One molecule of apolipoprotein B (apo B) is present in all atherogenic lipoproteins, including chylomicrons, very low density lipoprotein, intermediate density lipoprotein, low density lipoprotein (LDL), and lipoprotein(a). Measurement of apo B is available through automated and standardized immunoassays and provides an efficient and inexpensive method to reflect the number of atherogenic particles (1).
The 2018 American College of Cardiology/American Heart Association guideline for the management of blood cholesterol has recommended apo B as a risk assessment enhancer for individuals with intermediate atherosclerotic cardiovascular disease (ASCVD) risk when evaluated with traditional risk factors. The 2020 European Society of Cardiology and the European Atherosclerosis Society guidelines have ranked apoB as the most accurate marker representing atherogenic lipoproteins for predicting cardiovascular risk. However, it is well recognized too that apo B is highly correlated with metrics in the standard lipid profile, LDL-cholesterol (LDL-C) and non-high density lipoprotein-cholesterol (non-HDL-C). Therefore, the clinical utility of measuring apo B in addition to a standard lipid profile is not fully appreciated.
A number of studies have reported higher ASCVD risk among people with discordantly high apo B concentrations relative to LDL-C or non-HDL-C. The source of discordance is the relatively small and dense LDL particles in these individuals, that are commonly seen in metabolic syndrome and diabetes. On the other hand, lower risk of ASCVD is reported among those with discordantly low apo B. Definitions of concordance/discordance vary in these studies and typically use medians, percentile differences, or residuals. Nevertheless, apoB has consistently improved risk assessment by traditional ASCVD markers.
Two recent studies examined discordance between apo B and cholesterol measurements on their association with a subclinical outcome variable, coronary artery calcium (CAC), which is an early surrogate of atherosclerosis. In the Coronary Artery Risk Development in Young Adults (CARDIA) study, black and white participants were followed for 25 years beginning at the very young age of 25 years. A dose-response association between apoB at the young age and the presence of midlife CAC was demonstrated to be independent of traditional ASCVD risk factors (2).
In contrast, the Multi-Ethnic Study of Atherosclerosis (MESA) is composed of a racially/ethnically diverse population aged ≥45 years that were non-statin users at baseline. This population represents the target age range for ASCVD risk screening, although CAC already has a high prevalence (>45%) at this age. Without adjusting for other common ASCVD risk factors, modest associations were observed between discordant apo B levels relative to LDL-C or non-HDL-C and prevalent or incident CAC over the time of 12-year follow-up, but when additionally accounting for factors such as triglycerides, diabetes, and body mass index, associations were generally no longer statistically significant. One exception is that the association between discordantly high apo B relative to non-HDL-C remained significant after adjusting for other factors (3).
The disparate findings from CARDIA and MESA suggest that the discordance between apoB and cholesterol measurement is highly correlated with overweight, diabetes, and hypertriglyceridemia. Additional measurement of apo B at younger age is particularly beneficial for improving ASCVD risk classification in discordant individuals. Furthermore, interventional trials of patients receiving statin therapy have shown greater reduction of LDL-C than LDL particle concentration, thus apo B serves as a better assessment of treatment residual risk.
To summarize, apo B measurement to assess ASCVD risk is especially important in modern society with the burden of overweight and obesity, metabolic syndrome and diabetes. Current evidence supports screening of apo B in addition to standard lipid profile at early ages to reduce lifetime ASCVD risk, and to monitor apo B following lipid-lowering treatment.
- Contois JH, McConnell JP, Sethi AA, Csako G, Devaraj S, Hoefner DM, and Warnick GR. Apolipoprotein B and Cardiovascular Disease Risk: Position Statement from the AACC Lipoproteins and Vascular Diseases Division Working Group on Best Practices. Clinical Chemistry. 2009; 55 (3): 407–419.
- Wilkins JT, Li RD, Sniderman A, Chan C, Lloyd-Jones DM. Discordance between Apolipoprotein B and LDL-cholesterol in young adults predicts coronary artery calcification the CARDIA study. J Am Coll Cardiol. 2016; 67: 193-201.
- Cao J, Nomura SO, Steffen BT, Guan W, Remaley AT, Karger AB, Ouyang P, Michos ED, Tsai MY. Apolipoprotein B discordance with low-density lipoprotein cholesterol and non–high-density lipoprotein cholesterol in relation to coronary artery calcification in the Multi-Ethnic Study of Atherosclerosis (MESA). Journal of Clinical Lipidology. 2020; 14 (1): 109-121