Atrial fibrillation and ischaemic stroke have common risk factors
The results of this study suggest that age, heart failure, hypertension, CKD, creatinine level, aortic atherosclerosis, PWV, and CHADS2 scores are associated with ischaemic stroke and AF.
Previous studies have shown that age, male sex, hypertension, DM, valvular heart disease, heart failure, coronary artery disease, CKD, inflammatory disease, obstructive sleep apnoea syndrome and smoking are common risk factors for AF and ischaemic stroke[9, 11, 12]. Potential risk factors, such as obesity and metabolic syndrome, contribute to the development of AF and atrial cardiomyopathy through a variety of mechanisms . The Framingham Heart Study  pointed out that the lifetime risk of AF was approximately 20% with an optimal risk profile, lower than that with a high-risk profile (38.4%). The UK Biobank study  confirmed that there were significant differences in AF risk between the ideal lifestyle group, the general lifestyle group, and the weak lifestyle group, regardless of genetic risk. As more common risk factors were considered, the association between AF and ischaemic stroke was reduced, suggesting a confounding pattern.
Possible mechanism of ischaemic stroke in patients with coronary artery disease complicated with AF
In patients with coronary heart disease, the univariate analysis showed that AF was associated with ischaemic stroke, while the association between AF and ischaemic stroke decreased or even disappeared after the multivariate analysis, which adjusted for other risk factors. In the subgroup analysis, AF appeared to be a protective factor in the CHADS2 ≥3 subgroup. It is speculated that the risk of ischaemic stroke does not increase after the CHADS2 score reaches a certain threshold in patients with coronary artery disease. These findings suggest that atherosclerotic factors may play an important role in ischaemic stroke in patients with coronary heart disease.
Relationship between atrial fibrillation burden and ischaemic stroke
In this study, the univariate analysis showed that paroxysmal AF was not associated with ischaemic stroke, while nonparoxysmal AF was associated with ischaemic stroke. The trend test showed that with increasing AF burden, the rate of ischaemic stroke increases continuously. These findings suggest that compared with patients with paroxysmal AF, patients with nonparoxysmal AF have a higher risk of ischaemic stroke; that is, AF burden is positively correlated with ischaemic stroke.
Although many studies have found a dose-response relationship between AF load and ischaemic stroke [15-17], not all the results are consistent. The recent KP-Rhythm study identified a higher risk of stroke in the high-load group (>11%, approximately 2.5 h/24 h) . There is no uniform standard for AF burden thresholds that significantly increase the risk of thrombosis [52, 53]. The current guidelines [9, 10] generally consider that if the duration of AF is less than 48 hours, there is no need to perform transoesophageal echocardiography. Regardless of the CHA2DS2-VASc score and the method used to restore the sinus rhythm, cardioversion can be performed without anticoagulation. However, whether the 48-hour threshold applies to all patients with AF is debatable. In addition, a brief episode of subclinical AF doubles the risk of ischaemic stroke in elderly patients . However, there was no significant increase in the risk of ischaemic stroke in young, healthy patients with AF . Additionally, the atrial remodelling seen in animal models of AF occurred at least a week after continuous rapid pacing . Therefore, any atrial changes caused by AF are unlikely to explain the association between a short (6-minute) AF episode and an increased risk of ischaemic stroke . Overall, these conflicting data are insufficient to establish a clear dose-response relationship between AF burden and the risk of ischaemic stroke.
In addition, if AF, an arrhythmia, is the primary cause of thromboembolism, then rhythm control to reduce the AF load should significantly reduce or eliminate the risk of ischaemic stroke. However, in a meta-analysis of eight randomized clinical trials, rhythm control did not affect the risk of ischaemic stroke . The CABANA study, involving 2,204 patients in 126 centres in 10 countries, suggested that catheter ablation of AF, although more effective for rhythm control than drug therapy, also did not reduce the incidence of ischaemic stroke . At present, no large-scale clinical study has demonstrated that maintaining sinus rhythm in patients with AF can prevent ischaemic stroke, and there is no substantial evidence to support the safety of discontinuation of anticoagulant drugs after AF ablation. There is no reliable evidence that AF is a necessary condition for atrial thrombus formation.
Antithrombotic therapy in coronary artery disease patients with atrial fibrillation
Beyond one year after coronary stenting, current guidelines[9, 24-26] have consistently recommended lifelong oral anticoagulant medication without antiplatelet therapy in patients with AF. However, the evidence for discontinuation of antiplatelet therapy in the above guidelines is insufficient, and the above decision was made based on a small number of observational studies . The 2018 ESC guidelines for myocardial revascularization  suggested that aspirin should be taken lifelong for secondary prevention of SCAD after PCI, and even the duration of dual antiplatelet therapy should be extended for acute coronary syndrome (ACS). In patients with AF and SCAD beyond one year after PCI or ACS, the optimal antithrombotic regimen remains uncertain. According to this study of patients with coronary artery disease, there are many risk factors for systemic atherosclerosis, which can cause ischaemic stroke through atrial and nonatrial mechanisms. These patients may require a dual antithrombotic combination of oral anticoagulation and single antiplatelet therapy to avoid systemic embolism and stroke. The OAC-ALONE trial failed to establish the noninferiority of oral anticoagulation alone compared with a regimen of oral anticoagulation and single antiplatelet therapy because patient enrolment was prematurely terminated, leading to an underpowered sample size . The AFIRE study demonstrated that rivaroxaban monotherapy was noninferior to combination anticoagulant therapy for efficacy and superior for major bleeding events in patients with AF and stable coronary artery disease . However, the available evidence falls short of level 1 and class A status, and whether the current recommendation of anticoagulation alone beyond one year after coronary stenting is an optimal strategy remains to be further studied [31, 32].
Study strength and limitations
The innovation of this study is that the object of this study is specifically patients with coronary artery disease, who tend to have a higher degree of atherosclerosis than patients with AF alone, and atherosclerotic factors may play a more significant role in the mechanism of ischaemic stroke.
The limitations of this study are that it was a retrospective cross-sectional study, and ischaemic stroke, CHADS2 score, and AF were measured at the same time. Complex aortic plaques and peripheral artery disease were not examined in these patients, so we cannot calculate the CHA2DS2-VASc score and explore its relationship with ischaemic stroke, which still needs further research.