Role of apolipoprotein B in the clinical management of cardiovascular risk in adults: An Expert Clinical Consensus from the National Lipid Association

Abstract

This National Lipid Association (NLA) Expert Clinical Consensus provides an overview of the physiologic and clinical considerations regarding the role of apolipoprotein B (apoB) measurement to guide clinical care based on the available scientific evidence and expert opinion. ApoB represents the total concentration of atherogenic lipoprotein particles in the circulation and more accurately reflects the atherogenic burden of lipoproteins when compared to low-density lipoprotein cholesterol (LDL-C). ApoB is a validated clinical measurement that augments the information found in a standard lipoprotein lipid panel; therefore, there is clinical value in using apoB in conjunction with a standard lipoprotein lipid profile when assessing risk and managing lipid-lowering therapy (LLT). ApoB has been shown to be superior to LDL-C in risk assessment both before and during treatment with LLT. In individuals, there can be discordance between levels of LDL-C and apoB, as well as LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C), despite high levels of population-wide correlation. When there is discordance between LDL-C and apoB, or LDL-C and non-HDL-C, atherosclerotic cardiovascular disease risk generally aligns better with apoB or non-HDL-C. Additionally, apoB can be used in tandem with standard lipoprotein lipid measurements to diagnose distinct lipoprotein phenotypes. ApoB testing can inform clinical prognosis and care, as well as enable family cascade screening, when an inherited lipoprotein syndrome is identified. The NLA and other organizations will continue to educate clinicians about the role of apoB measurement in improving clinical risk assessment and dyslipidemia management. An urgent need exists to improve access and reimbursement for apoB testing.

Keywords: Apolipoprotein B; Atherosclerosis; Discordance; Low-density lipoprotein cholesterol; Non-high-density lipoprotein cholesterol.

Figure 1.. Association between concordant or discordant apoB and LDL-C and corresponding atherogenic lipoprotein risk.

When apoB and LDL-C are concordantly low (Panel A), atherogenic lipoprotein risk is not elevated. When apoB and LDL-C are concordantly elevated (Panel D), atherogenic lipoprotein risk is elevated. When apoB and LDL-C are discordant (Panels B and C), lipoprotein risk follows apoB. Image created with BioRender. Abbreviations: ApoB=apolipoprotein B; LDL-C=low-density lipoprotein cholesterol.

Figure 2.. Population-based relationship between LDL-C (Friedewald calculated) and apoB from an untreated sample (NHANES 2005–2016) and two on-treatment samples (IMPROVE-IT and FOURIER).

Panel A is the untreated NHANES sample (n=12,696, 18–85 years of age). Panel B is the achieved 1-year values for IMPROVE-IT or 48-week values for FOURIER, separated into statin monotherapy (n=18,812 [6,878 in IMPROVE-IT and 11,934 in FOURIER]), statin + ezetimibe (n=7,475 [6,851 in IMPROVE-IT and 660 in FOURIER]), and statin + PCSK9i (n=12,645, all in FOURIER). Panel C is both the untreated and on-treatment scatterplots on the same graph. The solid grey line in each graph represents the line of identity. Abbreviations: ApoB=apolipoprotein B; FOURIER=Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk; IMPROVE-IT= Improved Reduction of Outcomes: Vytorin Efficacy International Trial; LDL-C=low-density lipoprotein cholesterol; NHANES=National Health and Nutrition Examination Survey; PCSK9i=proprotein convertase subtilisin-kexin type 9 inhibitor.