Biochemical determination of Lp(a)

Hyperlipoproteinemia(a) is defined as elevated lipoprotein(a) [Lp(a)] concentrations in blood, and it represents a major health concern worldwide. Between 10% and 30% of the world’s population has high Lp(a) levels, depending on their ethnicity. However, it has been described to show a higher incidence among patients with established cardiovascular disease and aortic stenosis.

Lipoprotein(a) has been defined as a crucial independent risk factor for atherosclerotic plaque development due to its proatherogenic, prothrombotic, and proinflammatory properties. In fact, high Lp(a) levels have a continuous causal association with risk of ischemic cardiovascular disease (CVD), aortic valve stenosis, and heart failure. Conversely, attention is recently being paid to very low Lp(a) levels (<5mg/dl, <10-12 nmol/l), as they could be associated with increased risk of diabetes mellitus.

According to the guidelines by the main scientific societies, the risk conferred by Lp(a) is considered to be significant when levels are >50 mg/dl (>125 nmol/l), and non-significant at levels <30 mg/dl (<75 nmol/l). In the grey zone, from 30 to 50 mg/dl (75-125 nmol/l), it is also relevant when considering the risk attributable to Lp(a) in the presence of other risk factors, as well as for the patient’s global risk stratification.

Lp(a) may increase the risk of developing CVD even when LDL (C-LDL) levels are within the recommended range, which is known as residual cardiovascular risk.

Since Lp(a) is composed of ~30–45% cholesterol in terms of mass and this is reported as part of C-LDL laboratory measurements, it has been estimated that around 25% of patients clinically diagnosed with familial hypercholesterolemia (FH) could be misdiagnosed due to high Lp(a) levels. Moreover, both conditions can coexist, thus multiplying the risk of atherosclerotic CVD in these patients.

Very high Lp(a) levels (>180 mg/dL, >400 nmol/l) have been described to confer a risk of atherosclerotic CVD equivalent to that of patients with a family history of early CVD or patients with heterozygous FH.

Plasma Lp(a) levels show high interindividual variability in the general population. Nevertheless, its concentration remains relatively stable throughout an individual’s life (with some exceptions) and is mainly (>90%) determined by genetic variability in the LPA locus, which encodes apolipoprotein(a). Lp(a) inheritability has been demonstrated to be very high (from 70% to more than 90%).

Depending on ethnicity, between 10% and 30% of the world’s population has high Lp(a) levels, with en estimated 1,43 billion people affected worldwide. However, it has been described to show a higher incidence among patients with established cardiovascular disease and aortic stenosis.

Determining Lp(a) levels provides relevant information about cardiovascular risk. Lp(a) may increase the risk of cardiovascular disease even at normal C-LDL levels (residual cardiovascular risk). Moreover, in patients with defined FH, high Lp(a) values multiply the risk of atherosclerotic cardiovascular disease. 

On the other hand, this test could be useful to refine diagnosis in some patients clinically diagnosed with FH, as it has been estimated that about 25% of these patients could be misdiagnosed due to high Lp(a) levels.

Finally, it has been described that very low Lp(a) levels (<5mg/dl, <10-12 nmol/l) could be associated with a higher risk of diabetes mellitus, which in turn constitutes an independent risk factor for atherosclerotic plaque development.

The guidelines by the main scientific societies recommend measuring Lp(a) concentration at least once in adults and interpreting the results within the context of the patient’s absolute global cardiovascular risk. In addition, Lp(a) measurement must be considered in patients with personal or family history of early atherosclerotic CVD and a family history of high Lp(a) levels or FH. Lp(a) detection is also recommended in young individuals with a history of ischemic stroke with no additional identifiable risk factors.