Lipoprotein(a) [Lp(a)] is one of the strongest genetically determined risk factors for cardiovascular
disease (CVD) (1).
It contains besides an LDL particle an additional apolipoprotein that is called apolipoprotein (a)
[apo(a)]. This apolipoprotein shows a high homology with plasminogen. After more than 50 years of
research, the physiological function of Lp(a) is still unexplained.
An astonishing characteristic of Lp(a) is the more than 1,000-fold range of concentrations between
individuals from almost zero to more than 300 mg/dL (1). The distribution of Lp(a) is very skewed in
most populations: for example, roughly 50% of the Europeans have concentrations below 10 mg/dL
and about 25% have concentrations above 30 mg/dL.
Apo(a) is synthesized in the liver (2, 3).
Variation in Lp(a) concentrations among individuals is determined by the rate of production rather
than by differences in the catalytic rate (4). After secretion of apo(a), it binds to LDL-apoB lysinebinding
residues by its lysinebinding sites with subsequent forming of a disulfide bond. Whether the
assembly occurs in the circulation at the hepatic surface or intracellularly is a matter of debate (5).
The physiological function of Lp(a) is still in the dark. It is believed that Lp(a) has proatherogenic and
prothrombotic properties.
The apo(a) glycoprotein has a high degree of homology to plasminogen (6) suggesting that Lp(a)
might not only be a link between the cholesterol transport system in plasma and the fibrinolytic
system but may also act as a modulator of the balance between blood clotting and fibrinolysis. At
least in vitro, Lp(a) indeed interferes with the blood clotting/fibrinolytic cascades at several steps
(7).
Binding of Lp(a) to fibrin has been proposed as a mechanism to deliver cholesterol to sites of injury
and wound healing of the vascular wall with the negative side effect that Lp(a) also deposits
cholesterol in growing atherosclerotic plaques and inhibits fibrinolysis at the plaque surface (8)
The evidence is quite strong that high Lp(a) concentrations are associated with an increasing risk for
cardiovascular disease (1, 9). The Copenhagen City Heart Study observed for individuals from a
general population with concentrations between 30 and 76 mg/dL (corresponding to the 67th–90th
percentile) a 1.60-fold increased risk for incident myocardial infarction compared to individuals with
Lp(a) concentrations below 5 mg/dL (corresponding to the lower 22% of the population).
An estimated 20% to 30% of people worldwide have high levels of plasma lipoprotein(a), which
are independently associated with atherosclerotic cardiovascular disease (ASCVD) and increased
risk of myocardial infarction and stroke, among other conditions (1).
Lp(a) levels are established in early childhood and remain relatively consistent over an individual’s
lifetime.
Although some evidence is conflicting, Lp(a) seems to increase cardiovascular risk through multiple
mechanisms, including those attributable to both its LDL-like moiety as well as the unique apo(a)
protein.
The latter may confer prothrombotic and additional proinflammatory effects that can cause vascular
cell dysfunction (10)
Factors that influence Lp(a) levels include age, sex, ethnicity and comorbid conditions, such as
familial hypercholesterolemia and liver or kidney disease (11).
Despite the positive effects of diet and exercise in