Predictive value of CHA2DS2‐VASc score for in‐hospital prognosis of patients with acute ST‐segment elevation myocardial infarction undergoing primary PCI

Abstract Background This study aimed to explore the predictive value of CHA2DS2‐VASc score for in‐hospital major adverse cardiac events (MACEs) in ST‐elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary artery intervention. Methods A total of 746 STEMI patients were divided into four groups according to CHA2DS2‐VASc score (1, 2–3, 4–5, >5). The predictive ability of the CHA2DS2‐VASc score for in‐hospital MACE was made. Subgroup analysis was made between gender differences. Results In a multivariate logistic regression analysis model including creatinine, total cholesterol, and left ventricular ejection fraction, CHA2DS2‐VASc score was an independent predictor of MACE as a continuous variable (adjusted odds ratio: 1.43, 95% confidence interval [CI]: 1.27–1.62, p < .001). As a category variable, using the lowest CHA2DS2‐VASc score of 1 as a reference, CHA2DS2‐VASc score 2–3, 4–5, >5 groups for predicting MACE was 4.62 (95% CI: 1.94–11.00, p = .001), 7.74 (95% CI: 3.18–18.89, p < .001), and 11.71 (95% CI: 4.14–33.15, p < .001). The CHA2DS2‐VASc score was also an independent risk factor for MACE in the male group, either as a continuous variable or category variable. However, CHA2DS2‐VASc score was not a predictor of MACE in the female group. The area under the curve value of the CHA2DS2‐VASc score for predicting MACE was 0.661 in total patients (74.1% sensitivity and 50.4% specificity [p < .001]), 0.714 in the male group (69.4% sensitivity and 63.1% specificity [p < .001]), but there was no statistical significance in the female group. Conclusions CHA2DS2‐VASc score could be considered as a potential predictor of in‐hospital MACE with STEMI, especially in males.


| INTRODUCTION
Acute myocardial infarction (AMI), especially ST-elevating myocardial infarction (STEMI), caused by occlusion of the coronary artery, 1 is a fetal disease that represents a major cause of worldwide mortality. The mortality of STEMI has been greatly reduced by the primary percutaneous coronary intervention (pPCI). 2 However, the incidence of major adverse cardiac events (MACE) including heart failure (HF), cardiac rupture, reinfarction, arrhythmia, angina, and death is very high during the in-hospital stage of STEMI patients. 3 So, there is an urgent need to take early action to find predictors of these complications of STEMI and to reduce mortality. CHA 2 DS 2 -VASc score is a clinical decision rule developed by Lip et al., 4 which is clinically used to assess the risk of thromboembolism in atrial fibrillation (AF) patients and guide anticoagulation treatment. 5 This scoring system consists of several factors including HF, hypertension, age, diabetes mellitus (DM), previous stroke or transient ischemic attack, vascular disease, and female gender. 4 In addition to evaluating the thromboembolism risk of nonvalvular AF, it was also proven to be a risk factor for adverse clinical outcomes in stable coronary artery disease (CAD), 6 acute coronary syndrome (ACS), 7 including STEMI 8 and non-ST-elevation myocardial infarction (NSTEMI). 9 However, the prognostic value of the CHA 2 DS 2 -VASc score for MACE in STEMI patients who underwent pPCI remains unclear. Thus, this study aimed to investigate the predictive value of preprocedural CHA 2 DS 2 -VASc score for in-hospital MACE in all subjects, and in subgroups with gender differences.

| Blood sample collecting and laboratory testing
Venous blood samples were obtained from patients by standard venipuncture techniques on admission before the pPCI procedure.      Table 1. Also, we divided the patients into two groups according to CHA 2 DS 2 -VASc score levels (low <2, high ≥2). As shown in Supporting Information: Table 1, the difference in age, smoking, DM, hypertension, family history, gender, hemoglobin, WBC, creatinine, and Fib between the two groups was also statistically significant, respectively. Subgroup analysis was made according to gender difference, the basic characteristics are shown in Supporting Information: Tables 2 and 3.

| Clinical outcomes of adverse cardiovascular events
In-hospital MACE was calculated among all the patients.
Incidence of MACE was 19.2% (143 out of 746 patients), including instances of cardiovascular death (n = 14), angina (n = 49), revascularization (n = 3), reinfarction (n = 4), and new onset of HF (n = 73). The total MACE rate in the high CHA 2 DS 2 -VASc score group was higher compared with that of the low group (22.0% vs. 4.8%, p < .001). Furthermore, the incidence of angina and new-onset HF between the two groups was statistically significant (p < .05 and p = .001, respectively). However, there was no difference in the incidence of death, revascularization, or reinfarction (as shown in Table 2).

| Logistic regression analysis for prediction of MACE
In the multivariate logistic regression analysis model including creatinine, TC, and LVEF, the CHA 2 DS 2 -VASc score was an independent predictor of MACE as a continuous variable (AOR:

| DISCUSSION
The main finding of this study is that the CHA 2 DS 2 -VASc scoring system plays an extra role in the prediction of in-hospital MACE in STEMI patients undergoing pPCI. High scores were independent predictors of total MACE and may be useful for risk stratification. The results of the ROC curve analysis indicated that the CHA 2 DS 2 -VASc score had moderate predictive efficiency for predicting in-hospital MACE and the predictive value of the CHA 2 DS 2 -VASc score for MACE is superior to LVEF and creatinine. Moreover, for subgroup analysis, our data uncovered that the CHA 2 DS 2 -VASc score is associated with the incidence of in-hospital MACE in male patients, but not in the female.
Previously, the CHA 2 DS 2 -VASc score was used in the clinic to assess the risk of thromboembolism in AF patients and guide anticoagulation treatment. 5 A study found that a higher CHA 2 DS 2 -VASc score was associated with a significant increase in 1-year mortality in patients with ACS. 7 They also found that patients with a | 953 CHA 2 DS 2 -VASc score > 5 had the highest 1-year mortality risk, sixfold higher compared to patients with a score of 0-1. 7 Another study by Akboga et al. 9 demonstrated that CHA 2 DS 2 -VASc score was independently associated with a higher risk of in-hospital mortality in NSTEMI patients without AF in a multiple Cox-regression model. Chen et al. 11 found that the CHA 2 DS 2 -VASc score was correlated with the 1-year major adverse cardiocerebral vascular event in 29 452 AMI patients who were discharged alive. Additionally, studies illustrated that CHA 2 DS 2 -VASc scores were significantly associated with hospitalization time and adverse events during hospitalization in STEMI patients. 8,12 In this study, we found that the CHA 2 DS 2 -VASc score was an independent predictor for in-hospital MACE in STEMI patients undergoing pPCI, which is in agreement with previous studies. Our study further elucidated that there is a gender-related difference in CHA 2 DS 2 -VASc score in predicting MACE.
The gender-related difference has been demonstrated to exist in the assessment, treatment, and outcomes of CAD, 13,14 and it has been a hot area of investigation in the past few years. Clinically, female patients are more prone to have atypical symptoms such as pain in the jaw, throat, neck, shoulder, arm, hand, and back, mild pain, and nausea rather than typical chest pain. 15 Moreover, females are older and have more coronary risk factors such as hypertension, diabetes, and stroke than males. [16][17][18] Also, women presenting with AMI had a lower likelihood of receiving guideline-based AMI T A B L E 1 Basic characteristics of patients with CHA 2 DS 2 -VASc score difference.  agreement with previous studies, our study showed that creatinine was independently correlated with short-term in-hospital MACE.
Moreover, we did a subgroup analysis and found that creatinine was also positively correlated with short-term in-hospital MACE in the male group and female group. Further studies to illustrate the difference between mild, moderate, and severe kidney injury on MACE are warranted.

| LIMITATION
There are several limitations to our study. First, all the data of this study came from only one center and a small sample size, multicenter studies including a greater sample size may be needed in the future.
Second, mechanism research was lacking in this study, and further research to fully understand the mechanism behind the association between CHA 2 DS 2 -VASc score and the prognosis of patients who suffered from AMI undergoing pPCI is needed. Third, this is a retrospective study, we hope further prospective study should be made in the future.

| CONCLUSION
In conclusion, this study indicated that the CHA 2 DS 2 -VASc scoring system plays an extra role in the prediction of in-hospital MACE in STEMI patients undergoing pPCI. High scores were an independent predictor of in-hospital MACE and may be useful for risk stratification. Furthermore, for subgroup analysis, our data uncovered that the CHA 2 DS 2 -VASc score is associated with the incidence of MACE in male patients, but not in the female group.