Lipoprotein(a) - Diagnostic Testing

Diagnostic Testing

Numerous studies confirming a strong correlation between elevated Lp(a) and heart disease have led to the consensus that Lp(a) is an important, independent predictor of cardiovascular disease. Animal studies have shown that Lp(a) may directly contribute to atherosclerotic damage by increasing plaque size, inflammation, instability, and smooth muscle cell growth. Genetic data also support the theory that Lp(a) causes cardiovascular disease.

The European Atherosclerosis Society currently recommends that patients with a moderate or high risk of cardiovascular disease have their lipoprotein (a) levels checked. Any patient with one of the following risk factors should be screened;

• premature cardiovascular disease
• familial hypercholesterolaemia
• family history of premature cardiovascular disease
• family history of elevated lipoprotein (a)
• recurrent cardiovascular disease despite statin treatment
• ≥3% 10-year risk of fatal cardiovascular disease according to the European guidelines
• ≥10% 10-year risk of fatal and/or non-fatal cardiovascular disease according to the US guidelines

If the level is elevated, treatment should be initiated with a goal of bringing the level below 50 mg/dL. In addition, the patient's other cardiovascular risk factors (including LDL levels) should be optimally managed. Apart from the total Lp(a) plasma concentration, the apo(a) isoform might be an important risk parameter as well.

Prior studies of the relationship between LP(a) and ethnicity have shown inconsistent results. Lipoprotein (a) levels seem to differ in different populations. For example, in some African populatation, Lp(a) levels are, on average higher, than other groups, so that using a risk threshold of 30 mg/dl would classify up to > 50% of the individuals as higher risk. Some part of this complexity may be related to the different genetic factors involved in determining Lp(a) levels. One recent study showed that in different ethic groups, different genetic alterations were associated with increased Lp(a) levels.

More recent data suggest that prior studies were under-powered. The Atherosclerosis Risk in Communities (ARIC) followed 3467 African Americans and 9851 whites for 20 years. The researchers found that an elevated Lp(a) conferred the same risk in each group. However, African Americans had roughly three times the level of Lp(a), and Lp(a) also predicted an increased risk of stroke.

Approximate levels of risk are indicated by the results below, although at present there are a variety of different methods by which to measure Lp(a). A standardized international reference material has been developed and is accepted by the WHO Expert Committee on Biological Standardization and the International Federation of Clinical Chemistry and Laboratory Medicine. Although further standardization is still needed, development of a reference material is an importance step towards standardizing results.

Lipoprotein(a) - Lp(a)

Desirable: < 14 mg/dL (< 35 nmol/l)

Borderline risk: 14 - 30 mg/dL (35 - 75 nmol/l)

High risk: 31 - 50 mg/dL (75 - 125 nmol/l)

Very high risk: > 50 mg/dL (> 125 nmol/l)

LP(a) appears with different isoforms (per kringle repeats) of apolipoprotein - 40% of the variation in Lp(a) levels when measured in mg/dl can be attributed to different isoforms. Lighter Lp(a) are also associated with disease. Thus a test with simple quantitative results may not provide a complete assessment of risk.