Relationship between Hemoglobin Concentration at Admission with the Incidence of No-Reflow Phenomenon and In-Hospital Mortality in Acute Myocardial Infarction with Elevation of ST Segments in Patients who underwent Primary Percutaneous Coronary Intervention

Abstract

Anemia in acute ST-segment elevation myocardial infarction (STEMI) is associated with a pro-coagulant state, contributing to the incidence of no-reflow phenomenon and increased mortality following primary percutaneous coronary intervention (PPCI). However, clinical data remain contradictory. The objective of our study was to evaluate the association of admission hemoglobin (Hb) concentration and in-hospital mortality of STEMI patients' post-PPCI, as well as final thrombolysis in myocardial infarction (TIMI) flow. A cross-sectional study was performed from the database of Jakarta Acute Coronary Syndrome Registry, consisting of 3,071 STEMI patients who underwent PPCI between January 2014 and December 2019. No-reflow phenomenon was defined as final TIMI flow <3 of the infarct-related artery. Outcome measures were the occurrence of no-reflow and in-hospital mortality. Anemia criteria were based on the World Health Organization. Anemia was found in 550 patients (17.9%). Patients with anemia were older (60 ± 10 years, p  < 0.001), predominantly women (20.7 vs. 11.2%, p  < 0.001), TIMI risk score >4 (45.8 vs. 30.4%, p  < 0.00), and Killip classification >1 (25.8 vs. 20.8%, p  < 0.009). Anemia at admission was not associated with no-reflow phenomenon (odds ratio [OR] = 0.889; 95% confidence interval [CI] = 0.654–1.209, p  = 0.455). Multivariate regression models showed that anemia was not associated with in-hospital mortality (OR = 0.963; 95% CI = 0.635–1.459, p  = 0.857) and with no-reflow phenomenon (OR = 0.939; 95% CI = 0.361–2.437, p  = 0.896). Anemia upon admission was not related to the no-reflow phenomena or in-hospital mortality in STEMI patients undergoing PPCI.

Background

Coronary artery disease (CAD) is a worldwide issue that leads to death at all ages following stroke. ¹ Riset Kesehatan Dasar (Riskesdas) in 2018 showed that almost 2.8 million people in Indonesia had cardiovascular disease. ¹ Outcomes of patients with acute ST-segment elevation myocardial infarction (STEMI), an acute clinical presentation of CAD, who were undergoing primary percutaneous coronary intervention (PPCI) were related to the incidence of the no-reflow phenomenon, with 11 to 41% of these events being calculated based on the achievement of final thrombolysis in myocardial infarction (TIMI) flow. ² Anemia was believed to be an independent factor affecting the condition of the occurrence of the no-reflow phenomenon. However, the exact mechanism of anemia contributing to this phenomenon was not clear. The existing hypothesis suggests that anemia increases the production of erythropoietin in the spinal cord, leading to platelet and plasminogen activator inhibitor-1 activation, which, in turn, creates a pro-coagulant state and causes this phenomenon. ^{3 4}

Several studies regarding anemia in STEMI patients who underwent PPCI are still contradictory. In Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications study ( n  = 1,030), no differences were found between final TIMI flow values and peak serum creatinine levels in patients with or without anemia. ⁵ However, different results were shown in the study by Yaylak et al ⁶ ( n  = 3,804), who demonstrated an association between anemia and the incidence of no-reflow evaluated from the final TIMI flow. In a study by Karabulut et al, ⁷ consisting of 556 STEMI patients who underwent PPCI, it was found that the distribution of red blood cells is an independent predictor of abnormal reperfusion as indicated by TIMI flow <3.

Anemia is also said to increase the mortality of STEMI patients undergoing PPCI. A meta-analysis study concluded that anemia is an independent risk factor that increases short- and long-term mortalities. ⁸ This mechanism is also not known with certainty. Several hypotheses suggest that increased sympathetic tone, up to cardiogenic shock, is a potential underlying mechanism.

Studies that analyze the relationship between anemia and the incidence of no-reflow phenomena and anemia with mortality are still very contradictory, and studies that simultaneously observe anemia with the incidence of no-reflow phenomena and in-hospital mortality are still limited. Thus, this study was conducted to find the relationship between admission hemoglobin (Hb) concentration and the incidence of the post-PPCI no-reflow phenomenon and to correlate it with in-hospital mortality in STEMI patients undergoing PPCI.

Methods

This study was a single-center, observational, retrospective study based on the Jakarta Acute Coronary Syndrome registry in Indonesia. STEMI patients were defined according to the Fourth Universal Definition of Myocardial Infarction from the European Society of Cardiology. ⁹ The inclusion criteria for this study were all STEMI patients undergoing PPCI from the period of January 2014 until December 2019. The exclusion criteria were patients without admission Hb data and/or lack of final TIMI flow data from medical records. Baseline characteristics collected included patient profile (age and gender), medical history and comorbid (smoker, hypertension, diabetes mellitus, dyslipidemia, and family history), anterior infarct, the onset of symptoms, TIMI risk score, laboratory profile (leucocyte, cardiac enzyme, glucose level, and creatinine level), and Killip class.

The no-reflow phenomenon was defined as final TIMI flow after PPCI with values less than 3, and in-hospital mortality was defined as death from all-cause within hospitalization. The study was approved by the Indonesian Ministry of Health Research Ethics Committee (LB.02.01/VII/445/KEP.043/2020).

Statistical analysis was performed using SPSS software for Windows, version 26 (IBM, NY). Categorical variables were stated in frequencies and proportions. Continuous variables were expressed as means + standard deviation or medians with ranges when appropriate. For numeric variables, the differences between the two groups were analyzed with a t -test or Mann–Whitney test, whichever was appropriate. For discrete variables, the differences between the two groups were analyzed with the χ ² or Fisher's exact test, whichever was appropriate. Certain variables such as age, onset of symptoms, creatinine, TIMI risk score, and Killip class were categorized accordingly. Variables with p  < 0.25 in the bivariate analysis were included in multivariate analysis using logistic regression. A two-tailed p -value of <0.05 was considered statistically significant.

Results

From 11,439 patients with acute coronary syndromes from January 1st, 2014 to December 31st, 2019, approximately 3,071 (27%) STEMI patients undergoing PPCI were included in the final study analysis. There were 550 (17.9%) patients who had Hb below the normal range. The picture of the research flow is shown in Fig. 1 .

Fig. 1.

Research flow chart.

Patient Characteristics

Comparison of the baseline characteristics of patients based on the initial Hb grouping based on WHO criteria in the form of anemia and nonanemia groups is presented in Table 1 . Compared with non-anemia group ( n  = 2,521), the anemia group tended to have older age (60 ± 10 vs. 54 ± 10 years, p  < 0.001), TIMI risk score >4 (45.8 vs. 30.4%, p  < 0.001), higher median admission creatinine values (1.15 vs. 1.00 mg/dL, p  < 0.001), lower proportion for anterior infarct event (44.7 vs. 56.9%, p  < 0.001), lower smoking risk factors (50.4 vs. 67.8%, p  < 0.001), a greater proportion of diabetes mellitus (36.7 vs. 27.1%, p  < 0.001), and lower median leukocyte value (11,975 vs. 13,450, p  < 0.001). In addition, the proportion of female sex (20.7 vs. 11.2%, p  < 0.001), Killip class 2 to 4 (25.8 vs. 20.8%, p  = 0.009), and median baseline troponin T (440.5 vs. 346.5, p  = 0.017) were higher.

Table 1. Patient characteristics.

Variable	Missing data	All patient( n  = 3,071)	Non-anemia ( n  = 2,521)	Anemia ( n  = 550)	p -Value
Age, y	0	55 ± 10	54 ± 10	60 ± 10	<0.001
Off hours admission	0	1,953 (63.6%)	1,608 (63.8%)	345 (62.7%)	0.641
Anterior infarct	0	1,680 (54.7%)	1,434 (56.9%)	246 (44.7%)	<0.001
Onset of symptoms ≤2 h	0	110 (3.6%)	88 (3.5%)	22 (4%)	0.560
Onset of symptoms >6–12 h	0	1,217 (39.6%)	987 (39.2%)	230 (41.8%)	0.247
TIMI risk score >4	0	1,018 (33.1%)	766 (30.4%)	252 (45.8%)	<0.001
Women	0	397 (12.9%)	283 (11.2%)	114 (20.7%)	<0.001
Cardiovascular risk
Smoker	0	1,987 (64.7%)	1,710 (67.8%)	277 (50.4%)	<0.001
Hypertension	0	1,670 (54.4%)	1,356 (53.8%)	314 (57.1%)	0.159
Diabetes mellitus	0	885 (28.8%)	683 (27.1%)	202 (36.7%)	<0.001
Dyslipidemia	0	771 (25.1%)	644 (25.5%)	127 (23.1%)	0.229
Family history	0	431 (14.0%)	358 (14.2%)	73 (13.3%)	0.570
First 24 h double antiplatelet
Salisylic acid	0	2,973 (96.8%)	2,446 (97.0%)	527 (95.8%)	0.145
Clopidogrel	0	2,618 (85.2%)	2,144 (85.0%)	474 (86.2%)	0.496
Laboratorium
Leucocyte (/µL)	0	13,170 (10,930–15,770)	13,450 (11,120–15,960)	11,975 (9,997.5–14,762.5)	<0.001
HsTropT (ng/L)	155 (5.0%)	365 (128–1,168)	346.5 (124.75–1,063.25)	440.5 (140–1,510)	0.017
Creatinin (mg/dL)	0	1.02 (0.84–1.28)	1.0 (0.84–1.22)	1.15 (0.86–1.6	<0.001
Blood glucose (mg/dL)	73 (2.4%)	143(120–203)	143 (120–201.5)	144 (118–213.5)	0.810
Echocardiography
Left ventricle ejection fraction (%)	455 (14.8%)	46 (38.7–55)	46 (39–55)	45 (38–54)	0.117
Total ischemic time, min
Door-to-device	540 (17.6%)	75 (60–98)	75 (60–97)	76 (60–100)	0.417
Killip class  Class 1  Class 2–4	0 0	2,405 (78.3%) 666 (21.7%)	1,997 (79.2%) 524 (20.8%)	408 (74.2%) 142 (25.8%)	0.009 0.009

Abbreviation: TIMI, thrombolysis in myocardial infarction.

The Relationship between Anemia and the Incidence of No-Reflow

Patients with low Hb concentrations on admission were not significantly associated with the incidence of no-reflow in STEMI patients who underwent PPCI ( Tabel 2 ). In univariate analysis, anemia showed no significant result ( p  = 0.635), and the incidence of symptom onset >6–12 hours was the only variable that was significantly associated with the incidence of no-reflow ( p  < 0.001) ( Table 2 ).

Table 2. Univariate and multivariate analyses between anemia and the incidence of no-reflow ( n  = 3,071) .

Variable	Univariate analysis		p -Value	Multivariate analysis		p -Value
	OR	CI 95%		OR	CI 95%
Anemia	0.931	0.694–1.250	0.635	0.889	0.654–1.209	0.455
Age ≥65 y	0.945	0.684–1.305	0.732	0.935	0.671–1.304	0.692
Men	0.911	0.660–1.257	0.570	0.940	0.675–1.310	0.716
Diabetes mellitus	1.135	0.893–1.443	0.301	1.110	0.869–1.417	0.403
Onset of symptoms >6–12 h	1.541	1.234–1.925	< 0.001	1.521	1.216–1.902	< 0.001
Creatinin >1.3 g/dL	1.230	0.959–1.578	0.103	1.274	0.982–1.652	0.069
Anterior infarct	1.198	0.957–1.501	0.114	1.191	0.946–1.500	0.137
Killip class >1	1.086	0.834–1.414	0.542	1.000	0.761–1.313	0.998

Abbreviations: CI, confidence interval; OR, odds ratio.

From multivariate analysis, the onset of symptoms >6–12 hours had a significant relationship with the incidence of no-reflow with an odds ratio (OR) of 1.521 (95% confidence interval [CI] = 1.216–1.902, p  < 0.001). For the anemia group, the results were not much different from the univariate analysis with an OR of 0.889 (95% CI = 0.654–1.209, p  = 0.455) ( Table 2 ).

The Relationship between Anemia and the Incidence of In-Hospital Mortality

Patients with low Hb concentrations on admission had higher in-hospital mortality compared with patients with normal Hb concentrations ( Table 3 ). Univariate analysis of anemia with in-hospital mortality showed significant results ( p  = 0.004) with an OR of 1.7 compared with patients without anemia for the incidence of in-hospital mortality ( Table 3 ).

Table 3. Univariate and multivariate analyses between anemia and in-hospital mortality ( n  = 3,071) .

Variable	Univariate analysis		p -Value	Multivariate analysis		p- Value
	OR	CI 95%		OR	CI 95%
Anemia	1.719	1.182–2.499	0.004	0.963	0.635–1.459	0.857
Age ≥65 y	2.494	1.720–3.618	< 0.001	1.686	1.121–2.537	0.012
Men	0.527	0.351–0.790	0.002	0.504	0.321–0.790	0.003
Diabetes mellitus	1.644	1.174–2.304	0.004	1.298	0.903–1.864	0.159
Onset of symptoms >6–12 h	1.046	0.749–1.462	0.790	0.943	0.662–1.343	0.744
Creatinin >1.3 g/dL	4.891	3.494–6.847	< 0.001	3.667	2.552–5.270	< 0.001
Anterior infarct	0.971	0.698–1.349	0.859	0.909	0.635–1.302	0.603
Killip class >1	6.486	4.612–9.122	< 0.001	5.329	3.721–7.633	< 0.001

Abbreviations: CI, confidence interval; OR, odds ratio.

Multivariate analysis showed most related variables to patient mortality were age more than 65 years, creatinine serum 1.3 mg/dL, and Killip class more than 1. Patients with anemia did not show significant results in multivariate analysis with an OR of 0.963 (95% CI = 0.635–1.459, p  = 0.857). Patients with creatinine 1.3 mg/dL had an association with in-hospital mortality with an OR of 2.5 compared with patients with creatinine <1.3 mg/dL. Patients over the age of 65 years had an association with in-hospital mortality with an OR of 1.6 compared with patients aged less than 65 years. Killip class more than 1 in patients had an OR of 5 on in-hospital compared with patients with Killip class 1 ( Table 3 ).

Relationship between Anemia and the Incidence of No-Reflow Associated with In-Hospital Mortality

Patients with low Hb concentrations and no-reflow events had a significantly higher in-hospital mortality than patients with normal Hb concentrations and without no-reflow events ( Tabel 4 ). Univariate analysis of anemia and TIMI flow <3 with in-hospital mortality showed significant results ( p  = 0.014). Patients with anemia and TIMI flow <3 had an OR of 2.6 for the incidence of in-hospital mortality compared with patients without anemia and TIMI flow 3 ( Tabel 4 ).

Table 4. Univariate and multivariate analyses between anemia and no-reflow with in-hospital mortality ( n  = 3,071) .

Variable	Univariate analysis		p -Value	Multivariate analysis		p -Value
	OR	CI 95%		OR	CI 95%
Anemia and TIMI flow <3	2.649	1.183–5.930	0.014	0.939	0.361–2.437	0.896
TIMI flow <3	2.594	1.752–3.841	< 0.001	2.688	1.680–4.301	< 0.001
Age ≥ 65 y	2.494	1.720–3.618	< 0.001	1.713	1.139–2.577	0.010
Men	0.527	0.351–0.790	0.002	0.523	0.332–0.824	0.005
Diabetes mellitus	1.644	1.174–2.304	0.004	1.297	0.899–1.872	0.165
Onset of symptoms >6–12 h	1.046	0.749–1.462	0.790	0.880	0.614–1.260	0.486
Creatinin >1.3 g/dL	4.891	3.494–6.847	< 0.001	3.558	2.484–5.097	< 0.001
Anterior infarct	0.971	0.698–1.349	0.859	0.856	0.595–1.230	0.399
Killip class >1	6.486	4.612–9.122	< 0.001	5.445	3.788–7.827	< 0.001

Abbreviations: CI, confidence interval; OR, odds ratio; TIMI, thrombolysis in myocardial infarction.

In multivariate analysis, the variables most related to in-hospital mortality were anemia patients who had TIMI flow <3, diabetes mellitus, age more than 65 years, serum creatinine level of 1.3 mg/dL, and Killip class greater than 1. After analysis, patients with anemia and TIMI flow <3 showed no significant results with an OR of 0.939 (95% CI = 0.361–2,437, p  = 0.896) after being associated with in-hospital mortality. Patients with the creatinine level of 1.3 mg/dL had an OR of 3.5 for the incidence of in-hospital mortality compared with patients with the creatinine level of <1.3 mg/dL. Patients older than 65 years had an OR of 1.7 for the incidence of in-hospital mortality compared with patients aged less than 65 years. Patients with a Killip class of more than 1 had an OR of 5.4 on the incidence of in-hospital mortality compared with those with a Killip class of 1. Patients with TIMI flow <3 had an OR of 2.6 on an incidence of in-hospital mortality compared with patients with TIMI flow 3 ( Tabel 4 ).

Discussion

In this study, there were 550 STEMI patients (17.9%) who underwent PPCI with low Hb concentration at the time of admission. In the two previous studies, ^{10 11} the ratio between STEMI patients who had anemia and who underwent PPCI and STEMI patients who were not anemic was more than 1:5. Our study results are not much different from the 1:6 ratio of STEMI patients who are not anemic. Patients with low Hb concentrations at admission tended to have a higher age, diabetes mellitus, predominantly female sex, TIMI risk score >4, Killip grade 2 to 4, median creatinine, troponin T, and more than 12 hours of symptom onset compared to patients with normal Hb concentrations. In line with previous studies which stated that the anemia group had an older age profile, ¹² the results of this study also stated that the anemia group had an older age profile (60 ± 10 vs. 54 ± 10 years, p  < 0.001). The gender factor also plays its role in the relationship with the incidence of mortality in STEMI. In the anemia group, women had a higher incidence of in-hospital mortality than women in the non-anemia group, and this result follows the studies of Guo et al ¹³ and Carrabba et al ¹⁴ who assessed the independent effect on female sex associating reperfusion therapy with mortality. Another study from Dreyer et al, ¹⁵ that woman with STEMI were lower rate receiving PCI and had higher long-term mortality. ¹⁵ Coronary microcirculation infiltration by neutrophils and platelets occurs after reperfusion, resulting in a prothrombogenic and proinflammatory state due to endothelial necrosis and activation. An increase in neutrophils is related to many unfavorable outcomes following STEMI. Wang et al ¹⁶ showed that baseline neutrophil was an independent predictor of no-reflow after PPCI in STEMI patients. Furthermore, Kojima et al ¹⁷ in their study reported the importance of baseline leukocytes as an independent predictor of no-reflow and mortality after PPCI in STEMI patients. The study discovered a substantial difference in the occurrence of the no-reflow phenomenon between patients in the highest quartile and patients in the first and second quartile ( p  < 0.05). Highest quartile patients also had a 2.9 higher hazard ratio than those in the lowest quartile for the mortality rate ( p  = 0.02). The STEMI outcomes are strongly influenced by myocardial necrosis site and extent. The necrotic region (often termed as “infarction size”) and the area under the curve of cardiac troponin T (cTnT) strongly associate; thus, cTnT can be considered as a specific marker of myocardial necrosis. ¹⁸ Giannitsis et al ¹⁹ found that TIMI flow <3 more frequently occur in cTnT-positive patients (25%) compared with cTnT-negative patients (9%). Furthermore, the study conducted by Hong et al ²⁰ showed that baseline cTnT was greater in the no-reflow group than in the group with normal flow ( p  = 0.001). In STEMI patients who underwent PPCI, lower levels of Hb can be a signal of severity, as is shown by the higher Killip class and TIMI risk score >4 on admission, in accordance with earlier studies that have shown comparable outcomes in our anemia group. ^{10 21}

The no-reflow phenomenon mechanism can be caused by various factors, including spasm by increased microvascular resistance and microvascular dysfunction, increased inflammatory response, and erythropoietin release which creates a pro-coagulant state ³ or decreased availability of NO. The results of the study by Yaylak et al ⁶ showed an association between anemia and the incidence of no-reflow evaluated from the final TIMI flow. Our study showed different results where there was no relation between the incidence of no-reflow and anemia group ( n  = 550) compared with the group without anemia with an OR of 0.931 (95% CI = 0.694–1.250, p  = 0.635). In several studies that looked at the relationship between anemia and the incidence of no-reflow, there were non-significant results between the two variables, ^{5 10} including the results of our study. Apart from the variation in cut-off values between studies (Yaylak et al ⁶ used Hb 11.5 g/dL generated from the area under the receiver operating characteristic curve in that study), there was the possibility of other mechanisms influencing the incidence of no-reflow because the no-reflow phenomenon is a multifactorial mechanism, such as coronary artery spasm, increased intravascular leukocytes, cellular edema, or the presence of tissue contractures in the ischemic zone compressing the microvasculature may play a role more than the anemia itself.

The results of our study showed that the onset of symptoms for >6 to 12 hours showed significant results with no-reflow events with an OR of 1.521 (95% CI = 1.216–1.902, p  < 0.001). These results do not differ from those of Nallamothu et al, ²² where there was a greater prevalence of incidence and size of the no-reflow area over a longer period associated with reperfusion. Furthermore, by Tarantini et al, ²³ in the study using cardiac magnetic resonance imaging in STEMI patients undergoing PPCI, time to balloon was significantly associated with transmural myocardial necrosis and more severe microvascular obstruction.

Anemia is most common in the elderly, reaching a prevalence of 17% in the elderly group of >65 years. ²⁴ Increasing age has linear correlation with in-hospital mortality in STEMI patients. The underlying mechanism is an increase in the expression of coagulation proteins and inflammatory markers ²⁵ and a shorter erythrocyte life span, all of which increase the incidence of the no-reflow phenomenon in older people. ²⁶ In our study, age of 65 years increased in-hospital mortality with an OR of 1.686 (95% CI = 1.121–2,537, p  = 0.012). In line with the results of Parodiet al, ²⁷ where mortality increased with the age of 70 years both at 30 days (OR 1.067; 95% CI = 1.036–1.099, p  < 0.0001) and 5 years (OR 1.054; 95% CI = 1.039- 1.069, p  < 0.0001). This result was also confirmed by Thompson et al, ²⁸ who found an increase of both myocardial infarction and death from all causes in the first 30 days with an increase in the age group.

The gender factor plays its role in the relationship with the incidence of mortality in acute myocardial infarction. A large-scale meta-analysis conducted by Guo et al ¹³ showed that both in-hospital and 2-year mortality after PPCI in patients with STEMI were lower in males than in females. Furthermore, this result was also obtained in the study of Park et al. ²⁹ who found that women had higher in-hospital mortality than men with an OR of 1.19 (95% CI = 1.05–1.34, p  = 0.006). Not different from the results of the two studies, we found a lower incidence of in-hospital mortality in men compared with women with an OR of 0.504 (95% CI = 0.302–0.790, p  = 0.003). This result is because women have a more adverse cardiovascular risk profile which is an important factor for the high incidence of major adverse cardiac events in female patients with coronary heart disease. ¹³

The adverse impact of clinical outcomes on anemic patients in previous studies showed an increase in mortality in STEMI patients undergoing PPCI with anemia as an independent risk factor that increased short-term or long-term mortality. ⁸ In linear with our study study, from the results of the univariate analysis, STEMI patients who underwent PPCI tend to have a high proportion of intra-care mortality, although after multivariate analysis the results were not significant, probably due to other determinants that were stronger than anemia which affected the incidence of mortality. Similar results were demonstrated by the study by Moghaddam et al ¹⁰ that patients with anemia at admission had a higher likelihood of having comorbid conditions that could predispose to mortality, including advanced age, diabetes mellitus, and previous cardiovascular events. Each of these factors stands alone as a predictor of poorer prognosis in patients with acute coronary syndromes. This association was further attenuated after the inclusion of baseline demographics, comorbidities, clinical status at presentation, and reperfusion time. It can be concluded that anemia on admission may be merely a marker of risk of death but may not directly contribute to death itself.

Final TIMI flow post-PPCI was associated with short-term or long-term patient mortality. ^{2 30} No-reflow phenomenon had a higher risk of in-hospital mortality compared with patients with normal flow (13 vs. 4%, p  < 0.0001). ² Our study also showed higher in-hospital mortality in the group of patients with a final TIMI flow <3. In the multivariate analysis, a TIMI flow <3 was significantly associated with in-hospital mortality. This group of patients had 2.6 times higher in-hospital mortality compared with patients with final TIMI flow 3. Research conducted by Ndrepepa et al ³⁰ showed that patients with no-reflow phenomenon had 1.66 times higher risk of dying compared with patients without the phenomenon. The results of our study are relevant to that research, patients with TIMI flow <3 after the PPCI procedure are significantly associated with in-hospital mortality with heart rate 2.688 (95% CI = 1.680–4301, p  < 0.001). Furthermore, the left ventricular ejection fraction was found to be lower in the no-reflow group. Brain natriuretic peptide levels, a highly sensitive marker of left ventricular dysfunction, were also higher in the no-reflow group. ^{30 31} However, in the anemia and TIMI groups, a final flow rate <3 did not show significant results in our study after multivariate analysis. This may be due to the determination of anemia factor that is not so strong against other factors that influence the incidence of no-reflow.

There are several limitations to this study. This observational study was conducted retrospectively from a single registry. The completeness of the data is one of the limitations of this study. The course of patients with anemia was not followed up on whether interventions such as transfusions were performed and when they were performed and whether this would affect the clinical outcomes during treatment. Patients with low Hb levels also did not have a history of the previous disease, whether the patient had anemia in a short or acute period or whether it was recurrent or chronic. This study did not analyze the condition of acute anemia with a significant decrease in Hb concentration with chronic anemia because it is very difficult to determine clinically. Medication status either at the time of treatment or previous history could not be analyzed due to limited or incomplete data where the role of drugs may affect the patient's clinical course.

Conclusion

Hb concentration at admission was not associated with the incidence of no-reflow and in-hospital mortality of STEMI patients undergoing PPCI.