Bidirectional Causal Association Between Chronic Obstructive Pulmonary Disease and Cardiovascular Diseases: A Mendelian Randomization Study

Background: A large number of studies have demonstrated links between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVDs). However, the causal relationship between COPD and CVDs and the reverse causality remains divergent. Methods: Exposure and outcome data from the largest available genome-wide association studies were extracted for Mendelian randomization (MR) studies. Univariate MR analysis was performed using IVW as the primary analysis method, and multiple sensitivity analyses were used to enhance the robustness of the results. Furthermore, this was followed by mediation MR analysis of positive results after excluding confounding factors with multivariable MR analysis. Results: The MR estimation based on IVW method indicated a strong association between genetically determined COPD and heart failure (HF) (OR = 1.117, 95% CI: 1.066-1.170, p <0.001), coronary heart disease (CHD) (OR = 1.004, 95% CI: 1.002-1.006, p <0.001), essential hypertension (EH) (OR = 1.009, 95% CI: 1.005-1.013, p <0.001) as well as Stroke (OR = 1.003, 95% CI: 1.001-1.004, p <0.001). The results of multivariable MR analysis revealed that COPD is not significantly associated with CHD after adjusting for IL-6, LDL, or total cholesterol (p>0.05). Our findings indicated that BMI, smoking initiation, smoking status, obesity, and FEV1 played a role in the causal effect of COPD on HF, EH, and Stroke. Conclusion: We found positive causal relationships between COPD and HF, EH, and Stroke essentially unaffected by other confounding factors. The causal relationship exhibited between COPD and CHD was influenced by confounding factors. BMI, obesity, initiation of smoking, smoking status, and FEV1 were the mediators between COPD and CVDs.