Lexicon
Lipoprotein(a)
Also known as Lp(a), Lpa, apo(a)
Definition
Lipoprotein(a) [Lp(a)] is an apoB100-containing lipoprotein whose two major protein components are apoB100 and apolipoprotein(a), and high levels are an independent and causal risk factor for atherosclerotic cardiovascular disease. [1] Lp(a) is predominantly a monogenic (genetically determined) cardiovascular risk determinant, with roughly 70% to 90% of the interindividual variation in levels being genetically determined. [1] High Lp(a) concentrations are present in about 10% to 20% of the population and, on a genetic basis, affect an estimated more than one billion individuals worldwide. [2]
How it works
High Lp(a) drives atherosclerotic cardiovascular disease through mechanisms associated with increased atherogenesis, inflammation, and thrombosis. [1] Epidemiologic and genetic studies involving hundreds of thousands of individuals strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes across different ethnicities, and elevated Lp(a) remains a risk factor even at very low levels of LDL cholesterol. [3] Lp(a) has pro-inflammatory and pro-atherosclerotic properties that may partly relate to the oxidized phospholipids it carries, and high Lp(a) is associated with both microcalcification and macrocalcification of the aortic valve. [3] Effect sizes are most pronounced for myocardial infarction, peripheral arterial disease, and aortic valve stenosis, where high Lp(a) concentrations predict roughly 2- to 3-fold increases in risk. [2]
Connected concepts
How it's measured
Lp(a) measurement should be performed using well-validated assays with traceability to a recognized calibrator so that common cut-offs for high concentrations and risk assessment can be applied. [2] A recognised limitation is that the field still lacks full standardization and harmonization of assays and universal guidelines for diagnosis and risk assessment. [1] Multiple cardiovascular societies now recommend measuring Lp(a) concentration at least once in all adults, with cascade testing having potential value in familial hypercholesterolaemia or with a family or personal history of very high Lp(a) or premature ASCVD. [3] [4] European consensus recommendations note that Lipoprotein(a) cholesterol is contained within the LDL cholesterol reported on the standard Lipid Panel, and advise estimating it in all patients at risk of atherosclerotic cardiovascular disease [5]
What levels mean / management
Community knowledge
## Biology And Inherited Risk
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- 1.Reyes-Soffer G, Ginsberg HN, Berglund L, Duell PB, Heffron SP, Kamstrup PR, Lloyd-Jones DM, Marcovina SM. Lipoprotein(a): A Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular Disease: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol · 2022
- 2.Kamstrup PR. Lipoprotein(a) and Cardiovascular Disease. Clin Chem · 2021
- 3.Kronenberg F, Mora S, Stroes ESG, Ference BA, Arsenault BJ, Berglund L, Dweck MR, Koschinsky M. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J · 2022
- 4.Anchouche K, Baass A, Thanassoulis G. Lp(a): A Clinical Review. Clin Biochem · 2025
- 5.Nordestgaard BG, Langlois MR, Langsted A, Chapman MJ, Aakre KM, Baum H, Borén J, Bruckert E, Catapano A, Cobbaert C, Collinson P, Descamps OS, Duff CJ, von Eckardstein A, Hammerer-Lercher A, Kamstrup PR, Kolovou G, Kronenberg F, Mora S, Pulkki K, Remaley AT, Rifai N, Ros E, Stankovic S, Stavljenic-Rukavina A, Sypniewska G, Watts GF, Wiklund O, Laitinen P. Quantifying atherogenic lipoproteins for lipid-lowering strategies: Consensus-based recommendations from EAS and EFLM.
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