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

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.

Lp(a) CHOLESTEROL

                  Normal: <3 mg/dL          

                  Suggests increased risk of coronary

                  artery disease: > or = 3 mg/dL

LpX

                  Undetectable

Patients with increased Lp(a) cholesterol values have an

approximate 2-fold increased risk for developing cardiovascular

disease and events.

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.

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