Lipoprotein (a) Cholesterol, Serum
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Lipoprotein (a) (Lp[a]) is a highly heterogeneous molecule, consisting of a low-density lipoprotein (LDL) with a highly glycosylated apolipoprotein(a) (apo[a]) covalently linked to the apolipoprotein B moiety of LDL via a single disulfate bond. Lp(a) has been associated with atherogenesis and promotion of thrombosis. Increased levels of Lp(a) have been estimated to confer a 1.5 to 3.0-fold increased risk for coronary artery disease (CAD) in many but not all studies. Apo(a) has approximately 80% structural homology with plasminogen, but does not contain the active site for fibrin cleavage. One proposed mechanism for Lp(a)’s atherogenicity is competition for binding sites with plasminogen during fibrin clot formation and the resulting inhibition of fibrinolysis. Recently a high correlation was demonstrated between Lp(a) and oxidized LDL, suggesting that the atherogenicity of Lp(a) lipoprotein may be mediated in part by associated proinflammatory oxidized phospholipids.
Lack of standardization of assays and apo(a) heterogeneity may partially account for these discrepancies. The heterogeneity of Lp(a) arises mainly from the variable number of kringle repeats in the apo(a) portion of the molecule. Kringles are specific structural domains containing 3 intra-strand disulfide bonds that are highly homologous to similar repeats found in plasminogen.
In the clinical laboratory, immunologic methods are generally used to quantify Lp(a) protein mass. Reagents for Lp(a) mass measurement are available from multiple manufacturers and although standardization efforts are underway, currently available methods are not standardized. Difficulties in standardizing Lp(a) mass measurement arise from the variability in signals produced by different reagents due to the size polymorphisms of apo(a). For this reason, some elevations of Lp(a) mass are associated with low levels of Lp(a) cholesterol. Lp(a) quantification can be done by densitometric measurement of Lp(a) cholesterol. This method measures only the cholesterol contained in the Lp(a) particles and is thus not influenced by the relative size of the apo(a) size, it may provide a more specific assessment of cardiovascular risk than Lp(a) mass measurement. Lp(a) cholesterol measurement may be used in concert with Lp(a) mass determination, or may be used as a stand-alone test for assessment of risk.
Evaluation of increased risk for cardiovascular disease and events:
-Most appropriately measured in individuals at intermediate risk for cardiovascular disease according to the individuals’ Framingham risk score
-Patients with early atherosclerosis or strong family history of early atherosclerosis without explanation by traditional risk factors should also be considered for testing
Patients with increased Lp(a) cholesterol values have an approximate 2-fold increased risk for developing cardiovascular disease and events.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Lp(a) cholesterol values should not be confused with Lp(a) mass values, although they are highly correlated. Lp(a) cholesterol values will be approximately 10X lower than Lp(a) mass values, but the difference between the measures is not uniform. Lp(a) mass values are considered elevated when >30 mg/dL. Lp(a) cholesterol is increased if > or =3 mg/dL.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Normal: <3 mg/dL
Suggests increased risk of coronary artery disease: > or =3 mg/dL
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Berg K: Lp(a) lipoprotein: an overview. Chem Phys Lipids 1994;67-68:9-16
2. Rhoads GG, Dahlen G, Berg K et al: Lp(a) lipoproteins as a risk factor for myocardial infarction. JAMA 1986;256:2540-2544
3. Bostom AG, Cupples LA, Jenner JL, et al: Elevated plasma lipoprotein(a) and coronary heart disease in men aged 55 years and younger. A prospective study. JAMA 1996;276:544-548
4. Ridker PM, Hennekens CH, Stampfer MJ: A prospective study of lipoprotein(a) and the risk of myocardial infarction. JAMA 1993;270:2195-2199
5. Tsimikas S, Brilakis ES, Miller ER, et al: Oxidized phospholipids, Lp(a) lipoprotein, and coronary artery disease. N Engl J Med 2005;353(1):46-57