Coronary heart disease (CAD) and atrial fibrillation, the most common cardiovascular diseases and arrhythmia, respectively, have become significant threats to human health. The correlation between the two has been confirmed by a large number of studies [31–33]. The main risk factors for atrial fibrillation include age, race, blood lipid levels, obesity, hypertension, and certain lifestyle factors, which are also risk factors for coronary heart disease [34–36]. Among them, blood lipid levels are an established risk factor for coronary heart disease. In recent years, the relationship between blood lipid levels and atrial fibrillation has also become a research hotspot [16, 17]. Both coronary heart disease and atrial fibrillation show strong genetic correlations. This study attempted to explore the internal connection between coronary heart disease and atrial fibrillation through the differences in the expression of blood lipids and the regulatory gene APOE in patients with coronary heart disease and atrial fibrillation.
In the comparison of clinical data, it was found that, compared with the control group, the age of patients with AF or CAD was significantly higher, and the proportion of male, hypertension, diabetes, smoking, and BMI were significantly higher in CAD patients. In CAD patients, the age of patients with AF was significantly higher compared with patients without AF. This is in line with the epidemiological manifestations of coronary heart disease and atrial fibrillation [29, 30]. Our study found that compared with the control group, the TC, LDL-C, and Lp (a) levels of patients with CAD were significantly increased, and HDL-C was significantly reduced. Since TG has been controversial in recent years, it is worth nothing that although the number of patients with coronary heart disease were found to have an increasing trend in this study, no statistical significance was found. Recently, a report from Navar AM  has attracted much attention. This study pointed out that hypertriglyceridemia should not be regarded as a single entity but should be regarded according to the multiple conditions of total particle number and composition, which seems to explain the ongoing controversy over TG in the research of coronary heart disease. Research data on the relationship between blood lipid levels and atrial fibrillation have been inconclusive and controversial. Among the studies, the study of Jiang Q, et al.  seems more convincing. They used Mendelian random methods to assess the risk of blood lipid levels and atrial fibrillation. Regarding causality, large-scale MVMR studies have shown that there is a positive causal relationship between high Lp (a) levels and an increased risk of atrial fibrillation. Similar to results of this study. Among CAD patients, the Lp (a) levels of patients with AF was significantly higher compared with the patients without AF. However, in patients without CAD, the Lp (a) levels of patients with AF did not show significant differences. This may be caused by the relatively low sample size of patients or different comorbid diseases, which requires more data from large samples for further discussion.
Next, we compared the expression of APOE genotypes in each group. Compared with the control group, the frequency of E3/E4, E4/E4 and ε4 genotypes in CAD patients increased significantly, and the frequency of E3/E3 and ε3 genotypes decreased significantly. This is similar to the results of previous studies [25, 26] that indicated that the APOE genotype is closely related to the occurrence and development of CAD. It is worth noting that among CAD patients, the frequency of ε4 in patients with AF was significantly higher than that in patients without AF. Previous studies on AF and APOE are lacking, and currently, studies mainly focus on cerebrovascular diseases, especially studies on Alzheimer’s disease [27, 28, 39, 40]. Falsetti L, et al.  has shown that in Alzheimer's disease, the ε4 genotypes of AF was associated with a higher risk of rapid cognitive deterioration. Another population-based CAIDE study from Finland  showed that AF was an independent risk factor for dementia and Alzheimer's disease, and this association was related to the ε4 genotype. Similar to these results, it seems that ε4 plays an important role in patients with CAD and AF.
APOE is an apolipoprotein gene, and ε4 carriers have been shown to have higher TC and Lp (a) levels [41, 42]. This study found that in CAD patients, Lp (a) levels in the with ε4 group were significantly higher than that in the group without ε4. Although the subsequent Spearman correlation analysis showed that there was a significant correlation between ε4 carriers and Lp (a) levels, the correlation coefficient was low. Therefore, we included Lp (a) levels, the ε4 genotype and other possible risk factors in the multiple logistics regression analysis. The results indicate that age and Lp (a) levels may be independent risk factors for CAD patients to develop AF, which is a brand new idea that provides information for coronary heart disease with atrial fibrillation.
There are some shortcomings in this study. First, this was a single-center study, and the ethnicity of the patients was Han, which leads to a lack of universal representativeness of the research results. In addition, we did not observe similar results when comparing AF in patients with CAD to patients without CAD. At present, we could not provide a satisfactory explanation. Future multicenter or larger sample studies are needed to further clarify this hypothesis.