What are apolipoprotein B (apo-B) and lipoprotein(a) (Lp(a))?

From the Guidelines

Apolipoprotein B (apo-B) and lipoprotein(a) [Lp(a)] are crucial markers for cardiovascular risk assessment, with apo-B being a direct measure of the total number of potentially atherogenic particles in circulation and Lp(a) being a modified LDL particle with pro-atherogenic and pro-thrombotic properties. Apo-B is a protein found on all atherogenic lipoproteins (LDL, VLDL, IDL, and lipoprotein(a)), with one molecule of apo-B per particle, providing better risk prediction than LDL cholesterol alone, especially in patients with metabolic syndrome, diabetes, or hypertriglyceridemia 1. Some key points about apo-B and Lp(a) include:

• Apo-B levels are a good estimate of the number of atherogenic particles in plasma, and several prospective studies have shown that apo-B is equal to LDL-C in risk prediction 1.
• Lp(a) levels are primarily genetically determined, with elevated levels (>50 mg/dL or >125 nmol/L) associated with increased cardiovascular risk independent of other risk factors 1.
• Unlike other lipoproteins, Lp(a) is minimally affected by lifestyle changes and most lipid-lowering medications, with the exception of PCSK9 inhibitors and the investigational antisense oligonucleotide pelacarsen, which can reduce levels by 20-30% and up to 80%, respectively 1.
• The European Society of Cardiology (ESC) guidelines recommend measuring Lp(a) in patients at high risk of cardiovascular disease (CVD) and to target levels below 50 mg/dL 1. Target apo-B levels are generally <80 mg/dL for high-risk patients and <65 mg/dL for very high-risk patients, and Lp(a) levels should be targeted below 50 mg/dL in patients at high risk of CVD. Both markers provide valuable information for risk stratification and can guide more aggressive lipid-lowering therapy in patients with elevated levels 1.

From the Research

Definition and Composition

• Apolipoprotein B (apo-B) is a protein that serves as a primary component of low-density lipoprotein (LDL) cholesterol particles 2, 3, 4.
• Lipoprotein(a) (Lp(a)) is a type of LDL cholesterol-like particle that is bound to apolipoprotein(a) 5, 6.
• Lp(a) is composed of two components: a central core with apoB and an additional glycoprotein, called apo(a) 6.

Role in Cardiovascular Disease

• Elevated levels of Lp(a) have been associated with an increased risk of cardiovascular disease (CVD), including atherosclerotic cardiovascular disease and calcific aortic valve stenosis 5, 6.
• ApoB has been shown to be a more accurate measure of cardiovascular risk than LDL-C or non-HDL-C 2, 3, 4.
• The European Atherosclerosis Society has noted that Lp(a) levels of 50 mg/dL or higher confer increased cardiovascular risk 5.

Measurement and Clinical Significance

• Measuring apoB is essential for accurate diagnosis and follow-up of dyslipoproteinemia 4.
• ApoB integrates the risk due to atherogenic lipoprotein particles, making it a useful index for quantitating atherogenic risk 4.
• The addition of apoB measurement to the routine lipid panel may enhance patient management and assessment of cardiovascular risk 3.