Exploration of the Causal Relationship between Plasma Lipids and Heart Failure Based on the Mendelian Randomization Method
LIU Zonglian
CUI Yangyang
XIONG Lijuan
DU Linqin
Ofe Eugene Kwaku
ZENG Lang
LI Shikang
YUE Rongchuan
Abstract：Objective:To investigate the causal relationship between plasma lipids and the risk of developing heart failure.Methods:The relationship between 179 lipids and heart failure was analyzed using a bidirectional,two-sample Mendelian randomization approach.The inverse variance weighted(IVW)method was used as the primary analysis,and the results were validated through heterogeneity testing,sensitivity analysis,and Bayesian weighted Mendelian randomization(BWMR)analysis.Results:The IVW results of forward MR analysis showed that sterol ester(27:1/22:6)(OR=0.947,95%CI 0.904-0.992,P=0.023),phosphatidylcholine(14:0_18:1)(OR=0.940,95%CI 0.893-0.990,P=0.020),phosphatidylcholine(15:0_18:1)(OR=0.939,95%CI 0.894-0.985,P=0.011)were negatively correlated with heart failure.While diacylglycerol(18:1_18:3)(OR=1.055,95%CI 1.008-1.105,P=0.021),phosphatidylcholine(16:0_20:1)(OR=1.092,95%CI 1.013-1.178,P=0.022),phosphatidylcholine(17:0_18:1)(OR=1.102,95%CI 1.043-1.164,P=0.001),phosphatidylcholine(O-16:1_20:3)(OR=1.050,95%CI 1.007-1.095,P=0.023),triacylglycerol(50:1)(OR=1.060,95%CI 1.015-1.106,P=0.008),triacylglycerol(51:3)(OR=1.058,95%CI 1.016-1.102,P=0.006)were positively correlated with heart failure.The heterogeneity test,sensitivity analysis,and BWMR method confirmed the reliability of the results.The IVW results of reverse MR analysis showed a positive causal relationship between heart failure and triglyceride(50:1)(OR=1.233,95%CI 1.016-1.497,P=0.034),However,there was no causal relationship with the other 8 lipids(P＞0.05).Conclusion:Sterol ester(27:1/22:6),phosphatidylcholine(14:0_18:1),and phosphatidylcholine(15:0_18:1)are protective factors for heart failure;Diacylglycerol(18:1_18:3),phosphatidylcholine(16:0_20:1),phosphatidylcholine(17:0_18:1),phosphatidylcholine(O-16:1_20:3),triacylglycerol(51:3)are risk factors for heart failure,However,there was an interaction between heart failure and triacylglycerol(50:1).
Keywords：heart failureplasma lipidsMendelian randomizationcausality
Publication Date：2026-02-25
Online Publishing Date：2026-03-16(First online date of this platform, not the publication date of the document)
Pages：15( 493-507 )