- Author: Abimbola Farinde, PharmD, PhD; Chief Editor: Eric B Staros, MD more...
Reference ranges of lipoprotein (a) (Lp[a]) vary and depend on assay and reporting laboratories. They also differ by population and may differ regionally worldwide. Nonetheless, many US lipidologists generally consider an Lp(a) level of less than 10 mg/dL to indicate a lower cardiovascular risk. levels higher than 10 mg/dL are associated with an increase in cardiovascular risk (see Interpretation).
The apolipoproteins have a primary responsibility for the transport of lipids and cholesterol. Apolipoprotein B (apoB) is a nonexchangeable lipoprotein that exists in two forms in humans, apoB-100 and apoB-48.
Many US lipidologists consider a Lp(a) level < 10.0 mg/dL to be indicative of lower cardiovascular risk, with higher levels associated with an increase in cardiovascular risk.
As noted by Davidson, the odds ratio for significant coronary heart disease on angiography in patients with a Lp(a) level greater than 30 mg/dL versus a level less than or equal to 5 mg/dL increased from 1.67 to 6.0, as LDL concentrations increased as well.
In addition, a number of prospective trials have demonstrated that Lp(a) predicts risk in a nonlinear fashion; thus, increases in cardiovascular risk are extremely small until Lp(a) levels are within the top 5-10%.[3, 4]
Collection and Panels
Collection method: Routine venipuncture
Container: Varies widely by reference laboratory and type of assay
Lipoprotein(a) is collected as part of various panels constituting what is known as "advanced lipid testing." These panels are offered by various commercial entities and include those which offer LDL particle testing.
Lipoprotein (a) (Lp[a]) is composed of a low density lipoprotein (LDL) particle with an apolipoprotein B-100 (apo B100) component that is covalently linked via a disulfide bridge to an apolipoprotein (a) molecule, which is highly homologous to plasminogen.[3, 5] See image below.
As a result of the the apo(a) component of Lp(a) is a complex molecule with great heterogeneity, plasma Lp(a) concentrations are inversely dependent on apo(a) size. Perhaps unsurprisingly, given this level of complexity, more than 25 genetic forms of Lp(a) are known to exist; thus, the importance of the genome in determining plasma levels cannot be understated. This, in turn, has implications for cardiovascular risk prediction across different populations.
In the Copenhagen Heart study, Kamstrup et al found that genetic elevations of Lp(a) were associated with an increased risk of myocardial infarction. Furthermore, several prospective epidemiological studies have indicated a causal role for Lp(a) in cardiovascular disease; thus, measurement of Lp(a) may be used as a determinant of cardiovascular risk within the context of a global cardiovascular risk assessment.
Lp(a) is not recommended to be used alone as a sole test for determining cardiovascular risk, but rather as an additional measure to be combined with assessment of traditional cardiovascular risk factors. The measurement of Lp(a) may be most useful in intermediate-risk patients or in those in whom the test result would affect treatment or the aggressiveness of treatment of known cardiovascular risk factors.
As noted by Ridker and Libby, it is uncertain whether the assessment of Lp(a) truly adds prognostic information to overall risk in primary prevention; however, in most studies, Lp(a) has predictive value for those already known to be at high risk because of the presence of other risk factors, in particular elevated LDL-C levels.
The standardization of commercial assays for Lp(a) has been problematic owing to dependence on apo(a) size; however, commercial assays that can measure Lp(a) independently and separate from apo(a) size are available now in numerous reference laboratories.[3, 7]
Several prospective studies have shown that Lp(a) predicts cardiovascular risk in a nonlinear fashion, such that the increase in risk is quite small until the highest levels (top 5-10%) of Lp(a) are reached.[3, 4]
Data regarding the use of Lp(a) as a biomarker in certain high-risk groups, such as those with chronic kidney disease or known coronary artery disease, remain controversial.
The observation of extremely high levels of Lp(a) seem to be almost entirely limited to patients with concomitantly high levels of LDL cholesterol brings into question the use of Lp(a) as an independent marker of increased cardiovascular risk and highlights the limitations presented by interactions with LDL cholesterol.
Few interventions have been found to lower Lp(a) levels, with the exception of high-dose niacin. Therapy specifically targeted at modifying Lp(a) also remains controversial.[3, 2, 8, 9]
There are emerging data on the use of apheresis as an effective method to lower Lp(a). No drugs are approved for this, but recent trials have shown that Lp(a) can be substantially lowered with a decrease in other apolioprotein B-100(apoB).
Ghorbani A, Rafieian-Kopaei M, Nasri H. Lipoprotein (a): More than a bystander in the etiology of hypertension? A study on essential hypertensive patients not yet on treatment. J Nephropathol. 2013 Jan. 2(1):67-70. [Medline]. [Full Text].
Michael H. Davidson. Management of Dyslipidemia by Patient Profiles. The Mobile Lipid Clinic: A Companion Guide. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005. 197-98.
Ridker PM and Libby P. Risk Markers for Atherothrombotic Disease. Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 9th ed. Philadelphia, PA: Elsevier Saunders; 2012. 927-28.
Kamstrup PR, Benn M, Tybjaerg-Hansen A, Nordestgaard BG. Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: the Copenhagen City Heart Study. Circulation. 2008 Jan 15. 117(2):176-84. [Medline].
Genest J and Libby P. Lipoprotein Disorders and Cardiovascular Disease. Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 9th ed. Philadelphia, PA: Elsevier Saunders; 2012. 983.
Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, Nordestgaard BG. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA. 2009 Jun 10. 301(22):2331-9. [Medline].
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Gotto A, Pownall H. Manual of Lipid Disorders: Reducing the Risk for Coronary Heart Disease. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2003.
Stone NJ, Blum CB. Management of Lipids in Clinical Practice. 5th Ed. Caddo, OK: Professional Communications, Inc.; 2005.
Kolski B1, Tsimikas S. Emerging therapeutic agents to lower lipoprotein (a) levels. Curr Opin Lipidol. Dec 2012. 23:560-8.
Paul E. Richardson, Medha Manchekar, [...], and Jere P. Segrest. Assembly of Lipoprotein Particles Containing Apolipoprotein-B: Structural Model for the Nascent Lipoprotein Particle. Biophysical Journal. 2005. 88:2789-2800. [Full Text].