Causal associations between chronic obstructive pulmonary disease and cardiovascular diseases: a Mendelian randomization study

Abstract

Abstract Background A large number of studies have demonstrated links between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVDs). Due to the presence of numerous shared risk factors, it is currently unknown whether there is an independent or reverse causal relationship between the two. 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 methods, and multiple sensitivity analyses were used to enhance the robustness of the results. This was further 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 HF (OR = 1.12, 95%CI: 1.07–1.17, p = 3.15E-06), CHD (OR = 1.00, 95% CI: 1.00–1.01, p = 4.03E-05), EH (OR = 1.01, 95%CI: 1.01–1.01, p = 3.48E-06) as well as Stroke (OR = 1.00, 95% CI: 1.00–1.00, p = 3.14E-05). The results of multivariable MR analysis revealed that COPD is not significantly associated with CHD after adjusting for IL-6 or 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. Conclusions We found positive causal relationship between COPD and HF, EH, 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.