Coronary Artery Disease

Angiology
2016, Vol. 67(7) 683-689
Predictors of No-Reflow Phenomenon ª The Author(s) 2015
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in Young Patients With Acute ST-Segment DOI: 10.1177/0003319715605977
ang.sagepub.com
Elevation Myocardial Infarction Undergoing
Primary Percutaneous Coronary
Intervention

Turgay Celik, MD1, Sevket Balta, MD1, Cengiz Ozturk, MD1,

Mehmet Gungor Kaya, MD2, Mustafa Aparci, MD1,
Osman A. Yildirim, MD1, Mustafa Demir, MD1, Murat Unlu, MD1,
Sait Demirkol, MD1, Selim Kilic, MD3, and Atila Iyisoy, MD1

Abstract
No-reflow is of prognostic value in ST-segment elevation myocardial infarction (STEMI) but has not been extensively investigated
in young patients. Young patients with STEMI admitted within 12 hours from symptom onset and treated by primary percutaneous
coronary intervention (pPCI) were recruited. Patients were classified into 2 groups based on postintervention thrombolysis in
myocardial infarction (TIMI) flow grade; no-reflow: TIMI flow grade 0, 1 or 2 (group 1; n ¼ 27; 21 men, mean age: 42 + 4 years);
and angiographic success: TIMI flow grade 3 (group 2; n ¼ 118; 110 men, mean age: 43 + 4 years). Adjusted odds ratios were
13.79 for female gender (P < .001; confidence interval [CI] ¼ 1.88-101.26), 2.09 for pain to balloon time (P < .017; CI ¼ 1.14-
3.812), 12.29 for high TIMI thrombus grade (P ¼ .012; CI ¼ 1.74-86.94), 0.04 for tirofiban use (P < .001; CI ¼ 0.01-0.22), 5.19 for
mean platelet volume (MPV; P < .001; CI ¼ 2.44-11.01), and 1.008 for platelet–lymphocyte ratio (PLR; P ¼ .034; CI ¼ 1.001-1.016).
In conclusion, female gender, pain to balloon time, high TIMI thrombus grade, tirofiban, MPV, and PLR were independent pre-
dictors of no-reflow in young patients with STEMI after pPCI.

Keywords
ST-segment elevation myocardial infarction, primary percutaneous coronary intervention, young patients, pain to balloon time,
thrombus grade, female gender

Introduction illicit drug use, and acquired or congenital hypercoagulability

Myocardial infarction (MI) among adults aged <46 years old is
unusual, comprising 2% to 10% of all MIs.1 Clarification of
how young patients differ from older ones with ST-segment
elevation MI (STEMI) treated with primary percutaneous cor-
onary intervention (pPCI) might help focus resources to pre-
vent these premature events. Coronary heart disease (CHD)
in older age-groups has been extensively documented, and clin-
ical practice guidelines focus on these patients, but younger
patients have rarely been studied.2
Some cardiovascular risk factors, common in the young
nowadays, such as smoking, obesity, impaired glucose toler-
ance, diabetes, dyslipidemia, hyperhomocysteinemia, and
emotional stress, may contribute to premature coronary ather-
osclerosis.3 In addition, conditions such as congenital coron-
ary abnormalities, connective tissue disorders, increased
matrix metalloproteinase activity, coronary artery aneurysm,
coronary artery dissection, myocardial bridging, irradiation,
syndromes may cause abrupt blood flow cessation.3
The ‘‘no-reflow’’ phenomenon manifests as an acute reduc-
tion in coronary blood flow in the absence of major epicardial
coronary vessel obstruction, flow-limiting dissection, vessel
spasm, or thrombosis.4 No-reflow is an important complica-
tion among patients with acute STEMI undergoing pPCI.5
1
Department of Cardiology, School of Medicine, Gulhane Military Medical
Academy, Etlik, Ankara, Turkey
2
Department of Cardiology, School of Medicine, Erciyes University, Kayseri,
Turkey
3
Department of Epidemiology, School of Medicine, Gulhane Military Medical
Academy, Etlik, Ankara, Turkey
Corresponding Author:
Sevket Balta, Department of Cardiology, Gulhane School of Medicine, Tevfik
Saglam St, 06018 Etlik, Ankara, Turkey.
Email: drsevketb@gmail.com
684
The pathophysiological mechanisms are not completely under-
stood, and its etiology appears to be multifactorial. The term
‘‘no-reflow’’ should be reserved for patients with thrombolysis
in myocardial infarction (TIMI) grade 0 or 1 flow in the
absence of other etiologies with ‘‘slow flow’’ referring to TIMI
grade 2 flow.6 Experimental models for no-reflow phenom-
enon include neutrophil accumulation, reactive oxygen species,
and the coagulation cascade via endothelial dysfunction and
microvascular constriction.7 Thrombus and soft, friable athero-
matous plaque are present in the majority of young patients
with STEMI and may result in distal embolization and no-
reflow during pPCI.8 No-reflow following pPCI is indepen-
dently associated with increased in-hospital mortality, arrhyth-
mias, and cardiac failure.9 Persistent no-reflow may also result
in postprocedural MI or extension of MI and is associated with
a poor long-term prognosis.9
Young women with acute MIs (AMIs) have more comorbid-
ity, longer length of stay (LOS), and greater in-hospital mortality
than young men, although their mortality rates are decreasing.10
The prediction of postprocedural no-reflow and in-hospital
major adverse cardiovascular events (MACEs) among young
patients with STEMI undergoing pPCI is poorly documented.
Accordingly, we assessed the relationship between potential pre-
dictors of no-reflow phenomenon and pPCI for STEMI in young
patients.
Materials and Methods
Patients
Consecutive patients with STEMI (n ¼ 885) treated by pPCI in
2 tertiary referral centers from 2014 to 2015 were assessed. We
excluded 565 patients older than 45 years. Among patients
younger than 45 years, 175 patients were excluded from the
study because of not undergoing pPCI (n ¼ 80), missing data
(n ¼ 65), or ineligibility (n ¼ 30; see exclusion criteria subse-
quently). As a result, 145 young patients with STEMI (90.3%
men, mean age 42 + 3 years; range 26-45 years) admitted
within 12 hours from symptom onset were included into the
study. All the patients underwent pPCI. The diagnosis of acute
STEMI was established using The joint European Society of
Cardiology, American College of Cardiology Foundation, the
American Heart Association, and the World Heart Federation
committee definition of STEMI.11,12 Coronary blood flow was
analyzed according to TIMI flow grade.6 Coronary no-reflow
was defined as TIMI flow grade <3 without clear evidence of
dissection, stenosis, or vasospasm.13 Patients were classified
into 2 groups based on postintervention TIMI flow grade.6
No reflow was defined as TIMI flow grades 0 to 2,13-15 and
reflow was defined as TIMI 3 flow grade.
Patients older than 45 years or with left main coronary artery
culprit lesion, left main stenosis >50%, previous coronary artery
bypass surgery, cardiogenic shock, pain to balloon time >12
hours, treatment with fibrinolytics in the previous 24 hours,
active infectious or inflammatory disease, chronic inflamma-
tory autoimmune disease including rheumatological disorders,
Angiology 67(7)
hematological diseases, end-stage liver and renal failure, or
malignancy were excluded from the study. The study protocol
was approved by the local ethics committee.
Coronary Intervention
All 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 mg nitroglycerine.
All pPCI procedures were carried out using the standard
femoral route with 6 or 7F guiding catheters. The choice of bal-
loon predilatation, primary stenting, and stent type (bare-metal
stent and drug-eluting stent) were at the discretion of the oper-
ator. Coronary blood flow was analyzed according to TIMI
flow grade. The TIMI flow grades were analyzed by 2 inter-
ventional 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 (ICC) coef-
ficients. Both (intra- and interobserver) ICC coefficients were
higher than 0.70 and statistically significant (P < .001).
Intra- and interobserver variability for TIMI 0 and 1 flow
grades were 3% and 4%, respectively, and 2% and 2.5%,
respectively, for TIMI 2 flow grade, and both intra- and inter-
observer variability for TIMI 3 flow grade were 0%.
Multivessel disease was defined as presence of 1 lesion
with >50% stenosis in 1 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.16 In
TIMI thrombus grade 0, no cine-angiographic characteristics of
thrombus are present; TIMI thrombus grade 1, possible throm-
bus 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 dimensions
1/2 the vessel diameter; in TIMI thrombus grade 3, there is
definite thrombus but with the largest linear dimension >1/2
but <2 vessel diameters; TIMI thrombus grade 4, there is defi-
nite thrombus, with the largest dimension 2 vessel diameters;
and TIMI thrombus grade 5, there is total occlusion. In the cur-
rent 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).17,18
Upon admission, all the patients received aspirin 300 mg/d,
bolus intravenous unfractioned heparin 5000 IU (70 U/kg), clo-
pidogrel at a loading dose of 300 mg, and maintenance dose of
75 mg and nitroglycerine. Primary stenting was performed
whenever possible although balloon predilatation was used in
the remaining cases. The technical aspects of the procedure,
duration, and pressure of inflation were determined by individ-
ual operators. The pPCI was performed with an average door to
first balloon time 75 + 15 minutes. The use of other medica-
tions, including intravenous tirofiban (12 hours), was left at the
discretion of the attending operator (including bolus tirofiban
Celik et al 685

administration). In patients undergoing tirofiban infusion, this Table 1. Baseline Demographic, Clinical, and Laboratory Character-
was administered after pPCI in the coronary care unit. istics of the Study Patients.a

No-reflow Reflow
Blood Analysis and Echocardiography (n ¼ 27) (n ¼ 118) P
Venous blood samples were drawn from antecubital veins
Age, years 42 + 4 43 + 4 .776
immediately after obtaining the electrocardiogram. Whole- Sex (M), n (%) 21 (77.8) 110 (93.2) .014
blood counting parameters were analyzed by a Sysmex K- BMI, kg/m2 26.10 + 2.41 26.41 + 2.28 .528
1000 (Block Scientific Inc., NY, USA) autoanalyzer within 5 Previous CAD, n (%) 8 (29.6) 18 (15.3) .079
minutes of blood sampling. In all study participants, transthor- Diabetes, n (%) 8 (29.6) 13 (11.0) .013
acic echocardiography was performed before pPCI in the cor- Hypertension, n (%) 16 (59.3) 32 (27.1) .001
onary care unit. Estimated glomerular filtration rate (eGFR) Smoking, n (%) 17 (63.0) 83 (70.3) .455
Family history, n (%) 37 (18.7) 85 (22.2) .318
was calculated using with the Chronic Kidney Disease Epide-
Preprocedural Aspirin, 19 (70.4) 71 (60.2) .324
miology Collaboration equation.19 All echocardiographic mea- medications n (%)
surements were carried out using commercially available Diuretic, 4 (14.8) 9 (7.6) .238
machines (Vivid 3 and Vivid 7; GE Medical System, Horten, n (%)
Norway) with a 3.5-MHz transducer. Simpson method was BAB, n 20 (74.1) 73 (61.9) .233
used to evaluate left ventricular ejection fraction.20 (%)
ACE-I, 21 (77.8) 80 (67.8) .309
n (%)
Statistical Analysis Statin, 20 (74.1) 75 (63.6) .300
Continuous variables were tested for normal distribution by the n (%)
Kolmogorov-Smirnov test. Continuous data were expressed as Peak CKMB, U/L 100 (25-126) 81 (17-112) .258
mean + standard deviation or median (interquartile range) if TC, mg/dL 182 (145-231) 192 (165-220) .332
Triglyceride, mg/dL 126 (95-153) 128 (85-193) .574
not normally distributed and compared using independent sam- LDL-cholesterol, mg/dL 130 (96-157) 119 (94-145) .496
ples t test or Mann-Whitney U tests. Categorical variables were HDL-cholesterol, mg/dL 35 (29-44) 37 (31-45) .523
expressed as percentages and analyzed with the chi-square test. TC–HDL-cholesterol ratio 4.7 (4.0-5.7) 5.0 (4.2-6.2) .416
Differences between groups were considered significant at TG–HDL-cholesterol ratio 3.4 (2.4-5.0) 3.3 (2.1-5.7) .808
P < .05 2-sided. Serum glucose, mg/dL 122 (97-138) 128 (109-155) .127
We investigated the effects of different variables on no- Serum urea, mg/dL 29.5 (28.0-36.5) 32.0 (27.0-38.7) .672
reflow by calculating odds ratios in univariate analysis for all Creatinine, mg/dL 0.92 (0.80-1.08) 0.99 (0.89-1.11) .338
eGFR, mL/min/1.73m2 87 (74.6-104.2) 92 (78.6-102.1) .800
the variables. Variables with an unadjusted P < .10 in logistic Uric acid, mg/dL 5.8 (4.5-7.1) 6.0 (5.0-7.0) .322
regression analysis for clinically important variables were
identified as potential risk markers and included in the full Abbreviations: BMI, body mass index; CAD, coronary artery disease; BAB, beta
model. We reduced the model using forward elimination, and adrenergic blocker; ACE-I, angiotensin-converting enzyme inhibitor; CKMB,
creatine kinase-MB isoenzyme; TC, total cholesterol; LDL, low-density lipo-
we eliminated potential risk markers using likelihood ratio protein; HDL, high-density lipoprotein; eGFR, estimated glomerular filtration
tests. A 2-sided P < .05 was considered significant. Statistical rate; M, male; TG, triglyceride; SD, standard deviation.
a
analyses were performed by using SPSS 15.0 for Windows Data are presented as mean + SD, median (interquartile range), or n (%).
(SPSS Inc, Chicago, Illinois).
tirofiban use (Table 2). Pain to balloon time in the no-reflow
group was longer than that of the patients in the reflow group
Results (Table 2; 6.0 vs 4.5 hours, P < .001). Also, the no-reflow group
We included 145 young patients with STEMI (90.3% men, mean had a higher frequency of tirofiban use (Table 2; 59.3% vs
age 42 + 3 years) undergoing pPCI. The patients were divided 25.4%, P ¼ .001). There were more patients with multivessel
into 2 groups according to TIMI flow grades after pPCI. No- disease in the no-reflow group compared to the reflow group,
reflow group 1 with flow grades 0 to 2 (n ¼ 27, 21 men, mean although no statistically significant difference was observed
age 42 + 4 years) and the reflow group 2 with flow TIMI grade (Table 2; 51.9% vs 32.2%, P ¼ .055). The left anterior des-
3 (n ¼ 118, 110 men, mean age 43 + 4 years). Baseline clinical, cending coronary artery was the most common IRA in both
demographic, and laboratory parameters are listed in Table 1. study groups. The pPCI procedure including percentage of pri-
Regarding demographic parameters, there were more women mary stent implantations and type of stents was similar among
in the no-reflow group (22.2% vs 6.8%, P ¼ .014). Regarding the groups.
risk factors, patients with no reflow were more likely to have The comparison of admission hematological parameters of
diabetes or hypertension (29.6% vs 11.0%, P ¼ .013 and both groups is listed in Table 3. According to admission whole
59.3% vs 27.1%, P ¼ .001, respectively; Table 1). blood cell count results, the patients in the no-reflow group had
The comparison of angiographic and echocardiographic significantly higher mean platelet volume (MPV) and platecrit
characteristics of the 2 groups showed no statistically signifi- compared to the reflow patients (Table 3; MPV: 10.8 vs 8.8 fL,
cant difference apart from chest pain to balloon time and P ¼ .001; platecrit: 0.26 vs 0.23, P ¼ .013).
686 Angiology 67(7)

Table 2. Angiographic and Echocardiographic Characteristics of the Table 4. Effects of Various Variables on no-reflow in Multivariate
Study Patients.a Logistic Regression Analyses.

No-reflow Reflow Adjusted ORa 95% CI P

(n ¼ 27) (n ¼ 118) P
Age, years 1.02 0.82-1.28 .307
Pain to balloon time, h 6.0 (6.0-7.0) 4.5 (5.5-6.0) <.001 Female gender 13.79 1.88-101.26 .010
Tirofiban use, n (%) 16 (59.3) 30 (25.4) .001 Present of hypertension 1.41 0.25-8.05 .700
Admission LVEF (%) 50 (40-50) 50 (43-55) .587 Present of diabetes 3.78 0.46-31.11 .216
TIMI thrombus grade Present of previous CAD 0.98 0.15-6.32 .982
Low thrombus grade, n (%) 10 (37.0) 56 (47.5) .327 Pain to balloon time, h 2.09 1.14-3.82 .017
High thrombus grade, n (%) 17 (63.0) 62 (52.5) Present of multivessel disease 2.46 0.44-13.87 .307
Number of narrowed vessel, n (%) Stent length, mm 0.88 0.74-1.06 .180
Single vessel, n (%) 13 (48.1) 80 (67.8) .055 Stent diameter, mm 0.15 0.02-1.40 .096
Multivessel, n (%) 14 (51.9) 38 (32.2) High TIMI thrombus grade 12.29 1.74-86.94 .012
Infarct related artery, n (%) Present of Tirofiban use 0.04 0.01-0.22 <.001
LAD, n (%) 11 (40.7) 62 (52.5) .483 Mean platelet volume, fL 5.19 2.44-11.01 <.001
CFX, n (%) 7 (25.9) 21 (17.8) Platecrit 1.17 0.97-1.41 .095
RCA, n (%) 9 (33.3) 35 (29.7) Neutrophil–lymphocyte ratio 1.27 0.85-1.89 .248
PCI procedure, n (%) Platelet–lymphocyte ratio 1.008 1.001-1.016 .034
Balloon þ stenting, n (%) 23 (85.0) 94 (79.7) .511 a
Primary Stenting, n (%) 4 (15.0) 24 (20.3) Adjusted for age, gender, diabetes, hypertension, previous coronary artery
disease, pain to balloon time, multivessel disease, stent length, stent diameter,
Stent type, n (%)
high thrombus burden, tirofiban, mean platelet volume, platecrit, neutrophil–
BMS, n (%) 25 (92.5) 107 (90.7) .753 lymphocyte ratio, and platelet–lymphocyte ratio.
DES, n (%) 2 (7.5) 11 (9.3)
Final balloon pressure, Atm. 16.37 + 2.48 16.42 + 2.63 .924
Stent length, mm 17.63 + 3.30 17.93 + 5.30 .349 variables were analyzed in multivariate analysis as predictors
Stent diameter, mm 3.11 + 0.44 3.19 + 0.37 .081 of no-reflow (Table 4). Some variables associated with
Abbreviations: LVEF, left ventricular ejection fraction; LAD, left anterior descend- impaired flow after pPCI were significantly different between
ing artery; CFX, circumflex coronary artery; RCA, right coronary artery; PCI, per- the 2 study groups. Independent contributions of age, gender,
cutaneous coronary intervention; BMS, bare-metal stent; DES, drug-eluting stent; diabetes, hypertension, previous CHD, pain to balloon time,
TIMI, thrombolysis in myocardial infarction; SD, standard deviation. multivessel disease, stent length, stent diameter, high TIMI
a
Data are presented as mean + SD, median (interquartile range) or n (%).
thrombus grade, tirofiban, MPV, platecrit, neutrophil–lympho-
cyte ratio (NLR), and platelet–lymphocyte ratio(PLR) were
Table 3. Comparison of Hematological Parameters of the Study
analyzed in multivariate forward logistic regression (Table 4).
Groups.a
On multivariate analysis, female gender, pain to balloon time,
No-reflow Reflow high TIMI thrombus grade, tirofiban, MPV, and PLR remained
(n ¼ 27) (n ¼ 118) P independent predictors of no-reflow after pPCI. Adjusted odds
ratios were calculated as 13.79 for female gender (P < .001;
White blood cell count, 12.8 (8-15) 12.0 (10-14) .720
109/L CI ¼ 1.88-101.26), 2.09 for pain to balloon time (P < .017;
Neutrophil (%) 60.0 (43-75) 58 (41-73) .508 CI ¼ 1.14-3.812), 12.29 for high TIMI thrombus grade (P ¼
Lymphocyte (%) 18.0 (9-25) 17.6 (12-27) .408 .012; CI ¼ 1.74-86.94), 0.04 for tirofiban (P < .001; CI ¼
Eosinophil (%) 1.36 (0.93-2.42) 1.56 (1.04-2.16) .759 0.01-0.22), 5.19 for MPV (P < .001; CI ¼ 2.44-11.01), and
Basophil (%) 0.70 (0.35-0.83) 0.73 (0.42-1.11) .416 1.008 for PLR (P ¼ .034; CI ¼ 1.001-1.016). There were no
Monocyte (%) 7.69 (6.55-8.07) 7.43 (5.48-8.91) .944 significant differences in preprocedural medications (Table 1).
Neutrophil–lymphocyte 3.8 (2.4-5.0) 2.7 (1.9-4.5) .078
ratio
Platelet–lymphocyte ratio 151 (90-221) 111 (81-168) .087
Hemoglobin, g/dL 14.8 (13.4-16.5) 15.1 (14.1-16.1) .837 Discussion
Red cell distribution 13.3 (12.8-14.0) 13.2 (12.4-13.7) .368
width (%) The present study demonstrated that female gender, pain to bal-
Platelet count, 109/L 266 (214-308) 257 (209-293) .516 loon time, high TIMI thrombus grade, tirofiban, MPV, and
Mean platelet volume, fL 10.8 (8.3-11.3) 8.8 (8.1-9.8) .001 PLR were independent predictors of no reflow after pPCI in
Platecrit 0.26 (0.20-0.33) 0.23 (0.18-0.26) .013 young patients.
a Acute MI is one of the common causes of death in world-
Data are presented as mean + standard deviation or median (interquartile
range). wide. Age is well established as one of the most important
determinants of prognosis in patients with STEMI.21 Young
patients might have less favorable, or at least different,
The effects of clinically important variables on no-reflow risk factor profiles compared to older patients. Those aged
were analyzed using univariate and multivariate logistic regres- 45 years were more likely to be male, smokers, South
sion analyses. Data for the 2 groups were combined, and all the Asian ethnicity, and have family history of premature CHD,
Celik et al
increased incidence of impaired fasting glucose, high trigly-
ceride, low high-density lipoprotein levels, and increased
waist to hip ratio.22 However, the young patients had less
hypertension, hypercholesterolemia, diabetes mellitus, his-
tory of MI, myocardial revascularization, impaired left ventri-
cular systolic function, or renal impairment.22 The young
patients had higher prevalence of angiographically normal
coronary arteries.23 This is partly due to the increased preva-
lence of risk factors for atherosclerosis in the younger age-
group; however, nonatherosclerotic CHD or hypercoagulabil-
ity should also be investigated or at least suspected in younger
patients.3
In patients with STEMI undergoing coronary angiography,
short-term mortality risk varies considerably. Early and indivi-
dualized risk stratification in each patient allows for better
decision making with regard to the choice of pharmacologic
and interventional treatments, allocation of clinical resources,
and triage among different levels of hospital care. For such
planning, one must be aware of the risk factors related to mor-
bidity and mortality in patients with STEMI undergoing pPCI.
No-reflow phenomenon is known as one of the early late mor-
tality factors for even adequate recanalization of the occluded
artery after pPCI in patients with STEMI. Distal embolization
after PCI is one of the major mechanisms of no-reflow. High
thrombus burden on angiography before PCI and right coronary
artery of ischemia-related artery and female sex are the signif-
icant predictors of distal embolization in patients with STEMI
after PCI. In addition, distal embolization on angiography pre-
dicts an adverse short-term outcome in patients with STEMI.24
Due to the growing understanding of the role of inflamma-
tory status in the initiation and progression of atherosclerosis,
epidemiological studies have focused on markers of the inflam-
matory status and its relation to adverse outcomes in patients
with different CHD phenotypes. Furthermore, recent studies
have shown that no-reflow phenomenon is associated with a
higher prevalence of early and late morbidity and mortal-
ity.5,25,26 The complete blood count (CBC) is an easy, inexpen-
sive, and routine examination. Many studies have evaluated
whether CBC parameters can be used as markers of inflamma-
tion and mortality in patients with CHD and STEMI.27 For
example, platelets play a central role in the pathophysiology
of AMI.28 In addition to platelet count, MPV and PLR are also
inexpensive and easily available markers. High MPV values on
admission are independently associated with long-term adverse
outcomes in patients with STEMI who undergo primary angio-
plasty.5,29 Also, the PLR is a strong and independent predictor
of slow flow/no-reflow after pPCI in patients with acute
STEMI.30 Our results showed that MPV and PLR were inde-
pendent predictors of no-reflow in patients with young STEMI
undergoing pPCI.
Door to balloon time is an important factor determining the
outcome of patients with STEMI undergoing PCI. Prognostic
factors for door to balloon time can be categorized as patient
characteristics, hospital characteristics, health care practices,
physician characteristics as well as a limited group of ‘‘other’’
characteristics.31 We have also shown that door to balloon time
687
is independently associated with no-reflow in young patients
with STEMI undergoing pPCI.
Preprocedural thrombus is a harbinger of procedural com-
plications following pPCI in patients with STEMI. Baseline
thrombus predicts increased ischemic complications at 30 days
including a 3-fold increased risk of death as well as MI.32 In
addition, Dong Bao et al33 investigated the clinical factors and
angiographic findings that predict no-reflow phenomenon and
long-term prognosis of patients with STEMI having angio-
graphic no-reflow. They showed that high thrombus burden
on baseline angiography was a significant and independent pre-
dictor of angiographic no-reflow. They concluded that high
thrombus burden on baseline angiography can be used to stra-
tify patients with STEMI into a lower or higher risk for angio-
graphic no-reflow during PCI. We showed similar results in the
present study.
Sex disparities in reperfusion therapy, short-, and long-
term mortality for patients with acute STEMI have been well
documented. Carrabba et al34 assessed the independent effect
of female gender on management and early and 1-year mortal-
ity. They concluded that women with STEMI have a lower
rate of coronary reperfusion therapy and a higher in-hospital
and 1-year mortality. Young women experience a 2- to 3-
fold greater mortality risk than younger men after STEMI
undergoing pPCI. Compared with men, younger women have
a higher risk for readmission, even after adjusting for con-
founders.35 Young women with STEMI are less likely to
receive reperfusion therapy and more likely to have reperfu-
sion delays than similarly aged men. Sex disparities are more
pronounced among patients transferred to percutaneous cor-
onary intervention institutions or who received fibrinolytic
therapy.36 A previous study37 concluded that although the
time from onset of symptoms to hospital admission was sim-
ilar among younger men and women, the overall 1-year mor-
tality was significantly higher in women than in men in the
younger age-groups. This may be related to a variety of fac-
tors such as gender differences in plaque composition, differ-
ences in thrombotic activity, and a higher prevalence of
microvascular disease in younger women.
Our findings are limited by the relatively small sample size
and the nonrandomized and retrospective design. Because
high-sensitivity CRP is not evaluated routinely in patients
undergoing coronary angiography in our department, we could
not compare the inflammatory status between the groups.
Furthermore, we did not use intravascular ultrasonography
(IVUS) to quantitatively evaluate thrombus burden and plaque
content. However, IVUS can prolong PCI procedures and is
expensive. Owing to the limitation of image resolution in
angiography, we do not know the exact percentage of patients
with distal embolization.
Conclusions
Female gender, pain to balloon time, high TIMI thrombus
grade, tirofiban, MPV, and PLR were independent predic-
tors of no reflow in young patients with STEMI undergoing
688
pPCI. These predictors of no-reflow in young patients with
STEMI should be further confirmed in multicenter, prospec-
tively designed studies.
Authors’ Note
The authors made substantial contributions to conception, design,
acquisition of data, analysis and interpretation of data, drafting
the article and revising it critically for important intellectual content.
All authors approved the final version of the article.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
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