Introduction
Atrial fibrillation (AF) dominates the field of cardiac arrhythmias by being the most common arrhythmia globally, with a rapidly increasing occurrence and an extensive disease burden [
1,
2]. The paramount risk though for patients with AF remains the high incidence of stroke and other thrombotic events [
3]. Thus, stroke risk assessment with CHA
2DS
2-VASc score [Congestive heart failure, Hypertension, Age ≥75 years (doubled), Diabetes mellitus, prior Stroke, transient ischemic attack, or systemic thromboembolism (doubled), Vascular disease, Age 65 to 74 years, Sex category (female)] is essential to AF management. By recommendation of recent guidelines, an elevated CHA
2DS
2-VASc score necessitates the initiation of oral anticoagulant (OAC) therapy as a protective strategy. Notably, despite acknowledging that the risk of stroke is dynamic, no specific recommendations are made regarding the frequency of reassessments [
4,
5].
As the majority of AF patients are among the elderly population, they present with an inconstant variety of stroke risk-contributing comorbidities [
6]. Yet, the evaluation of their outcomes has been conducted solely with the consideration of baseline risk factors in score validation studies [
7].
In this study we aimed to assess the connection between the accumulation of new-onset comorbidities, depicted as changes in CHA2DS2-VASc score (i.e., Delta CHA2DS2-VASc score) over time, and the incidence of ischemic stroke in a population of AF patients receiving OAC treatment. The prognostic significance of the Delta CHA2DS2-VASc score has not been yet fully understood; therefore, we evaluated its relationship with ischemic stroke occurrence, as opposed to the baseline and follow-up score values.
Discussion
This observational study indicates the dynamic state of stroke risk in patients with AF, as assessed through the CHA2DS2-VASc score. It was found that a substantial proportion (20.6%) of our study cohort developed at least one new comorbidity, other than increasing age, during follow-up. It was also revealed that the majority (83.3%) of patients who experienced an ischemic stroke in the course of follow-up had at least one point increase in their CHA2DS2-VASc score (Delta CHA2DS2-VASc score ≥1). Correspondingly, a greater Delta CHA2DS2-VASc score was indicative of higher risk of stroke occurrence.
The predictive value of Delta CHA
2DS
2-VASc score was firstly assessed in a sample of 31,039 patients with AF, by Chao et al. [
12]. The investigated cohort consisted exclusively of patients without a prescription for OACs or any CHA
2DS
2-VASc score-related comorbidities, other than age and gender. Among them, the ones that experienced an ischemic stroke during follow-up had a significantly higher Delta CHA
2DS
2-VASc score (1.86 vs 0.89,
p<0.001). The authors also revealed the association of higher Delta CHA
2DS
2-VASc scores with a higher risk of stroke, whereas it also performed better as a stroke predictor, when compared to baseline or follow-up CHA
2DS
2-VASc scores. Our study’s findings confirm these associations, except for the better performance of Delta CHA
2DS
2-VASc score in predicting the occurrence of stroke, compared to the follow-up score. However, in our study, follow-up as well as Delta CHA
2DS
2-VASc scores performed significantly better than the baseline score. This finding combined with the not significant correlation of the baseline score with stroke risk, is not in agreement with the guidelines’ recommendation to use the CHA
2DS
2-VASc score for the assessment of stroke risk [
4,
5]. It should be noted though that this is a real-world observational study and non-recognized confounders might have influenced our adjusted analyses. Regardless, our results support the non-static nature of stroke risk in AF and the validity of the CHA
2DS
2-VASc score as a reliable tool for reassessment.
The Delta CHA
2DS
2-VASc score was further evaluated in a retrospective study which included roughly 160,000 AF patients with CHA
2DS
2-VASc score-related comorbidities, although those receiving OACs at baseline were excluded [
13]. A significantly higher risk of stroke was associated with the reclassification of a patient to a higher CHA
2DS
2-VASc score category, during a 10-year follow-up. Additionally, in agreement with our findings, the most recently calculated CHA
2DS
2-VASc score and Delta CHA
2DS
2-VASc score, held a superior predictive role in prognosticating stroke occurrence.
A more recent study appraised the association of Delta CHA
2DS
2-VASc score and the prevalence of stroke, in more than 600,000 individuals [
14]. It was demonstrated that the majority (67.1%) of patients who experienced an ischemic stroke had a Delta CHA
2DS
2-VASc score ≥1. Distinctly, both follow-up and Delta CHA
2DS
2-VASc scores performed better than the baseline score, in outcome predicting, with a slight lead of the follow-up score, which is corroborated by our study.
Evidently, the previous studies enforced strict enrollment criteria to their participants. With the exception of the study by Yoon et al. [
13], the remaining researchers excluded patients with baseline comorbidities from their investigations [
12,
14]. Patients on OAC therapy were notably excluded from all prior analyses. Nevertheless, it is acknowledged that the majority of patients suffering from AF present with several comorbidities and the recipients of OAC treatment account for almost 80% [
15,
16]. Hence, our study aimed to include a more representative sample of patients with non-valvular AF, as they are encountered under real-world circumstances. The involvement of patients with various prior risk-contributing comorbidities, indicated that whatever the previous co-existing conditions, the accumulation of additional ones was associated with an increase in the overall risk of stroke, even when on OAC treatment. These conclusions, however, do not deviate from the preceding ones, while applying to a wider range of patients. The lack of correlation between the risk of stroke and prescription for and adherence to OAC treatment in our study can be explained by the presence of the aforementioned comorbidities, as well as the fact that OAC is a risk-reducing strategy that does not completely eliminate stroke risk [
5].
Interestingly, despite the known association of the sustained types of AF with a higher incidence of CHF [
17], in our cohort, new-onset CHF was not significantly associated with a history of persistent or permanent AF. This finding can be attributed to the high prevalence of pre-existing CHF with comorbid persistent or permanent AF at baseline.
Based on the results of our study, future research should assess the effectiveness of an increased vigilance management strategy for patients with higher-than-baseline follow-up CHA2DS2-VASc scores, with regular reassessments, detailed explanation of the risk for and signs of stroke and maximized efforts to control the associated comorbidities. Furthermore, our primary aim was not the proposition of a novel assessment tool for AF patients, based on the Delta CHA2DS2-VASc score, rather than to highlight the derivation of AF-associated stroke risk from the development of new comorbidities. It is, therefore, essential that stroke risk is reassessed frequently, regardless of the patient’s OAC status, since an updated CHA2DS2-VASc score presents a more reliable risk indicator.
Limitations of the study
The observational nature of the study may involve limitations. The relatively small study sample may be a potential liability compared to previously performed research. However, the less restrictive enrollment criteria allowed a more adequate representation of real conditions. The determination of only two CHA2DS2-VASc scores – baseline and follow-up – without the inclusion of intermediate score values may also pose a limitation. Nonetheless, the follow-up CHA2DS2-VASc score was considered as indicative of the entirety of the patients’ prior and acquired comorbidities. A variety of patient data were provided by the patients themselves. Even though that might had involved limitations, the information regarding their prescribed medication, comorbidities, and mortality was cross-referenced as to its validity through the Greek national prescription registry. Moreover, the low sample size in the higher delta CHA2DS2-VASc score subgroups has resulted in wide confidence intervals in the survival analysis. Despite their statistical significance, results should be interpreted with caution with regards to the stroke risk associated with individual delta score values. The inclusion of participants solely of Greek origin may have resulted in reduced applicability of the findings to other races.
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