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The most common complication of AF is thromboembolism, especially IS. AF-related IS has the characteristics of a high mortality rate and a high disability rate. Because of the combination of high morbidity with a low diagnosis rate of cardiogenic stroke, it is of great significance to accurately identify high-risk patients and give corresponding treatment in time to prevent the occurrence of IS for patients with AF. Currently, there is no risk model that can accurately predict IS in patients with AF. Even the widely used CHA2DS2-VASc score has only moderate predictive value [15]. Therefore, the present study explored the risk factors for IS in patients with NVAF in Xinjiang and provided the basis for further clinical treatment. First, multivariate logistic regression analysis showed that LDL-C/HDL-C > 1.22, smoking and BMI ≥ 24 kg/m2 were independent risk factors for IS in patients with NVAF. Second, principal component regression analysis showed that LDL-C/HDL-C, age, smoking, drinking, LDL-C and hypertension were risk factors for IS in NVAF patients.
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In our study, we found that high LDL-C/HDL-C was an independent risk factor for IS after adjusting for age and other related factors, indicating that high LDL-C/HDL-C may influence the progression of IS through particular pathways. The potential mechanism of the positive correlation between LDL-C/HDL-C and IS in NVAF patients remains unclear, however, there are several possible mechanisms to explain this phenomenon. First, LDL-C/HDL-C indicates the proportion of atherosclerosic and anti-atherosclerotic lipoproteins, which has better predictive power for the development of atherosclerosis. High LDL-C/HDL-C may indicate vulnerability of atherosclerotic plaques, which are prone to plaque rupture and thrombosis and eventually lead to IS. Okuzumi A et al. [16] indicated that LDL-C/HDL-C was significantly correlated with aortic plaques and that a ratio of 2.23 might reflect an increase in the amount of mobile and ulcerative aortic plaques in patients with IS. Second, LDL-C/HDL-C may be closely related to inflammation because HDL-C has anti-inflammatory and antioxidant properties [17], and LDL-C may be correlated with inflammation [18]. The high LDL-C/HDL-C ratio may be due to an increase in inflammatory components and a decrease in the anti-inflammatory and antioxidative components reflected in the denominator or both. Pinto A et al. [19] identified that inflammatory markers, including TNF-α, IL-6 and von Willebrand factor (vWF), were predictors of new-onset IS in patients with chronic NVAF. Inflammation has been confirmed to be associated with left atrial thrombosis in AF patients [20]. Previous studies have found that inflammatory biomarkers were significantly associated with left atrium or left atrial appendage thrombus outcomes in AF patients [21]. In conclusion, LDL-C/HDL-C may cause IS in NVAF patients by promoting atherosclerosis and left atrial or left atrial appendage thrombosis.
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Nicotine and oxygen free radicals in tobacco cause or aggravate vascular endothelial dysfunction, atherosclerosis and hypercoagulability through a variety of mechanisms. These factors can promote thrombosis. Previous studies have shown that smoking increases the risk of thromboembolism or death in AF patients [22–23]. A recent meta-analysis showed that smoking increased the risk of all-cause and cardiovascular death in AF patients but not stroke or thromboembolism events [24]. A multicentre study identified that smoking was associated with atherosclerosis or thromboembolism in elderly patients with NVAF who did not quit smoking [25]. Incorporating smoking as a risk factor for IS in CHADS2 and CHA2DS2-VASc scores could better predict the risk of IS in male patients [26]. The present study found that an increase in BMI is an important risk factor for IS in NVAF patients. Previous studies have shown that BMI is negatively correlated with IS in AF patients [27], which is contrary to the results of the present study. At present, the relationship between obesity and IS remains controversial [27–28]. Large-scale and prospective studies are needed to further explore the impact of BMI on adverse event outcomes in AF patients. We believe that the blood viscosity of obese patients is high and that blood viscosity leads to a decrease in blood flow velocity, which is one of the risk factors for thrombosis.
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Age is an important component of the CHA2DS2-VASc score and is one of the risk factors for IS in AF patients. Previous studies have shown that AF is an ageing disease, and with increasing age, the incidence of AF and stroke increases [29–30]. Alcohol intake is a risk factor for thromboembolism. Studies have found that long-term drinking can cause vascular haemodynamic changes, altered blood viscosity, and enhanced platelet aggregation, which subsequently promote the occurrence of IS [31]. Atherosclerosis Risk in Communities (ARIC) studies found that alcohol consumption was not associated with the composite endpoint of IS or cardiovascular death in AF patients [32]. The Stroke Prevention in Atrial Fibrillation (SPAF) I-III trials found that the incidence of IS in patients with AF who regularly drank a small amount of alcohol was lower than that in patients who did not drink alcohol [33]. In contrast, heavy drinking was associated with a higher risk of IS [34]. Hypertension is closely related to stroke, and active and effective control of blood pressure is an important basis for reducing the incidence of IS [35]. Anti-hypertensive treatment could reduce the incidence of stroke in hypertension patients [36]. In terms of mechanisms, hypertension can cause vascular haemodynamic changes, lead to atherosclerosis, further lead to stenosis of the lumen, and affect the blood supply of brain tissue. At the same time, hypertension can promote the remodelling of left atrial structure and function and eventually lead to atrial fibrosis and electrical activity changes. These changes, together with local or systemic inflammatory reactions, lead to local thrombosis or atherosclerotic thrombosis in the left atrium [37].
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The results showed that the contribution rate of PC1 was the highest (17.27%), and the loads of LDL-C/HDL-C and HDL-C were the highest. HDL-C was negatively correlated with IS, and LDL-C/HDL-C was positively correlated with IS. The contribution rate of PC2 was 14.25%, and the factor load of smoking and drinking was the highest, suggesting that bad living habits are one of the risk factors for IS in AF patients. The PC4 contribution rate was 12.49%. The LDL-C and age factor load were the highest, and they were positively correlated with IS. The contribution rate of PC5 was the lowest (10.78%), and the load of the hypertension factor was the highest, suggesting that blood pressure is the influencing factor of IS in AF patients. These results suggest that in clinical practice, in addition to the classic CHA2DS2-VASc score to assess the risk of AF stroke, we should also pay attention to blood lipid-related parameters, poor living habits and other factors. The blood lipid-related parameters include LDL-C/HDL-C, which comprehensively considers the impact of LDL-C and HDL-C parameters on stroke and is a better indicator than either measure alone.
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In conclusion, we found that LDL-C/HDL-C, smoking, BMI, age, alcohol consumption, LDL-C and hypertension were risk factors for IS in NVAF patients. LDL-C/HDL-C is the most important risk factor, which indicates that LDL-C/HDL-C may help identify AF individuals who are at high risk of IS and who may benefit from intensive LDL-lowering therapy. In clinical practice, AF patients often have various diseases, such as hypertension, diabetes, coronary atherosclerotic heart disease, etc., which create challenges for the overall management of AF for medical staff. In addition to focusing on the CHA2DS2-VASc score, we should also pay attention to factors such as blood lipid levels, smoking and drinking in AF patients, carry out comprehensive health education, strengthen interventions for unhealthy lifestyles and formulate comprehensive management measures to reduce the incidence rate and harm of IS.