Causal Relationship Between Lipids and Heart Failure Risk and Mediating Effect of Coronary Artery Disease:A Mendelian Randomization Study
Objective A univariable Mendelian randomization(MR)analysis was conducted to explore the causal relationship between lipids and the risk of heart failure(HF)and the potential mediating effect of coronary artery disease(CAD).Methods The inverse-variance weighting was mainly applied for the MR analysis to examine the causal relationship between blood lipids(triglyceride,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,apolipoprotein A1 and apolipoprotein B)and HF in European population.Additionally,mediation analysis was conducted to investigate the potential mediating effect of CAD.Results The results of the univariable MR analysis revealed a significant association between blood lipids and the risk of HF.Elevated levels of triglyceride(OR=1.15,95％CI 1.09～1.21),low-density lipoprotein cholesterol(OR=1.15,95％CI 1.05～1.25)and apolipoprotein B(OR=1.16,95％CI 1.07～1.26)were significantly associated with increased risk of HF.In addition,this analysis showed that elevated high-density lipoprotein cholesterol(OR=0.88,95％CI 0.84～0.93)and apolipoprotein A1(OR=0.92,95％CI 0.87～0.97)were inversely associated with the risk of HF.Sensitivity analysis confirmed the robustness of these results.The results of the mediation analysis showed that CAD partially mediated the causal relationship between the above lipid indices(triglyceride,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,apolipoprotein A1 and apolipoprotein B)and the risk of HF(10.63％,16.72％,18.78％,16.14％and 23.82％,respectively).Conclusion MR indicates that elevated levels of triglyceride,low-density lipoprotein cholesterol and apolipoprotein B increase the risk of HF,whereas higher levels of high-density lipoprotein cholesterol and apolipoprotein A1 may reduce this risk.CAD partially mediates this causal relationship.
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