Abstract

Key Points

• The prognostic value of the CHA₂DS₂-VASc score in patients with stroke is unclear, especially in patients without AF.

• The rate of MACE was statistically significantly higher in patients with CHA₂DS₂-VASc scores greater than 2 than in patients with scores of 0 through 2.

• The risk for MACE in patients with CHA₂DS₂-VASc scores of at least 2 were 3.22 higher than patients with scores of 0 and 1.92 times higher than patients with scores of 1.

• The CHA₂DS₂-VASc scoring system provides a simple but very useful way to stratify risk for patients with stroke but without AF.

Abbreviations

AF

atrial fibrillation

AIS

acute ischemic stroke

BMI

body mass index

CHA₂DS₂-VASc

congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65-74 years, and female sex

HF

heart failure

HR

hazard ratio

MACE

major adverse cardiovascular events

PSM

propensity score matching

TIA

transient ischemic attack

TOAST

Trial of ORG 10172 in Acute Stroke Treatment

Introduction

Stroke is the most common cause of mortality and disability in China.¹ Although there have been substantial improvements in stroke care in past decades, long-term prognosis is still a challenge. Five years after a stroke, poor outcomes (death or disability) were found in 70.6% of patients with acute ischemic stroke (AIS).² Early screening and active treatment are therefore required to improve prognosis.

The CHA₂DS₂-VASc (congestive heart failure [HF], hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack [TIA], vascular disease, age 65-74 years, and female sex) scoring system is normally used for the prediction of thromboembolic risk in patients with atrial fibrillation (AF).³ Considering that many of the individual components included in the CHA₂DS₂-VASc score have been reported as risk factors for stroke, some studies have explored the predictive value of CHA₂DS₂-VASc scores in poststroke prognosis.^1,4 There is a research gap, however, when it comes to the application of this predictive value because of short-term follow-up and limited studies, especially in patients with stroke but without AF.

This study evaluated the association of CHA₂DS₂-VASc score with 1-year major adverse cardiovascular events (MACE) in patients with AIS but without AF.

Patients and Methods

This retrospective study included consecutive patients with AIS admitted to the study hospital between January 2019 and December 2022. Patients were included if they (1) were aged 18 years or older, (2) were diagnosed with AIS by computed tomography or magnetic resonance imaging, (3) had no diagnosis of AF, and (4) had complete CHA₂DS₂-VASc score data at admission. This study was approved by the Ethics Committee of Tinglin Hospital (approval No. 2023026). All procedures involving human participants were performed according to the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. As this was a retrospective study, the Ethics Committee of Tinglin Hospital waived the need for informed consent. All data were fully anonymized and kept confidential.

Patients’ baseline demographic profiles, medical histories, CHA₂DS₂-VASc scores, Trial of ORG 10172 in the Acute Stroke Treatment (TOAST) categories, and medications at discharge were retrieved by reviewing medical records. Demographic profiles included data for age, sex, body mass index (BMI), and smoking habits. Medical history included diagnoses of hypertension, dyslipidemia, diabetes, stroke or TIA, HF, and vascular disease. The CHA₂DS₂-VASc score was calculated for all patients during their index hospitalization, and patients were allocated to 1 of 3 groups according to their score: low risk (score, 0-1), moderate risk (score, 2), and high risk (score, >2). This classification has been used in several previous studies to explore the association of CHA₂DS₂-VASc score with prognosis in populations with and without AF.^5,6

The primary outcome of this study was the rate of MACE within 12 months of enrollment, a rate that included data for all-cause mortality, myocardial infarction, and recurrent stroke. The secondary outcomes were the occurrences of all-cause mortality and recurrent stroke within 12 months. The outcomes were collected from medical records and telephone interviews.

Results

The baseline characteristics of patients in the 3 groups before and after PSM are presented in Table I. Before PSM, a total of 933 patients were included and categorized into high-risk (n = 424), moderate-risk (n = 218), and low-risk (n = 351) groups based on their CHA₂DS₂-VASc scores. Statistically significant differences were observed in age, sex, BMI, smoking status, medical history (hypertension, dyslipidemia, diabetes, stroke or TIA, HF, and vascular disease), large artery atherosclerosis, and antihypertension agents among the 3 groups (all P < .01). After PSM, 159 patients were included in each group, and differences in all baseline characteristics were no longer statistically significant.

TABLE I.Baseline Characteristics of the Study Population According to CHA₂DS₂-VASc Score Before and After PSM

View Fullscreen

The median (IQR) follow-up time was 365 (340-376) days. In the overall population, the rate of MACE during this 12-month follow-up was statistically significantly higher (P < .01) in patients with a CHA₂DS₂-VASc score greater than 2 (34.7%) compared with patients with a score of 2 (23.9%) and with a score of 0 or 1 (14.8%). As shown in Figure 1, the Kaplan-Meier survival curve showed that compared with patients with a CHA₂DS₂-VASC score of 0 or 1, the risks of MACE, all-cause mortality, and recurrent stroke were statistically significantly higher in patients with a score of at least 2 (all P < .01). After PSM, the risks of MACE, all-cause mortality, and recurrent stroke remained statistically significantly higher in patients with a CHA₂DS₂-VASC score of at least 2 (all P < .01).

View Figure

• Download as Powerpoint
• Download Figure

Multivariate Cox proportional hazard regression analysis was performed to identify prognostic factors associated with the risk of outcomes (Table II). After adjusting for potential confounding factors, compared with a CHA₂DS₂-VASc score of 0 or 1, the hazard ratio (HR) of MACE occurrence was 3.22 (95% CI, 1.93-5.37; P < .01) for a score greater than 2 and 1.92 (95% CI, 1.24-2.98; P < .01) for a score of 2. The risks for all-cause mortality (>2 vs 0-1: HR, 3.47 [95% CI, 1.84-6.56], P < .01; 2 vs 0-1: HR, 2.04 [95% CI, 1.18-3.53], P =.01) and recurrent stroke (>2 vs 0-1: HR, 2.39 [95% CI, 1.25-4.56], P < .01; 2 vs 0-1: HR, 1.87 [95% CI, 1.10-3.20], P = .02) were also statistically significantly increased for the high-risk and moderate-risk groups. When the CHA₂DS₂-VASc score was treated as a continuous variable in the Cox regression model, an increase of 1 point in the CHA₂DS₂-VASc score was associated with a 1.19-fold increase in the risk of MACE (95% CI, 1.11-1.26; P < .01), a 1.14-fold increase in the risk of all-cause mortality (95% CI, 1.05-1.23; P < .01), and a 1.15-fold increase in the risk of recurrent stroke (95% CI, 1.06-1.256; P < .01). Sensitivity analyses based on populations generated by PSM yielded similar results.

TABLE II.Univariate and Multivariate Cox Regression for Exploring the Association of CHA₂DS₂-VASc Score and Prognosis at 12 Months in the Population Before and After PSM

View Fullscreen

Discussion

The present study indicated that CHA₂DS₂-VASc score was independently related to MACE in patients with AIS but without AF during a 12-month follow-up period. This finding is of clinical relevance as CHA₂DS₂-VASc score can be easily calculated, thereby offering a simple but reliable tool for risk assessment after stroke.

The CHA₂DS₂-VASc score was originally developed to refine the assessment of stroke risk in patients with AF.⁷ This scoring system has subsequently been associated with poor clinical outcomes in various cardiovascular diseases.⁸ Mitchell et al⁹ and Koene et al¹⁰ found that CHA₂DS₂-VASc scores effectively predicted ischemic stroke risk in patients with acute coronary syndrome but without AF and in community-dwelling individuals without AF, respectively. Studies by Perna et al¹¹ and Harb et al¹² provide additional evidence supporting the value of the CHA₂DS₂-VASc score. Perna and team's research¹¹ underscores the broader applicability of the score beyond AF, emphasizing its role in predicting cardiovascular events in patients with underlying heart conditions. Findings by Harb and colleagues¹² further validate the CHA₂DS₂-VASc score as an effective tool for stratifying patients based on future cardiovascular risk, regardless of the presence of AF and anticoagulation status.

An increasing number of studies have explored the predictive value of CHA₂DS₂-VASc score in prognosis after stroke, but the conclusions are inconsistent. In a study conducted by Lee et al,¹ an increase of each point in the CHA₂DS₂-VASc score corresponds with a 1.10-times-higher (95% CI, 1.06-1.15) risk of MACE within 1 year in patients with AIS and AF. In another study involving patients both with and without AF, a CHA₂DS₂-VASc score of at least 2 was associated with higher risks for death and serious adverse cardiac events after 3 months.⁵ Ntaios et al⁶ demonstrated that CHA₂DS₂-VASc scores predict long-term outcomes in patients with stroke but without AF. Their findings indicate that patients in the intermediate-risk and high-risk subgroups faced a 3.56-fold increase in mortality risk, a 2.93‑fold increase in the risk for stroke recurrence, and a 2.71-fold increase in the risk for cardiovascular events over a 5-year follow-up period. Yang et al,¹³ however, reported that the CHA₂DS₂-VASc score cannot predict both mortality and recurrent stroke in patients with stroke but without AF. The current study showed that even in patients with stroke but without AF, a higher CHA₂DS₂-VASc score was still statistically significantly associated with an increased risk for poor outcomes.

A study by Chua et al¹⁴ adds another important layer to this discussion. In their observational study among patients with acute coronary syndrome, the authors demonstrated that both CHADS₂ (congestive HF; hypertension; age ≥75 years; diabetes; and stroke, TIA, or thromboembolism) and CHA₂DS₂-VASc scores were statistically significant predictors of adverse events such as myocardial infarction, stroke, and death within 1 year of discharge. They found that the CHA₂DS₂-VASc score performed better than the CHADS₂ score, with an improvement in the area under the receiver operating characteristic curve from 0.66 to 0.70, which suggests that the CHA₂DS₂-VASc score is a more accurate tool for predicting cardiovascular outcomes, even in populations without AF.

These studies, including the current one, illustrate the consistent value of the CHA₂DS₂-VASc score in predicting adverse cardiovascular outcomes. Although traditionally used in populations with AF, its application in broader contexts, such as for patients with acute coronary syndrome and patients with stroke but without AF, is supported by growing evidence. This scoring system offers clinicians a practical, noninvasive method for identifying high-risk patients and potentially optimizing management strategies to reduce the risk of subsequent adverse events.

Conclusion

The CHA₂DS₂-VASc score is a strong and independent risk predictor of 1-year MACE in patients with AIS but without AF. Increased use of the CHA₂DS₂-VASc scoring system may therefore help improve the holistic clinical assessment of AIS, even in patients without AF.