Differences Between Lipoprotein(a) and Low-Density Lipoprotein
Lipoprotein(a) [Lp(a)] is a distinct lipoprotein class consisting of an LDL-like particle with an additional apolipoprotein(a) protein attached via a disulfide bridge, while standard LDL contains only apolipoprotein B-100 without this additional protein component. 1
Structural Differences
LDL (Low-Density Lipoprotein):
- Contains apolipoprotein B-100 (apoB-100)
- Core consists of cholesteryl esters and triglycerides
- Outer layer contains phospholipids and free cholesterol
- Primary carrier of cholesterol in the bloodstream
Lipoprotein(a) [Lp(a)]:
- Contains an LDL-like particle plus apolipoprotein(a)
- The apolipoprotein(a) is covalently linked to apoB-100 by a disulfide bridge
- The lipid core is virtually indistinguishable from that of LDL
- Apolipoprotein(a) has a unique "kringle" structure similar to plasminogen 1
- Contains multiple repetitive protein segments called "kringles" that are highly homologous to plasminogen 1
Genetic and Metabolic Differences
LDL:
- Levels are influenced by diet, lifestyle, and genetics
- Can be significantly lowered by statins and other lipid-lowering therapies
- Metabolized primarily through LDL receptors
Lp(a):
Clinical Significance and Risk Assessment
LDL:
- Well-established risk factor for cardiovascular disease
- Target of primary therapy for cardiovascular risk reduction
- Has established treatment targets based on risk categories
Lp(a):
- Independent risk factor for cardiovascular disease and calcific aortic valve disease 3
- Associated with increased risk even when LDL is well-controlled
- Risk thresholds: low risk (<30 mg/dL), intermediate risk (30-50 mg/dL), high risk (≥50 mg/dL) 4
- The risk associated with elevated Lp(a) attenuates at very low LDL-C levels (<2.5 mmol/L) in primary prevention 5
Measurement Considerations
LDL:
- Routinely measured in standard lipid panels
- Can be directly measured or calculated using the Friedewald formula
- Reported in mg/dL or mmol/L
Lp(a):
- Not included in routine lipid panels
- Should be measured at least once in patients with premature CVD, intermediate cardiovascular risk, family history of premature CVD, or familial hypercholesterolemia 4
- Preferably reported in nmol/L for standardization (conversion factor: 1 mg/dL = 3.17 nmol/L) 4
- Conventional "LDL-C" assays include the cholesterol content from both LDL and Lp(a) particles, potentially overestimating true LDL-C in patients with high Lp(a) 6
Treatment Approaches
LDL:
- Primary target for lipid-lowering therapy
- Effectively lowered by statins, ezetimibe, PCSK9 inhibitors
- Clear treatment targets based on cardiovascular risk
Lp(a):
- Limited options for specific Lp(a) reduction
- Modest reduction with PCSK9 inhibitors (15-30%) 2
- Lipoprotein apheresis is effective but impractical for routine use 4
- Emerging therapies like antisense oligonucleotides (pelacarsen) and small interfering RNA (olpasiran) show promise with >80% reduction 4, 3
Clinical Implications
When evaluating cardiovascular risk, it's important to consider both LDL and Lp(a) levels, especially in:
- Patients with premature cardiovascular disease
- Those with family history of premature CVD
- Patients with recurrent cardiovascular events despite optimal LDL control
- Young women with low LDL-C may have elevated cardiovascular risk associated with high Lp(a) and apoB levels 7
For accurate risk assessment, consider correcting LDL-C for Lp(a) cholesterol content, as conventional LDL-C measurements include cholesterol from both LDL and Lp(a) particles, which can lead to misclassification of patients into incorrect risk categories 6.