Apolipoprotein B and Cardiovascular Risk
Despite advances in understanding the pathogenesis and prevention of atherosclerotic cardiovascular disease (ASCVD), coronary heart disease (CHD) remains the leading cause of death in the United States.1,2 Approximately 1 of every 4 deaths in the United States is related to CHD.1,2
Key contributors to risk reduction for cardiovascular disease (CVD) include management of traditional risk factors (eg, smoking, high blood pressure) and lowering low-density lipoprotein cholesterol (LDL-C).2 Earlier interventions provide greater benefits.2 Managing inflammation also plays an important role in reducing the buildup of cholesterol and decreasing CVD risk.3 However, managing traditional risk factors and lowering LDL-C to conventional target concentrations may not adequately reduce risk for some patients.2 Once identified, patients with risk-enhancing factors (see Sidebar) may benefit from more intensive treatment to improve outcomes.2
High serum levels of apolipoprotein B-100 (ApoB), the primary apolipoprotein attached to atherogenic particles (LDL-C and others), are associated with increased risk of CHD.4 Recent studies have indicated that ApoB may have predictive value beyond that of LDL-C and triglyceride (TG) levels, especially in certain at-risk patients.5 This article will discuss ApoB in the context of ASCVD and the inclusion of ApoB in guidelines for risk stratification.
ASCVD, lipoproteins, and ApoB
ASCVD is driven by infiltration of the arterial wall by atherogenic particles that are <70 nm in diameter, including LDL-C, intermediate-density lipoprotein cholesterol (IDL-C), very low-density lipoprotein cholesterol (VLDL-C), and lipoprotein (Lp) (a).2,5,6 Trapped lipoprotein particles cause atherosclerosis through inflammation, the development of a “fatty streak” that leads to smooth muscle proliferation, and eventual development of a plaque.2,5 Plaques can become large enough that they occlude blood flow, or they can become unstable and rupture, leading to distal artery occlusion.2,5
The concentration of ApoB represents the concentration of atherogenic lipoprotein particles because each lipoprotein particle contains 1 molecule of ApoB.7 As such, ApoB is a better indicator of atherogenic lipid status than is LDL-C because it also reflects atherogenic TG-rich lipoproteins, such as IDL-C, VLDL-C, and Lp (a).8
LDL-C cutpoints and targets may underestimate the risk of developing ASCVD, particularly in conditions associated with very high TG levels, such as insulin resistance, diabetes, metabolic syndrome, and obesity (see Sidebar).9,10 In persons with these conditions, high TG levels lead to high levels of TG-rich lipoproteins and ApoB levels that are disproportionally high relative to LDL-C. Consequently, LDL-C may be normal, but the overall lipid profile is atherogenic.6 Thus, ApoB levels may be a better indicator of atherogenic lipid status than is LDL-C, which may underrepresent ASCVD risk in these patients.10 High-risk patients on lipid-lowering therapies who have achieved desirable LDL-C levels (eg, <70 mg/dL) may also benefit from measurement of ApoB if their TG levels and, hence, total atherogenic particle concentration remain high.6