Residual Atherosclerotic Cardiovascular Disease Risk: Focus on Non-High-Density Lipoprotein Cholesterol

Cardiovascular disease (CVD) caused by atherosclerosis is the leading cause of death worldwide. The level of low-density lipoprotein cholesterol (LDL-C), considered as the initiator of atherosclerosis, is the most widely used predictor for CVD risk and LDL-C has been the primary target for lipid-lowering therapies. However, residual CVD risk remains high even with very low levels of LDL-C. This residual CVD risk may be due to remnant cholesterol, high triglyceride levels, and low high-density lipoprotein cholesterol (HDL-C). Non-high density lipoprotein cholesterol (non-HDL-C), which is calculated as total cholesterol minus HDL-C (and represents the cholesterol content of all atherogenic apolipoprotein B-containing lipoproteins), has emerged as a better risk predictor for CVD than LDL-C and an alternative target for CVD risk reduction. Major international guidelines recommend evaluating non-HDL-C as part of atherosclerotic CVD risk assessment, especially in people with high triglycerides, diabetes, obesity, or very low LDL-C. A non-HDL-C target of <130 mg/dL (3.4 mmol/L) has been recommended for patients at very high risk, which is 30 mg/dL (0.8 mmol/L) higher than the corresponding LDL-C target goal. Non-HDL-C lowering approaches include reducing LDL-C and triglyceride levels, increasing HDL-C, or targeting multiple risk factors simultaneously. However, despite the growing evidence for the role of non-HDL-C in residual CVD risk, and recommendations for its assessment in major guidelines, non-HDL-C testing is not routinely done in clinical practice. Thus, there is a need for increased awareness of the need for non-HDL-C testing for ascertaining CVD risk and concomitant prevention of CVD.