.6)

.407

TG/HDL ratio

3.0 (1.9-4.8)

3.0 (1.8-5.0)

.933

Serum glucose (mg/dL)

147 (119-210)

141 (112-197)

.079

Uric acid (mg/dL)

6.0 (5.4-7.1)

6.0 (5.0-7.7)

.314

Serum urea (mg/dL)

39 (30-51)

36 (29-52)

.467

Creatinine (mg/dL)

1.0 (0.9-1.3)

1.0 (0.9-1.1)

.135

eGFR (mL-1 min-1 1.73 m-2)

70 (52-86)

76 (63-92)

.001

Data are presented as mean +- SD, median (interquartile range), or number (percentage).

Abbreviations: ACE-I, angiotensin-converting enzyme inhibitor; BAB, ?-adrenergic bloker; BMI, body mass index; BMS, bare metal stent; CFX, circumflex coronary artery; CKMB, creatine kinase MB isoenzyme; DES, drug-eluting stent; LAD, left anterior descending artery; RCA, right coronary artery; TC, total cholesterol; TG, triglyceride.

inhibitor usage (Pb .001; CI, 0.18-0.55), 1.09 for MHR (Pb .001; CI,

1.07-1.12), and 2.33 for MPV (Pb .001; CI, 1.84-2.97) as shown in

Table 2. The logit model for NR was calculated as;

Logit (NR) = – 16.805 + 0.034 x age + 0.715 x multivessel disease + 0.398 x pain to balloon time + 1.193 x GpIIb/IIIa inhibitor use + 0.881 x MPV + 0.089 x MHR+ 1.127 x high thrombus burden. Sensitivity and specifity of the logit model were found as 68.3% and

92.1%, respectively. Overall accuracy of the model was 83.6%.

receiver operating characteristic curve analysis suggested that the optimum MHR level cutoff point for patients with NR was 22.5, with a sensitivity and specificity of 70.2% and 73.3%, respectively (AUC, 0.768; 95% CI, 0.725-0.811) as shown in Fig. 2. In addition, ROC curve

analysis suggested that the optimum MPV level cutoff point for patients with NR was 9.75, with a sensitivity and specificity of 63.4.2% and 69%, respectively (AUC, 0.696; 95% Ci, 0.690-0.702) as shown in Fig. 2.

Discussion

In this study, we have shown that MHR levels were independent predictors of NR in patients with STEMI after pPCI. In addition, age, pain to balloon time, multivessel disease, high TIMI thrombus grade, GpIIb/IIIa inhibitor usage, and MPV remained independent predictors of NR after primary PCI on multivariate analysis in the current study.

Table 2

Effects of various variables on NR in univariate and multivariate logistic regression analyses

Unadjusted OR

95% CI

P

Adjusted ORa

95% CI

P

Age

1.03

1.01-1.04

b.001

1.04

1.02-1.07

.002

Sex (female)

1.59

1.07-2.38

.023

1.46

0.77-2.77

.242

Hypertension

1.32

0.94-1.86

.111

0.79

0.46-1.37

.403

Diabetes

1.95

1.34-2.82

b.001

1.19

0.67-2.13

.560

LVEF

0.97

0.95-0.99

.002

0.98

0.95-1.01

.290

eGFR

0.99

0.98-1.00

.243

1.01

0.99-1.03

.113

Pain to balloon time

1.50

1.31-1.71

b.001

1.49

1.22-1.83

b.001

Multivessel disease

2.84

1.98-4.08

b.001

2.10

1.23-3.56

.006

High TIMI thrombus grade

1.69

1.18-2.41

.004

2.88

1.51-5.51

.001

GpIIb/IIIa inhibitor

0.53

0.36-0.77

.001

0.31

0.18-0.55

b.001

Previous CAD

2.22

1.50-3.28

b.001

1.47

0.82-2.65

.198

MHR

1.10

1.08-1.12

b.001

1.09

1.07-1.12

b.001

MPV

1.72

1.50-1.97

b.001

2.33

1.84-2.97

b.001

NLR

1.13

1.06-1.20

b.001

1.06

0.97-1.16

.173

Abbreviations: CI, confidence interval; NLR, neutrophil-lymphocyte ratio; OR, odds ratio.

a Adjusted for age, sex, hypertension, diabetes, LVEF on admission, eGFR, pain to balloon time, multivessel disease, high TIMI thrombus grade, Gp IIb/IIIa inhibitor, previous CAD, NLR, MHR, MPV.

Primary PCI is the most efficient Reperfusion strategy for STEMI. In patients with STEMI undergoing coronary angiography, various early and late mortality risk scores have been well known. One of these scores, NR phenomenon, is significantly associated with poor outcome after pPCI. One should be aware of the risk factors related to morbidity and mortality in patients with STEMI undergoing pPCI. Therefore, early, precise and individualized interventions in these patients take an advantage for life quality. Furthermore, although many conditions of the etiopathogenesis for the NR phenomenon are considered, distal embolization after PCI plays a key role in mechanisms of NR [3]. Many previously published studies have emphasized that some factors like high thrombus burden on angiography before PCI, right coronary artery as ischemia-related artery, and female sex are the predictors of distal embolization in patients with STEMI after PCI, but higher Inflammatory conditions are also significantly associated with distal embolization in these patients [3]. Because of the growing understanding of the role of inflammatory status in the NR phenomenon, epidemiological studies have focused on markers of the inflammatory status and its relation to adverse outcomes in patients with STEMI after PCI. Furthermore, recent studies have shown that the NR phenomenon is importantly associated with a higher inflammatory status in patients with STEMI after PCI [2,22,23].

As far as all clinicians know, the complete blood count is one of the most frequently ordered laboratory tests in clinical practice. Various studies have evaluated the performance of these hematological

parameters like leukocytes to predict NR phenomenon and long-term mortality risk [4]. Monocytes, a distinct type of leukocytes, are the key player during this process. Mononuclear leukocytes like macrophages and monocytes are the most crucial cell types for secretion of proinflam- matory cytokines. Monocytes and their descendant macrophages are essential to the development and exacerbation of atherosclerosis, a lipid-driven inflammatory disease. These cells may have an important role in the pathogenesis of atherosclerotic plaque formation [9]. During development of atherosclerotic lesions, blood monocytes are recruited into the intima and subintimal layers of the vessel wall, where these cells can take up oxidized low-density lipoprotein and other lipids through their scavenger receptors [9]. Contrarily, HDL moleculescan ef- fectively inhibit the migration of macrophages and promote efflux of oxidized low-density lipoprotein from these cells. Thus, HDL has been proven to be a potent inhibitor of inflammation, acting on a number of pathways, and this may suggest that HDL could be applied as an anti- inflammatory molecule for a number of diseases. It is also well established that increased HDL levels protect against atherosclerosis and significantly correlate with improved prognosis for vascular disease associated events [24]. Therefore, we have speculated that an increased MHR may be a good predictor for atherosclerosis development, progres- sion, and cardiovascular outcomes. As it known, MHR is a novel vascular inflammatory marker. Its relation with inflammation has been investi- gated some previous clinical studies. Kanbay et al [10] reported that MHR-cholesterol ratio was increased with decreasing eGFR in

Fig. 2. Receiver operating characteristic curve analysis suggested that the optimum MHR level and MPV level cutoff point for patients with NR phenomenon. The MHR was 22.5, with a sensitivity and specificity of 70.2% and 73.3%, respectively (AUC, 0.768; 95% confidence interval, 0.725-0.811). The MPV was 9.75, with a sensitivity and specificity of 63.4% and 69.0%, re- spectively (AUC, 0.696; 95% confidence interval, 0.690-0.702).

predialytic patients with chronic kidney disease. Those results support the notion that MHR can be used as an inflammatory marker. Indeed, they reported an increased MHR associated with a worse cardiovascular profile and arose as independent predictors of major cardiovascular events during follow-up [10]. Canpolat et al [25] concluded that higher MHR, which indicates an enhanced inflammation and oxidative stress, was significantly and independently associated with the pres- ence of slow coronary phenomenon. They [26] also showed that MHR was an independent predictor of atrial fibrillation recurrence after cryoballoon-based Catheter ablation. These results also denoted that MHR may be routinely available in future clinical practice.

Kundi et al [27] showed that MHR is significantly associated with the severity of coronary atherosclerosis, as assessed by the SYNTAX score. Hence, Cetin et al [28] concluded that MHR was a novel marker of in- flammation seemed to be an independent predictor of Stent thrombosis in patients with STEMI. Finally, Cicek et al [29] have recently investigat- ed whether MHR may be of short-term and long-term prognostic value in STEMI. They concluded that that admission MHR is associated inde- pendently and significantly with short-term and long-term mortality in patients with STEMI undergoing successful pPCI [29]. They also showed that rates of in-hospital mortality, MACEs, cardiopulmonary re- suscitation, dialysis, use of inotropic agents, shock, late mortality, target vessel revascularization, stroke, and reinfarct were higher in the higher MHR group compared with the other MHR groups. Differently, we also found that age, pain to balloon time, multivessel disease, high TIMI thrombus grade, GpIIb/IIIa inhibitor usage, and MPV remained indepen- dent predictors of NR after primary PCI on multivariate analysis in the current study.

Conclusions

Monocyte to high density lipoprotein ratio levels may be used as an inflammatory marker for the prediction of NR among patients with STEMI undergoing pPCI. We strongly believe that the predictive perfor- mance of the MHR should be further confirmed in future multicenter, prospectively designed studies.

Limitations of this study

The main limitations of this study are the relatively small sample size and the nonrandomized and retrospective design of it. Because high- sensitivity CRP is not evaluated routinely in patients undergoing pPCI in our department, this test was not included to compare inflammatory status between the groups. Furthermore, we did not use intravascular ultrasonography to quantitatively evaluate thrombus burden and plaque content. However, because intravascular ultrasonography can prolong PCI procedures and is expensive, it may increase risk of adverse cardiovascular events. Owing to the limitation of image resolution in an- giography, we do not know the exact percentage of patients with distal Declaration of interest“>embolization. Finally, we did not perform the myocardial blush grade in these patients.

Declaration of interest

The authors reported that there is no conflict of interests.

Author contribution details

The authors made substantial contributions to conception, design, acquisition of data, analysis and interpretation of data, drafting the arti- cle and revising it critically for important intellectual content. All au- thors approved the final version of the paper.

References

  1. Durante A, Camici PG. Novel insights into an “old” phenomenon: the no reflow. Int J Cardiol 2015;187:273-80.
  2. Celik T, Kaya MG, Akpek M, Gunebakmaz O, Balta S, Sarli B, et al. Predictive value of ad- mission platelet volume indices for in-hospital major adverse cardiovascular events in Acute ST-segment elevation myocardial infarction. Angiology 2015;66(2):155-62.
  3. Celik T, Balta S, Ozturk C, Kaya MG, Aparci M, Yildirim OA, et al. Predictors of no-reflow phenomenon in young patients with acute ST-segment elevation myocardial in- farction undergoing primary percutaneous coronary intervention. Angiology 2015.
  4. Celik T, Balta S, Demir M, Yildirim AO, Kaya MG, Ozturk C, et al. Predictive value of admission red cell distribution width-platelet ratio for no-reflow phenomenon in acute ST segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Cardiol J 2016;23(1):84-92.
  5. Schwartz BG, Kloner RA. Coronary no reflow. J Mol Cell Cardiol 2012 Apr;52(4): 873-82.
  6. Young JJ, Cox DA, Stuckey T, Babb J, Turco M, Lansky AJ, et al. Prospective, multicen- ter study of thrombectomy in patients with acute myocardial infarction: the X-tract AMI registry. J Interv Cardiol 2007 Feb;20(1):44-50.
  7. Mehta RH, Harjai KJ, Boura J, Cox D, Stone GW, O’Neill W, et al. Prognostic signifi- cance of transient no-reflow during primary percutaneous coronary intervention for ST-elevation acute myocardial infarction. Am J Cardiol 2003;92(12):1445-7.
  8. Balta S, Celik T, Mikhailidis DP, Ozturk C, Demirkol S, Aparci M, et al. The relation be- tween atherosclerosis and the neutrophil-lymphocyte ratio. Clin Appl Thromb Hemost 2015 [pii: 1076029615569568, Epub ahead of print].
  9. Hilgendorf I, Swirski FK, Robbins CS. Monocyte fate in atherosclerosis. Arterioscler Thromb Vasc Biol 2015;35(2):272-9.
  10. Kanbay M, Solak Y, Unal HU, Kurt YG, Gok M, Cetinkaya H, et al. Monocyte count/ HDL cholesterol ratio and cardiovascular events in patients with chronic kidney dis- ease. Int Urol Nephrol 2014;46(8):1619-25.
  11. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third uni- versal definition of myocardial infarction. Circulation 2012;126(16):2020-35.
  12. Colaco R, Reay P, Beckett C, Aitchison TC, Mcfarlane PW. False positive ECG reports of

    anterior myocardial infarction in women. J Electrocardiol 2000;33:239-44 [Suppl.].

    The Thrombolysis in Myocardial Infarction trial Phase I findings TIMI study groupN Engl J Med 1985;312(14):932-6.

  13. Rezkalla SH, Kloner RA. No-reflow phenomenon. Circulation 2002;105(5):656-62.
  14. Rezkalla SH, Dharmashankar KC, Abdalrahman IB, Kloner RA. No-reflow phenome- non following percutaneous coronary intervention for acute myocardial infarction: incidence, outcome, and effect of Pharmacologic therapy. J Interv Cardiol 2010; 23(5):429-36.
  15. Ito H. No-reflow phenomenon and prognosis in patients with acute myocardial in- farction. Nat Clin Pract Cardiovasc Med 2006;3(9):499-506.
  16. Gibson CM, de Lemos JA, Murphy SA, Marble SJ, McCabe CH, Cannon CP, et al. Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction: a TIMI 14 substudy. Circulation 2001;103(21):2550-4.
  17. Miranda-Guardiola F, Rossi A, Serra A, Garcia B, Rumoroso JR, Iniguez A, et al. Angio- graphic quantification of thrombus in ST-elevation acute myocardial infarction pre- senting with an occluded infarct-related artery and its relationship with results of percutaneous intervention. J Interv Cardiol 2009;22(3):207-15.
  18. Sianos G, Papafaklis MI, Serruys PW. Angiographic thrombus burden classification in patients with ST-segment elevation myocardial infarction treated with percutane- ous coronary intervention. J Invasive Cardiol 2010;22(10 Suppl. B):6B-14B.
  19. Balta S, Cakar M, Demirkol S, Kurt O, Unlu M, Kucuk U. The relationship between ankle-brachial index and estimated glomerular filtration rate in type 2 diabetes. Angiology 2013 Apr;64(3):242.
  20. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recom- mendations for chamber quantification. Eur J Echocardiogr 2006 Mar;7(2):79-108.
  21. Kurtul A, Murat SN, Yarlioglues M, Duran M, Celik IE, Kilic A. Mild to moderate renal

    impairment is associated with no-reflow phenomenon after primary percutaneous coronary intervention in acute myocardial infarction. Angiology 2014.

    Ndrepepa G, Tiroch K, Fusaro M, Keta D, Seyfarth M, Byrne RA, et al. 5-Year prognostic value of no-reflow phenomenon after percutaneous coronary intervention in pa- tients with acute myocardial infarction. J Am Coll Cardiol 2010;55(21):2383-9.

  22. van de Woestijne AP, van der Graaf Y, Liem A-H, Cramer MJM, Westerink J, Visseren FLJ, et al. Low high-density lipoprotein cholesterol is not a risk factor for recurrent vascular events in patients with vascular disease on intensive lipid-lowering medi- cation. J Am Coll Cardiol 2013;62(20):1834-41.
  23. Canpolat U, Cetin EH, Cetin S, Aydin S, Akboga MK, Yayla C, et al. Association of monocyte-to-HDL cholesterol ratio with slow coronary flow is linked to systemic in- flammation. Clin Appl Thromb Hemost 2015.
  24. Canpolat U, Aytemir K, Yorgun H, Sahiner L, Kaya EB, Cay S, et al. The role of preprocedural monocyte-to-high-density lipoprotein ratio in prediction of atrial fi- brillation recurrence after cryoballoon-based catheter ablation. Europace 2015; 17(12):1807-15.
  25. Kundi H, Kiziltunc E, Cetin M, Cicekcioglu H, Cetin ZG, Cicek G, et al. Association of monocyte/HDL-C ratio with SYNTAX scores in patients with stable coronary artery disease. Herz 2016.
  26. Cetin EHO, Cetin MS, Canpolat U, Aydin S, Topaloglu S, Aras D, et al. Monocyte/HDL- cholesterol ratio predicts the definite stent thrombosis after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Biomark Med 2015;9(10):967-77.
  27. Cicek G, Kundi H, Bozbay M, Yayla C, Uyarel H. The relationship between admission monocyte HDL-C ratio with short-term and long-term mortality among STEMI pa- tients treated with successful primary PCI. Coron Artery Dis 2016.

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