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Lipoprotein, Lp(a)
PBB Protein LPA image.jpg
PDB rendering based on 1i71.
Symbol(s) LPA; AK38; APOA; LP
External IDs OMIM: 152200 Homologene87856
RNA expression pattern

PBB GE LPA 207584 at tn.png

PBB GE LPA 209978 s at tn.png

More reference expression data

Human Mouse
Entrez 4018 na
Ensembl ENSG00000198670 na
Uniprot P08519 na
Refseq XM_941792 (mRNA)
XP_946885 (protein)
na (mRNA)
na (protein)
Location Chr 6: 160.87 - 161.01 Mb na
Pubmed search [1] na

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]


Lipoprotein(a) (also called Lp(a)) is a lipoprotein subclass. Studies have identified Lp(a) as a putative risk factor for atherosclerotic diseases as coronary heart disease and stroke.[1][2][3] Lp (a) is elevated in some types of hyperlipoproteinemia. The reference range for Lp (a) is < 300 mg/l.


Lipoprotein(a) [Lp(a)] consists of an LDL-like particle and the specific apolipoprotein(a) [apo(a)], which is covalently bound to the apoB of the LDL like particle. Lp(a) plasma concentrations are highly heritable and mainly controlled by the apolipoprotein(a) gene [LPA] located on chromosome 6q26-27. Apo(a) proteins vary in size due to a size polymorphism [KIV-2 VNTR], which is caused by a variable number of so called kringle IV repeats in the LPA gene. This size variation at the gene level is expressed on the protein level as well, resulting in apo(a) proteins with 10 to > 50 kringle IV repeats (each of the variable kringle IV consists of 114 amino acids).[4][5] These variable apo(a) sizes are known as "apo(a) isoforms". There is a general inverse correlation between the size of the apo(a)isoform and the Lp(a) plasma concentration[6] which is caused by a variable rate of degradation before the apo(a) protein has matured for Lp(a) assembly.[7][8] Apo(a) is express by the liver cells (hepatocytes), and the assembly of apo(a) and LDL particles seems to take place at the outer hepatocyte surface. The half-life of Lp(a) in the circulation is about 3 to 4 days.[9]

Catabolism and Clearance

The mechanism and sites of Lp(a) catabolism are largely unknown. Uptake via the LDL receptor is not a major pathway of Lp(a)metabolism.[10][11] The kidney has been identified as playing a role in Lp(a) clearance from plasma.[12]


Lp(a) concentrations vary over one thousandfold between individuals, from < 0.2 to > 200 mg/dL. This range of concentrations is observed in all populations studied so far. The mean and median concentrations between different world populations show distinct particularities, the main being the two- to threefold higher Lp(a) plasma concentration of populations of African descent compared to Asian, Oceanic, or European populations. The general inverse correlation between apo(a) isoform size and Lp(a)plasma concentration is observed in all populations, however, mean Lp(a) associated with certain apo(a) isoforms varies between populations.


The physiological function of Lp(a)/apo(a) is still unknown. A function within the coagulation system seems plausible, given the aspect of the high homology between apo(a) and plasminogen.[4] In fact, the LPA gene derives from a duplication of the plasminogen gene.

Other functions have been related to recruitment of inflammatory cells through interaction with Mac-1 integrin, angiogenesis, and wound healing.

However, individuals without Lp(a) or with very low Lp(a) levels seem to be healthy. Thus plasma Lp(a) is certainly not vital, at least under normal environmental conditions. Since apo(a)/Lp(a) derived rather recently in mammalian evolution - only old world monkeys and humans have been shown to harbour Lp(a) - its function might not be vital but just evolutionary advantageous under certain environmental condition, e.g. in case of exposure to certain infectious disease.


Lipoprotein's structure is similar to plasminogen and tPA (tissue plasminogen activator) and it competes with plasminogen for its binding site, leading to reduced fibrinolysis. Also because Lp(a) stimulates secretion of PAI-1 it leads to thrombogenesis. In addition, because of LDL cholesterol content, Lp-a contributes to atherosclerosis.[3][13]

Causes of Low Lp (a)

Causes of High Lp (a)

Lipoprotein(a) and Disease

High Lp(a) in blood is a risk factor for coronary heart disease (CHD), cerebrovascular disease (CVD), atherosclerosis, thrombosis, and stroke.[18] Lp-a concentrations may be affected by disease states, but are only slightly affected by diet, exercise, and other environmental factors. Commonly prescribed lipid-reducing drugs have little or no effect on Lp(a) concentration. Niacin (nicotinic acid) and aspirin are two relatively safe, easily available and inexpensive drugs known to significantly reduce the levels of Lp(a) in some individuals with high Lp(a); they should be used under the supervision of a qualified physician.

High Lp(a) predicts risk of early atherosclerosis similar to high LDL, but in advanced atherosclerosis, Lp(a) is an independent risk factor not dependent on LDL. Lp(a) then indicates a coagulant risk of plaque thrombosis. Apo(a) contains domains that are very similar to plasminogen (PLG). Lp(a) accumulates in the vessel wall and inhibits binding of PLG to the cell surface, reducing plasmin generation which increases clotting. This inhibition of PLG by Lp(a) also promotes proliferation of smooth muscle cells. These unique features of Lp(a) suggest Lp(a) causes generation of clots and atherosclerosis.[19]

Vegetarians have higher levels of Lp-a than fish eaters in one homogeneous tribal population of Tanzania raising the possibility that pharmacologic amounts of fish oil supplements may be helpful to lower the levels of Lp-a.

Low fat-high carbohydrate diet raises Lp-a.

Fibrates such as benzafibrate or gemfibrozil have significantly lowered Lp-a in some individuals.

Prolonged and daily intake of large amounts of milk protein (casein) or alcohol extracted soy protein in the diet leads to a very significant decline in the levels of plasma Lp-a. However, consumption of regular soy protein does not lower the levels of Lp-a.

Regular consumption of moderate amounts of alcohol leads to significant decline in plasma levels of Lp-a.

High levels of Apo AI HDL cholesterol are protective against atherogenic potential of Lp-a.

Cardiology diagnostic tests

Lp(a) cannot yet be regarded as a conventional, well established risk factor for cardiovascular disease, although studies show an ASSOCIATION of Lp(a) and cardiovascular disease, which does not automatically mean a causal relation.[1] While it might well be indicated to measure Lp(a) in high risk patients, the association of Lp(a) and cardiovascular disease is rather complicated.[20] Apart from the total Lp(a) plasma concentration, the apo(a) isoform might be an important risk parameter.[21][22] Furthermore, the ethnic origin of an individual must be considered when evaluating its Lp(a) concentration in respect of the risk for cardiovascular events.[23][24] E.g. the "conventional" risk threshold of 30 mg/dl would classify up to > 50% of the individuals in some African populations as being at risk.[25][26][27] Furthermore, Lp(a) measurement is in urgent need of standardisation.[28]

Thus the threshold values given below should be seen very critically. They are -if at all- only applicable to individuals of European descent.

Lipoprotein(a) - Lp(a)[29]

Desirable: < 14 mg/dL
Borderline risk: 14 - 30 mg/dL
High risk: 31 - 50 mg/dL
Very high risk: > 50 mg/dL


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  21. Klausen IC, Sjøl A, Hansen PS, Gerdes LU, Møller L, Lemming L, Schroll M, Faergeman O (1997). "Apolipoprotein(a) isoforms and coronary heart disease in men: a nested case-control study". Atherosclerosis. 132 (1): 77–84. PMID 9247362. doi:10.1016/S0021-9150(97)00071-3. 
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  26. Cobbaert C, Mulder P, Lindemans J, Kesteloot H (1997). "Serum LP(a) levels in African aboriginal Pygmies and Bantus, compared with Caucasian and Asian population samples". J Clin Epidemiol. 50 (9): 1045–53. PMID 9363039. doi:10.1016/S0895-4356(97)00129-7. 
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  29. Ryan, George M; Julius Torelli (2005). Beyond cholesterol: 7 life-saving heart disease tests that your doctor may not give you. New York: St. Martin's Griffin. pp. page 91. ISBN 0-312-34863-0.