What is the difference between Lipoprotein(a) (Lp(a)) and Apolipoprotein B (ApoB)?

Difference Between Lp(a) and ApoB

Lp(a) and ApoB are fundamentally different entities: ApoB is a structural protein found on all atherogenic lipoproteins (including VLDL, IDL, LDL, and Lp(a)), while Lp(a) is a distinct lipoprotein particle that contains both ApoB-100 and an additional unique glycoprotein called apolipoprotein(a). 1

Structural Differences

ApoB-100

• ApoB-100 is the major protein constituent of LDL and serves as the structural scaffold for all apoB-containing lipoproteins 1
• Each atherogenic lipoprotein particle (VLDL, IDL, LDL, and Lp(a)) contains exactly one molecule of ApoB-100 per particle 2, 3
• ApoB directly reflects LDL particle numbers, making it a marker of total atherogenic particle burden 2

Lp(a) Structure

• Lp(a) consists of an LDL-like core lipoprotein (containing ApoB-100) plus apolipoprotein(a) [apo(a)] covalently linked by a disulfide bridge 1
• The disulfide bridge specifically links Cys4326 in ApoB-100 with Cys4057 in apo(a) 1
• The lipid core of Lp(a) is virtually indistinguishable from that of LDL 1
• Apo(a) has a unique structure consisting of repetitive protein segments called kringles that are highly homologous to plasminogen 1, 4

Metabolic Differences

ApoB Metabolism

• ApoB-containing lipoproteins are cleared primarily through the LDL receptor (LDLR) pathway 1
• Statins effectively reduce LDL-ApoB levels by upregulating the LDLR 1

Lp(a) Metabolism

• Lp(a) assembly occurs through two sources: 53% derived from preformed lipoproteins (IDL and LDL), and 47% from ApoB directly secreted by the liver 5
• The fractional catabolic rate of Lp(a) (0.24-0.27 pools per day) is less than half that of LDL 5
• Lp(a) clearance mechanisms remain poorly understood and involve multiple receptors beyond the LDLR, including SR-BI, LRP1, plasminogen receptors (PlgRKT), and CD36 1, 6
• Statins upregulate the LDLR but do not reduce Lp(a) levels, demonstrating that Lp(a) clearance differs fundamentally from LDL clearance 1
• Plasma Lp(a) levels are primarily determined by synthetic rate rather than catabolic rate and are highly genetically determined 4

Clinical Significance Differences

ApoB as a Risk Marker

• ApoB measurement captures the total number of all atherogenic particles (VLDL, IDL, LDL, and Lp(a)) 2, 3
• For high-risk patients, target ApoB <100 mg/dL; for very high-risk patients, <80 mg/dL 2
• ApoB can be effectively lowered with statins and PCSK9 inhibitors 1

Lp(a) as a Distinct Risk Factor

• Elevated Lp(a) is an independent risk factor for cardiovascular disease and aortic stenosis, with risk more than two times higher in individuals with increased Lp(a) 1, 2
• Lp(a) is approximately 6-fold more atherogenic than LDL on a per-particle basis 7
• Traditional thresholds for elevated Lp(a) are >30 mg/dL or >75 nmol/L 1, 2
• Lp(a) carries oxidized phospholipids (OxPL) bound to apo(a), which stimulate proinflammatory pathways—a key property underlying its pathogenicity 6
• Lp(a) has anti-fibrinolytic/pro-thrombotic effects due to its structural homology with plasminogen 1, 4

Measurement Considerations

Quantifying Lp(a) Contribution to ApoB

• Lp(a) comprises on average 3% of all ApoB-containing particles in the general population, but 15% at the highest Lp(a) deciles 3
• The fraction Lp(a)-P/ApoB-P increases with rising Lp(a) levels and decreases at higher triglyceride and LDL-C levels 3
• Lp(a) is composed of 30-45% cholesterol by mass, which is reported as part of the "LDL-C" laboratory measurement, potentially overestimating true LDL-C in patients with elevated Lp(a) 1

Clinical Testing Recommendations

• Standard lipid profiles should be prioritized first for cardiovascular risk assessment 2
• For refined risk assessment in selected patients, measure ApoB and Lp(a) separately rather than seeking a combined score 2
• Lp(a) measurement is recommended in patients with premature CVD, familial hypercholesterolemia, family history of premature CVD or elevated Lp(a), recurrent CVD despite optimal therapy, or ≥5% 10-year risk of fatal CVD 1

Key Clinical Pitfall

A critical distinction: while ApoB can be effectively targeted with statins and PCSK9 inhibitors, Lp(a) levels are largely unresponsive to these therapies and require different therapeutic approaches 1, 4. This means that a patient may have well-controlled LDL-C and ApoB levels but still harbor significant residual cardiovascular risk from elevated Lp(a) that goes unrecognized without specific Lp(a) measurement.