Lp(a)
Lipoprotein(a) — a genetically determined lipoprotein that is a potent driver of atherosclerosis and thrombosis.
Optimal Range
< 30 nmol/L (low risk) · > 125 nmol/L (high risk)
Risk-Stratified Targets
| Population / Context | Target |
|---|---|
| Low riskEquivalent to approximately < 12 mg/dL | < 30 nmol/L |
| Borderline | 30–50 nmol/L |
| ElevatedWarrants aggressive management of other risk factors | 50–125 nmol/L |
| High riskEquivalent to approximately > 50 mg/dL | > 125 nmol/L |
Why It Matters
Lp(a) is ~90% genetically determined and does not respond to diet or exercise. Elevated Lp(a) is an independent, causal risk factor for heart attack and aortic stenosis. It only needs to be measured once in a lifetime.
Understanding Lp(a)
Lipoprotein(a) is often called the 'silent' cardiovascular risk factor because it is largely determined by genetics, is not measured on standard lipid panels, and does not respond to diet or exercise. Your Lp(a) level is approximately 90% determined by the LPA gene you inherited, making it one of the most stable and heritable biomarkers in medicine.
What makes Lp(a) particularly dangerous is its dual mechanism of harm. Structurally, Lp(a) is an LDL-like particle with an additional protein called apolipoprotein(a) attached to it. This gives it both the atherogenic properties of LDL (driving plaque formation) and prothrombotic properties similar to plasminogen (promoting blood clot formation). This combination makes elevated Lp(a) an independent risk factor for heart attack, stroke, and aortic valve stenosis.
Approximately 20% of the global population has elevated Lp(a), yet most have never had it measured. Current guidelines recommend measuring Lp(a) at least once in every adult's lifetime. If elevated, the focus shifts to aggressively managing all other modifiable risk factors — particularly LDL-C and ApoB — since there are currently no approved therapies that specifically lower Lp(a). However, several targeted antisense oligonucleotide therapies (pelacarsen, olpasiran) are in Phase 3 clinical trials and may become available within the next few years.
Key Research
Lipoprotein(a) as a cardiovascular risk factor: current status
Nordestgaard BG et al. · Eur Heart J (2010)
Key finding: Established Lp(a) as a causal, independent risk factor for cardiovascular disease through convergent genetic and epidemiologic evidence.
Association of LPA Variants With Risk of Coronary Disease and the Implications for Lipoprotein(a)-Lowering Therapies
Burgess S et al. · JAMA Cardiol (2018)
Key finding: Mendelian randomization supports a causal role for Lp(a) in coronary disease and suggests that large absolute reductions would be needed for clinical benefit.