Unraveling the causal link between lipidomes and unstable angina pectoris: A Mendelian randomization analysis

Unstable angina pectoris remains a significant global health burden. Understanding the causal relationships between lipidomes and unstable angina pectoris is crucial for preventive strategies. We conducted a Mendelian randomization (MR) analysis to explore these relationships. This study utilized lipidome data from 377,277 participants and included 14,281 unstable angina pectoris cases and 364,801 controls. We applied inverse-variance weighted (IVW) methods for MR analysis, considering 179 lipid species as exposures and unstable angina pectoris as the outcome. This MR analysis investigated the causal relationship between various lipidomes and the risk of unstable angina pectoris using the IVW method. The results revealed that several sterol esters, including those with specific fatty acid compositions, were significantly associated with an increased risk of unstable angina pectoris. Similarly, diacylglycerols, particularly those containing certain fatty acid combinations, demonstrated a significant increase in risk. Multiple triacylglycerols across a range of fatty acid chain lengths and degrees of unsaturation were also linked to higher risk. Additionally, sphingomyelins with specific acyl chain compositions showed significant risk increases, while certain phosphatidylcholines were associated with both increased and decreased risk depending on their fatty acid profiles. Phosphatidylethanolamines and phosphatidylinositols, specifically those with particular fatty acid compositions, also exhibited significant risk increases. Our findings suggest a causal link between specific lipid species and unstable angina pectoris risk, providing valuable insights for future research on the role of lipid metabolism in unstable angina pectoris prevention.