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Bidirectional Causal Association Between Chronic Obstructive Pulmonary Disease and Cardiovascular Diseases: A
Guangzan Yu1, Lulu Liu1, Qian Ma1
1Cardiac Division of Emergency Intensive Care Unit, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, People's Republic of China.
Insights
This study used Mendelian randomization to investigate the causal links between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVDs). COPD causally increases the risk of heart failure, essential hypertension, and stroke, with BMI and smoking as key mediators.
Area of Science:
- Cardiovascular Research
- Pulmonary Medicine
- Genetic Epidemiology
Background:
- Established links exist between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVDs).
- The precise causal direction and potential reverse causality between COPD and CVDs remain incompletely understood.
Purpose of the Study:
- To elucidate the causal relationship between genetically predicted COPD and various CVDs using Mendelian randomization.
- To identify potential mediating factors in the causal pathway from COPD to CVDs.
Main Methods:
- Utilized large-scale genome-wide association study data for Mendelian randomization (MR) analysis.
- Employed inverse variance weighting (IVW) for primary univariate MR analysis, supplemented by sensitivity and multivariable MR analyses.
- Investigated mediation effects of factors like BMI, smoking status, and FEV1.
Main Results:
- Genetically predicted COPD showed a significant causal association with heart failure (HF), essential hypertension (EH), and stroke.
- The association between COPD and coronary heart disease (CHD) was not significant after adjusting for confounders.
- Body Mass Index (BMI), obesity, smoking initiation, smoking status, and FEV1 were identified as significant mediators.
Conclusions:
- Confirmed positive causal relationships between COPD and HF, EH, and stroke, largely independent of confounding factors.
- The causal link between COPD and CHD appears to be influenced by confounding variables.
- BMI, obesity, smoking behaviors, and lung function (FEV1) mediate the causal effects of COPD on cardiovascular outcomes.
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.
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