Association of triglyceride and cholesterol content in fourteen lipoprotein subfractions with coronary heart disease: A mendelian randomisation analysis

Background and Aims : The causal relevance of the cholesterol and triglyceride (TG) content of lipoproteins other than low-density lipoproteins (LDL-C) in coronary heart disease (CHD) is uncertain.Results: Univariable MR indicated a causal association with CHD of the TG content of six lipoprotein subfractions and the cholesterol content of 10 lipoprotein subfractions. In MVMR analysis, the TG content of four subfractions displayed associations with CHD independently of the cholesterol content in the same subfraction, while the cholesterol content of 10 subfractions displayed a causal association with CHD independent of the TG content of the corresponding subfractions. The cholesterol but not the triglyceride content in subfractions referred to as triglyceride-rich lipoproteins (TRL) displayed the largest association with CHD (MVMR odds ratio [OR] 2.73 to 14.31 per 1 SD increase in the subfraction), though the large effect estimates may reflect model instability.Conclusions: The cholesterol and TG content of certain lipoprotein subfractions other LDL may contribute to risk of CHD and may be relevant risk factors to target in drug development. Background and Aims : The causal relevance of the cholesterol and triglyceride (TG) content of lipoproteins other than low-density lipoproteins (LDL-C) in coronary heart disease (CHD) is uncertain. Results: Univariable MR indicated a causal association with CHD of the TG content of six lipoprotein subfractions and the cholesterol content of 10 lipoprotein subfractions. In MVMR analysis, the TG content of four subfractions displayed associations with CHD independently of the cholesterol content in the same subfraction, while the cholesterol content of 10 subfractions displayed a causal association with CHD independent of the TG content of the corresponding subfractions. The cholesterol but not the triglyceride content in subfractions referred to as triglyceride-rich lipoproteins (TRL) displayed the largest association with CHD (MVMR odds ratio [OR] 2.73 to 14.31 per 1 SD increase in the subfraction), though the large effect estimates may reflect model instability. Conclusions: The cholesterol and TG content of certain lipoprotein subfractions other LDL may contribute to risk of CHD and may be relevant risk factors to target in drug development.