An ABC of apolipoprotein C‐III: a clinically useful new cardiovascular risk factor?

Summary Background:  Hypertriglyceridaemia, commonly found in subjects with obesity and type 2 diabetes mellitus, is associated with increased risk of coronary heart disease (CHD). Apolipoprotein C‐III (apoC‐III) plays an important role in regulating the metabolism of triglyceride‐rich lipoproteins (TRLs) and may provide a new approach to assessing hypertriglyceridaemia. Aims:  We review the role of apoC‐III in regulating TRL metabolism and address the potential importance of apoC‐III in clinical practice. Discussion:  Hypertriglyceridaemia is chiefly a consequence of alterations in the kinetics of TRLs, including overproduction and delayed clearance of very‐low density lipoprotein (VLDL). ApoC‐III is an inhibitor of lipoprotein lipase and of TRLs remnant uptake by hepatic lipoprotein receptors. Elevated apoC‐III, usually resulting from hepatic overproduction of VLDL apoC‐III, may cause accumulation of plasma TRLs leading to hypertriglyceridaemia. The results from recent observational studies demonstrate that apoC‐III is a strong predictor of risk for CHD, but this chiefly relates to apoC‐III in apoB‐containing lipoproteins. Lifestyle and pharmacological intervention can correct hypertriglyceridaemia by a mechanism of action that regulates apoC‐III transport. Conclusions:  Targeting apoC‐III metabolism may therefore be an important, new therapeutic approach to managing dyslipidaemia and CHD risk in obesity, insulin resistance and type 2 diabetes mellitus. However, further work is required to establish the practical aspects of measuring apoC‐III in routine laboratory service and the precise therapeutic targets for serum total apoC‐III and/or apoC‐III in apoB‐containing lipoproteins. While showing much promise as a potentially useful cardiovascular risk factor, apoC‐III is not yet ready for prime time use in clinical practice.