The study population consisted of 6,191 consecutive non-STEMI patients enrolled in the Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH) between November 2011 and March 2015. Patients with no laboratory data or no vital sign were excluded, and 6,157 patients (65±12.4 years, male 69%) were included in the final analysis (Fig. 1).

All patients were categorized into 3 groups by using the median value of N/L (4.42) and the presence of anemia: group I, low N/L & no anemia (n=3,170); group II, no group I or III (n=2,168); group III, high N/L & anemia (n=819).

The KAMIR-NIH was a Korean prospective multicenter data collection registry reflecting real-world treatment practices and outcomes in Asian patients diagnosed with acute myocardial infarction (AMI). The registry includes data from 20 hospitals with facilities for primary PCI and on-site cardiac surgery. Data were collected by a trained study coordinator using a standardized case report from and protocol. All management decisions were at the discretion of the treating cardiologists. Before the initiation or the KAMIR-NIH study, several investigator meetings were held, and a steering committee was selected to standardize the care given in clinical practice to minimize the differences in medical care among the hospitals. The ethics committee at each participating institution approved the study.

Eligible patients were on admission for and non-STEMI, and had ≥1 of the following: electrocardiographic changes consistent with an non-STEMI (defined as ST-segment depression and T-wave inversion of 0.2 mV in 2 contiguous leads), serial increases in serum biochemical markers of myocardial necrosis, and documentation of coronary artery disease (CAD) by coronary angiogram (CAG).2 Patients with ST-segment elevation or presumed new left bundle branch block were excluded, and ST-segment depression being defined as new horizontal or downsloping depression 0.05 mV in 2 contiguous leads. Cut-off value of cardiac troponin was defined as the lowest concentration with a value of coefficient of variation<10%.

CBC values were obtained just after admission, before the patient's transfer to the catheter laboratory. It was possible to collect the data of 99% of all patients. Automated analyzers were used for hematologic measurements. Anemia was defined according to the World Health Organization definition as admission hemoglobin (Hb) level <13 mg/dL in men and <12 mg/dL in women.9

All patients received aspirin ≥100 mg and a loading dose of clopidogrel 300 to 600 mg and unfractionated heparin 50 to 70 U/kg to maintain an activated clotting time of >250 to 300 seconds before or during the procedure. Primary PCI was performed using standard techniques if the coronary anatomy was suitable for angioplasty. Successful PCI was defined as thrombolysis in myocardial infarction (TIMI) grade 3 flow with residual stenosis ≤50% in the infarct-related artery. Multivessel coronary disease was defined as >50% diameter stenosis by quantitative coronary angiography in ≥2 coronary arteries or a left main coronary artery lesion. Coronary artery lesion type was determined according to American College of Cardiology and American Heart Association (ACC/AHA) classification.10 Platelet glycoprotein IIb/IIIa receptor inhibition was at the discretion of the operator. During the in-hospital period and at discharge, patients received essential medical treatment that included β-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or statins. All patients were prescribed lifelong aspirin and clopidogrel (75 mg/day) for 3 to 12 months, depending on stent type. The left ventricular ejection fraction (LVEF) was determined by echocardiography. Impaired renal function was defined as an estimate of the glomerular filtration rate of <60 mL/min/1.73 m², as calculated using Cockcroft vault equation, including age, race, gender, and serum creatinine. Global Registry of Acute Coronary Events (GRACE) risk scores were calculated in all patients.11 Age, initial vital signs (systolic blood pressure [BP] and heart rate [HR]), and Killip classification on admission, ST-segment depression on electrocardiogram, and blood chemistry (baseline serum creatinine) were implemented. Major adverse cardiac events (MACEs) included death, myocardial infarction, repeat PCI and coronary artery bypass grafting.

All statistical analyses were performed using SPSS version 20.0 (SPSS, Inc., Chicago, IL, USA). Categorical variables were presented as number of cases and percentage and continuous variables as means±standard deviations. The relation between 2 continuous variables was assessed using bivariate correlation analysis. Comparative analysis was performed using Student's t-test or analysis of variance for continuous variables and Pearson χ² test or Fisher's exact test for categorical variables. We used TIMI risk score, which is a well-known useful tool for early risk stratification in patients with non-STEMI undergoing primary PCI,12 to assess the prognostic discriminatory capacity of the combined use of Hb level and N/L in patients having higher mortality risk based on the risk score. Also, we used the GRACE score to estimate risk in individual patients. The risk factors included in the TIMI risk score and GRACE score were considered as covariates on logistic regression analysis.

The independent discriminatory capacity of the combined use of Hb level and N/L on short-term mortality was assessed by logistic regression models. Candidate covariates for logistic regression analysis were chosen based on previous medical knowledge and independent of their p value, namely age, gender, diabetes mellitus (DM), hypertension (HTN), previous CAD, systolic BP, HR, Killip class, LVEF, creatinine clearance, multivessel coronary disease, ACC/AHA class. A 2-sided p-value of <0.05 was considered statistically significant for all analyses.

Mean and median values of N/L in all patients were 4.42±5.24 and 2.96, respectively. Mean and median values of Hb in all patients were 13.4±2.25 and 13.7 mg/dL, respectively. Of the 6,157 patients, anemia was found in 1,853 patients (30.1%). The correlation between values of N/L and age was positive but weak. Hb level was correlated moderately with age and decreased with increasing age (Fig. 2).

Baseline characteristics of the patients' groups are listed in Table 1. Group III were older and more frequently female, and had lower body weight, lower body mass index, lower admission blood pressure, more increased HR, higher rates of HTN, lower rates of DM and dyslipidemia, worse LVEF, worse renal function, and more multivessel coronary disease. Group III showed higher GRACE score and Killip class than other groups. Other significant differences included lower rates of history of smoking and lower low-density lipoprotein cholesterol levels.

The baseline coronary angiographic characteristics are shown in Table 2. There are more patients with multivessel disease in group III. Patients in group III less underwent CAG and PCI. In lesion type, there are no significant differences between groups.

During 180-day follow-up, there were 124 in-hospital cardiac death (2.0%), 40 in-hospital non-cardiac death (0.6%) and 87 cardiac deaths (1.4%), 52 non-cardiac death (0.8%) at 180-day. Table 3 showed clinical outcomes in-hospital and 180-day after PCI according to either the presence of anemia or N/L. Patients with anemia or high N/L had worse clinical outcomes for MACEs and deaths in-hospital or at 180-day. When patients were stratified by Hb level and N/L, there was a stepwise association with 180-day mortality (Fig. 3A) and MACEs (Fig. 3B).

Clinical outcomes in-hospital and 180-day after PCI according to 3 groups based on Hb level and N/L are listed in Table 4. There were significant differences on clinical outcomes among 3 groups. The 180-day mortality rate and MACEs were respectively 10-fold, 6-fold higher in group III compared with group I.

The 180-day mortality rates according to 3 groups in patients having higher mortality risk based on TIMI risk score and GRACE score are presented in Fig. 4. The TIMI risk score showed peak mortality in patients with TIMI score 3, 4 (Fig. 4A). GRACE score showed a strong association with mortality in all patients except score 201–220 (Fig. 4B). In MACEs, similar pattern was observed (Fig. 5). The TIMI risk score showed peak MACEs in patients with TIMI score 3, 4 (Fig. 5A). GRACE score showed a strong association with MACEs in all patients except score 141–160, 201–220 (Fig. 5B).

Logistic regression analysis showed the independent prognostic value of the combined use of Hb level and N/L for MACEs (Table 5) and 180-day mortality (Table 6). After adjusting for multiple covariates, the coexistence of pre-procedural anemia and high N/L was still a significant predictor of MACEs after PCI in patients with non-STEMI. In 180-day mortality, after adjustment of age and sex, the coexistence of pre-procedural anemia and high N/L was still a significant predictor of mortality. But, after adjusting for multiple covariates, there was no significant difference among groups to predict mortality in patients with non-STMI undergoing PCI.