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Mendelian randomization of chronic hepatitis B and cardiovascular disease
Dongjie Wu1, Feiyang Xiong2, Qingzhi Ran3
1Department of Infectious Diseases, Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing, China.
Insights
Chronic hepatitis B (CHB) increases the risk of atherosclerosis and coronary heart disease. However, CHB is associated with a reduced risk of ischemic stroke, challenging previous observational findings.
Area of Science:
- Cardiovascular Epidemiology
- Hepatology
- Genetics
Background:
- Observational studies suggest a link between chronic hepatitis B (CHB) and cardiovascular disease (CVD), but causality is unclear.
- Inconsistent findings necessitate robust methods to establish a causal relationship between CHB and various CVDs.
Purpose of the Study:
- To investigate the potential causal association between CHB and CVD using Mendelian randomization (MR).
- To examine the relationship between CHB and specific cardiovascular outcomes: atherosclerosis, coronary heart disease, hypertension, and ischemic stroke.
Main Methods:
- Employed two-sample Mendelian randomization (MR) analysis.
- Utilized genome-wide association studies (GWAS) data for exposure (CHB) and endpoints (CVDs).
- Applied inverse-variance weighted (IVW) as the primary method, supplemented by weighted median, MR-Egger, and other MR techniques.
Main Results:
- Genetic susceptibility to CHB was significantly associated with increased risk of atherosclerosis (OR=1.048, P=3.08E-04) and coronary heart disease (OR=1.039, P=0.020).
- CHB showed an inverse correlation with the risk of ischemic stroke (OR=0.972, P=4.13E-04).
- No significant association was found between CHB and hypertension (OR=1.021, P=0.121).
Conclusions:
- Chronic hepatitis B is causally linked to an elevated risk of atherosclerosis and coronary heart disease.
- CHB is associated with a reduced risk of ischemic stroke, indicating a complex relationship with cardiovascular outcomes.
Background:
Evidence from observational studies suggests that chronic hepatitis B (CHB) is associated with cardiovascular disease (CVD). However, results have been inconsistent and causality remains to be established. We utilized two-sample Mendelian randomization (MR) to investigate potential causal associations between CHB and CVD, including atherosclerosis, coronary heart disease, hypertension, and ischemic stroke.
Methods:
The analysis was conducted through genome-wide association studies (GWAS), considering chronic hepatitis B as the exposure and cardiovascular disease as the endpoint. The primary method for evaluating causality in this analysis was the inverse-variance weighted (IVW) technique. Additionally, we employed the weighted median, MR-Egger regression, weighted mode, and simple mode methods for supplementary analyses. Finally, heterogeneity tests, sensitivity analyses, and multiple effects analyses were conducted.
Results:
In a random-effects IVW analysis, we found that genetic susceptibility to chronic hepatitis B was associated with an increased risk of atherosclerosis [OR = 1.048, 95% CI (1.022-1.075), P = 3.08E-04], as well as an increased risk of coronary heart disease [OR = 1.039, 95% CI (1.006-1.072), P = 0.020]. However, it was found to be inversely correlated with ischemic stroke risk [OR = 0.972, 95% CI (0.957-0.988), P = 4.13E-04]. There was no evidence that chronic hepatitis B was associated with hypertension [OR = 1.021, 95% CI (0.994-1.049), P = 0.121].
Conclusion:
Our research indicates that chronic hepatitis B has a correlation with an elevated risk of developing atherosclerosis and coronary heart disease, while it is associated with a decreased risk of experiencing an ischemic stroke.
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