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ApoB-containing lipoproteins and the risk of cardiovascular events

last modified Jan 31, 2019 01:27 PM

Dr Brian Ference and colleagues have published a landmark study in JAMA that clarifies the potential clinical benefit of lowering plasma triglycerides.

Although both triglycerides and cholesterol are carried in plasma by ApoB-containing lipoproteins, it is unknown whether lowering triglycerides will reduce the risk of cardiovascular events to the same extent as lowering low-density lipoprotein cholesterol (LDL-C).   

Indeed, all clinical practice guidelines recommend lowering LDL-C to reduce the risk of cardiovascular events, but none recommend lowering triglycerides because it is uncertain if lowering triglycerides will reduce the risk of cardiovascular disease.    
 
Using Mendelian randomization, this study of more than 650,000 participants who experienced >90,000 cardiovascular events found that that the clinical benefit of lowering triglycerides is determined entirely by the corresponding absolute change in ApoB-containing lipoproteins, regardless of the change in plasma triglycerides.

Furthermore, the study found that the clinical benefit of lowering triglycerides was very similar to the clinical benefit of lowering LDL-C per unit change in ApoB, thus suggesting that all ApoB-containing lipoproteins have approximately the same effect on the risk of coronary heart disease.  
 
As a result, the clinical benefit of any lipid-lowering therapy should be proportional to the absolute change in ApoB, regardless of the observed changes in LDL-C, triglycerides, or both.

This study should substantially improve the design of randomized trials evaluating novel triglyceride-lowering therapies currently in development; clarify the role of lowering triglycerides in cardiovascular medicine; and inform clinical practice guidelines for measuring and treating lipids to reduce cardiovascular disease.

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